Guillermo I Perez-Perez

The seroprevalence of Helicobacter pylori and its relationship to malaria in Ugandan children
Gupta V.; Perez-Perez G.I.; Dorsey G.; Rosenthal P.J.; Blaser M.J.
2012 ;106(1):35-42, Transactions of the Royal Society of Tropical Medicine & Hygiene
Helicobacter pylori epidemiology in sub-Saharan Africa, particularly among children, has been little investigated. A secondary endpoint of our study was to examine for associations between the seroprevalence of H. pylori and the incidence of malaria. We explored H. pylori prevalence by measuring serum IgG antibodies to H. pylori whole cell and cytotoxin-associated gene A (CagA) antigens by ELISA in a longitudinal cohort of 200 Ugandan children, aged 1-10 years at enrollment, in whom malaria incidence was followed over 572 person-years. First-sample seroprevalence for H. pylori -specific IgG (63%) and for the H. pylori protein CagA (78.5%) were both high, and they were positively associated with advancing age (per each 1-year age increase, OR (95% CI): 1.60 (1.39-1.85), P< 0.001). We observed nearly universal prevalence of CagA+ H. pylori by the age of 10 years in Kampala and found no evidence that H. pylori-positivity is protective against malaria. 2011 Royal Society of Tropical Medicine and Hygiene
— id: 147750, year: 2012, vol: 106, page: 35, stat: Journal Article,

Rapid detection of clarithromycin resistant Helicobacter pylori strains in Spanish patients by polymerase chain reaction-restriction fragment length polymorphism
Agudo, S; Perez-Perez, G; Alarcon, T; Lopez-Brea, M
2011 Mar;24(1):32-36, Revista espanola de quimioterapia
INTRODUCTION: The aim of this study was to characterize the mutations types present in the 23S rRNA gene related to H. pylori clarithromycin-resistance strains in Spain and evaluate a novel PCR-RFLP method for detection of the most frequent point mutation in our population. METHODS: Gastric biopsies were obtained by endoscopy from patients with gastric symptoms. H. pylori was cultured according to standard microbiological procedures and clarithromycin resistance was determined by E-test. DNA extraction was performed by NucliSens platform with the NucliSens magnetic extraction reagents (bioMerieux) according to the manufacturer instructions. Analyses for point mutations in 23S rRNA gene strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using BsaI enzyme to detect restriction sites that correspond to the mutation (A2143G). RESULTS: We found 42 out of 118 (35.6%) strains resistant to clarithromycin by E-test. E-test results were confirmed for the presence of point mutation in 34 (88.1%) of these strains. Mutation A2143G was found in 85.3% of the strains. Analyses with the restriction enzyme BsaI was able to confirm the presence of A2143G mutation. There were 8 H. pylori strains resistant to clarithromycin by E-test but without any point mutation in the 23 rRNA gene. CONCLUSIONS: We conclude that PCR-RFLP is a reliable method to detect clarithromycin-resistance H. pylori strains in countries with a high prevalence of clarithromycin-resistance as Spain. It may be useful before choosing regimens of H. pylori eradication
— id: 134135, year: 2011, vol: 24, page: 32, stat: Journal Article,

Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture
Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Penaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Munoz, Leopoldo; Berg, Douglas E; Torres, Javier
2011 ;6(11):e27212-e27212, PLoS ONE
It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America
— id: 146164, year: 2011, vol: 6, page: e27212, stat: Journal Article,

Simultaneous detection of helicobacter pylori infection and clarithromycin resistance by fluorescence in situ hybridization (FISH) in Turkish dyspeptic patients
Demiray-Gurbuz E.; Perez Perez G.; Olivares A.; Yilmaz O.; Gonen C.; Sariotlu S.; Soyturk M.; Simsek I.; Utur Kantar F.
2011 ;16:112-112, Helicobacter
Aim: Clarithromycin resistance in H. pylori is considered a major cause of treatment failure. We aimed to evaluate the efficacy of fluorescence in situ hybridization (FISH) method for the simultaneous detection of H. pylori and to determine clarithromycin resistance due to mutations in the 2143 and 2144 positions of 23SrRNA gene compared with traditional culture and antimicrobial susceptibility technics. We assessed cagA status and correlated cagA positivity and clarithromycin resistance. Methods: We studied 179 patients with dyspepsia (45M, 134F; 43.7 +/- 13.7 years). Antrum and corpus biopsy specimens were obtained for rapid urease test, histopathology and culture. H. pylori status was defined when at least two of three tests were positive. Clarithromycin susceptibility in H. pylori strains was assessed by E-test and H. pylori and clarithromycin susceptibility were determined by FISH (BactFISH H. pylori Combi Kit) using formalin-fixed paraffinembedded antrum and corpus biopsy specimens. cagA status in H. pylori strains was also determined by PCR. Results: A total of 119 (66.5%) were H. pylori positive. Among those, 84 (70.6%) were culture positive and 100 (84.0%) were FISH positive. The sensitivity, specificity, PPV and NPV of FISH was 84.0%, 95.0%; 97.1%, and 75.0%, respectively (Kappa = 0.741). FISH detected clarithromycin resistance in 22.0% and by E-test 27.4% of the strains. The concordance was 74.8%. Of the 84 H. pylori strains, 42 (50.0%) were cagA positive. Conclusion: FISH increases the sensitivity to detect H. pylori when compared with microbiology routine methods. FISH is a reliable and highly sensitive method, especially when a quick decision is necessary for treating dyspeptic patient with previous treatment failures
— id: 142067, year: 2011, vol: 16, page: 112, stat: Journal Article,

Helicobacter pylori and the birth cohort effect: evidence for stabilized colonization rates in childhood
den Hoed, Caroline M; Vila, Anne J; Holster, Ingrid L; Perez-Perez, Guillermo I; Blaser, Martin J; de Jongste, Johan C; Kuipers, Ernest J
2011 Oct;16(5):405-409, Helicobacter
Background: The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely because of a birth cohort effect. We previously observed a decline in H. pylori prevalence in 6- to 8-year-old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions. Aim: The aim of this study was to investigate whether the birth cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods: Anti-H. pylori IgG antibodies and anti-CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7-9 years who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort. The H. pylori and CagA antibodies were determined by enzyme-linked immunosorbent assays that have been extensively validated in children, with a 94% sensitivity for H. pylori colonization and a 92.5% sensitivity for colonization with a cagA-positive strain. Results: Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6-11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1-1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion: The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA(+) H. pylori strains has become very low, consistent with prior observations that cagA(+) strains are disappearing in Western countries
— id: 137846, year: 2011, vol: 16, page: 405, stat: Journal Article,

The effect of H. pylori eradication on meal-associated changes in plasma ghrelin and leptin
Francois, Fritz; Roper, Jatin; Joseph, Neal; Pei, Zhiheng; Chhada, Aditi; Shak, Joshua R; de Perez, Asalia Z Olivares; Perez-Perez, Guillermo I; Blaser, Martin J
2011 ;11:37-37, BMC gastroenterology
ABSTRACT: BACKGROUND: Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight. METHODS: Veterans referred for upper GI endoscopy were evaluated at baseline and >/=8 weeks after endoscopy, and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h after a standard high protein meal, and levels of eight hormones determined. RESULTS: Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate. Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed eradication. After a median of seven months following eradication, six hormones related to energy homeostasis showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI significantly increased (5 +/- 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not significantly changed in those who were H. pylori-negative or indeterminant at baseline. CONCLUSIONS: Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with consequent effects on body morphometry
— id: 132313, year: 2011, vol: 11, page: 37, stat: Journal Article,

Novel gastric helicobacters and oral campylobacters are present in captive and wild cetaceans
Goldman, Cinthia G; Matteo, Mario J; Loureiro, Julio D; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Catalano, Mariana; Heredia, Sergio Rodriguez; Mantero, Paula; Boccio, Jose R; Zubillaga, Marcela B; Cremaschi, Graciela A; Solnick, Jay V; Perez-Perez, Guillermo I; Blaser, Martin J
2011 Aug 26;152(1-2):138-145, Veterinary microbiology
The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-H. pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are commonly distributed in marine mammals, and identify taxonomic clusters that may represent novel species
— id: 136497, year: 2011, vol: 152, page: 138, stat: Journal Article,

Helicobacter pylori induction of eosinophil migration is mediated by the cag pathogenicity island via microbial-epithelial interactions
Nagy, Toni A; Allen, Shannon S; Wroblewski, Lydia E; Flaherty, David K; Slaughter, James C; Perez-Perez, Guillermo; Israel, Dawn A; Peek, Richard M Jr
2011 Apr;178(4):1448-1452, American journal of pathology
The host immune response directed against Helicobacter pylori is ineffective in eliminating the organism and strains harboring the cag pathogenicity island augment disease risk. Because eosinophils are a prominent component of H. pylori-induced gastritis, we investigated microbial and host mechanisms through which H. pylori regulates eosinophil migration. Our results indicate that H. pylori increases production of the chemokines CCL2, CCL5, and granulocyte-macrophage colony-stimulating factor by gastric epithelial cells and that these molecules induce eosinophil migration. These events are mediated by the cag pathogenicity island and by mitogen-activated protein kinases, suggesting that eosinophil migration orchestrated by H. pylori is regulated by a virulence-related locus
— id: 133350, year: 2011, vol: 178, page: 1448, stat: Journal Article,

Genotypic and Phenotypic Variation of Lewis Antigen Expression in Geographically Diverse Helicobacter pylori Isolates
Pohl, Mary Ann; Zhang, William; Shah, Sunny N; Sanabria-Valentin, Edgardo L; Perez-Perez, Guillermo I; Blaser, Martin J
2011 Dec;16(6):475-481, Helicobacter
Background: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and beta-(1,3)galT loci in 113 H. pylori strains. Results: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). Conclusion: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression
— id: 141081, year: 2011, vol: 16, page: 475, stat: Journal Article,

Association Between Oral Health And Gastric Precancerous Lesions
Salazar CR; Francois F; Li Y; Corby P; Hays R; Leung C; Bedi S; Segers S; Queiroz E; Sun J; Wang B; Ho H; Craig R; Cruz G; Blaser MJ; Perez-Perez G; Hayes RB; Dasanayake A; Pei Z; Chen Y
2011 Dec 1;:399-403 #, Carcinogenesis
Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared to non-cases, cases were significantly more likely to not floss their teeth (Odds Ratio [OR] = 2.89, 95% Confidence Interval [CI]: 1.09-7.64), adjusting for age, sex, race, BMI, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n=28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases (OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites [equivalent to 19.7%]), independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions
— id: 147670, year: 2011, vol: , page: 399, stat: Journal Article,

High Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains and Risk Factors Associated with Resistance in Madrid, Spain
Agudo, Sonia; Perez-Perez, Guillermo; Alarcon, Teresa; Lopez-Brea, Manuel
2010 OCT ;48(10):3703-3707, Journal of clinical microbiology
Clarithromycin is one of the antibiotics used for the treatment of Helicobacter pylori infections, and clarithromycin resistance is the most important factor when it comes to predicting eradication failure. The present study analyzed H. pylori isolates for the presence of 23S rRNA gene mutations and determined the risk factors associated with resistance among H. pylori isolates collected in Madrid, Spain, in 2008. We studied 118 H. pylori strains isolated from the same number of patients. A total of 76.3% of the patients were born in Spain, 52.7% were children, 20.3% had previously been treated, and 66.1% were female. Clarithromycin resistance was determined by Etest. H. pylori strains were considered resistant if the MIC was >= 1 mg/liter. DNA extraction was carried out by use of the NucliSens easyMAG platform with NucliSens magnetic extraction reagents (bioMerieux). The DNA sequences of the 23S rRNA genes of clarithromycin-resistant and -sensitive strains were determined to identify specific point mutations. The vacA genotype and cagA status were determined by PCR. We found that 42 (35.6%) strains were resistant to clarithromycin by Etest. Etest results were confirmed by detection of the presence of point mutations in 34 (88.1%) of these strains. Eight H. pylori strains were resistant to clarithromycin by Etest but did not have a point mutation in the 23S rRNA gene. Mutation at A2143G was found in 85.3% of the strains, mutation at A2142G in 8.8%, and mutation at T2182C in 5.9%. Dual mutations were found in 8.8% of the strains. H. pylori clarithromycin-resistant strains were strongly associated with pediatric patients, with patients born in Spain, and with patients who had previously been treated (P <= 0.02). In addition, H. pylori strains resistant to clarithromycin more frequently presented the vacA s2/m2 genotype and were more likely to be cagA negative than susceptible strains (39.1% and 11.2%, respectively; P value < 0.001). We concluded that, in the present study, H. pylori clarithromycin-resistant strains are more frequently found in children, in patients mostly born in Spain, and in individuals who were previously treated for H. pylori infection and that these individuals are more likely colonized with a less virulent H. pylori strain
— id: 113921, year: 2010, vol: 48, page: 3703, stat: Journal Article,

Diversity of VacA intermediate region among Helicobacter pylori strains from several regions of the world
Chung, Christine; Olivares, Asalia; Torres, Eugenia; Yilmaz, Ozlem; Cohen, Henry; Perez-Perez, Guillermo
2010 Mar;48(3):690-696, Journal of clinical microbiology
Helicobacter pylori is known to be a major cause of gastric carcinoma and peptic ulceration. cagA positivity and vacA's signal regions and mid-regions are well-characterized markers of H. pylori's virulence. Recently, an intermediate region has been identified as another strong marker of H. pylori-associated disease, and its i1 allele has been linked with severe diseases in colonized hosts. The goal of this study was to determine the prevalence of the intermediate alleles in H. pylori isolates from China, Turkey, and Uruguay and from U.S. Africans and to compare their distribution with other well-characterized virulence factors. Originally, 123 H. pylori strains were studied, but 3 were excluded due to the failure to amplify the intermediate region in these samples. Therefore, a total of 120 strains were analyzed: 30 Chinese isolates, 35 Turkish isolates, 30 Uruguayan isolates, and 25 U.S. African isolates. The s type and the m type were determined by PCR amplification. The i type was identified by PCR amplification and DNA sequencing. CagA status was determined by PCR methodology. There was a strong correlation among CagA positivity, s1, and i1 in Chinese, U.S. African, and Uruguayan isolates, but less correlation among these markers in Turkish isolates. A new intermediate variant (i3) was identified in 25.7% of Turkish strains and 3.3% of the Chinese strains. In summary, the distribution of CagA positivity and s1 correlated with the i1 in the three populations, except in the Turkish population, which showed a disproportionate representation of the i3 allele. Phylogenetic mapping confirmed the i-typing method previously defined and adopted for this study. The phylogenetic tree showed country-specific correlation with the intermediate region. Our results showed that the i1 allele is strongly associated with CagA positivity and the vacA s1 allele, suggesting its role as a virulence marker and potential predictor for clinical outcome
— id: 107926, year: 2010, vol: 48, page: 690, stat: Journal Article,

Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study
Cook, Michael B; Dawsey, Sanford M; Diaw, Lena; Blaser, Martin J; Perez-Perez, Guillermo I; Abnet, Christian C; Taylor, Philip R; Albanes, Demetrius; Virtamo, Jarmo; Kamangar, Farin
2010 Aug;19(8):1966-1975, Cancer epidemiology biomarkers & prevention
BACKGROUND: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved. METHODS: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24). CONCLUSIONS: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect. IMPACT: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC
— id: 134354, year: 2010, vol: 19, page: 1966, stat: Journal Article,

Dietary folate and vitamin B12 intake before diagnosis decreases gastric cancer mortality risk among susceptible MTHFR 677TT carriers
Galvan-Portillo, Marcia V; Onate-Ocana, Luis F; Perez-Perez, Guillermo I; Chen, Jia; Herrera-Goepfert, Roberto; Chihu-Amparan, Lilia; Flores-Luna, Lourdes; Mohar-Betancourt, Alejandro; Lopez-Carrillo, Lizbeth
2010 Feb;26(2):201-208, Nutrition
OBJECTIVE: To assess gastric cancer survival in relation to dietary intake of methyl donors and the methylenetetrahydrofolate reductase 677C>T (MTHFR 677C>T) polymorphism. METHODS: A prospective cohort of 257 incidental, histologically confirmed gastric cancer cases was assembled in January 2004 and followed until June 2006. Patients were recruited from the main oncology and/or gastroenterology units in Mexico City and were queried regarding their sociodemographic information, clinical history, and dietary habits 3 y before the onset of their symptoms. The intake of methyl donors was estimated with a food-frequency questionnaire and the MTHFR 677C>T polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. Cox's multivariate regression models were used to estimate the mortality risk of gastric cancer. RESULTS: MTHFR 677TT carriers with low folate and vitamin B12 intakes had the lowest survival rate in cases of gastric cancer. High intakes of folate and vitamin B12 before diagnosis was associated with decreased gastric cancer mortality risk in susceptible MTHFR 677TT carriers (mortality risk for folate 0.14, 95% confidence interval 0.04-0.46, P for trend=0.001; mortality risk for vitamin B12 0.23, 95% confidence interval 0.08-0.66, P for trend=0.008). CONCLUSION: Folate and related B vitamins may be used as an intervention strategy to improve the survival outcome of gastric cancer
— id: 133455, year: 2010, vol: 26, page: 201, stat: Journal Article,

Quantitation of major human cutaneous bacterial and fungal populations
Gao, Zhan; Perez-Perez, Guillermo I; Chen, Yu; Blaser, Martin J
2010 Oct;48(10):3575-3581, Journal of clinical microbiology
Because the human skin microbiota may play roles in the causation or modification of skin diseases, we sought to provide initial quantitative analysis from different cutaneous locations. We developed quantitative PCRs to enumerate the total bacterial and fungal populations, as well as the most common bacterial and fungal genera present in six locales, in eight healthy subjects. We used a set of primers and TaqMan MGB probes based on the bacterial 16S rRNA and fungal internally transcribed spacer region, as well as bacterial genus-specific probes for Propionibacterium, Corynebacterium, Streptococcus, and Staphylococcus and a fungal genus-specific probe for Malassezia. The extent of human DNA contamination of the specimen was determined by quantitating the human housekeeping GAPDH gene. The highest level of 16S rRNA copies of bacteria was present in the axilla (4.44 +/- 0.18 log(10) copies/mul [mean +/- standard error of the mean]), with normalization based on GAPDH levels, but the other five locations were similar to one another (range, 2.48 to 2.89 log(10) copies/mul). There was strong symmetry between the left and right sides. The four bacterial genera accounted for 31% to 59% of total bacteria, with the highest percent composition in the axilla and the lowest in the forearm. Streptococcus was the most common genus present on the forehead and behind the ear. Corynebacterium spp. were predominant in the axilla. Fungal levels were 1 to 2 log(10) lower than for bacteria, with Malassezia spp. accounting for the majority of fungal gene copies. These results provide the first quantitation of the site and host specificities of major bacterial and fungal populations in human skin and present simple methods for their assessment in studies of disease
— id: 114044, year: 2010, vol: 48, page: 3575, stat: Journal Article,

Genetic risk factors for inflammatory bowel disease in a North-eastern Mexican population
Garza-Gonzalez, E.; Perez-Perez, G. I.; Mendoza-Ibarra, S. I.; Flores-Gutierrez, J. P.; Bosques-Padilla, F. J.
2010 OCT ;37(5):355-359, International journal of immunogenetics
P>The purpose of this study was to assess the role of Helicobacter pylori and several genetic polymorphisms in relation to inflammatory bowel disease (IBD). We studied 44 unrelated patients with IBD and 75 subjects with no history of IBD as controls. Using pyrosequencing technology, we identified gene polymorphisms in IL-10, TNF-A, ILB-31, and TLR4. H. pylori status was determined by serology. Individuals homozygous for IL10-592 A or IL10-1082 A genotypes show significantly lower occurrence of IBD (P = 0.03 and P < 0.01, respectively). Individuals heterozygous at IL10-1082 have significantly increased occurrence of IBD, both ulcerative colitis and Crohn's disease (P < 0.01). There was no difference in the prevalence of H. pylori infection between cases and controls. This study provides evidence that variation in IL10 is correlated with IBD occurrence in this Mexican population
— id: 113650, year: 2010, vol: 37, page: 355, stat: Journal Article,

Characterization of H-pylori CagA EPIYA motifs in H-pylori strains of Turkish Origin
Guvenir, M.; Yilmaz, O.; Olivares, A.; Gonen, C.; Sarioglu, S.; Ellidokuz, H.; Soyturk, M.; Simsek, I.; Perez, G. I. Perez
2010 AUG ;15(4):370-370, Helicobacter
— id: 114023, year: 2010, vol: 15, page: 370, stat: Journal Article,

Longitudinal Analysis of Serological Responses of Adults to Helicobacter pylori Antigens
Perez-Perez, Guillermo I; Maw, Anna M; Feingold-Link, Lani; Gunn, Jennifer; Bowers, Andrea L; Minano, Cecilia; Rautelin, Hilpi; Kosunen, Timo U; Blaser, Martin J
2010 Sep 15;202(6):916-923, Journal of infectious diseases
Because Helicobacter pylori persist for decades in the human stomach, the aim of this study was to examine the long-term course of H. pylori-specific serum immunoglobulin G (IgG) responses with respect to subclass and antigenic target. We studied paired serum samples obtained in 1973 and in 1994 in Vammala, Finland, from 64 healthy H. pylori-positive adults and from other healthy control subjects. H. pylori serum immunoglobulin A, IgG, and IgG subclass responses were determined by antigen-specific enzyme-linked immunosorbent assays. H. pylori-specific IgG1 and IgG4 subtype responses from 47 subjects were similar in 1973 and 1994, but not when compared with unrelated persons. H. pylori-specific IgG1:IgG4 ratios among the participants varied >1000-fold; however, 57 (89.1%) of 64 subjects had an IgG1:IgG4 ratio >1.0, consistent with a predominant IgG1 (Th1) response. Furthermore, ratios in individual hosts were stable over the 21-year period ([Formula: see text]; [Formula: see text]). The immune response to heat shock protein HspA was unchanged in 49 (77%) of the 64 subjects tested; of the 15 whose serostatus changed, all seroconverted and were significantly younger than those whose status did not change. These findings indicate that H. pylori-specific antibody responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1 responses predominating, and HspA seroconversion with aging
— id: 111828, year: 2010, vol: 202, page: 916, stat: Journal Article,

Identification of Helicobacter spp. in bile and gallbladder tissue of patients with symptomatic gallbladder disease
Sabbaghian, M Shirin; Ranaudo, Jeffrey; Zeng, Lin; Alongi, Alexandra P; Perez-Perez, Guillermo; Shamamian, Peter
2010 Mar;12(2):129-133, HPB : the official journal of the International Hepato Pancreato Biliary Association
BACKGROUND: This experimental study was designed to determine if Helicobacter spp. contribute to benign gallbladder disease using polymerase chain reaction (PCR) methods. METHODS: Patients with benign gallbladder disease scheduled for elective cholecystectomy at New York University Langone Medical Center were recruited from February to May 2008. Bile, gallbladder tissue and gallstones were collected. DNA was isolated from these specimens and amplified via PCR using C97F and C98R primers specific for Helicobacter spp. Appropriate positive and negative controls were used. Products were analysed with agarose gel electrophoresis, sequenced and results aligned using sequencher. Plasma was collected for detection of anti-Helicobacter pylori antibodies via enzyme-linked immunosorbent assay. RESULTS: Of 36 patients, 12 patients' bile and/or tissue were positive for Helicobacter spp. by PCR. Species were most homologous with H. pylori, although other Helicobacter spp. were suggested. Six of 12 patients demonstrated anti-Helicobacter antibodies in plasma, suggesting that the remaining six might have demonstrated other species besides H. pylori. Four of six plasma samples with anti-Helicobacter antibodies were anti-CagA (cytotoxin associated gene) negative. DISCUSSION: Helicobacter spp. can be detected in bile and gallbladder tissue of patients with benign gallbladder disease. The contribution of these bacteria to the pathophysiology of gallbladder disease and gallstone formation requires further study
— id: 109804, year: 2010, vol: 12, page: 129, stat: Journal Article,

Helicobacter pylori-Induced Loss of the Inhibitor-of-Apoptosis Protein Survivin Is Linked to Gastritis and Death of Human Gastric Cells
Valenzuela, Manuel; Perez-Perez, Guillermo; Corvalan, Alejandro H.; Carrasco, Gonzalo; Urra, Hery; Bravo, Denisse; Toledo, Hector; Quest, Andrew F. G.
2010 OCT 1 ;202(7):1021-1030, Journal of infectious diseases
Helicobacter pylori infects the human stomach and modifies signaling pathways that affect gastric epithelial cell proliferation and viability. Chronic exposure to this pathogen contributes to the onset of gastric atrophy, an early event in the genesis of gastric cancer associated with H. pylori infection. Susceptibility to H. pylori-induced cell death ultimately depends on the presence of protective host cell factors. Although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Thus, we investigated in human gastric tissue samples and cell lines whether H. pylori infection is linked to loss of survivin and increased cell death. Our results show that infection with H. pylori decreased survivin protein levels in the mucosa of patients with gastritis. Furthermore, survivin down-regulation correlated with apoptosis and loss of cell viability in gastrointestinal cells cocultured with different H. pylori strains. Finally, overexpression of survivin in human gastric cells was sufficient to reduce cell death after infection. Taken together, these findings implicate survivin as an important survival factor in the gastric mucosa of humans
— id: 113756, year: 2010, vol: 202, page: 1021, stat: Journal Article,

Repeat-associated plasticity in the Helicobacter pylori RD gene family
Shak, Joshua R; Dick, Jonathan J; Meinersmann, Richard J; Perez-Perez, Guillermo I; Blaser, Martin J
2009 Nov;191(22):6900-6910, Journal of bacteriology
The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host
— id: 104893, year: 2009, vol: 191, page: 6900, stat: Journal Article,

Antimicrobial susceptibility of Helicobacter pylori and mechanisms of clarithromycin resistance in strains isolated from patients in Uruguay
Torres-Debat, M E; Perez-Perez, G; Olivares, A; Fernandez, L; Raisler, K; Gonzalez, N; Stein, S; Bazet, M C; Alallon, W; Cohen, H
2009 Nov;101(11):757-762, Revista espanola de enfermedades digestivas
The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains
— id: 133755, year: 2009, vol: 101, page: 757, stat: Journal Article,

Prevalence of H. pylori in Georgian pediatric patients with peptic ulcer diseases
Buadze, M; Olivares, A; Kutubidze, T; Labauri, L; Chavchanidze, D; Lobzhanidze, G; Perez-Perez, GI
2008 OCT ;13(5):447-448, Helicobacter
— id: 86817, year: 2008, vol: 13, page: 447, stat: Journal Article,

Helicobacter pylori seroprevalence in Amerindians from isolated locations
Contreras, Monica; Pujol, Flor H; Perez-Perez, Guillermo I; Marini, Elisabetta; Michelangeli, Fabian A; Ponce, Liliana; Dominguez-Bello, Maria G
2008 Apr;78(4):574-576, American journal of tropical medicine & hygiene
Helicobacter pylori seems universally distributed in all human populations, with high prevalence in the third world. Because H. pylori is an ancestral indigenous microbe of the human stomach, we hypothesized that its prevalence in isolated Amerindians would be high. A serologic study was performed on 19 Guahibo-Piaroa and 17 Warao in Venezuela, using H. pylori whole cell (WC) and CagA antigens from US strains. For Guahibo-Piaroa Amerindians, CagA seropositivity was 95%, but WC seropositivity was only 74%. For Warao, both CagA and WC seropositive proportions were low (65% and 76%, respectively). Because all CagA-seropositive individuals carry H. pylori, the results suggest that there has been bacterial antigen divergence, probably caused by genetic drift/natural selection, on humans and their microbes in isolated human groups
— id: 79186, year: 2008, vol: 78, page: 574, stat: Journal Article,

Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii
Epplein, Meira; Nomura, Abraham M Y; Hankin, Jean H; Blaser, Martin J; Perez-Perez, Guillermo; Stemmermann, Grant N; Wilkens, Lynne R; Kolonel, Laurence N
2008 Oct;19(8):869-877, Cancer causes & control. ccc
OBJECTIVE: The risk factors most strongly associated with gastric cancer are the gastric bacteria Helicobacter pylori and diet. Utilizing data from a case-control study among residents in Hawaii, we examined the association of diet, presence of H. pylori, and non-cardia gastric cancer risk. METHODS: Serum taken at diagnosis for cases (n = 212) and at interview for controls (n = 336) was assayed for IgG antibodies to H. pylori group antigens and to a recombinant fragment of the cytotoxin-associated antigen A (CagA) protein, and subjects completed food frequency questionnaires. Risk measures were calculated using logistic regression. The likelihood ratio test was used to assess interactions. RESULTS: Inverse associations were found between gastric cancer risk and increasing intake of several micronutrients and vegetables among all individuals. For H. pylori/CagA-positive subjects, significant trends were present for total, green, and yellow vegetables, while a significant trend was present only for yellow vegetables among H. pylori/CagA-negative individuals. For intestinal gastric cancer, there was a suggestion that intake of vegetables, especially cruciferous vegetables, had a stronger protective effect for the H. pylori/CagA-positive group. CONCLUSIONS: Diet may play a greater role in the etiology of non-cardia gastric cancer among individuals with evidence of H. pylori infection than among those without
— id: 79187, year: 2008, vol: 19, page: 869, stat: Journal Article,

The association of gastric leptin with oesophageal inflammation and metaplasia
Francois, F; Roper, J; Goodman, A J; Pei, Z; Ghumman, M; Mourad, M; de Perez, A Z Olivares; Perez-Perez, G I; Tseng, C-H; Blaser, M J
2008 Jan;57(1):16-24, Gut: journal of the British Society of Gastroenterology
BACKGROUND: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. AIMS: To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia. METHODS: From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. RESULTS: Of 269 individuals enrolled, 105 were Helicobacter pylori-negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123-333) pg/mg) compared with normal (126 (78-221) pg/mg) or inflamed (114 (76-195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus. CONCLUSIONS: Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression
— id: 75709, year: 2008, vol: 57, page: 16, stat: Journal Article,

mRNA levels of TLR4 and TLR5 are independent of H pylori
Garza-Gonzalez, Elvira; Bocanegra-Garcia, Virgilio; Bosques-Padilla, Francisco-Javier; Flores-Gutierrez, Juan-Pablo; Moreno, Francisco; Perez-Perez, Guillermo-Ignacio
2008 Sep 14;14(34):5306-5310, World journal of gastroenterology : WJG
AIM: To determine if the presence H pylori or its virulence affect toll-like receptor 4 (TLR4) and TLR5 mRNA expression levels. METHODS: For the in vivo assays, gastric biopsies were obtained from 40 patients and H pylori status was determined. For the in vitro assays, human gastric adenocarcinoma mucosal cells (AGS) were cultured in the presence or absence of twelve selected H pylori strains. H pylori strains isolated from culture-positive patients and selected strains were genotyped for cagA and vacA. The cDNA was obtained from mRNA extracted from biopsies and from infected AGS cells. TLR4 and TLR5 mRNA levels were examined by real-time PCR. RESULTS: The presence of H pylori did not affect the mRNA levels of TLR4 or TLR5 in gastric biopsies. The mRNA levels of both receptors were not influenced by the vacA status (P > 0.05 for both receptors) and there were no differences in TLR4 or TLR5 mRNA levels among the different clinical presentations/histological findings (P > 0.05). In the in vitro assay, the mRNA levels of TLR4 or TLR5 in AGS cells were not influenced by the vacAs1 status or the clinical condition associated with the strains (P > 0.05 for both TLR4 and TLR5). CONCLUSION: The results of this study show that the mRNA levels of TLR4 and TLR5 in gastric cells, both in vivo and in vitro, are independent of H pylori colonization and suggest that vacA may not be a significant player in the first step of innate immune recognition mediated by TLR4 or TLR5
— id: 102589, year: 2008, vol: 14, page: 5306, stat: Journal Article,

Asthma is inversely associated with Helicobacter pylori status in an urban population
Reibman, Joan; Marmor, Michael; Filner, Joshua; Fernandez-Beros, Maria-Elena; Rogers, Linda; Perez-Perez, Guillermo I; Blaser, Martin J
2008 ;3(12):e4060-e4060, PLoS ONE
BACKGROUND: Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma. METHODS: Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured. RESULTS: As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36-0.89). Median age of onset of asthma (doctor's diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006). CONCLUSION: These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection
— id: 91964, year: 2008, vol: 3, page: e4060, stat: Journal Article,

Effect of Helicobacter pylori eradication on gastric carcinogenesis
Romero-Gallo, Judith; Harris, Elizabeth J; Krishna, Uma; Washington, Mary Kay; Perez-Perez, Guillermo I; Peek, Richard M Jr
2008 Mar;88(3):328-336, Laboratory investigation
Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo-adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in >60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-gamma within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states
— id: 79188, year: 2008, vol: 88, page: 328, stat: Journal Article,

Leptin and ghrelin in relation to Helicobacter pylori status in adult males
Roper, Jatin; Francois, Fritz; Shue, Peter L; Mourad, Michelle S; Pei, Zhiheng; Olivares de Perez, Asalia Z; Perez-Perez, Guillermo I; Tseng, Chi-Hong; Blaser, Martin J
2008 Jun;93(6):2350-2357, Journal of clinical endocrinology & metabolism
Context: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. Objective: We sought to determine whether the presence of Helicobacter pylori affects local and systemic levels of leptin and ghrelin. Design: Prospective Setting: Veterans Affairs outpatient endoscopy center Patients: 256 patients referred for upper endoscopy Outcomes: We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies and gastric juice were determined by specific ELISAs. Results: Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminant status were excluded. Serum and fundic leptin levels correlated with Body Mass Index in the H. pylori+ (R=0.35, p<0.0001 and R=0.35, p<0.0001, respectively) and H. pylori- (R=0.65, p<0.0001 and R=0.41, p<0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml, IQR (0.9-4.6) vs. 4.0 ng/ml, (1.7-7.2); p=0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml, IQR (845-2247) vs. 1629 pg/ml, (992-2886); p=0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log10 (<80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (R=0.68, p<0.0001). Conclusions: These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions
— id: 78624, year: 2008, vol: 93, page: 2350, stat: Journal Article,

The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones
Shak, Joshua R; Roper, Jatin; Perez-Perez, Guillermo I; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A; Ren, Christine; Blaser, Martin J
2008 Sep;18(9):1089-1096, Obesity surgery
BACKGROUND: We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. METHODS: Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. RESULTS: Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p < 0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p < 0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p > 0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. CONCLUSIONS: LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term
— id: 78623, year: 2008, vol: 18, page: 1089, stat: Journal Article,

Relation of atrophic gastritis with Helicobacter pylori-CagA(+) and interleukin-1 gene polymorphisms
Sierra, Rafaela; Une, Clas; Ramirez, Vanessa; Alpizar-Alpizar, Warner; Gonzalez, Maria-I; Ramirez, Jose-A; De Mascarel, Antoine; Cuenca, Patricia; Perez-Perez, Guillermo; Megraud, Francis
2008 Nov 14;14(42):6481-6487, World journal of gastroenterology : WJG
AIM: To determine the association of Helicobacter pylori (H pylori) CagA(+) infection and pro-inflammatory polymorphisms of the genes interleukin (IL)-1RN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 consecutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA(+) was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) and PCR respectively. RESULTS: In this dyspeptic population, 86% were H pylori positive and of these, 67.8% were positive for CagA. Atrophic antral gastritis (AAG) was associated with CagA(+) status [odd ratio (OR) = 4.1; P < 0.000] and fruit consumption (OR = 0.3; P < 0.00). Atrophic body gastritis (ABG) was associated with pepsinogen PGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcohol consumption (OR = 7.3; P < 0.02). Duodenal ulcer was associated with CagA(+) (OR = 2.9; P < 0.04) and smoking (OR = 2.4; P < 0.04). PGI < 60 microg/L as well as PGI/PGII < 3.4 were associated with CagA(+). CONCLUSION: In a dyspeptic population in Costa Rica, H pylori CagA(+) is not associated with ABG, but it is a risk factor for AAG. The pro-inflammatory cytokine polymorphisms IL-1B + 3945 and IL-1RN are not associated with the atrophic lesions of this dyspeptic population
— id: 102590, year: 2008, vol: 14, page: 6481, stat: Journal Article,

Evaluation of serum pepsinogen I and II levels, gastrin-17 and H. pylori antibodies in patients with dyspepsia
Yilmaz, O; Demiray, E; Soyturk, M; Perez, GIP; Sagol, O; Bekmen, N; Simsek, I; Akpinar, H
2008 OCT ;13(5):454-454, Helicobacter
— id: 86819, year: 2008, vol: 13, page: 454, stat: Journal Article,

The effect of H. pylori eradication on serum pepsinogen I and II levels, gastrin-17, and H. pylori antibodies in patients with dyspepsia
Yilmaz, O; Demiray, E; Soyturk, M; Perez, GIP; Sarioglu, S; Bekmen, N; Simsek, I; Akpinar, H
2008 OCT ;13(5):453-454, Helicobacter
— id: 86818, year: 2008, vol: 13, page: 453, stat: Journal Article,

Early-life family structure and microbially induced cancer risk
Blaser, Martin J; Nomura, Abraham; Lee, James; Stemmerman, Grant N; Perez-Perez, Guillermo I
2007 Jan;4(1):e7-e7, PLoS medicine
BACKGROUND: Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. METHODS AND FINDINGS: We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. CONCLUSIONS: These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions
— id: 79193, year: 2007, vol: 4, page: e7, stat: Journal Article,

A new approach in the determination of clarithromycin resistance in Helicobacter pylori infection
Demiray, E; Tumer, S; Perez, GIP; Olivares, AZ; Sagol, O; Altungoz, O; Soyturk, M; Yilmaz, O
2007 AUG ;12(4):389-389, Helicobacter
— id: 74188, year: 2007, vol: 12, page: 389, stat: Journal Article,

G796A nucleotide-binding oligomerization domain (NOD) 1 and C-590T interleukin-4 polymorphisms in Helicobacter pylori related diseases
Garza-Gonzalez, E; Mendoza-Ibarra, SI; Bosques, F; Perez-Perez, GI
2007 JAN ;54(1):151-151, Zoonoses & public health
— id: 87171, year: 2007, vol: 54, page: 151, stat: Journal Article,

Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer
Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Mendoza-Ibarra, Sandra I; Flores-Gutierrez, Juan P; Maldonado-Garza, Hector J; Perez-Perez, Guillermo I
2007 ;7:70-70, BMC cancer
BACKGROUND: The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses.Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. METHODS: We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR. RESULTS: The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1-4.2) (p = 0.023). CONCLUSION: This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population
— id: 73822, year: 2007, vol: 7, page: 70, stat: Journal Article,

Serological Assays for Identification of Human Gastric Colonization by Helicobacter pylori Strains Expressing VacA m1 or m2
Ghose, Chandrabali; Perez-Perez, Guillermo I; Torres, Victor J; Crosatti, Marialuisa; Nomura, Abraham; Peek, Richard M Jr; Cover, Timothy L; Francois, Fritz; Blaser, Martin J
2007 Apr;14(4):442-450, Clinical & vaccine immunology
The Helicobacter pylori vacA gene encodes a secreted protein (VacA) that alters the function of gastric epithelial cells and T lymphocytes. H. pylori strains containing particular vacA alleles are associated with differential risk of disease. Because the VacA midregion may exist as one of two major types, m1 or m2, serologic responses may potentially be used to differentiate between patients colonized with vacA m1- or vacA m2-positive H. pylori strains. In this study, we examined the utility of specific antigens from the m regions of VacA as allele-specific diagnostic antigens. We report that serological responses to P44M1, an H. pylori m1-specific antigen, are observed predominantly in patients colonized with m1-positive strains, whereas responses to VacA m2 antigens, P48M2 and P55M2, are observed in patients colonized with either m1- or m2-positive strains. In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer
— id: 71774, year: 2007, vol: 14, page: 442, stat: Journal Article,

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China
Kamangar, F; Qiao, YL; Blaser, MJ; Sun, XD; Katki, H; Fan, JH; Perez-Perez, GI; Abnet, CC; Zhao, P; D Mark, S; Taylor, PR; Dawsey, SM
2007 JAN 15 ;96(1):172-176, British journal of cancer
In a cohort of 29 584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case - cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N = 1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori ( Hazard ratios (HRs) and 95% confidence intervals 1.64; 1.26 - 2.14, and 1.60; 1.15 - 2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88 - 1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies
— id: 70170, year: 2007, vol: 96, page: 172, stat: Journal Article,

Utility of diagnostic tests for detection of Helicobacter pylori in children in northeastern Mexico
Mendoza-Ibarra, Sandra Iveth; Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Urquidi-Rivera, Martha; Rodriguez-Esquivel, Zulma; Garza-Gonzalez, Elvira
2007 Dec;49(6):869-874, Pediatrics International
BACKGROUND: The presence of Helicobacter pylori in pediatric population has been associated with recurrent abdominal pain (RAP), although this association is unclear. One of the major problems in studying the role of H. pylori in RAP is that methods used to detect the bacteria in children have poor sensitivity and specificity. The aims of the present study were to determine the prevalence of H. pylori in pediatric patients with RAP in northeastern Mexico and to assess the diagnostic utility of invasive tests and serology in this population. METHODS: A total of 40 patients (mean age, 7.9 years; range 2-16 years; F: M, 0.81), who underwent an endoscopy procedure for RAP, were studied. The presence of H. pylori was assessed using invasive diagnostic tests (culture, rapid urease test, polymerase chain reaction and histology) and one non-invasive test: determination of IgG antibodies. The prevalence of H. pylori in the present group and the diagnostic utility for each test were evaluated. RESULTS: The prevalence of H. pylori in the present pediatric group with RAP was 12.5-42.5% depending on the criteria of positivity used. The non-invasive methods (serology) had acceptable values in sensitivity and specificity in comparison with invasive tests. CONCLUSIONS: This is the first report on prevalence of H. pylori in pediatric patients with RAP from the northeastern region of Mexico. The prevalence of H. pylori was low compared with the adult population in the same geographic region. Serology had the best diagnostic utility
— id: 79189, year: 2007, vol: 49, page: 869, stat: Journal Article,

Analysis of genetic diversity associated with ethnicity in Helicobacter pylori strains isolated in Montevideo, Uruguay
Perez Perez, GI; Torres, E; Raisler, K; Olivares, AZ; Reynolds, SP; Gonzalez, N; Fernandez, L; Cohen, H
2007 JAN ;54(1):112-112, Zoonoses & public health
— id: 87170, year: 2007, vol: 54, page: 112, stat: Journal Article,

Isolation and characterisation of Helicobacter pylori in dyspeptic patients for Izmir, Turkey
Perez, GIP; Olivares, AZ; Yilmaz, O
2007 JAN ;54(1):111-111, Zoonoses & public health
— id: 87169, year: 2007, vol: 54, page: 111, stat: Journal Article,

[Development of a protocol of pyrosequencing for determination of the polymorphism at position -31 of the interleukin-1beta gene in the study of risk of development of stomach cancer]
Perez-Perez, Guillermo Ignacio; Portal-Celhay, Cynthia; Bosques-Padilla, Francisco Javier; Garza-Gonzalez, Elvira
2007 Jan-Mar;72(1):10-14, Revista de gastroenterologia de Mexico
BACKGROUND: Single nucleotide polymorphism association studies among cases and controls have been widely used for genetic analysis. The pyrosequencing method is based on indirect luminometric quantification of the pyrophosphate that is released as a result of nucleotide incorporation onto an amplified template. It has the advantages of accuracy, flexibility, automatization and speed when compared with PCR-RFLP method. AIM: To develop a protocol for allele frequency determination using pyrosequencing technology in the detection of the polymorphism at position -31 of the interleukin-1beta (IL-1beta) gene. METHODS: 162 patients (F/M = 0.93) who were enrolled at the Hospital Universitario Dr 'Jose Eleuterio Gonzalez' were studied. 123 patients had non-ulcer dyspepsia and 39 had histologically confirmed gastric cancer (GC). The polymorphism of IL-1beta -31 was determined by both RFLP and pyrosequencing methods. PCR-RFLP method used Alul restriction endonuclease. The same specific primers for PCR-RFLP and pyrosequencing were used for initial amplification and an additional biotinylated specific primer was designed for sequencing. RESULTS: 157 (96.9%) samples were clearly typed by the pyrosequencing method and the results were in accordance with the results of the PCR-RFLP method. The results of 5 samples (3.1%) were not in accordance between both methods. Two of them were T/T and 2 were C/T by sequencing method and all four were C/C by RFLP. Another sample was C/ C by sequencing and T/T by RFLP. CONCLUSION: The pyrosequencing method is not only suitable for the IL-1beta -31 genotyping but is a fast and unexpensive way of genotyping since requires smaller amounts of DNA, and required significantly less time in the generation of results than the RFLP technique. The protocol developed is useful for the typing of the IL-1beta -31 polymorphism
— id: 73954, year: 2007, vol: 72, page: 10, stat: Journal Article,

Correlation between gastric cancer markers and prevalence of Helicobacter pylori CagA in different populations of eastern Siberia
Tsukanov, VV; Butorin, NN; Maady, AS; Barkalov, SV; Amelchugova, OS; Perez-Perez, GI
2007 AUG ;12(4):453-453, Helicobacter
— id: 74189, year: 2007, vol: 12, page: 453, stat: Journal Article,

Fasting gastric leptin levels are elevated in diabetics independent of BMI
Young, B; Roper, H; Mourad, M; Olivares de Perez, AZ; Perez-Perez, GI; Pei, ZH; Blaser, MJ; Francois, F
2007 SEP ;102(6):S163-S163, American journal of gastroenterology
— id: 74153, year: 2007, vol: 102, page: S163, stat: Journal Article,

Molecular analysis of the bacterial microbiota in the human stomach
Bik, Elisabeth M; Eckburg, Paul B; Gill, Steven R; Nelson, Karen E; Purdom, Elizabeth A; Francois, Fritz; Perez-Perez, Guillermo; Blaser, Martin J; Relman, David A
2006 Jan 17;103(3):732-737, Proceedings of the National Academy of Sciences of the United States of America
The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease
— id: 62128, year: 2006, vol: 103, page: 732, stat: Journal Article,

Follow-up care after a diagnosis of Helicobacter pylori infection in an Asian immigrant cohort
Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David L; Marcus, Stuart G; Gany, Francesca M
2006 Jan;40(1):29-32, Journal of clinical gastroenterology
GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a 'regular doctor' was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a 'regular doctor' appeared to increase the likelihood of receiving appropriate follow-up care
— id: 61482, year: 2006, vol: 40, page: 29, stat: Journal Article,

Acceptance of repeat esophagogastroduodenoscopy to detect gastric cancer in a chinese immigrant cohort
Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David; Marcus, Stuart G; Gany, Francesca M
2006 Aug;40(7):606-611, Journal of clinical gastroenterology
GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer 'nearly always' in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes
— id: 68529, year: 2006, vol: 40, page: 606, stat: Journal Article,

Factors associated with H. pylori epidemiology in symptomatic children in Buenos Aires, Argentina
Goldman, Cinthia; Barrado, Andres; Janjetic, Mariana; Balcarce, Norma; Cueto Rua, Eduardo; Oshiro, Masaru; Calcagno, Maria L; Sarrasague, Margarita-Martinez; Fuda, Julian; Weill, Ricardo; Zubillaga, Marcela; Perez-Perez, Guillermo I; Boccio, Jose
2006 Sep 7;12(33):5384-5388, World journal of gastroenterology : WJG
AIM: To determine prevalence of H pylori infection in symptomatic children in Buenos Aires, Argentina, and to investigate factors associated with H pylori positivity. METHODS: A total of 395 children with upper gastrointestinal symptoms referred to the Gastroenterology Unit of the Children Hospital 'Sor Maria Ludovica' were evaluated for the presence of H pylori by the (13)C-Urea Breath Test ((13)C-UBT). A questionnaire was applied to the recruited population. RESULTS: Prevalence of H pylori infection was 40.0% in this population (mean age 9.97 +/- 3.1 years). The factors associated with H pylori positivity were number of siblings (P < 0.001), presence of pet cats (P = 0.03) and birds (P = 0.04) in the household, and antecedents of gastritis among family members (P = 0.01). After multivariate analysis, number of siblings [Odds ratio (OR) = 1.39; 95% CI, 1.20-1.61] and contact with pet cats (OR = 1.76; 95% CI, 1.00-3.09) remained as variables associated with H pylori infection. CONCLUSION: The prevalence of H pylori infection in children with upper gastrointestinal symptoms in Argentina was similar to that reported in developed countries. Children from families with a higher crowding index and presence of pet cats have a higher risk of being colonized with H pylori
— id: 79195, year: 2006, vol: 12, page: 5384, stat: Journal Article,

Guillain-Barre syndrome: association with Campylobacter jejuni and Mycoplasma pneumoniae infections in India
Gorthi, S P; Kapoor, Lata; Chaudhry, Rama; Sharma, Nidhi; Perez-Perez, Guillermo I; Panigrahi, Pinaki; Behari, Madhuri
2006 May-Jun;19(3):137-139, National medical journal of India
BACKGROUND: Guillain-Barre syndrome is the most common cause of acute neuromuscular paralysis and is considered a post-infectious disease. METHODS: Twenty patients with Guillain-Barre syndrome admitted to the Neurosciences Centre at the All India Institute of Medical Sciences from November 1997 to August 1998 were investigated for evidence of antecedent infections. This case-control study included 2 controls for each patient, one a household control and the other an age- and sex-matched hospital control suffering from a neurological illness other than Guillain-Barre syndrome. Evidence of recent Campylobacter jejuni infection was investigated by culture and serology, and for Mycoplasma pneumoniae by serology. RESULTS: There was evidence of recent C. jejuni infection in 35% of the patients compared with 25% of household controls and none of the hospital controls. M. pneumoniae infection was seen in 50% of patients compared with 25% of household controls and 15% of hospital controls. About one-third of the patients (30%) had evidence of both infections. The association of both infections in patients was found to be statistically significant as compared to hospital controls. CONCLUSION: C. jejuni and M. pneumoniae may be important antecedent illnesses in patients with Guillain-Barre syndrome in India
— id: 79196, year: 2006, vol: 19, page: 137, stat: Journal Article,

Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity
Kamangar, Farin; Dawsey, Sanford M; Blaser, Martin J; Perez-Perez, Guillermo I; Pietinen, Pirjo; Newschaffer, Craig J; Abnet, Christian C; Albanes, Demetrius; Virtamo, Jarmo; Taylor, Philip R
2006 Oct 18;98(20):1445-1452, Journal of the National Cancer Institute
BACKGROUND: Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions. METHODS: Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. RESULTS: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively. CONCLUSION: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries
— id: 79194, year: 2006, vol: 98, page: 1445, stat: Journal Article,

Association of Helicobacter pylori and chronic idiopathic urticaria
Marcano-Lozada, MJ; Urrestarazu, MI; Serrano, NM; Perez-Perez, GI
2006 AUG ;11(4):369-369, Helicobacter
— id: 68674, year: 2006, vol: 11, page: 369, stat: Journal Article,

In vivo and in vitro expression of the TLR-4 and TLR-5 receptors during Helicobacter pylori infection
Moreno-Gutierrez, FJ; Garza-Gonzalez, E; Bosques-Padilla, FJ; Perez-Perez, GI
2006 AUG ;11(4):349-349, Helicobacter
— id: 68673, year: 2006, vol: 11, page: 349, stat: Journal Article,

Prevalence of Helicobacter pylori in Georgian patients with dyspepsia
Olivares, Asalia; Buadze, Merab; Kutubidze, Tina; Lobjanidze, Manana; Labauri, Levani; Kutubidze, Ramaz; Chikviladze, Daredjan; Zhvania, Manana; Kharzeishvili, Omar; Lomidze, Nodar; Perez-Perez, Guillermo I
2006 Apr;11(2):81-85, Helicobacter
BACKGROUND: Georgia has showed a high prevalence of peptic ulcer disease (PUD), but the prevalence of Helicobacter pylori in this country is practically unknown. The purpose of this study was to determine the prevalence of H. pylori and specific genotypes in different populations in Georgia. MATERIALS AND METHODS: We studied 62 patients from several hospitals in Tbilisi, Georgia. More than 55% of patients had PUD. We determined H. pylori presence as well as specific genotypes cagA and vacA by polymerase chain reaction. In addition, we studied serum samples from 94 healthy persons to determine H. pylori and CagA prevalence by ELISA. RESULTS: We found a high prevalence of H. pylori and CagA in the healthy population (70.2 and 57.4%, respectively) and a high prevalence of CagA among the H. pylori-positive persons (71.2%). Prevalence increased with age as reported in other countries (p = .05). Among symptomatic persons, we found nearly the same high prevalence of H. pylori (64.5%) as in the asymptomatic population. Furthermore, in symptomatic H. pylori patients, we found 65.0 and 67.5% prevalence of cagA and vacA, respectively. For 33 patients with PUD, 24 patients (72.7%) were H. pylori positive and 66.7% of them were cagA positive. In contrast, among the patients with non-ulcer dyspepsia (NUD), 16 (55.2%) were H. pylori positive and 62.5% of them were colonized with cagA-positive strains. H. pylori and cagA prevalence were not significantly different between PUD and patients with NUD. CONCLUSIONS: We confirmed that among individuals in Georgia, the prevalence of H. pylori is high and cagA-positive strains were equally present among H. pylori-positive patients with PUD and NUD and asymptomatic persons
— id: 64075, year: 2006, vol: 11, page: 81, stat: Journal Article,

Specific geographic genotypes among Helicobacter pylori strains
Perez-Perez, GI; Andersson, M; Olivares, AZ; Gonzalez, EG; Padilla, FB; Torres, J; Blaser, MJ
2006 AUG ;11(4):342-342, Helicobacter
— id: 68671, year: 2006, vol: 11, page: 342, stat: Journal Article,

Differences in the 3 ' cagA region between Helicobacter pylori strains of East Asian and African origin
Perez-Perez, GI; Chao, L; Minhong, C; Andersson, M; Olivares, AZ
2006 AUG ;11(4):343-344, Helicobacter
— id: 68672, year: 2006, vol: 11, page: 343, stat: Journal Article,

Stability and variability of cagA and its correlation with disease outcome
Perez-Perez, GI; Wong, C; Olivares, AZ; Gonzalez, EG; Padilla, FB; Blaser, MJ
2006 AUG ;11(4):333-333, Helicobacter
— id: 68670, year: 2006, vol: 11, page: 333, stat: Journal Article,

Gastroenteritis and transmission of Helicobacter pylori infection in households
Perry, Sharon; de la Luz Sanchez, Maria; Yang, Shufang; Haggerty, Thomas D; Hurst, Philip; Perez-Perez, Guillermo; Parsonnet, Julie
2006 Nov;12(11):1701-1708, Emerging infectious diseases
The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection
— id: 79192, year: 2006, vol: 12, page: 1701, stat: Journal Article,

Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes
Portal-Celhay, Cynthia; Perez-Perez, Guillermo I
2006 Mar;110(3):305-314, Clinical science (London, 1979)
Helicobacter pylori colonizes the stomachs of half of the world's population and usually persists in the gastric mucosa of human hosts for decades or life. Although most H. pylori-positive people are asymptomatic, the presence of H. pylori is associated with increased risk for the development of peptic ulcer disease, gastric adenocarcinoma and gastric lymphoma. The development of a sustained gastric inflammatory and immune response to infection appears to be pivotal for the development of disease. During its long co-existence with humans, H. pylori has evolved complex strategies to maintain a mild inflammation of the gastric epithelium while limiting the extent of immune effector activity. In this review, the nature of the host immune response to H. pylori infection and the mechanism employed by the bacterium to evade them is considered. Understanding the mechanisms of colonization, persistence and virulence factors of the bacterium as well as the innate and adaptive immune responses of the host are critically important for the development of new strategies to prevent the development of H. pylori-induced gastroduodenal disease
— id: 64076, year: 2006, vol: 110, page: 305, stat: Journal Article,

Helicobacter pylori infection diagnosis in gastroduodenal disease in La Habana, Cuba
Vidal, T; Gutierrez, B; Valmana, CE; Ochoa, R; Megraud, F; Perez-Perez, GI; Paniagua, M; Mendz, GL
2006 AUG ;11(4):384-385, Helicobacter
— id: 68675, year: 2006, vol: 11, page: 384, stat: Journal Article,

Diagnostic utility of invasive tests and serology for the diagnosis of Helicobacter pylori infection in different clinical presentations
Zuniga-Noriega, Jaime Raul; Bosques-Padilla, Francisco Javier; Perez-Perez, Guillermo Ignacio; Tijerina-Menchaca, Rolando; Flores-Gutierrez, Juan Pablo; Maldonado Garza, Hector Jesus; Garza-Gonzalez, Elvira
2006 Jan;37(1):123-128, Archives of medical research (Mexico)
BACKGROUND: Invasive and noninvasive tests are used for the diagnosis of Helicobacter pylori infection. The aim of this study was to determine the diagnostic utility of rapid urease test (RUT), culture, histology and serology for the diagnosis of H. pylori in patients with different clinical presentations. METHODS: We studied 527 consecutive patients (mean age, 52.5 years; F:M, 1.3; age range 15-89 years) enrolled at the Hospital Universitario, Universidad Autonoma de Nuevo Leon. Patients had gastric cancer (GC, 9.1%), non-ulcer dyspepsia (NUD, 81.4%), or peptic ulcer disease (PUD, 9.1%). The infection by H. pylori was determined by histology, rapid urease test, culture, and serology. Patients were determined as infected with H. pylori if at least a) two invasive tests were positive and b) two tests were positive (invasive or non-invasive). Diagnostic utility was calculated for each assay. RESULTS: Prevalence of infection in the whole studied population was 50.9%. In NUD patients the prevalence was 51.3%, in PUD patients 58.3%, and in GC patients 39.6%. When we used the first diagnostic criteria, for the whole studied population, the RUT was the most reliable test, followed by the culture. Histology had the best sensitivity for the whole studied population and NUD patients and RUT had the best sensitivity value for the GC patients. In the whole studied population, NUD and GC patients, RUT and culture had the best specificity, accuracy and PPV. For PUD patients, serology had the best performance. When we used the second diagnostic criteria, histology and serology had a better performance compared with the results obtained with the first diagnostic criteria. CONCLUSIONS: Diagnostic utility of the tests varies according to the clinical presentations, which should be considered in the selection of the diagnostic test for the detection of H. pylori
— id: 64078, year: 2006, vol: 37, page: 123, stat: Journal Article,

Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica
Alpizar-Alpizar, W; Perez-Perez, G I; Une, C; Cuenca, P; Sierra, R
2005 Dec;5(4):169-176, Clinical & experimental medicine
Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed
— id: 64077, year: 2005, vol: 5, page: 169, stat: Journal Article,

Local and systemic immune and inflammatory responses to Helicobacter pylori strains
Bhat, Niranjan; Gaensbauer, James; Peek, Richard M; Bloch, Karen; Tham, Kyi-Toe; Blaser, Martin J; Perez-Perez, Guillermo
2005 Dec;12(12):1393-1400, Clinical & diagnostic laboratory immunology
Colonization with Helicobacter pylori eventuates in varied clinical outcomes, which relate to both bacterial and host factors. Here we examine the relationships between cagA status, serum and gastric juice antibody responses, and gastric inflammation in dyspeptic patients. Serum, gastric juice, and gastric biopsy specimens were obtained from 89 patients undergoing endoscopy. H. pylori colonization and cagA status were determined by histology, culture, and PCR methods, and acute inflammation and chronic inflammation in the gastric mucosa were scored by a single pathologist. Serum and gastric juice antibodies to H. pylori whole-cell and CagA antigens were determined by enzyme-linked immunosorbent assay. Relationships between variables were sequentially analyzed using univariate and multivariate statistical methods. Of the 89 subjects, 62 were colonized by H. pylori. By univariate analyses, levels of serum immunoglobulin G (IgG) and IgA and gastric juice IgA antibodies against whole-cell and CagA antigens each were significantly higher in the H. pylori-positive group than in the H. pylori-negative group (P<0.001). H. pylori and CagA sero-positivities were both significantly associated with enhanced inflammation in gastric antrum and body (P<0.02). The presence of gastric juice antibodies to H. pylori antigens was associated with more severe gastric inflammation. However, in multivariate analyses, only the presence of serum antibodies against CagA and, to a lesser extent, whole-cell antigens remained significantly associated with acute and chronic inflammation in antrum and body (P<0.05). Thus, serum antibody response to CagA correlates with severity of gastric inflammation. Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response
— id: 79197, year: 2005, vol: 12, page: 1393, stat: Journal Article,

Preliminary report of the prevalence of Helicobacter pylori and distribution of vacA genotypes in Montevideo, Uruguay
Cooperberg BA; Bini EJ; Cohen H; Olivares AZ; Dacoll C; Perez-Perez GI
2005 ;62(7):290-294, Revista Brasileira de Medicina
Background: Little is known about the prevalence of Helicobacter pylori and the presence of specific genotypes in Uruguay. Aims: To determine the prevalence of H. pylori in symptomatic individuals in Uruguay, to assess the prevalence of bacterial genotypes, and evaluate the association between specific genotypes and endoscopic findings. Patients: 32 patients presenting to the Hospital de Clinicas in Montevideo for upper endoscopy were enrolled. Methods: H. pylori status was determined by rapid urease test and by culture of gastric biopsy specimens from the antrum and body. H. pylori vacA genotypes were determined by PCR. Results: The prevalence of H. pylori was 66% based on culture and rapid urease test. Analysis of the vacA gene by PCR, we found a high proportion of multiple infections (42.9%). The s1a allele was found in 47.6% of patients and s1b was found in 33.3%. We could not demonstrate a significant association between infection with H. pylori, nor specific bacterial genotypes, and endoscopic findings. Conclusions: The prevalence of H. pylori in symptomatic patients in Montevideo is lower than typically found in developing countries probably as result of the low sensitivity of the two invasive tests used. The vacA genotypes of H. pylori found in Uruguay differs from the rest of Latin America with 47.6% bearing the s1a vacA allele. These results confirmed that European descendents different from Spain and Portugal are important part of the Uruguayan population. copyright Copyright Moreira Jr. Editora. Todos os direitos reservados
— id: 57965, year: 2005, vol: 62, page: 290, stat: Journal Article,

Activation of beta-catenin by carcinogenic Helicobacter pylori
Franco, Aime T; Israel, Dawn A; Washington, Mary K; Krishna, Uma; Fox, James G; Rogers, Arlin B; Neish, Andrew S; Collier-Hyams, Lauren; Perez-Perez, Guillermo I; Hatakeyama, Masanori; Whitehead, Robert; Gaus, Kristin; O'Brien, Daniel P; Romero-Gallo, Judith; Peek, Richard M Jr
2005 Jul 26;102(30):10646-10651, Proceedings of the National Academy of Sciences of the United States of America
Persistent gastritis induced by Helicobacter pylori is the strongest known risk factor for adenocarcinoma of the distal stomach, yet only a fraction of colonized persons ever develop gastric cancer. The H. pylori cytotoxin-associated gene (cag) pathogenicity island encodes a type IV secretion system that delivers the bacterial effector CagA into host cells after bacterial attachment, and cag+ strains augment gastric cancer risk. A host effector that is aberrantly activated in gastric cancer precursor lesions is beta-catenin, and activation of beta-catenin leads to targeted transcriptional up-regulation of genes implicated in carcinogenesis. We report that in vivo adaptation endowed an H. pylori strain with the ability to rapidly and reproducibly induce gastric dysplasia and adenocarcinoma in a rodent model of gastritis. Compared with its parental noncarcinogenic isolate, the oncogenic H. pylori strain selectively activates beta-catenin in model gastric epithelia, which is dependent on translocation of CagA into host epithelial cells. Beta-catenin nuclear accumulation is increased in gastric epithelium harvested from gerbils infected with the H. pylori carcinogenic strain as well as from persons carrying cag+ vs. cag- strains or uninfected persons. These results indicate that H. pylori-induced dysregulation of beta-catenin-dependent pathways may explain in part the augmentation in the risk of gastric cancer conferred by this pathogen
— id: 64079, year: 2005, vol: 102, page: 10646, stat: Journal Article,

Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico
Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco Javier; El-Omar, Emad; Hold, Georgina; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector Jesus; Perez-Perez, Guillermo Ignacio
2005 Mar 20;114(2):237-241, International journal of cancer
Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL-1B-31, IL-1RN and TNF-A-308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon. The subjects were divided into 2 groups. Sixty-three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22-84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18-92, F:M = 1.17). The IL-1B-31 and the TNF-A-308 polymorphisms were determined by PCR-RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L-1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non-cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL-1B-31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73-46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8-50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05-161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL-1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC
— id: 79200, year: 2005, vol: 114, page: 237, stat: Journal Article,

High Frequency of Gastric Colonization with Multiple Helicobacter pylori Strains in Venezuelan Subjects
Ghose, C; Perez-Perez, G I; van Doorn, L J; Dominguez-Bello, M G; Blaser, M J
2005 Jun;43(6):2635-2641, Journal of clinical microbiology
Multiple Helicobacter pylori strains may colonize an individual host. Using enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we analyzed the prevalence of mixed H. pylori colonization in 127 subjects from Venezuela, a country of high H. pylori prevalence, from three regions representing different population groups: the Andes (Merida), where Caucasian mestizos predominate, a major city near the coast (Caracas), where Amerindian-Caucasian-African mestizos predominate, and an Amazonian community (Puerto Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA-positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%) and m (mean, 26%) regions. In total, 55% of the individuals had genotypic evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian) origin, was present in all three populations, especially from Puerto Ayacucho (86%). These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested
— id: 55866, year: 2005, vol: 43, page: 2635, stat: Journal Article,

Guillain-Barre syndrome: association with Campylobacter jejuni and Mycoplasma pneumoniae infections in India
Gorthi, SP; Kapoor, L; Chaudhry, R; Sharma, N; Perez-Perez, GI; Panigrahi, P; Behari, M
2005 NOV 15 ;238(4):S186-S187, Journal of the neurological sciences
— id: 98078, year: 2005, vol: 238, page: S186, stat: Journal Article,

Significance of transiently positive enzyme-linked immunosorbent assay results in detection of Helicobacter pylori in stool samples from children
Haggerty, Thomas D; Perry, Sharon; Sanchez, Luz; Perez-Perez, Guillermo; Parsonnet, Julie
2005 May;43(5):2220-2223, Journal of clinical microbiology
In young children, the significance of stool samples transiently positive for Helicobacter pylori antigen is unknown. As part of a larger prospective study on enteric infections, stool samples were obtained from 323 children at two time points 3 months apart and tested for H. pylori antigen using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from positive to negative (transient positives), all 4 persistent antigen-positive pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter species were amplified from the first stool samples of 15/26 (58%) of the transient positives and 1 (25%) of 4 persistent positives. No Helicobacter species were amplified from the 10 persistent negatives. Among the 15 amplicons from transient-positive stool, H. pylori was sequenced and identified from 12 (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99-5504). Four of the 15 remained positive by PCR for the second (antigen-negative) stool sample, including all 3 initially identified as non-H. pylori. Helicobacter bilis was amplified from the second sample of a persistent positive. Two of eight transient positives from whom serum was available had accompanying transient elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H. pylori are common and represent H. pylori in the majority of cases where sequences can be obtained. A not-insignificant percentage of antigen-positive stools, however, may represent other Helicobacter species
— id: 79199, year: 2005, vol: 43, page: 2220, stat: Journal Article,

Relevance of adjusted cut-off values in commercial serological immunoassays for Helicobacter pylori infection in children
Harris, Paul; Perez-Perez, Guillermo; Zylberberg, Alejandro; Rollan, Antonio; Serrano, Carolina; Riera, Francisca; Einisman, Helly; Garcia, Daniela; Viviani, Paola
2005 Nov;50(11):2103-2109, Digestive diseases & sciences
We assessed the sensitivity and specificity of H. pylori IgG and IgA with a commercial immunoassay performed in Chile and a second non-commercial immunoassay performed in a reference laboratory in the United States, in serum of 80 children and adults referred for gastrointestinal endoscopies in a developing country. Overall, 56% of the patients were infected with H. pylori based on rapid urease test and staining techniques on gastric biopsies. When Receiver Operator Curves (ROC) were developed, the sensitivity and specificity were similar for IgG and IgA. Both immunoassays exhibited better specificity, positive and negative predictive value (NPV) in children than in adults when cut-off values were corrected according to the local population than when they were assessed using the cut-off values pre-defined in other populations. These results underline the need to establish more precise cut-off values corrected in the local populations where assessments of antibodies as diagnostic markers of H. pylori infection are planning
— id: 79198, year: 2005, vol: 50, page: 2103, stat: Journal Article,

Helicobacter pylori, pepsinogen, and gastric adenocarcinoma in Hawaii
Nomura, Abraham M Y; Kolonel, Laurence N; Miki, Kazumasa; Stemmermann, Grant N; Wilkens, Lynne R; Goodman, Marc T; Perez-Perez, Guillermo I; Blaser, Martin J
2005 Jun 15;191(12):2075-2081, Journal of infectious diseases
BACKGROUND: The objective was to investigate the association of Helicobacter pylori and serum pepsinogen (PG) levels with gastric adenocarcinoma. METHODS: Serum obtained from 299 patients at the time of cancer diagnosis and from 336 population-based control subjects was tested for PG I, PG II, and antibodies to H. pylori and to CagA. RESULTS: Subjects with low PG I levels or low PG I/II ratios were at increased risk for cardia and noncardia gastric cancer, whereas those with H. pylori or CagA seropositivity had an elevated risk for noncardia cancer only. Subjects seropositive for either H. pylori or CagA who had low PG I levels had the highest odds ratio (OR) (9.21 [95% confidence interval {CI}, 4.95-17.13]) for noncardia cancer, compared with subjects with neither factor. Elevated risks were also found among subjects with only 1 factor (OR, 5.40 [95% CI, 2.61-11.20] for low PG I level only; OR, 4.86 [95% CI, 5.90-8.13] for H. pylori or CagA seropositivity only). This pattern persisted when PG I/II ratio replaced PG I level and when CagA seropositivity alone replaced H. pylori immunoglobulin G or CagA seropositivity. CONCLUSIONS: The results suggest that persons with both H. pylori or CagA seropositivity and a low PG I level or PG I/II ratio are highly susceptible to development of noncardia gastric cancer
— id: 64080, year: 2005, vol: 191, page: 2075, stat: Journal Article,

[New era of Helicobacter pylori]
Perez Perez, Guillermo I
2005 Nov;70 Suppl 3:31-32, Revista de gastroenterologia de Mexico
— id: 79190, year: 2005, vol: 70 Suppl 3, page: 31, stat: Journal Article,

[When and why should we eradicate the Helicobacter pylori?]
Perez Perez, Guillermo I
2005 Nov;70 Suppl 3:26-27, Revista de gastroenterologia de Mexico
— id: 79191, year: 2005, vol: 70 Suppl 3, page: 26, stat: Journal Article,

Role of p53 codon 72 polymorphism in the risk of development of distal gastric cancer
Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Crosatti, Maria Luisa; Tijerina-Menchaca, Rolando; Garza-Gonzalez, Elvira
2005 Jan;40(1):56-60, Scandinavian journal of gastroenterology
OBJECTIVE: Mutations in the codon 72 of exon 4 in the p53 gene have been associated with higher risk in the development of several types of cancer. This polymorphism occurs with two alleles encoding either arginine (CGC) or proline (CCC). The aim of this study was to assess the role of the codon 72 polymorphism of p53 in the risk for the development of distal gastric cancer (GC) in a Mexican population. MATERIAL AND METHODS: We studied 247 patients who were enrolled at the Servicio de Gastroenterologia, Hospital Universitario 'Dr. Jose Eleuterio Gonzalez' Universidad Autonoma de Nuevo Leon. The study group included 65 distal GC cases [mean age, 58.2 (22-84), median = 60, F:M = 0.6] and 182 patients without evidence of GC [mean age 53.9 (18-89), median = 53, F:M = 1.07) as the control group. The polymorphism in the codon 72 of the p53 gene was determined by PCR-RFLP in all the patients. RESULTS: As expected, the majority of GC patients were old male. We found a previously unknown association of the Arg/Arg genotype and distal GC (OR: 1.96, 95% confidence interval [CI] = 1.06-3.61, p =0.03). Because of age and gender differences, cases and controls were matched in those two variables and the association of Arg/Arg genotype with distal GC persisted (OR: 2.29, 95% CI = 1.22-4.32, p = 0.01). When cases and controls were matched by age, gender, H. pylori positivity and excluding patients with atrophic gastritis and/or intestinal metaplasia (n=97) the association was stronger (OR = 2.37, 95% CI = 1.18-4.77, p = 0.01). CONCLUSIONS: The results of this study suggest that the carriage of the Arg/Arg genotype could be associated with the development of distal GC in this Mexican population
— id: 54111, year: 2005, vol: 40, page: 56, stat: Journal Article,

Seroprevalence of Helicobacter pylori in New York City populations originating in East Asia
Perez-Perez, Guillermo Ignacio; Olivares, Asalia Zuni; Foo, F Yeong; Foo, Sun; Neusy, Andre J; Ng, Christopher; Holzman, Robert S; Marmor, Michael; Blaser, Martin J
2005 Sep;82(3):510-516, Journal of urban health
Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2+/-14.7 years), the mean period of residence in the United States was 11.9+/-7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR) =2.3, 95% confidence interval (95% CI) =1.05-5.0] and inverse associations with period in the United States (OR per year of residency in the United States =0.95, 95% CI =0.91-0.99) and with a history of dyspepsia (OR for a history of stomach pain =0.52, 95% CI =0.3-1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.
— id: 58190, year: 2005, vol: 82, page: 510, stat: Journal Article,

Functional Adaptation of BabA, the H. pylori ABO Blood Group Antigen Binding Adhesin
Aspholm-Hurtig, Marina; Dailide, Giedrius; Lahmann, Martina; Kalia, Awdhesh; Ilver, Dag; Roche, Niamh; Vikstrom, Susanne; Sjostrom, Rolf; Linden, Sara; Backstrom, Anna; Lundberg, Carina; Arnqvist, Anna; Mahdavi, Jafar; Nilsson, Ulf J; Velapatino, Billie; Gilman, Robert H; Gerhard, Markus; Alarcon, Teresa; Lopez-Brea, Manuel; Nakazawa, Teruko; Fox, James G; Correa, Pelayo; Dominguez-Bello, Maria Gloria; Perez-Perez, Guillermo I; Blaser, Martin J; Normark, Staffan; Carlstedt, Ingemar; Oscarson, Stefan; Teneberg, Susann; Berg, Douglas E; Boren, Thomas
2004 Jul 23;305(5683):519-522, Science
Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations
— id: 43533, year: 2004, vol: 305, page: 519, stat: Journal Article,

Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States
Duck, William M; Sobel, Jeremy; Pruckler, Janet M; Song, Qunsheng; Swerdlow, David; Friedman, Cindy; Sulka, Alana; Swaminathan, Balasubra; Taylor, Tom; Hoekstra, Mike; Griffin, Patricia; Smoot, Duane; Peek, Rick; Metz, David C; Bloom, Peter B; Goldschmidt, Steven; Parsonnet, Julie; Triadafilopoulos, George; Perez-Perez, Guillermo I; Vakil, Nimish; Ernst, Peter; Czinn, Steve; Dunne, Donald; Gold, Ben D
2004 Jun;10(6):1088-1094, Emerging infectious diseases
Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice
— id: 44762, year: 2004, vol: 10, page: 1088, stat: Journal Article,

Age-Specific Immune Response to HspA in Helicobacter pylori-Positive Persons in Mexico
Eamranond, Peter P; Torres, Javier; Munoz, Onofre; Perez-Perez, Guillermo I
2004 Sep;11(5):983-985, Clinical & diagnostic laboratory immunology
The immune response to heat shock protein A (HspA) in Helicobacter pylori-positive adults increases with age in developed countries. This response has not been studied with children or in developing countries (G. I. Perez-Perez, J. M. Thiberge, A. Labigne, and M. J. Blaser, J. Infect. Dis. 174:1046-1050, 1996). As determined by using a specific enzyme-linked immunosorbent assay, HspA seropositivity among 592 individuals in Mexico was <10% in children and increased to >40% in adults
— id: 44760, year: 2004, vol: 11, page: 983, stat: Journal Article,

A three-component clinical model to predict reflux-related histopathology
Francois, F; Bini, EJ; Perez-Perez, GI; Yee, HT; Blaser, MJ
2004 ;126(4):A324-A324, Gastroenterology
— id: 108227, year: 2004, vol: 126, page: A324, stat: Journal Article,

Characterisation of Helicobacter pylori isolates from the north-eastern region of Mexico
Garza-Gonzalez, E; Bosques-Padilla, F J; Tijerina-Menchaca, R; Perez-Perez, G I
2004 Jan;10(1):41-45, Clinical microbiology & infection
The vacA and cagA genotypes of 50 Helicobacter pylori isolates from patients in the north-eastern region of Mexico were characterised by PCR, and the correlation between genotypes and different clinical outcomes was investigated. Strains of H. pylori that are vacA s1/m1 and cagA positive have previously been associated with more severe clinical outcomes, and some studies have shown differences in the vacA and cagA genotypes in different geographical regions. The six possible combinations of the vacA signal (s) and middle (m) regions were identified in this population, and the most frequent genotype was s2/m2. Thirty-two (64%) isolates were identified as cagA-positive. The s region was not amplified from seven of the cagA-positive isolates, and the m region was not amplified from one cagA-negative isolate, indicating that additional subfamilies of s and m genotypes may exist. The s1/m1 genotype was associated with cagA-positive strains (p < 0.05). No association was found between the vacA and cagA genotypes and clinical outcomes
— id: 44765, year: 2004, vol: 10, page: 41, stat: Journal Article,

Bacteriostatic and bactericidal activity of rabeprazole against Helicobacter pylori
Garza-Gonzalez, E; Tijerina-Menchaca, R; Perez-Perez, G I; Bosques-Padilla, F J
2004 Dec;16(6):612-613, Journal of chemotherapy
— id: 64081, year: 2004, vol: 16, page: 612, stat: Journal Article,

Association of gastric cancer, HLA-DQA1, and infection with Helicobacter pylori CagA+ and VacA+ in a Mexican population
Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Perez-Perez, Guillermo I; Flores-Gutierrez, Juan Pablo; Tijerina-Menchaca, Rolando
2004 Dec;39(12):1138-1142, Journal of gastroenterology
BACKGROUND: The goal of this study was to determine the importance of Helicobacter pylori CagA+, VacA+, and HLA-DQA1 alleles in a Mexican population with gastric cancer (GC). METHODS: We studied a group of Mexican patients (cases) with distal GC (n=22) or high-grade dysplasia (HGD; n=8) (mean age, 62.7 years, F : M=0.3; age range, 33-84 years) and 77 ethnically matched non-GC controls (mean age, 47.1 years; F : M=1.96; age range, 17-92 years). Both cases and controls were H. pylori-positive by at least two of the following diagnostic tests: rapid urease test, histology, culture, or serology. The presence of antibodies to CagA and VacA proteins was determined by Western blot, and the HLA-DQA1 typing was carried out by a polymerase chain reaction (PCR) sequence-specific primer method. RESULTS: The carriage of H. pylori CagA+, VacA+ strains was associated with GC or HGD (odds ratio [OR], 6.07; 95% confidence interval [CI], 1.56-27.57; P=0.005). The allele frequency of DQA1*0503 was significantly lower in the GC-HGD group than in the non-GC group (OR, 0.13; 95% CI, 0.02-0.59). Logistic regression analysis identified the carriage of HLA-DQA1*0503 as an independent protective factor for GC (OR, 0.19; 95% CI, 0.04-0.94) and colonization with H. pylori CagA+, VacA+ strains as an independent risk factor for GC (OR, 6.15; 95% CI, 1.69-22.37). CONCLUSIONS: Infection with H. pylori CagA+, VacA+ strains represents a significant risk for the development of GC. The absence of HLA-DQA1*0503 could be a host risk factor for the development of GC in Mexican patients
— id: 64082, year: 2004, vol: 39, page: 1138, stat: Journal Article,

Epidemiology of Helicobacter pylori Infection
Perez-Perez, Guillermo I; Rothenbacher, Dietrich; Brenner, Hermann
2004 ;9 Suppl 1(5):1-6, Helicobacter
ABSTRACT This review summarizes key results of epidemiologic studies published in peer-reviewed journals between April 2003 and March 2004. The prevalence of H. pylori infection continues to vary strongly between developing countries and developed countries, and according to ethnicity, place of birth and socioeconomic factors among people living in the same country. Intrafamilial spread appears to play a central role in transmission of the infection in both developing and developed countries. The role of H. pylori infection in development of noncardia gastric cancer appears to be even much stronger than previously assumed, whereas the lack of an association with cardia cancer and an inverse association with adenocarcinoma of the esophagus could be confirmed. Suggestions for an inverse association of the infection with atopic diseases have recently received further support, whereas evidence concerning the role of the infection (or its eradication) in GERD and a large variety of other extragastric diseases, including cardiovascular disease, remains inconclusive
— id: 44761, year: 2004, vol: 9 Suppl 1, page: 1, stat: Journal Article,

Plasticity of repetitive DNA sequences within a bacterial (Type IV) secretion system component
Aras, Rahul A; Fischer, Wolfgang; Perez-Perez, Guillermo I; Crosatti, MariaLuisa; Ando, Takafumi; Haas, Rainer; Blaser, Martin J
2003 Nov 3;198(9):1349-1360, Journal of experimental medicine
DNA rearrangement permits bacteria to regulate gene content and expression. In Helicobacter pylori, cagY, which contains an extraordinary number of direct DNA repeats, encodes a surface-exposed subunit of a (type IV) bacterial secretory system. Examining potential DNA rearrangements involving the cagY repeats indicated that recombination events invariably yield in-frame open reading frames, producing alternatively expressed genes. In individual hosts, H. pylori cell populations include strains that produce CagY proteins that differ in size, due to the predicted in-frame deletions or duplications, and elicit minimal or no host antibody recognition. Using repetitive DNA, H. pylori rearrangements in a host-exposed subunit of a conserved bacterial secretion system may permit a novel form of antigenic evasion
— id: 42650, year: 2003, vol: 198, page: 1349, stat: Journal Article,

Diarrhea Incidence and Farm-Related Risk Factors for Escherichia coli O157:H7 and Campylobacter jejuni Antibodies among Rural Children
Belongia, Edward A; Chyou, Po-Huang; Greenlee, Robert T; Perez-Perez, Guillermo; Bibb, William F; DeVries, Edna O
2003 May 1;187(9):1460-1468, Journal of infectious diseases
Serum samples were obtained from 215 farm-resident children and 396 non-farm-resident children living in a defined rural Wisconsin population. Antibodies to Campylobacter jejuni and Escherichia coli O157:H7 lipopolysaccharide (O157 LPS) immunoglobulin G were measured, and the incidence of clinic visits for diarrheal illness was determined. Risk factors were assessed in a telephone interview. There were 363 children (59%) with C. jejuni antibodies (seropositive for >/=2 immunoglobulin classes) and 86 (14%) with O157 LPS antibodies. Increasing age and farm residence were independently associated with C. jejuni seropositivity by multivariate analysis. O157 LPS antibodies were independently associated with increasing age, female sex, manure contact, and sheep contact. The incidence of clinically recognized diarrhea was similar among children with and without antibodies to C. jejuni and O157 LPS, but the clinic visit rate for diarrhea was 46% lower among farm-resident children. These results are consistent with reduced occurrence of clinical illness from repeated antigenic stimulation in a farm environment
— id: 34616, year: 2003, vol: 187, page: 1460, stat: Journal Article,

Comparison of Helicobacter pylori Prevalence in Symptomatic Patients in Northeastern Mexico with the Rest of the Country. Its Association with Gastrointestinal Disease
Bosques-Padilla, Francisco Javier; Tijerina-Menchaca, Rolando; Perez-Perez, Guillermo Ignacio; Flores-Gutierrez, Juan Pablo; Garza-Gonzalez, Elvira
2003 Jan-Feb;34(1):60-63, Archives of medical research (Mexico)
Prevalence of Helicobacter pylori varies among different geographic regions. The aim of this study was to assess H. pylori prevalence in symptomatic patients in northeastern Mexico and its possible association of H. pylori with disease.We studied 261 symptomatic patients (female/male 1.44, mean age 53 years) who underwent gastrointestinal endoscopy at Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Nuevo Leon, Mexico. Among patients included in this study, 209 (80.1%) had nonulcer dyspepsia (NUD), 30 (11.5%) peptic ulcer disease (PUD), and 22 (8.4%) high-grade dysplasia or gastric cancer. H. pylori status was determined by histology, positive rapid urease test, culture, or IgG whole-cell anti-H. pylori. Specific IgG antibodies for CagA status were determined by ELISA as previously described. Patients were defined as infected with H. pylori by positive results of two or more diagnostic tests used.Overall prevalence of H. pylori was 67.8%. According to clinical presentation, gender (male) was related with gastric cancer (p <0.01) and with PUD (p <0.05). Of 177 patients infected with H. pylori, 90 (50.8%) were seropositive for CagA antigen; in addition, H. pylori CagA+ was more common in patients with PUD (77.8%) than with NUD (43.2%) (p <0.05). However, no association was found between gastric cancer patients and presence of CagA+ H. pylori strains.H. pylori prevalence in symptomatic patients in northeastern Mexico is as high as the prevalence reported for the entire country. We confirmed that patients with gastric cancer and PUD are more likely to be male. CagA+ strains were associated with patients who presented PUD but not gastric cancer
— id: 34619, year: 2003, vol: 34, page: 60, stat: Journal Article,

Traces of human migrations in Helicobacter pylori populations
Falush, Daniel; Wirth, Thierry; Linz, Bodo; Pritchard, Jonathan K; Stephens, Matthew; Kidd, Mark; Blaser, Martin J; Graham, David Y; Vacher, Sylvie; Perez-Perez, Guillermo I; Yamaoka, Yoshio; Megraud, Francis; Otto, Kristina; Reichard, Ulrike; Katzowitsch, Elena; Wang, Xiaoyan; Achtman, Mark; Suerbaum, Sebastian
2003 Mar 7;299(5612):1582-1585, Science
Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade
— id: 34570, year: 2003, vol: 299, page: 1582, stat: Journal Article,

Do GERD symptoms predict Helicobacter pylori colonization?
Francois, F; Bini, EJ; Perez-Perez, GI; Blaser, MJ
2003 ;124(4):A624-A624, Gastroenterology
— id: 108237, year: 2003, vol: 124, page: A624, stat: Journal Article,

Relationship of Helicobacter pylori and strain characteristics to esophageal pathology
Francois, F; Bini, EJ; Perez-Perez, GI; Yee, HT; Blaser, MJ
2003 ;124(4):A55-A55, Gastroenterology
— id: 108235, year: 2003, vol: 124, page: A55, stat: Journal Article,

Endoscopic training: Looking past the surface
Francois, F; Weinshel, EH; Perez-Perez, GI; Yee, HT; Blazer, MJ; Bini, EJ
2003 ;57(5):AB109-AB109, Gastrointestinal endoscopy
— id: 108236, year: 2003, vol: 57, page: AB109, stat: Journal Article,

Comparision of endoscopy-based and serum-based methods for the diagnosis of Helicobacter pylori
Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Tijerina-Menchaca, Rolando; Flores-Gutierrez, Juan P; Maldonado-Garza, Hector J; Perez-Perez, Guillermo I
2003 Feb;17(2):101-106, Canadian journal of gastroenterology
Available commercial tests for the diagnosis of Helicobacter pylori infection are based on different types of antigen preparations and hence the diagnostic utility differs substantially. OBJECTIVE: To assess the diagnostic value of the determination of Immunoglobulin (Ig) A and IgG antibodies to H pylori whole cell (WC) and IgG antibodies to cytotoxin associated gene A (CagA) using an in-house ELISA in relation to the results obtained with different invasive methods. METHODS: The study population consisted of 251 Mexican adults, mean age 53 years, age range 15 to 92 years and female to male ratio of 1.5. Peptic ulcer disease was present in 10.8% of these patients, 5.2% had gastric cancer, 11.2% had esophagitis and 72.9% had nonulcer dyspepsia. Biopsy specimens from the body and the antrum of the stomach were obtained for culture, histology and rapid urease test. ELISAs to detect IgA and IgG WC and CagA antibodies were performed using serum. RESULTS: H pylori status was established by the results of the invasive tests. Eighty (31.9%) patients positive to the three tests and 38 (15.1%) negative to all the tests were identified. Based on this result, the sensitivity and specificity of the serology assays were 97.5% and 78.9% for the IgG WC and 70% and 73.7% for the IgA WC, respectively. However, if H pylori status was defined by the positive result of at least one or two invasive diagnostic tests, the sensitivity for the IgG WC decreased to 87.3% and 66.7% respectively, but the specificity was essentially the same. Similar results were obtained for the sensitivity and specificity of IgA using the same criteria. A low CagA prevalence was observed (39%). CONCLUSIONS: Testing for serological IgG antibodies to H pylori WC was the best to assess whether infection by H pylori was present. Neither the IgA WC nor the IgG CagA ELISAs add significant value in the diagnosis of H pylori
— id: 34618, year: 2003, vol: 17, page: 101, stat: Journal Article,

[Role of polymorphism of certain cytokines in gastric cancer in Mexico. Preliminary results]
Garza-Gonzalez, Elvira; Hold, Georgina; Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector Jesus; el-Omar, Emad
2003 Apr-Jun;68(2):107-112, Revista de gastroenterologia de Mexico
BACKGROUND: Interleukin-10, tumor necrosis factor alpha, Interleukin-1 beta and interleukin-1 receptor antagonist cytokines modulate the inflammatory response in presence of Helicobacter pylori. Pro-inflammatory interleukin 10 (IL-10-592, -1082), TNF alpha (TNF alpha-308), interleukin-1 beta and interleukin-1 receptor antagonist (IL-1B-31*C and IL-1RN*2/*2) genotypes have been associated with higher risk of gastric cancer in Caucasians. The aim of this study was to investigate whether these same genotypes are involved in susceptibility to gastric cancer in Mexican population. MATERIALS AND METHODS: DNA from 33 unrelated Mexican patients with histologically confirmed gastric cancer (n = 25) or high-grade dysplasia (n = 8) (mean age 62.7, F/M = 0.37) and 25 ethnically matched healthy controls (mean age = 39.9, F/M = 3.12) were studied. All cases and controls had evidence of H. pylori infection as shown by at least two positive results from the following diagnostic tests: rapid urease test; culture; histology, or detection of IgG anti-H. pylori antibodies. The -592, -1082 polymorphism in IL-10 gene, the -308 in TNF alpha gene, and the-31 polymorphism in the IL-1B gene were typed by 5' nuclease PCR assays (TaqMan) and the variable number of tandem repeats polymorphism in intron 2 of the 1L-1RN gene was typed by PCR and amplicon sizing as previously described (Nature 2000; 404: 398). RESULTS: Carriage of the pro-inflammatory IL-1B-31*C allele was associated with increased risk of gastric cancer or high-grade dysplasia (OR: 8.7, 95% confidence interval [CI] = 1.5-66.9). No association was found between any IL-IRN, IL-10 or TNF alpha genotypes and gastric cancer or high-grade dysplasia. Logistic regression analysis identified male gender and carriage of IL-1B-31*C as independent risk factors for gastric cancer (OR = 9.2, 95% CI = 2.4-34.5, and OR = 10, 95% CI = 1.6-64, respectively). CONCLUSIONS: The results of this preliminary study confirm that the pro-inflammatory IL-1B genotypes, as well as male gender, are risk factors for development of gastric cancer in Mexican population
— id: 44763, year: 2003, vol: 68, page: 107, stat: Journal Article,

Transient and persistent Helicobacter pylori colonization in Native American children
Perez-Perez, Guillermo I; Sack, R Bradley; Reid, Raymond; Santosham, Mathuram; Croll, Janne; Blaser, Martin J
2003 Jun;41(6):2401-2407, Journal of clinical microbiology
Helicobacter pylori is chiefly acquired in childhood, but the exact timing of acquisition is not well understood. The main goal of this study was to assess H. pylori acquisition in a pediatric population. We studied two cohorts of Native American children: a birth cohort of 50 children and 58 older children (mean age, 53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7 (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children, 49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori antibodies at study entry. During the next year, 7 (20.6%) children seroreverted, and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups, evaluation of CagA antibodies increased the sensitivity of H. pylori detection. Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly until age 6 months and remained constant for the next 19 months. At the time of H. pylori seroconversion, PGI peaked to levels significantly higher than in the never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but then declined to levels paralleling those of H. pylori-negative children. Thus, H. pylori acquisition, accompanied by a transient PGI increase, was frequent in this population, especially in the second and third years of life, but often was brief
— id: 39203, year: 2003, vol: 41, page: 2401, stat: Journal Article,

Relation of serum ascorbic acid to Helicobacter pylori serology in US adults: the Third National Health and Nutrition Examination Survey
Simon, Joel A; Hudes, Esther S; Perez-Perez, Guillermo I
2003 Aug;22(4):283-289, Journal of the American College of Nutrition
PURPOSE: To examine the relation between serum ascorbic acid and Helicobacter pylori serology from a probability sample of US adults. Subjects and Methods: Data from 6,746 adults (ages 20 to 90 years) enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994 were analyzed. Multiple logistic regression models were examined taking into account sample weights and the complex survey design of NHANES III, and controlling for the effects of potential confounders. Because race appeared to modify the association between serum ascorbic acid and seropositivity to H. pylori, we conducted the analyses stratified by race. RESULTS: A total of 2,189 adults (32%) had a positive serology for H. pylori, and, of these, 1,175 (54%) were positive for the CagA antigen. Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82-0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12-0.79, p < 0.05). Serum ascorbic acid levels were not significantly associated with H. pylori serology among non-whites (all p > 0.05). CONCLUSIONS: Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites. If these associations are related causally and are not the result of residual confounding by factors such as socioeconomic status, ascorbic acid may affect the risk of H. pylori infection and in turn, the risk for peptic ulcer disease and gastric cancer among white Americans
— id: 44766, year: 2003, vol: 22, page: 283, stat: Journal Article,

The association of intestinal parasitosis and H. pylori infection in children and adults from a Mexican community with high prevalence of parasitosis
Torres, Javier; Perez, G Perez; Ximenez, C; Munoz, L; Camorlinga-Ponce, M; Ramos, F; Gomez, A; Munoz, O
2003 Jun;8(3):179-185, Helicobacter
BACKGROUND: Experimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. MATERIALS AND METHODS: The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. RESULTS: In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). CONCLUSIONS: Intestinal parasitic infections and serum IgE levels showed an age-dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence
— id: 45297, year: 2003, vol: 8, page: 179, stat: Journal Article,

Simultaneous experimental colonization of Eriones unguiculatus (Mongolian gerbil) with PAI+ and PAI- Helicobacter pylori strains
Camorlinga, MP; Celis-Cruz, C; Romero, J; Ortiz, M; Lopez-Corella, E; Perez-Perez, G; Coria-Jimenez, R
2002 SEP ;51(2):A49-A49, Gut: journal of the British Society of Gastroenterology
— id: 55588, year: 2002, vol: 51, page: A49, stat: Journal Article,

Prevalence of Helicobacter pylori and characterization of genotypes among symptomatic patients from Uruguay
Cooperberg, BA; Bini, EJ; Perez-Perez, G; Weinshel, EH; Cohen, H; Dacoll, C
2002 ;122(4):T1164-T1164, Gastroenterology
— id: 108248, year: 2002, vol: 122, page: T1164, stat: Journal Article,

Reliability of Helicobacter pylori and CagA serological assays
Everhart, James E; Kruszon-Moran, Deanna; Perez-Perez, Guillermo
2002 Mar;9(2):412-416, Clinical & diagnostic laboratory immunology
Background serological assays for Helicobacter pylori are commonly used without knowledge of reliability. This information is needed to define the ability of serological tests to determine either new cases of infection or loss of infection in longitudinal studies. We evaluated the reproducibility and the interrelationships of serological test results for H. pylori and cytotoxin-associated gene product A (CagA) enzyme-linked immunoassays within a subset of participants in a population-based study. Stored samples from 1,229 participants in the third U.S. National Health and Nutrition Examination Survey were replicate serologically tested for H. pylori and CagA. Overall disagreement was 3.4% between duplicate tests for H. pylori (or 2.3% if equivocal results were disregarded). Six percent of samples positive on the first test had an immune serum ratio at least 30% lower on repeat testing. The odds ratio for H. pylori seropositivity on retesting was 2.8 (95% confidence interval [CI] = 1.8 to 4.5) when CagA serology was positive versus when it was negative. CagA antibody was found among 47.8% of H. pylori-equivocal and 7.0% of H. pylori-negative samples. CagA-positive yet H. pylori-negative samples were more likely to occur among Mexican Americans (odds ratio, 5.2; 95% CI = 2.4 to 11.4) and non-Hispanic blacks (odds ratio, 5.5; 95% CI = 2.3 to 13.0) than among non-Hispanic whites. Relying on repeated H. pylori serological tests over time to determine infection rates may result in misinterpretation due to limits in test reproducibility. CagA testing may have a role in verifying infection
— id: 34621, year: 2002, vol: 9, page: 412, stat: Journal Article,

Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant
Freedman, Abigail; Afonja, Olubunmi; Chang, Mary Wu; Mostashari, Farzad; Blaser, Martin; Perez-Perez, Guillermo; Lazarus, Herb; Schacht, Robert; Guttenberg, Jane; Traister, Michael; Borkowsky, William
2002 Feb 20;287(7):869-874, JAMA
A 7-month-old infant with cutaneous anthrax developed severe systemic illness despite early treatment with antibiotics. The infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia. These findings are unusual with cutaneous anthrax, but have been described in illness resulting from spider toxin and may delay correct diagnosis. The systemic manifestations of the disease persisted for nearly a month despite corticosteroid therapy, but resolved
— id: 26017, year: 2002, vol: 287, page: 869, stat: Journal Article,

Potential correlation of HLA-DQ alleles and clinical outcomes related to H-pylori CagA plus and VacA
Garza-Gonzalez, E; Bosques-Padilla, FJ; Perez-Perez, GI; Tijerina-Menchaca, R
2002 SEP ;51(2):A25-A26, Gut: journal of the British Society of Gastroenterology
— id: 55587, year: 2002, vol: 51, page: A25, stat: Journal Article,

Role of the polymorphic cytokines genes in gastric cancer in Mexico
Garza-Gonzalez, E; Hold, GL; Perez-Perez, GI; Bosques-Padilla, FJ; Tijerina-Menchaca, R; El-Omar, EM
2002 SEP ;51(2):A23-A23, Gut: journal of the British Society of Gastroenterology
— id: 55586, year: 2002, vol: 51, page: A23, stat: Journal Article,

Antibiotic susceptibility patterns of Helicobacter pylori strains isolated from northeastern Mexico
Garza-Gonzalez, E; Perez-Perez, G I; Alanis-Aguilar, O; Tijerina-Menchaca, R; Maldonado-Garza, H J; Bosques-Padilla, F J
2002 Aug;14(4):342-345, Journal of chemotherapy
There are reports of increased antibiotic resistance rates in Helicobacter pylori strains around the world. The aim of this study was to determine the susceptibility patterns in H. pylori strains isolated in Monterrey, Mexico. We studied 62 strains isolated from the same number of symptomatic adult patients. Metronidazole (Mtz), clarithromycin (Cla), amoxicillin (Amx) and tetracycline (Tet) were tested by the E-test method. We observed that 37.1% of the strains were resistant to Mtz (MIC > or = 8 mg/L), and 8.1% to Cla (MIC > or = 8 mg/L), but we did not observe resistance to Amx (MIC > or = 2 mg/L) or Tet (MIC > or = 4 mg/L). In northeastern Mexico, the percentage of resistant strains was similar to that observed in developed countries. These results confirm that it is necessary to evaluate the susceptibility patterns of H. pylori strains by geographic area
— id: 34620, year: 2002, vol: 14, page: 342, stat: Journal Article,

[Helicobacter pylori genotypes and their association with host's immune response]
Garza-Gonzalez, Elvira; Perez-Perez, Guillermo I; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector J; Bosques-Padilla, Francisco J
2002 Jul-Sep;67(3):155-160, Revista de gastroenterologia de Mexico
BACKGROUND DATA: The study of Helicobacter pylori phenotypes and genotypes is mainly focused on two groups of putative bacterial virulence factors: the cag pathogenicity island (PAI), for which CagA is a marker, and the vacuolating cytotoxin VacA. Several studies have shown the clinical relevance of the determination of IgG anti-CagA antibodies. OBJECTIVE: To assess the prevalence of vacA and cagA genotypes of H. pylori and the association with IgG anti-CagA antibodies in symptomatic patients. METHODS: We studied 50 patients (mean age 53 years, range 15-92). PCR amplification of the vacA s and m regions was performed using the primers described (J Biol Chem 1995; 270: 17771). For cagA PCR, primers described by Rugge et al. were used (Cancer 1999; 85: 2506) and determination of IgG anti-CagA antibodies was done according to the method described by Blaser and Perez (Cancer Res 1995; 55: 2111). RESULTS: All 50 patients studied were positive for H. pylori. Of the 50 H. pylori strains, 7 (14%) were isolated from patients with peptic ulcer disease and 43 (86%) from patients with non-ulcer dyspepsia. The most frequent vacA genotype was s2/m2, associated with cagA-H. pylori strains (p < 0.01). Presence of cagA+ H. pylori strains correlated with the presence of IgG antibodies (Kappa = 0.680). Determination of IgG anti-CagA antibodies showed a sensitivity of 77.4%, specificity of 94.7%, positive value of 96% and negative predictive value of 72%. CONCLUSIONS: The most frequent H. pylori genotype found in northeastern Mexico was vacA s2/m2, cagA-. The presence of this genotype correlated with the clinical presentations observed in these patients. In addition, CagA serology showed a great specificity and good sensitivity that allow us to use this assay to assess the prevalence of CagA+ strains in Mexico
— id: 34617, year: 2002, vol: 67, page: 155, stat: Journal Article,

East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage
Ghose, Chandrabali; Perez-Perez, Guillermo I; Dominguez-Bello, Maria-Gloria; Pride, David T; Bravi, Claudio M; Blaser, Martin J
2002 Nov 12;99(23):15107-15111, Proceedings of the National Academy of Sciences of the United States of America
Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that carry them. Conversely, polymorphisms may be used to date the spread of a microbial species when information about their host populations is available. Therefore, we examined polymorphisms in Helicobacter pylori, which persistently colonize the human stomach, to test the hypothesis that they have been ancient inhabitants of humans. Three H. pylori loci that previously have been shown to have phylogeographic affinity have been analyzed for two populations with different ethnic origins from Venezuela. In a group of Amerindian subjects from Amazonia, East Asian H. pylori genotypes were present for each of the loci examined but were absent in a mestizo population from Caracas. These findings provide evidence that H. pylori has been present in humans at least since ancestors of Amerindians migrated from Asia more than 11,000 years ago
— id: 34577, year: 2002, vol: 99, page: 15107, stat: Journal Article,

Serum antibodies to Helicobacter pylori and the CagA antigen do not explain differences in the prevalence of precancerous gastric lesions in two Chinese populations with contrasting gastric cancer rates
Groves, Frank D; Perez-Perez, Guillermo; Zhang, Lian; You, Wei-cheng; Lipsitz, Stuart R; Gail, Mitchell H; Fraumeni, Joseph F Jr; Blaser, Martin J
2002 Oct;11(10 Pt 1):1091-1094, Cancer epidemiology biomarkers & prevention
Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA was significantly greater in Bei Duan. Although age, sex, and both H. pylori seromarkers were associated with APGL in the logistic regression model, the effect of village of residence remained strong after adjustment for all four covariates. Only a relatively small proportion of the difference in prevalence of APGL between these two rural Chinese populations can be explained by differences in H. pylori or CagA seroprevalence
— id: 34582, year: 2002, vol: 11, page: 1091, stat: Journal Article,

PCR-based detection of Bacillus anthracis in formalin-fixed tissue from a patient receiving ciprofloxacin
Levine, Steven M; Perez-Perez, Guillermo; Olivares, Asalia; Yee, Herman; Hanna, Bruce A; Blaser, Martin J
2002 Nov;40(11):4360-4362, Journal of clinical microbiology
We demonstrate that Bacillus anthracis may be detected from a formalin-fixed, paraffin-embedded biopsy specimen, even after the patient has received antibiotic treatment. Although traditional PCR methods may not be sufficiently sensitive for anthrax detection in such patients, cycle numbers can be increased or PCR can be repeated by using an aliquot from a previous PCR as the template
— id: 34579, year: 2002, vol: 40, page: 4360, stat: Journal Article,

Helicobacter pylori seropositivity and colorectal cancer risk: a prospective study of male smokers
Limburg, Paul J; Stolzenberg-Solomon, Rachael Z; Colbert, Lisa H; Perez-Perez, Guillermo I; Blaser, Martin J; Taylor, Philip R; Virtamo, Jarmo; Albanes, Demetrius
2002 Oct;11(10 Pt 1):1095-1099, Cancer epidemiology biomarkers & prevention
Because Helicobacter pylori colonization can produce systemic as well as local effects, it may be associated with carcinogenesis in extra gastric target organs. The currently available data regarding a possible link between H. pylori seropositivity and colorectal cancer risk are limited and inconclusive. In this prospective case-control study nested within the Alpha-Tocopherol, Beta-Carotene Study cohort of Finnish male smokers aged 50-69 years, we examined the association between H. pylori seropositivity and incident colorectal adenocarcinoma. Separate risk estimates were derived by colorectal cancer anatomical subsite and by H. pylori CagA seropositivity status. Demographic, dietary, and lifestyle variables were accounted for in the data analyses using information obtained from a prerandomization questionnaire and physical examination. Baseline serum samples from 118 cases and 236 matched controls were assayed for both H. pylori whole cell and H. pylori CagA antibodies. In total, 258 (73%) and 212 (60%) subjects expressed whole cell and CagA antibodies, respectively. H. pylori seropositivity, defined as one or both antibody assays positive, was present in 273 (77%) subjects. None of the seropositivity results were statistically different between cases and controls. Multivariate odds ratio (95% confidence interval) estimates for whole cell, cagA, and H. pylori seropositivity were 1.05 (0.63-1.74), 1.17 (0.74-1.84), and 0.91 (0.53-1.55), respectively. Stratification by colorectal cancer subsite yielded similarly unremarkable results. On the basis of these data, H. pylori carriage does not appear to be an important risk factor for colorectal adenocarcinoma
— id: 34581, year: 2002, vol: 11, page: 1095, stat: Journal Article,

Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population
Nomura, Abraham M Y; Lee, James; Stemmermann, Grant N; Nomura, Ryan Y; Perez-Perez, Guillermo I; Blaser, Martin J
2002 Oct 15;186(8):1138-1144, Journal of infectious diseases
Helicobacter pylori colonization is associated with gastric cancer, but whether and to what extent the risk is greater for strains with the cagA gene than for those without needs to be determined. Between 1967 and 1977, 9963 Japanese American men were recruited and examined. By 1996, incident cases of gastric carcinoma of the distal stomach had been diagnosed in 261 men. Stored serum samples from these case patients and 261 age-matched control subjects were tested for immunoglobulin G antibodies to H. pylori and to the CagA product of H. pylori, using antibody-specific enzyme-linked immunosorbent assays. Compared with H. pylori-negative, CagA-negative men, H. pylori-positive, CagA-negative men had an odds ratio (OR) of 2.7 (95% confidence interval [CI], 1.3-5.6) for intestinal gastric carcinoma. Men seropositive for both H. pylori and CagA had an OR of 4.1 (95% CI, 2.2-7.7). This suggests that colonization by an H. pylori strain with the cagA gene is associated with a greater risk of intestinal gastric carcinoma
— id: 34583, year: 2002, vol: 186, page: 1138, stat: Journal Article,

Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease
Nomura, Abraham M Y; Perez-Perez, Guillermo I; Lee, James; Stemmermann, Grant; Blaser, Martin J
2002 Jun 1;155(11):1054-1059, American journal of epidemiology
Although colonization with any Helicobacter pylori strain is associated with peptic ulcer, it is uncertain whether the risk is greater with cagA(+) or cagA(-) strains, which differ in their biology. A nested case-control study was done, based on a cohort of 5,443 Japanese-American men examined on the Hawaiian island of Oahu from 1967 to 1970. A total of 150 men with gastric ulcer, 65 with duodenal ulcer, and 14 with both diseases were identified. The authors matched the 229 cases with 229 population controls and tested their serum for immunoglobulin G antibodies to H. pylori and immunoglobulin G antibodies to the cagA product of H. pylori using enzyme-linked immunosorbent assays. Persons with H. pylori positivity had an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95% CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for duodenal ulcer. The results suggest that colonization with a cag(+) H. pylori strain elevates the risk beyond that of a cag(-) H. pylori strain for both gastric and duodenal ulcers
— id: 34587, year: 2002, vol: 155, page: 1054, stat: Journal Article,

Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly than cagA(-) strains
Perez-Perez, G I; Salomaa, A; Kosunen, T U; Daverman, B; Rautelin, H; Aromaa, A; Knekt, P; Blaser, M J
2002 Mar;50(3):295-298, Gut: journal of the British Society of Gastroenterology
Background and aims: The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining, as shown by community based serological surveys of adults in Vammala, Finland in 1973 and 1994. In this study, we determined whether the proportion of subjects colonised by cagA(+) or cagA(-) H pylori strains has changed as the overall prevalence of H pylori(+) has declined. Methods: We examined 911 sera from Vammala's study for antibodies to the CagA antigen of H pylori using a truncated CagA protein as the antigen in an ELISA and we examined the trend in acquisition and carriage of cagA(+) strains. Results: As expected, the prevalence of carriage of both cagA(+) and cagA(-) strains fell between 1973 and 1994 (p<0.001). However, the prevalence of cagA(+) strains among those <45 years declined (34% to 8%) significantly (p<0.001) more than for cagA(-) strains (12% to 6%). Of 221 subjects with paired serum samples, 12 (5.4%) changed H pylori status; the estimated seroconversion and reversion rates were 0.4% and 0.13% per year, respectively. Except for the few individuals who changed serostatus, absolute antibody levels to H pylori antigens, including CagA, changed little over the 21 year period. Conclusions: The decline in CagA seroprevalence predominantly reflects declining acquisition of cag(+) strains in younger subjects. In addition, these data confirm that H pylori acquisition chiefly occurs during childhood but continues to occur during adulthood, albeit at low rates, in developed countries
— id: 25600, year: 2002, vol: 50, page: 295, stat: Journal Article,

Detection of Helicobacter pylori in gastric juice by PCR
Perez-Perez, GI; Olivares, AZ; Peek, RM; Tham, K; Blaser, MJ
2002 SEP ;51(2):A110-A110, Gut: journal of the British Society of Gastroenterology
— id: 55589, year: 2002, vol: 51, page: A110, stat: Journal Article,

Responses of endoscopy patients in Ladakh, India, to Helicobacter pylori whole-cell and Cag A antigens
Romero-Gallo, Judith; Perez-Perez, Guillermo I; Novick, Richard P; Kamath, Patrick; Norbu, Tsering; Blaser, Martin J
2002 Nov;9(6):1313-1317, Clinical & diagnostic laboratory immunology
Although Helicobacter pylori is a cosmopolitan colonizer of the human stomach, the responses among persons in remote populations from whom H. pylori was cultured have not been studied. We report on studies of 189 persons in the Ladakh region of India in whom serum immunoglobulin G responses to H. pylori whole-cell and Cag A antigens were measured. H. pylori was isolated from 68 of these patients. An H. pylori whole-cell antigen derived from Ladakhi strains outperformed a similar antigen from U.S. strains, as determined by antigen-specific enzyme-linked immunosorbent assays. In total, 95% of the population was seropositive, including individuals responding only to the Cag A antigen. Correlation with culture results showed that these were true positives and, therefore, that the H. pylori whole-cell serology was falsely negative in some cases. In addition to establishing a collection of H. pylori isolates from a remote area in the world, we show that use of H. pylori whole-cell and Cag A serology together increases the sensitivity for the detection of colonization
— id: 34578, year: 2002, vol: 9, page: 1313, stat: Journal Article,

Validacion del Western blot para la deteccion del genotipo de Helicobacter pylori
Tijerina-Menchaca R; Bosques-Padilla FJ; Perez-Perez GI; Maldonado-Garza HJ; Garza-Gonzalez E
2002 Oct-Dec;4(17):212-216, Medicina universitaria
— id: 38480, year: 2002, vol: 4, page: 212, stat: Journal Article,

Specific serum immunoglobulin G response to urease and CagA antigens of Helicobacter pylori in infected children and adults in a country with high prevalence of infection
Torres, Javier; Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Munoz, Leopoldo; Munoz, Onofre
2002 Jan;9(1):97-100, Clinical & diagnostic laboratory immunology
Few studies have analyzed the immune response to Helicobacter pylori CagA and urease antigens across age groups in the same population. The aim of this study was to analyze the serologic immunoglobulin G (IgG) response to CagA and urease proteins in children and adults with gastrointestinal symptoms and belonging to the same population and similar socioeconomic levels. The serologic response was studied in 352 children and 293 adults with gastrointestinal symptoms. IgG antibodies against CagA and urease were tested by enzyme-linked immunosorbent assay methods using highly purified recombinant antigens. H. pylori infection was defined as a positive result in a serologic assay using whole-cell H. pylori extracts as the antigen. We found, in H. pylori-positive children, a seroprevalence of 46.9% to CagA and 16.2% to urease, whereas in H. pylori-positive adults, a seroprevalence of 78.9% to CagA and 59% to urease was found. In children, the magnitude of the response to CagA was significantly higher and the response to urease was significantly lower than those in adults. The kinetics of serologic response to CagA and to urease across age groups was contrastably different. Whereas CagA is a strong immunogen, urease is a poor immunogen during natural infection. These differences in the humoral response may be important for the short-term or long-term outcome of the infection. These results add to our knowledge of the epidemiology of H. pylori infection
— id: 34622, year: 2002, vol: 9, page: 97, stat: Journal Article,

Quantitative molecular electrochemical detection of Helicobacter pylori
Dominguez-Bello, MG; Godette, G; Sundseth, R; Perez-Perez, GI; Wojciechowski, M; Bonaventura, C; Henkens, R
2001 SEP ;49(4):A99-A99, Gut: journal of the British Society of Gastroenterology
— id: 54874, year: 2001, vol: 49, page: A99, stat: Journal Article,

Seroprevalence of Helicobacter pylori and CagA in areas of Venezuela with different gastric cancer risks
Dominguez-Bello, MG; Perez-Perez, GI; Pacheco, N; Gonzalez, E; Garza-Gonzalez, E; Mora, R; Mago, V; Gomez, I
2001 SEP ;49(4):A36-A36, Gut: journal of the British Society of Gastroenterology
— id: 54873, year: 2001, vol: 49, page: A36, stat: Journal Article,

Assessment of Helicobacter pylori vacA and cagA Genotypes and Host Serological Response
Figueiredo C; Quint W; Nouhan N; van Den Munckhof H; Herbrink P; Scherpenisse J; de Boer W; Schneeberger P; Perez-Perez G; Blaser MJ; van Doorn LJ
2001 Apr;39(4):1339-1344, Journal of clinical microbiology
Helicobacter pylori strains can be distinguished by genotyping of virulence-associated genes, such as vacA and cagA. Because serological discrimination between strain types would reduce the need for endoscopy, 61 patients carrying H. pylori were studied by vacA and cagA genotyping of H. pylori in gastric biopsy specimens and by detection of specific serum antibodies. Serological responses to H. pylori were determined by Helicoblot (versions 2.0 and 2.1). Antibodies to CagA also were determined by a rapid anti-CagA assay (Pyloriset screen CagA) as well as by two noncommercially developed enzyme immunoassays, each using a recombinant CagA protein. Assessment of performance of the Helicoblot assays indicated substantial interobserver variation, with kappa values between 0.20 and 0.93. There was no relationship between the serological profiles on the Helicoblot and the genotypes from the same patients, except for strong associations between the presence of anti-CagA and the cagA-positive and vacA s1 H. pylori genotypes. Detection of anti-CagA by the five different assays varied considerably, with kappa values ranging from 0.21 to 0.78. Using the cagA genotype as the 'gold standard,' the sensitivity and specificity of the anti-CagA assays varied from 71.4 to 85.7% and from 54.2 to 100%, respectively. Thus, serological profiles of antibodies to H. pylori are heterogeneous and, with the exception of anti-CagA antibodies, show no relation to the H. pylori vacA and cagA genotypes. Detection of anti-CagA antibodies is strongly dependent on the test used
— id: 19027, year: 2001, vol: 39, page: 1339, stat: Journal Article,

Characterization of Helicobacter pylori strains isolated from the northeast region of Mexico
Garza-Gonzalez, E; Bosques-Padilla, FJ; Maldonado-Garza, H; Tijerina-Menchaca, R; Perez-Perez, GI
2001 SEP ;49(4):A34-A35, Gut: journal of the British Society of Gastroenterology
— id: 54872, year: 2001, vol: 49, page: A34, stat: Journal Article,

Helicobacter pylori among indigenous peoples of Venezuela: European or Asian origin?
Ghose, C; Perez-Perez, GI; Dominguez-Bello, MG; Blaser, MJ
2001 OCT 1 ;33(7):1233-1233, Clinical infectious diseases
— id: 54859, year: 2001, vol: 33, page: 1233, stat: Journal Article,

Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China
Limburg P; Qiao Y; Mark S; Wang G; Perez-Perez G; Blaser M; Wu Y; Zou X; Dong Z; Taylor P; Dawsey S
2001 Feb 7;93(3):226-233, Journal of the National Cancer Institute
BACKGROUND: Helicobacter pylori carriage (i.e., persistent exposure to the organism without gastric epithelial cell invasion) is an established risk factor for noncardia gastric cancer. However, its association with the risk of cancer of the gastric cardia is controversial. Consequently, we designed this prospective, nested case-control study to further explore the subsite-specific gastric cancer risks associated with H. pylori seropositivity (a surrogate marker for persistent exposure). METHODS: A total of 99 patients with gastric cardia cancer, 82 patients with noncardia gastric cancer, and 192 cancer-free subjects were selected from among the participants (n = 29 584) of a nutrition intervention trial previously conducted in Linxian, China. H. pylori seropositivity was determined by assaying for the presence of H. pylori whole cell and CagA antibodies in baseline serum samples from all subjects. Seropositivity was defined as one or both serum assays being positive. Odds ratios (ORs) for subsite-specific gastric cancer were estimated by multivariate logistic regression analyses. All statistical comparisons were two-sided (alpha =.05). RESULTS: H. pylori seropositivity rates for subjects with gastric cardia cancer, noncardia gastric cancer, and gastric cardia and noncardia cancers combined were 70% (P =.02), 72% (P: =.01), and 71% (P =.003) compared with 56% for cancer-free control subjects. OR estimates for H. pylori seropositivity were 1.87 (95% confidence interval [CI] = 1.10 to 3.17) for gastric cardia cancer, 2.29 (95% CI = 1.26 to 4.14) for noncardia gastric cancer, and 2.04 (95% CI = 1.31 to 3.18) for gastric cardia and noncardia cancers combined. CONCLUSIONS: H. pylori seropositivity was associated with increased risks for both gastric cardia cancer and noncardia gastric cancer in this well-characterized cohort. Thus, H. pylori carriage may increase the risk of cancer throughout the stomach
— id: 34627, year: 2001, vol: 93, page: 226, stat: Journal Article,

Increased gastric epithelial cell apoptosis associated with colonization with cagA + Helicobacter pylori strains
Moss SF; Sordillo EM; Abdalla AM; Makarov V; Hanzely Z; Perez-Perez GI; Blaser MJ; Holt PR
2001 Feb 15;61(4):1406-1411, Cancer research
Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated 'blindly' using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization
— id: 19030, year: 2001, vol: 61, page: 1406, stat: Journal Article,

A comparison of Lewis x and Lewis y expression in Helicobacter pylori obtained from children and adults
Munoz L; Gonzalez-Valencia G; Perez-Perez GI; Giono-Cerezo S; Munoz O; Torres J
2001 Apr 1;183(7):1147-1151, Journal of infectious diseases
There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le(x) were more common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and Le(y) was more common in adults than in children (81.6% vs. 66%, respectively; P<.01). A trend analysis showed a significant decline in frequency of clones expressing Le(x) with age (P=.021). In this community, expression of Le antigens differs in H. pylori isolates obtained from children versus adults
— id: 25603, year: 2001, vol: 183, page: 1147, stat: Journal Article,

Presence of specific Asian Helicobacter pylori genotypes in Amerindians in Venezuela
Perez-Perez, GI; Dominguez-Bello, MG; Ghose, C; Pacheco, N; Gonzalez, E; Mago, V; de Novoa, PG; Gomez, I; Mora, R; Blaser, MJ
2001 SEP ;49(4):A33-A33, Gut: journal of the British Society of Gastroenterology
— id: 54871, year: 2001, vol: 49, page: A33, stat: Journal Article,

Comparison of invasive and serological tests for the diagnostic of Helicobacter pylori
Perez-Perez, GI; Garza-Gonzalez, E; Flores-Gutierrez, JP; Maldonado-Garza, HJ; Bosques-Padilla, FJ; Tijerina-Menchaca, R
2001 SEP ;49(4):A104-A104, Gut: journal of the British Society of Gastroenterology
— id: 54875, year: 2001, vol: 49, page: A104, stat: Journal Article,

Helicobacter pylori seropositivity as a risk factor for pancreatic cancer
Stolzenberg-Solomon RZ; Blaser MJ; Limburg PJ; Perez-Perez G; Taylor PR; Virtamo J; Albanes D
2001 Jun 20;93(12):937-941, Journal of the National Cancer Institute
BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer
— id: 34624, year: 2001, vol: 93, page: 937, stat: Journal Article,

Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease
Tham KT; Peek RM; Atherton JC; Cover TL; Perez-Perez GI; Shyr Y; Blaser MJ
2001 Mar;32(3):264-273, Human pathology
From 183 patients undergoing upper gastrointestinal endoscopy, we used antral and corpus gastric biopsies for bacterial culture and histopathologic examination, blood samples to detect immunoglobulin G antibodies against Helicobacter pylori, and H pylori genomic DNA to analyze cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) genotypes. As expected, among H pylori biopsy-positive patients, those with duodenal ulcer (DU) (n = 34) had significantly more severe chronic and acute inflammation (P <.001) and epithelial degeneration (P =.004) in the gastric antrum than in the gastric corpus. Each of those 3 parameters and H pylori density were significantly higher in the antrum of patients with DU than in patients with gastric ulcer (GU) or no ulcer. Colonization with vacA s1/cagA-positive strains of H pylori was associated with inflammation and epithelial degeneration in gastric mucosa and increased risk for peptic ulcer disease (PUD), whereas colonization with vacA s2m2/cagA-negative strains was associated with mild gastric histopathology and was not associated with any significant risk for PUD. The predominant H pylori strains in African Americans were vacA s1bm1/cagA-positive, whereas all genotypes were well represented in non-Hispanic-Caucasians. By multivariate analysis, H pylori colonization was significantly associated with DU (Adjusted odds ratio [AdjOR] = 3.2 [1.4-7.2]) and nonsteroidal anti-inflammatory drugs (NSAID) use was inversely associated (AdjOR = 0.3 [0.2-0.7]). NSAID use (AdjOR = 4.3 [1.02-18.5]) and African-American ethnicity (AdjOR = 10.9 [2.6-50]) were significantly associated with GU. Smoking and age were not significantly associated with either DU or GU. These data indicate that DU is associated with an antral-dominant gastritis, and H pylori genotype and NSAID use independently contribute to the pathogenesis of PUD. HUM PATHOL 32:264-273. This is a US Government work. There are no restrictions on its use
— id: 19028, year: 2001, vol: 32, page: 264, stat: Journal Article,

Validation of the string test for the recovery of Helicobacter pylori from gastric secretions and correlation of its results with urea breath test results, serology, and gastric pH levels
Torres J; Camorlinga M; Perez-Perez G; Gonzalez G; Munoz O
2001 Apr;39(4):1650-1651, Journal of clinical microbiology
The efficacy of the string culture test to isolate Helicobacter pylori from gastric secretions of 28 volunteers was studied. With the urea breath test (UBT) as the 'gold standard,' the string culture test showed a sensitivity of 75% and a specificity of 100%. The results of string culture did not correlate with the UBT results, with serum antibody levels, or with the pH levels of gastric secretions
— id: 34625, year: 2001, vol: 39, page: 1650, stat: Journal Article,

Increasing multidrug resistance in Helicobacter pylori strains isolated from children and adults in Mexico
Torres J; Camorlinga-Ponce M; Perez-Perez G; Madrazo-De la Garza A; Dehesa M; Gonzalez-Valencia G; Munoz O
2001 Jul;39(7):2677-2680, Journal of clinical microbiology
The susceptibilities to three antimicrobials of 195 Helicobacter pylori strains isolated from Mexican patients is reported; 80% of the strains were resistant to metronidazole, 24% were resistant to clarithromycin, and 18% presented a transient resistance to amoxicillin. Resistance to two or more antimicrobials increased significantly from 1995 to 1997
— id: 34623, year: 2001, vol: 39, page: 2677, stat: Journal Article,

Helicobacter pylori prevalence and CagA status among children in two counties of China with high and low risks of gastric cancer
You WC; Zhang L; Pan KF; Jiang J; Chang YS; Perez-Perez GI; Liu WD; MA JL; Gail MH; Blaser MJ; Fraumeni JF; Xu GW
2001 Nov;11(8):543-546, Annals of epidemiology
BACKGROUND: Studies in adult populations in selected countries with widely varying rates of gastric cancer have shown a weak correlation between gastric cancer mortality rates and the prevalence of CagA+ strains of H. pylori. However, only limited data are available in ethnically homogenous populations with varying rates in the same region. METHODS; We compared the prevalence of H. pylori in general and of CagA+ strains in particular among children in Shandong Province, China in areas at high (Linqu County) and low risk (Cangshan County) of gastric cancer. H. pylori status among children aged 3 to 12 years was determined by 13C-UBT, and CagA status was determined by enzyme-linked immunosorbent assay (ELISA). Because of the difficulty in obtaining blood from young children aged 3 to 4 years and from some children aged 5 years, CagA status was determined among part of children 5 years old and children 6 to 12 years old. RESULTS; Among 98 children aged 3 to 12 years in Linqu, 68 (69.4%) was H. pylori-positive, as compared with 29 (28.7%) among 101 children in Cangshan. Among children positive for 13C-UBT, the proportion of the CagA+ strains were identified was 46 (88.5%) of 52 in Linqu and 13 (81.3%) of 16 in Cangshan, respectively. CONCLUSIONS: The prevalence of H. pylori was nearly three times higher among children in Linqu than in Cangshan, which may contribute to the large differential in gastric cancer rates for two neighboring populations in Shandong Province
— id: 25601, year: 2001, vol: 11, page: 543, stat: Journal Article,

Anti-CagA immunoglobulin G responses correlate with interleukin-8 induction in human gastric mucosal biopsy culture
Ando T; Perez-Perez GI; Kusugami K; Ohsuga M; Bloch KC; Blaser MJ
2000 Sep;7(5):803-809, Clinical & diagnostic laboratory immunology
Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA(+). As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8+/-3.5 versus 10.1+/-4.3 ng/mg of biopsy protein; P<0.001) and IL-6 levels (2.8+/-0.3 versus 0.26+/-0.2 ng/mg of protein; P<0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P<0.005) and neutrophil infiltration (P<0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P<0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P<0.005) and with IgG responses to whole-cell antigens (P<0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r = 0.75, P<0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts
— id: 19041, year: 2000, vol: 7, page: 803, stat: Journal Article,

Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States
Everhart JE; Kruszon-Moran D; Perez-Perez GI; Tralka TS; McQuillan G
2000 Apr;181(4):1359-1363, Journal of infectious diseases
The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32. 5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those > or =70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2. 6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection
— id: 25605, year: 2000, vol: 181, page: 1359, stat: Journal Article,

Association between H-pylori seropositivity and atrophic Gastritis in HIV-infected persons
Haley, CA; D'Agata, EM; Perez-Perez, GI; Blaser, MJ; McGowan, CC
2000 JUL ;31(1):234-234, Clinical infectious diseases
— id: 54483, year: 2000, vol: 31, page: 234, stat: Journal Article,

Acute gastritis with hypochlorhydria: report of 35 cases with long term follow up
Harford WV; Barnett C; Lee E; Perez-Perez G; Blaser MJ; Peterson WL
2000 Oct;47(4):467-472, Gut: journal of the British Society of Gastroenterology
BACKGROUND: Between 1976 and 1987, 35 cases of acute gastritis with hypochlorhydria (AGH) were seen in our research laboratory. The aims of this study were to determine the natural history of AGH and the role of Helicobacter pylori in its pathogenesis. METHODS: Archived serum and gastric biopsy samples obtained from AGH subjects were examined for evidence of H pylori colonisation. Twenty eight of 33 (85%) surviving AGH subjects returned a mean of 12 years after AGH for follow up studies, including determination of H pylori antibodies, basal and peak acid output, endoscopy, and gastric biopsies. A matched control group underwent the same studies. RESULTS: Archived material provided strong evidence of new H pylori acquisition in a total of 14 subjects within two months, in 18 within four months, and in 22 within 12 months of recognition of AGH. Prevalence of H pylori colonisation at follow up was 82% (23 of 28) in AGH subjects, significantly (p<0.05) higher than in matched controls (29%). Basal and peak acid output returned to pre-AGH levels in all but two subjects. CONCLUSIONS: One of several possible initial manifestations of H pylori acquisition in adults may be AGH. While H pylori colonisation usually persists, hypochlorhydria resolves in most subjects
— id: 19040, year: 2000, vol: 47, page: 467, stat: Journal Article,

A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection
Keenan J; Day T; Neal S; Cook B; Perez-Perez G; Allardyce R; Bagshaw P
2000 Jan 15;182(2):259-264, FEMS microbiology letters
Helicobacter pylori infection in humans is associated with diverse of clinical outcomes which are partly attributed to bacterial strain differences. Secreted bacterial products are thought to be involved in the pathogenesis caused by this non-invasive bacterium. Electron microscopy of gastric biopsies from infected individuals revealed blebbing of the H. pylori outer membrane, similar to the process of outer membrane vesicle shedding which occurs when the bacterium is grown in broth. Porins, a class of proinflammatory proteins, were observed in the outer membrane vesicles. The VacA cytotoxin, which is produced by 50-60% of H. pylori strains and associated with increased pathogenesis of infection, was also found to be vesicle-associated and biologically active. This supports the hypothesis that these vesicles represent a vehicle for the delivery of damaging bacterial products to the gastric mucosa
— id: 34631, year: 2000, vol: 182, page: 259, stat: Journal Article,

Long term stability of serum IgG1/IgG2 antibody ratios to Helicobacter pylori in healthy adults
Legath, AJ; Perez-Perez, GI; Rautelin, H; Kosunen, TU; Blaser, MJ
2000 JUL ;31(1):233-233, Clinical infectious diseases
— id: 54482, year: 2000, vol: 31, page: 233, stat: Journal Article,

Serum IgG recognition of Helicobacter pylori antigens after acute acquisition or persistent carriage of the organism
Legath, AJ; Perez-Perez, GI; Rautelin, H; Kosunen, TU; Peek, RM; Sack, RB; Blaser, MJ
2000 JUL ;31(1):233-233, Clinical infectious diseases
— id: 54481, year: 2000, vol: 31, page: 233, stat: Journal Article,

Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus
Loffeld RJ; Werdmuller BF; Kuster JG; Perez-Perez GI; Blaser MJ; Kuipers EJ
2000 ;62(2-3):95-99, Digestion
AIM: The hypothesis that colonization with cagA(+) Helicobacter pylori strains protects against the development of gastroesophageal reflux disease (GERD) and its complications is tested. METHODS: Patients with reflux esophagitis and Barrett's esophagus were studied. Antral biopsy specimens were obtained for detection of H. pylori. A serum sample was obtained for determination of IgG antibodies to H. pylori and to the CagA protein. RESULTS: 736 patients were studied. 118 patients had reflux esophagitis, 36 had Barrett's esophagus, 108 had hiatal hernia without signs of inflammation (the reflux group), and 20 patients had esophageal or stomach cancer. The remaining 454 patients had no signs of GERD. The 262 patients with reflux disease had a significantly lower prevalence of H. pylori (34.9%) than the 454 controls (54.6%; p<0. 001). Among 310 H. pylori-positive patients from whom serum was available, colonization with cagA(+) strains was detected in 59% in the control group versus 35% in the reflux group (p<0.001). Conclusion: Patients with reflux esophagitis and Barrett's esophagus have a significantly lower prevalence of H. pylori colonization than controls, in particular of the cagA(+) type. These data suggest that colonization with cagA(+) H. pylori strains may be protective against the development of GERD
— id: 19035, year: 2000, vol: 62, page: 95, stat: Journal Article,

Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: a randomized, controlled trial in Vietnamese patients with duodenal ulcer
Mao HV; Lak BV; Long T; Chung NQ; Thang DM; Hop TV; Chien NN; Hoan PQ; Henley KS; Perez-Perez GI; Connor BA; Stone CD; Chey WD
2000 Jan;14(1):97-101, Alimentary pharmacology & therapeutics
AIM: To evaluate the effectiveness of triple therapy containing either omeprazole or ranitidine bismuth citrate (RBC) to treat H. pylori infection in Vietnamese duodenal ulcer patients. METHODS: Patients infected with H. pylori were randomized to receive either omeprazole (20 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (OAC), or RBC (400 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (RAC). H. pylori eradication and ulcer healing was established by a follow-up oesophagogastroduodenoscopy (EGD) at least 4 weeks after therapy. Side-effects and compliance were assessed. RESULTS: One hundred and four out of 108 (96%) patients with a duodenal ulcer were infected with H. pylori. Eighty per cent of infected patients had detectable CagA IgG antibodies. Fifty-seven patients received OAC and 47 received RAC. OAC eradicated H. pylori in 91 and 86% of patients by per protocol (PP) and intention-to-treat (ITT) analysis, respectively. PP and ITT eradication rates for RAC were 96 and 91%. Ulcer healing at the follow-up EGD was 89% with OAC and 100% with RAC. Side-effects were minor. No patient failed to complete the protocol due to side-effects. CONCLUSION: Triple therapy with either omeprazole or RBC is highly effective in eradicating H. pylori and healing duodenal ulcer in Vietnamese patients
— id: 25607, year: 2000, vol: 14, page: 97, stat: Journal Article,

Accurate diagnosis of Helicobacter pylori. Culture, including transport
Perez-Perez GI
2000 Dec;29(4):879-884, Gastroenterology clinics of North America
Bacteriology laboratories are interested in culturing H. pylori for several reasons: (1) to investigate its growth requirements and metabolism; (2) for diagnostic purposes; (3) to establish the antibiotic susceptibility of isolates; (4) to identify potential virulence factors; and (5) to investigate microbial host-cell interactions. Despite the reasons listed, culture of H. pylori from gastric biopsy specimens is becoming less popular among clinical laboratories and physicians. The main reason is that it has become generally accepted that culture techniques are too demanding with many factors that must be controlled, in addition to simple and less expensive methods now available. Some of the disadvantages of culture include (1) special conditions for specimen transportation, (2) speed in processing of the sample to increase the probability of recovering the organism, (3) the use of expensive and complicated media with special conditions for maintenance, (4) the need for special incubation conditions, and (5) the length of time necessary to obtain a result for establishing treatment options in the patient. This article reviews aspects of H. pylori culture that could explain use being relegated to only a few clinical laboratories, some regional laboratories, and reference centers. There are several misconceptions in relation to culture techniques, such as transport and the processing of biopsy specimens. This article has mentioned simple and clear points that optimize the recovery rates of H. pylori by culture
— id: 21247, year: 2000, vol: 29, page: 879, stat: Journal Article,

[Is the association of Helicobacter pylori with humans a classical example of parasitism?]
Perez-Perez GI
2000 Oct-Dec;65(4 Suppl 2):7-12, Revista de gastroenterologia de Mexico
Since the first report of the potential role of Helicobacter pylori as cause of disease of the upper intestinal tract of humans, a major controversial has developed. First, the role of H. pylori as the etiological agent of duodenal and gastric ulcer has been questioned. Second, the possibility of H. pylori as a major risk factor in the development of distal gastric cancer has not been fully accepted. It is interesting that at the time when the etiological role of H. pylori is almost universally accepted, series of publications have suggested that the elimination of H. pylori from asymptomatic individuals might represent a risk for the development of other upper gastrointestinal diseases such as GERD and cancer of the esophagus. The main goal of this revision is to describe the virulence factors associated with H. pylori as well as its interaction with the human host, to establish whether H. pylori should be considered a true pathogen or only a commensal
— id: 25602, year: 2000, vol: 65, page: 7, stat: Journal Article,

Role of iron in Helicobacter pylori: its influence in outer membrane protein expression and in pathogenicity
Perez-Perez GI; Israel DA
2000 Dec;12(12):1263-1265, European journal of gastroenterology & hepatology
The acquisition of iron is a necessity for bacterial growth in Helicobacterpylori, as it is for other organisms. In addition, iron is a critical factor for the virulence of this organism. Therefore, it is not surprising that H. pylori isolates have the potential to express at least three major iron acquisition mechanisms. The association of H. pylori infection with host iron deficiency might indicate that the iron-scavenging systems play a role in the virulence of H. pylori
— id: 25604, year: 2000, vol: 12, page: 1263, stat: Journal Article,

Long-term stability of serum IgG1/IgG2 antibody ratios to Helicobacter pylori in healthy adults
Perez-Perez, GI; Legath, AJ; Rautelin, H; Kosunen, TU; Blaser, MJ
2000 OCT ;47(4):A35-A36, Gut: journal of the British Society of Gastroenterology
— id: 54409, year: 2000, vol: 47, page: A35, stat: Journal Article,

Circular and linear DNA molecules in the Entamoeba histolytica complex molecular karyotype
Riveron AM; Lopez-Canovas L; Baez-Camargo M; Flores E; Perez-Perez G; Luna-Arias JP; Orozco E
2000 ;29(1):48-56, European biophysics journal
Entamoeba histolytica genome was analysed by pulsed field gel electrophoresis under conditions to separate linear chromosomes in the 170-1400 kb range. We identified linear DNA molecules of 227, 366, 631, 850, 1112 and 1361 kb (mean sizes obtained by three different methods) and we estimated their reorientation times and migration velocities at various experimental conditions. DNA shift mobility assays, using ethidium bromide, suggested that bands migrating at 227 and 631 kb contain linear and circular DNA, whereas a band at 436 kb has only circular DNA. We obtained a regression equation relating sizes of supercoiled DNA molecules with their migration velocities during a pulse at constant electric field and temperature. We also developed a computer program (EHPATTERNS) that predicts the migration per pulse and the resolution order of circular and linear E. histolytica DNA at different pulse times and constant driving and frictional forces. The simulation showed that linear DNA molecules frequently co-migrate with circular molecules, but circular molecules change when the pulse time varies. This molecular mixture generates broad bands and difficulties in the interpretation of the molecular karyotype of E. histolytica
— id: 34630, year: 2000, vol: 29, page: 48, stat: Journal Article,

Algorithm to predict MiniCHEF electrophoresis patterns of Entamoeba histolytica DNA
Riveron AM; Lopez-Canovas L; Flores E; Perez-Perez G; Luna-Arias JP; Orozco E
2000 Jul-Aug;31(4 Suppl):S279-S281, Archives of medical research (Mexico)
— id: 34628, year: 2000, vol: 31, page: S279, stat: Journal Article,

A comprehensive review of the natural history of Helicobacter pylori infection in children
Torres J; Perez-Perez G; Goodman KJ; Atherton JC; Gold BD; Harris PR; la Garza AM; Guarner J; Munoz O
2000 Sep-Oct;31(5):431-469, Archives of medical research (Mexico)
Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life
— id: 34626, year: 2000, vol: 31, page: 431, stat: Journal Article,

CagA-positive strains of Helicobacter pylori may protect against Barrett's esophagus
Vaezi MF; Falk GW; Peek RM; Vicari JJ; Goldblum JR; Perez-Perez GI; Rice TW; Blaser MJ; Richter JE
2000 Sep;95(9):2206-2211, American journal of gastroenterology
OBJECTIVE: Helicobacter pylori (H. pylori) colonization is associated with chronic gastritis, peptic ulcer disease, and adenocarcinoma of the distal stomach. However, the role of H. pylori strain variation in complicated gastroesophageal reflux disease, especially Barrett's esophagus, is unknown. Therefore, the aim of this study was to evaluate the prevalence of colonization by cagA+ and cagA- H. pylori strains in the spectrum of gastroesophageal reflux disease, including Barrett's esophagus. METHODS: A total of 251 patients undergoing endoscopy were categorized into four groups: controls, patients with gastroesophageal reflux disease alone, and patients with short- and long-segment Barrett's esophagus. All patients underwent upper endoscopies with biopsies and serum collections. H. pylori and degree of mucosal inflammation in gastric biopsies were assessed and serological assessment made for H. pylori and cagA status. RESULTS: The overall prevalence of H. pylori colonization in the study population was 35% (95% confidence interval = 29.5-41.4%) which did not differ significantly among the groups. However, colonization by cagA+ H. pylori strains was significantly more prevalent among controls (11/25; 44%) and patients with gastroesophageal reflux disease (13/36; 36%) than in patients with short-segment (2/10; 20%) or long-segment Barrett's esophagus (0/18; 0%). Patients with Barrett's esophagus were less likely to be colonized by cagA+ H. pylori strains than reflux patients without Barrett's esophagus (odds ratio = 0.27, 95% confidence interval = 0.11-0.67, p = 0.004). CONCLUSIONS: Colonization by cagA+ H. pylori strains may be protective against the formation of short- and long-segment Barrett's esophagus and its malignant complications
— id: 19038, year: 2000, vol: 95, page: 2206, stat: Journal Article,

Comparison of invasive and noninvasive methods for the diagnosis and evaluation of eradication of Helicobacter pylori infection in children
Yanez P; la Garza AM; Perez-Perez G; Cabrera L; Munoz O; Torres J
2000 Jul-Aug;31(4):415-421, Archives of medical research (Mexico)
BACKGROUND: Acquisition of Helicobacter pylori infection occurs mainly during childhood. To study the events associated with H. pylori colonization in children it is important to have reliable diagnostic methods. Our objective was to validate invasive and noninvasive tests for diagnosis of H. pylori infection in children before and after antimicrobial treatment. METHODS: Before treatment, invasive rapid urease test (RUT) culture and histology, as well as the noninvasive carbon-13 urea breath test (13C-UBT) and serology were validated in 59 children. The gold standard for H. pylori infection was any of three positives of the five tests. After antimicrobial treatment culture, histology, and 13C-UBT were validated in 43 children to determine eradication. The gold standard for eradication was negative in all three tests. RESULTS: For primary diagnosis, RUT was the most sensitive and specific test, followed by 13C-UBT, which performed better than serology, culture, and histology. Concordance tests also showed that RUT and 13C-UBT performed better. For determination of eradication, 13C-UBT and histology were better than culture, which showed poor sensitivity. CONCLUSIONS: RUT performed better for primary diagnosis. However, as endoscopy might not be indicated in most children, 13C-UBT could be the test of choice for diagnosis of H. pylori infection both before and after eradication treatment
— id: 34629, year: 2000, vol: 31, page: 415, stat: Journal Article,

Host specificity of Helicobacter pylori strains and host responses in experimentally challenged nonhuman primates
Dubois A; Berg DE; Incecik ET; Fiala N; Heman-Ackah LM; Del Valle J; Yang M; Wirth HP; Perez-Perez GI; Blaser MJ
1999 Jan;116(1):90-96, Gastroenterology
BACKGROUND & AIMS: The specificity of colonization by Helicobacter pylori and complex host-bacterium interactions cannot be readily examined in humans. The aim of this study was to perform such analyses in rhesus monkeys. METHODS: Four animals that had been cured of natural H. pylori colonization were challenged with a mixture of 7 strains of human origin, and bacteria recovered during periodic videogastroscopy were DNA fingerprinted. RESULTS: Three animals carried mixtures of several strains for 4 months, after which strain J166 predominated. In the fourth animal, only strain J238 was isolated from the earliest phase of colonization through 7 months, but strain J166 again became predominant by 10 months after the challenge. Gastritis scores and plasma gastrin and anti-H. pylori immunoglobulin G titers reached levels observed in naturally colonized animals by 4 months after the challenge; however, no plasma immunoglobulin A response was observed up to 10 months. CONCLUSIONS: These results show that (1) natural colonization does not elicit protective immunity against subsequent H. pylori challenge; (2) individuals differ in susceptibility to different H. pylori strains during initial stages of colonization; and (3) certain strains are better suited than others for long-term survival in different hosts. These observations show the complexity of H. pylori-host interactions
— id: 19077, year: 1999, vol: 116, page: 90, stat: Journal Article,

Serologic IgG response to urease in Helicobacter pylori-infected persons from Mexico
Leal-Herrera Y; Torres J; Perez-Perez G; Gomez A; Monath T; Tapia-Conyer R; Munoz O
1999 Apr;60(4):587-592, American journal of tropical medicine & hygiene
Helicobacter pylori urease is required to counteract acidity during colonization of the stomach, and has been suggested as a major immunodominant antigen. The aim of this study was to determine the anti-urease response in a representative national serologic survey in Mexico. The population surveyed included persons 1-90 years of age from all socioeconomic levels and geographic zones of the country. Helicobacter pylori status was determined by ELISA serology. The IgG anti-urease was studied by ELISA using a recombinant apoenzyme. We found that 2,930 of the 7,720 infected patients (38%) were seropositive for IgG urease. The rate of IgG anti-urease positivity increased with age; in children < 10 years old it was < 20% and in persons > 40 years old it was > 50%. Age and a region with a high level of development were risk factors for seropositivity, whereas gender, educational level, crowding, and socioeconomic level were not associated with seropositivity. In conclusion, in natural infection with H. pylori, the response to urease is poor, mainly during the first years of infection. This inconsistent immune response to the enzyme may favor persistence of infection. A vaccine eliciting a consistent anti-urease response might overcome immune evasion and enhance clearance of bacteria after exposure
— id: 34632, year: 1999, vol: 60, page: 587, stat: Journal Article,

Helicobacter pylori heat shock protein A: serologic responses and genetic diversity
Ng EK; Thompson SA; Perez-Perez GI; Kansau I; van der Ende A; Labigne A; Sung JJ; Chung SC; Blaser MJ
1999 May;6(3):377-382, Clinical & diagnostic laboratory immunology
Helicobacter pylori synthesizes an unusual GroES homolog, heat shock protein A (HspA). The present study was aimed at an assessment of the serological response to HspA in a group of Chinese patients with defined gastroduodenal pathologies and determination of whether diversity is present in the nucleotide sequences encoding HspA in isolates from these patients. Serum samples collected from 154 patients who had an upper gastrointestinal pathology and the presence of H. pylori defined by biopsy were tested for an immunoglobulin G (IgG) serologic response to H. pylori HspA by an enzyme linked immunosorbant assay. HspA-encoding nucleotide sequences in H. pylori isolates from 14 patients (7 seropositive and 7 seronegative for HspA) were analyzed by PCR and direct sequencing of the PCR products. The sequencing results were compared to those of 48 isolates from other parts of the world. Of the 154 known H. pylori-positive patients, 54 (35.1%) were seropositive for HspA. The A domain (GroES homology) of HspA was highly conserved in the 14 isolates tested. Although the B domain (metal-binding site unique to H. pylori) resembled that in the known major variant, particular amino acid substitutions allowed definition of an HspA variant associated with isolates from East Asia. There were no associations between patient characteristics and HspA seropositivity or amino acid sequences. We confirmed in this study that the clinical outcomes of H. pylori infection are not related to HspA antigenicity or to sequence variation. However, B-domain sequence variation may be a marker for the study of the genetic diversity of H. pylori strains of different geographic origins
— id: 19073, year: 1999, vol: 6, page: 377, stat: Journal Article,

Role of Helicobacter pylori cagA(+) strains and specific host immune responses on the development of premalignant and malignant lesions in the gastric cardia
Peek RM Jr; Vaezi MF; Falk GW; Goldblum JR; Perez-Perez GI; Richter JE; Blaser MJ
1999 Aug 12;82(4):520-524, International journal of cancer
The incidence rates of gastric cardia and esophageal adenocarcinomas are increasing, but data suggest that carriage of cagA(+) Helicobacter pylori strains may protect against development of Barrett's esophagus and esophageal adenocarcinoma. Our aims were to examine the relationship between pre-malignant and malignant lesions in the gastric cardia and serum antibodies to H. pylori antigens in patients with and without complications of Barrett's esophagus. The prevalence of carditis was 40% in controls compared with 13% in patients with complicated or uncomplicated Barrett's esophagus and cardia adenocarcinoma (p < 0.001). Cardia intestinal metaplasia (IM) and atrophy were present and concordant in 28% of controls but less frequent in patients with Barrett's alone or with dysplasia/adenocarcinoma (0% for each, p < 0.001). Carriage of cagA(+) strains was present in 34% of patients with carditis and significantly associated with increased frequency and severity of cardia inflammation, IM, and atrophy but not with adenocarcinoma. IgA and HspA seropositivity were significantly increased in H. pylori-colonized patients with carditis compared to persons with normal cardia histology (p </= 0.005) but not in persons with esophageal disease or cardia adenocarcinoma. We conclude that carriage of cagA(+) H. pylori strains and induction of particular serological responses are significantly associated with marked histological findings in the gastric cardia but not with adenocarcinoma of either the gastric cardia or esophagus
— id: 32251, year: 1999, vol: 82, page: 520, stat: Journal Article,

Detection of anti-VacA antibody responses in serum and gastric juice samples using type s1/m1 and s2/m2 Helicobacter pylori VacA antigens
Perez-Perez GI; Peek RM; Atherton JC; Blaser MJ; Cover TL
1999 Jul;6(4):489-493, Clinical & diagnostic laboratory immunology
Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori, and they encode products with differing functional activities. H. pylori strains containing certain types of vacA alleles have been associated with an increased risk for peptic ulcer disease. In this study, we tested serum samples and gastric juice from 19 H. pylori-negative and 39 H. pylori-positive patients for enzyme-linked immunosorbent assay reactivity with two different types of VacA antigens (types s1/m1 and s2/m2), which were purified from H. pylori 60190 and 86-338, respectively. Both antigens were recognized better by serum immunoglobulin G (IgG) from H. pylori-positive persons than by serum IgG from H. pylori-negative persons (P < 0.01). The s1/m1 VacA antigen was better recognized by sera from patients carrying vacA type s1/m1 strains than by sera from patients carrying vacA type s2/m2 or s1/m2 strains (P < 0.01). Conversely, the s2/m2 VacA antigen was better recognized by sera from patients carrying type s2/m2 or s1/m2 strains (P = 0.03). Serum IgG anti-VacA antibodies were present more frequently in patients carrying type s1/m1 strains than in other H. pylori-positive patients (P = 0.0002). In addition, the highest levels of IgA anti-VacA antibodies were detected in the gastric juice of patients carrying type s1/m1 strains. These data indicate that different VacA isoforms have distinct antigenic properties and that multiple forms of VacA elicit antibody responses in H. pylori-positive humans
— id: 19067, year: 1999, vol: 6, page: 489, stat: Journal Article,

The role of CagA status in gastric and extragastric complications of Helicobacter pylori
Perez-Perez GI; Peek RM; Legath AJ; Heine PR; Graff LB
1999 Dec;50(5):833-845, Journal of physiology & pharmacology
Two major markers of virulence have been described in H. pylori. The first is a secreted protein (VacA) that is toxic to human cells in tissue culture. This cytotoxin causes vacuolation of epithelial cells in vitro and induces epithelial cell damage in mice. The second is a 40-Kb pathogenicity island for which the gene cagA (cytotoxin-associated gene A) is a marker. Approximately 60% of H. pylori isolates in Western countries are cagA+. The protein encoded by cagA+ has a molecular weight of 120-140 kDa and exhibits sequence heterogeneity among strains isolated from Western and Eastern countries. Although no specific function has been identified for CagA, there is increasing evidence that cagA+ strains are associated with increased intensity of gastric inflammation and increased mucosal concentration of particular cytokines including interleukin 8. Inactivation of picB (Hp 0544) or any of several other genes in the cag island ablates the enhanced IL-8 secretion of human gastric epithelial cells in tissue culture. Furthermore, persons colonized with cagA+ strains have an increased risk of developing more severe gastric diseases such as peptic ulcer and distal (non-cardia) gastric cancer than those harboring cagA- strains. We investigated the role of cagA status in both gastroduodenal and extragastroduodenal disease with H. pylori. Among the diseases limited to the antrum and body of the stomach and the duodenum, we demonstrated a correlation between CagA seropositivity and peptic ulcer disease. We also showed correlation between distal gastric cancer rated and CagA prevalence in populations in both developed and developing countries. In addition, we found that for several Asian populations, the relationship between CagA seropositivity and gastroduodenal diseases was complex. For extragastroduodenal diseases, our results confirmed previous reports that demonstrated that CagA status did not play a role in diseases such as rheumatoid arthritis and hyperemesis gravidarum. However, we found a clear negative association between the presence of a positive response to CagA and esophageal diseases. Therefore, CagA seropositivity (and thus gastric carriage) is associated with increased risks of certain diseases (involving the lower stomach and duodenum) and decreased risks of GERD and its sequelae. This apparent paradox can best be explained by differences in the interaction of cagA+ and cagA- strains with their hosts
— id: 25606, year: 1999, vol: 50, page: 833, stat: Journal Article,

Insensitivity of the CLOtest for H. pylori, Especially in the Elderly
Abdalla AM; Sordillo EM; Hanzely Z; Perez-Perez GI; Blaser MJ; Holt PR; Moss SF
1998 Jul;115(1):243b-244, Gastroenterology
— id: 19089, year: 1998, vol: 115, page: 243b, stat: Journal Article,

Validation of a serologic test for the diagnosis of Helicobacter pylori infection and the immune response to urease and CagA in children
Camorlinga-Ponce M; Torres J; Perez-Perez G; Leal-Herrera Y; Gonzalez-Ortiz B; Madrazo de la Garza A; Gomez A; Munoz O
1998 Aug;93(8):1264-1270, American journal of gastroenterology
OBJECTIVE: Little is known about Helicobacter pylori infections and the immune response to urease and CagA in pediatric populations. Our aims were: 1) to validate serological assays for antibodies against whole cell extract, CagA, and urease of H. pylori; 2) to examine their role in diagnosis of infection in children with recurrent abdominal pain (RAP); and 3) to examine the antibody responses to CagA and urease in children. METHODS: An enzyme-linked immunosorbent assay (ELISA) for diagnosis of H. pylori infection using whole cell extracts was validated in 50 children with biopsy-confirmed infection. The IgG and IgA antibody responses against recombinant CagA and urease were compared by ELISA in 82 children with RAP and in 246 age- and sex-matched healthy children. RESULTS: The whole-cell extract ELISA had a sensitivity of 85 % and specificity of 87%. Children with RAP were more infected with H. pylori than were healthy control subjects; however, IgG and IgA CagA seropositivity was lower among those with RAP than among asymptomatic children (34% and 23% vs 76% and 55%, respectively; p < 0.0001). In both groups of children, the immune response to urease was low. CONCLUSION: A serodiagnosis of H. pylori infection using native strains was developed. The difference in the immune response between children with RAP and control subjects suggests that RAP occurs during the acute phase of H. pylori infection. Our results also suggest that urease is a poor immunogen
— id: 34634, year: 1998, vol: 93, page: 1264, stat: Journal Article,

An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma
Chow WH; Blaser MJ; Blot WJ; Gammon MD; Vaughan TL; Risch HA; Perez-Perez GI; Schoenberg JB; Stanford JL; Rotterdam H; West AB; Fraumeni JF
1998 Feb 15;58(4):588-590, Cancer research
Gastric colonization with Helicobacter pylori, especially cagA+ strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA+ strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA- strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA+ strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries
— id: 19105, year: 1998, vol: 58, page: 588, stat: Journal Article,

Cure of Helicobacter pylori infection by omeprazole-clarithromycin-based therapy in non-human primates
Dubois A; Berg DE; Fiala N; Heman-Ackah LM; Perez-Perez GI; Blaser MJ
1998 Feb;33(1):18-22, Journal of gastroenterology
Rhesus monkeys raised in colonies tend to become naturally infected by Helicobacter pylori early in life. Earlier attempts to cure H. pylori infection with a 10-day triple therapy (metronidazole, amoxicillin, and peptobismol) were only partially (60%) successful, probably because of preexisting metronidazole resistance. This study was carried out to determine the efficacy of an alternative clarithromycin-omeprazole-based therapy for curing H. pylori infection in Rhesus monkeys (Macaca mulatta), and to examine histologic and serologic correlates of curing. Five monkeys were endoscoped under ketamine anesthesia. Histology and culture of gastric biopsies and serologic tests demonstrated that they were H. pylori-positive. Two animals had not received prior anti-H. pylori treatment, while three other animals had failed triple therapy and carried metronidazole-resistant H. pylori strains. Quadruple therapy with omeprazole, clarithromycin, amoxicillin, and bismuth subsalicylate was given for 10 days to these five animals. All five animals were cured of the infection, and remained H. pylori-free, based on histology and culture at regular intervals for the 5 months posttherapy during which they were followed. Gastritis scores and anti-H. pylori IgG levels decreased in each animal during this period to levels characteristic of uninfected animals. These results indicate that an omeprazole-clarithromycin-based regimen can cure H. pylori infection in Rhesus monkeys, with resolution of abnormal histology and serologic responses. They suggest that this preclinical animal model is useful for testing new anti-H. pylori therapies
— id: 19102, year: 1998, vol: 33, page: 18, stat: Journal Article,

A community-based seroepidemiologic study of Helicobacter pylori infection in Mexico
Torres J; Leal-Herrera Y; Perez-Perez G; Gomez A; Camorlinga-Ponce M; Cedillo-Rivera R; Tapia-Conyer R; Munoz O
1998 Oct;178(4):1089-1094, Journal of infectious diseases
A nationwide community-based survey for Helicobacter pylori infection had not been done. This study sought to determine the seroprevalence of infection in Mexico, and the socioeconomic and demographic variables that are risk factors for infection. The survey assessed 11,605 sera from a sample population representing persons ages 1-90 years from all socioeconomic and demographic levels and from all regions of Mexico. Antibodies against H. pylori were studied by ELISA using whole cell antigen. Among the findings were that 66% of the population was infected and that age was the strongest risk factor for infection. By age 1 year, 20% were infected and by age 10 years, 50% were infected. Crowding (odds ratio [OR], 1.4), low educational level (OR, 2.42), and low socioeconomic level (OR, 1.43) were risk factors for infection. Prevalence was similar in urban and in rural communities (OR, 0.95). This study is the largest community-based seroepidemiologic study of H. pylori to date
— id: 34633, year: 1998, vol: 178, page: 1089, stat: Journal Article,

Infection with CagA+ Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico
Torres J; Perez-Perez GI; Leal-Herrera Y; Munoz O
1998 Oct 29;78(3):298-300, International journal of cancer
Helicobacter pylori strains possessing the Cag pathogenicity island have been associated with increased gastric inflammation and with duodenal ulcer. In contrast, studies on the association of cagA+ H. pylori infections and gastric cancer have shown conflicting results. The aim of our study was to determine whether H. pylori and CagA status are associated with gastric cancer in Mexico. We selected serum samples from 3 geographic areas with gastric cancer mortality rates per 100,000 inhabitants of 2.5 (low risk), 4.5 (medium risk) and 6.4 (high risk). H. pylori infection was determined by the detection of antibodies to H. pylori whole cell antigen by an enzyme-linked immunosorbent assay (ELISA). To study the prevalence of infection with cagA+ strains, serum IgG antibodies to CagA were determined by ELISA using a recombinant CagA antigen. Of the 2,775 individuals studied, 1,931 were H. pylori seropositive and 1,710 had antibodies against CagA. The risk for gastric cancer in the 3 populations studied increased proportionally as infection with cagA+ strains increased (p < 0.001 for trend). H. pylori infection also showed association with gastric cancer (p < 0.05). Individuals seropositive for CagA, but seronegative for H. pylori whole cell antigen, were more frequent in areas with higher gastric cancer rates (p < 0.01). These results support the possible role of CagA(+) status as predictor of risk for gastric adenocarcinoma in Mexico; this is in agreement with results in European and American populations, but contrary to studies in some Asian countries
— id: 25608, year: 1998, vol: 78, page: 298, stat: Journal Article,

The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease
Vicari JJ; Peek RM; Falk GW; Goldblum JR; Easley KA; Schnell J; Perez-Perez GI; Halter SA; Rice TW; Blaser MJ; Richter JE
1998 Jul;115(1):50-57, Gastroenterology
BACKGROUND & AIMS: The role of Helicobacter pylori in the pathogenesis of gastroesophageal reflux disease (GERD) is unknown. We determined the prevalence of cagA-positive (cagA+) H. pylori strains in patients with GERD or its complications compared with controls of similar age. METHODS: A total of 153 consecutive patients with GERD, Barrett's esophagus, and Barrett's esophagus complicated by dysplasia or adenocarcinoma were compared with 57 controls who underwent upper endoscopy for reasons other than GERD. H. pylori infection and CagA antibody status were determined by histology and enzyme-linked immunosorbent assay. RESULTS: H. pylori prevalence was lower (34%) in patients with GERD and its sequelae than in the control group (45.6%)(P = 0.15). Regardless of the group, increasing age was associated with higher prevalence of H. pylori (P = 0.003). When compared with controls (42.3%), the prevalence of cagA+ H. pylori strains decreased (P = 0.008) in patients with more severe complications of GERD (GERD, 36.7% [nonerosive GERD, 41.2%; erosive GERD, 30.8%]; Barrett's esophagus, 13.3%; and Barrett's with adenocarcinoma/dysplasia, 0%). CONCLUSIONS: Prevalence of H. pylori in patients with GERD and its sequelae was lower but not significantly different than that of a control group. However, patients carrying cagA+ strains of H. pylori may be protected against the complications of GERD, especially Barrett's esophagus and its associated dysplasia and adenocarcinoma
— id: 19090, year: 1998, vol: 115, page: 50, stat: Journal Article,

Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells
Beales I; Blaser MJ; Srinivasan S; Calam J; Perez-Perez GI; Yamada T; Scheiman J; Post L; Del Valle J
1997 Aug;113(2):465-471, Gastroenterology
BACKGROUND & AIMS: The pathophysiology of hypergastrinemia in Helicobacter pylori infection is undefined, but the infected antrum shows a marked inflammatory response with local production of cytokines. Hypergastrinemia and inflammatory infiltrate clear with successful eradication. The aim of this study was to examine whether the cytokines tumor necrosis factor alpha or interleukin 8 (IL-8), which are produced in the gastric mucosa of patients with H. pylori-induced peptic disease or H. pylori products, can stimulate gastrin release from isolated cultured canine G cells. METHODS: Canine G cells were isolated by collagenase digestion, enriched by centrifugal elutriation, incubated with cytokines, bacterial components, or both, and gastrin release was measured by radioimmunoassay. RESULTS: IL-8 (1 and 10 nmol/L) stimulated gastrin release by 34% +/- 13% and 43% +/- 23% (P < 0.05) above basal, respectively. H. pylori sonicates, water extract preparations, and lipopolysaccharide had no stimulatory actions, but the sonicates from two of four strains potentiated the effects of IL-8, leading to maximal gastrin release of 230% +/- 130% and 232% +/- 33% above basal, respectively (P < 0.05). CONCLUSIONS: IL-8 stimulated gastrin release from isolated G cells, and the effect was potentiated by H. pylori products. The interaction of cytokines and H. pylori may contribute to the hypergastrinemia seen in vivo
— id: 19122, year: 1997, vol: 113, page: 465, stat: Journal Article,

Lack of serologic evidence for Helicobacter pylori infection in head and neck cancer
Grandis JR; Perez-Perez GI; Yu VL; Johnson JT; Blaser MJ
1997 May;19(3):216-218, Head & neck
BACKGROUND: Several epidemiologic investigations have established a link between Helicobacter pylori infection and gastric malignancies. Because the stomach is in continuity with the oral cavity and the bacterium has been isolated from dental plaque and saliva, we hypothesized that H. pylori infection of the upper aerodigestive tract might result in mucosal disruption, allowing for subsequent transformation by known carcinogens such as tobacco and alcohol. METHODS: To test this hypothesis, we assayed for the presence of IgG antibodies to H. pylori in the serum of 21 patients with squamous cell carcinoma of the head and neck (SCCHN) and 21 matched controls without a history of head and neck cancer. RESULTS: The incidence of seropositivity in the SCCHN patients was 57% and in the controls, 62% (p > 0.05). CONCLUSIONS: These data do not support an etiologic role for H. pylori infection in head and neck cancer
— id: 19131, year: 1997, vol: 19, page: 216, stat: Journal Article,

Comparison of two enzyme-linked immunosorbent assay tests for diagnosis of Helicobacter pylori infection in China
Groves FD; Zhang L; Li JY; You WC; Chang YS; Zhao L; Liu WD; Rabkin CS; Perez-Perez GI; Blaser MJ; Gail MH
1997 Jul;6(7):551-552, Cancer epidemiology biomarkers & prevention
An ELISA based on a pool of United States strains of Helicobacter pylori was compared with a newly developed ELISA based on a pool of Chinese strains. Both assays were tested using sera from 132 Chinese study subjects with biopsy-proven H. pylori infection. Using cutpoints designed to yield equal specificities of 94.9% in an uninfected control population, the sensitivity of the Chinese assay was 100.0%, compared to 97.7% for the United States assay (P = 0.25 by McNemar test). These results suggest that a H. pylori assay based on pooled antigens from United States strains will perform as well in the rural Chinese population as one based on antigens from Chinese strains
— id: 19126, year: 1997, vol: 6, page: 551, stat: Journal Article,

Antigenic characterization of Helicobacter pylori strains from different parts of the world
Hook-Nikanne J; Perez-Perez GI; Blaser MJ
1997 Sep;4(5):592-597, Clinical & diagnostic laboratory immunology
Although Helicobacter pylori is considered to be relatively homogeneous at the phenotypic level, our aim was to describe its antigenic heterogeneity and to examine differences in host response. Whole-cell lysates of H. pylori strains originally isolated from persons from Africa, the People's Republic of China, Japan, Peru, Thailand, or the United States or from monkeys were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoblots were performed by using sera from H. pylori-infected persons from different areas of the world and rabbit immune sera against H. pylori antigens. Specific H. pylori antibody responses in persons from the United States and the People's Republic of China were analyzed by enzyme-linked immunosorbent assay with antigens prepared from U.S. or Chinese strains. Despite diverse origins, the strains showed conserved major bands of 84, 60, 56, 31, and 25 kDa. Although there were clear differences in minor bands, there was no obvious geographic pattern. The anti-CagA serum recognized 120- to 140-kDa bands in cagA+ strains from around the world. Although antigenic preparations from individual U.S. or Chinese strains were not optimally sensitive for serologic detection of infection in the heterologous country, use of pools of strains largely overcame this phenomenon. We conclude that conserved H. pylori antigens exist and are recognized by sera from persons from many parts of the world. The heterogeneity of H. pylori antigens and the serological responses of infected hosts is not fully explained by geographic differences. Use of pools may allow development of antigens for serologic testing in any country
— id: 19120, year: 1997, vol: 4, page: 592, stat: Journal Article,

Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells
Kidd M; Miu K; Tang LH; Perez-Perez GI; Blaser MJ; Sandor A; Modlin IM
1997 Oct;113(4):1110-1117, Gastroenterology
BACKGROUND & AIMS: Helicobacter pylori alterations in gastric acid output and mucosal proliferation may involve the enterochromaffin-like (ECL) cell. To test whether H. pylori affects ECL cell histamine secretion and proliferation, the effect of lipopolysaccharide (LPS) on ECL cell function in vitro was investigated. METHODS: Using a rat ECL cell preparation of high purity (+/-95%), basal and stimulated histamine secretion and DNA synthesis were measured by enzyme immunoassay and bromodeoxyuridine (BrdU) uptake, respectively. RESULTS: Escherichia coli LPS (10(-12) to 10(-6) mol/L) had no effect on basal and stimulated histamine secretion at concentrations of > 10(-6) mol/L. H. pylori LPS stimulated basal and gastrin-stimulated histamine secretion. These effects were completely inhibited by somatostatin (10(-10) mol/L) but not by the gastrin receptor antagonist L365,260 at 10(-6) mol/L. E. coli LPS had a weak stimulatory effect on ECL cell BrdU uptake at 10(-6) mol/L but had no effect on gastrin-stimulated BrdU uptake. H. pylori LPS did not stimulate basal synthesis but significantly increased (1.5-fold) gastrin-stimulated BrdU uptake. CONCLUSIONS: H. pylori influences both ECL cell proliferation and secretion in vitro. An interaction between H. pylori LPS and ECL cells may contribute to the reported abnormalities in acid secretion and gastric pathobiology noted in H. pylori infections
— id: 19118, year: 1997, vol: 113, page: 1110, stat: Journal Article,

Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14
Kirkland T; Viriyakosol S; Perez-Perez GI; Blaser MJ
1997 Feb;65(2):604-608, Infection & immunity
Helicobacter pylori persistently colonizes the human gastrointestinal tract and is associated with chronic gastritis and, in some cases, peptic ulcer disease or gastric neoplasms. One factor in the persistence of this organism may be its inability to elicit a strong inflammatory response. Lipopolysaccharide (LPS) is a proinflammatory substance found in the cell walls of all gram-negative bacteria. H. pylori LPS has been found by several different measures to be less active than LPS from Enterobacteriaceae. This study addresses the role of CD14 and LPS-binding protein in the cellular response to H. pylori LPS. We report that H. pylori LPS activates mammalian cells expressing CD14 at much lower LPS concentrations than those for control cells not expressing CD14. The maximal activation of CD14-70Z/3 cells by H. pylori LPS also requires LPS-binding protein. H. pylori LPS at concentrations as high as 30 microg/ml does not elicit an interleukin-8 (IL-8) response from the epithelial cell line SW620 in the presence of CD14; 10 ng of Escherichia coli LPS per ml elicits a maximal IL-8 response. Furthermore, in contrast to some other types of LPS with little activity, H. pylori LPS does not inhibit the CD14-70Z/3 cell response to E. coli LPS. From these studies, we conclude that H. pylori LPS, though much less active than E. coli LPS, stimulates cells via CD14
— id: 19137, year: 1997, vol: 65, page: 604, stat: Journal Article,

Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis
Peek RM; Moss SF; Tham KT; Perez-Perez GI; Wang S; Miller GG; Atherton JC; Holt PR; Blaser MJ
1997 Jun 18;89(12):863-868, Journal of the National Cancer Institute
BACKGROUND: Infection with Helicobacter pylori induces chronic gastritis in virtually all infected persons, and such gastritis has been associated with an increased risk of developing gastric cancer. This risk is further enhanced with cagA+ (positive for cytotoxin-associated gene A) H. pylori strains and may be a consequence of induced gastric cell proliferation and/or alteration in apoptosis (programmed cell death) in the gastric epithelium. PURPOSE: To determine whether the H. pylori cagA genotype and another virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial cell proliferation, apoptosis, and the histologic parameters of inflammation and injury, we quantitated these characteristics in infected and uninfected persons. METHODS: Fifty patients underwent upper gastrointestinal endoscopy, and biopsy specimens were taken. Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored by immunohistochemical analysis of the proliferation-associated antigen Ki-67. Antibodies directed against H. pylori and CagA protein were measured in the serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell degeneration, mucin depletion, intestinal metaplasia, glandular atrophy, and vacuolation were each scored in a blinded manner. Reported P values are two-sided. RESULTS: Persons harboring cagA+ strains (n = 20) had significantly higher gastric epithelial proliferation scores than persons infected with cagA-strains (n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but the difference in cell proliferation between the latter two groups was not statistically significant. The number of apoptotic cells per 100 epithelial cells (apoptotic index) in persons infected with cagA+ strains was lower than in persons infected with cagA-strains (P = .05). Apoptotic indices in the cagA+ group were similar to those in the uninfected group (P = .2). Epithelial cell proliferation was significantly correlated with acute gastric inflammation, but only in the cagA+ group (r = .44; P = .006). The cagA+ and vacA s1a genotypes were found to be concordant, confirming the close relationship between these virulence-related genotypes. CONCLUSIONS: Gastric mucosal proliferation was significantly correlated with the severity of acute gastritis in persons infected with cagA+ vacA s1a strains of H. pylori. This increased proliferation was not accompanied by a parallel increase in apoptosis. IMPLICATIONS: Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the heightened risk for gastric carcinoma that is associated with infection by cagA+ vacA s1a strains of H. pylori
— id: 19128, year: 1997, vol: 89, page: 863, stat: Journal Article,

Role of Helicobacter pylori infection in the development of pernicious anemia
Perez-Perez GI
1997 Nov;25(5):1020-1022, Clinical infectious diseases
It is now accepted that most patients with atrophic gastritis of the stomach have been infected with Helicobacter pylori. Several investigators have also suggested the possibility that H. pylori is involved in the early stages of pernicious anemia, which leads to severe atrophic gastritis of the fundus. In this article, studies investigating the association of this specific form of atrophic gastritis and H. pylori infection are reviewed. Most of the published studies indicate that patients with pernicious anemia are infected with H. pylori less often than are age-matched controls. However, because H. pylori infection may be present before the development of pernicious anemia, prospective studies during the pre-pernicious anemia stage of gastritis are needed
— id: 25609, year: 1997, vol: 25, page: 1020, stat: Journal Article,

Country-specific constancy by age in cagA+ proportion of Helicobacter pylori infections
Perez-Perez GI; Bhat N; Gaensbauer J; Fraser A; Taylor DN; Kuipers EJ; Zhang L; You WC; Blaser MJ
1997 Jul 29;72(3):453-456, International journal of cancer
Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal studies, infection with a cagA+ strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates
— id: 19124, year: 1997, vol: 72, page: 453, stat: Journal Article,

Value of serology as a noninvasive method for evaluating the efficacy of treatment of Helicobacter pylori infection
Perez-Perez GI; Cutler AF; Blaser MJ
1997 Nov;25(5):1038-1043, Clinical infectious diseases
The systemic humoral response to Helicobacter pylori was studied in 86 infected adult patients before antimicrobial therapy and at intervals following therapy. Endoscopy with collection of biopsy specimens was performed immediately before treatment; a 13C-labeled urea breath test was performed, and blood specimens were collected before treatment and at 1, 3, 6, 9, and 12 months after treatment. Serum samples from three patient groups (eradication success [n = 50], eradication failure [n = 16], and no treatment [n = 20]) were assayed for IgA and IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Levels of antibody to H. pylori before treatment were similar in all three groups. As expected, the no treatment and eradication failure groups had no significant changes in antibody levels during the study period. In contrast, for the eradication success group, the specific IgA and IgG antibody levels decreased progressively and significantly. We conclude that serology is a potentially useful way to monitor the success of treatment of H. pylori infection without using invasive or more expensive methods
— id: 19106, year: 1997, vol: 25, page: 1038, stat: Journal Article,

T-cell, antibody, and cytokine responses to homologs of the 60-kilodalton heat shock protein in Helicobacter pylori infection
Sharma SA; Miller GG; Peek RA; Perez-Perez G; Blaser MJ
1997 Jul;4(4):440-446, Clinical & diagnostic laboratory immunology
For Helicobacter pylori, the hsp60 heat shock protein encoded by hspB is being considered as a potential candidate for subunit vaccines. We investigated the humoral and cellular responses to H. pylori hsp60 and its cross-reactivity with the homologous Mycobacterium bovis p65 protein and autologous human hsp60 protein. H. pylori-infected persons had significantly higher levels than uninfected persons of serum immunoglobulin G antibodies recognizing H. pylori hsp60, but not M. bovis p65 or human hsp60, as determined by enzyme-linked immunosorbent assay. In contrast, immunoblotting demonstrated cross-reactivity of H. pylori hsp60 with human hsp60. T-cell recognition of H. pylori hsp60 was found in both infected and uninfected subjects, and there was no recognition of human hsp60. T cells from infected and uninfected subjects that had been activated in response to H. pylori hsp60 or M. bovis p65 were phenotypically similar but appeared to secrete different levels of gamma interferon and interleukin-10. These results demonstrate an apparent difference in the epitopes recognized by the T and B cells responding to H. pylori hsp60 in H. pylori-infected persons. In contrast to the T-cell responses, which were highly variable in all subjects and showed no recognition of autologous proteins, a specific B-cell response that may have cross-reactivity to human hsp60 is evident in some infected subjects
— id: 19125, year: 1997, vol: 4, page: 440, stat: Journal Article,

Transient and persistent experimental infection of nonhuman primates with Helicobacter pylori: implications for human disease
Dubois A; Berg DE; Incecik ET; Fiala N; Heman-Ackah LM; Perez-Perez GI; Blaser MJ
1996 Aug;64(8):2885-2891, Infection & immunity
Helicobacter pylori can establish chronic infection in the human gastric mucosa, and it is a major cause of peptic ulcer disease and a principal risk factor for gastric cancer. This creates a need for H. pylori infection models that mimic the human condition. To test the suitability of rhesus monkeys as infection models, H. pylori-free animals were inoculated intragastrically with mixtures of H. pylori strains, bacteria recovered from colonized animals were typed by arbitrarily primed PCR, and host inflammatory and immunologic responses were monitored. Among five H. pylori-free animals inoculated with a mixture of two human strains plus one monkey strain, one became persistently infected and one became only transiently infected. The recovered bacteria matched the monkey input strain in DNA fingerprint. A subsequent trial using two new human isolates and three animals that had resisted colonization by the monkey strain resulted in persistent infection in one animal and transient infection in two others. Antral gastritis, anti-H. pylori serum immunoglobulin G, and atrophy all increased, but with patterns that differed among animals. We conclude that (i) rhesus monkeys can be infected experimentally with H. pylori, (ii) individuals differ in susceptibility to particular bacterial strains, (iii) infections may be transient, and (iv) the fitness of a particular strain for a given host helps determine the consequences of exposure to that strain
— id: 19147, year: 1996, vol: 64, page: 2885, stat: Journal Article,

Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori. Federal Hyperimmune Immunoglobulin Therapy Study Group
Ellison RT; Perez-Perez G; Welsh CH; Blaser MJ; Riester KA; Cross AS; Donta ST; Peduzzi P
1996 Dec;24(12):1974-1981, Critical care medicine
OBJECTIVE: To determine the role of preexisting Helicobacter pylori infection in the development of acute upper gastrointestinal (GI) hemorrhage in intensive care unit (ICU) patients in relation to other potential predisposing risk factors. DESIGN: Prospective, multicenter, cohort study. SETTING: Medical and surgical ICUs in six tertiary care Department of Veterans Affairs Medical Centers. PATIENTS: Eight-hundred seventy-four patients without previous GI bleeding or peptic ulcer disease who were enrolled in a multicenter, randomized, controlled trial of prophylactic intravenous immunoglobulin to prevent ICU-associated infections. INTERVENTIONS: This substudy of the larger intravenous immunoglobulin study only involved data analysis and had no intervention. All patients were enrolled in the larger study where they received intravenous immunoglobulin or placebo as intervention. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated for the development of acute upper GI hemorrhage while in an ICU. Anti-H. pylori immunoglobulin G and immnoglobulin A concentrations were determined by enzyme immunoassay on preintervention serum samples. Seventy-six (9%) patients had over upper GI bleeding and a mortality rate of 49%, as compared with a 15% mortality rate in patients who did not bleed (p < .001). By logistic regression analysis, the following factors were associated with an increased risk of bleeding: acute hepatic failure, prolonged duration of nasogastric tube placement, alcoholism, and an increased serum concentration of anti-H. pylori immunoglobulin A. CONCLUSIONS: Increased anti-H. pylori immunoglobulin A concentrations, prolonged nasogastric intubation, alcoholism, and acute hepatic failure were found to be independently correlated with the development of acute GI bleeding in an ICU setting. These observations should be prospectively confirmed in an independent population before being used for treatment guidelines
— id: 19139, year: 1996, vol: 24, page: 1974, stat: Journal Article,

Susceptibility of Helicobacter pylori to the bactericidal activity of human serum
Gonzalez-Valencia G; Perez-Perez GI; Washburn RG; Blaser MJ
1996 Mar;1(1):28-33, Helicobacter
BACKGROUND: Human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation. If at all present, Helicobacter pylori within gastric tissue is rare, and bacteremia for this organism has been described only once. METHODS: To assess the susceptibility of H. pylori to the bactericidal activity present in normal human serum (NHS), we examined 13 H. pylori isolates. To assess the contributions of the classical and alternative complement pathways to killing, we added either C2-deficient or factor B-deficient serum, respectively, to heat-inactivated NHS. Also we assessed the ability of the strains to bind 125I-C3. RESULTS: After incubation for 60 minutes at 37 degrees C, all 13 H. pylori strains were killed by NHS; heating to 56 degrees C for 30 minutes ablated killing, indicating complement dependence for this phenomenon. In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used. Adding B-deficient serum to heat-inactivated normal human serum did not restore killing, but adding C2-deficient serum permitted partial killing. All of the 13 strains bound 125I-C3. Although the kinetics varied from strain to strain, C3 bound was significantly correlated (r = 0.61, p = 0.03) with serum susceptibility. CONCLUSIONS: H. pylori are susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major locus of variability
— id: 19108, year: 1996, vol: 1, page: 28, stat: Journal Article,

Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production
Harris PR; Mobley HL; Perez-Perez GI; Blaser MJ; Smith PD
1996 Aug;111(2):419-425, Gastroenterology
BACKGROUND & AIMS: Helicobacter pylori surface proteins induce the production of proinflammatory mediators by mononuclear phagocytes, but the protein responsible for this stimulation has not been identified. This study determined whether urease, the major component of the soluble proteins extracted from H. pylori grown in culture, activates mononuclear phagocytes and stimulates them to produce proinflammatory cytokines. METHODS: Primary human blood monocytes were incubated with column-purified H. pylori urease and assayed by flow cytometry, Immunoassay, and reverse-transcription polymerase chain reaction for phenotypic, functional, and molecular evidence of activation. RESULTS: H. pylori urease induced monocyte expression of surface interleukin 2 receptors and increased expression of HLA-DR, phenotypic changes consistent with activation. Urease also stimulated dose-dependent production of interleukin 1 beta, interleukin 6, interleukin 8, and tumor necrosis factor alpha peptides and messenger RNA. These urease-induced phenotypic and functional changes were inhibited by preincubation of the urease with antisera to H. pylori whole bacteria, purified urease, or the 31-kilodalton subunit of urease. CONCLUSIONS: Among the soluble proteins released by H. pylori, urease is capable of activating monocytes for proinflammatory cytokines production. The local production of cytokines by urease-stimulated mononuclear phagocytes may play a central role in the development of H. pylori gastroduodenal inflammation
— id: 19148, year: 1996, vol: 111, page: 419, stat: Journal Article,

Relationship of immune response to heat-shock protein A and characteristics of Helicobacter pylori-infected patients
Perez-Perez GI; Thiberge JM; Labigne A; Blaser MJ
1996 Nov;174(5):1046-1050, Journal of infectious diseases
Heat-shock protein A (HspA) is a GroES homolog in Helicobacter pylori. Using a recombinant HspA-maltose-binding protein fusion, the serologic response to HspA were determined. For 139 H. pylori-uninfected persons, responses to HspA were low-level or absent. In a survey of 273 infected persons, 105 (38.5%) were seropositive; there was no relationship between clinical outcome of infection and HspA seropositivity. Using paired sera obtained from 39 subjects (mean, 7.1 years apart), the stability of seroresponsiveness to HspA was examined. For 34 persons there was no change in status between the paired sera, but 5 (20%) of 25 initially seronegative persons seroconverted. The hypothesis that HspA seropositivity was related to patient age was examined using sera from 121 asymptomatic H. pylori-infected persons. Both the HspA seropositivity rate and the intensity of the response rose with age. In total, these findings indicate that HspA seropositivity is not universal but may be a consequence of prolonged H. pylori infection
— id: 19141, year: 1996, vol: 174, page: 1046, stat: Journal Article,

Campylobacter and helicobacter
Perez-Perez, Guillermo I; Blaser, Martin J
Medical microbiology [Galveston, Tex.] : University of Texas Medical Branch at Galveston, c1996,
— id: 5808, year: 1996, vol: , page: ?, stat: Chapter,

Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach
Blaser MJ; Perez-Perez GI; Kleanthous H; Cover TL; Peek RM; Chyou PH; Stemmermann GN; Nomura A
1995 May 15;55(10):2111-2115, Cancer research
To determine whether infection with a Helicobacter pylori strain possessing cagA is associated with an increased risk of development of adenocarcinoma of the stomach, we used a nested case-control study based on a cohort of 5443 Japanese-American men in Oahu, Hawaii, who had a physical examination and a phlebotomy during 1967 to 1970. We matched 103 H. pylori-infected men who developed gastric cancer during a 21-year surveillence period with 103 H. pylori-infected men who did not develop gastric cancer and tested stored serum specimens from patients and controls for the presence of serum IgG to the cagA product of H. pylori using an ELISA. The serum IgG assay using a recombinant CagA fragment had a sensitivity of 94.4% and a specificity of 92.5% when used in a clinically defined population; serological results were stable for more than 7 years. For men with antibodies to CagA, the odds ratio of developing gastric cancer was 1.9 (95% confidence interval, 0.9-4.0); for intestinal type cancer of the distal stomach, the odds ratio was 2.3 (95% confidence interval, 1.0-5.2). Age < 72 years and advanced tumor stage at diagnosis were significantly associated with CagA seropositivity. We conclude that infection with a cagA-positive H. pylori strain in comparison with a cagA-negative strain somewhat increases the risk for development of gastric cancer, especially intestinal type affecting the distal stomach
— id: 19171, year: 1995, vol: 55, page: 2111, stat: Journal Article,

Serologic detection of infection with cagA+ Helicobacter pylori strains
Cover TL; Glupczynski Y; Lage AP; Burette A; Tummuru MK; Perez-Perez GI; Blaser MJ
1995 Jun;33(6):1496-1500, Journal of clinical microbiology
Approximately 60% of Helicobacter pylori isolates possess the cagA gene and express its 120- to 140-kDa product (CagA). In this study, the cagA gene was detected in H. pylori isolates from 26 (81.3%) of 32 patients with duodenal ulcers (DU), 17 (68.0%) of 25 patients with gastric ulcers, and 23 (59.0%) of 39 patients with nonulcer dyspepsia (NUD). By Western blotting (immunoblotting) with antiserum to CagA, in vitro CagA expression was demonstrated for 95.5% of cagA+ strains compared with 0% of strains lacking cagA. Sera from patients infected with cagA+ strains (n = 66) reacted with recombinant CagA in an enzyme-linked immunosorbent assay to a significantly greater extent than either sera from patients infected with strains lacking cagA (n = 30) or sera from uninfected persons (n = 25) (P < 0.001). A strain lacking cagA was isolated from eight patients who had serum immunoglobulin G antibodies to CagA, which suggests that these patients were infected with multiple strains. Serum immunoglobulin G antibodies to CagA were present in 87.5, 76.0, and 56.4% of patients with DU, gastric ulcers, and NUD, respectively (odds ratio, 5.41; 95% confidence interval, 1.44 to 24.72; P = 0.004 [DU versus NUD]). These data demonstrate an association between infection with cagA+ H. pylori and the presence of duodenal ulceration and indicate that serologic testing is a sensitive method for detecting infection with cagA+ strains
— id: 19168, year: 1995, vol: 33, page: 1496, stat: Journal Article,

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection
Cutler AF; Havstad S; Ma CK; Blaser MJ; Perez-Perez GI; Schubert TT
1995 Jul;109(1):136-141, Gastroenterology
BACKGROUND & AIMS: Multiple tests are available for determining Helicobacter pylori infection. Our aim was to compare the sensitivity, specificity, and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori. METHODS: A total of 268 patients (mean age, 53.7 +/- 15.8 years; 142 male and 126 female; 125 white and 143 nonwhite) was tested for H. pylori infection by [13C]urea breath test (UBT), measurement of serum immunoglobulin (Ig) G and IgA antibody levels, and antral biopsy specimens for CLO test, histology, and Warthin-Starry stain. No patient received specific treatment for H. pylori before testing. The infection status for each patient was established by a concordance of test results. RESULTS: Warthin-Starry staining had the best sensitivity and specificity, although CLO test, UBT, and IgG levels were not statistically different in determining the correct diagnosis. The absence of chronic antral inflammation was the best method to exclude infection. Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age. IgA was a better predictor in white patients. CONCLUSIONS: The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry
— id: 19165, year: 1995, vol: 109, page: 136, stat: Journal Article,

Seroepizootiology of Helicobacter pylori gastric infection in nonhuman primates housed in social environments
Dubois A; Fiala N; Weichbrod RH; Ward GS; Nix M; Mehlman PT; Taub DM; Perez-Perez GI; Blaser MJ
1995 Jun;33(6):1492-1495, Journal of clinical microbiology
We determined the seroepizootiology of Helicobacter pylori infection in rhesus monkeys. Plasma was obtained from 196 animals (age range, 1 to 22 years) that were housed in social environments, either in indoor gang cages, in outdoor corrals, or in free-ranging forested conditions. Plasma immunoglobulin G levels were determined with a specific enzyme-linked immunosorbent assay, and the cutoff immunoglobulin G value for H. pylori seropositivity was determined from a study of 25 monkeys whose infection status was assessed by light microscopy and culture. One-year-old animals of both genders in all housing conditions had the lowest rate of positivity (60% in monkeys 1 year old versus 81% in monkeys 2 to 10 years old, P = 0.026). In addition, females tended to have higher rates of positivity than males. Seroconversion during a 1-year observation period occurred in 7 (28%) of 25 seronegative animals. Seroreversion occurred in 3 (4%) of the 78 positive animals; all 3 of these animals had received antimicrobial agents during the year. These observations demonstrate that the epizootiology of H. pylori infection in rhesus monkeys may serve as a model for human infection
— id: 19169, year: 1995, vol: 33, page: 1492, stat: Journal Article,

Seroepidemiology of Helicobacter pylori infection in heart transplant recipients
Dummer JS; Perez-Perez GI; Breinig MK; Lee A; Wolff SN; Kormos R; Griffith BP; Blaser MJ
1995 Nov;21(5):1303-1305, Clinical infectious diseases
We analyzed serum samples obtained from 100 heart transplant recipients before and after transplantation for the presence of IgG antibodies to Helicobacter pylori. Enzyme-linked immunosorbent assay revealed that 35 patients were seropositive before the procedure. Seropositive patients were older than seronegative patients, but the two groups did not differ in terms of cardiac diagnosis, gender, survival, or the number of admissions or rejection episodes. In addition, seropositive patients did not have more-frequent episodes of gastritis, ulcer disease, or gastrointestinal bleeding. Over a mean serological follow-up of 3.4 years, only one of 65 seronegative patients seroconverted. Of the 35 seropositive patients, 14 became seronegative for H. pylori a median of 194 days (range, 47-2,657 days) after transplantation. Seroreverters, as compared with serofast patients, had received more intravenous and total antibiotics during follow-up (P = .01), were more likely to have received a combination of antibiotics active against H. pylori (P < .025), and had received more antirejection treatment (P = .01). The incidence of H. pylori infection is not increased after heart transplantation, and many seropositive patients serorevert after transplantation when antibacterial and immunosuppressive agents are administered
— id: 19159, year: 1995, vol: 21, page: 1303, stat: Journal Article,

Helicobacter pylori and atrophic gastritis: importance of the cagA status
Kuipers EJ; Perez-Perez GI; Meuwissen SG; Blaser MJ
1995 Dec 6;87(23):1777-1780, Journal of the National Cancer Institute
BACKGROUND: Infection with Helicobacter pylori is a major risk factor for the development of atrophic gastritis and gastric cancer. H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen. H. pylori strains possessing cagA have been associated with enhanced induction of acute gastric inflammation. PURPOSE: We investigated the relationship between cagA status and the development of atrophic gastritis in a cohort of subjects infected with H. pylori. METHODS: Gastrointestinal endoscopy with biopsy sampling was used to study the natural history of gastritis in 58 subjects infected with H. pylori. Biopsy specimens were obtained before and after a mean follow-up period of 11.5 years (range, 10-13 years). The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein. Two-sided Fisher's exact tests, McNemar's tests, Student's t tests, and Wilcoxon sum rank tests were used to analyze the data. RESULTS: Twenty-four (41%) of the 58 evaluated subjects had serum antibodies against CagA (i.e., they were cagA positive), and 34 subjects were cagA negative. At the initial visit, moderate to severe atrophic gastritis was observed in eight (33%) of the cagA-positive subjects and in six (18%) of the cagA-negative subjects. At that time, positive cagA status and gastric atrophy were not significantly related (P = .22; Fisher's exact test; odds ratio [OR] 2.33; 95% confidence interval [CI] = 0.58-9.65). During follow-up, 16 (36%) of the 44 initially atrophy-negative subjects developed atrophic gastritis (eight [50%] of 16 cagA-positive subjects versus eight [29%] of 28 cagA-negative subjects; P = .20, Fisher's exact test; relative risk [RR] = 1.75; 95% CI = 0.82-3.76). In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0). One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer. Four (29%) of the 14 subjects initially diagnosed with atrophic gastritis showed regression of atrophy during follow-up (one cagA positive and three cagA negative). Therefore, at the end of follow-up, 15 (62%) of the 24 cagA-positive subjects had atrophic gastritis compared with 11 (32%) of the 34 cagA-negative subjects (P = .02; Fisher's exact test; OR = 3.48; 95% CI = 1.02-12.18). CONCLUSION: Infection with cagA-positive H. pylori strains is associated with an increased risk for the eventual development of atrophic gastritis and intestinal metaplasia
— id: 19157, year: 1995, vol: 87, page: 1777, stat: Journal Article,

Detection of Helicobacter pylori gene expression in human gastric mucosa
Peek RM; Miller GG; Tham KT; Perez-Perez GI; Cover TL; Atherton JC; Dunn GD; Blaser MJ
1995 Jan;33(1):28-32, Journal of clinical microbiology
Mucosal and systemic immunologic recognition of cagA by Helicobacter pylori-infected individuals is associated with peptic ulcer disease; however, in the laboratory, expression of cagA is subject to artificial conditions which may not accurately reflect the conditions in host tissues. Gastric antral and body biopsy specimens and serum for anti-H. pylori immunoglobulin G serology were obtained from 42 patients. Biopsy specimens were studied by histology, culture, and reverse transcription PCR (RT-PCR). Oligonucleotide primers specific for H. pylori (16S rRNA, ureA, and cagA) were used to detect bacterial mRNA in gastric biopsy specimens. PCR was performed on DNA from corresponding H. pylori isolates to detect genomic 16S rRNA, ureA, and cagA. Of the 42 patients from whom clinical specimens were obtained, 25 were infected with H. pylori on the basis of both serology and histology or culture (i.e., tissue positive); 13 were negative by serology, histology, and culture; and 4 were positive by serology only. RT-PCR with 16S rRNA primers detected 24 of 25 tissue-positive and 0 of 17 tissue-negative patients (P < 0.001). RT-PCR with ureA primers detected 16 of 25 tissue-positive and 0 of 17 tissue-negative patients (P < 0.001). CagA mRNA was detected by RT-PCR in 14 of 25 gastric biopsy specimens in the tissue-positive group and in 0 of 17 gastric biopsy specimens in the tissue-negative group. PCR of genomic DNA for the presence of the cagA gene in the corresponding bacterial isolates correlated absolutely with cagA gene expression in gastric tissue. These results indicate that RT-PCR is a sensitive and specific method for the detection of the presence of H. pylori and the expression of H. pylori genes in human gastric tissue. Detection of H. pylori gene expression in vivo by this approach may contribute to improving the diagnosis and understanding the pathogenesis of H. pylori infections
— id: 19179, year: 1995, vol: 33, page: 28, stat: Journal Article,

Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains
Peek RM; Miller GG; Tham KT; Perez-Perez GI; Zhao X; Atherton JC; Blaser MJ
1995 Dec;73(6):760-770, Laboratory investigation
BACKGROUND: Helicobacter pylori strains that possess the cytotoxin-associated gene (cagA) are highly associated with peptic ulcer disease, but the role of cagA in pathogenesis is unknown. EXPERIMENTAL DESIGN: To test the hypothesis that cagA+ stains elicit a greater proinflammatory cytokine response in the gastric mucosa than cagA- strains, gastric biopsies were obtained from 52 patients and studied by histology, culture, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction. RESULTS: Of 52 patients, 32 (62%) were infected with H. pylori based upon both serology and histology or culture, 16 (31%) were negative by serology, histology, and culture, and four (7%) were positive by serology only. Of 15 H. pylori-infected patients with peptic ulceration, 14 (92%) were infected with cagA+ strains compared with 8 (50%) of 16 patients with gastritis alone, and those infected with cagA+ strains had significantly higher grades of inflammation in the gastric mucosa. Antral inflammation score was significantly associated with IL-8 production. Antral biopsies from infected patients, compared with uninfected patients, significantly more often demonstrated IL-1 beta, IL-2, and IL-8 expression, and those infected with cagA+ compared with cagA- strains significantly more often expressed IL-1 alpha and IL-1 beta and showed elevated antral IL-8 protein levels. Similarly, patients with ulcer disease significantly more often expressed antral IL-1 alpha and IL-8 than those without ulceration. CONCLUSION: These results indicate that infection with cagA+ H. pylori strains is associated with higher grades of gastric inflammation, correlating with enhanced mucosal levels of IL-8, and increased risk of peptic ulceration
— id: 19156, year: 1995, vol: 73, page: 760, stat: Journal Article,

Activation of human THP-1 cells and rat bone marrow-derived macrophages by Helicobacter pylori lipopolysaccharide
Perez-Perez GI; Shepherd VL; Morrow JD; Blaser MJ
1995 Apr;63(4):1183-1187, Infection & immunity
The mechanism by which Helicobacter pylori, which has little or no invasive activity, induces gastric-tissue inflammation and injury has not been well characterized. We have previously demonstrated that water-extracted proteins of H. pylori are capable of activating human monocytes by a lipopolysaccharide (LPS)-independent mechanism. We have now compared activation of macrophages by purified LPS from H. pylori and from Escherichia coli. LPS was prepared by phenol-water extraction from H. pylori 88-23 and from E. coli O55. THP-1, a human promyelomonocytic cell line, and macrophages derived from rat bone marrow each were incubated with the LPS preparations, and cell culture supernatants were assayed for production of tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), and nitric oxide. THP-1 cells showed maximal activation by the LPS molecules after cell differentiation was induced by phorbol 12-myristate 13-acetate. Maximal TNF-alpha and PGE2 production occurred by 6 and 18 h, respectively, in both types of cells. In contrast, NO was produced by rat bone marrow-derived macrophages only and was maximal at 18 h. The minimum concentration of purified LPS required to induce TNF-alpha, PGE2, and NO responses in both types of cells was 2,000- to 30,000-fold higher for H. pylori than for E. coli. Purified LPS from three other H. pylori strains with different polysaccharide side chain lengths showed a similarly low level of activity, and polymyxin B treatment markedly reduced activity as well, suggesting that activation was a lipid A phenomenon. These results indicate the low biological activity of H. pylori LPS in mediating macrophage activation
— id: 19175, year: 1995, vol: 63, page: 1183, stat: Journal Article,

Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease
Szelc-Kelly CM; Goral S; Perez-Perez GI; Perkins BA; Regnery RL; Edwards KM
1995 Dec;96(6):1137-1142, Pediatrics
OBJECTIVE. To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. DESIGN. Prospective, controlled trial. SETTING: Referral clinic and hospitalized patients in a university medical center. PARTICIPANTS. Eighty patients with CSD and 57 healthy control subjects of similar age. MAIN OUTCOME MEASURES. The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. RESULTS. Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. CONCLUSION. Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD
— id: 25610, year: 1995, vol: 96, page: 1137, stat: Journal Article,

Helicobacter pylori infection and food-cobalamin malabsorption
Carmel R; Perez-Perez GI; Blaser MJ
1994 Feb;39(2):309-314, Digestive diseases & sciences
Two entities of considerable recent interest, Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody to H. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT < 1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0-1.99%) and 42% of 59 subjects with normal absorption (EYCAT > or = 2.0%) (chi 2 = 9.52, P < 0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03 +/- 1.83% vs 3.11 +/- 2.13%, t = 2.913, P = 0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence of H. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced by H. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status
— id: 19197, year: 1994, vol: 39, page: 309, stat: Journal Article,

Natural gastric infection with Helicobacter pylori in monkeys: a model for spiral bacteria infection in humans
Dubois A; Fiala N; Heman-Ackah LM; Drazek ES; Tarnawski A; Fishbein WN; Perez-Perez GI; Blaser MJ
1994 Jun;106(6):1405-1417, Gastroenterology
BACKGROUND/AIMS: There is no generally accepted model for Helicobacter pylori infection in humans. The aim of this study was to examine the natural history and effect of treatment in rhesus monkeys and sequentially define the immune response to H. pylori in relation to treatment. METHODS: Infection and gastritis were graded blindly by histological analysis and culture of biopsy specimens harvested during gastroduodenoscopies in 26 anesthetized colony-bred monkeys. Plasma H. pylori-specific immunoglobulin (Ig) G levels were determined by enzyme-linked immunosorbent assay. RESULTS: H. pylori and Gastrospirilum hominis-like organisms were present in 13 and 9 monkeys, respectively; 3 animals harbored both organisms, whereas 4 monkeys were not infected. Gastritis score was < or = 1.5 in animals uninfected or infected only with G. hominis-like organisms and > or = 2.0 in all H. pylori-infected animals. IgG ratios were > or = 0.5 in 12 of 13 H. pylori-infected animals and in 2 of 13 H. pylori-negative animals (P < 0.001). One monkey became infected with H. pylori during the observation period, with concurrent increase of gastritis and plasma IgG levels. In untreated animals, infection, gastritis, and plasma IgG levels remained unchanged over 7-15 months. Triple therapy eradicated H. pylori at 6 months in 4 of 6 animals while suppressing gastritis and plasma IgG levels. CONCLUSIONS: Rhesus monkeys harboring H. pylori are persistently infected and have gastritis and elevated specific IgG levels, all of which may respond to appropriate therapy, whereas G. hominis infection is associated with little inflammation
— id: 19190, year: 1994, vol: 106, page: 1405, stat: Journal Article,

Immunological and molecular characterization of Helicobacter felis urease
Gootz TD; Perez-Perez GI; Clancy J; Martin BA; Tait-Kamradt A; Blaser MJ
1994 Mar;62(3):793-798, Infection & immunity
Urease activity has recently been shown to be an important virulence determinant for Helicobacter pylori, allowing it to survive the low pH of the stomach during colonization. Experimental murine infection with Helicobacter felis is now being used as a model for H. pylori infection to study the effects of vaccines, antibiotics, and urease inhibitors on colonization. However, little information comparing the ureases of H. felis and H. pylori is available. Urease was partially purified from the cell surface of H. felis ATCC 49179 by A-5M agarose chromatography, resulting in an eightfold increase in specific activity over that of crude urease. The apparent Km for urea for the partially purified urease was 0.4 mM, and the enzyme was inhibited in a competitive manner by flurofamide (50% inhibitory concentration = 0.12 microM). Antiserum to whole cells of H. pylori recognized both H. pylori and H. felis urease B subunits. Antiserum raised against H. felis whole cells recognized the large and small autologous urease subunits and the cpn60 heat shock molecule in both H. felis and H. pylori. However, this antiserum showed only a weak reaction with the B subunit of H. pylori urease. Two oligomeric DNA sequences were used as probes to evaluate the relatedness of H. felis and H. pylori urease gene sequences. One 30-mer from the ureA sequence, which had been shown previously to be specific for H. pylori, failed to hybridize to H. felis genomic DNA. A probe to the putative coding sequence for the active site of the H. pylori ureB subunit hybridized at low intensity to a 2.8-kb fragment of BamHI-HindIII-digested H. felis DNA, suggesting that the sequences were homologous but not identical, a result confirmed from the recently published sequences of ureA and ureB from H. felis
— id: 19196, year: 1994, vol: 62, page: 793, stat: Journal Article,

Helicobacter pylori infection and the risk for duodenal and gastric ulceration
Nomura A; Stemmermann GN; Chyou PH; Perez-Perez GI; Blaser MJ
1994 Jun 15;120(12):977-981, Annals of internal medicine
OBJECTIVE: To determine whether a preexisting Helicobacter pylori infection increases the risk for developing duodenal or gastric ulcer. DESIGN: A nested case-control study based on a cohort of 5443 Japanese-American men who had a physical examination and a phlebotomy from 1967 to 1970. SETTING: All 10 general hospitals on the Hawaiian island of Oahu. PATIENTS: 150 patients with gastric ulcer and 65 patients with duodenal ulcer identified in the cohort of study participants after a hospital surveillance period of more than 20 years. MEASUREMENTS: Stored serum specimens from patients and from matched controls were tested for the presence of serum IgG antibody to H. pylori using enzyme-linked immunosorbent assay. RESULTS: 93% of the 150 patients with gastric ulcer and 78% of the matched controls had a positive antibody level for H. pylori-specific IgG, yielding an odds ratio of 3.2 (95% CI, 1.6 to 6.5). For duodenal ulcer, 92% of the 65 patients and 78% of the matched controls had a positive test result, yielding an odds ratio of 4.0 (CI, 1.1 to 14.2). As the level of antibody to H. pylori increased, a statistically significant increase was noted in the risk for gastric and duodenal ulcer. The association with H. pylori infection was statistically significant for both types of ulcer, even when the diagnosis was made 10 or more years after the serum sample had been obtained. CONCLUSION: Preexisting H. pylori infection increases the risk for subsequent development of either duodenal or gastric ulcer disease
— id: 19189, year: 1994, vol: 120, page: 977, stat: Journal Article,

Correlation between serological and mucosal inflammatory responses to Helicobacter pylori
Perez-Perez GI; Brown WR; Cover TL; Dunn BE; Cao P; Blaser MJ
1994 May;1(3):325-329, Clinical & diagnostic laboratory immunology
In 82 patients who underwent gastroduodenoscopy, acute and chronic gastric mucosal inflammation was scored for severity, and systemic humoral immune responses to Helicobacter pylori antigens were assessed by enzyme-linked immunosorbent assays. On the basis of culture, gastric histology, and serologic evaluation, 33 patients were classified as H. pylori infected and 36 were classified as uninfected. Thirteen patients had negative cultures and stains but were seropositive and were analyzed separately from the other two groups. Specific serum immunoglobulin G (IgG) subclass responses to H. pylori whole-cell antigens and specific IgG responses to the 54-kDa heat shock protein homolog (Hp54K) and vacuolating cytotoxin were significantly greater in infected than in uninfected patients as were specific IgA responses to whole-cell antigens and cytotoxin (P < 0.001). Among the H. pylori-infected persons, serum IgG responses to Hp54K and to the vacuolating cytotoxin were correlated with acute mucosal inflammatory scores. In contrast, serum IgA responses to whole-cell sonicate and to vacuolating cytotoxin were inversely related to chronic inflammatory scores. By multivariant regression analysis, only specific serum IgG responses to Hp54K correlated with severity of inflammation (both acute and chronic; P < 0.001); these responses may be markers of inflammation or these antibodies could play a direct role in the pathogenesis of H. pylori-induced inflammation
— id: 19193, year: 1994, vol: 1, page: 325, stat: Journal Article,

Effects of cations on Helicobacter pylori urease activity, release, and stability
Perez-Perez GI; Gower CB; Blaser MJ
1994 Jan;62(1):299-302, Infection & immunity
The urease of Helicobacter pylori is an important antigen and appears critical for colonization and virulence. Several studies have indicated a superficial localization for the H. pylori urease, and the purpose of this study was to determine the effects of cations on the release and stability of urease activity from H. pylori cells. Incubation of partially purified H. pylori urease in water containing 1, 5, or 10 mM Ca2+, Mg2+, K+, Na+, EDTA, or EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] had little effect on activity. In contrast, 1 mM Fe3+, Cu2+, Co2+, or Zn2+ substantially (> 80%) inhibited activity, and 10 mM Fe2+, Mn2+, and Ni2+ inhibited about 30% of the activity. Addition of Ca2+ or Mg2+ markedly decreased extraction of urease from intact H. pylori cells by water, but 1 mM Na+, K+, EGTA, or EDTA each had minimal effects on release, suggesting that divalent cations have a role in attachment of urease to H. pylori cells. The stability of enzymatic activity at 4 degrees C was enhanced by addition of glycerol or 2-mercaptoethanol; however, even after loss of activity, full antigenicity for human serum was retained
— id: 19199, year: 1994, vol: 62, page: 299, stat: Journal Article,

Seroprevalence of Helicobacter pylori infection is not increased in pediatric inflammatory arthritides
Shabib S; Laxer R; Silverman E; Perez-Perez G; Blaser M; Sherman P
1994 Aug;21(8):1548-1552, Journal of rheumatology
OBJECTIVE. To determine the seroprevalence of H. pylori infection among children with inflammatory arthritides receiving antiinflammatory drug therapy. METHODS. An enzyme linked immunosorbent assay (ELISA) was used to detect H. pylori specific immunoglobulin G antibody in 95 children with inflammatory arthritides, 53 children with chronic inflammatory bowel diseases and 47 parents of children with inflammatory arthritis. RESULTS. The frequency of seropositivity in children with arthritis (9/95, 9.5%) was not significantly higher than in children with chronic inflammatory bowel diseases (1/53, 1.9%; p = 0.16). Serum samples from parents were positive in 16 of 47 (34%), including 4 parents with children who also demonstrated a positive immune response. CONCLUSION. These data do not provide evidence for an increased frequency of H. pylori infection among children with inflammatory arthritides. The therapeutic use of ulcerogenic medications is likely to be an independent risk factor predisposing to dyspeptic symptoms and gastritis in this patient population
— id: 34635, year: 1994, vol: 21, page: 1548, stat: Journal Article,

Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant
Sharma SA; Miller GG; Perez-Perez GI; Gupta RS; Blaser MJ
1994 Jul;97(1):126-132, Clinical & experimental immunology
Helicobacter pylori is a major cause of chronic antral gastritis and peptic ulcer disease. Further definition is needed of the factors that determine whether infected individuals remain asymptomatic, or ultimately develop ulceration of the mucosa or transformation to malignancy. To explore the possibility that host response to H. pylori may play a role in the outcome of this infection, we have examined humoral and cellular recognition of several H. pylori proteins by seropositive and seronegative persons. A complex mixture of water-extractable cell proteins, which did not include lipopolysaccharide (LPS), was recognized by serum antibodies only in seropositive or infected individuals. IgG from seropositive subjects also bound to urease and to a heat shock protein (hsp)60 that is homologous to the 65-kD mycobacterial heat shock protein, while sera from uninfected individuals were negative. Although antibody responses to these antigens were restricted to seropositive subjects, T cell recognition of the same proteins was found in both seropositive and seronegative subjects. The water extract of H. pylori stimulated peripheral blood mononuclear cells (PBMC) from all subjects, while purified proteins activated lymphocytes of only some seropositive and seronegative subjects. PBMC that were activated by the H. pylori hsp60 did not respond to the autologous human p60 heat shock protein. These results demonstrate that, in contrast to antibody responses, T cell recognition of H. pylori proteins may occur in non-infected persons. In addition, the data suggest that in these subjects, peripheral lymphocytes that are activated by bacterial heat shock proteins do not mediate tissue damage by recognition of human heat shock homologues
— id: 19187, year: 1994, vol: 97, page: 126, stat: Journal Article,

Helicobacter pylori infection in Japanese patients with adenocarcinoma of the stomach
Blaser MJ; Kobayashi K; Cover TL; Cao P; Feurer ID; Perez-Perez GI
1993 Nov 11;55(5):799-802, International journal of cancer
To examine the association of Helicobacter pylori infection with adenocarcinoma of the stomach in Japanese patients, we studied 29 patients and 58 matched controls. Ascertainment of H. pylori status was based on the presence of specific IgG to H. pylori. For the entire group, an association of this infection with gastric adenocarcinoma was suggested but not statistically significant. For patients in a putatively high-risk subgroup (non-cardia tumors and age < or = 70 years), the association was significant. Assays detecting serum IgA to whole H. pylori cells and cytotoxin, IgG to cytotoxin and Hp54K (the heat-shock protein homolog) and serum neutralization of cytotoxin activity each showed clear differences between H. pylori-infected and uninfected persons in this population. However, for none of these assays was there a significant difference between values for H. pylori-infected persons with or without gastric cancer. Thus, while H. pylori infection was associated with non-cardia gastric cancer in Japanese persons < or = 70 years of age, use of these additional serologic markers did not define additional factors that might be associated with increased risk
— id: 19202, year: 1993, vol: 55, page: 799, stat: Journal Article,

Identification and characterization of Helicobacter pylori phospholipase C activity
Weitkamp JH; Perez-Perez GI; Bode G; Malfertheiner P; Blaser MJ
1993 Sep;280(1-2):11-27, Zentralblatt fur bakteriologie
We analyzed 11 H. pylori isolates from humans using the artificial chromogenic substrate paranitrophenylphosphorylcholine to detect phospholipase C (PLC) activity. The range of PLC in sonicates was 8.8-92.3 (Mean 56.9 +/- 6.5) nmol of substrate hydrolysed min-1 mg-1 protein; the amount of activity was not associated with urease or cytotoxin levels. Addition of sorbitol or glycerol enhanced PLC activity of H. pylori sonicate and purified PLC from C. perfringens (PLC1) but not purified PLC from B. cereus (PLC3). H. pylori sonicates had little acid phosphatase and no detectable alkaline phosphatase activity, and H. pylori PLC showed markedly different biochemical characteristics from either phosphatase. In total, these studies indicate that activity measured in H. pylori sonicate by PLC assay is due to PLC and not phosphatase activity. The temperature optimum for PLC activity of H. pylori sonicate was 56 degrees C and for PLC 1 was 65 degrees C. For H. pylori PLC and PLC1, optimal activity occurred at pH 8. Despite multiple similarities between H. pylori PLC and PLC1, known PLC inhibitors show different interactions with each enzyme. Although PLC activity is present in many subcellular constituents of H. pylori, including culture supernatants and water extracts, highest specific activity is associated with a membrane-enriched fraction
— id: 19208, year: 1993, vol: 280, page: 11, stat: Journal Article,

Humoral immune response to Lipopolysaccaride antigens of Campylobacter jejuni
Blaser, Martin J; Perez-Perez, Guillermo I
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1992,
Campylobacter jejuni and the closely related organism Campylobacter coli have been established as among the most common bacterial causes of acute diarrheal disease of humans in developed and developing countries (5.8). A wide variety of mammalian and avian species also are infected by those organisms and thus represent an important reservoir for transmission to humans. Development of vaccines against these organisms would therefore be worthwhile, but knowledge of their antigens is rudimentary
— id: 1616, year: 1992, vol: , page: , stat: ,

Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori
Dunn BE; Roop RM; Sung CC; Sharma SA; Perez-Perez GI; Blaser MJ
1992 May;60(5):1946-1951, Infection & immunity
Helicobacter pylori is associated with gastritis and peptic ulcer disease in humans. We have identified a homolog of the chaperonin cpn60 family of heat shock proteins in H. pylori, referred to as Hp54K. Hp54K, purified from water-extractable H. pylori proteins, migrated as a single band at 54 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its native molecular mass was 740 kDa; thus, Hp54K apparently comprises a 14-mer. The N-terminal 33 residues of Hp54K exhibited 60.6, 57.6, 54.5, 54.5, 51.5, and 51.5% identity with corresponding sequences in the following cpn60 homologs: HtpB (Legionella pneumophila), P1 (human mitochondria), GroEL (Escherichia coli), BA60K (Brucella abortus), HypB (Chlamydia trachomatis), and the 65-kDa immunodominant protein of Mycobacterium bovis BCG, respectively. Hp54K was the only protein recognized in whole-cell preparations of H. pylori by immunoblotting using monospecific antisera against cpn60 homologs from L. pneumophila, E. coli, C. trachomatis, and M. bovis BCG. Antiserum against Hp54K recognized proteins with molecular masses of 50 to 60 kDa in a large number of gram-negative bacteria, consistent with the known highly conserved nature of cpn60 proteins. Hp54K is a major protein and is immunogenic in humans infected with H. pylori. Thus, Hp54K shares many similarities with known cpn60 homologs. On the basis of the proposed role of other cpn60 proteins in induction of chronic inflammation, immune cross-reactivity between Hp54K and gastric tissue may provide an important link between H. pylori infection and gastritis
— id: 19228, year: 1992, vol: 60, page: 1946, stat: Journal Article,

Helicobacter pylori seroprevalence in patients with rheumatoid arthritis: effect of nonsteroidal anti-inflammatory drugs and gold compounds
Gubbins GP; Schubert TT; Attanasio F; Lubetsky M; Perez-Perez GI; Blaser MJ
1992 Oct;93(4):412-418, American journal of medicine
PURPOSE: To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) intolerance and the effect of gold use on the seroprevalence of H. pylori. PATIENTS AND METHODS: We examined the frequency of discontinuation of NSAIDs in 132 unselected patients with rheumatoid arthritis attending an outpatient subspecialty clinic, and the effect of gold compound use on the seroprevalence (by IgG enzyme-linked immunosorbent assay) of H. pylori infection in this population. Logistic and multivariate regression analysis was performed adjusting for age, gender, ethnic origin, history of ulcer, and duration of rheumatoid arthritis. RESULTS: Fifty-four patients had a positive serology for H. pylori (41%). Twenty-seven of the seropositive patients (50%), versus 45 of the seronegative patients (57.7%), had to discontinue NSAIDs (aspirin and/or nonaspirin) at least once since their diagnosis of rheumatoid arthritis because of gastrointestinal side effects (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.63 to 1.38). Forty-one of the seropositive patients (76%) had received gold compounds as compared with 62 of the seronegative patients (79.5%) (OR: 0.96; 95% CI: 0.61 to 1.50). CONCLUSION: We did not find any relationship between H. pylori seropositivity and NSAID intolerance in patients with rheumatoid arthritis. In addition, our results do not demonstrate a reduction in H. pylori seroprevalence in rheumatoid arthritis patients treated with gold compounds
— id: 19220, year: 1992, vol: 93, page: 412, stat: Journal Article,

Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa
Mai UE; Perez-Perez GI; Allen JB; Wahl SM; Blaser MJ; Smith PD
1992 Feb 1;175(2):517-525, Journal of experimental medicine
The mechanism by which Helicobacter pylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. pylori releases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. pylori whole bacteria or H. pylori-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. pylori urease (a major component of the surface proteins) exhibited dose-dependent, antibody-inhibitable chemotactic activity. In addition, a synthetic 20-amino acid peptide from the NH2-terminal portion of the 61-kD subunit, but not the 30-kD subunit, of urease exhibited chemotactic activity for monocytes and neutrophils, localizing the chemotactic activity, at least in part, to the NH2 terminus of the 61-kD subunit of urease. The ability of leukocytes to chemotax to H. pylori surface proteins despite formyl-methionyl-leucyl-phenylalanine (FMLP) receptor saturation, selective inhibition of FMLP-mediated chemotaxis, or preincubation of the surface proteins with antiserum to FMLP indicated that the chemotaxis was not FMLP mediated. Finally, we identified H. pylori surface proteins and urease in the lamina propria of gastric antra from patients with H. pylori-associated gastritis but not from uninfected subjects. These findings suggest that H. pylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides
— id: 19230, year: 1992, vol: 175, page: 517, stat: Journal Article,

Symptoms and risk factors of Helicobacter pylori infection in a cohort of epidemiologists
Parsonnet J; Blaser MJ; Perez-Perez GI; Hargrett-Bean N; Tauxe RV
1992 Jan;102(1):41-46, Gastroenterology
To identify symptoms and risk factors associated with Helicobacter pylori infection, a cohort of 341 epidemiologists was studied. All subjects had one banked serum (collected between 1969 and 1987) and one recent serum sample (collected in 1988) evaluated for H. pylori immunoglobulin G by enzyme-linked immunosorbent assay; subjects provided information on gastrointestinal symptoms and risk factors for gastritis and peptic ulcer disease. Prevalence of infection decreased from the early 1970s to the present. Eleven subjects (3% of the total cohort) seroconverted during the interval between serum samples, giving a crude conversion rate of 0.49% per person-year (95% confidence interval, 0.3-0.9). Nonreactors on the 1988 serum sample described similar symptoms to reactors. However, subjects who seroconverted in the interval between the two serum samples were more likely than either persistent nonreactors [relative risk (RR), 4.1] or persistent reactors (RR, 3.7) to have experienced upper gastrointestinal symptoms in the interval years. Consumption of caffeinated beverages (RR, 4.6) and residence in the northeastern United States (RR, 5.3) seemed to increase risk for infection. Because pain was similarly common in H. pylori-positive and -negative patients, H. pylori cannot be summarily accepted as the cause of dyspeptic symptoms even when infection is confirmed
— id: 19233, year: 1992, vol: 102, page: 41, stat: Journal Article,

Characteristics of Helicobacter pylori variants selected for urease deficiency
Perez-Perez GI; Olivares AZ; Cover TL; Blaser MJ
1992 Sep;60(9):3658-3663, Infection & immunity
The urease of Helicobacter pylori is suspected to play a role in the pathogenesis of gastritis. Although all clinical isolates of H. pylori are urease positive (U+), we have selected and characterized several spontaneously arising urease-negative (U-) variants from wild-type strain 60190. Urease-negative variants were identified by growth in medium containing 60 mM urea and arose at a frequency of 10(-5) to 10(-6). The urease activity of the wild-type strain inhibited growth of this strain in the presence of 60 mM urea. U- variants retained the U- phenotype for more than 100 passages on medium with or without urea. The urease activities of the original U+ and derived U- cells were 9.55 to 16.7 and 0.01 to 0.17 U/mg of protein, respectively. Colonial growth and other biochemical characteristics were identical for the strains. U- variants showed three classes of whole-cell sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles: (i) identical to U+; (ii) change in the migration of the 61-kDa urease subunit; and (iii) lack of 61- and 30-kDa subunits. These differences were confirmed by immunoblotting and by protein separation using fast protein liquid chromatography. The U+ strain but not U- variants tolerated exposure to pH 4.0 for 60 min in the presence of urea. Supernatants of the U+ strain and U- variants contained vacuolating cytotoxin activity for HeLa cells in similar titers. By enzyme-linked immunosorbent assay, human serum samples recognized water extract from the U+ strain significantly better than extract from a U- variant lacking urease subunits. In conclusion, this study demonstrates that U- H. pylori variants may arise spontaneously, that urease activity enhances survival at acid pH, and that urease and cytotoxin activities are disparate phenotypes
— id: 19224, year: 1992, vol: 60, page: 3658, stat: Journal Article,

Lack of Evidence of Enterotoxin Involvement in Pathogenesis of Campylobacter Diarrhea
Perez-Perez, Guillermo I; Taylor, David N; Echerverria, Peter D; Blaser, Martin J
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1992,
Several Campylobacter species are now recognized as important pathogens causing human diarrheal disease (7,8), but specific virulence mechanisms are not yet well defined. Campylobacter jejuni and C. coli infection may result in classical dysentery with fever and the presence of blood and Leukocytes in the stools, suggestive of an invasive process or cytotoxin production (3,27,37,38). Campylobacter diarrhea may also be associated with episodes of loose or watery stools and the absence of fever, consistent with the effect of a choleralike enterotoxin
— id: 1618, year: 1992, vol: , page: , stat: ,

Association of infection due to Helicobacter pylori with specific upper gastrointestinal pathology
Blaser MJ; Perez-Perez GI; Lindenbaum J; Schneidman D; Van Deventer G; Marin-Sorensen M; Weinstein WM
1991 Jul-Aug;13 Suppl 8(8):S704-S708, Reviews of infectious diseases
The association of infection with Helicobacter pylori and antral (type B) gastritis now is clear, and the development of sensitive and specific serologic assays for IgA and IgG allows for diagnosis of this infection by noninvasive means. With use of these assays, we studied the association of infection with H. pylori and four other upper gastrointestinal inflammatory conditions: Barrett's esophagus, pernicious anemia (which accompanies type A gastritis), and duodenal and gastric ulcers. H. pylori was present in only 39% of 41 patients with Barrett's esophagus whose gastric biopsy specimens were examined histologically. Each serologic assay correctly categorized 39 (95.1%) of the 41 patients. For both assays the frequency of seropositivity noted for 58 patients with Barrett's esophagus was not different from that noted for age- and sex-matched healthy controls. Among 40 patients with pernicious anemia, the results of assays for IgA and IgG were positive for 17.5% and 0%, respectively; these prevalences were significantly less than the 50% (IgA) and 40% (IgG) positivities noted for matched controls (P less than .01 for each; McNemar's test). Among 57 patients with documented duodenal or gastric ulcers, the results of assays for IgG and IgA were positive for 100% and 98.2%, respectively; these prevalences were significantly higher than the rate noted for matched controls (P less than .001 for duodenal ulcers and P = .02 for gastric ulcers for IgA assay). These data suggest that infection with H. pylori is strongly associated with duodenal and gastric ulcers, negatively associated with pernicious anemia, and independent of Barrett's esophagus
— id: 19242, year: 1991, vol: 13 Suppl 8, page: S704, stat: Journal Article,

Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin
Cover TL; Puryear W; Perez-Perez GI; Blaser MJ
1991 Apr;59(4):1264-1270, Infection & immunity
Concentrated broth culture supernatants from 50 to 60% of Helicobacter pylori strains induce eukaryotic cell vacuolation in vitro. A quantitative assay for cell vacuolation was developed on the basis of the rapid uptake of visibly vacuolated HeLa cells was significantly greater than that of nonvacuolated cells. By using the rapid NRU assay, we sought to determine the roles of H. pylori cytotoxin, urease, and ammonia in the vacuolation of HeLa cells. The NRU of HeLa cells incubated in medium containing ammonium chloride or ammonium sulfate was significantly greater than that of cells incubated in medium alone. In addition, ammonium salts augmented the NRU induced by H. pylori supernatants. The NRU induced by jack bean urease was augmented by the addition of urea to cell culture medium; this suggests that urease-mediated NRU occurs via the generation of ammonia. Acetohydroxamic acid blocked the NRU induced by jack bean urease and urea but failed to block the uptake induced by H. pylori supernatants. Supernatant from a non-urease-producing H. pylori mutant strain induced NRU identical to that of the urease-positive parental strain. These observations indicate that the vacuolating activity in H. pylori supernatants is not mediated solely by urease activity but that it may be potentiated by urease-mediated ammonia production
— id: 19246, year: 1991, vol: 59, page: 1264, stat: Journal Article,

High prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic Hispanics
Dehesa M; Dooley CP; Cohen H; Fitzgibbons PL; Perez-Perez GI; Blaser MJ
1991 Jun;29(6):1128-1131, Journal of clinical microbiology
In this study, we estimated the prevalence of Helicobacter pylori infection and histologic gastritis in 58 asymptomatic Hispanic adult volunteers (mean age, 41 years; 59% male) by endoscopic biopsy of the upper gastrointestinal tract. Forty-six subjects (79%) were found to harbor H. pylori in gastric biopsies, and all had histologic gastritis. Four other subjects were found to have gastritis in the absence of H. pylori. Similar prevalences of H. pylori and gastritis were noted in all age groups and also in American-born and immigrant Hispanics. Biopsy data and serologic studies of H. pylori antibodies correlated well. We conclude that H. pylori infection is an almost universal finding in the gastric mucosa of asymptomatic adult Hispanics, regardless of age. The clinical significance of these findings is unknown, but we speculate that H. pylori and its associated gastritis could have a role in the high incidence of gastric carcinoma in Hispanic populations
— id: 19244, year: 1991, vol: 29, page: 1128, stat: Journal Article,

Helicobacter pylori infection in pernicious anemia: a prospective controlled study
Fong TL; Dooley CP; Dehesa M; Cohen H; Carmel R; Fitzgibbons PL; Perez-Perez GI; Blaser MJ
1991 Feb;100(2):328-332, Gastroenterology
Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process
— id: 19250, year: 1991, vol: 100, page: 328, stat: Journal Article,

Soluble surface proteins from Helicobacter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism
Mai UE; Perez-Perez GI; Wahl LM; Wahl SM; Blaser MJ; Smith PD
1991 Mar;87(3):894-900, Journal of clinical investigation
The inflammatory lesions associated with Helicobacter pylori gastritis and duodenitis contain large numbers of mononuclear cells. The close proximity of H. pylori to gastric mucosa suggests that the organism interacts with mononuclear cells, thereby modulating the inflammatory response. To investigate the role of monocytes/macrophages in this response, we examined the effect of whole H. pylori bacteria, H. pylori surface proteins, and H. pylori lipopolysaccharide (LPS) on purified human monocytes. Whole H. pylori and the extracted LPS induced expression of the monocyte surface antigen HLA-DR and interleukin-2 receptors, production of the inflammatory cytokines interleukin 1 and tumor necrosis factor (peptide and messenger RNA), and secretion of the reactive oxygen intermediate superoxide anion. Since H. pylori in vivo does not invade mucosal tissue, we determined whether soluble constituents of the bacteria could activate monocytes. Soluble H. pylori surface proteins, which are enriched for urease and do not contain LPS, stimulated phenotypic, transcriptional, and functional changes consistent with highly activated monocytes. These findings indicate that H. pylori is capable of activating human monocytes by an LPS-independent as well as an LPS-dependent mechanism. H. pylori activation of resident lamina propria macrophages and monocytes trafficking through the mucosa, leading to the secretion of increased amounts of inflammatory cytokines and reactive oxygen intermediates, could play an important role in mediating the inflammatory response associated with H. pylori gastritis and duodenitis
— id: 19248, year: 1991, vol: 87, page: 894, stat: Journal Article,

Long-term follow-up of voluntary ingestion of Helicobacter pylori
Morris AJ; Ali MR; Nicholson GI; Perez-Perez GI; Blaser MJ
1991 Apr 15;114(8):662-663, Annals of internal medicine
— id: 19245, year: 1991, vol: 114, page: 662, stat: Journal Article,

Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii
Nomura A; Stemmermann GN; Chyou PH; Kato I; Perez-Perez GI; Blaser MJ
1991 Oct 17;325(16):1132-1136, New England journal of medicine
BACKGROUND. Helicobacter pylori are gram-negative spiral bacteria that are associated with chronic gastritis, a known precursor of gastric carcinoma. Persons at high risk for gastric carcinoma have been shown to have a high prevalence of H. pylori infection. METHODS. We studied the relation of H. pylori infection and gastric carcinoma in a cohort of Japanese American men living in Hawaii. The 5908 men were enrolled and examined from 1967 to 1970. By 1989, 109 cases of pathologically confirmed gastric carcinoma had been identified. The store serum of each patient with gastric carcinoma and of each matched control subject were tested for the presence of serum IgG antibody to H. pylori. RESULTS. Ninety-four percent of the men with gastric carcinoma and 76 percent of the matched control subjects had a positive test for H. pylori antibodies, for an odds ratio of 6.0 (95 percent confidence interval, 2.1 to 17.3). As the level of antibody to H. pylori increased, there was a progressive increase in the risk of gastric carcinoma (P for trend = 0.0009). The association was strong even for men in whom the diagnosis was made 10 or more years after the serum sample was obtained (odds ratio, 10.5; 95 percent confidence interval, 2.5 to 44.8). CONCLUSIONS. Infection with H. pylori is strongly associated with an increased risk of gastric carcinoma. However, most persons infected with H. pylori will never have gastric carcinoma. Therefore, other factors that increase the risk of gastric carcinoma among persons infected with H. pylori need to be identified
— id: 19237, year: 1991, vol: 325, page: 1132, stat: Journal Article,

Seroprevalence of helicobacter pylori infection in couples
Perez-Perez GI; Witkin SS; Decker MD; Blaser MJ
1991 Mar;29(3):642-644, Journal of clinical microbiology
We investigated the prevalence of Helicobacter pylori in 277 couples attending an infertility clinic. In total, 96 (17.3%) of the 554 persons were positive; in only 18 (6.6%) of the couples were both persons seropositive. Age was an important predictor for H. pylori infection. For 177 couples, information regarding birthplace, duration of cohabitation, history of ulcer or gastritis, and use of antacid or bismuth compounds was available. None of these variables correlated with H. pylori infection except place of birth; 69.1% of 55 persons born outside the United States were seropositive compared with 8.7% of persons born within the United States (P less than 0.0001). Being a partner of an H. pylori-infected person increased the risk of being infected; however, by multiple logistic regression analysis this effect was entirely explained by age and national origin. These data suggest that in young sexually active adults, person-to-person transmission of H. pylori does not occur or at most occurs infrequently
— id: 19247, year: 1991, vol: 29, page: 642, stat: Journal Article,

Characterization of risk factors for Helicobacter pylori infection among men attending a sexually transmitted disease clinic: lack of evidence for sexual transmission
Polish LB; Douglas JM; Davidson AJ; Perez-Perez GI; Blaser MJ
1991 Oct;29(10):2139-2143, Journal of clinical microbiology
The mechanism of transmission of Helicobacter pylori is unknown. To investigate the role of sexual behavior and demographic factors in the acquisition of H. pylori infection, we evaluated the seroprevalence of antibody to H. pylori in 370 men attending an urban sexually transmitted diseases clinic. Sera from the following three groups were analyzed by enzyme-linked immunosorbent assay for H. pylori-specific immunoglobulin G: 78 human immunodeficiency virus (HIV)-seropositive homosexual men, 102 HIV-seronegative homosexual men, and 190 HIV-seronegative heterosexual men. Overall, the seroprevalence of H. pylori was 100 of 370 men (27%), with rates of 18% in HIV-seropositive homosexual men and 20% in HIV-seronegative homosexual men versus 35% in heterosexual men (P less than 0.005, chi 2 test). By ethnic group, 21 (12%) of 181 Caucasian men, 40 (41%) of 97 black men, and 37 (43%) of 87 Hispanic men were seropositive (P less than 0.001, chi 2 test). Multivariate analysis revealed that race was associated with H. pylori seropositivity independent of HIV status, sexual preference, or age. There was no relationship between H. pylori seropositivity and the number of lifetime sexual partners or previous sexually transmitted diseases. Three HIV-seropositive men with H. pylori immunoglobulin G had essentially identical antibody titers over 8 to 16 months of follow-up. In conclusion, black and Hispanic men have significantly higher H. pylori seroprevalence rates than do Caucasian men, but neither sexual behavior nor HIV infection influences the presence or persistence of H. pylori antibody. Further evaluation of the factors associated with these ethnic differences may lead to a better understanding of H. pylori acquisition and transmission
— id: 19238, year: 1991, vol: 29, page: 2139, stat: Journal Article,

Serodiagnosis of Helicobacter pylori: comparison of enzyme-linked immunosorbent assays
Talley NJ; Newell DG; Ormand JE; Carpenter HA; Wilson WR; Zinsmeister AR; Perez-Perez GI; Blaser MJ
1991 Aug;29(8):1635-1639, Journal of clinical microbiology
Enzyme-linked immunosorbent assays (ELISAs) have been developed to diagnose Helicobacter pylori infection. However, the methods are not standardized. We therefore prospectively evaluated the sensitivities and specificities of ELISAs developed in the United States and the United Kingdom in a study population comprising 41 consecutive symptomatic outpatients and 35 volunteers. At endoscopy, multiple biopsies were obtained for histology and culture and stained sections were graded for chronic gastritis, active chronic gastritis, and density of H. pylori. Serum samples were analyzed for H. pylori by ELISA. The first set of assays for immunoglobulin G (IgG) and IgA used a pool of sonicated isolates of H. pylori from five patients in the United States (antigen A). The second set of assays, developed in the United Kingdom, used three different antigens: antigen 1, an acid-extractable surface antigen; antigen 2, an acid-extractable antigen from an aflagellate variant; and antigen 3, a urease-containing fraction. Cutoff scores for positive results were determined a priori on the basis of previous serological studies. There was close agreement between histology and culture. In the study population, 36% of the individuals were H. pylori positive. The diagnostic value of the different ELISAs were highly comparable, and the crude antigens performed as well as the more purified antigens. The antigen A IgG had a sensitivity and specificity of 96 and 94%, respectively; the values for antigen 1 were 93 and 96%, respectively. The antigen A IgA and antigen 3 assays were the least sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 19241, year: 1991, vol: 29, page: 1635, stat: Journal Article,

Gastric adenocarcinoma and Helicobacter pylori infection
Talley NJ; Zinsmeister AR; Weaver A; DiMagno EP; Carpenter HA; Perez-Perez GI; Blaser MJ
1991 Dec 4;83(23):1734-1739, Journal of the National Cancer Institute
Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma
— id: 19235, year: 1991, vol: 83, page: 1734, stat: Journal Article,

Evaluation of cytotoxic activity in fecal filtrates from patients with Campylobacter jejuni or Campylobacter coli enteritis
Cover TL; Perez-Perez GI; Blaser MJ
1990 Aug;58(3):301-304, FEMS microbiology letters
We sought to determine the prevalence of cytotoxic activity in fecal filtrates from persons with C. jejuni or C. coli enteritis. Stool specimens were collected from 20 persons with C. jejuni or C. coli enteritis, 20 persons with acute diarrheal illnesses of other causes, and 9 healthy, asymptomatic persons. Fecal filtrates were then incubated with Chinese hamster ovary (CHO) or HeLa cells. The fecal filtrate from 1 of the 20 (5%) persons with Campylobacter enteritis was cytotoxic for HeLa cells at a titer of 1:40, and 10 (50%) were cytotoxic for CHO cells at maximum titers of 1:20. Cytotoxic activity for CHO cells at a median titer of 1:20 was also present in 40% of the fecal filtrates from persons with diarrhea due to causes other than Campylobacter enteritis, and in 33% of filtrates from healthy, asymptomatic persons. The observed low level of cytotoxicity in fecal filtrates from all patient groups studied likely resulted from non-specific factors, unrelated to the pathogenesis of Campylobacter enteritis
— id: 19261, year: 1990, vol: 58, page: 301, stat: Journal Article,

Evaluation of Cytotoxic Activity in Fecal Filtrates from Patients with Campylobacter jejuni or Campylobacter coli enteritis
Cover, Timothy L; Perez-Perez, Guillermo I; Blaser, Martin J
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1990,
Although Campylobacter jejuni and C. coli are important causes of diarrheal illness worldwide, the pathophysiologic mechanisms whereby these organisms cause human disease remain poorly understood (1). Cytotoxic activity has been demonstrated in culture supernatants of C. jejuni and C. coli grown in vitro (2-7), but the in vivo relevance of these observations is not clear. We therefore sought to detect cytotoxic activity in fecal filtrates from persons with campylobacter enteritis. Fecal filtrates from persons with diarrhea due to other causes and from asymptomatic healthy persons were tested as controls
— id: 1617, year: 1990, vol: , page: , stat: ,

Intrafamilial clustering of Helicobacter pylori infection
Drumm B; Perez-Perez GI; Blaser MJ; Sherman PM
1990 Feb 8;322(6):359-363, New England journal of medicine
Colonization of the gastric antrum by Helicobacter pylori (formerly Campylobacter pylori) has been associated with primary gastritis. We determined the frequency of colonization by H. pylori in gastric-antrum biopsy specimens from 93 children undergoing gastroscopy for the evaluation of upper gastrointestinal symptoms. We also determined H. pylori IgG antibody levels by enzyme-linked immunosorbent assay in coded serum samples from these children, family members, and control subjects of comparable ages. Among 27 children with primary, or unexplained, gastritis, H. pylori was identified by silver staining in 24 biopsy specimens and by culture in 22; specific antibodies were present in 23 children (96 percent). Three children with unexplained gastritis had no evidence of H. pylori in the antrum, nor did any of 13 children with secondary gastritis or any of 53 children with normal antral histologic features; specific antibodies were present in only 1 of these 69 children. H. pylori antibody was detected in 25 of 34 parents of colonized children, but in only 8 of 33 parents of noncolonized children (P less than 0.001). Of 22 siblings of children colonized by H. pylori, 18 had specific antibodies, as compared with only 5 of 37 controls (P less than 0.001). We conclude that H. pylori-specific IgG antibodies are associated with bacterial colonization of the gastric antrum by this organism. The intrafamilial clustering of H. pylori infection suggests that there may be person-to-person spread of these bacteria
— id: 19268, year: 1990, vol: 322, page: 359, stat: Journal Article,

Purification and characterization of urease from Helicobacter pylori
Dunn BE; Campbell GP; Perez-Perez GI; Blaser MJ
1990 Jun 5;265(16):9464-9469, Journal of biological chemistry
Urease was purified 112-fold to homogeneity from the microaerophilic human gastric bacterium, Helicobacter pylori. The urease isolation procedure included a water extraction step, size exclusion chromatography, and anion exchange chromatography. The purified enzyme exhibited a Km of 0.3 +/- 0.1 mM and a Vmax of 1,100 +/- 200 mumols of urea hydrolyzed/min/mg of protein at 22 degrees C in 31 mM Tris-HCl, pH 8.0. The isoelectric point was 5.99 +/- 0.03. Molecular mass estimated for the native enzyme was 380,000 +/- 30,000 daltons, whereas subunit values of 62,000 +/- 2,000 and 30,000 +/- 1,000 were determined. The partial amino-terminal sequence (17 residues) of the large subunit of H. pylori urease (Mr = 62,000) was 76% homologous with an internal sequence of the homohexameric jack bean urease subunit (Mr = 90,770; Takashima, K., Suga, T., and Mamiya, G. (1988) Eur. J. Biochem. 175, 151-165) and was 65% homologous with amino-terminal sequences of the large subunits of heteropolymeric ureases from Proteus mirabilis (Mr = 73,000) and from Klebsiella aerogenes (Mr = 72,000; Mobley, H. L. T., and Hausinger, R. P. (1989) Microbiol. Rev. 53, 85-108). The amino-terminal sequence (20 residues) of the small subunit of H. pylori urease (Mr = 30,000) was 65 and 60% homologous with the amino-terminal sequences of the subunit of jack bean urease and with the Mr = 11,000 subunit of P. mirabilis urease (Jones, B. D., and Mobley, H. L. T. (1989) J. Bacteriol. 171, 6414-6422), respectively. Thus, the urease of H. pylori shows similarities to ureases found in plants and other bacteria. When used as antigens in an enzyme-linked immunosorbent assay, neither purified urease nor an Mr = 54,000 protein that co-purified with urease by size exclusion chromatography was as effective as crude preparations of H. pylori proteins at distinguishing sera from persons known either to be infected with H. pylori or not
— id: 19262, year: 1990, vol: 265, page: 9464, stat: Journal Article,

Helicobacter pylori-related gastroduodenal disease in children. Diagnostic utility of enzyme-linked immunosorbent assay
Glassman MS; Dallal S; Berezin SH; Bostwick HE; Newman LJ; Perez-Perez GI; Blaser MJ
1990 Aug;35(8):993-997, Digestive diseases & sciences
To evaluate the accuracy of IgG and IgA serological tests in establishing a diagnosis of Helicobacter (Campylobacter) pylori gastric infection, 60 children presenting with chronic abdominal pain were prospectively studied. Endoscopic antral biopsies were obtained and analyzed for the presence of H. pylori using three standard methods: culture and identification of bacterial isolates, microscopic examination for morphologically characteristic bacteria, and urease production by the biopsy specimen. Concomitantly obtained serum samples were analyzed for the presence of IgG and IgA antibodies against H. pylori surface antigens using enzyme-linked immunosorbent assay (ELISA). Thirty-four of 60 (56.6%) had histological evidence of chronic active gastritis, eight of whom (13.3%) also had evidence of H. pylori infection by at least one criteria. Six of the eight infected patients had H. pylori demonstrated by all three methods. Of the eight infected patients, seven had IgG antibodies against H. pylori (sensitivity of 87%) and six had IgA antibodies (sensitivity of 75%). Among the six patients who had H. pylori infection confirmed by all three methods, all had IgG antibodies (sensitivity of 100%). In the patients without evidence of H. pylori infection, the IgG ELISA had a specificity of 96% (50/52), and the IgA ELISA had a specificity of 100% (52/52). Our data suggest that serological testing for the presence of antibodies against H. pylori may be a useful diagnostic tool in screening children with chronic abdominal pain for the presence of gastric infection with H. pylori
— id: 19260, year: 1990, vol: 35, page: 993, stat: Journal Article,

Seroprevalence of Helicobacter pylori infections in Thailand
Perez-Perez GI; Taylor DN; Bodhidatta L; Wongsrichanalai J; Baze WB; Dunn BE; Echeverria PD; Blaser MJ
1990 Jun;161(6):1237-1241, Journal of infectious diseases
Serologic studies in developed countries indicate that Helicobacter (formerly Campylobacter) pylori infection is uncommon until the third decade of life and achieves a peak prevalence of 50% in the seventh decade. In developing countries the epidemiology of H. pylori has not well been described. A sensitive and specific serologic assay for H. pylori infection was validated in Thai patients also studied by culture and histologic examination of biopsy specimens. The prevalence of H. pylori antibodies in persons from a rural Thai community began early (17.5% of children 5-9 years old), increased to 55% during the third decade of life, and peaked (75%) in the 30- to 49-year age group. At a Bangkok orphanage where enteric infections are hyperendemic, 74% of children 1-4 years old were seropositive. This study shows that the prevalence of H. pylori infection in Thailand is higher than in industrialized countries. The high infection rate at the orphanage suggests that person-to-person transmission of H. pylori may be occurring
— id: 19263, year: 1990, vol: 161, page: 1237, stat: Journal Article,

Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy
Strauss RM; Wang TC; Kelsey PB; Compton CC; Ferraro MJ; Perez-Perez G; Parsonnet J; Blaser MJ
1990 Oct;89(4):464-469, American journal of medicine
PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism
— id: 19256, year: 1990, vol: 89, page: 464, stat: Journal Article,

Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons
Dooley CP; Cohen H; Fitzgibbons PL; Bauer M; Appleman MD; Perez-Perez GI; Blaser MJ
1989 Dec 7;321(23):1562-1566, New England journal of medicine
We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion
— id: 19270, year: 1989, vol: 321, page: 1562, stat: Journal Article,

Two-dimensional gel electrophoresis and immunoblotting of Campylobacter pylori proteins
Dunn BE; Perez-Perez GI; Blaser MJ
1989 Jun;57(6):1825-1833, Infection & immunity
Whole-cell, outer-membrane protein, flagellum-associated antigens and partially purified urease of Campylobacter pylori were analyzed by two-dimensional gel electrophoresis. C. pylori strains were readily distinguished from strains of Campylobacter jejuni, C. coli, and C. fetus by absence of major outer membrane proteins with Mrs of 41,000 to 45,000. C. pylori strains also lacked the acidic surface-array proteins at Mr 100,000 to 149,000 identified previously in serum-resistant strains of C. fetus. Surface labeling of intact C. pylori cells with 125I revealed two common major proteins, which we have designated protein 2 (pI 5.6 to 5.8, Mr 66,000) and protein 3 (pI 5.2 to 5.5, Mr 63,000). Proteins 2 and 3 were also the major components (subunits) observed in partially purified urease. Partially purified preparations of flagella consistently contained proteins 2 and 3. Thus, urease appears to be associated with both outer membranes and flagella of C. pylori. C. pylori strains also possessed an antigen at Mr 59,000 which was cross-reactive with antiserum against flagella of C. jejuni. However, the antigen did not appear to be associated with flagella per se in C. pylori. Protein 2 was unique to C. pylori among the Campylobacter species studied. It was not recognized by antibody against whole cells of C. jejuni or C. fetus or flagella of C. jejuni. Protein 3 was cross-reactive with antiserum against whole cells of C. jejuni and C. fetus, as were several other major protein antigens. Because protein 2 is a major outer membrane protein that is apparently unique to C. pylori, development of monospecific antibodies against this antigen may be useful for the identification of C. pylori in tissues, and purified antigen may be useful for serologic tests for specific diagnosis of C. pylori infections
— id: 19274, year: 1989, vol: 57, page: 1825, stat: Journal Article,

Clinical and immunologic significance of cholera-like toxin and cytotoxin production by Campylobacter species in patients with acute inflammatory diarrhea in the USA
Perez-Perez GI; Cohn DL; Guerrant RL; Patton CM; Reller LB; Blaser MJ
1989 Sep;160(3):460-468, Journal of infectious diseases
The humoral immune response to both Campylobacter jejuni cell surface antigens and to potential toxins of the organism was studied in 64 adults with inflammatory diarrhea. In an enzyme-linked immunosorbent assay (ELISA) for surface antigens, 17 (71%) of 24 persons with Campylobacter enteritis showed seroconversion in more than one immunoglobulin class, versus only 2 (5%) of 40 patients with non-Campylobacter enteritis. In a GM1, ganglioside-based ELISA for detecting serum IgG to cholera-like enterotoxin, only one patient studied showed seroconversion to the enterotoxin. Of 22 Campylobacter isolates studied for production of cholera-like toxin, none of the supernatants from the Campylobacter strains were positive. Supernatants were also tested for enterotoxin and cytotoxic activity on Chinese hamster ovary cells; all isolates were negative for enterotoxin activity. In contrast, cytotoxin was produced by 7 (32%) isolates but was usually low-level and was not neutralized by patient's serum. These findings indicate that production of cholera-like toxin and cytotoxin by Campylobacter strains in the United States occurs in few strains and that host immune response is absent; their biologic significance in the pathogenesis of Campylobacter infections remains unclear
— id: 19273, year: 1989, vol: 160, page: 460, stat: Journal Article,

Production of a Shiga-like cytotoxin by Campylobacter
Moore MA; Blaser MJ; Perez-Perez GI; O'Brien AD
1988 Jun;4(6):455-462, Microbial pathogenesis
Cell lysates and culture supernatants of 36 Campylobacter isolates from patients with enteritis were tested for cytotoxic activity on HeLa cells. Cytotoxic activity was considered Shiga-like if neutralized by monoclonal antibody to the B subunit of Shiga-like toxin I of Escherichia coli and rabbit anti-Shiga toxin. Fifteen of the Campylobacter isolates produced no detectable cytotoxin, 10 produced a non-neutralizable cytotoxin, and 11 produced low levels of a cell-associated SLT. However, under low stringency conditions no hybridization was observed between a DNA fragment containing cloned SLT-I genes and restriction enzyme-digested total DNA from a Campylobacter strain that produced low levels of a Shiga-like toxin I. The Shiga-like toxin neutralizing titers in sera from 15 patients with C. jejuni infections, 5 patients infected with S. sonnei, and 20 healthy persons were then determined. No rise in neutralizing titer between acute and convalescent sera of patients with C. jejuni infection or S. sonnei infection was observed, although 27% of C. jejuni-infected patients, 40% of S. sonnei-infected patients, and 30% of the healthy controls had neutralizing activity in their sera. These data indicate that low levels of Shiga-like toxin are produced by some Campylobacter isolates but that SLT is genetically distinct from the SLT-I toxin produced at high levels by certain E. coli. The findings also suggest that exposure to SLTs is common in the adult population but not as a consequence of infection with C. jejuni or S. sonnei
— id: 19283, year: 1988, vol: 4, page: 455, stat: Journal Article,

Campylobacter pylori antibodies in humans
Perez-Perez GI; Dworkin BM; Chodos JE; Blaser MJ
1988 Jul 1;109(1):11-17, Annals of internal medicine
STUDY OBJECTIVE: To determine the diagnostic value of assays to measure serum antibodies to Campylobacter pylori, and to use these assays to determine the prevalence of C. pylori infection in a healthy population. DESIGN: A survey of patients having endoscopies for upper gastrointestinal symptoms, patients with other gastrointestinal illnesses, and healthy controls. SETTING: Outpatients attending endoscopy suites in two university-affiliated medical centers. PATIENTS: One hundred and twenty patients who had gastroduodenoscopies, 61 patients with lower intestinal illnesses, and 166 healthy controls. INTERVENTION: Assay to detect serum IgA, IgG, and IgM antibodies specific for C. pylori. MEASUREMENTS AND MAIN RESULTS: Absorption with other gram-negative pathogens showed that IgG and IgA assays, but not IgM assays, were specific for C. pylori. In patients in whom C. pylori had been isolated and who had gastritis diagnosed by histologic methods, significantly higher mean IgA and IgG levels were seen compared with patients without demonstrable C. pylori or gastritis. The sensitivity and specificity of a positive value in both IgA and IgG assays were more than 93%. Among healthy persons, IgG and IgA antibodies were rarely seen in patients less than 20 years old, but antibody prevalence progressed with age, reaching 50% in patients more than 60 years old. High IgA and IgG levels to C. pylori in five persons tested remained stable for more than 1 year, suggesting the organism persists for at least that period. In 61 patients with acute bacterial enteritis, acute pancreatitis, Crohn disease, or ulcerative colitis, prevalence of antibodies to C. pylori was consistent with age and unrelated to current disease. CONCLUSIONS: Campylobacter pylori infection, which is highly associated with active gastritis, may be diagnosed by serologic assay. Acquisition of infection begins in adult life, and prevalence increases with age
— id: 19282, year: 1988, vol: 109, page: 11, stat: Journal Article,

Non-01 Vibrio cholerae infections in Cancun, Mexico
Finch MJ; Valdespino JL; Wells JG; Perez-Perez G; Arjona F; Sepulveda A; Bessudo D; Blake PA
1987 Mar;36(2):393-397, American journal of tropical medicine & hygiene
To determine the role of Vibrio cholerae as a cause of diarrheal illness in Cancun, Mexico, an investigation was conducted in July and August 1983. Although toxigenic V. cholerae 01 were not found, non-01 V. cholerae were isolated from 22 (16%) of 134 stools from persons with diarrheal illness and none of 22 stools from well persons; 58 (92%) of 63 sewage samples; 12 (86%) of 14 untreated well water samples; a home storage tank for treated water; and 5 (21%) of 24 samples of raw seafood. None of the V. cholerae isolates from patients were toxigenic. The illness occurred mainly in small children, and were characterized principally by diarrhea and abdominal pain. No patient was seriously ill, and all recovered without sequelae. Seven different serotypes of non-01 V. cholerae were isolated from the stool specimens, and Smith serotype 12 accounted for 10 (46%) of the 22 isolates. A matched-pair case-control study found that cases were more likely than controls to have eaten home prepared gelatin (P = 0.03, OR = 5/0) and seafood (P = 0.06, OR = 4/0)
— id: 34636, year: 1987, vol: 36, page: 393, stat: Journal Article,

Conservation and diversity of Campylobacter pyloridis major antigens
Perez-Perez GI; Blaser MJ
1987 May;55(5):1256-1263, Infection & immunity
Infection with Campylobacter pyloridis has been strongly associated with gastritis in humans although its etiologic significance is currently undefined. We examined the structure and antigenicity of whole-cell, outer-membrane, acid-extractable surface protein, and proteinase K-treated whole cell lysate preparations from eight C. pyloridis strains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with homologous and heterologous immune rabbit serum. Whole-cell and outer-membrane profiles observed in all strains of C. pyloridis were nearly identical; none were similar to those of C. jejuni and C. fetus. Major whole-cell bands migrated at 26,000, 29,000, 56,000, and 62,000 molecular weights. The acid-extracted protein profiles of all C. pyloridis strains also were similar to one another and showed similarities with acid-extracted proteins from C. jejuni, with major bands migrating at 29,000, 48,000 to 53,000, and 62,000. All proteinase K-treated lysates showed different lipopolysaccharide (LPS) profiles, ranging from rough to smooth with multiple repeating side chains. Immunoblots of whole-cell and proteinase K-treated preparations of the C. pyloridis strains showed that there was antigenic cross-reactivity of proteins migrating at 62,000 and 56,000, but not in other regions, and cross-reactivity between LPS core regions but not side chains. These results suggest that C. pyloridis has both protein and core LPS group antigens and strain-specific protein and LPS side chain antigens
— id: 19297, year: 1987, vol: 55, page: 1256, stat: Journal Article,

Antigenicity of Campylobacter jejuni flagella
Blaser MJ; Hopkins JA; Perez-Perez GI; Cody HJ; Newell DG
1986 Jul;53(1):47-52, Infection & immunity
We studied the antigenicity of a wild-type flagellate and motile (F+M+) Campylobacter jejuni strain (81116) and two daughter mutants, one flagellate and immotile (F+M-) and one aflagellate and immotile (F-M-). By sodium dodecyl sulfate-polyacrylamide gel electrophoresis of acid-extracted surface proteins, a 63-kilodalton (kDa) band identified from sheared flagella as the flagellar protein was present in the F+M+ and F+M- strains but not in the F-M- strain. No other differences in protein profile among the three strains were noted. By Western blotting, serum from rabbits immunized with either the F+M+ or F-M- strain detected a 63-kDa protein in the F+M+ and F+M- strains but not in the F-M- strain. That the F-M- antiserum recognized the 63-kDa band suggests that small amounts of this protein or a cross-reacting antigen is present on the F-M- strain. By counterimmunoelectrophoresis of the acid-extracted preparations with immune sera, all three strains were found to share three major antigens, but a fourth antigen with a net positive charge was present only in the F+M+ and F+M- strains. Antisera to five C. jejuni and two Campylobacter fetus strains recognized the 63-kDa protein of purified F+M+ flagella in Western blots, demonstrating a common antigen is present, but enzyme-linked immunosorbent assay results suggest that the sharing of this antigen among Campylobacter strains is variable
— id: 19304, year: 1986, vol: 53, page: 47, stat: Journal Article,

Antigenicity of Campylobacter Jejuni Flagella
Blaser, Martin J; Hopkins, Janet A; Perez-Perez, Guillermo I; Cody, Henry J; Newell, Diane G
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1986,
We studied the antigenicity of a wild-type flagellate and motile F(+) M(+) Campylobacter jejuni strain (81116) and two daughter mutants, one flagellate and immotile F (+)M(-) and one aflagellate and immotile F(-)M(-). By solium dodecyl sulfate-polyacrylamide gel electrophoresis of acid-extracted surface proteins, a 63-kilodalton (kDa) band identified from sheared flagella as the flagellar protein was present in the F(+)M(+) and F(+)M(-) strains but not in the F(-)M(-) strain. No other differences in protein profile among the three strains were noted. By Western blotting, serum from rabbits immunized with either the F(+)M(+) or F(-)M(-) strain detected a 63-kDa protein in the F(+)M(+) and F(+)M(-) strains but not in the F(-)M(-) strain. That the F(-)M(-) antiserum recognized the 63-kDa band suggests that small amounts of this protein or a cross-reacting antigen is present on the F(-)M(-) strain. By counterimmunoelectrophoresis of the acid-extracted preparations with immune sera, all three strains were found to share three major antigens, but a fourth antigen with a net positive charge was present only in the F(+)M(+) and F(+)M(-) strains. Antisera to five C. jejuni and two Campylobacter fetus strains recognized the 63-kDa protein oif purified F(+)M(+) flagella in Western blots, demonstrating that a common antigen is present, but enzyme-linked immunosorbent assay results suggest that the sharing of this antigen among Campylobacter strains is variable
— id: 1620, year: 1986, vol: , page: , stat: ,

Extraintestinal Campylobacter Jejuni and Campylobacter Coli Infections: Host Factors and Strain Characteristics
Blaser, Martin J; Perez, Guillermo; Smith, Paul F; Patton, Charlotte; Fenover, Fred C
[S.l.] : Ft. Belvoir Defense Technical Information Center, 1986,
To determine whether extraintestinal isolates of Campylobacter jejuni and Campylobacter coli are the consequence of unusual host or bacterial characteristics, we studied clinical and bacteriologic features of 24 extraintestinal infections. Common serotypes and auxotypes were present among the extraintestinal isolates. Gastrointestinal isolates were more susceptible to normal human serum than were the systemic isolates; however, the ranges overlapped considerably. Predispositions to systemic spread were present in 52% of patients with extraintestinal infections; isolates from these patients were more often (73%) serum sensitive than were isolates from patients without predispositions (9%; P = .002). By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no specific protein band was associated with serum resistance, and all isolates of C. jejuni and C. coli had rough-type lipopolysaccharide profiles. Serum susceptibility was inversely correlated with carbohydrate or ketodeoxyoctonate (KDO) fraction of cell weight and directly correlated with KDO:carbohydrate ratio. Our results suggest that either host defects or specific bacterial virulence characteristics, such as serum resistance, possibly related to length of lipopolysaccharide side chain, may be responsible for extraintestinal infections due to C. jejuni and C. coli
— id: 2046, year: 1986, vol: , page: , stat: ,

Isolation of Campylobacter jejuni from intestinal contents of chickens in Mexico City
Perez Perez GI; Hinojosa AM; Bessudo D
1986 Jan-Mar;28(1):37-38, Revista latinoamericana de microbiologia
— id: 25611, year: 1986, vol: 28, page: 37, stat: Journal Article,

Lipopolysaccharide structures of Campylobacter fetus are related to heat-stable serogroups
Perez-Perez GI; Blaser MJ; Bryner JH
1986 Jan;51(1):209-212, Infection & immunity
To determine whether lipopolysaccharide (LPS) structures of Campylobacter fetus are related to the three known heat-stable serogroups, proteinase K-treated whole cell lysates obtained from strains of each serogroup were electrophoresed in polyacrylamide gels. All strains had smooth-type LPS with multiple high-molecular-weight repeating units. The profiles of serogroup A from C. fetus subsp. fetus and from C. fetus subsp. venerealis were identical, but they were different from those of C. fetus subsp. fetus serogroups B and AB. When we immunoblotted the LPS of these serogroups with normal or immune rabbit serum we found homologous recognition between serogroups A from C. fetus subsp. fetus and C. fetus subsp. venerealis. Similarly, serogroups AB and B from C. fetus subsp. fetus showed homologous recognition. However, antiserum against serogroup A did not recognize serogroups B and AB and vice versa. Absorption studies confirmed the identity of LPS from all serogroup A C. fetus strains and cross-reactivity of the serogroup B and AB strains with one another. Serogroup A strains were resistant to the bactericidal activity in normal human serum, whereas serogroup B and AB strains generally were susceptible; isolates from humans predominantly belonged to serogroup A. Results of these studies suggest that the LPS composition forms the basis for the heat-stable serotyping system for C. fetus and that the structural and antigenic variants are associated with differential serum susceptibility
— id: 19317, year: 1986, vol: 51, page: 209, stat: Journal Article,

Lipopolysaccharide structures in Enterobacteriaceae, Pseudomonas aeruginosa, and Vibrio cholerae are immunologically related to Campylobacter spp
Perez-Perez GI; Hopkins JA; Blaser MJ
1986 Jan;51(1):204-208, Infection & immunity
To determine whether lipopolysaccharide (LPS) structures of Campylobacter species are immunologically related to those of 11 other gram-negative organisms, we immunoblotted from polyacrylamide gels the LPS of these strains with immune rabbit serum raised against six Campylobacter jejuni strains and two Campylobacter fetus strains. The LPS studied were from Salmonella minnesota wild type and Ra to Re mutants, Salmonella typhi, Escherichia coli, Yersinia enterocolitica, Vibrio cholerae, and Pseudomonas aeruginosa. None of the 11 LPS preparations was recognized by the eight antisera, but antisera to each of the Campylobacter strains recognized core determinants of some LPS preparations. Antiserum directed against the most serum-sensitive C. jejuni strain, 79-193, was the only antiserum sample that recognized core regions of the rough Salmonella mutants. In converse experiments, when LPS preparations from five Campylobacter strains were blotted with antiserum to Salmonella lipid A, recognition of core structures of each was shown; data from an enzyme-linked immunosorbent assay confirmed this result. In contrast, antiserum to Salmonella typhimurium Re LPS showed no reactivity. We conclude that LPS of Campylobacter strains share lipid A antigenic determinants with the core region of LPS of several other gram-negative organisms
— id: 19320, year: 1986, vol: 51, page: 204, stat: Journal Article,

Actividad in vitro de tetroxoprim sulfadiazina "PRIM" sobre cepa de Salmonella enteritidis = [In vitro activity of tetroxoprim sulfadiazine (PRIM) on strain of Salmonella enteritidis]
Perez-Perez, Guillermo I; Ahumada, A Marina Hinojosa; Madjar, David Bessudo
1986 ;13(2):117-121, Investigacion medica internacional
— id: 90071, year: 1986, vol: 13, page: 117, stat: Journal Article,

Lipopolysaccharide Structures of Campylobacter fetus are Related to Heat-Stable Serogroups
Perez-Perez, Guillermo I; Blaser, Martin J; Bryner, John H
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1986,
To determine whether lipopolysaccharide (LPS) structures of Campylobacter fetus are related to the three known heat-stable serogroups, proteinase K-treated whole cell lysates obtained from strains of each serogroup were electrophoresed in polyacrylamide gels. All strains had smooth-type LPS with multiple high-molecular-weight repeating units. The profiles of serogroup A from C. fetus subsp. fetus and from C. fetus subsp. venerealis were identical, but they were different from those of C. fetus susp. fetus serogroups B and AB. When we immunoblotted the LPS of these serogroups with normal or immune rabbit serum we found homologous recognition between serogroups A from C. fetus subsp. fetus and C. fetus subsp. venerealis. Similarly, serogroups AB and B from C. fetus subsp. fetus showed homologous recognition. However, antiserum against serogroup A did not recognize serogroups B and AB and vice versa. Absorption studies confirmed the identity of LPS from all serogroup A C. fetus strains and cross-reactivity of the serogroup B and AB strains with one another. Serogroup A strains were resistant to the bactericidal activity in normal human serum, whereas serogroup B and AB strains generally were susceptible; isolates humans predominantly belonged to serogroup A. Results of these studies suggest that the LPS composition forms the basis for the heat-stable serotyping system for C. fetus and that the structural and antigenic variants are associated with differential serum susceptibility
— id: 1619, year: 1986, vol: , page: , stat: ,

Sensibilidad a diez antimicrobianos de Salmonella aislada de diverssas fuentes = [Sensibility of Salmonella isolated from different sources to 10 antimicrobials agents]
Perez-Perez, Guillermo Ignacio; Perira Puello, Deisy del C; Ahumada, Marina Hinojosa; Bessudo, David
1986 ;6(11):459-463, Infectologia
Se estudio la sensibilidad de 219 cepas de Salmonella aisladas de humanos y otras fuentes, (alimentos, aguas de drenaje y otros) a 10 antimicrobianas: gentamicina, estreptomicina, ampicilina, kanamicina, sisomicina, tetraciclina, amikacina, acido nalidixico, cloranfenicol y cefalotina. Los porcentajes de susceptibilidad mas altos fueron obtenidos con amikacina (100%) y acido nalidixico (92.2%). Con el resto de los antimicrobianos los porcentajes variaron de 60.7 a 86%. En relacion con la fuente de aislamiento, los porcentajes de resistencia mas altos fueron obtenidos con las cepas aisladas de humanos. Los serotipos que fueron encontrados con mayor frecuencia en estos, fueron tambien los que presentaron mayor porcentaje de resistencia. Del total de las cepas, el 35.1% presento resistencia multiple, el 13.2% fue resistente a dos antimicrobianos, y el 27.3% a solo uno (AU)
— id: 90072, year: 1986, vol: 6, page: 459, stat: Journal Article,

Antigenic heterogeneity of lipopolysaccharides from Campylobacter jejuni and Campylobacter fetus
Perez GI; Hopkins JA; Blaser MJ
1985 May;48(2):528-533, Infection & immunity
The lipopolysaccharide (LPS) structure of Campylobacter spp. can be visualized with polyacrylamide gel electrophoresis by examining proteinase K-treated whole cell lysates. Polyacrylamide gel electrophoresis LPS profiles of C. jejuni strains are rough type with low concentrations of low-molecular-weight polysaccharide side chains, serum-resistant C. fetus strains have smooth-type LPS, and serum-sensitive C. fetus strains have rough-type LPS. We electroblotted the proteinase K-treated whole cell lysates of 17 C. jejuni and 9 C. fetus strains from polyacrylamide gel electrophoresis to nitrocellulose paper to examine antigenicity to immune rabbit sera. There was virtually no antigenic cross-reactivity of C. jejuni and C. fetus LPS. Among C. jejuni strains, core LPS structures were cross-reactive, but the O-polysaccharide side chains were best recognized by homologous antisera. Antisera to several serum-resistant C. fetus strains recognized only the polysaccharide side-chain regions of serum-resistant strains and no part of the LPS from the sensitive strain. Antiserum raised against a serum-sensitive C. fetus strain but not homologous antisera recognized the core region of the LPS of the serum-resistant C. fetus strains. These findings suggest that core LPS antigens are widely shared within C. fetus subsp. fetus strains but that in the serum-resistant strains this core region is not surface exposed and therefore not immunogenic to rabbits infected with whole cells
— id: 19325, year: 1985, vol: 48, page: 528, stat: Journal Article,

Lipopolysaccharide characteristics of pathogenic campylobacters
Perez Perez GI; Blaser MJ
1985 Feb;47(2):353-359, Infection & immunity
Most Campylobacter jejuni strains are sensitive and most Campylobacter fetus strains are resistant to the bactericidal activity in normal human serum. We purified lipopolysaccharides from Campylobacter strains to determine whether their composition and structure relate to serum susceptibility. The lipopolysaccharide of two serum-sensitive strains was best isolated by the Galanos procedure, but for two serum-resistant strains a cold-ethanol extraction was optimal. For each lipopolysaccharide preparation, the ratio of 2-keto-3-deoxyoctonate to protein was increased by 100 to 1,000-fold over that of whole cells. For serum-resistant strains, total carbohydrates was a high proportion of lipopolysaccharide weight; for serum-sensitive strains, 2-keto-3-deoxyoctanate was a high proportion of total carbohydrates. By polyacrylamide gel electrophoresis, the lipopolysaccharide of serum-sensitive strains appeared rough, but for serum-resistant strains a smooth-type ladder was seen, with a minimal core region and several high-molecular-weight complexes. Proteinase K-treated whole-cell lysates showed polyacrylamide gel electrophoresis profiles similar to that of pure lipopolysaccharide. Proteinase K-treated whole-cell lysates from seven serum-sensitive C. jejuni strains all had rough profiles, and five serum-resistant C. fetus strains all had smooth profiles. These studies indicate that lipopolysaccharide composition may be an important determinant of serum susceptibility among Campylobacter species and that serum resistance is usually associated with a smooth-type lipopolysaccharide
— id: 19330, year: 1985, vol: 47, page: 353, stat: Journal Article,

Susceptibilidad de Salmonella y Shigella a los antimicrobianos en el Hospital Infantil de Mexico, 1979-1980 = [Susceptibility of Salmonella and Shigella to antimicrobial agents at the Hospital Infantil de Mexico, 1979-1980]
Perez-Perez GI; Hernandez-Albinez A
1985 Aug;42(8):488-493, Boletin medico del Hospital Infantil de Mexico
Se estudio la respuesta a los antimicrobianos en 546 cepas de Salmonella enteritidis, y 260 cepas de Shigella en el periodo de enero de 1979 a diciembre de 1980. Se encontro que mas del 50% de las cepas analizadas presentaron resistencia a tetraciclina, estreptomicina, gentamicina y kanamicina. Se observo um incremento en la resistencia a varios de los antimicrobianos en este estudio en comparacion a trabajos realizados en anos anteriores. La multirresistencia fue mayor para el genero Salmonella que para el genero Shigella y para confirmarla, se determino la concentracion minima inhibitoria a los mismos antimicrobianos. El patron de resistencia mas frecuente fue a la ampicilina, cloranfenicol, estreptomicina, tetraciclina, cefalotina, gentamicina y kanamicina para Salmonella. Mientras que en el caso de Shigella, la resistencia a tetraciclina y estreptomicina fue el patron mas frecuente (AU).
— id: 25612, year: 1985, vol: 42, page: 488, stat: Journal Article,

Lipopolysaccharide Structures in Enterobacteriaceae, Pseudomonas Aeruginosa, and Vibrio Cholerae are Immunologically Related to Campylobacter Spp
Perez-Perez, Guillermo I; Hopkins, Janet A; Blaser, Martin J
[Alexandria, VA] : Ft. Belvoir Defense Technical Information Center, 1985,
To determine whether lipopolysaccharide (LPS) structures of Campylobacter species are immunologically related to those of 11 other gram- negative organisms, we immunoblotted from polyacrylamide gels the LPS of these strains with immune rabbit serum raised against six Campylobacter jejuni strains and two Campylobacter fetus strains. The LPS studied were from Salmonella minnesota wild type and Ra to Re mutants, Salmonella typhi, Escherichia Coli, Yersinia Enterocolitica, Vibrio cholerae, and Pseudomonas aeruginosa. None of the 11 LPS preparations was recognized by the eight antisera, but antisera to each of the Campylobacter strains recognized core determinants of some LPS preparations. Antiserum directed against the most serum-sensitive C. jejuni strain, 79-193, was the only antiserum sample that recognized core regions of the rough Salmonella mutants. In converse experiments, when LPS preparations from five Campylobacter strains were blotted with antiserum to Salmonella lipid A, recognition of core structures of each was shown; data from an enzyme-linked immunosorbent assay confirmed this result. In contrast, antiserum to Salmonella typhimurium Re LPS showed no reactivity. We conclude that LPS of Campylobacter strains share lipid A antigenic determinants with the core region of LPS of several other gram-negative organisms
— id: 1621, year: 1985, vol: , page: , stat: ,

Lipopolysaccharide Structures in Enterobacteriaceae, Pseudomonas Aeruginosa, and Vibrio Cholerae are Immunologically Related to Campylobacter Spp
Perez-Perez, Guillermo I; Hopkins, Janet A; Blaser, Martin J
[S.l.] : Ft. Belvoir Defense Technical Information Center, 1985,
To determine whether lipopolysaccharide (LPS) structures of Campylobacter species are immunologically related to those of 11 other gram- negative organisms, we immunoblotted from polyacrylamide gels the LPS of these strains with immune rabbit serum raised against six Campylobacter jejuni strains and two Campylobacter fetus strains. The LPS studied were from Salmonella minnesota wild type and Ra to Re mutants, Salmonella typhi, Escherichia Coli, Yersinia Enterocolitica, Vibrio cholerae, and Pseudomonas aeruginosa. None of the 11 LPS preparations was recognized by the eight antisera, but antisera to each of the Campylobacter strains recognized core determinants of some LPS preparations. Antiserum directed against the most serum-sensitive C. jejuni strain, 79-193, was the only antiserum sample that recognized core regions of the rough Salmonella mutants. In converse experiments, when LPS preparations from five Campylobacter strains were blotted with antiserum to Salmonella lipid A, recognition of core structures of each was shown; data from an enzyme-linked immunosorbent assay confirmed this result. In contrast, antiserum to Salmonella typhimurium Re LPS showed no reactivity. We conclude that LPS of Campylobacter strains share lipid A antigenic determinants with the core region of LPS of several other gram-negative organisms
— id: 2045, year: 1985, vol: , page: , stat: ,