Joan Reibman, M.D.

Stepping down asthma treatment: how and when
Rogers, Linda; Reibman, Joan
2012 Jan;18(1):70-75, Current opinion in pulmonary medicine
PURPOSE OF REVIEW: Guidelines suggest that asthma medication should be reduced once asthma control is sustained. Moderate-dose inhaled corticosteroids (ICS) can typically be reduced, but questions remain about the lowest effective ICS dose and the role of non-ICS controllers in treatment reduction. Long-acting beta agonist (LABA) safety concerns have created controversy about how to step down patients on ICS/LABA therapy. This review will focus on the current status of these issues. RECENT FINDINGS: Intermittent ICS treatment, often in fixed combination with short-acting beta agonist, is an emerging strategy for control of mild asthma. Addition of leukotriene modifiers, LABAs, and omalizumab to ICS can allow for reduced ICS dosing. Doses of ICS that control symptoms may be inadequate to control exacerbations. Reducing ICS dose before discontinuing LABAs may be the more effective approach for patients on combination therapy. SUMMARY: Use of non-ICS controllers allows for ICS dose reduction with superior outcomes. Tapering of ICS prior to LABA discontinuation may be the favored approach for patients on ICS/LABA therapy, but an understanding of long-term outcomes and further safety data are required. The lowest ICS dose that adequately controls both asthma impairment and risk remains to be determined
— id: 145767, year: 2012, vol: 18, page: 70, stat: Journal Article,

Lung pathologic findings in a local residential and working community exposed to world trade center dust, gas, and fumes
Caplan-Shaw, Caralee E; Yee, Herman; Rogers, Linda; Abraham, Jerrold L; Parsia, Sam S; Naidich, David P; Borczuk, Alain; Moreira, Andre; Shiau, Maria C; Ko, Jane P; Brusca-Augello, Geraldine; Berger, Kenneth I; Goldring, Roberta M; Reibman, Joan
2011 Sep;53(9):981-991, Journal of occupational & environmental medicine
OBJECTIVE: : To describe pathologic findings in symptomatic World Trade Center-exposed local workers, residents, and cleanup workers enrolled in a treatment program. METHODS: : Twelve patients underwent surgical lung biopsy for suspected interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests (group 2, n = 6). High-resolution computed axial tomography and pathologic findings were coded. Scanning electron microscopy with energy-dispersive x-ray spectroscopy was performed. RESULTS: : High-resolution computed axial tomography showed reticular findings (group 1) or normal or airway-related findings (group 2). Pulmonary function tests were predominantly restrictive. Interstitial fibrosis, emphysematous change, and small airway abnormalities were seen. All cases had opaque and birefringent particles within macrophages, and examined particles contained silica, aluminum silicates, titanium dioxide, talc, and metals. CONCLUSIONS: : In symptomatic World Trade Center-exposed individuals, pathologic findings suggest a common exposure resulting in alveolar loss and a diverse response to injury
— id: 137445, year: 2011, vol: 53, page: 981, stat: Journal Article,

Case-Control Study of Lung Function in World Trade Center Health Registry Area Residents and Workers
Friedman SM; Maslow CB; Reibman J; Pillai PS; Goldring RM; Farfel MR; Stellman SD; Berger KI
2011 Sep 1;184(5):582-589, American journal of respiratory & critical care medicine
RATIONALE: Residents and area workers who inhaled dust and fumes from the World Trade Center disaster reported lower respiratory symptoms in two World Trade Center Health Registry surveys (2003-2004 and 2006-2007), but lung function data were lacking. OBJECTIVES: To examine the relationship between persistent respiratory symptoms and pulmonary function in a nested case-control study of exposed adult residents and area workers 7-8 years post-9/11/2001. METHODS: Registrants reporting post-9/11 onset of a lower respiratory symptom in the first survey and the same symptom in the second survey were solicited as potential cases. Registrants without lower respiratory symptoms in either Registry survey were solicited as potential controls. Final case-control status was determined by lower respiratory symptoms at a third interview (the study), when spirometry and impulse oscillometry were also performed. MAIN RESULTS: We identified 180 cases and 473 controls. Cases were more likely than controls to have abnormal spirometry (19% versus 11%, P<0.05), and impulse oscillometry measurements of elevated airway resistance, R5 (68% versus 27%, P<0.0001) and frequency dependence of resistance, R5-20 (36% versus 7%, P<0.0001). When spirometry was normal, cases were more likely than controls to have elevated R5 and R5-20 (62% versus 25% and 27% versus 6% respectively, both P<0.0001). Associations between symptoms and oscillometry held when factors significant in bivariate comparisons (BMI, spirometry, exposures) were analyzed using logistic regression. CONCLUSIONS: This study links persistent respiratory symptoms and oscillometric abnormalities in WTC-exposed residents and area workers. Elevated R5 and R5-20 in cases despite normal spirometry suggested distal airway dysfunction as a mechanism for symptoms
— id: 137969, year: 2011, vol: 184, page: 582, stat: Journal Article,

Genetic Variants of TSLP and Asthma in an Admixed Urban Population
Liu, Mengling; Rogers, Linda; Cheng, Qinyi; Shao, Yongzhao; Fernandez-Beros, Maria Elena; Hirschhorn, Joel N; Lyon, Helen N; Gajdos, Zofia K Z; Vedantam, Sailaja; Gregersen, Peter; Seldin, Michael F; Bleck, Bertram; Ramasamy, Adaikalavan; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Kuokkanen, Mikko; Laitinen, Tarja; Eriksson, Johan; Lehtimaki, Terho; Raitakari, Olli T; Reibman, Joan
2011 ;6(9):e25099-e25099, PLoS ONE
BACKGROUND: Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations. OBJECTIVES: To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. METHODOLOGY AND MAIN RESULTS: Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09-2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04-3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93-1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10-2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07-1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08-1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94-1.17, p = 0.33). CONCLUSIONS: Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction
— id: 138030, year: 2011, vol: 6, page: e25099, stat: Journal Article,

Pharmacologic approaches to life-threatening asthma
Rogers, Linda; Reibman, Joan
2011 Dec;5(6):397-408, Therapeutic advances in respiratory disease
Following a peak in asthma mortality in the late 1980s and early 1990s, we have been fortunate to see a substantial decrease in asthma deaths in recent years. Although most asthma deaths occur outside the hospital, near-fatal events are commonplace, with anywhere from 2-20% of patients with acute asthma admitted to intensive care, and 2-4% intubated for respiratory failure. Standard therapies for acute severe and near-fatal asthma include administration of systemic corticosteroids, and frequent or continuous inhaled beta agonists. Controversy remains regarding the optimal therapy of those who fail to respond to these initial treatments, those who remain at risk of acute respiratory failure, and patients requiring mechanical ventilation. There remain significant gaps in our knowledge regarding relative benefits of intravenous versus oral corticosteroids, intermittent versus continuous beta agonists, and the role of various adjunctive treatments including intravenous magnesium, systemic beta agonists, aminophylline, and helium-oxygen mixtures. Using models and radiolabeled aerosols, there is a greater understanding regarding effective administration of inhaled beta-agonists in ventilated patients. There is limited available evidence for treatment of near-fatal asthma, a fact reflected by the significant variability in asthma critical care practice. Much of the data guiding treatment in this setting has been generalized from studies of acute asthma in the ED and from general populations of hospitalized patients with acute asthma. This review will focus on pharmacologic approaches to life-threatening asthma by reviewing current guideline recommendations, reviewing the scientific basis of the guidelines, and highlighting gaps in our knowledge in treatment of refractory acute or near-fatal asthma
— id: 150555, year: 2011, vol: 5, page: 397, stat: Journal Article,

Disparity between proximal and distal airway reactivity during methacholine challenge
Segal, Leopoldo N; Goldring, Roberta M; Oppenheimer, Beno W; Stabile, Alexandra; Reibman, Joan; Rom, William N; Weiden, Michael D; Berger, Kenneth I
2011 Jun;8(3):145-152, COPD: Journal of Chronic Obstructive Pulmonary Disease
There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV(1) change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R(5,) R(20)) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5-20 Hz (R(5-20)) and reactance area (AX). R(5) varied widely during MCT (range -0.8 - 11.3 cmH(2)O/L/s) and correlated poorly with change in FEV(1) (r = 0.17). Changes in R(5) reflected changes in both R(20) and R(5-20) (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R(20) increased only 0.3 cmH(2)O/L/s, while R(5-20) increased 0.7 cmH(2)O/L/s for every 1cmH(2)O/L/s change in R(5,) indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV(1) change (<5%), while R(5) increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV(1) and R(20)) and distal airway heterogeneity (R(5-20) and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV(1). This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment
— id: 134171, year: 2011, vol: 8, page: 145, stat: Journal Article,

Diesel exhaust particle-treated human bronchial epithelial cells upregulate Jagged-1 and OX40 ligand in myeloid dendritic cells via thymic stromal lymphopoietin
Bleck, Bertram; Tse, Doris B; Gordon, Terry; Ahsan, Mohammad R; Reibman, Joan
2010 Dec 1;185(11):6636-6645, Journal of immunology
Ambient particulate matter, including diesel exhaust particles (DEP), promotes the development of allergic disorders. DEP increase oxidative stress and influence human bronchial epithelial cell (HBEC)-dendritic cell interactions via cytokines, including thymic stromal lymphopoietin (TSLP). Upregulation of TSLP results in Th2 responses. Using primary culture HBEC and human myeloid dendritic cell (mDC) cocultures, we show in this study that DEP upregulation of Th2 responses occurred via HBEC-dependent mechanisms that resulted from oxidative stress. Moreover, DEP-treated HBEC and ambient particulate matter-treated HBEC upregulated OX40 ligand (OX40L) and the Notch ligand Jagged-1 mRNA and expression on mDC. Upregulation of OX40L as well as Jagged-1 on mDC required HBEC and did not occur in the presence of N-acetylcysteine. Furthermore, OX40L and Jagged-1 upregulation was inhibited when HBEC expression of TSLP was silenced. Thus, DEP treatment of HBEC targeted two distinct pathways in mDC that were downstream of TSLP expression. Upregulation of OX40L and Jagged-1 by mDC resulted in mDC-driven Th2 responses. These studies expand our understanding of the mechanism by which ambient pollutants alter mucosal immunity and promote disorders such as asthma
— id: 114828, year: 2010, vol: 185, page: 6636, stat: Journal Article,

Headache and Mental Health Symptoms in Residents and Workers Exposed to World Trade Center (WTC) Dust, Gas and Fumes Presenting for Medical Care
Crystal, S. C.; Julian, M. -C.; Reibman, J.; Liu, M.; Shao, Y.; Oh, C.; Henry, K. A.
2010 AUG ;50(8):S2-S2, Headache
— id: 112182, year: 2010, vol: 50, page: S2, stat: Journal Article,

Lower respiratory symptoms among residents living near the World Trade Center, two and four years after 9/11
Lin, Shao; Jones, Rena; Reibman, Joan; Morse, Dale; Hwang, Syni-An
2010 Jan-Mar;16(1):44-52, International journal of occupational & environmental health
We investigated whether residents living near the World Trade Center (WTC) continued to experience respiratory problems several years after September 11, 2001 (9/11). Residents living within one mile of the WTC surveyed after 9/11 responded two and four years later to follow-up surveys that asked about lower respiratory symptoms (LRS), medical history, psychological stress, and indoor environmental characteristics. There were declines in the proportion of residents reporting LRS, new lower respiratory diagnoses, unplanned medical visits, and asthma medication use. However, the proportion of residents reporting any LRS in the affected area at follow-up remained higher than the original proportion in the control area; residents with multiple sources of potential 9/11-related exposures were at greatest risk for LRS at follow-up. Psychological stress, dust/odors, and moisture were significantly associated with LRS at follow-up. These data demonstrate that LRS continue to burden residents living in the areas affected by the WTC disaster
— id: 134423, year: 2010, vol: 16, page: 44, stat: Journal Article,

Genetics and asthma disease susceptibility in the US Latino population
Reibman, Joan; Liu, Mengling
2010 Mar;77(2):140-148, Mount Sinai journal of medicine
The US Latino population is heterogeneous with diversity in environmental exposures and socioeconomic status. Moreover, the US Hispanic population derives from numerous countries previously under Spanish rule, and many Hispanics have complex proportions of European, Native American, and African ancestry. Disparities in asthma severity and control are due to complex interactions between environmental exposures, socioeconomic factors, and genetic variations. In addition, diseases within the Latino community may also differ by country of origin. Although US Census data show low asthma rates in the Hispanic population as a whole, there is a lot of variability in the prevalence and morbidity of asthma, with a prevalence of 5.0% in Mexican Americans versus 17.0% in Puerto Ricans. The diversity and population admixture make the study of the genetics of asthma complex in Latino populations. However, an understanding of the genetics of asthma in all populations, including the Latino population, can enhance risk identification, help us to target pharmacological therapy, and guide environmental regulations, all of which can promote a reduction in health disparities. The inclusion of markers of ancestral diversity and the incorporation of techniques to adjust for stratification now make these studies feasible in complex populations, including the Latino population. To date, studies using linkage analyses, genome-wide associations, or candidate gene analyses have identified an association of asthma or asthma-related phenotypes with candidate genes, including interleukin 13, beta-2 adrenergic receptor, a disintegrin and metalloproteinase 33, orosomucoid 1-like 3, and thymic stromal lymphopoietin. As reviewed here, although these genes have been identified in diverse populations, limited studies have been performed in Latino populations, and they have had variable replication. There is a need for the development of registries with well-phenotyped pediatric and adult Latino populations and subgroups for inclusion in the rapidly expanding field of genetic studies, and these studies need to be used to reduce health disparities
— id: 108925, year: 2010, vol: 77, page: 140, stat: Journal Article,

Emerging exposures and respiratory health: world trade center dust
Rom, William N; Reibman, Joan; Rogers, Linda; Weiden, Michael D; Oppenheimer, Beno; Berger, Kenneth; Goldring, Roberta; Harrison, Denise; Prezant, David
2010 May;7(2):142-145, Proceedings of the American Thoracic Society
The attack on the World Trade Center (WTC) on 9/11/2001 produced a massive dust cloud with acute exposure, and the rubble pile burning over 3 months exposed more than 300,000 residents, rescue workers, and clean-up workers. Firefighters in the New York City Fire Department had significant respiratory symptoms characterized by cough, dyspnea, gastroesophageal reflux, and nasal stuffiness with a significant 1-year decline in FVC and FEV(1). Bronchial hyperreactivity measured by methacholine challenge correlated with bronchial wall thickening on CT scans. Compared with the NHANES III data for FVC and FEV(1), 32% of 2,000 WTC dust-exposed residents and clean-up workers were below the lower 5th percentile. The most common abnormality was a low FVC pattern, a finding similar to that also described for individuals in rescue and recovery activities. Among those complaining of respiratory symptoms and normal spirometry, almost half had abnormalities detected with impedance oscillometry consistent with distal airways' disease. Follow-up with the WTC Health Registry and the WTC Environmental Health Center will help discern whether treatment with anti-inflammatory medications or bronchodilators in those with respiratory symptoms may prevent the development of chronic obstructive pulmonary disease
— id: 109531, year: 2010, vol: 7, page: 142, stat: Journal Article,

Replication Of An Association Of The Interleukin-1 Receptor Antagonist Gene With Asthma In An Adult Urban Admixed Population
Shao Y; Liu M; Rogers Q; Cheng M; Fernandez-Beros P; Gregersen M; Seldin J; Hirschhorn J; Reibman J
2010 ;181:?-? #A1321, American journal of respiratory & critical care medicine
— id: 114874, year: 2010, vol: 181, page: ?, stat: Journal Article,

Effects of Asymptomatic Proximal and Distal Gastroesophageal Reflux on Asthma Severity
DiMango, E; Holbrook, JT; Simpson, E; Reibman, J; Richter, J; Narula, S; Prusakowski, N; Mastronarde, JG; Wise, RA
2009 NOV 1 ;180(9):809-816, American journal of respiratory & critical care medicine
Rationale Silent gastroesophageal reflux (GER) is common in patients with asthma, but it is unclear whether GER is associated with worse asthma symptoms or reduced lung function. Objectives: To determine in patients with poorly controlled asthma, whether proximal or distal esophageal reflux is associated with asthma severity, symptoms, physiology, or functional status. Methods: Baseline asthma characteristics were measured in patients with asthma enrolled in a multicenter trial assessing the effectiveness of esomeprazole on asthma control. All participants underwent 24-hour esophageal pH probe monitoring. Lung function, methacholine responsiveness, asthma symptoms, and quality-of-life scores were compared in subjects with and without GER. Measurements and Main Results: Of 304 participants with probe recordings, 53% had reflux. Of 242 participants with recordings of proximal pH, 38% had proximal reflux. There was no difference in need for short-acting bronchodilators, nocturnal awakenings, dose of inhaled corticosteroid, use of long-acting beta-agonists, lung function, or methacholine reactivity between individuals with and without proximal or distal GER. Participants with GER reported more use of oral corticosteroids and had worse asthma quality of life and subjects with proximal GER had significantly worse asthma quality of life and health-related quality of life compared with participants without GER. Conclusions: Asymptornatic GER is not associated with distinguishing asthma symptoms or lower lung function in individuals with suboptimal asthma control who are using inhaled corticosteroids. Patients with proximal reflux report significantly worse asthma and health-related quality of life despite lack of physiologic impairment or increase in asthma symptoms
— id: 105234, year: 2009, vol: 180, page: 809, stat: Journal Article,

Characteristics of a residential and working community with diverse exposure to World Trade Center dust, gas, and fumes
Reibman, Joan; Liu, Mengling; Cheng, Qinyi; Liautaud, Sybille; Rogers, Linda; Lau, Stephanie; Berger, Kenneth I; Goldring, Roberta M; Marmor, Michael; Fernandez-Beros, Maria Elena; Tonorezos, Emily S; Caplan-Shaw, Caralee E; Gonzalez, Jaime; Filner, Joshua; Walter, Dawn; Kyng, Kymara; Rom, William N
2009 May;51(5):534-541, Journal of occupational & environmental medicine
OBJECTIVE: To describe physical symptoms in those local residents, local workers, and cleanup workers who were enrolled in a treatment program and had reported symptoms and exposure to the dust, gas, and fumes released with the destruction of the World Trade Center (WTC) on September 11, 2001. METHODS: Symptomatic individuals underwent standardized evaluation and subsequent treatment. RESULTS: One thousand eight hundred ninety-eight individuals participated in the WTC Environmental Health Center between September 2005 and May 2008. Upper and lower respiratory symptoms that began after September 11, 2001 and persisted at the time of examination were common in each exposure population. Many (31%) had spirometry measurements below the lower limit of normal. CONCLUSIONS: Residents and local workers as well as those with work-associated exposure to WTC dust have new and persistent respiratory symptoms with lung function abnormalities 5 or more years after the WTC destruction
— id: 98897, year: 2009, vol: 51, page: 534, stat: Journal Article,

Does Helicobacter pylori protect against asthma and allergy?
Blaser, Martin J; Chen, Yu; Reibman, Joan
2008 May;57(5):561-567, Gut: journal of the British Society of Gastroenterology
The microbes that persistently colonize their vertebrate hosts are not accidental (1). Although highly numerous and diverse, there is specificity by site and substantial conservation between individuals. The genus Helicobacter includes spiral, highly motile, urease-positive, gram-negative bacteria that colonize the stomach in many mammals. Each mammal has one or more dominant Helicobacter species and they are highly, if not exclusively, host species-specific (2). Such observations are consistent with the hypothesis that when ancestral mammals diverged from reptiles about 150 million years ago, they contained ancestral helicobacters, which then diverged as their hosts changed. According to this hypothesis, helicobacters represent ancestral biota (flora) in the mammalian stomach. The human-adapted strain is H. pylori (3), which has not been reproducibly observed in any animals other than humans and other primates (3)
— id: 76054, year: 2008, vol: 57, page: 561, stat: Journal Article,

Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation and polarization via thymic stromal lymphopoietin
Bleck, Bertram; Tse, Doris B; Curotto de Lafaille, Maria A; Zhang, Feijie; Reibman, Joan
2008 Mar;28(2):147-156, Journal of clinical immunology
Human exposure to air pollutants, including ambient particulate matter, has been proposed as a mechanism for the rise in allergic disorders. Diesel exhaust particles, a major component of ambient particulate matter, induce sensitization to neoallergens, but the mechanisms by which sensitization occur remain unclear. We show that diesel exhaust particles upregulate thymic stromal lymphopoietin in human bronchial epithelial cells in an oxidant-dependent manner. Thymic stromal lymphopoietin induced by diesel exhaust particles was associated with maturation of myeloid dendritic cells, which was blocked by anti-thymic stromal lymphopoietin antibodies or silencing epithelial cell-derived thymic stromal lymphopoietin. Dendritic cells exposed to diesel exhaust particle-treated human bronchial epithelial cells induced Th2 polarization in a thymic stromal lymphopoietin-dependent manner. These findings provide new insight into the mechanisms by which diesel exhaust particles modify human lung mucosal immunity
— id: 79452, year: 2008, vol: 28, page: 147, stat: Journal Article,

Mycobacterium tuberculosis induces CCL18 expression in human macrophages
Ferrara, G; Bleck, B; Richeldi, L; Reibman, J; Fabbri, L M; Rom, W N; Condos, R
2008 Dec;68(6):668-674, Scandinavian journal of immunology
The interaction of Mycobacterium tuberculosis (MTB) with the immune system is mediated by cytokine and chemokine responses of macrophages and/or dendritic cells. Chemokine (C-C motif) ligand 18 (CCL18) and interleukin (IL)-10 are major factors secreted by phagocytes, postulated to recruit naive T lymphocytes and inhibit pro-inflammatory cells. Our study investigated the role of CCL18 and IL-10 in an in vitro model of infection by MTB in human macrophages. CD14(+) monocytes, obtained from the peripheral blood of eight healthy donors, differentiated in monocyte-derived macrophages (MDM) with monocyte-colony stimulating factor (100 ng/ml) for 6 days, were stimulated in vitro with lipopolysaccharide (LPS) (1 microg/ml) and with heat killed MTB Hv37Ra (multiplicity of infection 1:5) for 24 h. Alveolar macrophages from five healthy donors were infected with MTB Hv37RA. CCL18 protein and mRNA were detected by enzyme-linked immunosorbent assay (ELISA) and real-time PCR, IL-10 levels by ELISA. Stimulation of MDM with LPS or MTB led to a significant increase in CCL18 protein (control 2.67 +/- 0.46 ng/ml, LPS 4.05 +/- 0.56 ng/ml, with MTB 6.70 +/- 1.59 ng/ml, n = 5, P < 0.05) and specific mRNA levels (control 0.09 +/- 0.01, LPS 0.24 +/- 0.11, with MTB 0.34 +/- 0.08 CCL18/Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), n = 3, P < 0.05). A significant increase of the production of CCL18 was observed in infected alveolar macrophages. IL-10 levels increased from 38.52 +/- 26.38 pg/ml in control cells to 1129.32 +/- 235.00 and 974.25 +/- 164.46 pg/ml in LPS and MTB treated cells, respectively (P < 0.05). Up-regulation of CCL18 and IL-10 in macrophages by MTB may be involved in the recruitment of naive T cells in association with local suppressive immunity against intracellular pathogens. This could represent a mechanism of tolerance during the early phases of infection
— id: 91453, year: 2008, vol: 68, page: 668, stat: Journal Article,

A Follow-Up of Respiratory Health Among Residents Living Near Ground Zero
Lin, S; Jones, R; Reibman, J; Hwang, S
2008 NOV ;19(6):S84-S84, Epidemiology
— id: 91470, year: 2008, vol: 19, page: S84, stat: Journal Article,

Post 9/11 GERD: a new entity
Rajapaksa, R; Cheng, Q; Liu, M; Fernandez-Beros, ME; Reibman, J
2008 SEP ;103(9):S33-S34, American journal of gastroenterology
— id: 86595, year: 2008, vol: 103, page: S33, 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,

Reported respiratory symptoms and adverse home conditions after 9/11 among residents living near the World Trade Center
Lin, Shao; Jones, Rena; Reibman, Joan; Bowers, James; Fitzgerald, Edward F; Hwang, Syni-An
2007 May;44(4):325-332, Journal of asthma
This study investigated whether self-reported damage, dust, and odors in homes near the World Trade Center (WTC) after September 11, 2001, were related to increased rates of respiratory symptoms among residents and if multiple sources of exposure were associated with greater health risk. We mailed questionnaires to homes within 1.5 km of the WTC site (affected area) and in upper Manhattan (control area). Surveys asked about respiratory symptoms, unplanned medical visits, physician diagnoses, medication use, and conditions in the home after 9/11. Adverse home conditions were associated with new-onset (i.e., began after 9/11) and persistent (i.e., remained 1 year after 9/11) upper and lower respiratory symptoms in the affected area (Cumulative Incidence Ratios [CIRs] 1.20-1.71). Residents reporting longer duration of dust/odors or multiple sources of exposure had greater risk for symptoms compared to those reporting shorter duration and fewer sources. These data suggest that WTC-related contamination in the home after 9/11 was associated with new and persistent respiratory symptoms among residents living near the site. While we cannot eliminate potential biases related to self-reported data, we took strategies to minimize their impact, and the observed effects are biologically plausible
— id: 94401, year: 2007, vol: 44, page: 325, stat: Journal Article,

Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure
Oppenheimer, Beno W; Goldring, Roberta M; Herberg, Matthew E; Hofer, Ira S; Reyfman, Paul A; Liautaud, Sybille; Rom, William N; Reibman, Joan; Berger, Kenneth I
2007 Oct;132(4):1275-1282, Chest
RATIONALE: Following collapse of the World Trade Center (WTC), individuals reported new-onset respiratory symptoms. Despite symptoms, spirometry often revealed normal airway function. However, bronchial wall thickening and air trapping were seen radiographically in some subjects. We hypothesized that symptomatic individuals following exposure to WTC dust may have functional abnormalities in distal airways not detectable with routine spirometry. METHODS: One hundred seventy-four subjects with respiratory symptoms and normal spirometry results were evaluated. Impedance oscillometry (IOS) was performed to determine resistance at 5 Hz, 5 to 20 Hz, and reactance area. Forty-three subjects were also tested for frequency dependence of compliance (FDC). Testing was repeated after bronchodilation. RESULTS: Predominant symptoms included cough (67%) and dyspnea (65%). Despite normal spirometry results, mean resistance at 5 Hz, 5 to 20 Hz, and reactance area were elevated (4.36 +/- 0.12 cm H(2)O/L/s, 0.86 +/- 0.05 cm H(2)O/L/s, and 6.12 +/- 0.50 cm H(2)O/L, respectively) [mean +/- SE]. Resistance and reactance normalized after bronchodilation. FDC was present in 37 of 43 individuals with improvement after bronchodilation. CONCLUSIONS: Symptomatic individuals with presumed WTC dust/fume exposure and normal spirometry results displayed airway dysfunction based on the following: (1) elevated airway resistance and frequency dependence of resistance determined by IOS; (2) heterogeneity of distal airway function demonstrated by elevated reactance area on oscillometry and FDC; and (3) reversibility of these functional abnormalities to or toward normal following administration of a bronchodilator. Since spirometry results were normal in all subjects, these abnormalities likely reflect dysfunction in airways more distal to those evaluated by spirometry. Examination of distal airway function when spirometry results are normal may be important in the evaluation of subjects exposed to occupational and environmental hazards
— id: 75380, year: 2007, vol: 132, page: 1275, stat: Journal Article,

Environment, genes, and immune mechanisms in asthma
Reibman, Joan; Rogers, Linda; Fernandez-Beros, Maria Elena
Environmental and occupational medicine Philadelphia : Wolters Kluwer/Lippincott Williams & Wilkins, 2007,
— id: 5362, year: 2007, vol: , page: ?, stat: Chapter,

Prevalence of workplace exacerbation of asthma symptoms in an urban working population of asthmatics
Berger, Zackary; Rom, W N; Reibman, J; Kim, M; Zhang, S; Luo, L; Friedman-Jimenez, George
2006 Aug;48(8):833-839, Journal of occupational & environmental medicine
OBJECTIVES: We used an interviewer-administered questionnaire to investigate workplace exacerbation of asthma symptoms (WEAS) among low-income, minority, working asthmatics admitted Bellevue Hospital Center in New York City from 2001 to 2002. We hypothesized that a high prevalence of WEAS would be found in this population among all jobs held and a subset of individual occupational classifications. MEASUREMENTS AND MAIN RESULTS: Of 301 subjects, 51% reported WEAS in their current or most recent job; 71% reported WEAS in any job. Prevalences (95% confidence intervals) of WEAS in common job classifications were 61% (49-73%) in janitorial jobs, 50% (33-67%) in garment and textile manufacturing jobs, and 38% (23-55%) in construction jobs. CONCLUSION: WEAS is prevalent in this urban minority population
— id: 69582, year: 2006, vol: 48, page: 833, stat: Journal Article,

Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation
Bleck, Bertram; Tse, Doris B; Jaspers, Ilona; Curotto de Lafaille, Maria A; Reibman, Joan
2006 Jun 15;176(12):7431-7437, Journal of immunology
Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001-100 mug/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 +/- 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 +/- 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses
— id: 64794, year: 2006, vol: 176, page: 7431, stat: Journal Article,

"Lin et al. respond to ""Assessment of respiratory symptoms after September 11''"
Lin, S; Reibman, J; Jones, RR; Hwang, SA; Hoerning, A; Gomez, MI; Fitzgerald, EF
2005 SEP 15 ;162(6):511-512, American journal of epidemiology
— id: 98167, year: 2005, vol: 162, page: 511, stat: Journal Article,

Upper respiratory symptoms and other health effects among residents living near the World Trade Center site after September 11, 2001
Lin, Shao; Reibman, Joan; Bowers, James A; Hwang, Syni-An; Hoerning, Anne; Gomez, Marta I; Fitzgerald, Edward F
2005 Sep 15;162(6):499-507, American journal of epidemiology
The authors investigated changes in respiratory health after September 11, 2001 ('9/11') among residents of the area near the World Trade Center (WTC) site in New York City as compared with residents of a control area. In 2002, self-administered questionnaires requesting information on the presence and persistence of respiratory symptoms, unplanned medical visits, and medication use were sent to 9,200 households (22.3% responded) within 1.5 km of the WTC site (affected area) and approximately 1,000 residences (23.3% responded) in Upper Manhattan, more than 9 km from the site (control area). Residents of the affected area reported higher rates of new-onset upper respiratory symptoms after 9/11 (cumulative incidence ratio = 2.22, 95% confidence interval (CI): 1.88, 2.63). Most of these symptoms persisted 1 year after 9/11 in the affected area. Previously healthy residents of the affected area had more respiratory-related unplanned medical visits (prevalence ratio = 1.73, 95% CI: 1.13, 2.64) and more new medication use (prevalence ratio = 2.89, 95% CI: 1.75, 4.76) after 9/11. Greater impacts on respiratory functional limitations were also found in the affected area. Although bias may have contributed to these increases, other analyses of WTC-related pollutants support their biologic plausibility. Further analyses are needed to examine whether these increases were related to environmental exposures and to monitor long-term health effects
— id: 94402, year: 2005, vol: 162, page: 499, stat: Journal Article,

The World Trade Center residents' respiratory health study: new-onset respiratory symptoms and pulmonary function
Reibman, Joan; Lin, Shao; Hwang, Syni-An A; Gulati, Mridu; Bowers, James A; Rogers, Linda; Berger, Kenneth I; Hoerning, Anne; Gomez, Marta; Fitzgerald, Edward F
2005 Apr;113(4):406-411, Environmental health perspectives
The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the community surrounding the former WTC would have an increased incidence of persistent respiratory symptoms and abnormalities in screening spirometry. A hybrid cross-sectional and retrospective cohort study using a symptom-based questionnaire and onsite screening spirometry in residents in an exposed area and in a control area was performed 12 +/- 4 months after the collapse. Surveys were analyzed from 2,812 residents. New-onset respiratory symptoms were described by 55.8% of residents in the exposed area, compared with 20.1% in the control area after the event. Persistent new-onset symptoms were identified in 26.4 versus 7.5% of residents in the exposed area versus control area, respectively. No differences in screening spirometry between the groups were detected. A small pilot study suggested the possibility of an increase in bronchial hyperresponsiveness in exposed participants with persistent symptoms. The data demonstrate an increased rate of new-onset and persistent respiratory health effects in residents near the former WTC compared with a control population
— id: 55975, year: 2005, vol: 113, page: 406, stat: Journal Article,

A case-control study of workplace exacerbation of asthma symptoms
Berger, Z; Kim, M; Reibman, J; Shore, R; Friedman-Jimenez, G
2004 JUN 1 ;159(11):S78-S78, American journal of epidemiology
— id: 46558, year: 2004, vol: 159, page: S78, stat: Journal Article,

The association between ambient PM2.5 and biomarkers of airway inflammation in patients with asthma
De Leon, S; Ito, K; Hsu, HW; Reibman, J; Thurston, G
2004 JUL ;15(4):S24-S25, Epidemiology
— id: 47199, year: 2004, vol: 15, page: S24, stat: Journal Article,

Upper respiratory symptoms and other health effects among the residents living near the former world trade center after the September 11 disaster
Lin, S; Reibman, J; Bowers, J; Hwang, SA; Gomez, M; Fitzgerald, E
2004 JUL ;15(4):S127-S127, Epidemiology
— id: 47203, year: 2004, vol: 15, page: S127, stat: Journal Article,

The writer's voice: tuberculosis in the arts
Reibman J; Lennon T
Tuberculosis Philadelphia : Lippincott Williams & Wilkins, 2004,
— id: 3961, year: 2004, vol: , page: 3, stat: Chapter,

Impact of E1a modifications on tumor-selective adenoviral replication and toxicity
Sauthoff, Harald; Pipiya, Teona; Heitner, Sheila; Chen, Shu; Bleck, Bertram; Reibman, Joan; Chang, William; Norman, Robert G; Rom, William N; Hay, John G
2004 Oct;10(4):749-757, Molecular therapy
Replicating adenoviral vectors are capable of multiplying up to a thousandfold in the target cell, a property that might prove to be of tremendous potential for cancer therapy. However, restricting viral replication and toxicity to cancer cells is essential to optimize safety. It has been proposed that modifications of the E1a protein that impair binding to Rb or p300 will prevent S-phase induction in normal cells, resulting in selective viral replication in tumor cells. However, it remains uncertain which of the several possible E1a modifications would be most effective at protecting normal cells without compromising the oncolytic effect of the vector. In this study, we have expressed several E1a-deletion mutants at high levels using the CMV promoter and tested them for their ability to facilitate S-phase induction, viral replication, and cytotoxicity in both normal and cancer cells. Deletion of the Rb-binding domain within E1a only slightly decreased the ability of the virus to induce S phase in growth-arrested cells. The effect of this deletion on viral replication and cytotoxicity was variable. There was reduced cytotoxicity in normal bronchial epithelial cells; however, in some normal cell types there was equal viral replication and cytotoxicity compared with wild type. Deletions in both the N-terminus and the Rb-binding domain were required to block S-phase induction effectively in growth-arrested normal cells; in addition, this virus demonstrated reduced viral replication and cytotoxicity in normal cells. An equally favorable replication and cytotoxicity profile was induced by a virus expressing E1a that is incapable of binding to the transcriptional adapter motif (TRAM) of p300. All viruses were equally cytotoxic to cancer cells compared with wild-type virus. In conclusion, deletion of the Rb-binding site alone within E1a may not be the most efficacious means of targeting viral replication and toxicity. However, deletion within the N-terminus in conjunction with a deletion within the Rb-binding domain, or deletion of the p300-TRAM binding domain, induces a more favorable cytotoxicity profile
— id: 51518, year: 2004, vol: 10, page: 749, stat: Journal Article,

Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter
Reibman, Joan; Hsu, Yanshen; Chen, Lung Chi; Bleck, Bertram; Gordon, Terry
2003 Jun;28(6):648-654, American journal of respiratory cell & molecular biology
The initiation and maintenance of airway immune responses in Th2 type allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs). The cytokine microenvironment, produced by local cells, influences the recruitment of specific subsets of immature DCs and their subsequent maturation. In the airway, DCs reside in close proximity to airway epithelial cells (AECs). We examined the ability of primary culture human bronchial epithelial cells (HBECs) to synthesize and secrete the recently described CC-chemokine, MIP-3alpha/CCL20. MIP-3alpha/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3alpha/CCL20 induces selective migration of DCs because CCR6 is expressed on some immature DCs but not on CD14+ DC precursors or mature DCs. HBECs were stimulated with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells were also exposed to small size-fractions of ambient particulate matter. Each of these stimuli induced MIP-3alpha/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in HBECs. Inhibition of the ERK1/2 pathway or p38 reduced cytokine-induced MIP-3alpha/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway
— id: 39223, year: 2003, vol: 28, page: 648, stat: Journal Article,

Glucocorticoids inhibit lung cancer cell growth through both the extracellular signal-related kinase pathway and cell cycle regulators
Greenberg, Alissa K; Hu, Jing; Basu, Sharmila; Hay, John; Reibman, Joan; Yie, Ting-An; Tchou-Wong, Kam Meng; Rom, William N; Lee, Theodore C
2002 Sep;27(3):320-328, American journal of respiratory cell & molecular biology
Glucocorticoids inhibit the proliferation of various cell types, but the mechanism of this inhibition remains unclear. We investigated the effect of dexamethasone on non-small cell lung cancer cell growth and cell cycle progression. We showed that dexamethasone suppresses the proliferation of A549 and Calu-1 cells, with accumulation of cells in G1/G0 stage of the cell cycle, as determined by fluorescence-activated cell sorter analysis. Western blot analysis confirmed that this is associated with hypophosphorylation of retinoblastoma protein. Using Western blot analysis and in vitro kinase assays, we found that dexamethasone results in decreased activity of CDK2 and 4, decreased levels of cyclin D, E2F, and Myc, and increased levels of the CDK inhibitor p21(Cip1). In addition, we found that dexamethasone decreases activity of extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK). The kinetics of all these changes indicate that inhibition of the ERK/MAPK pathway precedes the cell cycle effects, suggesting that regulation of this MAPK-signaling pathway may be an alternative mechanism for glucocorticoid-induced cell cycle arrest and growth inhibition
— id: 39599, year: 2002, vol: 27, page: 320, stat: Journal Article,

Size fractions of ambient particulate matter induce granulocyte macrophage colony-stimulating factor in human bronchial epithelial cells by mitogen-activated protein kinase pathways
Reibman, Joan; Hsu, Yanshen; Chen, Lung Chi; Kumar, Asok; Su, Wei Cheng; Choy, Wanda; Talbot, Anita; Gordon, Terry
2002 Oct;27(4):455-462, American journal of respiratory cell & molecular biology
Environmental pollutants, including ambient particulate matter (PM), increase respiratory morbidity. Studies of model PM particles, including residual oil fly ash and freshly generated diesel exhaust particles, have demonstrated that PM affects inflammatory airway responses. Neither of these particles completely represents ambient PM, and therefore questions remain about ambient particulates. We hypothesized that ambient PM of different size fractions collected from an urban environment (New York City air), would activate primary culture human bronchial epithelial cells (HBECs). Because of the importance of granulocyte-macrophage colony-stimulating factor (GM-CSF) on inflammatory and immunomodulatory processes, we focused our studies on this cytokine. We demonstrated that the smallest size fraction (ultrafine/fine; < 0.18 micro m) of ambient PM (11 micro g/cm(2)), upregulated GM-CSF production (2-fold increase). The absence of effect of carbon particles of similar size, and the day-to-day variation in response, suggested that the chemical composition, but not the particle itself, was necessary for GM-CSF induction. Activation of the extracellular signal-regulated kinase and the p38 mitogen-activated protein kinase was associated with, and necessary for, GM-CSF release. These studies serve to corroborate and extend those on model particles. Moreover, they emphasize the role of the smallest size ambient particles in airway epithelial cell responses
— id: 34380, year: 2002, vol: 27, page: 455, stat: Journal Article,

Asthma in the elderly: cockroach sensitization and severity of airway obstruction in elderly nonsmokers
Rogers, Linda; Cassino, Cara; Berger, Kenneth I; Goldring, Roberta M; Norman, Robert G; Klugh, Thomas; Reibman, Joan
2002 Nov;122(5):1580-1586, Chest
STUDY OBJECTIVES: To test the hypothesis that the presence of sensitization to indoor allergens is associated with increased severity of airway obstruction in elderly subjects with asthma. DESIGN: Cohort study of subjects enrolled in a public hospital asthma clinic. SETTING: Asthma clinic in a municipal public hospital serving an indigent population in New York City. PATIENTS: Subjects aged > or = 60 years with asthma who were enrolled in the Bellevue Hospital Asthma Clinic. Total serum IgE and allergen-specific IgE measurements were performed in a cohort of elderly never-smokers who had asthma (45 patients) who had undergone spirometry before and after bronchodilator (BD) therapy. MEASUREMENTS AND RESULTS: The results of radioallergosorbent tests demonstrated that most subjects (ie, 60%) were sensitized to at least one allergen, with many sensitized to at least one indoor allergen. Cockroach (CR) was the most common allergen to which subjects were sensitized, with 47% displaying an elevated serum-specific IgE level. Fewer subjects were sensitized to dust mite, cat, dog, or ragweed. Subjects sensitized to CR (CR+) had greater reductions in airflow compared to subjects not sensitized to CR (CR-) [64 +/- 4.4% predicted vs 77.1 +/- 4.1% predicted FEV(1), respectively; p < 0.05]. Following BD administration, only 29% of CR+ subjects achieved a normal post-BD FEV(1) compared to 58% of CR- subjects. Lung volume measurements differed between CR+ and CR- subjects, with a greater elevation of functional residual capacity in CR+ subjects. CONCLUSION: In a population of elderly urban patients with asthma, the presence of CR-specific serum IgE is associated with more severe asthma, as reflected by an increase in airway obstruction and hyperinflation
— id: 39563, year: 2002, vol: 122, page: 1580, stat: Journal Article,

Duration of asthma and physiologic outcomes in elderly nonsmokers
Cassino C; Berger KI; Goldring RM; Norman RG; Kammerman S; Ciotoli C; Reibman J
2000 Oct;162(4 Pt 1):1423-1428, American journal of respiratory & critical care medicine
Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead to airway remodeling, which can result in physiologic abnormalities. Elderly lifetime nonsmokers are an ideal population in which to examine the consequences of longstanding asthma. To test the hypothesis that airflow limitation and hyperinflation are associated with the duration of asthma, we evaluated airflow and lung volumes in a cohort of elderly asthmatic individuals. All subjects were > 60 yr of age and were lifetime nonsmokers (n = 75). Patients with asthma of long duration (LDA; n = 38) had asthma for >/= 26 yr (median = 40.0 yr); patients with asthma of short duration (SDA; n = 37) had asthma for < 26 yr (median = 9 yr). Patients with LDA had a significantly lower FEV(1)% predicted than did those with SDA (59.5 +/- 2.6% versus 73.8 +/- 3.1% [mean +/- SEM], respectively; p < 0.007). Regression analysis demonstrated that duration of asthma was inversely associated with FEV(1)% predicted (r = 0.264, p < 0.03). After bronchodilator administration, the patients with LDA continued to show airflow obstruction (FEV(1)% predicted = 65.4 +/- 2.9). Only 18% of patients with LDA attained a normal postbronchodilator FEV(1), whereas 50% of those with SDA were able to do so (p < 0.003). The FRC% predicted was significantly higher in subjects with LDA than in those with SDA (142.9 +/- 5.6 versus 124.1 +/- 4.4, respectively, p < 0.01). Multiple regression analysis revealed an association between FRC and duration of asthma that was independent of the degree of airflow limitation. These data suggest that the duration of asthma is associated with the degree of airflow limitation and hyperinflation. Moreover, these abnormalities can become irreversible over time, and may reflect distal airway and/or parenchymal changes as well as proximal airway remodeling
— id: 39539, year: 2000, vol: 162, page: 1423, stat: Journal Article,

Cardiovascular toxicity of inhaled ambient particulate matter
Gordon T; Reibman J
2000 Jul;56(1):2-4, Toxicological sciences
— id: 11633, year: 2000, vol: 56, page: 2, stat: Journal Article,

Regulation of expression of granulocyte-macrophage colony-stimulating factor in human bronchial epithelial cells: roles of protein kinase C and mitogen-activated protein kinases
Reibman J; Talbot AT; Hsu Y; Ou G; Jover J; Nilsen D; Pillinger MH
2000 Aug 1;165(3):1618-1625, Journal of immunology
GM-CSF has a major role in the immune and inflammatory milieu of the airway. Airway epithelial cells (AEC) are among the first targets of environmental stimuli and local cytokines, in response to which they can produce GM-CSF. The regulation of GM-CSF is only minimally understood in AEC. We hypothesized that GM-CSF expression in AEC would result from activation of protein kinase C (PKC) and subsequent activation of the extracellular signal-regulated kinase (MAPKerk1/2) pathway, so we investigated signal transduction pathways in human primary culture bronchial epithelial cells (HBECs). TNF-alpha, IL-1beta, and PMA induced the release of GM-CSF in HBECs. The robust response to PMA was not detected in SV40 adenovirus-transformed normal human bronchial epithelial cells (BEAS-2B). PMA and TNF-alpha stimulation of GM-CSF required activation of PKC (inhibition by staurosporine and bisindolylmaleimide I). GM-CSF expression was up-regulated by a nonphorbol PKC activator, but not by an inactive PMA analogue. PMA-induced GM-CSF production in HBECs did not require a Ca2+ ionophore and was not inhibited by cyclosporin A. Activation of MAPKerk1/2 via PKC was associated with and was required for GM-CSF production induced by PMA and TNF-alpha. The data demonstrate regulation of GM-CSF in HBECs by PKC pathways converging on the MAPKerk1/2 pathway and further define cell-specific regulation critical for local airway responses
— id: 11588, year: 2000, vol: 165, page: 1618, stat: Journal Article,

Cigarette smoking and ozone-associated emergency department use for asthma by adults in New York City
Cassino C; Ito K; Bader I; Ciotoli C; Thurston G; Reibman J
1999 Jun;159(6):1773-1779, American journal of respiratory & critical care medicine
The association between ambient ozone (O3) and hospital use for asthma in children and adults is well documented. The question remains of whether there are susceptible subpopulations of asthmatic individuals who are particularly vulnerable to high O3 levels. Because tobacco use was prevalent in our cohort of inner-city adult asthmatic individuals (n = 1,216) in New York City (NYC), we investigated whether cigarette smoking was an effect modifier for asthma morbidity. We examined the relationship between personal tobacco use and O3-associated emergency department (ED) use for asthma in public hospitals in NYC. Three subpopulations were defined: never smokers (0 pack-yr), heavy smokers (>/= 13 pack-yr) and light smokers (< 13 pack-yr). Time-series regression analysis of ED use for asthma and daily O3 levels was done while controlling for temperature, seasonal/long-term trends, and day-of-week effects. Heavy smokers displayed an increased relative risk (RR) of ED visits for asthma in response to increases in 2-d lagged O3 levels (RR per 50 ppb O3 = 1.72; 95% confidence interval: 1.13 to 2.62). Logistic regression analysis confirmed that heavy cigarette use was a predictor of ED use for asthma following days with high O3 levels. Although adverse health effects of ambient O3 have also been documented in asthma populations not using cigarettes (e.g., children), our results suggest that in adult asthmatic individuals, heavy personal tobacco use may be an effect modifier for O3-associated morbidity
— id: 6126, year: 1999, vol: 159, page: 1773, stat: Journal Article,

Tobacco use among adult inner city patients with asthma
Cassino, C; Alcabes, P; Kammerman, S; Reibman, J
1999 MAR ;159(3):A759-A759, American journal of respiratory & critical care medicine
— id: 53892, year: 1999, vol: 159, page: A759, stat: Journal Article,

Personal exposure to PM of outdoor and indoor origin
Lippmann, M; Thurston, GD; Ito, K; Reibman, J; Xue, N; Heikkinen, M
1999 JUL ;10(4):140O-910, Epidemiology
— id: 98319, year: 1999, vol: 10, page: 140O, stat: Journal Article,

Elevated total end specific IgE in elderly inner city asthmatics
Rogers, L; Cassino, C; Ciotoll, C; Kramer, B; Reibman, J
1999 MAR ;159(3):A856-A856, American journal of respiratory & critical care medicine
— id: 53896, year: 1999, vol: 159, page: A856, stat: Journal Article,

Regulation of granulocyte-macrophage colony-stimulating factor in normal human bronchial epithelial cells: PKC and MAP kinase signalling
Talbot, A; Choy, W; Pillinger, M; Joyer, J; Reibman, J
1999 MAR ;159(3):A721-A721, American journal of respiratory & critical care medicine
— id: 53889, year: 1999, vol: 159, page: A721, stat: Journal Article,

Early inhibition of mycobacterial growth by human alveolar macrophages is not due to nitric oxide
Aston C; Rom WN; Talbot AT; Reibman J
1998 Jun;157(6 Pt 1):1943-1950, American journal of respiratory & critical care medicine
Phagocytic cells provide the first line of defense against mycobacteria. We examined the relative mycobacteriostatic contributions of normal human alveolar macrophages (HAM), peripheral blood monocytes (PBM), and polymorphonuclear leukocytes (PMN) in the early time period after infection with mycobacteria (48 h). Cells were infected with Mycobacterium bovis (BCG) or M. tuberculosis H37Ra and their ability to inhibit growth was determined by mycobacterial incorporation of [3H]uracil. HAM inhibited the growth of both mycobacteria (44.2 +/- 7.9 and 37.6 +/- 10.5% inhibition, respectively). Two populations of HAM donors were subsequently defined: inhibitors and noninhibitors. The ability to inhibit growth of H37Ra correlated with that of BCG. In contrast to HAM, PBM and PMN did not inhibit mycobacterial growth. Because nitric oxide (NO) has been proposed to mediate growth inhibition in murine models, we examined whether NO was responsible for the early growth inhibition of mycobacteria by HAM. As expected, in murine peritoneal macrophages (MPM) IFN-gamma (2,500 U/ml) enhanced growth inhibition of BCG; the effect was abolished by the nitric oxide synthase (NOS) inhibitor NMMA. In contrast, IFN-gamma failed to enhance growth inhibition by HAM or PBM and NMMA had no effect. MPM expressed inducible nitric oxide synthase (NOS2) mRNA in response to LPS and IFN-gamma and produced NO. Neither NOS2 mRNA nor NO could be detected in HAM stimulated with LPS and IFN-gamma or mycobacteria. These data demonstrate that HAM, but not PBM or PMN, have NO-independent mycobacteriostatic activity in the early time period after infection with mycobacteria
— id: 7492, year: 1998, vol: 157, page: 1943, stat: Journal Article,

Characterization of severity of asthma in elderly subjects
Cassino, C M; Ciotoli, C; Berger, K; Smith, S C; Reibman, J
1998 Dec 09-13;12(Supplement 29):11s-11s, European respiratory journal
— id: 15778, year: 1998, vol: 12, page: 11s, stat: Journal Article,

Effect of maternal asthma on performance of parenting tasks and children's school attendance
Cassino C; Auerbach M; Kammerman S; Birgfeld E; Bordman I; Ciotoli C; Reibman J
1997 ;34(6):499-507, Journal of asthma
We evaluated the effects of maternal asthma on specific parameters of family function including the children's school attendance and mother's performance of basic parenting tasks. A case-controlled study of mothers with asthma (MA; n = 24) with children under the age of 13 and matched mothers without asthma (CM; n = 27) was performed. Children of mothers with asthma had a significantly impaired ability to attend school compared to children of control mothers (odds ratio = 15, 95% CI). Twenty-two percent of MA reported that their asthma caused their children to miss school at least once per month. In addition, 27% of MA reported that their children were regularly late for school because of the mother's asthma. Only 5% of the control mothers reported that their health caused their children to miss school, and none reported lateness. Asthma also impaired the ability of the MA to perform basic parenting tasks such as dressing children and preparing meals for children. These adverse effects of parental asthma on children's school attendance and parenting represent previously unappreciated indirect costs of asthma and may have immediate as well as future consequences
— id: 57113, year: 1997, vol: 34, page: 499, stat: Journal Article,

Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases
Jagirdar J; Lee TC; Reibman J; Gold LI; Aston C; Begin R; Rom WN
1997 Sep;105 Suppl 5:1197-1203, Environmental health perspectives
Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases
— id: 12204, year: 1997, vol: 105 Suppl 5, page: 1197, stat: Journal Article,

Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model
Lee TC; Gold LI; Reibman J; Aston C; Begin R; Rom WN; Jagirdar J
1997 ;69(3):157-164, International archives of occupational & environmental health
Asbestosis is characterized by increased collagen deposition along the walls of terminal respiratory bronchioles that extends into the alveolar ducts and septae. Alveolar macrophages are activated and release growth factors that stimulate mesenchymal cell proliferation and enhanced formation of extracellular matrix. Both insulin-like growth factor-I (IGF-I), and transforming growth factor beta (TGF-beta) regulate cellular growth and promote matrix accumulation and are hypothesized to play important roles in asbestosis. We performed immunohistochemistry using polyclonal antibodies to specific synthetic peptides of the three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) and to IGF-I on lungs of sheep treated intratracheally with chrysotile asbestos. All three TGF-beta isoforms were found in bronchial and bronchiolar epithelium, macrophages, and bronchial and vascular smooth muscle in control lungs. The distribution of TGF-beta was increased in these lung constituents as fibrotic lesions developed. Fibrotic lesions additionally demonstrated intense immunostaining of all three TGF-beta isoforms that localized to the extracellular matrix zones with little staining of interstitial cells. In the control sheep lungs, IGF-I staining was detected in bronchial and bronchiolar epithelium, bronchial glands, bronchial and vascular smooth muscle, endothelium, and macrophages. IGF-I immunostaining was detected in macrophages in peribronchial fibrosis and in fibroblasts along the periphery of and within lesions, but not in the extracellular matrix. Metaplastic proliferating epithelium and macrophages were strongly immunoreactive for IGF-I in advanced lesions. Our data demonstrate different immunostaining patterns for IGF-I and TGF-beta in asbestosis, with IGF-I in the cellular periphery and TGF-beta in the extracellular matrix consistent with a complementary role in stimulating interstitial fibroblast proliferation and new collagen deposition in areas of active fibrosis
— id: 12416, year: 1997, vol: 69, page: 157, stat: Journal Article,

Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors
Montesinos MC; Gadangi P; Longaker M; Sung J; Levine J; Nilsen D; Reibman J; Li M; Jiang CK; Hirschhorn R; Recht PA; Ostad E; Levin RI; Cronstein BN
1997 Nov 3;186(9):1615-1620, Journal of experimental medicine
The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the G alpha s-linked adenosine receptors on the cells of an artificial wound dramatically alters the kinetics of wound closure. Excisional wound closure in normal, healthy mice was significantly accelerated by topical application of the specific A2A receptor agonist CGS-21680 (50% closure by day 2 in A2 receptor antagonists. In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats. Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing
— id: 7954, year: 1997, vol: 186, page: 1615, stat: Journal Article,

Phthisis and the arts
Reibman, Joan
Tuberculosis Boston : Little Brown, 1996,
— id: 4826, year: 1996, vol: , page: ?, stat: Chapter,

Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils
Cronstein BN; Molad Y; Reibman J; Balakhane E; Levin RI; Weissmann G
1995 Aug;96(2):994-1002, Journal of clinical investigation
Since colchicine-sensitive microtubules regulate the expression and topography of surface glycoproteins on a variety of cells, we sought evidence that colchicine interferes with neutrophil-endothelial interactions by altering the number and/or distribution of selectins on endothelial cells and neutrophils. Extremely low, prophylactic, concentrations of colchicine (IC50 = 3 nM) eliminated the E-selectin-mediated increment in endothelial adhesiveness for neutrophils in response to IL-1 (P < 0.001) or TNF alpha (P < 0.001) by changing the distribution, but not the number, of E-selectin molecules on the surface of the endothelial cells. Colchicine inhibited stimulated endothelial adhesiveness via its effects on microtubules since vinblastine, an agent which perturbs microtubule function by other mechanisms, diminished adhesiveness whereas the photoinactivated colchicine derivative gamma-lumicolchicine was inactive. Colchicine had no effect on cell viability. At higher, therapeutic, concentrations colchicine (IC50 = 300 nM, P < 0.001) also diminished the expression of L-selectin on the surface of neutrophils (but not lymphocytes) without affecting expression of the beta 2-integrin CD11b/CD18. In confirmation, L-selectin expression was strikingly reduced (relative to CD11b/CD18 expression) on neutrophils from two individuals who had ingested therapeutic doses of colchicine. These results suggest that colchicine may exert its prophylactic effects on cytokine-provoked inflammation by diminishing the qualitative expression of E-selectin on endothelium, and its therapeutic effects by diminishing the quantitative expression of L-selectin on neutrophils
— id: 56750, year: 1995, vol: 96, page: 994, stat: Journal Article,

Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components
Zhang Y; Broser M; Cohen H; Bodkin M; Law K; Reibman J; Rom WN
1995 Feb;95(2):586-592, Journal of clinical investigation
Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) participate in granulomatous inflammation. We hypothesized that interleukin-3, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-alpha and/or IL-1-alpha and beta blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis of M. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen
— id: 56733, year: 1995, vol: 95, page: 586, stat: Journal Article,

Mycobacterium tuberculosis alters expression of adhesion molecules on monocytic cells
Lopez Ramirez GM; Rom WN; Ciotoli C; Talbot A; Martiniuk F; Cronstein B; Reibman J
1994 Jun;62(6):2515-2520, Infection & immunity
The host response to Mycobacterium tuberculosis is characterized by interactions between mononuclear cells, with recruitment and fusion of these cells culminating in granuloma formation. In addition, the host response to M. tuberculosis requires CD4+ T-cell reactivity, mediated by antigen-independent as well as antigen-dependent mechanisms. Thus, we hypothesized that cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1; CD54) would participate in the response to infection with M. tuberculosis. Exposure of THP-1 cells derived from a monocyte/macrophage cell line to M. tuberculosis (1:1 bacterium/cell ratio) elicited a sustained increase (660% +/- 49% above resting level) in the expression of ICAM-1 that continued for at least 72 h. Neither the expression of vascular cell adhesion molecule 1 (VCAM-1; CD106) nor that of the integrins lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) or CR3 (CD11b/CD18) was increased to a similar extent at corresponding time points. The increase in ICAM-1 protein expression was accompanied by an increase in steady-state mRNA (Northern [RNA] analysis). Neutralizing monoclonal antibodies directed against tumor necrosis factor alpha but not interleukin 1 alpha or interleukin 1 beta substantially abrogated the response to M. tuberculosis consistent with a paracrine or autocrine response. Continuous upregulation of the expression of ICAM-1 on mononuclear phagocytes induced by M. tuberculosis may mediate the recruitment of monocytes and enhance the antigen presentation of M. tuberculosis, thus permitting the generation and maintenance of the host response
— id: 56558, year: 1994, vol: 62, page: 2515, stat: Journal Article,

Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin
Parekh T; Saxena B; Reibman J; Cronstein BN; Gold LI
1994 Mar 1;152(5):2456-2466, Journal of immunology
TGF-beta isoforms regulate numerous cellular functions including cell growth and differentiation, the cellular synthesis and secretion of extracellular matrix proteins, such as fibronectin (Fn), and the immune response. We have previously shown that TGF-beta 1 is the most potent chemoattractant described for human peripheral blood neutrophils (PMNs), suggesting that TGF-beta s may play a role in the recruitment of PMNs during the initial phase of the inflammatory response. In our current studies, we demonstrate that the maximal chemotactic response was attained near 40 fM for all mammalian TGF-beta isoforms. However, there was a statistically significant difference in migratory distance of the PMNs: TGF-beta 2 (556 microM) > TGF-beta 3 (463 microM) > TGF-beta 1 (380 microM) (beta 2: beta 3, p < or = 0.010; beta 3: beta 1, p < or = 0.04; beta 2: beta 1, p < or = 0.0012). A mAb to the cell binding domain (CBD) of Fn inhibited the chemotactic response to TGF-beta 1 and TGF-beta 3 by 63% and to TGF-beta 2 by 70%, whereas the response to FMLP, a classic chemoattractant, was only inhibited by 18%. In contrast, a mAb to a C-terminal epitope of Fn did not retard migration (< 1.5%). The Arg-gly-Asp-ser tetrapeptide inhibited chemotaxis by approximately the same extent as the anti-CBD (52 to 83%). Furthermore, a mAb against the VLA-5 integrin (VLA-5; Fn receptor) also inhibited TGF-beta-induced chemotaxis. These results indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin on the PMN cell surface, primarily the VLA-5 integrin. TGF-beta isoforms also elicited the release of cellular Fn from PMNs; we observed a 2.3-fold increase in Fn (389 to 401 ng/ml) in the supernatants of TGF-beta-stimulated PMNs compared with unstimulated cells (173.6 ng/ml). The concentration of TGF-beta required to cause maximal release of Fn from PMNs (4000 fM) is a concentration at which TGF-beta is no longer chemotactic, suggesting that PMNs only use Fn that is constitutively expressed for migration. At higher concentrations of TGF-beta, the Fn released may accumulate basal to the cell, ultimately retarding cellular migration and modulating the chemotactic response
— id: 6480, year: 1994, vol: 152, page: 2456, stat: Journal Article,

A NOVEL MODE OF ACTION FOR COLCHICINE - MODULATION OF ADHESION MOLECULES ON BOTH NEUTROPHILS AND ENDOTHELIUM
CRONSTEIN, BN; MOLAD, Y; REIBMAN, J; WEISSMANN, G; LEVIN, RI
1993 APR ;41(2):A138-A138, Clinical research
— id: 54258, year: 1993, vol: 41, page: A138, stat: Journal Article,

Chemoattraction of neutrophils by substance P and transforming growth factor-beta 1 is inadequately explained by current models of lipid remodeling
Haines KA; Kolasinski SL; Cronstein BN; Reibman J; Gold LI; Weissmann G
1993 Aug 1;151(3):1491-1499, Journal of immunology
'Classical' chemoattractants, such as FMLP, C5a, or leukotriene B4, not only elicit directed motility but also activate neutrophils (degranulation, release of active oxygen species). Signal transduction after ligation of receptors for these classical chemoattractants is mediated by pertussis toxin (PT)-sensitive, heterotrimeric G proteins and the early production of lipid messengers via phospholipases. In contrast, we have previously shown that substance P (SP) and transforming growth factor-beta 1 (TGF-beta 1) are 'pure' chemoattractants in that they elicit chemotaxis without activating neutrophils. Paradoxically, pure chemoattractants also activate G proteins (plasmalemmal GTPase activity) without eliciting increments in cytosolic calcium ([Ca]i) and thus inositol trisphosphate. We therefore determined lipid remodeling and signal transduction in response to pure chemoattractants. Increments in plasmalemmal GTPase activated by SP (0.1 microM) and TGF-beta 1 (40 fM), like that after FMLP, were PT-sensitive (SP = 6.6 +/- 2 pm/mg/min vs SP + PT = 1.1 +/- 0.9 over basal activity; TGF-beta 1 = 4.3 +/- 1.6 vs TGF-beta 1 + PT = 2.3 +/- 0.9). In parallel, treatment of PMN with PT (1 microgram/ml, 30 min) inhibited chemotaxis (under agarose) after FMLP (2175 +/- 176 (SEM) microns vs 726 +/- 267) and SP (411 +/- 99 microns vs 103 +/- 62 microns) and TGF-beta 1 (40 fM, 375 +/- 53 microns vs 83 +/- 47). However, G proteins coupled to receptors for SP and TGF-beta 1, unlike FMLP, did not appear to be linked to phospholipases in that neither increments in diacylglycerol were detected after receptor ligation (FMLP = 152 +/- 22% resting levels; SP = 101 +/- 5%; TGF-beta 1 = 105 +/- 4%) nor was alkylacylglycerol increased by exposure to SP or TGF-beta 1 (SP = 92 +/- 4%; TGF-beta 1 = 101 +/- 8%; FMLP = 226 +/- 40%). Moreover, polymorphonuclear leukocytes failed to generate phosphatidates (PA) of either species after SP (DA-PA = 79 +/- 9% resting at 60 s; EA-PA = 103 +/- 4%) or TGF-beta 1 (DA-PA = 101 +/- 5%; EA-PA = 98 +/- 9%) in contrast to FMLP (DA-PA = 155 +/- 22%; EA-PA = 149 +/- 16%). The data clearly contravene the current dogma that all chemoattractants use inositol trisphosphate and diglycerides as intracellular signals and suggest the presence of a unique subset of PT-sensitive G proteins, not coupled to 'classical' phospholipases, transduce chemoattraction
— id: 9821, year: 1993, vol: 151, page: 1491, stat: Journal Article,

THE ROLE OF IGF-I AND TGF-BETA IN A SHEEP MODEL OF ASBESTOSIS
LEE, TC; JAGIRDAR, J; ASTON, C; REIBMAN, J; GOLD, L; BEGIN, R; ROM, WN
1993 APR ;147(4):A758-A758, American review of respiratory disease
— id: 54167, year: 1993, vol: 147, page: A758, stat: Journal Article,

TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ISOFORMS IN ASBESTOS-RELATED DISEASES
LEE, TC; JAGIRDAR, J; REIBMAN, J; GOLD, L; ASTON, C; BEGIN, R; ROM, WN
1993 APR ;147(4):A759-A759, American review of respiratory disease
— id: 54168, year: 1993, vol: 147, page: A759, stat: Journal Article,

Mast cell degranulating (MCD) peptide analogs with reduced ring structure
Buku A; Reibman J; Pistelli A; Blandina P; Gazis D
1992 Jun;11(3):275-280, Journal of protein chemistry
Mast cell degranulating (MCD) peptide, a component of bee venom, is a 22 amino acid peptide with two disulfide bridges. In this first structure-activity study of MCD peptide, three analogs were synthesized and tested: two analogs shortened by omitting sequences 6-10 and 8-13, respectively, and one analog lacking the disulfide bridge between cysteine residues 5 and 19. These analogs were synthesized by solid-phase methods and were compared to MCD peptide in two assays for inflammation: histamine release from mast cells and superoxide anion release from neutrophils. All three analogs produced histamine release, although with only about one fifth of the activity of MCD peptide. Superoxide anion-releasing activity, however, did not parallel histamine release. MCD peptide did not release superoxide anion, while the 6-10 and 8-13 deletion analogs were strong and weak stimulants, respectively, of this anion. CD spectra showed that the secondary structures of the three analogs were very similar to that of MCD peptide, so that a change in secondary structure cannot completely explain the changes in releasing activities. Charge differences between the two deletion analogs and MCD peptide may explain some of the differences in activity. This is the first demonstration that the various activities of MCD peptide can be separated, and provides a lead through which the purported antiinflammatory activity of MCD peptide may possibly be explored in the future
— id: 65781, year: 1992, vol: 11, page: 275, stat: Journal Article,

Occupancy of G alpha s-linked receptors uncouples chemoattractant receptors from their stimulus-transduction mechanisms in the neutrophil
Cronstein BN; Haines KA; Kolasinski S; Reibman J
1992 Aug 15;80(4):1052-1057, Blood
Adenosine and adrenergic agonists modulate neutrophil function by ligating their specific receptors (adenosine A2 and beta-adrenergic) on the neutrophil. When occupied, adenosine A2 and beta-adrenergic receptors stimulate, presumably via G alpha s, an increase in intracellular 3', 5' cyclic adenosine monophosphate (cAMP). cAMP affects cellular functions, in part, via protein kinase-mediated phosphorylation. Therefore, we determined whether inhibition of protein kinase A activity by KT5720 (10 mumol/L) reversed the inhibition of FMLP-stimulated O2- generation by 5'N-ethylcarboxamidoadenosine (NECA), the most potent adenosine A2 agonist, and by isoproterenol a potent beta-adrenergic agonist. KT5720 did not affect O2- generation stimulated by FMLP (125% +/- 13% of control, n = 5). However, KT5720 completely reversed inhibition of O2- generation by dibutyryl cAMP (DbcAMP, 1 mmol/L, from 26% +/- 5% to 84% +/- 25% of control, n = 5, P less than .004), but not by NECA (1 mumol/L, 26% +/- 5% v 33% +/- 7% of control, n = 5) or isoproterenol (10 mumol/L, 20% +/- 8% to 38% +/- 6% of control, n = 5). Nearly identical results were obtained using the less specific protein kinase inhibitor H-7. To determine whether occupancy of adenosine A2 or beta-adrenergic receptors inhibits neutrophil (PMN) activation by uncoupling chemoattractant receptors from G proteins, we determined the effect of NECA and isoproterenol on guanosine triphosphatase (GTPase) activity, a parameter that reflects G protein 'activation,' of plasma membranes derived from human PMNs. Control GTPase activity was 138.9 pmol/mg protein/min; NECA (1 nmol/L to 1 mumol/L) and isoproterenol (10 nmol/L to 10 mumol/L) alone did not significantly affect GTPase activity. FMLP (0.1 mumol/L) increased GTPase activity by 31.9 +/- .9 pmol/mg/min, an increment that was markedly inhibited to approximately 50% of control by NECA (IC50 = 3 nmol/L, P less than .001, n = 5) and isoproterenol (IC50 = 30 nmol/L, P less than .001, n = 5). Neither cAMP nor dibutyryl cAMP (10 mumol/L and 1 mmol/L) affected resting or stimulated GTPase activity. In addition, neither adenosine nor DbcAMP affected protein phosphorylation in resting or stimulated neutrophils. Our studies are consistent with the hypothesis that ligation of G alpha s-linked receptors uncouples chemoattractant receptors from their signal-transduction mechanisms rather than inhibiting neutrophil function via cAMP-mediated effects
— id: 9826, year: 1992, vol: 80, page: 1052, stat: Journal Article,

SIGNAL TRANSDUCTION IN NEUTROPHILS - ACTIVATION OF PHOSPHOLIPASES IS NEITHER NECESSARY NOR SUFFICIENT FOR CHEMOTAXIS
HAINES, KA; CRONSTEIN, BN; REIBMAN, J; WEISSMANN, G
1992 APR ;40(2):A249-A249, Clinical research
— id: 51990, year: 1992, vol: 40, page: A249, stat: Journal Article,

CHEMOATTRACTION OF NEUTROPHILS BY SUBSTANCE-P AND TRANSFORMING GROWTH FACTOR-BETA-1 SHOWS THAT CURRENT MODELS OF LIPID REMODELING ARE INADEQUATE
HAINES, KA; TANG, XY; KOLASINSKI, SL; CRONSTEIN, BN; REIBMAN, J; WEISSMANN, G
1992 SEP ;35(9):S42-S42, Arthritis & rheumatism
— id: 51841, year: 1992, vol: 35, page: S42, stat: Journal Article,

A NEW MODE OF ACTION FOR AN OLD DRUG - COLCHICINE DECREASES SURFACE EXPRESSION OF ADHESION MOLECULES ON BOTH NEUTROPHILS (PMNS) AND ENDOTHELIUM (EC)
MOLAD, Y; REIBMAN, J; LEVIN, RL; CRONSTEIN, BN
1992 SEP ;35(9):S35-S35, Arthritis & rheumatism
— id: 51839, year: 1992, vol: 35, page: S35, stat: Journal Article,

MYCOBACTERIUM-TUBERCULOSIS AND ITS CELL-WALL COMPONENT LIPOARABINOMANNAN INCREASE THE EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 IN MONOCYTIC CELLS
RAMIREZ, GML; RON, WN; BONK, SJ; CRONSTEIN, BN; REIBMAN, J
1992 APR ;40(2):A288-A288, Clinical research
— id: 51996, year: 1992, vol: 40, page: A288, stat: Journal Article,

Acute reversible hypoxemia in systemic lupus erythematosus
Abramson SB; Dobro J; Eberle MA; Benton M; Reibman J; Epstein H; Rapoport DM; Belmont HM; Goldring RM
1991 Jun 1;114(11):941-947, Annals of internal medicine
OBJECTIVE: To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products. DESIGN: Cohort study. SETTING: Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases. PATIENTS: Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls. MEASUREMENTS: Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured. MAIN RESULTS: Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL. CONCLUSION: A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation
— id: 9755, year: 1991, vol: 114, page: 941, stat: Journal Article,

Non-steroidal anti-inflammatory drugs: effects on a GTP binding protein within the neutrophil plasma membrane
Abramson SB; Leszczynska-Piziak J; Haines K; Reibman J
1991 Jun 1;41(11):1567-1573, Biochemical pharmacology
Sodium salicylate and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil functions via unknown mechanisms. To examine their site of action in the neutrophil we have studied discrete events within the plasma membrane which depend upon the normal function of a GTP binding protein (G protein). We demonstrated that sodium salicylate and piroxicam inhibit neutrophil activation in response to stimuli which require signal transduction via a G protein (e.g. formyl-methionine-leucine-phenylalanine) but have no effect on stimuli which do not (e.g. phorbol myristate acetate, ionomycin). NSAIDs blocked the ADP-ribosylation of the pertussis toxin substrate in human neutrophils. This effect was associated with the capacity of NSAIDs to block pertussis toxin-dependent inhibition of neutrophil functions. Finally, NSAIDs inhibited the binding of GTP gamma S, a stable analog of GTP, to purified neutrophil membrane preparations. The data indicate that salicylate and other NSAIDs interact with a G protein in the neutrophil plasmalemma and thereby uncouple post-receptor signaling events
— id: 9756, year: 1991, vol: 41, page: 1567, stat: Journal Article,

Effects of protein I of Neisseria gonorrhoeae on neutrophil activation: generation of diacylglycerol from phosphatidylcholine via a specific phospholipase C is associated with exocytosis
Haines KA; Reibman J; Tang XY; Blake M; Weissmann G
1991 Aug;114(3):433-442, Journal of cell biology
Upon engagement of chemoattractant receptors, neutrophils generate inositol trisphosphate and diacylglycerol (DG) by means of a phosphatidylinositol-specific phospholipase C (PI-PLC) which is regulated by a GTP-binding protein(s). We have previously reported (Reibman, J., H. M. Korchak, L. B. Vosshall, K. A. Haines, A. M. Rich, and G. Weissmann. 1988. J. Biol. Chem. 263:6322-6328) a biphasic rise in DG after exposure of neutrophils to the chemoattractant FMLP: a rapid (less than or equal to 15 s) phase ('triggering') and a slow (greater than or equal to 30 s) phase ('activation'). These derive from distinct intracellular lipid pools. To study the source of rapid and slow DG, we have used a unique probe, protein I, a porin that is the major outer membrane protein of Neisseria gonorrhoeae. Treatment of neutrophils with protein I inhibits exocytosis and homotypic cell adhesion provoked by FMLP without inhibiting assembly of the NADPH oxidase responsible for O2-. generation. DG turnover in PMN labeled with [3H]arachidonate and [14C]glycerol was profoundly altered by protein I. Whereas the rapid peak of DG was only modestly diminished (FMLP vs. FMLP plus protein I = DG labeled with [3H]arachidonic acid (3H-a.a.-DG): 142 +/- 14% SEM vs. 125 +/- 22%; DG labeled with the glycerol backbone with [14C]glycerol (D-14C-G): 125 +/- 10% SEM vs. 107 +/- 8.5% SEM), the slow rise in both 3H-a.a.-DG and D-14C-G was essentially abolished. Moreover, treatment of neutrophils with 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), which, like protein I, inhibits exocytosis without affecting O2-. generation also inhibited slow DG. However, protein phosphorylation and dephosphorylation (47phox, 66phox) were unaffected in the absence of slow DG. To determine the source of the slow DG, we have analyzed radiolabeled phospholipid (PL) turnover after FMLP +/- protein I (P.I.). Treatment of PMN with FMLP (0.1 microM) resulted in breakdown of phosphatidylcholine (PC), beginning at 30 s, and reaching a nadir at 60 s (3H-PC = 59 +/- 10.2% SEM of resting, 14C-PC = 57 +/- 6.4%). Protein I (0.25 microM) significantly inhibited PC turnover after FMLP ([3H]PC = 95 +/- 5.6% and [14C]PC = 86 +/- 8.4% of resting at 60 s), but failed to alter the metabolism of 3H- or 14C-phosphatidylinositol after FMLP (91 +/- 19.6 and 88 +/- 16.5% vs. 92 +/- 9.2 and 91 +/- 16% at 60 s).(ABSTRACT TRUNCATED AT 400 WORDS)
— id: 13948, year: 1991, vol: 114, page: 433, stat: Journal Article,

Differences in signal transduction between Fc gamma receptors (Fc gamma RII, Fc gamma RIII) and FMLP receptors in neutrophils. Effects of colchicine on pertussis toxin sensitivity and diacylglycerol formation
Reibman J; Haines KA; Gude D; Weissmann G
1991 Feb 1;146(3):988-996, Journal of immunology
Studies on the role of microtubule integrity in stimulus-response coupling in neutrophils have generated contradictory data. To determine the role of microtubule integrity in stimulus-response coupling elicited by two different mechanisms, i.e., engagement of the Fc receptors (FcR gamma II, FcR gamma III) or engagement of the receptor for FMLP, we utilized colchicine (10 microM), which reduces pericentriolar microtubules to 29% of control, and compared its effect with that of nocodazole (50 microM) and lumicolchicine (10 microM). We now demonstrate that treatment of neutrophils with colchicine but not lumicolchicine, inhibits degranulation elicited by engagement of Fc receptors but augments degranulation in response to FMLP. In contrast to the ligand-specific effect of microtubule-disruption on degranulation, superoxide anion production (assembly of the NADPH oxidase) is unaffected by colchicine regardless of the ligand. To determine whether intact microtubules were required for responses elicited by ligation of Fc gamma RII(CD32) or Fc gamma RIII(CD16), mAb directed against these receptors were employed. Treatment of neutrophils with mAb KuFc79 directed against Fc gamma RII(CD32) or mAb 3G8 directed against Fc gamma RIII(CD16) inhibited degranulation of neutrophils elicited by immune complexes (IC). In contrast, removal of most of Fc gamma RIII by phosphatidylinositol-specific phospholipase C did not significantly alter degranulation in response to IC. We conclude that degranulation elicited by IC results from ligation of both Fc gamma RII and phosphatidylinositol-specific phospholipase C-insensitive Fc gamma RIII. The importance of microtubule integrity on the generation of intracellular signals was also examined. Degranulation of neutrophils proceeds via pertussis toxin-sensitive and insensitive pathways; treatment of cells with colchicine did not augment the action of pertussis toxin. Stimulation of neutrophils by chemoattractants results in a biphasic increase in 1,2-sn-diacylglycerol; a rapid increase ('triggering') secondary to the action of a phosphatidylinositol-specific phospholipase C, and a late increase ('activation') secondary to the action of a phosphatidylcholine-specific phospholipase C. Treatment of cells with colchicine altered the production of both [3H]-arachidonic acid-diacylglycerol and diacyl[14C]glycerol in parallel to its effect on degranulation. These studies indicate that the requirement of intact microtubules for degranulation is ligand-specific. Furthermore, assembly of the respiratory burst oxidase does not require intact microtubules. Microtubules most likely alter the cycling of specific receptors or the generation of specific intracellular signals required for stimulus-response coupling in the course of degranulation. Intact microtubules are not uniformly required for the discharge of granule contents during exocytosis
— id: 14149, year: 1991, vol: 146, page: 988, stat: Journal Article,

Transforming growth factor beta 1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways
Reibman J; Meixler S; Lee TC; Gold LI; Cronstein BN; Haines KA; Kolasinski SL; Weissmann G
1991 Aug 1;88(15):6805-6809, Proceedings of the National Academy of Sciences of the United States of America
Transforming growth factor beta 1 (TGF-beta 1), a homodimeric polypeptide (Mr 25,000), derives from inflammatory cells and acts as a chemoattractant for monocytes and fibroblasts. We report here that TGF-beta 1 is also the most potent chemoattractant yet described for human peripheral blood neutrophils. Recombinant TGF-beta 1 elicited dose-dependent directed migration of neutrophils under agarose that was inhibited in the presence of a neutralizing antibody to TGF-beta 1. Maximal chemotaxis was evoked by TGF-beta 1 at femtomolar concentrations, whereas conventional chemoattractants act at nanomolar concentrations: on a molar basis, TGF-beta 1 was 150,000 times more potent than fMet-Leu-Phe. In contrast, TGF-beta 1 provoked neither exocytosis nor the production of superoxide by neutrophils. We further analyzed the mechanism by which TGF-beta 1 elicits chemotaxis (GTPase activity, [Ca2+], and actin polymerization). In contrast to the conventional chemoattractant fMet-Leu-Phe, TGF-beta neither activated classic heterotrimeric guanine nucleotide-binding proteins nor provoked global mobilization of intracellular Ca2+. Chemoattraction by both fMet-Leu-Phe and TGF-beta 1 was inhibited by cycloheximide and actinomycin D. Moreover, chemotaxis in response to TGF-beta 1 was associated with the polymerization of actin. The selectivity and potency of TGF-beta 1 as a chemoattractant suggest that it elicits directed cell migration by means of a pathway that depends not on classic intracellular signals but on protein synthesis
— id: 9831, year: 1991, vol: 88, page: 6805, stat: Journal Article,

Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions
Buyon JP; Slade SG; Reibman J; Abramson SB; Philips MR; Weissmann G; Winchester R
1990 Jan 1;144(1):191-197, Journal of immunology
We sought to determine whether the activation event which renders the CD11/CD18 leukocyte integrin/Leu-CAM glycoproteins capable of promoting cell to cell adhesion was associated with the induced posttranslational modification of phosphorylation. In neutrophils, two species of alpha-chains, a predominant CD11b 165-kDa subunit and a minor 150-kDa CD11c subunit were found to be constitutively phosphorylated. However, the 95-kDa CD18 common beta-chain was not phosphorylated in resting cells but became strongly phosphorylated in cells incubated with PMA. The beta-chain was phosphorylated in a dose-related manner within 1 min of the addition of PMA, reached maximal intensity between 4 to 10 min, and remained fully phosphorylated at 30 min. The similarities of the kinetics of homotypic aggregation induced by PMA to the time course of phosphorylation suggest that phosporylation may be relevant to at least this type of Leu-CAM-dependent adhesion. In contrast, in the presence of FMLP which induces aggregation with different kinetics than PMA, no phosphorylation of the common beta-chain was observed over a time interval of from 30 s to 10 min further emphasizing the apparent differences in the two modes of activation to an adhesive state. The phosphorylated species on neutrophils were readily detected by immunoprecipitation with each CD18 mAb and most but not all CD11b mAb which otherwise precipitated 125I-labeled CD11b species suggesting that the CD11b alpha-chain labelled with 32P may differ slightly from the 125I-labeled species in terms of its recognition by certain CD11b mAb. In mononuclear cells, similar constitutive phosphorylation of the CD11a and CD11c alpha-chains was observed that remained unchanged in the presence of either FMLP or PMA. As was demonstrated in neutrophils, phosphorylation of the CD18 beta-chains of mononuclear cells was not constitutive but was induced in the presence of PMA and not FMLP. Taken together these data suggest the existence of specific recognition sites on beta-chains for a regulatory kinase-phosphatase system
— id: 9762, year: 1990, vol: 144, page: 191, stat: Journal Article,

Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase
Haines KA; Reibman J; Callegari PE; Abramson SB; Philips MR; Weissmann G
1990 Jun 15;144(12):4757-4764, Journal of immunology
Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses
— id: 9758, year: 1990, vol: 144, page: 4757, stat: Journal Article,

TRANSFORMING GROWTH FACTOR-BETA-1 - THE MOST POTENT CHEMOATTRACTANT FOR HUMAN NEUTROPHILS (PMN)
Reibman, J; Meixler, SM; Lee, TC; Cronstein, BN; Gold, LI; Weissmann, G
1990 Apr;38(2):A406-A406, Clinical research
— id: 31965, year: 1990, vol: 38, page: A406, stat: Journal Article,

PHOSPHORYLATION OF THE ALPHA-CHAINS AND BETA-CHAINS OF THE CD11/CD18 INTEGRIN FAMILY - CONSTITUTIVE AND ACTIVATED STATES
BUYON, JP; REIBMAN, J; ABRAMSON, SB; PHILIPS, M; SLADE, SG; WEISSMANN, G; WINCHESTER, RJ
1989 APR ;37(2):A425-A425, Clinical research
— id: 51439, year: 1989, vol: 37, page: A425, stat: Journal Article,

NEUTROPHIL ACTIVATION - PROTEIN-I OF N-GONORRHEA DEMONSTRATES A PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE-C IN NEUTROPHILS
Haines, KA; Reibman, J; Abramson, SB; Blake, M; Weissmann, G
1989 Apr;37(2):A564-A564, Clinical research
— id: 31713, year: 1989, vol: 37, page: A564, stat: Journal Article,

MICROTUBULE-DEPENDENT AND INDEPENDENT PATHWAYS OF NEUTROPHIL ACTIVATION
Reibman, J; Haines, KA; Weissman, G
1989 Apr;37(2):A481-A481, Clinical research
— id: 31704, year: 1989, vol: 37, page: A481, stat: Journal Article,

NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) INHIBIT NEUTROPHIL (PMN) FUNCTIONS VIA EFFECTS AT THE G-PROTEIN OF THE PLASMA- MEMBRANE
Abramson, S; Haines, K; Leszczynska, J; Reibman, J; Weissmann, G
1988 Apr;36(3):A548-A548, Clinical research
— id: 31506, year: 1988, vol: 36, page: A548, stat: Journal Article,

DIFFERENTIAL PHOSPHORYLATION OF THE ALPHA-CHAINS AND BETA- CHAINS OF THE LFA FAMILY GP165/95, P150/95 AND LFA-1
Buyon, JP; Abramson, SB; Slade, SG; Philips, M; Reibman, J; Weissmann, G; Winchester, RJ
1988 Sep;36(5):A799-A799, Clinical research
— id: 31447, year: 1988, vol: 36, page: A799, stat: Journal Article,

Neutrophil activation: evidence for two sources of diacylglycerol distinguished by protein I of Neisseria gonorrhoeae
Haines KA; Reibman J; Vosshall L; Weissmann G
1988 ;101:163-172, Transactions of the Association of American Physicians
— id: 11279, year: 1988, vol: 101, page: 163, stat: Journal Article,

NEUTROPHIL ACTIVATION - EVIDENCE FOR 2 SOURCES OF DIACYLGLYCEROL DISTINGUISHED BY PROTEIN-I OF N - GONORRHOEAE
Haines, KA; Reibman, J; Vosshall, L; Weissmann, G
1988 Apr;36(3):A620-A620, Clinical research
— id: 31518, year: 1988, vol: 36, page: A620, stat: Journal Article,

Changes in diacylglycerol labeling, cell shape, and protein phosphorylation distinguish "triggering" from "activation" of human neutrophils
Reibman J; Korchak HM; Vosshall LB; Haines KA; Rich AM; Weissmann G
1988 May 5;263(13):6322-6328, Journal of biological chemistry
Upon activation neutrophils release reactive oxygen intermediates such as superoxide anion (O2-) which are potent mediators of inflammation. Various agents elicit different responses; N-formylmethionylleucylphenylalanine (fMLP) (0.1 microM) provokes brisk generation of superoxide anion; leukotriene B4 (LTB4, 0.1 microM) is a poor stimulus. In contrast, phorbol myristate acetate (PMA, 1.6 microM) acting directly via protein kinase C is a potent stimulus for O2-. We compared the kinetics of appearance of various 'second messengers' with the capacity of these ligands to elicit O2- generation. Kinetic analysis showed a two-phase response to membrane ligands; both an 'early' (less than or equal to 15 s) and a 'late' (greater than 15 s) increase in [3H]- and [14C]diacylglycerol (DG) was noted in response to fMLP. In contrast, LTB4 elicited only a rapid early increase in DG. The rise in DG evoked by PMA was late. Cytochalasin B increased the late phase of DG labeling elicited by all agonists. Moreover, comparison of increases in [3H]DG versus those of [14C]DG at early and late time points suggested that DG was not formed exclusively from the hydrolysis of polyphosphoinositides. Early increments of DG were also accompanied by addition of plasma membrane (ultrastructural morphometry); the ratio of surface perimeter to area increased rapidly (10 s) and persisted (60 s) in response to fMLP. Increments were more gradual in response to PMA. Kinetic analysis of protein phosphorylation was compared to the early and late increments of DG labeling. A 47,000 Mr protein was phosphorylated with kinetics consistent with the production of O2- and DG in response to fMLP (early and late) and PMA (late). In contrast, LTB4 provoked only early phosphorylation of this protein. The temporal pattern of the formation of diacylglycerol and the phosphorylation of proteins describe a dual signal. The data suggest that neutrophils require not only 'triggering' (the rapid generation of a signal) but also 'activation' (the maintenance of a signal) to sustain responses
— id: 11095, year: 1988, vol: 263, page: 6322, stat: Journal Article,

COCAINE DERIVATIVES BLUNT NEUTROPHIL RESPONSES
Callegari, P; Abramson, S; Philips, M; Haines, K; Reibman, J; Weissmann, G
1987 Apr;35(3):A613-A613, Clinical research
— id: 31199, year: 1987, vol: 35, page: A613, stat: Journal Article,

Leukotriene B4 paradox: neutrophils can, but will not, respond to ligand-receptor interactions by forming leukotriene B4 or its omega-metabolites
Haines KA; Giedd KN; Rich AM; Reibman J; Korchak HM; Weissmann G
1987 ;17B:890-899, Advances in prostaglandin thromboxane & leukotriene research
— id: 11433, year: 1987, vol: 17B, page: 890, stat: Journal Article,

NEUTROPHIL ACTIVATION - CHEMOATTRACTANTS DIFFER IN THEIR CAPACITY TO ELICIT PROTEIN-PHOSPHORYLATION
Reibman, J; Haines, KA; Korchak, HM; Weissmann, G
1987 Mar 1;46(3):987-987, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 31268, year: 1987, vol: 46, page: 987, stat: Journal Article,

PHOSPHORYLATION OF THE 47KDA TARGET PROTEIN IS NOT SUFFICIENT FOR SUPEROXIDE ANION PRODUCTION IN NEUTROPHILS
Reibman, J; Korchak, HM; Haines, KA; Vosshall, LB; Weissmann, G
1987 Apr;35(3):A537-A537, Clinical research
— id: 31195, year: 1987, vol: 35, page: A537, stat: Journal Article,

SUPEROXIDE ANION GENERATION IN LTB4 ACTIVATED NEUTROPHILS - INADEQUACY OF CYTOSOLIC CALCIUM AND DIACYL GLYCEROL AS SIGNALS
KORCHAK, HM; VOSSHALL, LB; REIBMAN, J; RICH, AM; HAINES, KA
1986 NOV ;103(5):A504-A504, Journal of cell biology
— id: 41326, year: 1986, vol: 103, page: A504, stat: Journal Article,

DIACYL GLYCEROL INCREMENTS PRECEDE RISES OF CYTOSOLIC CALCIUM IN NEUTROPHIL ACTIVATION - A MODE OF ACTION OF CYTOCHALASIN-B
KORCHAK, HM; VOSSHALL, LB; REIBMAN, J; VIENNE, K; RICH, AM; WILKENFELD, C; WEISSMANN, G
1986 APR ;34(2):A719-A719, Clinical research
— id: 41412, year: 1986, vol: 34, page: A719, stat: Journal Article,

Colchicine inhibits ionophore-induced formation of leukotriene B4 by human neutrophils: the role of microtubules
Reibman J; Haines KA; Rich AM; Cristello P; Giedd KN; Weissmann G
1986 Feb 1;136(3):1027-1032, Journal of immunology
Neutrophils which ingest particles (serum-treated zymosan, monosodium urate crystals) or are exposed to calcium ionophore A23187 generate leukotriene B4 (LTB4). Earlier work has shown that cells exposed to colchicine before exposure to monosodium urate crystals produce less LTB4; the formation of 5-HETE is unaffected. To determine whether inhibition by colchicine of LTB4 generation was stimulus-specific and was mediated by microtubule integrity, the effects of colchicine (10 microM, 60 min) on the release of lipoxygenase products from neutrophils exposed to ionophore A23187 (10 microM, 5 min) were examined. In the presence of exogenous arachidonic acid (100 microM, 15 min), colchicine decreased LTB4 to 48% +/- 11.7 of control and 5-HETE to 60.5% +/- 5.7 of control (mean +/- SEM); 15-HETE was also decreased to 61% +/- 10.3 of control. In the absence of exogenous arachidonate, LTB4 was decreased to 22.2% +/- 11.7 of control and 5-HETE to 13% +/- 4.8 of control. Lumicolchicine did not significantly affect formation of 5-HETE or LTB4. However, vinblastine sulfate (20 microM, 60 min), another microtubule-disruptive agent, decreased the formation of both 5-lipoxygenase products. The effects of colchicine and vinblastine were not due to impairment of cell viability because the release of cytoplasmic lactic dehydrogenase was unaffected. Ultrastructural analysis of centriolar microtubules showed that decrements in microtubule numbers of colchicine- and vinblastine-treated cells paralleled decrements in 5-lipoxygenase products. These pharmacologic manipulations suggested that functional microtubules might be required for optimal lipoxygenase activity. Consequently, we prepared neutrophil-derived cytoplasts, devoid of an intact microtubule system. No significant decreases in the 5- or 15-lipoxygenase products were found when cytoplasts were exposed to colchicine in the presence of exogenous arachidonate and A23187. The data show that colchicine inhibits the formation of lipoxygenase products from neutrophils stimulated with A23187, most likely via its effect on microtubules, the integrity of which appears necessary for full expression of 5- and 15-lipoxygenases
— id: 59695, year: 1986, vol: 136, page: 1027, stat: Journal Article,

BETA-ADRENERGIC STIMULATION ALTERS FUNCTION BUT NOT CALCIUM MOVEMENTS IN HUMAN-NEUTROPHILS
REIBMAN, J; KORCHAK, HM; WILKENFELD, C; RUTHERFORD, L; WEISSMANN, G
1986 APR ;133(4):A134-A134, American review of respiratory disease
— id: 41467, year: 1986, vol: 133, page: A134, stat: Journal Article,

COLCHICINE INHIBITION OF LEUKOTRIENE-B4 PRODUCTION BY HUMAN- NEUTROPHILS REQUIRES INTACT MICROTUBULES
Reibman, J; Haines, KA; Rich, AM; Giedd, KN; Cristello, P; Weissmann, G
1985 ;33(2):A511-A511, Clinical research
— id: 30926, year: 1985, vol: 33, page: A511, stat: Journal Article,

SEPARATION OF YOUNGER RED-CELLS WITH IMPROVED SURVIVAL INVIVO - APPROACH TO CHRONIC TRANSFUSION THERAPY
Piomelli, S; Seaman, C; Reibman, J; Tytun, A; Graziano, J; Tabachnik, N; Corash, L
1978 ;75(7):3474-3478, Proceedings of the National Academy of Sciences of the United States of America
— id: 29677, year: 1978, vol: 75, page: 3474, stat: Journal Article,