Alvin E Friedman-Kien, M.D.

Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes
Curreli, Francesca; Friedman-Kien, Alvin E; Flore, Ornella
2005 Mar;115(3):642-652, Journal of clinical investigation
Kaposi sarcoma-associated herpesvirus (KSHV) is linked with all clinical forms of Kaposi sarcoma and several lymphoproliferative disorders. Like other herpesviruses, KSHV becomes latent in the infected cells, expressing only a few genes that are essential for the establishment and maintenance of its latency and for the survival of the infected cells. Inhibiting the expression of these latent genes should lead to eradication of herpesvirus infection. All currently available drugs are ineffective against latent infection. Here we show, for the first time to our knowledge, that latent infection with KSHV in B lymphocytes can be terminated by glycyrrhizic acid (GA), a triterpenoid compound earlier shown to inhibit the lytic replication of other herpesviruses. We demonstrate that GA disrupts latent KSHV infection by downregulating the expression of latency-associated nuclear antigen (LANA) and upregulating the expression of viral cyclin and selectively induces cell death of KSHV-infected cells. We show that reduced levels of LANA lead to p53 reactivation, an increase in ROS, and mitochondrial dysfunction, which result in G1 cell cycle arrest, DNA fragmentation, and oxidative stress-mediated apoptosis. Latent genes are involved in KSHV-induced oncogenesis, and strategies to interfere with their expression might prove useful for eradicating latent KSHV infection and have future therapeutic implications
— id: 49656, year: 2005, vol: 115, page: 642, stat: Journal Article,

Detection and quantitation of Kaposi's sarcoma-associated herpesvirus (KSHV) by a single competitive-quantitative polymerase chain reaction
Curreli, Francesca; Robles, Monica A; Friedman-Kien, Alvin E; Flore, Ornella
2003 Feb;107(2):261-267, Journal of virological methods
Kaposi's sarcoma-associated herpesvirus is a novel herpesvirus linked to AIDS-related neoplasms. Currently it is difficult to evaluate the number of virions in viral preparation or in samples obtained from patients with Kaposi's sarcoma (KS), since no protocol for determining the plaque forming units of KSHV exists. We constructed a fragment of a different size than the target viral DNA to carry out a competitive-quantitative PCR. Both fragment and viral DNA were added to a single PCR reaction to compete for the same set of primers. By knowing the amount of the competitor added to the reaction, we could determine the number of viral DNA molecules. We used this assay successfully to detect and quantify KSHV genomes from KS skin biopsies and pleural effusion lymphoma, and from different viral preparations. To date, this is the most convenient and economic method that allows an accurate and fast viral detection/quantitation with a single PCR
— id: 33606, year: 2003, vol: 107, page: 261, stat: Journal Article,

Kaposi's Sarcoma-associated Herpesvirus (KSHV/HHV8) Quantification and acute infection of human endothelial cell cultures
Diana S; Curreli F; Cerimele F; Friedman-Kien AE; Flore O
2003 ;119(3):181-190, L'igiene moderna
Kaposi's Sarcoma-associated herpesvirus (KSHV) is a novel herpesvirus linked to Kaposi's sarcoma and some lymphoproliferative diseases. Recently we demonstrated KSHV serial transmission and transformation of primary human endothelial cells and keratinocytes. In this study we characterize transcription and expression of KSHV genes during acute infection. Concentrated virions from TPA-induced BC-3 cell supernatant were quantitated by competitive PCR and used to infect in vitro primary and SV40-immortalized bone marrow endothelial cells and umbilical vein endothelial cells. Spindle cell morphology and lytic plaques were identified after infection, and viral DNA was detected by PCR after two passages. Six days post-infection, RT-PCRs and immunofluorescence revealed transcription of KSHV latent and lytic genes. No changes were evident in the production of human IL6, IL8, MIP-1a, MIP-1beta, RANTES, sTNFr 1/2 after infection. These studies confirm that KSHV can establish a productive infection in human endothelial cells in culture, and provide a rapid method for viral titration
— id: 70096, year: 2003, vol: 119, page: 181, stat: Journal Article,

Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the switch of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 from latency to lytic replication
Curreli, Francesca; Cerimele, Francesca; Muralidhar, Sumitra; Rosenthal, Leonard J; Cesarman, Ethel; Friedman-Kien, Alvin E; Flore, Ornella
2002 May;76(10):5208-5219, Journal of virology
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cellular dihydrofolate reductase (DHFR) homologue. Methotrexate (MTX), a potent anti-inflammatory agent, inhibits cellular DHFR activity. We investigated the effect of noncytotoxic doses of MTX on latency and lytic KSHV replication in two KSHV-infected primary effusion lymphoma cell lines (BC-3 and BC-1) and in MTX-resistant BC-3 cells (MTX-R-BC-3 cells). Treatment with MTX completely prevented tetradecanoyl phorbol acetate-induced viral DNA replication and strongly decreased viral lytic transcript levels, even in MTX-resistant cells. However, the same treatment had no effect on transcription of cellular genes and KSHV latent genes. One of the lytic transcripts inhibited by MTX, ORF50/Rta (open reading frame), is an immediate-early gene encoding a replication-transcription activator required for expression of other viral lytic genes. Therefore, transcription of genes downstream of ORF50/Rta was inhibited, including those encoding the viral G-protein-coupled receptor (GPCR), viral interleukin-6, and K12/kaposin, which have been shown to be transforming in vitro and oncogenic in mice. Resistance to MTX has been documented in cultured cells and also in patients treated with this drug. However, MTX showed an inhibitory activity even in MTX-R-BC-3 cells. Two currently available antiherpesvirus drugs, cidofovir and foscarnet, had no effect on the transcription of these viral oncogenes and ORF50/Rta. MTX is the first example of a compound shown to downregulate the expression of ORF50/Rta and therefore prevent viral transforming gene transcription. Given that the expression of these genes may be important for tumor development, MTX could play a role in the future management of KSHV-associated malignancies
— id: 39672, year: 2002, vol: 76, page: 5208, stat: Journal Article,

Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma
Miles, Steven A; Dezube, Bruce J; Lee, Jeannette Y; Krown, Susan E; Fletcher, Mary Ann; Saville, M Wayne; Kaplan, Lawrence; Groopman, Jerome; Scadden, David T; Cooley, Timothy; Von Roenn, Jamie; Friedman-Kien, Alvin
2002 Feb 15;16(3):421-429, AIDS
OBJECTIVE: To assess the efficacy, safety and tolerance of oral 9-cis-retinoic acid in HIV-infected patients with Kaposi's sarcoma. METHODS: Sixty-six patients with AIDS-related Kaposi's sarcoma were enrolled at 14 centers; 60 received the study medication and were analyzed and, of these, 45 (75%) had received prior therapy for Kaposi's sarcoma. Once daily oral 9-cis-retinoic acid (alitretinoin, Panretin) was administered at doses up to 140 mg/m2. Most patients (72%) received a maximum dose of 100 mg/m2. Response was assessed using AIDS Clinical Trials Group (ACTG) criteria. RESULTS: The median age was 38 years and the median absolute CD4 cell count was 194 x 10(6) cells/l (range 6-784 x 10(6)). Despite the use of three- and four-drug antiviral regimens (83%), the median HIV RNA at baseline was 8701 copies/ml [range < 500 (lower limit of detection) to 4.24 x 10(6)]. The tumor response rate was 37% (95% confidence interval 25-49). Tumor response was associated with improved quality-of-life measures. There was a significant increase in interleukin 6 (IL-6) levels from baseline to week 4. Responders had significantly lower baseline soluble IL-6 receptor levels (P = 0.029) than non-responders. The median time to response was 9 weeks (mean, 13 weeks; range, 4-36). HIV RNA levels did not change significantly during therapy nor did they correlate with tumor responses. Study drug was discontinued by 28 patients for adverse events, which included headache (13) and skin toxicity (10). CONCLUSION: Oral 9-cis-retinoic acid is an active antitumor drug for AIDS-related Kaposi's sarcoma. Treatment is associated with skin and constitutional toxicity and further studies are needed to improve its long-term tolerance
— id: 49658, year: 2002, vol: 16, page: 421, stat: Journal Article,

Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma
Tulpule, Anil; Groopman, Jerome; Saville, M Wayne; Harrington, William Jr; Friedman-Kien, Alvin; Espina, Byron M; Garces, Carlos; Mantelle, Lily; Mettinger, Karl; Scadden, David T; Gill, Parkash S
2002 Jul 1;95(1):147-154, Cancer
BACKGROUND: Treatment options are limited for patients with advanced acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS) whose disease has progressed after receiving therapy with liposomal anthracyclines or combination chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV). This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy. METHODS: This was an open-label, multicenter Phase II study. Eligible patients had advanced AIDS-KS consisting of at least 25 mucocutaneous lesions, visceral disease, or lymphedema, and had failed to respond to at least one previous systemic chemotherapy regimen. Patients were treated with paclitaxel at a dose of 100 mg/m(2) given intravenously over 3 hours, every 2 weeks. Primary efficacy end points were tumor response, time to progression, time to treatment failure, and survival. Quality of life and adverse events were evaluated using the Symptom Distress Scale (SDS) and the World Health Organization Toxicity Criteria, respectively. RESULTS: One hundred and seven male patients with advanced AIDS-KS were enrolled from nine participating sites. The median entry CD4+ lymphocyte count was 41/mm(3) (range 0-1139). Previous treatment regimens included ABV in 52, liposomal daunorubicin in 49, and liposomal doxorubicin in 40 patients. Forty-one patients (38%) received two or more previous chemotherapy regimens. Protease inhibitor use during the study was reported by 82 (77%) patients overall; 47 patients (44%) were receiving a protease inhibitor before study entry. Complete or partial response was documented in 60 patients (56%). The median duration of response was 8.9 months. Major response rate was similar when comparing patients not on a protease inhibitor at the time of response (59%) with patients on a protease inhibitor at time of response (54%). However, protease inhibitor use had a significant impact on survival (P = 0.04). Grade 4 neutropenia was reported in 35% of patients; other life-threatening side effects were uncommon. Significant improvements were seen in the total quality of life scores measured by the SDS, including significant improvement in KS-related symptoms such as facial disease, tumor-associated edema, and pulmonary involvement. CONCLUSION: Paclitaxel given every 2 weeks induces major tumor regression in the majority of patients with advanced KS who failed to respond to previous systemic chemotherapy. Paclitaxel is associated with significant improvement in quality of life with acceptable toxicity and should be considered as an effective treatment option for patients with advanced KS
— id: 49657, year: 2002, vol: 95, page: 147, stat: Journal Article,

Kaposi's Sarcoma-Associated Herpesvirus Can Productively Infect Primary Human Keratinocytes and Alter Their Growth Properties
Cerimele F; Curreli F; Ely S; Friedman-Kien AE; Cesarman E; Flore O
2001 Mar 1;75(5):2435-2443, Journal of virology
Previous studies have shown the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) DNA in endothelial cells, in keratinocytes in the basal layer of the epidermis overlying plaque-stage nodular lesions of cutaneous Kaposi's sarcoma (KS), and in the epithelial cells of eccrine glands within KS lesions. We infected primary cell cultures of human keratinocytes with KSHV/HHV8. At 6 days post infection, transcription of viral genes was detected by reverse transcriptase PCR (RT-PCR), and protein expression was documented by an immunofluorescence assay with an anti-LANA monoclonal antibody. To determine whether the viral lytic cycle was inducible by chemical treatment, KSHV/HHV8-infected keratinocytes were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and RT-PCR was performed to confirm the transcription of lytic genes such as open reading frame 26, (which encodes a capsid protein). Finally, to assess infectious viral production, other primary human cells (human umbilical vein endothelial cells), were infected with concentrated supernatant of KSHV-infected, TPA-induced keratinocytes and the presence of viral transcripts was confirmed by RT-PCR. The uninfected keratinocytes senesced 3 to 5 weeks after mock infection, while the KSHV/HHV8-infected keratinocytes continued to proliferate and to date are still in culture. However, 8 weeks after infection, viral genomes were no longer detectable by nested PCR. Although the previously KSHV/HHV8-infected keratinocytes still expressed epithelial markers, they acquired new characteristics such as contact inhibition loss, telomerase activity, anchorage-independent growth, and changes in cytokine production. These results show that KSHV/HHV8, like other herpesviruses, can infect and replicate in epithelial cells in vitro and suggest that in vivo these cells may play a significant role in the establishment of KSHV/HHV8 infection and viral transmission
— id: 16417, year: 2001, vol: 75, page: 2435, stat: Journal Article,

Methotrexate inhibits the switch of Kaposi S sarcoma-associated-herpesvirus from latency to lytic replication by transcriptional down-regulation of ORF50/Rta
Curreli, F; Cerimele, F; Cesarman, E; Friedman-Kien, AE; Flore, O
2001 NOV 16 ;98(11):503A-503A, Blood
— id: 55372, year: 2001, vol: 98, page: 503A, stat: Journal Article,

Opportunistic skin diseases associated with HIV infections
Natow S; Friedman-Kien A
Current dermatologic diagnosis & treatment Philadelphia : Lippincott Williams & Wilkins, 2001,
— id: 3730, year: 2001, vol: , page: 134, stat: Chapter,

Prevalence of HTLV-I-associated T-cell lymphoma
Poiesz BJ; Papsidero LD; Ehrlich G; Sherman M; Dube S; Poiesz M; Dillon K; Ruscetti FW; Slamon D; Fang C; Williams A; Duggan D; Glaser J; Gottlieb A; Goldberg J; Ratner L; Phillips P; Han T; Friedman-Kien A; Siegal F; Rai K; Sawitsky A; Sheremata LW; Dosik H; Cunningham C; Montagna R
2001 Jan;66(1):32-38, American journal of hematology
In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials
— id: 49659, year: 2001, vol: 66, page: 32, stat: Journal Article,

Kaposi's sarcoma-associated herpesvirus (KSHV) productive infection in primary human keratinocytes
Cerimele, F; Curreli, F; Ely, S; Cesarman, E; Friedman-Kien, AE; Flore, O
2000 SEP ;115(3):538-538, Journal of investigative dermatology
— id: 54504, year: 2000, vol: 115, page: 538, stat: Journal Article,

Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials [In Process Citation]
Duvic M; Friedman-Kien AE; Looney DJ; Miles SA; Myskowski PL; Scadden DT; Von Roenn J; Galpin JE; Groopman J; Loewen G; Stevens V; Truglia JA; Yocum RC
2000 Dec;136(12):1461-1469, Archives of dermatology
OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/&mgr;L) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated. Arch Dermatol. 2000;136:1461-1469
— id: 14743, year: 2000, vol: 136, page: 1461, stat: Journal Article,

Kaposi's sarcoma
Washenik K; Clark-Loeser L; Friedman-Kien A
2000 Aug 24;343(8):581-582, New England journal of medicine
— id: 10104, year: 2000, vol: 343, page: 581, stat: Journal Article,

A multicenter, dose escalating study in patients with AIDS-related Kaposi's sarcoma
Arasteh, K; Miles, S; Gill, P; Jacobs, M; Friedman-Kien, A; Gracey, S; Barkhimer, D; Hannah, A; Scigalla, P; Langecker, P
1999 NOV ;5(4):3731S-3731S, Clinical cancer research
— id: 53796, year: 1999, vol: 5, page: 3731S, stat: Journal Article,

A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group
Gilson RJ; Shupack JL; Friedman-Kien AE; Conant MA; Weber JN; Nayagam AT; Swann RV; Pietig DC; Smith MH; Owens ML
1999 Dec 3;13(17):2397-2404, AIDS
OBJECTIVE: To assess the safety of imiquimod, an immune response modifier, in the topical treatment of external anogenital warts in HIV-infected patients. SETTING: Clinical sites in the United Kingdom (eight) and the United States (five). DESIGN: A prospective, randomized, double-blind, vehicle-controlled study of imiquimod 5% cream or vehicle applied for 8+/-2 h three times per week for a maximum of 16 weeks in HIV-seropositive males (n = 97) and females (n = 3) aged 18 years or more with clinically diagnosed external anogenital warts, CD4 T lymphocyte count of > or = 100 x 10(6) cells/l and Karnofsky score > or = 70. MAIN OUTCOME MEASURES: Safety was assessed through the incidence and severity of local skin reactions and other adverse events, and through clinical laboratory tests. Wart clearance was documented by two-dimensional measurements of warts and by photography. RESULTS: Among the patients treated with imiquimod (n = 65) and vehicle (n = 35), the most common local skin reaction was erythema, (41.9 and 26.7%, respectively) and the incidence of patients reporting at least one adverse event was 69.2 and 65.7%, respectively. No clinically meaningful differences or changes in laboratory values were observed between treatment groups, nor were drug-related adverse effects observed in regard to HIV disease. While there was no significant difference between treatment groups in the number of patients who totally cleared their baseline warts (imiquimod 11% versus vehicle 6%, P = 0.488), more imiquimod-treated patients experienced a > or = 50% reduction in baseline wart area (38% versus 14%, P = 0.013). CONCLUSION: Most local skin reactions were mild and no adverse effects on HIV disease were observed. Topically applied imiquimod 5% cream reduced wart area and may have clinical utility in treating external anogenital warts in some HIV-infected patients
— id: 14744, year: 1999, vol: 13, page: 2397, stat: Journal Article,

Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group
Walmsley S; Northfelt DW; Melosky B; Conant M; Friedman-Kien AE; Wagner B
1999 Nov 1;22(3):235-246, Journal of acquired immune deficiency syndromes. JAIDS
BACKGROUND: Kaposi's sarcoma (KS) is the most frequent malignancy in patients with HIV. Given the promise that retinoids show in the treatment of various hyperproliferative skin disorders and in vitro evidence of inhibition of proliferation of KS cells, a randomized, controlled clinical trial was conducted. METHODS AND RESULTS: A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determined by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Of 268 patients entered in the blinded treatment phase of the study (alitretinoin group, n = 134; vehicle group, n = 134), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive response, compared with 24 patients (18%) treated with vehicle gel. Of 184 patients receiving open-label alitretinoin treatment following the blinded phase of the trial, 90 patients (49%) met criteria for a positive response. This superior efficacy of alitretinoin gel over vehicle gel was maintained when the data were adjusted or analyzed for age, race, Kamofsky scores, baseline CD4+ lymphocyte counts, number of raised lesions at baseline, and aggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies. Most adverse events were mild to moderate in severity, limited to the application site, and reversible on reduction in frequency or suspension of application. Relatively few patients (7%) discontinued alitretinoin therapy because of to related adverse events. CONCLUSIONS: The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoin 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS lesions
— id: 8553, year: 1999, vol: 22, page: 235, stat: Journal Article,

Detection and titration of human herpesvirus-8-specific antibodies in sera from blood donors, acquired immunodeficiency syndrome patients, and Kaposi's sarcoma patients using a whole virus enzyme-linked immunosorbent assay
Chatlynne LG; Lapps W; Handy M; Huang YQ; Masood R; Hamilton AS; Said JW; Koeffler HP; Kaplan MH; Friedman-Kien A; Gill PS; Whitman JE; Ablashi DV
1998 Jul 1;92(1):53-58, Blood
A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a whole virus lysate as antigen was developed and used to measure the seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of various patient groups and blood donors. The virus antigen was prepared from the KS-1 cell line, which produces lytic virus, and therefore contains a broad array of viral proteins. Seroprevalence studies using this ELISA showed the following: 10 of 91 blood donors (11%) had an average HHV-8 antibody titer of 118; 67 of 72 (93%) classic Kaposi's sarcoma (KS) patients were positive with an average titer of 14,111; and 57 of 62 (92%) KS/human immunodeficiency virus (HIV) patients were positive with an average titer of 4,000. A study on a very limited number of serial serum samples from patients before and after diagnosis with KS showed highly elevated antibody titers to HHV-8 virus after KS lesions developed. Preliminary data show that 50% of the sera from HIV-1(+) homosexual patients contain IgG antibodies to HHV-8 suggesting that this population is at high risk for developing KS. Antibody results correlated well with the confirmatory immunofluorescent assays (IFA) using KS-1 cells as the substrate. This HHV-8 IgG antibody detection ELISA is sensitive and specific and does not cross-react with Epstein-Barr virus (EBV) or other human herpesviruses. The results of this HHV-8 antibody survey suggest that this rapid ELISA assay can be used to screen large numbers of sera to find those at risk for developing KS
— id: 57331, year: 1998, vol: 92, page: 53, stat: Journal Article,

Herpes virus-like DNA (HHV-8) in immunosuppressive therapy-related, HIV-related and classical Kaposi's sarcoma in Norwegian patients
Jensen P; Huang YQ; Li JJ; Clausen OP; Friedman-Kien AE
1998 May;78(3):205-206, Acta dermato-venereologica
The recently discovered human herpes virus 8 (Kaposi's sarcoma-associated herpes virus) has been implicated in the pathogenesis of Kaposi's sarcoma. Using polymerase chain reaction we detected DNA sequences of this herpes virus in 11 of 14 biopsy specimens from Kaposi's sarcoma in Norwegian patients, including the immunosuppressive therapy-related type (3 of 3), the HIV-related type (4 of 5), and the classical type (4 of 6). The results support the hypothesis of a role for human herpes virus 8 in all types of Kaposi's sarcoma independent of geographical area
— id: 14745, year: 1998, vol: 78, page: 205, stat: Journal Article,

Detection of human herpesvirus 8 DNA sequences in tissues and bodily fluids
LaDuca JR; Love JL; Abbott LZ; Dube S; Freidman-Kien AE; Poiesz BJ
1998 Dec;178(6):1610-1615, Journal of infectious diseases
Human herpesvirus 8 (HHV-8) has been proposed as a sexually transmitted etiologic agent of Kaposi's sarcoma (KS). In this study, by use of a sensitive polymerase chain reaction assay, HHV-8 DNA was detected in the skin lesions (92%), normal skin (23%), peripheral blood mononuclear cells (PBMC) (46%), plasma (7%), saliva (37%), and semen (12%) but not stool samples from KS patients. The average number of HHV-8 copies per microgram of positive target DNA was 64, 000, 9000, 40, 33,000, and 300 for skin, PBMC, plasma, saliva, and semen samples, respectively. Only 1 non-KS donor sample, of saliva, was positive for HHV-8. Sequencing showed 5% divergence among HHV-8 strains. The data suggest that saliva may be more important than semen or stool in the sexual transmission of HHV-8. The relatively high prevalence of HHV-8 in PBMC raises the question as to why there is no evidence for bloodborne virus transmission
— id: 7643, year: 1998, vol: 178, page: 1610, stat: Journal Article,

Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth factor FGF3 in nude mice
Li JJ; Friedman-Kien AE; Cockerell C; Nicolaides A; Liang SL; Huang YQ
1998 ;124(5):259-264, Journal of cancer research & clinical oncology
Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were constructed by the overlap-extension method. The proteins translated from two FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be the initiation codon, were shown to have the same molecular mass. This result suggests that translation of human FGF3, which is different from mouse FGF3, begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3 cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously into athymic nude mice. Nodular lesions developed at the injection sites in all seven mice injected with the F3-1 cell clone, which showed high expression of FGF3, and in two out of six mice injected with the F3-2 cell clone, which expressed a low level of FGF3. Histopathological features of these tumors contained fascicles of spindle-shaped cells surrounding irregular endothelial lined vascular clefts, similar to those observed in human KS lesions. Immunohistochemical staining for factor V111 antigen revealed reactivity in multiple areas, especially in abundant vascular structures of the tumor sections examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2, and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some similarities to human KS tumors. In conclusion, our results demonstrate the potential tumorigenic and angiogenic role of human FGF3
— id: 7657, year: 1998, vol: 124, page: 259, stat: Journal Article,

Pulsed dye laser treatment of molluscum contagiosum in a patient with acquired immunodeficiency syndrome
Nehal KS; Sarnoff DS; Gotkin RH; Friedman-Kien A
1998 May;24(5):533-535, Dermatologic surgery
BACKGROUND: Molluscum contagiosum is usually a self-limited benign viral disease in children and young adults. In patients with acquired immunodeficiency syndrome (AIDS), however, the infection is often widespread, disfiguring, and recalcitrant to conventional therapy. OBJECTIVE: A treatment modality for widespread, recurrent molluscum contagiosum is necessary that is effective, safe, and simple. METHODS: Widespread molluscum contagiosum recalcitrant to conventional therapy in a patient with AIDS was treated with the 585-nm pulsed dye laser. RESULTS: There was a significant reduction in the number of molluscum contagiosum lesions following a single treatment with the pulsed dye laser. Treated-areas remained disease-free after 4 months. No complications were associated with the procedure. CONCLUSION: Pulsed dye laser treatment may offer another therapeutic modality that is effective and safe in the treatment of widespread and recurrent molluscum contagiosum
— id: 7704, year: 1998, vol: 24, page: 533, stat: Journal Article,

Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial
Northfelt DW; Dezube BJ; Thommes JA; Miller BJ; Fischl MA; Friedman-Kien A; Kaplan LD; Du Mond C; Mamelok RD; Henry DH
1998 Jul;16(7):2445-2451, Journal of clinical oncology
PURPOSE: Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS: Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS: Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION: Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS
— id: 7718, year: 1998, vol: 16, page: 2445, stat: Journal Article,

Update on cutaneous manifestations of HIV infection
Porras B; Costner M; Friedman-Kien AE; Cockerell CJ
1998 Sep;82(5):1033-80, v, Medical clinics of North America
The skin is affected in virtually all patients with HIV infection. Many articles and several books have been published that deal with these disorders for a number of reasons. First, cutaneous disease may serve as the initial or only problem that the patient suffers for much of the course of the HIV infection. Second, serious opportunistic infections may present for the first time in the skin, so that a skin lesion may be a harbinger of the patient's having a life-threatening illness. Third, skin disorders in these patients may appear unusual and hence may not be accurately diagnosed by clinical inspection alone. Furthermore, response to treatment may be poorer than expected. Thus, skin diseases in the HIV-infected patient are important and, in some cases, may be the most debilitating element of the patient's condition
— id: 57226, year: 1998, vol: 82, page: 1033, stat: Journal Article,

Management of AIDS-associated Kaposi's sarcoma: A multidisciplinary perspective - Proceedings of a Roundtable Symposium, March 10, 1997, New York
Von Roenn, JH; Krown, SE; Benson, CA; Mitsuyasu, RT; Friedman-Kien, AE; Scadden, DT; Stelzer, KJ
1998 FEB ;12(2):9-24, Oncology
— id: 53539, year: 1998, vol: 12, page: 9, stat: Journal Article,

Allergic reaction to varicella vaccine
Gerecitano J; Friedman-Kien A; Chazen GD
1997 May 15;126(10):833-834, Annals of internal medicine
— id: 49661, year: 1997, vol: 126, page: 833, stat: Journal Article,

Treatment of classic Kaposi's sarcoma with liposomal encapsulated doxorubicin
Gottlieb JJ; Washenik K; Chachoua A; Friedman-Kien A
1997 Nov 8;350(9088):1363-1364, Lancet
— id: 10106, year: 1997, vol: 350, page: 1363, stat: Journal Article,

Detection of the herpesvirus type 8 (HHV-8) DNA sequences in matched specimens of semen & blood from patients with AIDS-related Kaposi's sarcoma by PCR in situ hybridization
Huang YQ; Li JJ; Poiesz BJ; Kaplan MH; Friedman-Kien AE
1997 Jan 22-26;4:199-199, Conference on Retroviruses & Opportunistic Infections
The DNA sequences of a novel human gamma herpesvirus type 8 (HHV-8) have recently been detected in Kaposi's sarcoma (KS) lesions obtained from different populations in whom this neoplasm occurs, suggesting that this virus may be implicated in the etiology and/or pathogenesis of KS.(1-3) To study the distribution and possible means of transmission of the putative viral agent, specimens of KS skin lesions, matched uninvolved skin, peripheral blood mononuclear cells (PBMC), and semen were collected from 12 HIV-positive homosexual men with AIDS-related, KS (AIDS-KS) and 2 HIV-negative homosexual men with KS. HHV-8 virus DNA was detected by Polymerase Chain Reaction (PCR) studies in all 14 of these KS specimens, and in 6 biopsies of 14 'normal' appearing skin, distant from any KS lesions including 1 uninvolved skin specimen from an HIV-negative gay male with KS. Three of 12 PBMC samples, and 3 of 12 semen samples from the AIDS-KS patients were positive for HHV-8. The DNA sequences of HHV-8 were not detected in the matched semen and PBMC specimens obtained from 2 HIV-negative homosexual men with KS, 4 HIV-positive homosexual patients without KS, 2 HIV-seronegative, healthy homosexual men, 5 HIV-positive, heterosexual male intravenous drug users (IVDU), or 5 healthy HIV-negative heterosexual donors. Using PCR-in situ positive signals for HHV-8 were demonstrated in the B lymphocyte subsets of PBMC and/or in spermatozoa and mononuclear cell in the semen from some of the PCR positive specimens from the AIDS-KS patients examined. These data show that HHV-8 is present in, and could possibly be transmitted via semen and/or blood from some homosexual men with AIDS-KS
— id: 6005, year: 1997, vol: 4, page: 199, stat: Journal Article,

Detection of the herpesvirus-like DNA sequences in matched specimens of semen and blood from patients with AIDS-related Kaposi's sarcoma by polymerase chain reaction in situ hybridization
Huang YQ; Li JJ; Poiesz BJ; Kaplan MH; Friedman-Kien AE
1997 Jan;150(1):147-153, American journal of pathology
The DNA sequences of a novel human gamma-herpesvirus type 8 (HHV-8) have recently been detected in Kaposi's sarcoma (KS) lesions obtained from different populations in whom this neoplasm occurs, suggesting that this virus may be implicated in the etiology and/or pathogenesis of KS. To study the distribution and possible means of transmission of the putative viral agent, specimens of KS skin lesions, matched uninvolved skin, peripheral blood mononuclear cells (PB-MCs), and semen were collected from 12 HIV-positive homosexual men with acquired immune deficiency syndrome (AIDS)-related KS (AIDS-KS) and 2 human immunodeficiency virus (HIV)-negative homosexual men with KS. HHV-8 virus DNA was detected by polymerase chain reaction (PCR) studies in all 14 of these KS specimens and in 6 of 14 biopsies of normal-appearing skin distant from any KS lesions including 1 uninvolved skin specimen from an HIV-negative homosexual male with KS. In addition, 3 of 12 PBMC samples and 3 of 12 semen samples from the AIDS-KS patients were positive for HHV-8. The DNA sequences of HHV-8 were not detected in the matched semen and PBMC specimens obtained from 2 HIV-negative homosexual men with KS, 4 HIV-positive homosexual patients without KS, 2 HIV-seronegative healthy homosexual men, 5 HIV-positive heterosexual male intravenous drug users, or 5 healthy HIV-negative heterosexual donors. Using PCR in situ, positive signals for HHV-8 were demonstrated in the B lymphocyte subsets of PBMCs and/or in spermatozoa and mononuclear cells in the semen from some of the PCR-positive specimens from the AIDS-KS patients examined. These data show that HHV-8 is present in and could possibly be transmitted via semen and/or blood from some homosexual men with AIDS-KS
— id: 7073, year: 1997, vol: 150, page: 147, stat: Journal Article,

Expression and mutation of the tumor suppressor gene p53 in AIDS-associated Kaposi's sarcoma [see comments]
Li JJ; Huang YQ; Cockerell CJ; Zhang WG; Nicolaides A; Friedman-Kien AE
1997 Aug;19(4):373-378, American journal of dermatopathology
Alteration of the p53 gene is the most frequent event reported in human cancer, and p53 mutations have been observed in various neoplasms, including certain forms of skin cancer. Therefore, we postulated that p53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining. Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing data showed the mutation to be located in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also detected in five of the AIDS-KS specimens, two of which also contained p53-positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS
— id: 7198, year: 1997, vol: 19, page: 373, stat: Journal Article,

Absence of human herpes virus 8 DNA sequences in large granular lymphocyte (LGL) leukemia
Loughran TP Jr; Abbott L; Gentile TC; Love J; Cunningham C; Friedman-Kien A; Huang YQ; Poiesz BJ
1997 Jun;26(1-2):177-180, Leukemia & lymphoma
The etiology of large granular lymphocyte (LGL) leukemia is uncertain. Recently, a Kaposi's sarcoma-associated herpes virus, denoted as human herpes virus 8 (HHV-8), has been identified. Some data suggest that HHV-8 and Epstein-Barr virus (EBV) may interact to induce malignant transformation. Infection with EBV has been implicated in the pathogenesis of some cases of LGL leukemia. Therefore, we performed PCR analyses for HHV-8 detection in samples from nineteen patients with LGL leukemia; three of these samples contained the EBV genome. We could not detect HHV-8 sequences in any of these patients. Therefore, HHV-8 infection is not involved in the pathogenesis of T-LGL leukemia
— id: 49660, year: 1997, vol: 26, page: 177, stat: Journal Article,

Human herpesvirus 8 encodes a homolog of interleukin-6
Neipel F; Albrecht JC; Ensser A; Huang YQ; Li JJ; Friedman-Kien AE; Fleckenstein B
1997 Jan;71(1):839-842, Journal of virology
Kaposi's sarcoma is a multifocal lesion that is reported to be greatly influenced by cytokines such as interleukin-6 (IL-6) and oncostatin M. DNA sequences of a novel human gammaherpesvirus, termed human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus, have been identified in all epidemiological forms of Kaposi's sarcoma with high frequency. The presence of HHV-8 DNA is also clearly associated with certain B-cell lymphomas (body cavity-based lymphomas) and multicentric Castleman's disease. Sequence analysis of a 17-kb fragment revealed that adjacent to a block of conserved herpesvirus genes (major DNA-binding protein, glycoprotein B, and DNA polymerase), the genome of HHV-8 encodes structural homolog of IL-6. This cytokine is involved not only in the pathogenesis of Kaposi's sarcoma but also in certain B-cell lymphomas and multicentric Castleman's disease. The viral counterpart of IL-6 (vIL-6) has conserved important features such as cysteine residues involved in disulfide bridging or an amino-terminal signal peptide. Most notably, the region known to be involved in receptor binding is highly conserved in vIL-6. This conservation of essential features and the remarkable overlap between diseases associated with HHV-8 and diseases associated with IL-6 disregulation clearly suggest that vIL-6 is involved in HHV-8 pathogenesis
— id: 14746, year: 1997, vol: 71, page: 839, stat: Journal Article,

Color atlas of AIDS
Friedman-Kien, Alvin E.; Cockerell, Clay J
Philadelphia : Saunders, c1996,
— id: 535, year: 1996, vol: , page: , stat: ,

Transcription of human herpesvirus-like agent (HHV-8) in Kaposi's sarcoma
Huang YQ; Li JJ; Zhang WG; Feiner D; Friedman-Kien AE
1996 Jun 15;97(12):2803-2806, Journal of clinical investigation
Recently, DNA sequences of what appear to be a unique human herpesvirus-like agent (HHV-8) have been detected in different types of Kaposi's sarcoma (KS) tumors (Chang, Y., E.C. Cesarman, M.S. Pessin, F. Lee, J.C. Culpepper, D.M. Knowles, and P.S. Moore. 1994. Science (Wash. DC). 266:1865-1869). To further elucidate the possibility that HHV-8 plays a role in the pathogenesis of KS, the expression of HHV-8 RNA was examined in fresh KS tissue specimens which were found to harbor HHV-8 DNA by polymerase chain reaction (PCR). The transcription of HHV-8 RNA was detected by RT-PCR in 26 of 29 specimens (89.7%) of the KS tumors including 2 of 3 CKS and 24 of 26 AIDS-KS. No positive signal was detected in eight biopsy specimens of normal skin from healthy donors. By Northern blot analysis, the expression of HHV-8 was detected in 2 of 10 KS tumors examined. Furthermore, the RNA transcripts were observed in endothelial cells lining the irregular vascular spaces and perivascular spindle-shaped cells histologically characteristic of KS in 2 out of 8 different KS specimens examined by in situ hybridization using an antisense probe specific of HHV-8. The detection of RNA expression of HHV-8 in KS tumors further supports the possible etiopathogenic role of this virus in the development of KS
— id: 57412, year: 1996, vol: 97, page: 2803, stat: Journal Article,

Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi's sarcoma lesions by in situ hybridization
Li JJ; Huang YQ; Cockerell CJ; Friedman-Kien AE
1996 Jun;148(6):1741-1748, American journal of pathology
Kaposi's sarcoma (KS) is a neoplasm that develops as multifocal lesions characterized by a histological picture that includes irregularly shaped vascular spaces surrounded by perivascular and interstitial spindle-shaped cells, extravasated erythrocytes, and an inflammatory mononuclear cell infiltrate. Recently, the DNA sequences of a novel human gamma-herpesvirus-like (HHV-8) agent have been detected by polymerase chain reaction in KS associated with acquired immune deficiency syndrome (AIDS-KS), classical KS, and African endemic KS. The present study was done to identify the specific cells within KS tumors that contain the viral DNA. Fourteen skin biopsy specimens, including three classical KSs, six AIDS-KSs, three normal skin specimens, and two common warts from healthy individuals, were examined by polymerase chain reaction for the presence of the HHV-8 DNA sequences. HHV-8 DNA were present in all nine KS specimens but not detectable in the five non-KS tissue samples. Using in situ hybridization, we found the HHV-8 DNA sequences to be predominantly localized to the nuclei of endothelial cells lining the vascular slits and some perivascular spindle-shaped cells, in two of three KS and four of six AIDS-KS tissue sections examined. The HHV-8-positive cells of KS specimens were concurrently shown to also be positive for factor-VIII-related antigen by immunohistochemical staining. The presence of the DNA of HHV-8 in the nuclei of KS cells further supports the possibility that this agent may play a role in the pathogenesis of this tumor
— id: 7014, year: 1996, vol: 148, page: 1741, stat: Journal Article,

Prevalence of human herpesvirus 8 DNA sequences in several patient populations
Marchioli CC; Love JL; Abbott LZ; Huang YQ; Remick SC; Surtento-Reodica N; Hutchison RE; Mildvan D; Friedman-Kien AE; Poiesz BJ
1996 Oct;34(10):2635-2638, Journal of clinical microbiology
We have undertaken a large-scale study of various tissues from normal controls and patients with Kaposi's sarcoma (KS) or other malignancies, both with and without human immunodeficiency virus infection, to determine the prevalence of human herpesvirus 8 (HHV-8) DNA. A total of 566 specimens were analyzed by PCR for the presence of HHV-8 DNA. Of the samples tested, 251 were obtained from patients with KS and 315 were obtained from patients without KS. HHV-8 DNA was detected in 103 (41%) of the 251 samples from patients with KS. In particular, 92% of KS tumor specimens were positive. None of the tissues from patients without KS showed evidence of HHV-8 DNA. Sequencing and phylogenetic analyses indicate a high degree of conservation (97.5 to 100%) among the HHV-8 strains tested
— id: 14748, year: 1996, vol: 34, page: 2635, stat: Journal Article,

Urine-based diagnostic technologies
Urnovitz HB; Murphy WH; Gottfried TD; Friedman-Kien AE
1996 Oct;14(10):361-364, Trends in biotechnology
The worldwide dissemination of infectious agents has created a demand for simple diagnostic tests. Urine-based testing makes use of non-invasive collection of specimens, and there is no need for expensive facilities and equipment, or for highly trained personnel. As urine antibodies retain activity under normal conditions of transport and storage, such tests appear to have widespread application. Urine-based antibody tests have also indicated a compartmentalized antibody response to HIV-1 infection. Urine studies suggest that antibodies to the products of endogenous viral genes may be involved in the pathogenesis of chronic diseases of suspected viral etiology
— id: 14747, year: 1996, vol: 14, page: 361, stat: Journal Article,

Kaposi's sarcoma. How can epidemiology help find the cause?
Drotman DP; Peterman TA; Friedman-Kien AE
1995 Jul;13(3):575-582, Dermatologic clinics
Kaposi's sarcoma (KS) remains the most commonly diagnosed cancer in AIDS patients. Neither the cause nor a cure for AIDS-related KS is known. KS serves as a striking example of how epidemiologists seek the cause of any disease. Epidemiologic analysis of reported KS cases is revealing but not definitive. The leading hypotheses for the cause of AIDS-related KS are an as-yet-unidentified sexually transmitted infectious agent and exposure to inhalant alkyl nitrites, often called poppers. Epidemiology suggests that persons can reduce their risk of KS by avoiding nitrite inhalants and changing behavior to reduce the risk of sexually transmitted infections
— id: 14749, year: 1995, vol: 13, page: 575, stat: Journal Article,

Management of condylomata acuminata with Alferon N injection, interferon alfa-n3 (human leukocyte derived)
Friedman-Kien A
1995 Apr;172(4 Pt 2):1359-1368, American journal of obstetrics & gynecology
— id: 6624, year: 1995, vol: 172, page: 1359, stat: Journal Article,

DETECTION OF A NEW HERPES-LIKE VIRUS-DNA SEQUENCE IN AIDS-KS AND AIDS-LYMPHOMAS
FRIEDMANKIEN, AE
1995 JUL-AUG ;11(4):S96-S97, AIDS research & human retroviruses
— id: 87228, year: 1995, vol: 11, page: S96, stat: Journal Article,

POSSIBLE ROLE OF THE NOVEL HERPES-LIKE AGENT [HHV-8] IN THE PATHOGENESIS OF VARIOUS FORMS OF KAPOSIS-SARCOMA
FRIEDMANKIEN, AE
1995 JUL-AUG ;11(4):S172-S173, AIDS research & human retroviruses
— id: 87233, year: 1995, vol: 11, page: S172, stat: Journal Article,

RNA EXPRESSION OF THE HERPESVIRUS-LIKE AGENT (KSHV) IN VARIOUS TYPES OF KAPOSIS-SARCOMA (KS) LESIONS
FRIEDMANKIEN, AE; LI, JJ; HUANG, YQ
1995 JUL-AUG ;11(4):S97-S97, AIDS research & human retroviruses
— id: 87229, year: 1995, vol: 11, page: S97, stat: Journal Article,

Co-expression of FGF3 (Int-2) and its receptor (a splice variant of FGFR2) in Kaposi's sarcoma tumors
Huang YQ; Li JJ; Feiner DG; Zhang WG; Friedman-Kien AE
1995 Jan 29-Feb 2;2:79-79, National Conference on Human Retroviruses & Related Infections
The expression of FGF3 has recently been detected in 55% of fresh Kaposi's sarcoma lesions, but not in uninvolved skin for the same donors. Nude mouse transplanted with NIH3T3 cells transformed by human FGF3 cDNA developed KS-like tumors. These data suggest that FGF3 may be involved in the pathogenesis of KS. The expression of a splice variant of the FGF receptor 2 (FGF-R-2) which has recently been identified as a specific receptor for FGF3, was also detected in KS tumors. The mRNA transcripts of FGF3 and FGF- R-2 were detected in fresh KS tumor biopsies by the RT-PCR method, and confirmed by Northern blot analysis. The expression of the FGF-R-2 receptor is also studied in the FGF3 transformed NIH3T3 cells in vitro and in the mouse- induced tumors
— id: 5987, year: 1995, vol: 2, page: 79, stat: Journal Article,

Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma
Huang YQ; Li JJ; Kaplan MH; Poiesz B; Katabira E; Zhang WC; Feiner D; Friedman-Kien AE
1995 Mar 25;345(8952):759-761, Lancet
The association between a new human herpesvirus-like agent and various forms of Kaposi's sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposi's sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposi's sarcoma. Polymorphism of the herpesvirus-like DNA in the Kaposi's tissue from different populations was observed by both single-strand conformational polymorphism and direct sequencing. Furthermore, the presence and expression of the virus was detected in some Kaposi's tumours by Southern and northern blotting. This herpesvirus may be involved in the pathogenesis of different kinds of Kaposi's sarcoma seen among distinct and unrelated populations
— id: 56658, year: 1995, vol: 345, page: 759, stat: Journal Article,

OVEREXPRESSION OF CYCLIN-D IN KAPOSIS-SARCOMA (KS) TUMORS
HUANG, YQ; FRIEDMANKIEN, AE; LI, JJ
1995 JUL-AUG ;11(4):S95-S95, AIDS research & human retroviruses
— id: 87227, year: 1995, vol: 11, page: S95, stat: Journal Article,

DETECTION OF DNA-SEQUENCES OF KSHV IN BLOOD SEMEN, KS TUMOR, AND UNINVOLVED SKIN OF AIDS-KS PATIENTS
LI, JJ; HUANG, YQ; FRIEDMANKIEN, AE
1995 JUL-AUG ;11(4):S98-S98, AIDS research & human retroviruses
— id: 87230, year: 1995, vol: 11, page: S98, stat: Journal Article,

Evidence for an effect of human leukocyte antigens on susceptibility to Kaposi's sarcoma related to charge and peptide-binding properties of class I molecules
Marmor M; Winchester R; Zeleniuch-Jacquotte A; Weiss SH; Krasinski K; Saxinger WC; Friedman-Kien A; William DC; Demopoulos R
1995 Oct;9(10):1194-1195, AIDS
— id: 9091, year: 1995, vol: 9, page: 1194, stat: Journal Article,

Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections
Balfour HH Jr; Benson C; Braun J; Cassens B; Erice A; Friedman-Kien A; Klein T; Polsky B; Safrin S
1994 Mar;7(3):254-260, Journal of acquired immune deficiency syndrome
Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed
— id: 49662, year: 1994, vol: 7, page: 254, stat: Journal Article,

Rearrangement and expression of MDM2 oncogene in chronic lymphocytic leukemia
Huang YQ; Raphael B; Buchbinder A; Li JJ; Zhang WG; Friedman-Kien AE
1994 Oct;47(2):139-141, American journal of hematology
Since trisomy 12 is the most common chromosome abnormality found in CLL and MDM2 has been mapped to this chromosome, we examined the possible association of MDM2 in the pathogenesis of CLL. A rearrangement of the MDM2 gene was observed in 4 of 11 peripheral blood mononuclear cells (PBMC) from patients with CLL by Southern blot hybridization. Expression of MDM2 was detected in all of the CLL samples examined by Northern blot. However, neither gross amplification nor overexpression of the MDM2 gene was found in CLL. The data suggest that MDM2 may play a role in the pathogenesis of CLL and may help to explain how abnormalities of chromosome 12 are related to CLL
— id: 12881, year: 1994, vol: 47, page: 139, stat: Journal Article,

EXPRESSION OF INT-2 ONCOGENE IN KAPOSIS-SARCOMA LESIONS
HUANG, YQ; LI, JJ; MOSCATELLI, D; BASILICO, C; NICOLAIDES, A; ZHANG, WG; POIESZ, BJ; FRIEDMANKIEN, AE
1994 AUG ;10(3-4):S54-S54, AIDS research & human retroviruses
— id: 52370, year: 1994, vol: 10, page: S54, stat: Journal Article,

EXPRESSION OF FIBROBLAST GROWTH-FACTORS AND THEIR RECEPTORS IN AIDS-ASSOCIATED KAPOSIS-SARCOMA TISSUE AND DERIVED CELLS
LI, JJ; HUANG, YQ; MOSCATELLI, D; BASILICO, C; NICOLAIDES, A; ZHANG, WG; POIESZ, BJ; FRIEDMANKIEN, AE
1994 AUG ;10(3-4):S52-S52, AIDS research & human retroviruses
— id: 52369, year: 1994, vol: 10, page: S52, stat: Journal Article,

Gene amplification and multiple mutations of the K-ras oncogene in Kaposi's sarcoma
Nicolaides A; Huang YQ; Li JJ; Zhang WG; Friedman-Kien AE
1994 May-Jun;14(3A):921-926, Anticancer research
Thirty one biopsy samples of fresh Kaposi's sarcoma (KS) skin lesions were examined for alteration of the K-ras oncogene by differential PCR, SSCP and nucleic acid sequencing. Three KS specimens showed amplification of K-ras and 7 were found to have various mutations at exon 1 of the K-ras gene. Eight of the 10 K-ras gene alterations detected were found in more advanced nodular stage KS lesions, while only 2 were observed in the plaque stage KS tumors. Activation of the K-ras oncogene may play a role in the malignant progression of this unusual neoplasm
— id: 12970, year: 1994, vol: 14, page: 921, stat: Journal Article,

Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I
Zucker-Franklin D; Pancake BA; Friedman-Kien AE
1994 Sep;10(9):1173-1177, AIDS research & human retroviruses
Two homosexual HIV-infected patients with lymphocyte counts of < 50 presented with intense pruritis, hyperpigmentation, and skin lesions clinically suggestive of the cutaneous T cell lymphoma, mycosis fungoides. On light microscopy, the skin biopsies were difficult to interpret because of the sparseness of the lymphocytic infiltrates. However, electron microscopy revealed typical Sezary cells in the peripheral blood and skin. Cultures of blood mononuclear cells of one of the patients generated HTLV-I-like particles. Although both patients lacked antibodies to HTLV, their blood and skin specimens proved to harbor tax and pol HTLV-I proviral sequences as shown by the polymerase chain reaction and Southern blot analysis. Dual infection with HIV and HTLV should be considered in the diagnostic work-up of patients at risk, even in the absence of demonstrable antibodies. Dual infections could result in clinical manifestations and evolution of disease not anticipated in patients who harbor only one of these retroviruses
— id: 7921, year: 1994, vol: 10, page: 1173, stat: Journal Article,

HIV and HTLV-1 dual infection in a patient with mycosis fungoides (MF)
Franklin DZ; Pancake BA; Kien AE
1993 Dec 12-16;1:155-155, National Conference on Human Retroviruses & Related Infections
Dual infection with HIV and HTLV-I/II is no longer rare among homosexual and intravenous drug-abusing populations. The clinical implications of this development cannot yet be fully assessed. A synergistic effect on disease evolution seems likely. Therefore, we report here a HIV-infected homosexual male who presented with skin lesions, proven to be typical of the cutaneous T-cell lymphoma, mycosis fungoides (MF). Like most patients with MF, he was seronegative for antibodies to HTLV-I/II. Although his blood CD4+ lymphocyte count was only 6/cmm, Sezary cells were seen among his PBMC and in the skin infiltrate. Lysates of these tissues were subjected to PCR/Southern blot analysis utilizing primers SK43, 44 and probe SK45 to detect HTLV- I/II tax. Primers SK110, 111 and probe SK112 were used to detect Type-I-specific pol sequences. This revealed 159bp HTLV-I/II tax bands and 186 bp HTLV-I-pol-related bands which co-migrated with identically prepared samples of HTLV- I and HTLV-II positive controls, while cell lysates of 6 healthy volunteers run in parallel were negative. EM of cultures generated from the patient's PBMC showed HIV and HTLV-like particles within 2 weeks. We believe this to be the first report of a dually-infected patient who has developed a HTLV-I-associated T helper cell cutaneous lymphoma
— id: 5986, year: 1993, vol: 1, page: 155, stat: Journal Article,

Cultured Kaposi's sarcoma cell lines express factor XIIIa, CD14, and VCAM-1, but not factor VIII or ELAM-1 [published erratum appears in Arch Dermatol 1993 Dec;129(12):1622]
Huang YQ; Friedman-Kien AE; Li JJ; Nickoloff BJ
1993 Oct;129(10):1291-1296, Archives of dermatology
BACKGROUND AND DESIGN: Historically, the Kaposi's sarcoma (KS) tumor cell was generally thought to be derived from endothelial cells. However, by immunohistochemical staining of lesions, many spindle-shaped cells in KS express factor XIIIa, suggesting that they may be related to dermal dendrocytes, a perivascular cell of monocyte/macrophage lineage. To extend our observations on tissue sections of lesions, four different established KS-derived cell lines before and after cytokine exposure, as well as biopsy specimens of KS lesions, were studied for the expression of endothelial cell and monocyte/macrophage antigens. RESULTS: Multipassaged KS tumor cells grew predominantly as spindle-shaped cells. By immunohistochemical staining, all four KS-derived cell cultures were factor XIIIa and intercellular adhesion molecule 1 positive. Three KS-derived cell cultures were CD14 and vascular cell adhesion molecule 1 positive. Expression of factor XIIIa was upregulated by interferon gamma. By polymerase chain reaction (PCR) analysis, expression of CD4 mRNA was also detected in all four KS-derived cell cultures. Expression of these monocyte/macrophage markers (factor XIIIa, CD14, and vascular cell adhesion molecule 1) on KS in vitro was also detected on spindle cells of KS lesions in vivo. Endothelial leukocyte adhesion molecule 1 and factor VIII expression was not detected on KS-derived cells in vitro before or after exposure to interferon gamma or tumor necrosis factor alpha. While cultured KS cells strongly expressed smooth-muscle alpha-actin, no detection was observed on spindle-shaped cells in vivo. Conversely, while cultured KS cells were devoid of CD34, the tissue biopsy specimens contain strongly positive spindle-shaped cells. Our results demonstrate that while KS cell lines express one antigen shared by endothelial cells, ie, vascular cell adhesion molecule 1, they lack several other endothelial cell markers such as factor VIII and endothelial leukocyte adhesion molecule 1, either before or after cytokine activation. CONCLUSIONS: Kaposi's sarcoma cell lines express several antigens linking them to dermal dendrocytes such as factor XIIIa, CD4, and CD14
— id: 13069, year: 1993, vol: 129, page: 1291, stat: Journal Article,

HIV-1 infection and modulation of cytokine and growth factor expression in Kaposi's sarcoma-derived cells in vitro
Huang YQ; Li JJ; Kim KS; Nicolaides A; Zhang WG; Le J; Poiesz BJ; Friedman-Kien AE
1993 Mar;7(3):317-322, AIDS
OBJECTIVES: HIV-1 transcripts have been detected in AIDS-related Kaposi's sarcoma (KS) tissues within the factor XIIIa + dermal dendrocytes present in the tumor. Various cytokines and growth factors have been shown to influence the growth of KS-derived cells in vitro. HIV-1 preferentially infects CD4+ cells and has also been found to infect some CD4- cells in vitro. The susceptibility of cultured KS cells in vitro to infection with HIV-1 and the expression of interleukin (IL)-1 beta, IL-6 and basic fibroblast growth factor (bFGF) after exposure to HIV-1 was examined. METHODS: The susceptibility of two different KS-derived cell cultures to HIV-1 infection was examined by the expression of p24 antigen, detection of proviral sequence and electron microscopy. The expression of IL-1 beta, IL-6 and bFGF was detected by enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. RESULTS: KS-derived cells can be infected by HIV-1 in vitro. Both KS-derived cells were found to express CD4 mRNA. The expression of IL-1 beta and IL-6 was increased, whereas the expression of bFGF was not stimulated after exposure of KS cells to HIV-1. CONCLUSION: These experiments describe the in vitro infection of KS-derived cells by HIV-1 and the expression of various cytokines and growth factor following infection. The increased production of cytokines observed following such infection may be involved in the pathogenesis of AIDS-related KS
— id: 13222, year: 1993, vol: 7, page: 317, stat: Journal Article,

Expression of int-2 oncogene in Kaposi's sarcoma lesions
Huang YQ; Li JJ; Moscatelli D; Basilico C; Nicolaides A; Zhang WG; Poiesz BJ; Friedman-Kien AE
1993 Mar;91(3):1191-1197, Journal of clinical investigation
Fibroblast growth factors (FGFs), such as basic FGF, have been implicated in the growth of Kaposi's sarcoma (KS) cells in vitro. In the evaluation of the expression of the various genes of the different members of the FGF family and their receptors in fresh KS tissue specimens, int-2 was found to be expressed in more than half of the KS tumors examined. Using reverse transcription PCR, the expression of int-2 was detected in 21 of 38 (55.2%) fresh KS biopsy specimens. In contrast, int-2 mRNA transcripts were not found in normal appearing skin from the same patients except in one sample which was obtained from an AIDS patient with disseminated KS lesions. Sequence data confirmed that the amplified sequences were derived from int-2 mRNA with proper splicing. In addition, 12 nucleic acid alterations were identified in eight out of nine KS tumor samples sequenced. Using immunohistochemical methods, int-2 protein was detected in some of the spindle-shaped tumor cells surrounding the abnormal endothelial-lined vascular slits histologically characteristic of KS. Int-2 specific immunostaining was shown to be present in both the nuclei and cytoplasm of these spindle cells but was more pronounced in the nuclei. Neither amplification nor gross rearrangement of the int-2 gene was detected in KS lesions by Southern blot analysis. These results suggest that the expression of int-2 may play a role in the pathogenesis KS by stimulating local angiogenesis and cell proliferation
— id: 13228, year: 1993, vol: 91, page: 1191, stat: Journal Article,

Increased expression of fibroblast growth factors (FGFs) and their receptor by protamine and suramin on Kaposi's sarcoma-derived cells
Huang YQ; Li JJ; Nicolaides A; Zhang WG; Friedman-Kien AE
1993 Jul-Aug;13(4):887-890, Anticancer research
Growth factors, such as bFGF, have been shown to exert autocrine and paracrine effects on the growth of Kaposi's Sarcoma (KS)-derived cells, which suggested that the inhibitors of angiogenesis may be promising for KS treatment. However, KS lesions have been found to continue to enlarge after patients had been treated with FGF binding antagonists such as suramin. We investigated the effect of protamine and suramine on the growth of KS derived cells in vitro. Although both of these agents which are FGF binding antagonists were found to inhibit the incorporation of 3H thymidine in KS-derived cultured cells, increased expression of bFGF, FGF5 and the FGF receptor was observed after the KS cells were exposed to these substances. These results might explain the clinical observation that FGF binding antagonists such as suramin caused an apparent stimulation of KS tumor growth when administered systemically to patients with AIDS-related KS
— id: 13110, year: 1993, vol: 13, page: 887, stat: Journal Article,

Expression of fibroblast growth factors (FGF) their receptors (flg and bek) and cytokines in AIDS associated Kaposi's sarcoma (AIDS-KS)
Huang YQ; Li JJ; Nicolaides A; Zhang WG; Kien AE
1993 Dec 12-16;1:145-145, National Conference on Human Retroviruses & Related Infections
Several growth factors and cytokines including bFGF, IL-1 IL-6 and oncostatin M have been shown to be involved in the proliferation of KS-derived cells in vitro. However, their relevance to the pathogenesis of KS in vivo remains to be elucidated. The expression of growth factors (aFGF, bFGF, FGF3 (Int-2), FGF-4 (kFGF), FGF5, and FGF6) receptors (flg and bek) as well as cytokines: (IL-1 , IL-6, and oncostatin M) were examined in fresh biopsies of KS skin lesions, normal skin from distant sites and PBMC from patients with AIDS-KS by RT-CPR, RNA blot and immunostaining methods. Greater expression of bFGF was detected in normal skin than in KS tumors and the expression of IL-1 was detected in only 1 of 10 KS specimens examined. The expression of oncostatin M was observed in the KS and uninvolved skin specimens as well as the PBMC from patients with AIDS-KS and from healthy, HIV-1 negative individuals. However, mutated FGF3 was found to be expressed in 21 of 38 (52%) fresh KS specimens but only 1 of 12 normal skin biopsies. The expression of FGF5 was detected in 4 of 6 KS tumors but not detected in normal skin
— id: 5988, year: 1993, vol: 1, page: 145, stat: Journal Article,

Detection of false antibodies to HIV-1 in urine
Kostolansky F; Li JJ; Friedman-Kien AE
1993 Nov;7(11):1531-1532, AIDS
— id: 14750, year: 1993, vol: 7, page: 1531, stat: Journal Article,

Expression of fibroblast growth factors and their receptors in acquired immunodeficiency syndrome-associated Kaposi sarcoma tissue and derived cells
Li JJ; Huang YQ; Moscatelli D; Nicolaides A; Zhang WC; Friedman-Kien AE
1993 Oct 1;72(7):2253-2259, Cancer
BACKGROUND. Fibroblast growth factors (FGF), such as basic FGF, have been implicated in the development of Kaposi sarcoma (KS) in vitro. The expression of several genes of the FGF family and their receptors in KS tumor lesions and KS-derived cells were evaluated. METHODS. Cultures of KS-derived cells were established. The expression of FGF family members and their receptors in these cells and in fresh biopsies from KS tumors was evaluated by reverse transcription polymerase chain reaction (RTPCR). The RTPCR products were confirmed by nucleotide sequencing. RESULTS. The expression of basic FGF and FGF receptor-1 (flg) was detected in all the samples tested. Acidic FGF (aFGF) and FGF-5 were detected in two of six and four of six KS tumor specimens, respectively, whereas both of these growth factors were expressed in all of the cell cultures, including six KS-derived cell cultures and human endothelial cells and smooth muscle cells. FGF-6 was expressed in two of six KS tumor specimens, but was not expressed in any of the cultured KS cells. Like flg, bek was expressed in all tissue samples and KS-derived cell cultures except in one KS specimen obtained from the patient's tongue showing expression of a high level of FGF-6. CONCLUSIONS. These results suggest that the expression of FGF in KS tumors with the coexpression of FGF receptors may provide a basis for autocrine and paracrine mechanisms contributing to the development of KS
— id: 13066, year: 1993, vol: 72, page: 2253, stat: Journal Article,

Expression and amplification of the FGF-4 (kFGF/hst) gene in Kaposi's sarcoma
Li JJ; Kien AE; Zhang WG; Nicolaides A; Huang YQ
1993 Dec 12-16;1:145-145, National Conference on Human Retroviruses & Related Infections
FGF-4 (kFGF/hst) was isolated from the DNA to fresh Kaposi's Sarcoma (KS) biopsies by NIH3T3 transfection assay. Although the expression of FGF-4 is not detected in KS derived culture cells, the expression of this oncogene in KS tumor tissue has not been previously examined. The gene amplification and expression of FGF-4 in KS biopsies was examined by differential PCR, Southern blot, and RT-PCR methods. Gene amplification of FGF-4 was found in 4 of 32 (12.5%) specimens of KS, among these 4 samples, three which showed expression of this gene. A total of 6 of 14 (42%) of KS tumor samples showed low FGF-4. However, neither gene amplification nor expression of FGF-4 was detected in normal skin of patients with KS. Like other FGFs, the detection of FGF-4 in KS skin tumors but not in normal skin from the same host suggests that FGF-4 may be involved in the pathogenesis of KS
— id: 5989, year: 1993, vol: 1, page: 145, stat: Journal Article,

Kaposi's sarcoma presenting as lymphadenopathy in two HIV-negative elderly patients
Wang JC; Rosen Y; Goel PC; Teplitz H; Goldberg M; Friedman-Kien AE; Huang YQ
1993 Mar;94(3):342-344, American journal of medicine
— id: 14751, year: 1993, vol: 94, page: 342, stat: Journal Article,

Kaposi's sarcoma in a human immunodeficiency virus-negative patient with asymptomatic human T lymphotropic virus type I infection
Zucker-Franklin D; Huang YQ; Grusky GE; Friedman-Kien AE
1993 Apr;167(4):987-989, Journal of infectious diseases
— id: 8407, year: 1993, vol: 167, page: 987, stat: Journal Article,

Clinical aspects of Kaposi's sarcoma
Buchbinder A; Friedman-Kien AE
1992 Oct;4(5):867-874, Current opinion in oncology
Kaposi's sarcoma is the most common tumor found in patients with the acquired immunodeficiency syndrome. This opportunistic neoplasm has characteristics of a sexually transmitted disease. Growth factors, cytokines, immune suppression, and interaction with infectious organisms all appear to play a role in the pathogenesis of this enigmatic disorder. The manifestations of Kaposi's sarcoma are protean, and lesions may appear at any time in the course of human immunodeficiency virus disease, remain localized and asymptomatic, or spread aggressively and cause morbidity. Treatment, which must be individualized, ranges from observation, local therapy with cosmetic makeup, and cryotherapy with liquid nitrogen or local intralesional injection of agents, to radiotherapy and systemic therapy with interferon-alpha and cytotoxic chemotherapy
— id: 13402, year: 1992, vol: 4, page: 867, stat: Journal Article,

The absence of Tat sequences in tissues of HIV-negative patients with epidemic Kaposi's sarcoma
Huang YQ; Buchbinder A; Li JJ; Nicolaides A; Zhang WG; Friedman-Kien AE
1992 Oct;6(10):1139-1142, AIDS
OBJECTIVE: Tat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat. METHODS: We evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1. RESULTS: No evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found. CONCLUSION: These results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients
— id: 13401, year: 1992, vol: 6, page: 1139, stat: Journal Article,

Fibroblast growth factor 6 gene expression in AIDS-associated Kaposi's sarcoma
Huang YQ; Li JJ; Nicolaides A; Zhang WG; Freidman-Kien AE
1992 May 2;339(8801):1110-1111, Lancet
— id: 36165, year: 1992, vol: 339, page: 1110, stat: Journal Article,

HPV-16-related DNA sequences in Kaposi's sarcoma [see comments]
Huang YQ; Li JJ; Rush MG; Poiesz BJ; Nicolaides A; Jacobson M; Zhang WG; Coutavas E; Abbott MA; Friedman-Kien AE
1992 Feb 29;339(8792):515-518, Lancet
In the USA, Kaposi's sarcoma associated with the acquired immunodeficiency syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than in heterosexual men with AIDS. One explanation for this finding is that AIDS-KS may be caused by an infectious agent. Because there is a high incidence of human papillomavirus (HPV) infection, especially HPV-16, in homosexual men, we have sought HPV DNA sequences in Kaposi's sarcoma. We used the polymerase chain reaction with a primer pair specific for the highly conserved E6 region of HPV-16 to detect HPV-16 homologous DNA fragments in tumour tissues from 97 patients with KS and in KS-derived cell cultures. HPV DNA sequences were found in 11 of 69 KS skin tumours from homosexual men with AIDS-KS, in 3 of 11 KS biopsy specimens from homosexual men who had no clinical or laboratory evidence of HIV-infection, and in 5 of 17 KS skin lesions from HIV-1-negative elderly men and women with classic KS. The same primer pair amplified HPV-16 homologous fragments from two different continuous cell cultures derived from pleural effusion fluid of patients with pulmonary AIDS-KS and two continuous cell cultures derived from KS skin lesions. The findings suggest that HPV-16-related DNA sequences are associated with different forms of KS and may have a role in the pathogenesis of this neoplasm
— id: 13689, year: 1992, vol: 339, page: 515, stat: Journal Article,

LACK OF TAT-1 SEQUENCES IN HIV NEGATIVE PATIENTS WITH EPIDEMIC KAPOSIS-SARCOMA
HUANG, YQ; BUCHBINDER, A; LI, JJ; NICOLAIDES, A; ZHANG, WC; FRIEDMANKIEN, AE
1992 MAY ;8(5):878-878, AIDS research & human retroviruses
— id: 51932, year: 1992, vol: 8, page: 878, stat: Journal Article,

THE SICCA SYNDROME IN HIV-1 INFECTION IS DEPENDENT ON THE HOST IMMUNE-RESPONSE RATHER THAN THE INFECTING VIRAL STRAIN
ITESCU, S; DWYER, E; CHOI, S; ZHANG, H; HUANG, Y; FRIEDMANKIEN, A; WINCHESTER, R
1992 SEP ;35(9):S210-S210, Arthritis & rheumatism
— id: 51850, year: 1992, vol: 35, page: S210, stat: Journal Article,

PERINATAL HIV-1 INFECTION DESPITE MATERNAL ANTI-HIV-1 NEUTRALIZING ANTIBODY
KRASINSKI, K; CAO, YZ; FIDELIA, A; BEBENROTH, D; FRIEDMANKEIN, A; BORKOWSKY, W
1992 APR ;40(2):A381-A381, Clinical research
— id: 52008, year: 1992, vol: 40, page: A381, stat: Journal Article,

Detection of human immunodeficiency virus type 1 (HIV-1) in urine cell pellets from HIV-1-seropositive individuals
Li JJ; Huang YQ; Poiesz BJ; Zaumetzger-Abbot L; Friedman-Kien AE
1992 May;30(5):1051-1055, Journal of clinical microbiology
Fresh urine pellets from human immunodeficiency virus type 1 (HIV-1)-seropositive individuals were examined for the presence of the HIV-1 genomic sequence and gene products. By using the polymerase chain reaction technique, HIV-1 DNA proviral sequences were detected in 53 of 80 (66.25%) fresh urine pellets from HIV-1-seropositive individuals, while urine pellets from all 24 healthy heterosexual controls were negative. HIV-1 RNA in urine pellets was detected by reverse transcriptase polymerase chain reaction in 2 of 43 (4.7%) HIV-1-seropositive individuals. In addition, HIV-1 p24 core antigen was demonstrated in 3 of 80 urine pellets from HIV-1-seropositive individuals by enzyme-linked immunosorbent assay. Moreover, HIV-1 p24 core antigen and HIV-1 RNA were shown in the cellular component of urine pellets from HIV-1-seropositive individuals by immunohistochemical staining and in situ hybridization. These results indicate that HIV-1 can be present in urine pellets from HIV-1-infected individuals
— id: 13612, year: 1992, vol: 30, page: 1051, stat: Journal Article,

Human spumavirus antibodies in sera from African patients
Mahnke C; Kashaiya P; Rossler J; Bannert H; Levin A; Blattner WA; Dietrich M; Luande J; Lochelt M; Friedman-Kien AE; et al
1992 ;123(3-4):243-253, Archives of virology
Serum samples collected from patients with a wide variety of diseases from African and other countries were tested for antibodies to the human spumaretrovirus (HSRV). A spumaviral env-specific ELISA was employed as screening test. Out of 3020 human sera screened, 106 were found to be positive (3.2%). While the majority of patients' sera from Europe (1581) were negative, 26 were positive (1.6%). Sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), Graves' disease (45), and chronic fatigue syndrome (41) were negative or showed a very low prevalence for spumaviral env antibodies. A higher percentage of seropositives (6.3%) were found among 1338 African patients from Tanzania, Kenya, and Gabon. Out of 1180 patients from Tanzania, 708 suffered from tumors, 75 from AIDS, and 128 had gynecological problems; 51 of the Tanzanian patients were HSRV seropositive (4.3%). A particularly high percentage of 16.6% seropositives were identified among nasopharyngeal carcinoma patients (NPC) from Kenya and Tanzania consistent with results reported 10 years ago. However, 20 nasopharyngeal carcinoma patients from Malaysia were HSRV-seronegative. In selected cases, sera from seropositive individuals were reacted with proteins from HSRV-infected cells in vitro. HSRV env- and gag-specific antibodies were specifically detected by these sera in Western blots. The results indicate spumavirus infections in human patients with various diseases at a relatively low prevalence worldwide; in African patients, however, the prevalence of spumavirus infections is markedly higher
— id: 14756, year: 1992, vol: 123, page: 243, stat: Journal Article,

Immunohistochemical detection of papillomavirus antigens in Kaposi's sarcoma
Nickoloff BJ; Huang YQ; Li JJ; Friedman-Kien AE
1992 Feb 29;339(8792):548-549, Lancet
— id: 14755, year: 1992, vol: 339, page: 548, stat: Journal Article,

Cutaneous ulcerations secondary to interferon alfa therapy of Kaposi's sarcoma
Orlow SJ; Friedman-Kien AE
1992 Apr;128(4):566-566, Archives of dermatology
— id: 14753, year: 1992, vol: 128, page: 566, stat: Journal Article,

Kaposi's sarcoma and exposure to faeces
Peterman TA; Friedman-Kien AE; Jaffe HW; Beral V
1992 Mar 14;339(8794):685-686, Lancet
— id: 14754, year: 1992, vol: 339, page: 685, stat: Journal Article,

The clinical spectrum of bacillary angiomatosis
Webster GF; Cockerell CJ; Friedman-Kien AE
1992 Jun;126(6):535-541, British journal of dermatology
Bacillary angiomatosis is a recently recognized bacterial infectious disease that is seen mainly in patients with the acquired immunodeficiency syndrome. Including this publication, 45 patients have been described in the medical literature. In this report we describe examples of the clinical presentations of bacillary angiomatosis and review therapeutic strategies
— id: 14752, year: 1992, vol: 126, page: 535, stat: Journal Article,

Detection of human papillomavirus DNA in squamous cell carcinoma of the nail bed and finger determined by polymerase chain reaction
Ashinoff R; Li JJ; Jacobson M; Friedman-Kien AE; Geronemus RG
1991 Dec;127(12):1813-1818, Archives of dermatology
Increasing evidence supports the association of squamous cell carcinoma of the finger and nail bed with human papillomavirus infection. We treated 12 patients with squamous cell carcinoma of the finger and nail bed, none of whom was originally diagnosed as having a malignant lesion. Half of the patients were referred for carbon dioxide laser ablation of what was believed to be a recalcitrant verruca vulgaris. Our objective was to evaluate these lesions for the presence of human papillomavirus by in situ hybridization techniques and the polymerase chain reaction. This is the first report of use of the polymerase chain reaction to detect human papillomavirus in formalin-fixed, paraffin-embedded specimens of periungual squamous cell carcinoma. Seven of the 12 lesions were evaluated for the presence of human papillomavirus by both in situ hybridization and the polymerase chain reaction. Five of the seven periungual lesions were found to contain human papillomavirus type 16 but not type 18 DNA with use of the polymerase chain reaction technique. In situ hybridization failed to identify human papillomavirus in any of these patients' tumors. Our data confirm the association between human papillomavirus and squamous cell carcinoma of the periungual region and suggest that biopsies should be performed on chronic, isolated lesions of the finger in adults before therapy is initiated
— id: 9188, year: 1991, vol: 127, page: 1813, stat: Journal Article,

Clinical aspects of epidemic Kaposi's sarcoma
Buchbinder A; Friedman-Kien AE
1991 ;10:39-52, Cancer surveys
Whereas previously KS represented a very rare and obscure neoplasm, it has become over the past decade a significant disease. Its appearance in various well defined risk populations and in immunosuppressed individuals and the mounting epidemiological evidence that KS may well represent a sexually transmitted disease in certain groups make KS an important tumour to study as a model for carcinogenesis. Among the various forms of KS described, it is the epidemic form of KS, most frequently associated with HIV infection, that is now the most prevalent form seen around the world. Clinically, the mucocutaneous and lymph node involvement are its most frequently recognized manifestations. Skin lesions in epidemic KS, unlike those in classical KS, appear anywhere on the skin or oral mucosa and at any age in patients with AIDS. Visceral lesions are often present, sometimes in the absence of cutaneous KS. Epidemic KS is rarely the cause of death in AIDS patients, even in those with visceral involvement, unlike the HIV-1 unrelated African endemic form of KS, which is an aggressive and malignant tumour. HIV testing is necessary to establish the diagnosis of AIDS in patients with epidemic KS, even in those patients with risk factors for HIV infection, since epidemic KS may represent an epidemic disease caused by a yet unidentified transmissible agent distinct from HIV. Concurrent transmission of HIV and the putative 'KS agent' may have occurred in the homosexual patients with AIDS in whom KS has been so prevalent, and the recently identified form of epidemic KS in individuals not infected with HIV may well become yet a new form of this curious disease
— id: 14211, year: 1991, vol: 10, page: 39, stat: Journal Article,

Clinical, histologic, microbiologic, and biochemical characterization of the causative agent of bacillary (epithelioid) angiomatosis: a rickettsial illness with features of bartonellosis
Cockerell CJ; Tierno PM; Friedman-Kien AE; Kim KS
1991 Nov;97(5):812-817, Journal of investigative dermatology
It has been suggested that bacillary (epithelioid) angiomatosis (BEA) is a manifestation of cat scratch disease (CSD). Because of clinical similarity between this condition and the verruga peruana phase of bartonellosis, we sought to further characterize this disease as well as its causative agent and to compare it to bartonellosis. We isolated a small flagellated pleomorphic bacillus from skin lesions of two patients with BEA. Organisms were stained successfully with Warthin-Starry silver stains, but immunohistochemistry failed to demonstrate binding with a polyclonal antibody directed against the cat scratch bacillus. Whole cell fatty-acid gas chromatography performed on both BEA organisms and Bartonella bacilliformis demonstrated marked similarity between the two. Electron microscopy of BEA organisms in tissue and in suspension revealed features characteristic of a gram negative bacillus. Based on these findings, we propose that this unusual rickettsial infectious disease with vascular proliferation may represent an unusual variant of infection with a bartonella-like organism rather than a manifestation of cat scratch disease
— id: 14757, year: 1991, vol: 97, page: 812, stat: Journal Article,

THE AGENT OF BACILLARY ANGIOMATOSIS
COCKERELL, CJ; TIERNO, PM; FRIEDMANKIEN, AE; KIM, KS
1991 MAY 23 ;324(21):1511-1512, New England journal of medicine
— id: 51593, year: 1991, vol: 324, page: 1511, stat: Journal Article,

THE CAUSATIVE AGENT OF BACILLARY ANGIOMATOSIS
COCKERELL, CJ; TIERNO, PM; FRIEDMANKIEN, AE; KIM, KS
1991 NOV 14 ;325(20):1448-1448, New England journal of medicine
— id: 51534, year: 1991, vol: 325, page: 1448, stat: Journal Article,

American Academy of Dermatology Symposium on AIDS. Atlanta, Georgia, Dec. 1, 1990
Friedman-Kien AE; Harte JS
1991 Dec;25(6 Pt 1):1086-1091, Journal of the American Academy of Dermatology
— id: 13821, year: 1991, vol: 25, page: 1086, stat: Journal Article,

KAPOSIS-SARCOMA IN HIV UNINFECTED HOMOSEXUAL OR BISEXUAL MEN
FRIEDMANKIEN, AE; SALTZMAN, BR; HUANG, YQ; PETERMAN, T; LI, JJ
1991 FEB ;7(2):221-221, AIDS research & human retroviruses
— id: 51731, year: 1991, vol: 7, page: 221, stat: Journal Article,

Rapid detection of Epstein-Barr virus DNA in clinical samples of oral hairy leukoplakia with HRP-labeled DNA probes and in situ hybridization
McClintock JT; Chan IJ; Taub FE; Friedman-Kien AE; Resnick L
1991 Jun;33(1-2):155-164, Journal of virological methods
An in situ hybridization technique, using horseradish peroxidase (HRP)-labeled DNA probes containing a portion of the Epstein-Barr virus (EBV) genome, was used to detect EBV DNA in tongue sections and smears from patients with oral lesions resembling the clinical features of oral hairy leukoplakia (HL). Eleven biopsy specimens (six consistent with HL, four normal tongue controls, and one leukoplakia) and 11 tongue smears were evaluated for the presence of EBV, cytomegalovirus (CMV), herpes simplex virus (HSV), and human papillomavirus (HPV) type 16. Following hybridization, six biopsy specimens and 10 tongue smears were found positive for EBV. All biopsy cases were negative for CMV, HSV, HPV-16 and the negative control probe. The specificity of the in situ hybridization assay was 100%. These results suggest that in situ hybridization using HRP-labeled DNA probes may be useful as a rapid diagnostic method for the detection of EBV in tongue sections or smears from patients diagnosed with HL
— id: 14758, year: 1991, vol: 33, page: 155, stat: Journal Article,

The aetiology of Kaposi's sarcoma
Peterman TA; Jaffe HW; Friedman-Kien AE; Weiss RA
1991 ;10:23-37, Cancer surveys
The aetiology of KS remains unknown, but recent evidence suggests that the disease is caused by the presence of an infectious agent in an immunosuppressed host. Although there are a variety of clinical presentations, the putative infectious agent is likely to be the same in all cases. The pathophysiology of the lesions, the types of immunosuppression that facilitate disease expression, the response to therapy and the distribution of disease within immunosuppressed populations provide important clues to the nature of the unidentified infectious agent
— id: 14759, year: 1991, vol: 10, page: 23, stat: Journal Article,

Kaposi's sarcoma
Stickler MC; Friedman-Kien AE
1991 Jan-Mar;9(1):39-47, Clinics in dermatology
— id: 14184, year: 1991, vol: 9, page: 39, stat: Journal Article,

CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro
Cao YZ; Friedman-Kien AE; Huang YX; Li XL; Mirabile M; Moudgil T; Zucker-Franklin D; Ho DD
1990 Jun;64(6):2553-2559, Journal of virology
Five hepatoma cell lines, including CZHC/8571, PLC/PRF/5, Hep3B, HepG2, and HUH7, were inoculated with three diverse isolates of human immunodeficiency virus type 1 (HIV-1). Productive infection was noted in all hepatoma cell lines, and expression of viral p24 antigen lasted for over 3 months, but its level decreased in proportion to the number of viable cells. HIV-1 antigens were also found in the cells by immunohistochemical staining and radioimmunoprecipitation assay, as were viral RNA by in situ hybridization and HIV-1-like particles by electron microscopy. Virus yield assays were also positive on supernatant fluids collected from hepatoma cultures inoculated with HIV-1. Despite their susceptibility to infection, all five hepatoma cell lines were negative for CD4 by immunofluorescence and for CD4 mRNA by slot-blot hybridization. In addition, HIV-1 infection of hepatoma cell lines was not blocked by anti-CD4 monoclonal antibody or soluble CD4. Together, these findings clearly demonstrate that all five hepatoma cell lines were susceptible to productive infection by HIV-1 in vitro via a CD4-independent mechanism
— id: 14766, year: 1990, vol: 64, page: 2553, stat: Journal Article,

HIV-1 neutralizing antibodies in urine from seropositive individuals
Cao YZ; Friedman-Kien AE; Mirabile M; Li XL; Alam M; Dieterich D; Ho DD
1990 ;3(3):195-199, Journal of acquired immune deficiency syndrome
HIV-1 neutralizing activity was demonstrated in serum and 200-fold concentrated urine from individuals who were HIV-1 antibody positive in both their serum and urine, including AIDS-KS, AIDS-OI, ARC, and asymptomatic patients. Virus neutralization activity was detected in 23 of 56 (41.1%) of the serum samples and in 19 of 56 (33.9%) of the urine samples tested, with titers ranging from 1:8 to 1:256 and 1:1 to 1:4, respectively. The highest frequency of HIV-1 neutralizing activity (87.5%) and the highest mean neutralization titers (1:65) were found in the ARC patients. A high prevalence of p24 antigen in serum and low numbers of T4-lymphocytes correlated with a low frequency of neutralizing activity in either serum or urine in the infected individuals. HIV-1 neutralizing activity in the urine was shown to be due to immunoglobulins using a Sephadex G-100 filtration gel. All 19 urine samples with neutralizing activity contained antibodies reactive with envelope glycoproteins gp160, gp120, and gp41 by Western blot, similar to that seen with serum. The frequency of HIV-1 neutralizing activity in the urine concentrates was generally associated with high titers of neutralizing antibody in the corresponding serum. These findings suggest that HIV-1 neutralizing antibodies are lost in the urine by an as yet unknown mechanism
— id: 14768, year: 1990, vol: 3, page: 195, stat: Journal Article,

What we now know--and must do--about HIV disease and AIDS
Friedman-Kien AE
1990 Jun;22(6 Pt 2):1163-1166, Journal of the American Academy of Dermatology
— id: 14761, year: 1990, vol: 22, page: 1163, stat: Journal Article,

Human immunodeficiency virus infection: a survey with special emphasis on mucocutaneous manifestations
Friedman-Kien AE; Farthing C
1990 Jun;9(2):167-177, Seminars in dermatology
Since the first reports of acquired immunodeficiency syndrome (AIDS) in 1981, many dermatological conditions have been reported to occur more commonly in people infected with human immunodeficiency virus (HIV). Acute HIV infection may first present as a skin eruption; the onset of immunosuppression after years of infection with HIV may be heralded by the development of various viral, fungal, bacterial, papulosquamous, or neoplastic eruptions. HIV disease often presents first to dermatologists who must be aware of subtle presentations and the possibility of underlying HIV infection--as well as alert to danger signals that indicate the need for urgent treatment or referral
— id: 14762, year: 1990, vol: 9, page: 167, stat: Journal Article,

Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma
Friedman-Kien AE; Saltzman BR
1990 Jun;22(6 Pt 2):1237-1250, Journal of the American Academy of Dermatology
Kaposi's sarcoma, first described in 1972, is a rare, chronic neoplasm that occurs most often in elderly men of Eastern European origin. In the mid-twentieth century, more aggressive forms of Kaposi's sarcoma were found to be an endemic disease especially common among young black men in central Africa. Kaposi's sarcoma also occurs in iatrogenically immunosuppressed patients, such as kidney transplant recipients. In 1981, the sudden occurrence of an unusual, disseminated form of Kaposi's sarcoma in homosexual men in New York and California heralded the epidemic now known as the acquired immunodeficiency syndrome (AIDS). Ninety-five percent of all AIDS-associated Kaposi's sarcoma (AIDS-KS) has been in homosexual men; however, the incidence of AIDS-KS has diminished from greater than 40% of men with AIDS since 1981 to less than 20% in 1989. The remaining 5% of AIDS-KS has been seen in all other populations at risk for AIDS. The reasons for the remarkable persistent increased prevalence of AIDS-KS among homosexual men remains obscure. Clinically, AIDS-KS is a highly varied neoplastic disease characterized by multifocal mucocutaneous lesions often with lymphatic and visceral involvement. The etiology of Kaposi's sarcoma remains unknown although various hypotheses have been suggested, including endothelial-tumor growth factors, oncogenic expression, genetic predisposition, and environmental cofactors. An as-yet unidentified viruslike agent has been proposed as a possible direct cause of this neoplasm. Different treatment modalities for Kaposi's sarcoma have been employed with varying success, these include localized radiation therapy, cryotherapy, electrocauterization, surgical excision, and a variety of systemic chemotherapeutic regimens, as well as alpha-interferon. Although all available treatments help control the lesions, none lengthens survival
— id: 14764, year: 1990, vol: 22, page: 1237, stat: Journal Article,

Kaposi's sarcoma in HIV-negative homosexual men
Friedman-Kien AE; Saltzman BR; Cao YZ; Nestor MS; Mirabile M; Li JJ; Peterman TA
1990 Jan 20;335(8682):168-169, Lancet
— id: 14767, year: 1990, vol: 335, page: 168, stat: Journal Article,

The changing incidence of Kaposi's sarcoma among patients with AIDS
Haverkos HW; Friedman-Kien AE; Drotman DP; Morgan WM
1990 Jun;22(6 Pt 2):1250-1253, Journal of the American Academy of Dermatology
Kaposi's sarcoma (KS), the most common cancer in patients with acquired immunodeficiency syndrome (AIDS), occurs predominantly in homosexual men. However, the percentage of homosexual AIDS patients with KS has declined during the past 6 years. This and other findings suggest that one or more cofactors associated with the homosexual lifestyle, rather than a special viral strain, probably influence the development of KS in patients infected with the human immunodeficiency virus (HIV). Possible reasons for the decline include changes in homosexual behaviors, leading to the practice of safer sexual techniques, and a decrease in use of nitrite inhalants. Identification of the KS-AIDS cofactor(s) could be invaluable to developing prevention and treatment strategies
— id: 14763, year: 1990, vol: 22, page: 1250, stat: Journal Article,

Epidemic Kaposi's sarcoma
Krigel RL; Friedman-Kien AE
1990 Jun;17(3):350-360, Seminars in oncology
No significant impact of available treatments on survival among patients with epidemic KS has been demonstrated. Therefore, antitumor therapy now should be considered palliative. In the early stages of the disease, systemic treatment may not be needed, whereas advanced disease requires systemic treatment with one or more agents known to have antitumor activity. A complete therapeutic response is difficult to achieve and if such response is obtained, maintenance therapy may be necessary. The overall prognosis for survival in patients with epidemic KS appears to depend on the severity of immune suppression and HIV infection rather than on the neoplastic proliferation and tumor load. This is reflected in the new staging proposals for KS. Ultimately, the ideal treatment for the AIDS patient with KS will be a combination of antiretroviral therapy to suppress further effects of HIV, biological therapy to reverse the immunologic defects, chemotherapy to control tumor development, and hematopoietic growth factors to ameliorate treatment toxicities
— id: 14765, year: 1990, vol: 17, page: 350, stat: Journal Article,

HIV-1 DNA proviral sequences in fresh urine pellets from HIV-1 seropositive persons
Li JJ; Friedman-Kien AE; Huang YQ; Mirabile M; Cao YZ
1990 Jun 30;335(8705):1590-1591, Lancet
— id: 14760, year: 1990, vol: 335, page: 1590, stat: Journal Article,

Patient-applied podofilox for treatment of genital warts
Beutner KR; Conant MA; Friedman-Kien AE; Illeman M; Artman NN; Thisted RA; King DH
1989 Apr 15;1(8642):831-834, Lancet
In a double-blind trial, 0.5% podofilox (podophyllotoxin) or placebo was applied by patients to their own genital warts in up to four treatment cycles. At some time during the study, 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free. At the end of the treatment, 73.6% of the original warts in podofilox treated patients were gone compared with only 8.3% of those in the placebo group (mean percentage of total original wart area was reduced by 82.3% compared with 4.2%). 82% of the treated warts in the podofilox group and 13% in the placebo group had resolved at 6 weeks. Recurrence was observed in 34% of the previously resolved warts. Consistent with this rate of recurrence, new warts developed in a third of the subjects in each group at sites remote from the treatment site. There were no systemic adverse reactions, although transient inflammation, erosion, pain, and burning were common
— id: 14770, year: 1989, vol: 1, page: 831, stat: Journal Article,

Antibodies to human immunodeficiency virus type 1 in the urine specimens of HIV-1-seropositive individuals
Cao YZ; Hosein B; Borkowsky W; Mirabile M; Baker L; Baldwin D; Poiesz BJ; Friedman-Kien AE
1989 Jun;5(3):311-319, AIDS research & human retroviruses
Specific antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 200-fold concentrated urine samples, but none were detected in unconcentrated urine specimens, from 100 randomly selected HIV-1--seropositive individuals by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques using the manufacturer's recommended procedures. Using modified methods for both the ELISA and Western blot tests, antibodies to HIV-1 have also been detected in the unconcentrated urine specimens from the same HIV-1--seropositive individuals. No difference in the frequency of antibodies to HIV-1 were found between unconcentrated and 200-fold concentrated urine samples when tested by the modified methods. HIV-1 core antigen (p24) was not detected in either the concentrated or the unconcentrated HIV-1--seropositive adult urine samples; none of these individuals showed overt clinical or laboratory evidence of renal dysfunction. The titer of the antibodies to HIV-1 found in the urine specimens was found to be parallel with the titer of antibodies to HIV-1 in the corresponding individual's serum. Further elucidation of the pathophysiology and the nature of the specific antibodies to HIV-1 observed in the urine of HIV-1--seropositive individuals is under investigation in our laboratories
— id: 10608, year: 1989, vol: 5, page: 311, stat: Journal Article,

Prognostic factors and staging classification of patients with epidemic Kaposi's sarcoma
Chachoua A; Krigel R; Lafleur F; Ostreicher R; Speer M; Laubenstein L; Wernz J; Rubenstein P; Zang E; Friedman-Kien A
1989 Jun;7(6):774-780, Journal of clinical oncology
Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months)
— id: 10606, year: 1989, vol: 7, page: 774, stat: Journal Article,

Skin manifestations of HIV infection
Cockerell CJ; Friedman-Kien AE
1989 Sep;16(3):621-644, Primary care
The skin is quite commonly involved in patients with HIV infection and the resulting diseases may serve as presenting signs of AIDS or ARC. The most common infectious and non-infectious inflammatory disorders as well as common neoplasms that are seen in this patient population are reviewed and depicted in detail
— id: 14769, year: 1989, vol: 16, page: 621, stat: Journal Article,

Color atlas of AIDS
Friedman-Kien, Alvin E
Philadelphia : Saunders, 1989,
— id: 80, year: 1989, vol: , page: , stat: ,

Sperm and seminal plasma antibodies in acquired immune deficiency (AIDS) and other associated syndromes
Adams LE; Donovan-Brand R; Friedman-Kien A; el Ramahi K; Hess EV
1988 Mar;46(3):442-449, Clinical immunology & immunopathology
Although HIV has been established as the etiologic agent in AIDS, other contributory cofactors may be responsible for selective clinical manifestations of the syndrome. While the pathogenesis remains unclear, the development of immunologic abnormalities observed in some homosexual males with AIDS and AIDS-related complex may be attributed to repeated exposure to allogeneic sperm and seminal plasma components. Accordingly, antibody levels to semen fractions were measured in sera from 338 individuals (295 AIDS, 36 ARC, 16 randomly selected homosexuals, 29 patients with infectious hepatitis, 12 hemophiliacs, 20 rheumatic disease patients, and 24 healthy heterosexual adults). The methods were (i) passive hemagglutination for antibodies to human seminal plasma (HuSePl), and (ii) indirect immunofluorescence (IF) assay on methanol-fixed human sperm noting staining of acrosomal, equatorial, postnuclear, and tail main-piece regions. HuSePl was positive in 31% AIDS sera, while 39% were positive by IF. ARC sera were 30% positive for HuSePl and 38% positive IF. No control sera were positive. Results reveal a significant incidence of antibody to sperm and seminal plasma components in ARC and AIDS patients. Because of the known immunomodulating properties of both, it is possible that these responses may indicate risk factors for disease progression and severity
— id: 49663, year: 1988, vol: 46, page: 442, stat: Journal Article,

IgG antibodies to HIV-1 in urine of HIV-1 seropositive individuals
Cao Y; Friedman-Kien AE; Chuba JV; Mirabile M; Hosein B
1988 Apr 9;1(8589):831-832, Lancet
— id: 8189, year: 1988, vol: 1, page: 831, stat: Journal Article,

Oral candidiasis and AIDS
Chaudhry AP; Chachoua A; Saltzman BR; Friedman-Kien A
1988 Jun;116(7):818, 820-, Journal of the American Dental Association
— id: 14631, year: 1988, vol: 116, page: 818, 820, stat: Journal Article,

Epithelioid angiomatosis and cat scratch disease bacillus
Cockerell CJ; Friedman-Kien AE
1988 Jun 11;1(8598):1334-1335, Lancet
— id: 14773, year: 1988, vol: 1, page: 1334, stat: Journal Article,

AIDS-related Kaposi's sarcoma
Friedman-Kien AE
1988 ;112:27-36, Recent results in cancer research = Fortschritte der Krebsforschung = Progres dans les recherches sur le cancer
— id: 11266, year: 1988, vol: 112, page: 27, stat: Journal Article,

Natural interferon alfa for treatment of condylomata acuminata
Friedman-Kien AE; Eron LJ; Conant M; Growdon W; Badiak H; Bradstreet PW; Fedorczyk D; Trout JR; Plasse TF
1988 Jan 22-29;259(4):533-538, JAMA
The activity of natural (leukocyte) interferon alfa in the treatment of condylomata acuminata was assessed in a randomized, double-blind, placebo-controlled, multicenter trial. Interferon alfa (Alferon N Injection) or placebo was injected into lesions twice weekly for up to eight weeks. Eighty-six patients were given interferon alfa, and 72 were given placebo. Eighty-six percent of interferon alfa-treated patients and 89% of placebo-treated patients had received previous therapy for condylomata acuminata. Side effects, usually flulike symptoms, occurred briefly after the injections; if present, they disappeared before the end of the third week of therapy. Treatment completely eliminated warts in 62% of interferon alfa-treated patients compared with only 21% of placebo-treated patients. Natural interferon alfa given intralesionally is an effective and safe treatment even in patients with recurrent or recalcitrant genital warts
— id: 11205, year: 1988, vol: 259, page: 533, stat: Journal Article,

Intravenous acyclovir therapy of first episodes of genital herpes: a multicenter double-blind, placebo-controlled trial
Peacock JE Jr; Kaplowitz LG; Sparling PF; Durack DT; Gnann JW Jr; Whitley RJ; Lovett M; Bryson YJ; Klein RJ; Friedman-Kien AE; et al
1988 Sep;85(3):301-306, American journal of medicine
PURPOSE: A collaborative multicenter double-blind, placebo-controlled trial of intravenous acyclovir treatment of first-episode genital herpes was performed in order to substantiate previous findings on the efficacy and safety of this drug, to evaluate the influence of parenteral therapy on recurrence frequency, and to obtain further data on the natural history of genital herpes. PATIENTS AND METHODS: Eighty-two patients with first episodes of genital herpes simplex virus (HSV) infection were randomly assigned in a double-blind fashion to treatment with intravenous acyclovir (5 mg/kg every eight hours) or placebo for five days. Before therapy, all lesions in the genital/perineal area and in extragenital sites were cultured. New lesions appearing in both areas after the onset of therapy were cultured separately. Lesions in all groups were cultured until completely healed. Sera were collected from all patients on entry to the study and on Day 21 to determine presence or absence of antibodies to HSV-1 and HSV-2. Time to healing, time to crusting, time to cessation of viral shedding, and appearance of new lesions during therapy were compared for each treatment group. RESULTS: Patients receiving acyclovir experienced a significant reduction in the median duration of pain (4.3 versus 4.8 days, p = 0.019), viral shedding (1.9 versus 8.4 days, p less than 0.001), and time to healing (8.4 versus 11.5 days, p = 0.02) compared with placebo recipients. These differences were largely attributable to the effect of therapy in the subset of patients with primary disease in whom acyclovir reduced the median duration of pain from 10.6 days to 4.2 days, the median duration of viral shedding from 17.1 days to 1.9 days, and the median time to healing from 14.2 days to 8.3 days. The rate of subsequent recurrence of genital herpes was not altered by acyclovir treatment: 24 of 32 acyclovir recipients (75 percent) experienced one or more recurrences during a mean follow-up of 14 months compared with 19 of 27 placebo recipients (70 percent). Among patients experiencing recurrences, the mean number of recurrences per month among acyclovir recipients was 0.25 compared with 0.19 for patients given placebo. CONCLUSION: This multicenter trial confirms the efficacy of intravenous acyclovir in the management of first-episode genital herpes, especially in patients with primary infection. However, therapy did not alter the frequency of recurrences
— id: 14772, year: 1988, vol: 85, page: 301, stat: Journal Article,

Group specific component (Gc) and HIV diseases
Rosberger DF; Werner PA; Steinman R; Stevens CE; Friedman-Kien AE; Rubinstein P; Galbraith RM
1988 Oct-Dec;6(4):269-274, Disease markers
A previous report suggested a relationship between particular phenotypes of group specific component (Gc), and susceptibility or resistance to HIV infection, whereas other recent investigations failed to corroborate this finding. The present study demonstrated that Gc allele frequencies in white homosexual men corresponded to those expected, regardless of HIV serology and related disease. Assignment of phenotype was not influenced by Gc complexing secondary to tissue damage, or the process of infection per se. However, Gc allele frequencies in black patients with AIDS were significantly different from those in black control subjects, suggesting that the previously observed results might be in part explicable on the basis of gene admixture in ethnically mixed populations
— id: 14771, year: 1988, vol: 6, page: 269, stat: Journal Article,

Inactivation of HIV and safety precautions for the workplace
Saltzman BR; Friedman-Kien AE
1988 ;112:75-83, Recent results in cancer research = Fortschritte der Krebsforschung = Progres dans les recherches sur le cancer
— id: 11249, year: 1988, vol: 112, page: 75, stat: Journal Article,

Acquired immune deficiency syndrome (AIDS) and autoimmunity--mutually exclusive entities?
Solinger AM; Adams LE; Friedman-Kien AE; Hess EV
1988 Jan;8(1):32-42, Journal of clinical immunology
Loss of normal immune homeostasis occurs in acquired immune deficiency syndrome (AIDS). We evaluated patients at the University of Cincinnati and New York University Medical Centers for serologic evidence of autoimmune changes. Specifically, tests for antinuclear and organ-specific antibodies by immunofluorescence, antisperm and anti-seminal plasma antibodies, rheumatoid factor by latex and sensitized sheep cell agglutination techniques, anti-polyadenosine (poly A), and single-stranded DNA antibodies were performed in human immunodeficiency virus (HIV) antibody-positive sera. A parallel study of mitogen responsiveness was performed and showed inhibition of response by AIDS and AIDS-related complex (ARC) sera. In spite of evidence of polyclonal B-cell activation, hyperglobulinemia, and the presence of antibodies to many infectious agents, as well as the known cellular immune abnormalities, the patients tested had a striking absence of these autoantibodies. The only major difference noted from normal controls, was a low but significant level of antibody binding to poly A. The autoimmune connective tissue diseases were not observed in this group of patients
— id: 14774, year: 1988, vol: 8, page: 32, stat: Journal Article,

PREDICTORS OF AIDS IN HOMOSEXUAL MEN
Buimoviciklein, E; Sonnabend, JA; Lange, M; Friedmankien, AE; Klein, RJ; Vilcek, J
1987 Jul 23;317(4):245-245, New England journal of medicine
— id: 31160, year: 1987, vol: 317, page: 245, stat: Journal Article,

Detection of HIV antigen and specific antibodies to HIV core and envelope proteins in sera of patients with HIV infection
Cao YZ; Valentine F; Hojvat S; Allain JP; Rubinstein P; Mirabile M; Czelusniak S; Leuther M; Baker L; Friedman-Kien AE
1987 Aug;70(2):575-578, Blood
The sera of well-characterized populations were examined for three markers of human immunodeficiency virus (HIV) infection; HIV antigen (HIV Ag), and antibodies to HIV envelope (gp41) and core (p24) proteins. Of 563 serum samples tested, 251 were from HIV-infected patients diagnosed as having AIDS manifested by opportunistic infections (AIDS-OI), AIDS-associated Kaposi's sarcoma (AIDS-KS), or AIDS-related complex (ARC). One hundred seventy-six specimens tested were from asymptomatic high-risk individuals, and 136 were from heterosexual control subjects or patients with non-AIDS-related disease. None of the 136 control individuals tested had HIV Ag or HIV antibodies to either p24 or gp41. Of the 427 HIV-seropositive individuals, 99% to 100% were positive for gp41 antibodies to HIV. In contrast, the seroprevalence of p24 antibodies to HIV varied from 23% to 83% and appeared to be inversely associated with the severity of the patients' clinical symptoms. When specimens were analyzed for the presence of HIV Ag, in seropositive individuals the prevalence rate for this marker was lowest (1.4%) in asymptomatic individuals and highest (50%) in the AIDS-OI diagnosed group. Also, 240 cases with AIDS-KS, AIDS-OI, and ARC and the group of asymptomatic high-risk individuals were analyzed for T helper/T lymphocytes (T4) cell number and T4/T8 ratio; only one (2.0%) HIV Ag-positive case showed a T4 cell number greater than 400 and a normal T4/T8 ratio. These studies appear to demonstrate a direct correlation between the presence of HIV Ag and the severity of clinical complications of HIV infection
— id: 14776, year: 1987, vol: 70, page: 575, stat: Journal Article,

AIDS and occlusal trauma
Chaudhry AP; Chachoua A; Saltzman BR; Friedman-Kien A
1987 Nov;115(5):672, 674-, Journal of the American Dental Association
— id: 14633, year: 1987, vol: 115, page: 672, 674, stat: Journal Article,

AIDS-associated Kaposi's sarcoma
Chaudhry AP; Chachoua A; Saltzman BR; Friedman-Kien AE
1987 Dec;115(6):824, 826-, Journal of the American Dental Association
— id: 14632, year: 1987, vol: 115, page: 824, 826, stat: Journal Article,

Epithelioid angiomatosis: a distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex
Cockerell CJ; Whitlow MA; Webster GF; Friedman-Kien AE
1987 Sep 19;2(8560):654-656, Lancet
Unusual cutaneous vascular neoplasms distinct from Kaposi's sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor VIII antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour
— id: 14775, year: 1987, vol: 2, page: 654, stat: Journal Article,

Inactivation of human immunodeficiency, herpes simplex, and vaccinia viruses by sodium oxychlorosene
Klein RJ; Buimovici-Klein E; Ong KR; Czelusniak SM; Lange M; Friedman-Kien AE
1987 Jan 31;1(8527):281-282, Lancet
— id: 14777, year: 1987, vol: 1, page: 281, stat: Journal Article,

Identification of human immunodeficiency virus sequences by using in vitro enzymatic amplification and oligomer cleavage detection
Kwok S; Mack DH; Mullis KB; Poiesz B; Ehrlich G; Blair D; Friedman-Kien A; Sninsky JJ
1987 May;61(5):1690-1694, Journal of virology
Human immunodeficiency virus (HIV) has been associated with acquired immunodeficiency syndrome and related disorders. Assays to detect antibodies to HIV proteins have been developed and used to screen sera for the identification of individuals who have been exposed to the virus. Although these serological tests have significant sensitivity and specificity for detecting exposure to the virus, they do not provide direct identification of HIV. We report here the application of recently developed nucleic acid amplification and oligonucleotide-based detection procedures for the identification of HIV sequences in established infected cell lines and in cells cultured from infected individuals
— id: 49664, year: 1987, vol: 61, page: 1690, stat: Journal Article,

EPITHELIOID ANGIOMATOSIS - A VARIANT OF KAPOSIS-SARCOMA - REPLY
Webster, GF; Cockerell, CJ; Whitlow, MA; Friedmankein, AE
1987 Nov 21;2(8569):1215-1215, Lancet
— id: 31102, year: 1987, vol: 2, page: 1215, stat: Journal Article,

Tumor-associated antigen is expressed on lymphocytes from patients with acquired immunodeficiency syndrome
Berger CL; Friedman-Kien AE; DiFranco M; Rehle T; Ostreicher R; Knobler R; Donofrio S; Laubenstein LJ; Edelson RL
1986 Aug;87(2):280-283, Journal of investigative dermatology
Monoclonal antibody BE2 recognizes an antigen found on malignant T4+ lymphocytes from cutaneous T-cell lymphoma patients (CTCL). Normal peripheral blood lymphocytes do not express detectable levels of BE2 antigen. Forty-eight percent of patients with the acquired immunodeficiency syndrome (AIDS) had lymphocyte populations that were reactive with monoclonal antibody BE2. Peripheral blood lymphocytes from healthy homosexuals, patients with classical Kaposi's sarcoma or viral syndromes, and healthy normal controls were BE2-. Double-labeling studies demonstrated that BE2+ cells were T lymphocytes. This observation demonstrates that some AIDS patients as well as CTCL patients have circulating cells that express a common lymphocyte abnormality
— id: 14780, year: 1986, vol: 87, page: 280, stat: Journal Article,

Presence of chromosomal abnormalities and lack of AIDS retrovirus DNA sequences in AIDS-associated Kaposi's sarcoma
Delli Bovi P; Donti E; Knowles DM 2d; Friedman-Kien A; Luciw PA; Dina D; Dalla-Favera R; Basilico C
1986 Dec;46(12 Pt 1):6333-6338, Cancer research
The frequent occurrence of Kaposi's sarcoma (KS) in association with the acquired immune deficiency syndrome (AIDS) could be due to the fact that the etiological agent of this tumor is the same retrovirus causing AIDS, to another oncogenic virus frequently found in AIDS patients, or to the unmasking of the tumorigenic potential of KS cells by immunosuppression. We have therefore investigated the presence of DNA sequences homologous to the AIDS retrovirus, cytomegalovirus (CMV), and hepatitis B virus in 13 KS necropsies and biopsies from AIDS patients. All KS DNA samples were negative for AIDS retrovirus or hepatitis B DNA sequences. Two DNAs from necropsies contained CMV DNA, but the data suggested the presence of replicating CMV DNA due to generalized infection. We have also studied cell cultures derived from KS skin biopsies of AIDS patients. These cultures had a short lifetime in vitro and expressed some markers of endothelial cells. The cells were not tumorigenic in nude mice but contained a number of chromosomal rearrangements which were often monoclonal within the same culture. However, these abnormalities were different from culture to culture and even in cultures from the same biopsy. The presence of these chromosomal abnormalities seemed to correlate with the cell positivity for endothelial markers. Taken together these results indicate that neither the AIDS retrovirus, CMV, or hepatitis B virus is directly responsible for the altered growth of KS cells, that KS may be polyclonal even within the same lesion, and that KS cells have a tendency to karyotypic rearrangements
— id: 14431, year: 1986, vol: 46, page: 6333, stat: Journal Article,

CLASSICAL (NON AIDS) VERSUS AIDS KAPOSIS-SARCOMA - AN IMMUNOHISTOCHEMICAL STUDY
DUSCHET, P; SCHWARZ, T; FRIEDMANKIEN, AE; GSCHNAIT, F
1986 MAR ;86(3):334-334, Journal of investigative dermatology
— id: 41444, year: 1986, vol: 86, page: 334, stat: Journal Article,

Viral origin of hairy leukoplakia
Friedman-Kien AE
1986 Sep 20;2(8508):694-695, Lancet
— id: 14779, year: 1986, vol: 2, page: 694, stat: Journal Article,

Treatment of recurrent genital herpes with topical alpha interferon gel combined with nonoxynol 9
Friedman-Kien AE; Klein RJ; Glaser RD; Czelusniak SM
1986 Nov;15(5 Pt 1):989-994, Journal of the American Academy of Dermatology
A double-blind, placebo-controlled study was done to evaluate the efficacy of an alpha interferon preparation in 128 patients with recurrent genital herpes. The preparation containing 10(5) or 10(7) U alpha interferon with nonoxynol 9 in a cream base (Exovir-HZ) was applied three times daily for 5 days. The treatment did not cause any adverse reactions. Patients treated with either interferon concentration became negative for viral culture at a faster rate than placebo recipients. The end of new lesion formation, scabbing, and the healing of lesions were all superior in patients treated with 10(5) U to those treated with 10(7) U interferon. End of new lesion formation and scabbing were also statistically different in patients treated with 10(7) U from those patients treated with placebo. Results suggest that topical interferon might be useful in relieving symptoms of severe cases of genital herpes
— id: 14778, year: 1986, vol: 15, page: 989, stat: Journal Article,

Herpes zoster: a possible early clinical sign for development of acquired immunodeficiency syndrome in high-risk individuals
Friedman-Kien AE; Lafleur FL; Gendler E; Hennessey NP; Montagna R; Halbert S; Rubinstein P; Krasinski K; Zang E; Poiesz B
1986 Jun;14(6):1023-1028, Journal of the American Academy of Dermatology
Zoster is uncommon before the age of 50 years in immunologically normal individuals, but it occurs with increased frequency in people who are immunosuppressed. A retrospective review of 300 patients with acquired immunodeficiency syndrome associated with Kaposi's sarcoma, revealed that 8% had prior zoster, a rate that is sevenfold greater than historic controls of the same age. We prospectively examined forty-eight patients, with no known immunodeficiency or signs of AIDS or AIDS related complex (ARC), who presented with zoster localized to the thoracic region. Forty-one patients had known risk factors for AIDS and thirty-five had antibody to the AIDS-associated virus (AAV) at the time of presentation. One seropositive subject had no known risk factors. Absolute lymphocyte counts, lymphocyte OKT4/OKT8 ratios, and lymphocyte mitogen responses were all depressed in subjects with antibody to AAV when compared with seronegative individuals. Seven of thirty-three AAV antibody-positive subjects, who could be followed longitudinally, developed AIDS from 1 to 28 months (mean = 13) after zoster. One antibody-negative subject seroconverted to become AAV seropositive 16 months after zoster and developed Kaposi's sarcoma 1 month later. These eight subjects had persistently low lymphocyte OKT4/OKT8 ratios and elevated beta-2 microglobulin. In patients at risk for AIDS, the occurrence of zoster may be one sign that heralds the marked depression of cellular immunity associated with AIDS or ARC
— id: 14781, year: 1986, vol: 14, page: 1023, stat: Journal Article,

HERPES-ZOSTER - A POSSIBLE EARLY CLINICAL SIGN FOR DEVELOPMENT OF AIDS IN HIGH-RISK INDIVIDUALS
FRIEDMANKIEN, AE; LAFLEUR, FL; GENDLER, E; HENNESSEY, NP; MONTAGNA, R; HALBERT, S; RUBINSTEIN, P; KRASINSKI, K; ZANG, E; POIESZ, B
1986 APR ;34(2):A750-A750, Clinical research
— id: 41417, year: 1986, vol: 34, page: A750, stat: Journal Article,

HERPES-ZOSTER - A POSSIBLE EARLY CLINICAL SIGN FOR DEVELOPMENT OF AIDS IN HIGH-RISK INDIVIDUALS
FRIEDMANKIEN, AE; LAFLEUR, FL; GENDLER, E; HENNESSEY, NP; MONTAGNA, R; HALBERT, S; RUBINSTEIN, P; KRASINSKI, K; ZANG, E; POIESZ, B
1986 APR ;86(4):475-475, Journal of investigative dermatology
— id: 41471, year: 1986, vol: 86, page: 475, stat: Journal Article,

Oral hairy leucoplakia in two women, a haemophiliac, and a transfusion recipient
Greenspan D; Hollander H; Friedman-Kien A; Freese UK; Greenspan JS
1986 Oct 25;2(8513):978-979, Lancet
— id: 49665, year: 1986, vol: 2, page: 978, stat: Journal Article,

Antibody levels for cytomegalovirus, herpes simplex virus, and rubella in patients with acquired immune deficiency syndrome
Halbert SP; Kiefer DJ; Friedman-Kien AE; Poiesz B
1986 Feb;23(2):318-321, Journal of clinical microbiology
Significantly higher proportions of patients with acquired immune deficiency syndrome (AIDS) or lymphadenopathy syndrome (LAS) were positive for antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) compared with control groups of commercial blood donors. In contrast, no differences were found in the incidence of individuals positive for antibodies to rubella in these groups of subjects. Of those positive for antibodies to CMV and HSV in each group, the mean antibody levels were significantly higher in AIDS-LAS patients compared with the controls. The entire distribution of antibody concentrations to CMV and HSV in AIDS patients was shifted upward, so that significantly more patients showed high values and significantly fewer showed low values, indicating hyperactive humoral immune responses to these viruses. In sharp contrast, the AIDS patients with antibody levels for rubella showed the same distribution of antibody levels as did two groups of controls. No correlation was found between concentrations of CMV and HSV antibodies in individual AIDS-LAS patients
— id: 14784, year: 1986, vol: 23, page: 318, stat: Journal Article,

Quantitative estimation by a standardized enzyme-linked immunosorbent assay of human T-cell lymphotropic virus type I antibodies in adult T-cell leukemia and acquired immune deficiency syndrome
Halbert SP; Poiesz B; Friedman-Kien AE; Montagna R; Blattner WA; Anken M
1986 Feb;23(2):212-216, Journal of clinical microbiology
Sera from patients with adult T-cell leukemia and asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I) from widely separated areas of the world reacted strongly in a standardized quantitative enzyme-linked immunosorbent assay procedure with HTLV-I viral antigen prepared from a strain isolated in the United States. There was a sharp differentiation of the values seen in the patients as compared with a normal population. Of the 35 acquired immune deficiency syndrome patients with Kaposi's sarcoma, only 2 were positive for HTLV-I antibodies in this test, and the distribution of the negative assay values in the other acquired immune deficiency syndrome patient sera was similar to that seen in the normal sera. Sera which contained extremely high levels of antibodies to other unrelated viruses (rubella virus, cytomegalovirus, and herpes simplex virus) all showed negative anti-HTLV-I results, in a pattern similar to the normal sera. Sera from patients with several autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, thyroiditis) as well as those with infectious mononucleosis or myeloma all also showed the normal distribution of negative results, in spite of the presence of very high levels of the autoantibodies, etc., associated with their illnesses
— id: 14785, year: 1986, vol: 23, page: 212, stat: Journal Article,

Thymosin alpha 1 and thymosin beta 4 in serum: comparison of normal, cord, homosexual and AIDS serum
Naylor PH; Friedman-Kien A; Hersh E; Erdos M; Goldstein AL
1986 ;8(7):667-676, International journal of immunopharmacology
Thymosin alpha 1 and thymosin beta 4 were first isolated from thymosin fr. 5 and have demonstrated biological activities on the immune system. They are chemically distinct and differ in their immunological activity profiles. The levels of thymosin alpha 1 and thymosin beta 4 were assessed by radioimmunoassay in the same serum samples. Normal thymosin alpha 1 levels were 670 +/- 163 pg/ml for males and 652 +/- 162 pg/ml for females. Normal thymosin beta 4 levels were 974 +/- 400 ng/ml for males and 889 +/- 345 ng/ml for females. No correlation between the levels of the peptides in serum from normal donors was observed. Although many samples of serum from neonates (cord blood), homosexuals and AIDS patients had elevated levels of one or both peptides, no correlation between the two peptides was found. Of potential significance is the observation that while thymosin alpha 1 and beta 4 are elevated in many individuals with AIDS (57 and 48% respectively), the individuals with AIDS related immune dysfunctions had predominantly elevated thymosin alpha 1 (54 vs 15%). These studies suggest that serum levels of the two peptides are modulated separately and that both are of potential value in defining the risk of individuals for developing AIDS
— id: 49666, year: 1986, vol: 8, page: 667, stat: Journal Article,

Partial plasma exchange in patients with AIDS and Kaposi's sarcoma. Plasmapheresis in AIDS
Reiss RF; Rubinstein P; Friedman-Kien A; Laubenstein LJ; Ciavarella D; Smith J; Walker M
1986 Summer;2(3):183-190, AIDS research
Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated
— id: 49667, year: 1986, vol: 2, page: 183, stat: Journal Article,

The expression of endothelial cell surface antigens by AIDS-associated Kaposi's sarcoma. Evidence for a vascular endothelial cell origin
Rutgers JL; Wieczorek R; Bonetti F; Kaplan KL; Posnett DN; Friedman-Kien AE; Knowles DM 2d
1986 Mar;122(3):493-499, American journal of pathology
The authors investigated 19 cases of Kaposi's sarcoma (KS) obtained from patients with the acquired immune deficiency syndrome (AIDS) for their expression of Factor VIII-related antigen (FVIIIRAg), HLA-DR (Ia) antigens, OKM1, and three distinctive vascular, but not lymphatic, endothelial-cell-associated antigens, E92, OKM5, and HCl. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections. FVIIIRAg is strongly expressed by the cells lining the vascular spaces (VCs) but is absent, weakly or focally, and variably expressed by the spindle cell (SC) component of KS. The VC component of each KS lesion examined strongly expressed E92, moderately expressed HCl, and weakly expressed OKM5. In contrast, the entire SC component of each KS lesion studied strongly expressed E92 and OKM5 and weakly expressed HCl. Neither the VCs nor the SCs expressed OKM1. These studies provide strong and compelling evidence for the vascular endothelial cell histogenesis of both the vascular and spindle cell components of KS, demonstrate the intertumor and intratumor phenotypic heterogeneity of KS, and suggest that monoclonal antibodies OKM5 and anti-E92 are the best currently available immunohistochemical markers for identifying the spindle cell component of AIDS-associated KS in cryostat sections
— id: 14782, year: 1986, vol: 122, page: 493, stat: Journal Article,

Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis
Vilcek J; Klion A; Henriksen-DeStefano D; Zemtsov A; Davidson DM; Davidson M; Friedman-Kien AE; Le J
1986 Mar;6(2):146-151, Journal of clinical immunology
Production of interferon (IFN)-gamma by peripheral blood leukocytes (PBL) was examined in cultures of unseparated fresh whole blood exposed to phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). The yield of IFN-gamma was measured by a newly developed immunoradiometric assay. Nine of 14 patients with acute pulmonary tuberculosis (TB) showed a depressed IFN-gamma response to Con A and/or PWM. Only four of these TB patients also showed a depressed IFN-gamma response to PHA. Stimulation of the patients' PBL cultures with PHA in the presence of exogenous interleukin 2 (IL 2) produced normal IFN-gamma yields in all but the most severely depressed patients. PBL cultures of TB patients with defective IFN-gamma production in response to mitogenic lectins also produced less IFN-gamma after stimulation with tuberculin PPD. Although some patients showed a moderate degree of lymphopenia, their OKT4/T8 lymphocyte ratios were mostly normal or close to normal, with the notable exception of one TB patient who has been diagnosed to have the acquired immune deficiency syndrome (AIDS)
— id: 14783, year: 1986, vol: 6, page: 146, stat: Journal Article,

Dapsone, trimethoprim-sulfamethoxazole, and the acquired immunodeficiency syndrome
Edelson PJ; Metroka CE; Friedman-Kien A
1985 Dec;103(6 ( Pt 1)):963-963, Annals of internal medicine
— id: 49668, year: 1985, vol: 103, page: 963, stat: Journal Article,

AIDS AND KAPOSIS SARCOMA
Friedmankien, AE
1985 ;11(8):790-790, Journal of dermatologic surgery & oncology
— id: 30857, year: 1985, vol: 11, page: 790, stat: Journal Article,

Dapsone for AIDS-associated Kaposi's sarcoma
Hruza GJ; Friedman-Kien AE; Laubenstein LJ; Wernz JC; Lifshitz MS; Rubinstein P
1985 Mar 16;1(8429):642-642, Lancet
— id: 14788, year: 1985, vol: 1, page: 642, stat: Journal Article,

Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the acute local phase of herpes simplex virus-induced skin infections in mice and the establishment of latency
Klein RJ; Friedman-Kien AE
1985 May;27(5):763-768, Antimicrobial agents & chemotherapy
The effect of topical and systemic treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the evolution of herpes simplex virus-induced skin infection in hairless mice was investigated. Systemic (subcutaneous) treatment with a 10-mg/kg dose and topical applications with a 5% cream started up to 48 h after infection prevented the development of severe skin lesions and a fatal outcome. However, the establishment of latent infections was prevented only by topical treatment started at 6 h after infection. Systemic (50 mg/kg) and topical treatments started 48 h after infection reduced virus titers in the skin and ganglia and promoted rapid clearance of virus from these sites. The clearance of infectious virus from ganglia during the acute phase of infection was followed by early establishment of latency. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (0.03 microgram/ml) significantly inhibited the synthesis of infectious virus in explant cultures of latently infected ganglia, and at concentrations higher than 8 micrograms/ml no infectious virus was detectable in ganglia explant cultures
— id: 14787, year: 1985, vol: 27, page: 763, stat: Journal Article,

Therapeutic trial of interferon-gamma in patients with epidemic Kaposi's sarcoma
Krigel RL; Odajnyk CM; Laubenstein LJ; Ostreicher R; Wernz J; Vilcek J; Rubinstein P; Friedman-Kien AE
1985 Aug;4(4):358-364, Journal of biological response modifiers
An epidemic form of Kaposi's sarcoma associated with the acquired immune deficiency syndrome has been recently described. Seven homosexual men with biopsy-documented epidemic Kaposi's sarcoma were treated with a human interferon-gamma preparation. All patients had generalized disease. Only one patient had received prior chemotherapy, and one other patient had recovered from a prior opportunistic infection. Interferon-gamma was administered in a dose of 500,000 U intramuscularly daily, with two 10-day induction courses, separated by a 2-week medication-free period. This was followed by maintenance therapy in the same dose twice weekly. Toxicities consisted of a flu-like illness with high fevers, shaking chills, myalgias, and arthralgias. There were no complete or partial responses. All patients exhibited disease progression, with a rapid progression of previously stable disease necessitating discontinuation of therapy in three patients. We conclude that low doses of this human interferon-gamma preparation are ineffective in epidemic Kaposi's sarcoma
— id: 14786, year: 1985, vol: 4, page: 358, stat: Journal Article,

COMMON MEMBRANE ANTIGEN ON LYMPHOCYTES FROM CUTANEOUS T-CELL LYMPHOMA AND ACQUIRED IMMUNE-DEFICIENCY SYNDROME PATIENTS
BERGER, CL; REHLE, T; FRIEDMANKIEN, AE; DIFRANCO, M; OSTREICHER, R; KNOBLER, R; LAUBENSTEIN, LJ; EDELSON, R
1984 ;82(4):409-409, Journal of investigative dermatology
— id: 40971, year: 1984, vol: 82, page: 409, stat: Journal Article,

COMMON MEMBRANE ANTIGEN ON LYMPHOCYTES FROM CUTANEOUS T-CELL LYMPHOMA AND ACQUIRED IMMUNE-DEFICIENCY SYNDROME PATIENTS
BERGER, CL; REHLE, T; FRIEDMANKIEN, AE; DIFRANCO, M; OSTREICHER, R; KNOBLER, R; LAUBENSTEIN, LJ; EDELSON, R
1984 ;32(2):A571-A571, Clinical research
— id: 40987, year: 1984, vol: 32, page: A571, stat: Journal Article,

Factor VIII-related antigen in Kaposi's sarcoma in young homosexual men
Flotte TJ; Hatcher VA; Friedman-Kien AE
1984 Feb;120(2):180-182, Archives of dermatology
This study investigated the histogenesis of the Kaposi's sarcomas occurring in young homosexual men. Paraffin sections of seven tumors were stained for factor VIII-related antigen by the unlabeled peroxidase antiperoxidase method. Both the spindle cell component and the cells lining vascular channels contained factor VIII-related antigen, a marker for endothelial cells. Our study supports the hypothesis that both components of Kaposi's sarcoma are of endothelial cell origin
— id: 14795, year: 1984, vol: 120, page: 180, stat: Journal Article,

Kaposi's sarcoma: an opportunistic neoplasm
Friedman-Kien AE
1984 May;82(5):446-448, Journal of investigative dermatology
— id: 14794, year: 1984, vol: 82, page: 446, stat: Journal Article,

AIDS : the epidemic of Kaposi's sarcoma and opportunistic infections
Friedman-Kien, Alvin E.; Laubenstein, Linda J
New York : Masson Pub. USA, c1984,
— id: 16, year: 1984, vol: , page: , stat: ,

Intralesional administration of large doses of human leukocyte interferon for the treatment of condylomata acuminata
Geffen JR; Klein RJ; Friedman-Kien AE
1984 Oct;150(4):612-615, Journal of infectious diseases
— id: 14790, year: 1984, vol: 150, page: 612, stat: Journal Article,

Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia
Klein RJ; Friedman-Kien AE
1984 Nov;83(5):344-346, Journal of investigative dermatology
The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia
— id: 14789, year: 1984, vol: 83, page: 344, stat: Journal Article,

Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1
Klein RJ; Friedman-Kien AE; Kaley L; Brady E
1984 Jul;26(1):65-68, Antimicrobial agents & chemotherapy
The effects of topical application of phosphonoacetic acid on the colonization of mouse trigeminal ganglia by herpes simplex virus type 1 were examined. The results showed that the extent of colonization of ganglia by virus is related to the time elapsed between virus inoculation and application of this agent. In most cases, treatment started up to 12 h after inoculation prevented invasion of ganglia by virus. When started up to 24 h after inoculation, treatment reduced and stabilized the amount of virus detectable in trigeminal ganglia during the acute phase of the ganglionic infection. Treatments started 24 h after virus inoculation had little influence on total virus accumulations in trigeminal ganglia. The data also indicate that virus titers in specimens of inoculated and treated skin sites are less affected by topical phosphonoacetic acid treatment than virus titers in ganglia. The experiments may represent a model system for testing effects of other antiviral compounds on colonization of ganglia by virus and may provide some clues regarding the pathogenic mechanism of herpes simplex virus infections
— id: 14792, year: 1984, vol: 26, page: 65, stat: Journal Article,

Protection against establishment of latent infections in mice immunized with a non-pathogenic herpes simplex virus mutant and reinfected with the pathogenic parental strain
Klein RJ; Kaley LA; Friedman-Kien AE
1984 Sep;2(3):219-223, Vaccine
Immunization of hairless mice with a TK-, ACVr, non-pathogenic herpes simplex virus (HSV) type 1 mutant protected the mice against reinfection with lethal doses of the parental pathogenic HSV strain. The protection conferred by the mutant against the establishment of latency after reinfection with the parental strain was dependent on the site of reinfection; after reinfection at the same site, only 2% of mice became latently infected, compared to 32% after reinfection at a distant site. When inoculation with the mutant was done at two different sites, single reinfections at any site led to the establishment of latency in 4% of the mice. The mutant by itself was almost completely latency-negative: only 4.5% of the mice developed latency in trigeminal ganglia and 2.3% in the spinal ganglia. The rate of mutant-induced latent infections is partly related to the dose of the virus; however, lower doses of the mutant may not colonize the ganglia, and therefore fail to protect against challenge infections
— id: 14791, year: 1984, vol: 2, page: 219, stat: Journal Article,

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine
Laubenstein LJ; Krigel RL; Odajnyk CM; Hymes KB; Friedman-Kien A; Wernz JC; Muggia FM
1984 Oct;2(10):1115-1120, Journal of clinical oncology
An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome
— id: 15701, year: 1984, vol: 2, page: 1115, stat: Journal Article,

A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo
Luby JP; Gnann JW Jr; Alexander WJ; Hatcher VA; Friedman-Kien AE; Klein RJ; Keyserling H; Nahmias A; Mills J; Schachter J; et al
1984 Jul;150(1):1-6, Journal of infectious diseases
Patient-initiated treatment of recurrent genital herpes with topical acyclovir was compared with placebo treatment in a multicenter collaborative trial involving 309 patients. No differences were found between the group using acyclovir and that using placebo except that herpes simplex virus was excreted for a shorter period by women using acyclovir. This difference was partially accounted for by the fact that some patients whose viral culture results subsequently proved positive began to use their medication before lesions formed. One hundred patients initially applied ointment within 6 hr of onset of the prodrome and before actual lesion formation. Separate analysis of this group showed a diminished duration of viral excretion by women using acyclovir and a reduced interval between lesion formation and total crusting in men using acyclovir, but both differences were of only borderline significance (.05 less than P less than .10). The results indicate that patient-initiated therapy with topical acyclovir in polyethylene glycol exerts no clinically significant effect on recurrent genital herpes
— id: 14793, year: 1984, vol: 150, page: 1, stat: Journal Article,

Kaposi\'s sarcoma in homosexual men. A seroepidemiologic case-control study
Marmor M; Friedman-Kien AE; Zolla-Pazner S; Stahl RE; Rubinstein P; Laubenstein L; William DC; Klein RJ; Spigland I
1984 Jun;100(6):809-815, Annals of internal medicine
The cases of 20 male homosexuals with Kaposi\'s sarcoma and the acquired immunodeficiency syndrome were compared with those of 40 age- and race-matched male homosexual controls. Patients with Kaposi\'s sarcoma had lower OKT4/OKT8 (T-helper/T-suppressor) ratios than controls, due to smaller numbers of OKT4 cells. Serum IgG concentrations and antibody titers to cytomegalovirus in patients exceeded those in controls, but patients had lower antibody titers to Epstein-Barr virus. Logistic regression analysis comparing patients with controls showed significant relative risks for Kaposi\'s sarcoma associated with the number of partners per month in receptive anal-genital intercourse, occasions per month of \' fisting ,\' and cytomegalovirus antibody titers. Cytomegalovirus titers also were inversely correlated with OKT4 cell concentrations in the control group. Significantly greater OKT4 cell concentrations were found at diagnosis in HLA-DR5-positive patients than in HLA-DR5-negative patients. Patients who have HLA-DR5 may express disease at lesser degrees of immunodeficiency than HLA-DR5-negative patients.
— id: 9126, year: 1984, vol: 100, page: 809, stat: Journal Article,

Epidemic Kaposi's sarcoma: a manifestation of the acquired immune deficiency syndrome
Friedman-Kien AE
1983 Aug;9(8):637-640, Journal of dermatologic surgery & oncology
— id: 14796, year: 1983, vol: 9, page: 637, stat: Journal Article,

EPIDEMIC KAPOSIS SARCOMA - A MANIFESTATION OF THE ACQUIRED IMMUNE-DEFICIENCY SYNDROME (AIDS)
FRIEDMANKIEN, AE
1983 ;9(8):660-660, Journal of dermatologic surgery & oncology
— id: 40646, year: 1983, vol: 9, page: 660, stat: Journal Article,

National case-control study of Kaposi\'s sarcoma and Pneumocystis carinii pneumonia in homosexual men: Part 1. Epidemiologic results
Jaffe HW; Choi K; Thomas PA; Haverkos HW; Auerbach DM; Guinan ME; Rogers MF; Spira TJ; Darrow WW; Kramer MA; Friedman SM; Monroe JM; Friedman-Kien AE; Laubenstein LJ; Marmor M; Safai B; Dritz SK; Crispi SJ; Fannin SL; Orkwis JP; Kelter A; Rushing WR; Thacker SB; Curran JW
1983 Aug;99(2):145-151, Annals of internal medicine
To identify risk factors for the occurrence of Kaposi\'s sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposi\'s sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposi\'s sarcoma and pneumocystis pneumonia.
— id: 9131, year: 1983, vol: 99, page: 145, stat: Journal Article,

Effect of discontinuous acyclovir treatment on in vitro reactivation of herpes simplex virus from latently infected trigeminal ganglia
Klein RJ; Friedman-Kien AE; DeStefano E
1983 Jul;24(1):129-131, Antimicrobial agents & chemotherapy
Exposing explant cultures of latently infected mouse trigeminal ganglia alternately to acyclovir-containing and drug-free medium led to a significant decrease in the proportion of ganglia containing reactivatable herpes simplex virus. The loss of virus from the explant cultures was not caused by thermal inactivation during prolonged incubation periods. The efficiency of virus elimination may depend on the frequency and duration of the alternating treatment and on the number of latently infected neurons in the ganglia
— id: 14797, year: 1983, vol: 24, page: 129, stat: Journal Article,

Immunologic and immunogenetic findings in patients with epidemic Kaposi's sarcoma
Rubinstein P; Rothman WM; Friedman-Kien A
1983 ;32:87-98, Antibiotics & chemotherapy
— id: 49669, year: 1983, vol: 32, page: 87, stat: Journal Article,

AIDS: a medical conundrum
Stahl RE; Friedman-Kien A; Zolla-Pazner S
1983 Dec;10(6):550-558, Journal of cutaneous pathology
— id: 9314, year: 1983, vol: 10, page: 550, stat: Journal Article,

Acid-labile human leukocyte interferon in homosexual men with Kaposi's sarcoma and lymphadenopathy
DeStefano E; Friedman RM; Friedman-Kien AE; Goedert JJ; Henriksen D; Preble OT; Sonnabend JA; Vilcek J
1982 Oct;146(4):451-459, Journal of infectious diseases
Some immunologic parameters in homosexual patients with Kaposi's sarcoma (KS) or unexplained lymphadenopathy resemble findings in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Many patients with SLE have an unusual acid-labile form of human leukocyte interferon (HuIFN-alpha) in their serum. Sera from 91 homosexual men were tested for the presence of HuIFN. Of 27 patients with KS, 17 had significant titers of HuIFN in their serum. Ten of 35 patients with lymphadenopathy and three of four patients with other clinical symptoms also had circulating HuIFN. In contrast, only two of 25 apparently healthy subjects had serum HuIFN. All 32 samples of HuIFN had antiviral activity on bovine cells, a characteristic of HuIFN-alpha, and all of 14 representative samples tested were neutralized by antibody to HuIFN-alpha. In addition, the HuIFN-alpha in six of eight representative patients was inactivated at pH 2 and therefore appears to be similar to the HuIFN-alpha found in patients with SLE. These findings suggest that an autoimmune disorder may underly lymphadenopathy and KS in homosexual men
— id: 14798, year: 1982, vol: 146, page: 451, stat: Journal Article,

Disseminated Kaposi\'s sarcoma in homosexual men
Friedman-Kien AE; Laubenstein LJ; Rubinstein P; Buimovici-Klein E; Marmor M; Stahl R; Spigland I; Kim KS; Zolla-Pazner S
1982 Jun;96(6 Pt 1):693-700, Annals of internal medicine
Nineteen cases from an epidemic of disseminated Kaposi\'s sarcoma in homosexual men were studied by clinical, virologic, immunologic, and genetic methods. The patients were all male homosexuals ranging in age from 29 to 52 years, with histories of multiple sexually transmitted diseases and exposure to both prescription and recreational drugs. Sites of disease included skin (16 of 19 patients), lymph nodes (13 patients), gastrointestinal tract (12 patients), spleen (three patients), and lung (one patient). Most patients had elevated levels of serum immunoglobins, positive antibody titers to hepatitis A and B virus, cytomegalovirus and Epstein-Barr virus, and impairment of cell-mediated immunologic reactions. The frequency of HLA-DR5 in these patients was significantly elevated. Two of the 19 patients died. Although the precise cause of this epidemic is unknown, it is likely that a genetic predisposition, an acquired immunoregulatory defect, and one or more infectious agents and drugs may be involved.
— id: 9135, year: 1982, vol: 96, page: 693, stat: Journal Article,

KAPOSIS SARCOMA AND HEPATITIS-B VACCINE - REPLY
Friedmankein, AE; Stevens, CE
1982 ;97(5):787-787, Annals of internal medicine
— id: 30346, year: 1982, vol: 97, page: 787, stat: Journal Article,

Arabinosyladenine monophosphate in genital herpes: a double-blind, placebo-controlled study
Hatcher VA; Friedman-Kien AE; Marcus EL; Klein RJ
1982 Oct;2(5):283-290, Antiviral research
A double-blind, placebo-controlled study was performed in 55 male patients with recurrent herpes simplex genitalis. The 29 patients who received topical arabinosyladenine monophosphate (ara-AMP) showed no significant difference in viral shedding, duration of pain, healing time or development of new lesions as compared to 26 placebo-treated patients. Ara-AMP was well-tolerated when topically applied. Serum neutralizing antibody titers did not change significantly during the acute and convalescent periods of the patient's recurrent HSG attacks. We conclude that ara-AMP, when applied topically as a 10% gel five times a day within 24 h of onset of recurrent HSG, does not influence the virologic and clinical evolution of the recurrent episode
— id: 14799, year: 1982, vol: 2, page: 283, stat: Journal Article,

Failure of 2-deoxy-D-glucose in the treatment of experimental cutaneous and genital infections due to herpes simplex virus
Kern ER; Glasgow LA; Klein RJ; Friedman-Kien AE
1982 Aug;146(2):159-166, Journal of infectious diseases
The effectiveness of 2-deoxy-D-glucose (2-DG) was evaluated in the treatment of cutaneous infections with herpes simplex virus type 1 (HSV-1) in mice and genital infections with HSV type 2 (HSV-2) in mice and guinea pigs. Groups of mice were inoculated in the lumbosacral or orofacial area with HSV-1 and treated topically three times a day with 0.2% or 0.5% 2-DG solution beginning 3 hr after inoculation. No effect on skin lesions, mortality, or latency was observed. Mice were inoculated intravaginally with HSV-2 and treated intravaginally three times a day with 0.2%-5% 2-DG in solution or suspended in miconazole nitrate cream beginning 6 hr, 24 hr, or 48 hr after inoculation. Replication of HSV-2 in the vagina and final mortality were not affected. Guinea pigs were infected intravaginally with HSV-2 and treated both intravaginally and topically on the external genitalia four times a day with 1% or 5% 2-DG in miconazole nitrate cream. Treatment initiated just prior to development of lesions (on day 3 after inoculation) did not alter vaginal virus replication, lesion development and severity, or virus titers in lesions
— id: 14800, year: 1982, vol: 146, page: 159, stat: Journal Article,

Risk factors for Kaposi\'s sarcoma in homosexual men
Marmor M; Friedman-Kien AE; Laubenstein L; Byrum RD; William DC; D'onofrio S; Dubin N
1982 May 15;1(8281):1083-1087, Lancet
An investigation of 20 homosexual men with histologically confirmed Kaposi\'s sarcoma and 40 controls revealed significant associations between Kaposi\'s sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposi\'s sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).
— id: 9136, year: 1982, vol: 1, page: 1083, stat: Journal Article,

Immunologic abnormalities in homosexual men. Relationship to Kaposi\'s sarcoma
Stahl RE; Friedman-Kien A; Dubin R; Marmor M; Zolla-Pazner S
1982 Aug;73(2):171-178, American journal of medicine
Studies were performed to define the immunologic status of various groups of homosexual men including homosexual men with Kaposi\'s sarcoma, healthy homosexual men who were of similar ages to the homosexual patients with Kaposi\'s sarcoma and homosexual men with hyperplastic lymphadenopathy. Heterosexual men with Kaposi\'s sarcoma were also studied. Immunologic parameters which were examined included serum immunoglobulin levels, enumeration of B cells, T cells, and T-cell subsets, and quantitation of lymphocyte responsive to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Significant immunologic abnormalities were observed in all three groups of homosexuals studied. These were most severe in the homosexuals with Kaposi\'s sarcoma, somewhat less severe in homosexual men with lymphadenopathy, and least marked but still significant in healthy homosexual men. Heterosexual men with Kaposi\'s sarcoma displayed essentially normal immunologic profiles. The possible etiologic factors underlying the immunologic abnormalities in the male homosexual population studied and the role of an altered immune system in the development of and the fulminant course of Kaposi\'s sarcoma in these patients are discussed.
— id: 9134, year: 1982, vol: 73, page: 171, stat: Journal Article,

IMMUNE ABNORMALITIES IN HOMOSEXUAL MEN WITH KAPOSIS SARCOMA
Stahl, R; Friedmankien, A; Dubin, R; Marmor, M; Zollapazner, S
1982 ;41(4):955-955, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 30458, year: 1982, vol: 41, page: 955, stat: Journal Article,

THE HLA SYSTEM IN PATIENTS WITH KAPOSI SARCOMA
Walker, M; Rubinstein, P; Carrier, C; Carpenter, C; Krassner, J; Friedmankien, A
1982 ;5(2):178-178, Human immunology
— id: 30371, year: 1982, vol: 5, page: 178, stat: Journal Article,

Kaposi's sarcoma and pneumocystis pneumonia among homosexual men--New York City and California
Friedman-Kien A; Laubenstein L; Marmor M; et al.
1981 ;30:305-308, MMWR
— id: 9333, year: 1981, vol: 30, page: 305, stat: Journal Article,

Disseminated Kaposi's sarcoma syndrome in young homosexual men
Friedman-Kien AE
1981 Oct;5(4):468-471, Journal of the American Academy of Dermatology
— id: 14802, year: 1981, vol: 5, page: 468, stat: Journal Article,

PERIUNGUAL WARTS
FRIEDMANKIEN, AE
1981 ;246(15):1729-1729, JAMA
— id: 40191, year: 1981, vol: 246, page: 1729, stat: Journal Article,

A preliminary communication on extensively disseminated Kaposi's sarcoma in young homosexual men
Gottlieb GJ; Ragaz A; Vogel JV; Friedman-Kien A; Rywlin AM; Weiner EA; Ackerman AB
1981 Summer;3(2):111-114, American journal of dermatopathology
— id: 49670, year: 1981, vol: 3, page: 111, stat: Journal Article,

Effect of acyclovir on latent herpes simplex virus infections in trigeminal ganglia of mice
Klein RJ; DeStefano E; Friedman-Kien AE; Brady E
1981 May;19(5):937-939, Antimicrobial agents & chemotherapy
— id: 14803, year: 1981, vol: 19, page: 937, stat: Journal Article,

Pathogenesis of experimental skin infections induced by drug-resistant herpes simplex virus mutants
Klein RJ; Friedman-Kien AE; DeStefano E
1981 Dec;34(3):693-701, Infection & immunity
— id: 14801, year: 1981, vol: 34, page: 693, stat: Journal Article,

Experimental skin infection with an acyclovir resistant herpes simplex virus mutant: response to antiviral treatment and protection against reinfection
Klein RJ; DeStefano E; Brady E; Friedman-Kien AE
1980 ;65(3-4):237-246, Archives of virology
Skin infections induced in hairless mice with an Acyclovir resistant herpes simplex virus (HSV) mutant were not followed by the death of the animals, and the survivors had no evidence of latent infections in their sensory ganglia. However, mutant virus was detected in the ganglia during the acute phase of the infection. Mice inoculated with the mutant were fully protected against the fatal outcome of the infection when subsequently challenged with the relatively pathogenic parental virus. In addition the frequency of latent infections established after challenge was significantly reduced. Phosphonoacetic acid treatment of the primary mutant-induced infection abolished the protection against reinfection with parental virus. Acyclovir treatment of the primary infection with the mutant virus did not affect the protection against reinfection with parental virus. The results indicate that drug-resistant, latency-negative, HSV mutants are a promising starting point for the development of an attenuated HSV vaccine
— id: 14804, year: 1980, vol: 65, page: 237, stat: Journal Article,

Latent infections of sensory ganglia as influenced by phosphonoformate treatment of herpes simplex virus-induced skin infections in hairless mice
Klein RJ; DeStefano E; Brady E; Friedman-Kien AE
1979 Sep;16(3):266-270, Antimicrobial agents & chemotherapy
Topical treatment with 3% phosphonoformate of herpes simplex virus type 1 (HSV)-induced skin infections of hairless mice reduced the severity of skin lesions when the treatment was initiated 3 h after virus inoculation in the lumbosacral area or 3 and 24 h after inoculation in the orofacial area. The mortality was significantly reduced in lumbosacral-infected mice and was completely prevented in orofacial-infected mice when the treatment was initiated with a delay of 24 h after virus inoculation. However, phosphonoformate did not prevent the establishment of latent herpes simplex virus type 1 infections in the spinal and trigeminal ganglia, even when treatment was initiated as early as 3 h after infection
— id: 14805, year: 1979, vol: 16, page: 266, stat: Journal Article,

Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine
Klein RJ; Friedman-Kien AE; DeStefano E
1979 May;15(5):723-729, Antimicrobial agents & chemotherapy
— id: 14806, year: 1979, vol: 15, page: 723, stat: Journal Article,

Latent herpes simplex virus in ganglia of mice after primary infection and reinoculation at a distant site
Klein RJ; Friedman-Kien AE; Brady E
1978 ;57(2):161-166, Archives of virology
Herpes simplex virus (HSV)-infected hairless mice with evidence of latent infection in spinal ganglia did not develop latent HSV infections in trigeminal ganglia upon reinfection in the oro-facial area. HSV-infected and PAA-treated mice without evidence of latent HSV infection in spinal ganglia were resistant to reinfection in the lumbar region, but not to that performed in the oro-facial area
— id: 14808, year: 1978, vol: 57, page: 161, stat: Journal Article,

Orofacial herpes simplex virus infection in hairless mice: latent virus in trigeminal ganglia after topical antiviral treatment
Klein RJ; Friedman-Kien AE; Yellin PB
1978 Apr;20(1):130-135, Infection & immunity
— id: 14807, year: 1978, vol: 20, page: 130, stat: Journal Article,

DETECTION OF HUMAN-ANTIBODIES TO NEISSERIA-GONORRHOEAE ENVELOPE ANTIGENS BY CROSSED IMMUNOELECTROPHORESIS
SALTON, MRJ; FRIEDMANKIEN, AE; URBAN, C
1978 ;4(6):307-310, FEMS microbiology letters
— id: 40030, year: 1978, vol: 4, page: 307, stat: Journal Article,

Latent herpes simplex virus infections in sensory ganglia of mice after topical treatment with adenine arabinoside and adenine arabinoside monophosphate
Klein RJ; Friedman-Kien AE
1977 Nov;12(5):577-581, Antimicrobial agents & chemotherapy
— id: 14809, year: 1977, vol: 12, page: 577, stat: Journal Article,

Immune response and latent infection after topical treatment of herpes simplex virus infection in hairless mice
Klein RJ; Friedman-Kien AE; Fondak AA; Buimovici-Klein E
1977 Jun;16(3):842-848, Infection & immunity
Treatment of herpes simplex virus (HSV)-infected hairless mice with a 2% phosphonoacetic acid (PAA) ointment prevented the appearance of virus-induced skin lesions and subsequent central nervous system (CNS) involvement. Treatment started 24 h after infection significantly reduced the intensity of the skin lesions and also prevented CNS involvement. After four to six applications of PAA ointment, a moderate skin erythemia developed, followed by scaling and complete healing 7 days after cessation of the treatment. Mice treated early after HSV infection had low or undetectable levels of virus-specific antibodies but were completely resistant to reinfection. Early treatment prevented the development of a latent ganglionic infection, but treatment initiated 24 h after infection could not prevent the establishment of the latent infection. PAA-treated and HSV-infected mice with nondetectable levels of antibodies did not develop, with a single exception, a latent ganglionic infection unpon reinfection. The cell-mediated immune response determined by levels of [14C]thymidine incorporation in Ficoll-Hypaque-purified spleen lymphocytes cultures was low in PAA-treated mice; it increased slightly after challenge infection but was strong in mice that proved to harbor a latent HSV infection in the ganglia
— id: 14810, year: 1977, vol: 16, page: 842, stat: Journal Article,

The absence of human papilloma viral DNA sequences in condylomata acuminata
Delap RD; Friedman-klen A; Rush MG
1976 Oct 1;74(1):268-272, Virology
— id: 17456, year: 1976, vol: 74, page: 268, stat: Journal Article,

Phosphonoacetic acid treatment of shope fibroma and vaccinia virus skin infections in rabbits
Friedman-Kien AE; Fondak AA; Klein RJ
1976 Feb;66(02):99-102, Journal of investigative dermatology
The antiviral efficacy of phosphonoacetic acid (PAA) was studied in localized skin lesions of rabbits produced by the intradermal inoculation of vaccinia virus (VV) and of Shope fibroma virus (SFV). Systemic administration of PAA by intraperitoneal injections had no significant effect on the pustular lesions induced by VV or on the benign skin tumors caused by SFV. A complete suppression of the appearance of VV-induced pustular lesions was achieved by 2% PAA ointment applied twice daily for 4 days, starting 24 hr after virus inoculation. A significant effect against SFV-induced tumors was obtained by PAA ointment applied beginning either 24 or 72 hr after virus inoculation. A complete suppression of SFV-induced tumors was observed when a dose of 10 mg PAA was injected intralesionally once daily for 5 days, beginning treatment 24 hr after virus inoculation. A significant reduction of the intensity of the tumors was seen following the same treatment schedule but with a delay of 72 hr after virus inoculation or by reducing the length of treatment to 3 days or with a dose of 1 mg injected intradermally daily for 5 days. After the healing of the lesions, PAA-treated rabbits were resistant to reinfections to the same extent as those in which spontaneous healing had occurred
— id: 14812, year: 1976, vol: 66, page: 99, stat: Journal Article,

Immunoglobulin content and antibody activity in an artificial body cavity
Klein RJ; Teodorescu M; Friedman-Kien AE; Dray S; Brady E
1976 ;5(7-8):603-618, Immunological communications
Artificial body cavities (ABC) were created by the insertion of hollow polyethylene balls in the subcutaneous tissue of rabbits. After two months no inflammatory reaction could be detected, the ABC was enveloped by a membranous structure, and the cavity contained about 20 ml of fluid. The protein concentration was about 3 times, and the IgG about 8 times, lower in the ABC fluids than in the corresponding serum. At the same time the antibody titers against sheep red blood cells (SRBC), human IgG and herpes simplex virus type 1 (HSV) were about 20 200 times lower than in the corresponding serum samples. The IgG molecules appeared to be undamaged as shown by the presence of various allotypes and by the elution pattern from G-200 column. Testing the protective activity of ABC fluids and of serum against HSV infection showed that ABC fluids had no protective activity. The experiments suggest that the membranous structure selected among classes of Ig and probably among other serum proteins. In addition, the IgG molecules with antibody activity against various inoculated antigens were selectively excluded to penetrate in the ABC. The ABC might be considered analogous to virtual cavities of the body surrounded by membranes and possibly to the extravascular compartment
— id: 14813, year: 1976, vol: 5, page: 603, stat: Journal Article,

Antigenic analysis of Neisseria gonorrhoeae by crossed immunoelectrophoresis
Smyth CJ; Friedman-Kien AE; Salton MR
1976 Apr;13(4):1273-1288, Infection & immunity
Crossed immunoelectrophoresis was used to study two complex antigenic preparations from Neisseria gonorrhoeae, one of cytoplasmic origin and the other derived by Triton X-100 extraction of isolated washed gonococcal envelopes, with the aim of developing suitable reference antigen-antibody systems that could be subsequently used to investigate the immune response to gonococcal infection and to monitor envelope preparations for cytoplasmic contamination. A number of parameters were investigated to optimized and standardize antigen preparation, e.g., harvesting and washing of gonococci, methods of bacterial disruption, and washing of envelopes. The effects of Triton X-100 concentration, initial total envelope protein concentration, and the composition, pH, and concentration of buffer on cell envelope extractability were studied to obviate the need to concentrate material before use in crossed immunoelectrophoresis. The electroendoosmotic properties of agarose were a major determining factor in resolving envelope antigens. From 25 to 30 immunoprecipitates were revealed in the envelope antigen-antibody system; 75 to 80 were revealed in the cytoplasmic sytem. Envelope immunoprecipitates with reduced nicotinamide adenine dinucleotide and lactate dehydrogenase activities were identified. Crossed immunoelectrophoresis with intermediate gels revealed the presence of antibodies in a preimmune rabbit antiserum pool to a distinctive fact-moving component in both the envelope and cytoplasmic antigen preparations. The intermediate gel technique also demonstrated that extensive washing of envelope preparations with buffer did not remove cytoplasmic ontamination completely. The method provides a much more sensitive means of monitoring the purity of envelope fractions than the use of single enzy,e markers as indexes of such contamination. The use of rabbit antisera raised to formolized gonococci in intermediate gels indicated that both reference antigen-antibody systems were of potential use in screening immune responses to N. gonorrhoeae
— id: 14811, year: 1976, vol: 13, page: 1273, stat: Journal Article,

Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice
Klein RJ; Friedman-Kien AE
1975 Mar;7(3):289-293, Antimicrobial agents & chemotherapy
— id: 14814, year: 1975, vol: 7, page: 289, stat: Journal Article,

Herpes simplex virus skin infection in hairless mice: treatment with antiviral compounds
Klein RJ; Friedman-Kien AE; Brady E
1974 Mar;5(3):318-322, Antimicrobial agents & chemotherapy
— id: 14815, year: 1974, vol: 5, page: 318, stat: Journal Article,

Treatment of poxvirus infections in rabbits with 9-beta-D-arabinofuranosyladenine
Klein, R J; Friedman-Kien, A E; Brady, E
1974 Apr;5(4):409-412, Antimicrobial agents & chemotherapy
The antiviral efficacy of 9-beta-d-arabinofuranosyladenine (ara-A) was evaluated in localized lesions produced by the intradermal inoculation of rabbits with vaccinia virus (VV) and rabbit Shope fibroma virus (SFV). Ara-A administered intraperitoneally suppressed or significantly reduced the cutaneous pustular lesions produced by VV as well as the benign skin tumors caused by the SFV. With a daily dose of 300 mg/kg given for 5 days starting at the time of infection, or with 600 mg/kg daily starting 3 days after inoculation, we were able to suppress completely the formation of tumors induced by the SFV. The appearance of pustular lesions induced by VV was completely suppressed by a dose of 600 mg of ara-A per kg given for 3 days when the treatment was initiated at the time of infection, but a significant reduction in the number of pustular lesions was obtained with a single dose of 600 mg/kg, or with five doses of 300 mg/kg starting 24 h after inoculation. No toxic effect of ara-A was noted in the treated rabbits
— id: 106952, year: 1974, vol: 5, page: 409, stat: Journal Article,

Effect of rabbit interferon on immune responses
Thorbecke GJ; Friedman-Kien AE; Vilcek J
1974 May;12(2):290-295, Cellular immunology
— id: 8948, year: 1974, vol: 12, page: 290, stat: Journal Article,

Tetracycline therapy in acne vulgaris
Friedman-Kien A; Shalita AR; Baer RL
1972 Apr;105(4):608-608, Archives of dermatology
— id: 16147, year: 1972, vol: 105, page: 608, stat: Journal Article,

Suppression of the intracellular growth of Shigella flexneri in cell cultures by interferon preparations and polyinosinic-polycytidylic acid
Gober LL; Friedman-Kien AE; Havell EA; Vilcek J
1972 Mar;5(3):370-376, Infection & immunity
— id: 14816, year: 1972, vol: 5, page: 370, stat: Journal Article,

Morphogenesis of rabbit fibroma virus. Correlation with pathogenesis of the skin lesion
Prose, P H; Friedman-Kien, A E; Vilcek, J
1971 Sep;64(3):467-478, American journal of pathology
— id: 14817, year: 1971, vol: 64, page: 467, stat: Journal Article,

The Uptake of a Labeled Double-Stranded Polynucleotide by Cultured Rabbit Kidney Cells: An Electron Microscopic Study
Prose PH; Friedman-Kien A; Vilcek J
1970 Jul 1;56(1):99-109, Journal of general physiology
Polyribocytidylate-(3)H-polyriboinosinate (rC-(3)H:rI) enters cultured rabbit kidney cells from the surrounding medium within (1/2) hr after exposure. Grains are found in the cytoplasm, nucleus, and nucleolus. At 2 hr, grains are localized predominantly over the nucleolar regions. Subsequently, the grains in the nucleus become dispersed. A specific receptor site for the initiation of interferon production was not revealed
— id: 106953, year: 1970, vol: 56, page: 99, stat: Journal Article,

Mollucum contagiosum virus in adult human skin cultures. An electron microscopic study
Prose PH; Friedman-Kien AE; Vilcek J
1969 Jun;55(3):349-366, American journal of pathology
— id: 14818, year: 1969, vol: 55, page: 349, stat: Journal Article,

The molluscum contagiosum virus in chick embryo cell cultures: an electron microscopic study
Robinson HJ Jr; Prose PH; Friedman-Kien AE; Neistein S; Vilcek J
1969 Jan;52(1):51-56, Journal of investigative dermatology
— id: 14819, year: 1969, vol: 52, page: 51, stat: Journal Article,

Induction of interferon synthesis by synthetic double-stranded polynucleotides
Vilcek J; Ng MH; Friedman-Kien AE; Krawciw T
1968 Jun;2(6):648-650, Journal of virology
— id: 14820, year: 1968, vol: 2, page: 648, stat: Journal Article,

Induction of interference and interferon synthesis by non-replicating molluscum contagiosum virus
Friedman-Kien AE; Vilcek J
1967 Dec;99(6):1092-1098, Journal of immunology
— id: 14822, year: 1967, vol: 99, page: 1092, stat: Journal Article,

Ultrastructural studies of organ cultures of adult human skin. In vitro growth and keratinization of epidermal cells
Prose PH; Friedman-Kien AE; Neistein S
1967 Dec;17(6):693-716, Laboratory investigation
— id: 14821, year: 1967, vol: 17, page: 693, stat: Journal Article,

Culture of adult human skin: in vitro growth and keratinization of epidermal cells
Friedman-Kien, A E; Morrill, S; Prose, P H; Liebhaber, H
1966 Dec 31;212(5070):1583-1584, Nature
— id: 114847, year: 1966, vol: 212, page: 1583, stat: Journal Article,

Angioid streaks in Ehlers-Danlos syndrome
Green WR; Friedman-Kien A; Banfield WG
1966 Aug;76(2):197-204, Archives of ophthalmology
— id: 49671, year: 1966, vol: 76, page: 197, stat: Journal Article,

HAIR GROWTH CYCLE IN SUBCUTANEOUS IMPLANTS OF SKIN
FRIEDMAN-KIEN AE; DAWE CJ; VANSCOTT EJ
1964 Dec;43:445-450, Journal of investigative dermatology
— id: 49674, year: 1964, vol: 43, page: 445, stat: Journal Article,

LIFE AND DEATH IN THE LAW. II
PARKER JC; FRIEDMAN-KIEN AE; LEVIN S; BARTTER FC
1964 Dec 3;271:1206-1207, New England journal of medicine
— id: 49672, year: 1964, vol: 271, page: 1206, stat: Journal Article,

PSEUDOXANTHOMA ELASTICUM AND HYPERTENSION
PARKER JC; FRIEDMAN-KIEN AE; LEVIN S; BARTTER FC
1964 Dec 3;271:1204-1206, New England journal of medicine
— id: 49673, year: 1964, vol: 271, page: 1204, stat: Journal Article,

Milker's nodules: isolation of a poxvirus from a human case
FRIEDMAN-KIEN AE; ROWE WP; BANFIELD WG
1963 Jun 21;140:1335-1336, Science
— id: 49675, year: 1963, vol: 140, page: 1335, stat: Journal Article,

Double gall bladders in man: a case report
FRIEDMAN-KIEN AE
1960 Apr;32:353-360, Yale journal of biology & medicine
— id: 49676, year: 1960, vol: 32, page: 353, stat: Journal Article,