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Biomedical subjects

M S Hirsch

Publications and source records attributed to M S Hirsch.

At least 109 records · Page 6Linked to original sources
PubMed1990

Seroprevalence of human T cell leukemia viruses in selected populations of homosexual men.

This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests.

Blotting, Western↗
PubMed1990

Detection of HIV-1 DNA in crude cell lysates of peripheral blood mononuclear cells by the polymerase chain reaction and nonradioactive oligonucleotide probes.

The aim of this study was to detect HIV-1 proviral DNA in lysates of peripheral blood mononuclear cells (PBMCs) by the polymerase chain reaction (PCR) and hybridization with a nonradioactive probe. PBMCs were lysed in 1% Triton X-100. PCR was then carried out using primers complementary to a conserved region of the HIV-1 pol gene. Bracket and nested amplification protocols were used. Products were identified by dot-blot hybridization or agarose gel electrophoresis and Southern hybridization, using an alkaline phosphatase-linked oligonucleotide probe specific for amplified sequences. Colorimetric and chemiluminescent substrates were used. HIV-1 DNA was detected in PBMCs of 57/59 HIV-1-seropositive individuals, 8 of which were positive only following the use of nested primers. Of 12 seropositive samples that were negative by other HIV-1 diagnostic tests (PBMC coculture and serum p24 antigen detection), 11 were positive by PCR. PCR using PBMC lysates is a very sensitive method of detecting HIV-1 proviral sequences. The use of nested primers appears to increase the sensitivity of the procedure.

Base Sequence↗
PubMed1989

Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group.

A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

Adolescent↗
PubMed1989

Dual infection of retina with human immunodeficiency virus type 1 and cytomegalovirus.

We examined retinal tissue from eight human immunodeficiency virus type 1 (HIV-1) seropositive patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex for evidence of dual infection with HIV-1 and cytomegalovirus. Culture demonstrated simultaneous infection with HIV-1 and cytomegalovirus in two of 13 retinal specimens. This was confirmed by both immunofluorescence and immunohistochemical staining. Moreover, coinfection of individual cells with cytomegalovirus and HIV-1 was observed by immunohistochemical staining. Infection of retina with cytomegalovirus or HIV-1 alone occurred in one and six of the 13 retinal specimens, respectively. HIV-1 antigens were present on scattered cells in all layers of the retina and on retinal vascular endothelium. HIV-1 was isolated from retinal tissue derived from eyes both with and without gross ocular lesions. Cytomegalovirus antigens were found in all layers of the retina, but not on vascular endothelial cells. The atypically rapid clinical progression of retinitis in one of the patients with dual HIV-1 and cytomegalovirus infection suggests the possibility that interactions between these two viruses may influence retinal disease in patients with AIDS.

AIDS-Related Complex↗
PubMed1989

Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by recombinant soluble CD4 and 3'-azido-3'-deoxythymidine.

A combination of antiviral therapies that target different sites in the human immunodeficiency virus type 1 (HIV-1) replicative cycle may be necessary for optimal treatment of HIV-1 infections. We evaluated the interactions of a soluble virus receptor (recombinant soluble CD4 or rsT4) and a reverse transcriptase inhibitor (azidothymidine, AZT) against HIV-1 replication in vitro. A variety of cell types was studied including peripheral blood mononuclear cells, a CD4-positive T-cell line, and a CD4-positive human monocyte cell line. The combination of rsT4 and AZT inhibited HIV-1 synergistically over a broad range of drug concentrations and multiplicities of infection in several different HIV-1 replication assays. Drug interactions were evaluated by the median-effect principle and the isobologram technique using a computer analysis. In all of the cell types tested, combinations of rsT4 and AZT were synergistic in vitro, without additive cytotoxicity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Absence of infectious HIV-1 in the urine of seropositive viremic subjects.

Urine and peripheral blood samples from 48 human immunodeficiency virus type 1 (HIV-1) seropositive individuals (38 adults and 10 children) were evaluated for the presence of HIV-1 by cocultivation and for HIV-1 p24 antigen by ELISA. None of the urine samples contained replication-competent HIV-1; 41 (85%) of 48 simultaneously obtained peripheral blood mononuclear cell samples contained replication-competent HIV-1. None of 26 urine samples available for analysis contained HIV-1 p24 antigen as determined by ELISA; 12 (34%) of 35 simultaneously obtained peripheral blood samples had detectable serum HIV-1 p24 antigen. Two of the individuals studied had HIV nephropathy, three had pyuria, and five had microscopic hematuria. Culture sensitivity was maximal when mycostatin (and not amphotericin B) was used as an antifungal agent. Our findings indicate that urine from HIV-1-seropositive individuals is unlikely to contain infectious HIV-1. This would imply that the risk of transmission of HIV-1 by urine is low to nonexistent.

Adult↗
PubMed1989

Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3'-azido-3'-deoxythymidine.

Castanospermine and 3'-azido-3'-deoxythymidine (zidovudine) were evaluated in combination against human immunodeficiency virus (HIV) replication in vitro. Castanospermine and 3'-azido-3'-deoxythymidine inhibited HIV type 1 synergistically in acutely infected H9 cells. In addition, they synergistically inhibited both HIV type 1 and HIV type 2 in peripheral blood mononuclear cells. There were no additional toxic effects of these agents in combination. Drug interactions were evaluated by the median-effect principle and the isobologram technique. Combinations of a glycosylation inhibitor, such as castanospermine, with 3'-azido-3'-deoxythymidine deserve consideration for HIV-related chemotherapeutic intervention.

Alkaloids↗
PubMed1989

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells.

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU-E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti-HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.

Bone Marrow↗
PubMed1988

Antiviral drug development for the treatment of human immunodeficiency virus infections. An overview.

During 1987, a new era in the approach to treatment of severe human immunodeficiency virus (HIV)-I infections was entered. The increased availability of zidovudine and its licensure in many countries have resulted in its widespread use. With these developments have come a multitude of new questions. How long will clinical benefit be sustained? Will zidovudine be useful in asymptomatic HIV carriers and in other HIV-related conditions? How can the diversion of zidovudine to unproven indications be averted so that properly controlled clinical trials are conducted? Can better treatment regimens be developed to enhance the therapeutic/toxic ratio of zidovudine? What are the proper roles of governments in assuring patient access to zidovudine? How should newer anti-HIV drugs be compared with zidovudine? Will combinations of zidovudine and other active agents be useful? To address many of these issues in the United States, the Federal Government has established an AIDS Clinical Trials Group (ACTG) program. Over 3,000 patients have been enrolled in AIDS Clinical Trials Group trials, which span the spectrum from asymptomatic to advanced HIV-I infections. In addition, drug development and screening programs have been established to evaluate new compounds and regimens. Although control of AIDS will be a long and arduous journey, an important beginning has been made.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals.

Characterization of the host immune response to human immunodeficiency virus type 1 (HIV-1) is critical to the rational design of an effective AIDS vaccine. In this study, cytotoxic T lymphocytes (CTL) specific for HIV-1 reverse transcriptase (RNA-dependent DNA polymerase) were found in blood samples from HIV-1-infected individuals. CTL targets were prepared by immortalizing B cells from ten seropositive and six seronegative individuals, and then infecting these cells with recombinant vaccinia viruses containing HIV-1 genes. CTL directed against autologous B lymphoblasts expressing HIV-1 reverse transcriptase were detected in fresh blood samples from eight HIV-1 seropositive subjects, but in no seronegative controls. The effector cells were identified as major histocompatibility complex-restricted CD3+CD8+ lymphocytes. Because the HIV-1 pol gene is highly conserved among different isolates and generates both humoral and cellular immune responses, it bears consideration for inclusion in a candidate AIDS vaccine.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV infection is blocked in vitro by recombinant soluble CD4.

The T-cell surface glycoprotein, CD4 (T4), acts as the cellular receptor for human immunodeficiency virus, type 1 (HIV-1), the first member of the family of viruses that cause acquired immunodeficiency syndrome. HIV recognition of CD4 is probably mediated through the virus envelope glycoprotein (gp120) as shown by co-immunoprecipitation of CD4 and gp120 (ref.5) and by experiments using recombinant gp120 as a binding probe. Here we demonstrate that recombinant soluble CD4(rsT4) purified from the conditioned medium of a stably transfected Chinese hamster ovary cell line is a potent inhibitor of both virus replication and virus-induced cell fusion (syncytium formation). These results suggest that rsT4 is sufficient to bind HIV, and that it represents a potential anti-viral therapy for HIV infection.

Animals↗