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Biomedical subjects

M S Hirsch

Publications and source records attributed to M S Hirsch.

At least 127 records · Page 7Linked to original sources
PubMed1988

Peripheral neuropathy in the acquired immunodeficiency syndrome.

The histopathological and immunopathological features of peripheral neuropathy were investigated in 21 patients with the acquired immunopathological syndrome (AIDS) or AIDS-related complex (ARC). Clinical syndromes observed in the 11 (52%) symptomatic patients included distal symmetrical polyneuropathy (DSPN) and chronic inflammatory demyelinative polyneuropathy (CIDP). Specimens from 19 of 20 patients (95%), both symptomatic and asymptomatic, had histopathological evidence of moderate or severe demyelination (79%), axonal degeneration (36%), and mononuclear cell inflammation (37%). Nerves from patients with CIDP and DSPN showed similar degrees of demyelination and axonal degeneration, but inflammation was more intense in CIDP. Immunohistochemical staining identified the majority of inflammatory cells as T lymphocytes or macrophages, with a predominance of CD8+ cytotoxic/suppressor cells. Diffuse immunostaining for human leukocyte antigen (HLA)-DR was present on endothelial cells, mononuclear inflammatory cells, and Schwann cells, and variable patchy immunostaining for HLA-DR was present on nerve fibers. Control nerve specimens showed staining for HLA-DR limited to endothelial, and a few mononuclear cells. The patterns of immunostaining were similar for AIDS and ARC patients. Human immunodeficiency virus (HIV) was cultured from peripheral nerve in 3 patients, but HIV antigen was not detected by immunohistochemical staining of 8 specimens. The findings implicate HIV infection in nerve, with T cell- and macrophage-mediated tissue destruction as the pathogenetic mechanism of the AIDS/ARC neuropathy.

AIDS-Related Complex↗
PubMed1988

Enhanced in vitro inhibition of HIV-1 replication by 3'-fluoro-3'-deoxythymidine compared to several other nucleoside analogs.

Nucleoside analogs were synthesized and tested for anti-HIV-1 activity in two in vitro test systems using MT-4 cells and peripheral blood lymphocytes. Cytotoxicity was assessed in both assays and additionally in several human lymphoblastoid cell lines. One analog, 3'-fluoro-3'-deoxythymidine, exhibited higher antiviral potency and slightly higher cytotoxicity than 3'-azido-3'-deoxythymidine. Analogs showing lower cytotoxicity than 3'-azido-3'-deoxythymidine demonstrated reduced antiviral activity. 3'-fluoro-3'-deoxythymidine may become an alternative chemotherapeutic agent because of its high antiretroviral potency. Its toxicity, however, deserves further investigation.

Cell Line↗
PubMed1988

Bidirectional interactions between human immunodeficiency virus type 1 and cytomegalovirus.

Interactions between human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS, and human cytomegalovirus (CMV), a frequent opportunistic agent in AIDS, were studied in vitro. Coinfection of H9 cells with HIV-1 enhances productive CMV infection, as measured by immunofluorescence using monoclonal antibodies to late CMV proteins, slot-blot hybridization for CMV DNA, and cytopathic effects of CMV on human embryonic lung cells. Experiments using vaccinia virus recombinants and Jurkat cells transfected with the transactivating (tat) gene of HIV-1 suggest that this enhancement is not mediated primarily by the tat protein. In addition, coinfection of H9 cells or a monocyte cell line with CMV and HIV-1 results in enhanced HIV-1 replication, as measured in a virus-yield assay or by radioimmunoassay for the p24 antigen of HIV-1. The interactions between HIV-1 and CMV are thus bidirectional.

Antigens, Viral↗
PubMed1988

A serological investigation of BK virus and JC virus infections in recipients of renal allografts.

BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.

Antibodies, Viral↗
PubMed1988

Synergistic interaction of 2',3'-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1.

Effective treatment of infections with human immunodeficiency virus type 1 (HIV-1) may require a combination of antiviral drugs that act by different mechanisms. We report that the combination of 2',3'-dideoxycytidine (ddCyd) and recombinant interferon-alpha-A (rIFN-alpha-A) acts synergistically against HIV-1 replication in vitro. Various cell types (peripheral blood leukocytes, a CD4-positive T cell line, and two monocyte-macrophage lines) have been studied. For each set of dose-effect data, the degree of drug interaction was quantitatively assessed with the median-effect principle and the isobologram equation by using a computer analysis. Under various culture conditions using several concentrations of drugs, multiplicities of infectious virus, and assay systems, antiviral synergism was consistently observed against HIV-1 replication without enhanced cell toxicity. Synergism was seen at concentrations as low as 0.02 microM ddCyd plus 4 U of rIFN-alpha-A/mL or 0.01 microM ddCyd plus 8 U of rIFN-alpha-A/mL, whereas 10-fold higher concentrations were usually required to achieve similar effects with single drugs.

Antiviral Agents↗
PubMed1988

Human immunodeficiency virus (HIV) infection of the uterine cervix.

Human immunodeficiency virus (HIV) has been detected in cervical secretions from HIV-infected women. We report the isolation of HIV from four cervical biopsy specimens. Cervicitis was shown by immunohistochemical staining in cervical biopsy specimens from four HIV-seropositive women; cervicitis was not found in cervical biopsy specimens from four HIV-seronegative women. We found HIV antigens in monocyte-macrophages and endothelial cells within the submucosa of three of these cervices by specific immunohistochemical staining. Small numbers of HIV-infected cells resembling lymphocytes also were found in the cervical mucosa. The virus was not shown by culture or immunohistochemistry in cervical biopsy specimens from the four HIV-seronegative women. These findings suggest that HIV enters cervical secretions from selected infected cell populations within the cervical tissue. The HIV-infected cells in cervical tissue may be involved in transmission of HIV by heterosexual contact and to neonates born to HIV-infected women.

Adult↗
PubMed1987

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

AIDS-Related Complex↗
PubMed1987

Ribavirin antagonizes the effect of azidothymidine on HIV replication.

Azidothymidine and ribavirin both inhibit replication of human immunodeficiency virus in vitro and show promise of clinical utility in patients infected with this virus. In this study, the possible interactions of these drugs were examined in vitro, and a reproducible antagonism between azidothymidine and ribavirin was found to occur under a variety of experimental conditions. The mechanism responsible for this antagonism appeared to be inhibition of azidothymidine phosphorylation by ribavirin. Because similar effects may occur in vivo, clinical trials of these two drugs in combination must be performed only under carefully controlled conditions.

Cell Line↗
PubMed1987

Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis.

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Acyclovir↗
PubMed1987

Antiviral therapy.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro.

The antiviral activities of various interferon preparations against human immunodeficiency virus (HIV) were evaluated in vitro. Recombinant interferon alpha-A, and beta interferons and leukocyte-derived alpha interferons show similar concentration-dependent antiviral activity. Recombinant and lymphocyte-derived gamma interferons show minimal antiviral activity against HIV replication in normal peripheral blood mononuclear cells, but definite activity against HIV in the H9 lymphocytic and U937 monocyte-macrophage cell lines.

Cells, Cultured↗
PubMed1987

Effects of human immunodeficiency virus (HIV) on the cytotoxic response to Epstein Barr virus (EBV) transformed B lymphocytes.

The human immunodeficiency virus (HIV) may interact with the Epstein Barr virus (EBV) indirectly by effects on the T4 lymphocyte or directly by effects on EBV transformed B lymphocytes. We have confirmed the susceptibility of EBV transformed B lymphocytes to productive HIV infection, and have evaluated the cytotoxic activity of HIV seronegative and seropositive donors after sensitization by their autologous EBV infected (monoinfected) or EBV and HIV infected (coinfected) transformed cell lines in a 51Cr release cytotoxicity assay. When sensitized by the coinfected cell line and assayed against monoinfected and coinfected cell lines, the cytotoxic activity of the seronegative donors was inhibited when compared to the cytotoxic effectors sensitized by the monoinfected B cell line. The inhibition appeared to be unrelated to direct HIV infection of the T4 effector cells and was reversible by addition of recombinant interleukin-2. Although deficient in their EBV cytotoxic activity in comparison to the seronegative donors, the HIV seropositive donors lysed the coinfected cell line better than the monoinfected cell line, whether or not HIV superinfected cells were used during the sensitization phase. In HIV seronegative donors, HIV may inhibit the immune response to EBV transformed B lymphocytes. This inhibition is not observed in HIV seropositive donors. These studies suggest the development of cytolytic effector mechanisms directed at HIV infected cells during HIV infection.

B-Lymphocytes↗
PubMed1987

Effects of human immunodeficiency virus on the cellular immune response to Epstein-Barr virus in homosexual men: characterization of the cytotoxic response and lymphokine production.

We investigated Epstein-Barr virus (EBV)-specific T cell responses in homosexual men with, and at risk for, AIDS. We studied healthy laboratory workers, healthy homosexual men, and patients with AIDS-related complex or AIDS. The cytotoxic activity, absolute number of T4 lymphocytes, and interleukin-2 (IL-2) production decreased, whereas the relative number of Ia+ lymphocytes increased with the extent of infection with the human immunodeficiency virus (HIV). Cytotoxic activity correlated positively with the number of T4 lymphocytes (r = .56, P less than .001) and the amount of IL-2 produced (r = .47, P less than .01) but not with interferon production. Recombinant IL-2, but not gamma interferon, could restore cytotoxic T cell activity to control levels in patients with early HIV infection. EBV-specific serological studies paralleled the T lymphocyte investigations. The increased EBV activity observed in progressive HIV infection may be related to a diminution in the auto-reactive population of the T4 lymphocyte subset and may be amenable to IL-2 reconstitution.

AIDS-Related Complex↗
PubMed1987

Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus.

Human immunodeficiency virus (HIV) elicits the production of virus-specific antibodies in infected individuals. We investigated the ability of serum from HIV-infected individuals to mediate antibody-dependent cellular cytotoxicity in an in vitro 51Cr release assay system. Fresh peripheral blood mononuclear cells from healthy donors seronegative for HIV were used as cellular effectors against HIV-infected and uninfected H9 target cells in the presence of serum from HIV-infected or uninfected donors. Serum from HIV-infected, but not uninfected, donors significantly augmented cytolysis of virus-infected targets (P less than .005). There was no augmented killing of uninfected H9 cells with sera from either group. Studies using serum from mice that had been immunized with synthetic peptides from the HIV envelope region suggested that this response is directed, at least in part, at several determinants of the transmembrane portion of the HIV envelope glycoprotein.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon.

Both recombinant alpha A interferon and azidothymidine inhibit the replication of human immunodeficiency virus in peripheral blood mononuclear cells. Combinations of recombinant alpha A interferon and azidothymidine at concentrations that are easily achievable in patients synergistically inhibit human immunodeficiency virus in vitro with minimal toxicity. Combinations of antiretroviral compounds that act by different mechanisms may prove useful in the treatment of acquired immunodeficiency syndrome-related disorders.

Antiviral Agents↗