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Biomedical subjects

D M Israelski

Publications and source records attributed to D M Israelski.

10 recordsLinked to original sources
PubMed1992

Intracellular glutathione levels in T cell subsets decrease in HIV-infected individuals.

The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4+ and CD8+ T cells from HIV+ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4+ T cells, CD8+ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p less than 0.0001) and are 62% of normal in CD8+ T cells (p less than 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4+ T cells (p less than 0.003) and are 69% of normal in CD8+ T cells (p less than 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.

AIDS-Related Complex↗
PubMed1992

CD20 expression is increased on B lymphocytes from HIV-infected individuals.

In studies presented here, we show that expression of the pan B cell marker CD20 is markedly increased on B lymphocytes from HIV-infected individuals and that this increase tends to be greater in individuals with more advanced disease. By using multiparameter FACS analyses to quantitate surface density of CD20 and intracellular glutathione (GSH) levels simultaneously, we further show that the distribution of intracellular glutathione (GSH) levels in B cells of HIV-infected individuals is more heterogeneous than in uninfected controls. Finally, we show that the intracellular GSH levels correlate with CD20 expression on a per-cell basis in all infected individuals. These findings suggest that CD20 expression, which can be precisely measured, may prove to be a useful surrogate marker for monitoring HIV infection.

Antigens, CD↗
PubMed1992

Plasma viremia in human immunodeficiency virus infection: relationship to stage of disease and antiviral treatment.

Quantitative culture of human immunodeficiency virus (HIV) was performed on 121 plasma samples from 76 HIV-infected individuals to determine the sensitivity of the assay at different stages of disease and to measure the effect of antiviral therapy on plasma viremia. Plasma virus was detected in 49 of 76 (64%) of patients, primarily those with AIDS and AIDS-related complex (36 of 38) versus asymptomatic subjects (13 of 38) (p less than 0.001, chi 2). Similarly, plasma cultures were more often positive in patients with less than 250 CD4+ T cells per microliter (38 of 40) than in those with greater than 250 CD4+ T cells per microliter (11 of 36) (p less than 0.001, chi 2). Plasma virus cultures were also more likely to be positive in patients with detectable serum p24 antigen (24 of 26) than in those without detectable p24 antigen (25 of 50) (p = 0.0023, chi 2). An effect of zidovudine (ZDV) treatment on plasma viremia was seen in a comparison of treated and untreated patients with less than 250 CD4+ T cells per microliter. Geometric mean titers of plasma viremia from 16 patients treated with ZDV for more than 3 months were significantly lower than titers from 24 untreated patients (10(1.3) versus 10(2.1), p less than 0.05, Student's t test. A comparison of pre- and posttherapy titers in 33 patients receiving antiviral treatment showed that plasma virus was not detectable at either time in 17 patients; there was a fall in plasma virus titer in 12; and titers were unchanged or increased in 4. In patients with advanced disease, plasma viremia is a potential marker of antiviral drug activity.

AIDS-Related Complex↗
PubMed1991

Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group.

The interim results are presented of an ongoing large-scale, prospective, randomized study to determine the potential role of clindamycin in the treatment of toxoplasmic encephalitis. Patients were seropositive for Toxoplasma gondii antibodies and had clinical signs compatible with toxoplasmic encephalitis. Data was available on 33 patients, 15 of whom received pyrimethamine p.o./clindamycin i.v. and then p.o., and 18 of whom received pyrimethamine p.o./sulfadiazine p.o. The interim evaluation did not reveal a remarkable difference between the two regimens in the clinical or radiologic response. Adverse reactions to both regimens were common and frequently multiple, there being more adverse gastrointestinal reactions in patients on pyrimethamine/clindamycin and more adverse hematological reactions in those on pyrimethamine/sulfadiazine.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Toxoplasma serology, parasitemia and antigenemia in patients at risk for toxoplasmic encephalitis.

In order to further characterize the pathogenesis of Toxoplasma gondii infection in patients with AIDS and AIDS-related complex (ARC), a cohort of HIV- and Toxoplasma-infected individuals were identified and prospectively followed. Four hundred and 10 HIV-infected individuals followed in the San Francisco General Hospital AIDS Clinic were screened for antibodies to Toxoplasma between November 1986 and November 1988. Of the 67 (16%) individuals seropositive for Toxoplasma antibodies, 33 (49%) were followed monthly for a mean duration of 7.5 months. One hundred and 11 follow-up blood samples were obtained in order to determine Toxoplasma serology and the incidence of parasitemia. In general, Toxoplasma immunoglobulin (Ig) G antibodies remained stable over time. Detection of Toxoplasma antigenemia and parasitemia was uniformly negative, including those specimens obtained from two individuals within 45 days of their developing toxoplasmic encephalitis.

Animals↗
PubMed1991

Reduction in plasma human immunodeficiency virus ribonucleic acid after dideoxynucleoside therapy as determined by the polymerase chain reaction.

Cell-free HIV RNA in plasma was detected and quantitated after antiviral therapy by the polymerase chain reaction. RNA was extracted from plasma, reverse transcribed to cDNA, amplified by polymerase chain reaction, and quantitated by absorbance based on an enzyme-linked affinity assay. 72 HIV antibody-positive subjects had one plasma sample taken. 39 who were not receiving antiretroviral therapy at the time had a mean plasma HIV RNA copy number of 690 +/- 360 (mean +/- SEM) per 200 microliters of plasma, while 33 subjects who had been receiving zidovudine therapy for a minimum of 3 mo had a mean copy number of 134 +/- 219 (P less than 0.05). 27 additional HIV antibody-positive patients had two plasma samples taken before and 1 mo after initiating dideoxynucleoside therapy. Plasma HIV RNA copy number fell from 540 +/- 175 to 77 +/- 35 (P less than 0.05). Finally, nine of these subjects had two baseline samples obtained before initiating therapy and two posttreatment samples 1 and 2 mo after therapy was begun. Mean plasma RNA copy number declined from 794 +/- 274 to less than 40 (below the lower limit of sensitivity) after 1 mo of therapy, with suppression maintained after 2 mo of therapy. These results suggest that gene amplification can be used to detect and quantitate changes in plasma HIV RNA after dideoxynucleoside therapy. Plasma HIV polymerase chain reaction may be a more sensitive marker to monitor antiviral therapy, particularly in asymptomatic patients where measurement of p24 antigen or quantitative plasma cultures are negative.

CD4-Positive T-Lymphocytes↗
PubMed1989

Treatment with anti-L3T4 (CD4) monoclonal antibody reduces the inflammatory response in toxoplasmic encephalitis.

Toxoplasma gondii is an important cause of disease of the central nervous system in patients with AIDS. Among the variety of immunologic disorders encountered by AIDS patients is a depletion of CD4+ subpopulation of lymphocytes. In order to determine the role of this population of T lymphocytes in the generation of toxoplasmic encephalitis, mice chronically infected with T. gondii were treated with mAb GK1.5 directed against the cell surface glycoprotein L3T4 (CD4) of T lymphocytes. Histopathologic sections of brains of control and treated animals were examined at regular intervals during and after completion of treatment. The results demonstrated significantly less inflammation in brains of mice during treatment with GK1.5 mAb. In addition, recrudescence of the inflammatory process occurred after discontinuation of treatment. Similar results were observed in experiments in which different strains of mice and T. gondii were used.

Animals↗
PubMed1989

Zidovudine antagonizes the action of pyrimethamine in experimental infection with Toxoplasma gondii.

The effect of zidovudine (azidothymidine; AZT) on the action of pyrimethamine against Toxoplasma gondii was investigated. Zidovudine was found to antagonize the toxoplasmacidal effect of low concentrations of pyrimethamine in vitro, and in vitro synergism of pyrimethamine and sulfadiazine against T. gondii was reversed by zidovudine. Zidovudine also antagonized the therapeutic effect of pyrimethamine in mice acutely infected with T. gondii.

Animals↗
PubMed1989

Effect of recombinant tumour necrosis factor on acute infection in mice with Toxoplasma gondii or Trypanosoma cruzi.

Recombinant tumor necrosis factor (rTNF) has been shown to protect mice against lethal bacterial infections. We previously reported that in in vitro experiments with mouse peritoneal macrophages, rTNF inhibited intracellular multiplication of Trypanosoma cruzi but not of Toxoplasma gondii. These disparate results led us to study the effect of rTNF on the in vivo infection with these parasites. Daily administration of 0.5 and 5.0 micrograms rTNF resulted in a dose-dependent, significantly decreased time to death (p less than 0.05) in mice infected with lethal doses of T. cruzi. The same effect was found in mice infected with T. gondii and given a daily dose of 5.0 micrograms rTNF. Lower doses of rTNF did not significantly affect time to death of mice infected with either parasite.

Animals↗