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D M Israelski

Publications and source records attributed to D M Israelski.

16 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↗
PubMed1988

Diagnosis of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome by using a new serologic method.

The present study was performed to develop a serological method for diagnosing toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome (AIDS). The trophozoite form of Toxoplasma gondii, fixed with either Formalin or acetone, was used in a modification of an agglutination method previously shown to differentiate between the acute and the chronic (latent) stages of infection with toxoplasma in immunologically normal persons. By using these antigens in separate tests and evaluating the data for statistical significance, 70% of patients with AIDS with biopsy-proven toxoplasmic encephalitis were distinguished from control, ambulatory patients with AIDS with toxoplasma antibodies but without signs or symptoms of central nervous system involvement. In a separate study, the agglutination tests identified from controls 84% of patients with AIDS with two or more brain lesions detected by computed-tomographic or magnetic-resonance-imaging scans and suspected of having toxoplasmic encephalitis. Thus, these agglutination tests should prove valuable for the noninvasive diagnosis of toxoplasmic encephalitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Antibody response and antigen recognition in human infection with Trypanosoma cruzi.

Sequential serum samples of an individual accidentally infected with Trypanosoma cruzi were examined to study the evolution of the antibody response, particularly of those with the capacity to lyse trypanosomes, and to determine the antigens of each of the 3 stages of the life cycle of T. cruzi, recognized by antibodies formed as the infection progresses. T. cruzi specific IgM and subclasses of IgG antibodies were detected and reached peak levels at the same period of time. Lytic antibodies were detected 2 weeks before demonstration of parasitemia and of antibodies reacting in the ELISA and IFA tests. Western blots used to examine antigen recognition revealed a complex array of antigens of epimastigotes and amastigotes, but not of blood trypomastigotes, recognized by antibodies in the various serum samples. Most of the antigens recognized by antibodies were common to all 3 stages of T. cruzi, although a few were specific for each of the stages. Certain antigens were only recognized by antibodies in serum collected at distinct periods of time during the course of the infection. The pattern noted after immunoprecipitation of 125I labeled cell membrane surface antigens was simple. Antigens of molecular weight of 90, 72, 50, and 30 K were immunoprecipitated in higher quantities. Antibodies in serum collected early and late in the infection recognized similar antigens in epimastigotes of the infecting strain and in epimastigotes of 3 other strains of T. cruzi from widely separated geographic areas.

Animals↗
PubMed1988

Toxoplasmic encephalitis in patients with AIDS.

Toxoplasmic encephalitis has been recognized as a major CNS complication in patients with AIDS and is the most frequent cause of focal intracerebral lesions in these patients. This complication of AIDS is almost always observed in patients who have a chronic (latent) infection with Toxoplasma gondii. Therefore, patients who from the outset of their HIV infection or AIDS are known to have antibodies to T. gondii should be considered at risk for development of toxoplasmic encephalitis. Although serologic tests cannot distinguish active from latent infection, a patient who is seronegative for Toxoplasma antibodies is unlikely to have toxoplasmic encephalitis. Neuroradiologic studies may be highly suggestive of toxoplasmic encephalitis, but, at present, the definitive diagnosis can be made only by demonstration of Toxoplasma in brain tissue. The unique pathogenesis of toxoplasmic encephalitis in patients with AIDS makes intensive primary therapy followed by a lifelong suppressive regimen necessary. We recommend 6 weeks of high doses of pyrimethamine and sulfadiazine (or trisulfapyrimidines) as primary therapy for the acute disease followed by daily administration of reduced doses of these drugs. The use of clindamycin as an alternative drug for primary therapy, at least at present, must be regarded as investigational and should be reserved for patients who suffer severe reactions to the sulfonamides. As most patients will respond to their primary therapy, those who fail to improve clinically and radiologically to therapy within 10 days should be evaluated for additional or alternative causes of their intracerebral pathology. This will often necessitate brain biopsy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Treatment of toxoplasmic encephalitis with intravenous clindamycin.

At present, therapy for toxoplasmic encephalitis (TE) is the combination of pyrimethamine with sulfadiazine or trisulfapyrimidines. Unfortunately, due to adverse reactions to sulfonamides, many patients with acquired immunodeficiency syndrome (AIDS) are unable to receive a complete course of therapy. The promising results with clindamycin phosphate therapy in a mouse model of TE prompted us to seek further information about patients with AIDS with TE who had been treated with clindamycin. Fifteen such patients were identified in whom clindamycin was used to treat 18 episodes of TE. Eleven patients showed clinical or radiologic improvement after receiving clindamycin therapy, either alone or in combination with pyrimethamine. Twelve received oral clindamycin as suppressive therapy after discharge from the hospital. Adverse reactions possibly related to clindamycin therapy included diarrhea, reversible granulocytopenia, and skin reactions. The results of this retrospective study suggest that clindamycin, either alone or in combination with pyrimethamine, may represent an effective alternative therapy for TE in patients with AIDS. Whether this supposition can be substantiated by appropriately designed studies is presently being determined.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Toxoplasma peritonitis in a patient with acquired immunodeficiency syndrome.

Toxoplasma gondii was identified in a stained slide preparation of, and isolated from, peritoneal fluid specimens obtained from a patient with the acquired immunodeficiency syndrome (AIDS). At the time of admission to the hospital, the patient's serologic tests were positive for Toxoplasma. Toxoplasma was isolated from samples of the patient's blood by mouse inoculation. Findings of newly developed methods for diagnosis of the presence of T gondii in body fluids by assay for Toxoplasma-specific antigen and by use of a DNA probe were positive.

Acquired Immunodeficiency Syndrome↗