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J D Lifson

Publications and source records attributed to J D Lifson.

82 records · Page 5Linked to original sources
PubMed1986

AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen.

The formation of multinucleated giant cells with progression to cell death is a characteristic manifestation of the cytopathology induced by the AIDS retrovirus in infected T lymphoid cells. The mechanism of giant cell formation was studied in the CD4 (T4/Leu 3) positive T cell lines JM (Jurkat) and VB and in variants of these lines that are negative for cell surface CD4 antigen. By means of a two-color fluorescent labeling technique, multinucleated giant cells in infected cultures were shown to form through cell fusion. Antibody to CD4 specifically inhibited fusion, and uninfected CD4 negative cells, in contrast to uninfected CD4 positive cells, did not undergo fusion with infected cells, suggesting a direct role for the CD4 antigen in the process of syncytium formation. These results suggest that, in vivo, cell fusion involving the CD4 molecule may represent a mechanism whereby uninfected cells can be incorporated into AIDS virus infected syncytia. Because the giant cells die soon after they are formed, this process may contribute to the depletion of helper/inducer T cells characteristically observed in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Utility of formaldehyde fixation for flow cytometry and inactivation of the AIDS associated retrovirus.

To maximize safety in the setting of an increasing number of requests for flow cytometric analysis of specimens potentially contaminated with the AIDS retrovirus, we evaluated some commonly used fixatives for their ability to inactivate the infectious potential of the virus. We found that both formaldehyde (0.37% v/v) and paraformaldehyde (0.5% w/v) completely inactivated the infectious activity of both free and cell-associated lymphadenopathy associated virus (LAV), the etiologic agent for the acquired immunodeficiency syndrome (AIDS). Based on encouraging preliminary results we formally evaluated the effect of formaldehyde fixation on flow cytometric parameters. In addition to inactivating LAV, 0.37% formaldehyde in phosphate buffered saline preserved light scatter and fluorescence properties of cells stained with fluorescein isothiocyanate (FITC) and beta-phycoerythrin (PE) conjugated monoclonal antibodies. These findings suggest that formalin fixation may be useful for laboratories performing flow cytometric analysis of specimens potentially contaminated with the AIDS virus.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

The immunohistology of the persistent generalized lymphadenopathy syndrome (PGL).

The authors employed a large panel of monoclonal antibodies to characterize and quantitate lymphoid subpopulations within the paracortex, mantle, and germinal centers of frozen sections of lymph nodes from 18 patients with the persistent generalized lymphadenopathy (PGL) syndrome and five heterosexual controls. The authors' data indicate that Leu-3+ phenotypic T-helper cells (TH) are reduced within all three compartments, while T-cytotoxic-suppressor cells (Tcs) are increased. Using the antibody 9.3, which allows dissection of the Leu-2+ Tcs subset into 9.3+ cytotoxic cells (Tc) and 9.3- suppressor cells (Ts), the authors found that the Ts subset is increased in the lymph nodes of these patients. In contrast to acquired immune deficiency syndrome (AIDS) patients, paracortical total T-cells and Leu-8+ cells appear to be preserved in patients with PGL. Study of TH and Tcs subpopulations in peripheral blood in 12 of these patients revealed inverted ratios (mean, 0.59), which did not correlate with those seen in the lymph nodes. Although the paracortical TH/Tcs ratios were significantly reduced (mean, 1.44) they were not inverted, in contrast to some other reported series. In aggregate, these data suggest that, relative to AIDS, there is preservation of the paracortical T-cell microenvironment in PGL. Clinically, this correlates with more intact cell-mediated immunity and the absence of opportunistic infections and Kaposi's sarcoma in this patient group. Follicle lysis was present in 11 patients. Increased HLA-DR+ paracortical cells, aggregates of Leu-6+ dendritic cells, decreased TAC+ cells, increased OKT-10+ plasma cells, and increased interstitial immunoglobulin were among the other features observed in these patients.

AIDS-Related Complex↗
PubMed1985

Cerebrovascular reactivity to CO2: modulation by arterial pressure.

Cerebrovascular reactivity to CO2 (CO2R), measured in halothane-anesthetized rabbits, decreased as arterial pressure was increased either pharmacologically or mechanically. On the other hand, hypotension, induced by bleeding, led to an increase in CO2R. These responses were unaffected by denervation of baroreceptors.

Animals↗
PubMed1985

Variables affecting T-lymphocyte subsets in a volunteer blood donor population.

Inversion of the normal ratio of helper/inducer (Th) to suppressor/cytotoxic (Ts) T lymphocytes is a characteristic finding in symptomatic and presymptomatic patients with acquired immunodeficiency syndrome (AIDS). As an interim measure to prevent transmission of AIDS via blood transfusion, the Stanford Blood Center performed T-lymphocyte subset analysis as a screening procedure. In this report we present results from 8715 consecutive volunteer blood donors, aged 17-77. The mean Th:Ts ratio was 2.00 +/- 0.70 with a significant trend for increasing Th:Ts with increasing age. In all age groups, donors with antibody to cytomegalovirus (CMV) had lower Th:Ts ratios than CMV-seronegative donors. 1.9% of the donors had Th:Ts values less than or equal to 0.85 and blood from these donors was not used for clinical purposes. Compared to the overall donor population, individuals with Th:Ts less than or equal to 0.85 tended to be male, (79 vs 53%) and CMV sero-positive (71 vs 36%); a majority (83%) had a low absolute number of Th cells as well as a low Th:Ts value. Follow-up of donors with low Th:Ts values revealed that some belonged to AIDS high-risk populations, despite denials at the time of donation. One such donor was diagnosed with disseminated Kaposi's sarcoma 8 months after a markedly abnormal T-lymphocyte subset profile was noted during screening. These results suggest that T-lymphocyte subset analysis is capable of identifying at least some blood donors at risk for transmitting AIDS and also point to variable affecting T-cell subsets in apparently healthy blood donors.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Human recombinant interleukin-2 partly reconstitutes deficient in-vitro immune responses of lymphocytes from patients with AIDS.

The lymphokine interleukin-2 is required for the development of various cell-mediated immune functions that are known to be deficient in patients with acquired immunodeficiency syndrome (AIDS). The effects of pure human recombinant interleukin-2 (rIL-2), produced by Escherichia coli containing the cloned human gene, on in-vitro immune responses were studied in 16 patients with AIDS and 10 age-matched healthy heterosexual men. Exposure of lymphocytes from most AIDS patients to 1-100 U/ml rIL-2, increased mitogen and alloantigen induced proliferation and augmented natural killer (NK) cell function in a dose-dependent manner. NK activity was the function most consistently improved, with deficient patient responses uniformly restored to normal after incubation of effector cells with rIL-2. Patient responsiveness to rIL-2 did not appear to depend upon the primary manifestation of disease (opportunistic infection, Kaposi's sarcoma, or both) or other clinical variables. rIL-2 also augmented the responses of lymphocytes from health subjects, but to a lesser degree. Pure rIL-2 seems capable of at least partly reconstituting some in-vitro immunological defects characteristic of AIDS. The availability of highly purified rIL-2 makes in-vivo testing feasible.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Acute hemorrhagic obstructive uropathy as a complication of experimental autoimmune encephalomyelitis.

During studies related to immunoregulation in experimental allergic encephalomyelitis (EAE) in rats, acute hemorrhagic obstructive uropathy developed as an unexpected complication. The urinary retention was attributed to mucous plugs tightly impacted into the bladder neck. Although mucous plugs commonly are detected in the bladders of healthy adult rats, they could create a serious complication when impacted into the outflow tract as the result of malfunctioning sphincter actions by EAE-induced spinal cord injury.

Acute Disease↗
PubMedDate not supplied

Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein.

Formation of syncytia, with progression to cell death, is a characteristic feature of in vitro cultures of susceptible cells infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Viral antigen-positive multinucleated giant cells have also been observed in histological sections from infected individuals. In vitro, formation of these multinucleated giant cells occurs through cell fusion which is dependent on cell-surface expression of the differentiation antigen CD4. Utilizing a recombinant vaccinia virus containing the gene for the envelope glycoprotein of HTLV-III/LAV, we demonstrate that cell-surface expression of this protein, in the absence of other HTLV-III/LAV structural or regulatory proteins, is sufficient to induce CD4-dependent cell fusion, leading to cell death, one of the characteristic manifestations of AIDS (acquired immune deficiency syndrome) virus cytopathology. This process may contribute to the loss of CD4+ T cells seen in AIDS.

Cell Fusion↗