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Biomedical subjects

C Tsoukas

Publications and source records attributed to C Tsoukas.

At least 55 records · Page 3Linked to original sources
PubMed1988

B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes.

Growth and differentiation of thymocytes and mature T lymphocytes is regulated by cellular interactions that are in part mediated by soluble factors. We identify IL-6, formerly called B cell stimulating factor (BSF-2). IFN-beta 2, or hybridoma-plasmacytoma growth factor (HPGF) as a novel T cell costimulant rIL-6 induced a six-to seven-fold increase in proliferation of human thymocytes stimulated with suboptimal doses of PHA. A similar effect with added IL-6 could be observed using peripheral blood T lymphocytes, but only if the cultures were first rigorously depleted of monocytes that release high levels of IL-6. Analysis of the mechanism of the IL-6 effect on thymocytes and T lymphocytes showed that IL-6 did not lead to an increase in IL-2-R expression. Concentrations of antibody to IL-2-R inhibiting IL-2 effects did not block the IL-6-induced proliferation, indicating that the IL-6 effect was relatively IL-2 independent. These results identify IL-6 as a novel costimulant of human thymocytes and mature T lymphocytes, and suggest that IL-6 is also an important regulatory of cellular immunity.

Cell Division↗
PubMed1987

Pathogenicity of HIV in lymphatic organs of patients with AIDS.

HIV antigens were searched for in the thymus, lymph nodes, bone marrow, and spleen of AIDS patients, by means of immunofluorescence technique. Human IgG against HIV and monoclonal antibodies against viral gag P24 protein yielded strong cytoplasmic fluorescence of cells in sections of the thymus, lymph nodes and spleen. Some cells containing HIV antigens were morphologically multinucleated giant cells. They reacted with monoclonal antibodies against helper/inducer T-cells (OKT4+), and were complexed with antibody or with complement as demonstrated by double-staining immunofluorescence technique. A large number of inflammatory cells infiltrated the thymus in areas containing cells expressing HIV antigens. These studies demonstrated an association of HIV virus with cytopathic and immunopathogenic reactions in lymphatic organs of AIDS patients, and are consistent with previous results, as well as indicative of a primary aetiologic role for the virus.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Specific stimulation of lymphocytes from patients with AIDS by herpes simplex virus antigens.

Peripheral blood lymphocytes of patients with AIDS are generally anergic to stimulation by lectins or by alloantigens. We have succeeded in demonstrating that the lymphocytes of six AIDS patients, with histories of herpes simplex virus (HSV)-induced genital, anal and/or oral lesions, retained functional specificity with regard to HSV antigens. This was accomplished by treating patient lymphocytes with OKT8 monoclonal antibodies, in the presence of complement, to yield a cell population that was partially responsive to phytohaemagglutinin (PHA). Enhanced proliferation was obtained in the presence of exogenous interleukin-2, which was also employed to foster the growth of these cells over several generations. Lymphocytes derived from these AIDS patients, and maintained in vitro as described, were specifically stimulated in proliferation assays by a HSV antigen preparation in six of the ten cases studied.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Monocyte-macrophage (M-M) functions in asymptomatic hemophiliacs and supertransfused thalassemics.

Patients suffering from acquired immune deficiency syndrome (AIDS) succumb to opportunistic infections due to a generalized failure of their cell-mediated immune defenses. The monocyte-macrophage (M-M) system plays an important role in host defense against viruses, protozoa, mycobacteria, and tumours, all potentially involved in the terminal stages of AIDS. We studied M-M functions in 55 asymptomatic hemophiliacs, 20 supertransfused thalassemics, and 9 von Willebrand's syndrome patients over a period of 17 months to establish the part played by chronic repeated blood component transfusions on the macrophage defense system. We found a significant impairment of chemotaxis in 24 out of 55 hemophiliacs, 13 out of 20 thalassemics, and 4 out of 9 von Willebrand's patients. In contrast, Candida pseudotropicalis killing was markedly increased in all 3 patient groups, while Candida phagocytosis was most significantly diminished in thalassemics. Fc-receptor-dependent erythrophagocytosis showed wide variations in all patients, with a significant decrease only in thalassemics. Phorbol ester-activated nitroblue tetrazolium (NBT) reduction to formazan was normal in most cases, but background spontaneous NBT was often much higher than in the controls. Monocyte adhesion to plastic appeared impaired in hemophiliacs and von Willebrand's Syndrome patients, yet was of no statistical significance. It thus appears that continuous, repeated blood component transfusions cause an alteration of M-M functions. This may be either due to chronic, recurrent antigenic stimulation by foreign proteins transfused, or oncogenic and known immune suppressive viruses, like cytomegalovirus, Epstein-Barr virus, hepatitis, and human T cell lymphotropic virus III. This in turn may increase susceptibility to AIDS.

Adolescent↗
PubMed1986

Detection of HTLV-III/LAV antigens in peripheral blood lymphocytes from patients with AIDS.

HTLV-III was searched for in frozen sections of peripheral blood lymphocytes obtained from AIDS patients by an immunofluorescence technique. Human IgG against HTLV-III/LAV and monoclonal antibodies against HTLV-III/LAV P 24 antigen, yielded a strong cytoplasmic fluorescence in frozen sections of the lymphocytes. Some cells containing HTLV-III antigens displayed multinucleated giant forms. They also reacted with monoclonal antibodies against helper/inducer T-cells (OKT4+), as demonstrated by direct double staining immunofluorescence. Similarly, complexes of immunoglobulins and C3 component of complement were also detected on HTLV-III/LAV Ag expressing lymphocytes. Immunofluorescence study of frozen sections of peripheral blood lymphocytes appeared to be a simple, fast and reliable method for detection of HTLV-III/LAV Ag in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Characterization of recirculating lymphocytes in rheumatoid arthritis patients: selective deficiency of natural killer cells in thoracic duct lymph.

Five patients with rheumatoid arthritis (RA), who were treated by lymphocyte depletion by using thoracic duct drainage (TDD), provided an opportunity to characterize the phenotype and function of their recirculating lymphocytes. We found that: a) thoracic duct lymphocytes (TDL) were similar in their proportion of T cells (83% +/- 6 OKT3+), OKT4+ subset (65% +/- 8), and OKT8+ subset (22% +/- 6) to peripheral blood lymphocytes (PBL): b) fewer natural killer-like cells were present in TDL (5% +/- 4 Leu-7+; 2% +/- 2 Leu-11+: 8% +/- 2 OKM -1+) than in PBL (20% +/- 10 Leu-7+: 11% +/- 6 Leu-11+; 18% +/- 5 OKM -1) (p less than 0.01); c) TDL differed from synovial fluid lymphocytes ( SFL ) and synovial membrane lymphocytes ( SML ) in that TDL lacked a high percentage of activated lymphocytes (T cells bearing Ia antigen, OKT10 , and transferrin receptor): d) immature T cells (expressing either OKT6 antigen or reactive with peanut agglutinin) were not found in TDL even late in the course of TDD: and e) in vitro functional studies demonstrated that TDL were similar to PBL in their ability to synthesize immunoglobulin after mitogen stimulation and to generate cytotoxic T lymphocytes capable of lysing autologous EBV-transformed B cells. However, natural killer activity, as measured by lysis of K562 cells was significantly lower in TDL than PBL (p less than 0.05). These results demonstrate that natural killer cells defined by phenotype and function are excluded from thoracic duct lymph and thus have a circulation pattern different from most T cells.

Adult↗
PubMed1983

Immunologic dysfunction in patients with classic hemophilia receiving lyophilized factor VIII concentrates and cryoprecipitate.

The occurrence of the acquired immune deficiency syndrome (AIDS) in patients with hemophilia has suggested that an infectious agent transmitted through the frequent use of pooled blood products could be responsible. To determine if the amount or type of factor VIII preparation alters the risk of acquiring immune defects, three groups of asymptomatic heterosexual men were studied: 34 with severe classic hemophilia who were receiving lyophilized factor VIII concentrate, 10 with either mild classic hemophilia or moderately severe von Willebrand's disease who were receiving cryoprecipitate and 22 normal men who served as controls. Anergy was noted in 68%, 57% and 5% respectively of the three groups. In comparison with the control group, the group treated with lyophilized factor VIII concentrate had a significantly decreased mean ratio of helper to suppressor T lymphocytes, poor responses of the lymphocytes to mitogens, high unstimulated background activity of these cells and significantly elevated serum IgG levels. Although some of the patients with classic hemophilia who were treated with cryoprecipitate were also anergic, they did not manifest these in-vitro abnormalities. The data indicate that a majority of apparently immunocompetent individuals with classic hemophilia show in-vivo and in-vitro evidence of impaired cellular immunity and may be at risk for the development of opportunistic infections and neoplasms.

Acquired Immunodeficiency Syndrome↗
PubMed1980

Inheritance of immunoglobulin M rheumatoid-factor idiotypes.

The idiotypic determinants on IgM rheumatoid factor (RF) from a single family have been analyzed. Rabbit Fab'2 antiidiotypic antibody was prepared against purified IgM-RF from a patient with rheumatoid arthritis. As measured by radioimmunoassay, the antiidiotype reacted with at least 90% of the patient's RF, but not with non-RF immunoglobulins from the same serum, nor with 10 of 11 polyclonal and monoclonal RF from unrelated individuals. Cross-reacting idiotypes were detected on RF in four of the patients' first degree relatives, spanning three generations, without apparent relation of HLA type or clinical rheumatoid arthritis. These results suggest that IgM-RF associated idiotypes were inherited in this family.

Adult↗
PubMedDate not supplied

Antiviral activity and resistance profile of phosphazid--a novel prodrug of AZT.

Both AZT and its novel 5'-hydrogen phosphonate derivative, Phosphazid, possess similar in vitro activity and resistance profiles. Experiments involving AZT-resistant virus isolates revealed a strong correlation between resistance to AZT and cross-resistance to Phosphazid. In vitro selection for resistance to Phosphazid yielded viruses that were about 15-fold less sensitive than wild-type virus to this drug. Sequencing of the reverse transcriptase region of seven Phosphazid-selected viruses revealed a single codon mutation, D67N, that is associated with resistance to AZT.

Anti-HIV Agents↗