Treatment of cancer of the larynx.
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Biomedical subjects
Publications and source records attributed to B Zimmerman.
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The effect of anti-thymocyte serum (ATS) on functional T cell subsets within the immunoregulatory network was examined. We found that low doses of ATS depleted the IL 2-producing subset of T helper cells and higher doses of antiserum also eliminated cytotoxic precursors. It was estimated that a standard low dose of ATS, which reduced T helper cells 80-fold, depleted cytotoxic precursors only about four-fold. The data indicate that ATS acts on different T cell subsets in a dose-dependent fashion and suggest that monoclonal antibodies might be used to preferentially deplete specific T cell subpopulations. Two monoclonal rat anti-mouse Lyt sera, however, proved ineffective in inducing functional changes in vivo, although an alloantiserum to Lyt1.1 was able to reduce cell-mediated cytotoxicity in a dose-dependent fashion. The results support the feasibility of specific depletion of T cell subsets with anti-lymphoid antibodies.
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The delineation of discrete subpopulations of human T lymphocytes has permitted preliminary analyses of the complex cellular network regulating the immune response in man. We previously showed that a subset of T lymphocytes, designated as theophylline-sensitive because of their inability to bind sheep red blood cells in the presence of the drug, are responsible for antigen-specific suppression or regulation in an in vitro plaque-forming cell assay. We now show that 25 to 45% of these theophylline-sensitive T cells were Ia-positive by immunofluorescence with a rabbit antiserum raised against purified B lymphoblast surface antigenic material. These data suggested that 4 to 7% of peripheral blood T cells carry Ia determinants. The presence of Ia determinants on this T cell subset was confirmed by gel analysis of radioiodinated surface material. Furthermore, in mixed lymphocyte culture, the theophylline-sensitive cells demonstrated HLA-D determinants and were 10-fold more potent stimulators than equal numbers of B lymphocytes. The presence of Ia determinants on these T cells indicates the expression of major histocompatibility complex-related regulatory gene products on a specific human T lymphocyte subpopulation.
In these experiments, we have examined the effect of antilymphocyte serum (ALS) on T lymphocyte subpopulations in animals receiving nonimmunosuppressive, weakly immunosuppressive, and strongly immunosuppressive doses of different pools of ALS. Nonimmunosuppressive (inactive) sera were defined by their inability to prolong Fischer skin grafts on Lewis recipients. Weak immunosuppression was considered to have been achieved at doses of active ALS that induced prolonged survival of Fischer skin homografts but not the more strongly antigenic Wistar-Furth homografts. Similarly, strong immunosuppression was induced with doses of active ALS that resulted in prolonged survival of not only Fischer but also the Wistar-Furth grafts. Examination of Lewis rats treated under these conditions indicated that weakly immunosuppressive ALS created a shift in peripheral T lymphocyte subpopulations with an increase in the absolute numbers of one subpopulation (lymphocytes capable of forming rosettes with guinea pig red blood cells in fetal calf serum). This population shift induced by active ALS was dose dependent and occurred in spleen slightly before lymph nodes. Nonimmunosuppressive antisera failed to induce this change. Moreover, although these doses of ALS were capable of prolonging the survival of Fischer skin grafts and inducing the population change, there was no loss of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) in vitro. However, at doses of antiserum capable of prolonging the survival of Wistar-Furth skin grafts, the in vitro reactivity of T lymphocytes to these mitogens was more consistently suppressed. These data suggested that the degree of immunosuppression achieved with different pools or doses of ALS was attributable to variation in the susceptibility of different T lymphocyte subpopulations to suppression by ALS.
The relationship between Ia alloantigens and xenoantigens detected by immunosuppressive heterologous anti-lymphocyte sera has been investigated. Three rabbit anti-rat lymphocyte sera were examined for the presence of antibodies to Ia antigens. Two of these sera, an anti-thymus membrane and anti-lymphocyte sera detected labelled cell-surface Ia antigens (mol. wt 35,000 and 27,000) present on rat spleen B cells. The third antiserum, prepared against fractionated soluble lymphocyte antigens, was essentially non-reactive with these antigens. Of these three heterologous antisera, the anti-membrane serum reacted with the same antigens detected by two alloantisera. It seemed possible that such an antiserum could modify a recipient animal's immune response in vivo in a fashion identical to alloantibody to Ia antigens. In fact, all three heterologous antisera, including one devoid of antibody to Ia proved immunosuppressive in vivo. These results suggest that antibodies to antigens other than Ia can induce prolonged allograft survival. Since heterologous sera bind Ia antigens, it remains to be determined whether monospecific heterologous antisera to Ia antigens can allograft survival. The results raise the prospect that more than one antibody specificity may contribute to the immunosuppression achieved with ALS.
Short-term treatment of normal human B lymphocytes with low concentrations of papain resulted in selective and reversible removal of sIgD determinants, whereas HLA and Ia-like antigens, sIgM as well as receptors for E, C3, and FcIgG were unaffected. When studied for their capacity to generate antigen-specific direct PFC, papain-treated (delta-) B cells were highly sensitive to inactivation by even low concentrations of antigen. In addition, these cells were impaired in their ability to cooperate normally with T-helper cells or their humoral product(s).
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Fractionation of lactoperoxidase iodinated cell surface material on miniature DEAE-cellulose columns provided a rapid method for separating labeled lipid from cell surface antigens. The procedure also removed poorly solubilized aggregates yielding a labeled preparation which demonstrated stable, reproducible immunoprecipitation results. Using these fractionated antigens components tentatively designated as human 'T' cell specific antigens have been identified.
Iodinated cell surface components from human thymus lymphocytes labeled by the lactoperoxidase method, were solubilized by papain digestion and then 3 M KCl extraction of the residual cell pellet. Antiserum to human thymus bound three components from this material, mol. wt. approximately equal to 40 000, 20 000 and 12 000 daltons. This antiserum was absorbed with cultured human lymphoblasts (CHL) until it no longer bound CHL antigens or the HLA-beta 2-microglobulin complex. It continued to bind labeled antigens from thymus, peripheral blood lymphocytes and "T" cell-enriched fraction of tonsil lymphocytes. The absorbed antiserum bound a component from papain-solubilized thymus antigens which had an estimated molecular weight of approximately 40 000 daltons and which was not associated with beta 2-microglobulin. This component seemed to be a human T cell-specific antigen.
The influence of the ability to conserve length in the development of a size concept was investigated in a series of two experiments. The inability to conserve length influences the perceptual bias of young children using the linear vertical dimension of objects as a salient cue in a paired comparison task when stimulus objects do not share a common baseline. When both stimulus position and attributed functional direction are involved, the latter is more influential in serving an orienting function. Sex differences suggest that females are more field dependent than males in the use of the vertical linear dimension as a cue in the judgment of "bigger" in a paired comparison task.
Surface antigens from lymphocytes of patients with chronic lymphocytic leukemia (CLL) and from normal peripheral blood lymphocytes (PBL) were examined by radioimmunoassay; antisera to lymphocytes (ALS) were used to bind the labeled antigens. Cells from patients with CLL, normal PBL, thymus cells (THY), and cultured human lymphoblasts (CHL) were labeled by lactoperoxidase-catalyzed iodination. ALS (prepared against THY and CHL) were used to bind the labeled antigens solubilized in nonionic detergent. PBL resembled THY, but the CLL resembled CHL. Thus ALS(CHL) had greater potency for CLL antigens than for PBL antigens when compared to ALS(THY). Furthermore, the electrophoretic profiles of the immunoprecipitates from CLL cells revealed a peak of approximately 30,000-35,000 mol wt, which was not found for PBL or THY, but was associated with CHL.
Anti-lymphocyte sera against human thymus [ALS-(THY)] were absorbed serially with cultured human lymphoblasts (CHL) or thymus and residual antigen-binding activity was tested. The absorbed ALS were used to bind 125I-labeled antigens from lymphocytes labeled by the lactoperoxidase catalyzed iodination technique. Absorption of ALS(THY) with CHL led to the absorbed serum having less than 5 to 10% of its original antigen-binding activity against labeled CHL antigens while maintaining from 20 to 40% of its original activity against labeled THY. Serial absorption of ALS(THY) with THY led to an equal decrease in activity against both THY and CHI. When the immunoprecipitates from these experiments were examined on polyacrylamide gels containing SDS it was found that serial absorption of ALS(THY) with THY first removed activity against a component of m.w. similar to 48,000 leaving relatively greater activity against material of apparent high molecular wieght. In contrast, absorption of ALS-(THY) with CHL removed the antibodies against the high molecular weight material while leaving activity against the component of m.w. 48,000. When these absorbed ALS were used to induce in vitro lymphocyte proliferation, it was found that ALS(THY) absorbed with CHL, did not. The retention or loss of mitogenicity seemed to correlate with retention or loss of binding activity against the component(s) of m.w. similar to 48,000.
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