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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 361 records · Page 20Linked to original sources
PubMed1980

Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood.

A simple and rapid method for the determination of human T lymphocyte subclasses in buffy coat preparations or whole blood is described. This technique uses flow cytometry to distinguish lymphocytes from other leukocytes on the basis of their light-scattering properties. Lymnphocyte subclasses were enumerated by cellular immunofluorescence; the immunofluorescent signals were produced by monoclonal antibodies to surface differentiation antigens on T cells. Conventional techniques of enumerating T lymphocyte subclasses entail time-consuming (up to 2 days) density gradient and E rosette enrichement, and require at least 20 ml of blood. The method described here uses as little as 50 microliters of whole blood for each antibody tested and produces results within in 2 hr.

Antibodies↗
PubMed1980

Functional and developmental compartments of human T lymphocytes.

Hybridoma technology has made it possible to prepare a range of antibodies which define developmental and functional compartments of the T lymphocyte lineage in man. The feasibility of achieving this aim, and some immediate clinical applications, are illustrated in this report on seven monoclonal antibodies from seven selected hybridoma clones, which are shown to define subclasses of human T cells according to their immune function and developmental rank.

Antibodies↗
PubMed1980

Dichotic listening in psychiatric patients with and without diffuse brain damage.

A dichotic listening test was administered to a group of 49 psychiatric patients with mild diffuse brain damage and a group of 89 without. Despite the lack of difference between the groups on Verbal IQ, the performance of the brain-damaged group was significantly inferior to that of the non-brain-damaged group on a number of measures of error. The most striking difference between groups occurred on the report of digits presented to the left ear, where this report was made subsequent to the report of digits to the right ear. The finding was discussed with regard to its relevance to theories of hemisphetic asymmetry of language functioning.

Adult↗
PubMed1980

A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2.

A hybridoma-secreting monoclonal antibody was produced from the spleen cells of a mouse immunized with human thymocytes. This hybridoma antibody, termed OKT5, was reactive by indirect immunofluorescence with 80% of human thymocytes but only 20% of peripheral blood T cells. Moreover, OKT5 was unreactive with normal B cells, null cells, and macrophages at any dilution tested. A similar pattern of reactivity was seen with an equine antiserum to human thymocytes termed anti-TH2. Fluorescence-activated cell sorting demonstrated that the OKT5 antibody reactivity on peripheral T cells was restricted to the majority of the previously defined TH2+ subpopulation. In functional studies, the OKT5+ subset, like the TH2+ subset, proliferated well to the mitogen Con A and to alloantigens, and contained cytotoxic effector cells after sensitization in MLC, and suppressor effector cells after activation with Con A. In addition, like the TH2+ T cell, the OKT+ T cell was virtually unresponsive to soluble antigen. Thus, the OKT5 monoclonal antibody is reactive with the cytotoxic/suppressor T cell subset. OKT5 should provide an important probe to assess the status of suppressor cells in human disease.

Animals↗
PubMed1980

Functional effects of thymopoietin32-36 (TP5) on cytotoxic lymphocyte precursor units (CLP-U). I. Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulation.

Cytotoxic lymphocyte precursor units (CLP-U) were enumerated in the spleens of C57BL/6 mice 3 days after i.p. injections of synthetic thymopoietin32-36 (TP5). One hundred to 1000 ng TP5/mouse potentiated splenic CLP-U, this effect being detectable only after suboptimal allogeneic sensitization (with 1.2 x 10(5) mitomycin-C treated DBA cells). This elevation of CLP-U persisted in the injected mice for at least 14 days. Control peptide did not affect CLP-U. In vitro incubation of 0.01 to 0.1 ng/ml of TP5 with normal C57BL/6 spleen cells also enhanced CLP-U after suboptimal allogeneic stimulation; high concentrations of TP5 caused suppression of CLP-U and this was detectable with optimal sensitization conditions. Thus TP5, in vitro and in vivo, appears to regulate immune responsiveness and this regulation varies with TP5 dosage and with the immune stimulus.

Animals↗
PubMed1980

T cell requirements for generation of helper factor(s) in man: analysis of the subsets involved.

Lymphocyte mitogenic factor functions as a nonspecific helper molecule generated from antigen stimulation of T lymphocytes. As such, it induces proliferation of all major lymphocyte subclasses (T, B, and Null cells) and B cell immunoglobulin synthesis. In the present study, the specific T cell subset requirements for LMF production were determined in man. By utilizing the OKT4 monoclonal antibody directed at the human inducer T cell subset, T lymphocytes were separated into OKT4+ and OKT4- subpopulations. The antigen stimulated OKT4+ subset generated LMF in a fashion comparable to the unfractionated T cell population and was itself capable of directly inducing B cell proliferation and antibody production. In contrast, LMF could not be generated from the OKT4-T cell subset although this population accounted for 40% of the unfractionated T cell population. In addition, the OKT4- subset was unable to facilitate B cell differentiation in the presence of soluble antigen. These studies provide the first report of T cell subset restriction for generation of helper factors in man and further stress the importance of the OKT4+ inducer population in regulation of the human immune response.

Antigens↗
PubMed1980

Effect of thymopoietin pentapeptide (TP5) on autoimmunity. I. TP5 suppression of induced erythrocyte autoantibodies in C3H mice.

C3H mice (young and old), when immunized with the cross-reacting rat erythrocytes, produced erythrocyte autoantibodies that usually persisted for more than 10 weeks. I.P. injection of thymopoietin pentapeptide (TP5) once or thrice weekly accelerated the loss of erythrocyte autoantibodies 7 weeks after immunization; 10 ng of TP5 was the optimal dose. The rat agglutinin responses of these immunized mice were unaffected by TP5 during the whole period of study. Spleen cells from rat erythrocyte-immunized mice, when transferred to syngeneic recipients undergoing similar immunization schedules, delayed the appearance of erythrocyte autoantibodies in the recipients. A greater delay was observed when spleen cells were taken from mice that had also received TP5 treatment.

Agglutinins↗
PubMed1980

Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.

T-B and T-T interactions involved in the regulation of PWM-triggered human B cell differentiation were studied in vitro. Functionally distinct human T cell subsets were isolated by C-mediated lysis by using the monoclonal antibodies OKT4 and OKT8. Graded numbers of either untreated or irradiated T cell subsets were added to autologous B cells, and total antibody synthesis was measured after 5 to 6 days of culture by using a highly sensitive reverse hemolytic plaque assay. The data indicate that a) the helper activity that is exclusively contained within the OKT4+ population is radiosensitive. Only at high T/B ratios can this radiosensitivity be overcome; b) the OKT8+ population contains radiosensitive cells important in suppressing B cell differentiation, and c) the suppression induced with OKT8+ cells requires the presence of radiosensitive OKT4+ cells. Thus, OKT8+ cells added to cultures containing B cells and irradiated OKT4+ cells do not suppress the PFC response. Addition of unirradiated OKT4+ cells to these cultures permits reexpression of suppression by OKT8+ cells. It is concluded that two radiosensitive cells, one within the OKT4+ population and the other within the OKT8+ population, collaborate to induce suppression. Possible mechanisms for this suppressive interaction including induction of suppressor precursor cells within the OKT4+ population or inhibition of OKT4+ helper cells by OKT8+ cells are discussed.

Antibodies↗
PubMed1980

A monoclonal antibody reactive with human peripheral blood monocytes.

A monoclonal antibody directed at a determinant on human peripheral blood monocytes was produced and characterized. This hybridoma antibody, termed OKM1, was reactive by indirect immunofluorescence and complement- (C) mediated lysis with adherent mononuclear cells. OKM1 was unreactive with lymphocytes, thymocytes, lymphoblastoid cell lines, and tumor cells of the T or B cell lineage. In contrast, acute myelomonocytic leukemia cells and granulocytes were reactive with the antibody. Pretreatment of peripheral blood mononuclear cells with OKM1 and C before culture with soluble antigens totally abolished their antigen-induced proliferative response. This function was restored by addition of 1% adherent cells. These findings provided additional support for the notion that OKM1 was reactive with monocytes. In addition, OKM1 appeared to define two distinct populations of monocytes; an adherent population of large cells bearing surface Ia determinants and a nonadherent population of small, Ia-negative cells. These OKM1+ Ia- cells were found to be a contaminant of most fractionated mononuclear cell subsets including the E-SIg-Null cell population.

Animals↗
PubMed1980

Graphical determination of specific activity, binding constants, and antibody-site concentrations for radioimmunoassays, with application to thymopoietin.

A graphical procedure for determining the specific activity of radiolabeled ligands has been developed for use with radioimmunoassays. Although with this procedure we utilize the same experimental information required for displacement analysis, we are also able to determine both the specific activity and the binding constants of the labeled and unlabeled materials without assuming that these constants are equal; the concentration of antibody-binding sites can also be calculated. Thus, this graphical technique permits calculation of additional information without additional experimentation. We applied this procedure to the labeled materials used in a thymopoietin assay, testing two different preparations of radiolabeled material, and saw negligible differences between the two. The specific activity determined from the displacement analysis correlated well with that calculated by the graphical procedure.

Humans↗
PubMed1980

Comparison of the in vitro effects of thymopoietin pentapeptide and levamisole on peripheral E-rosette forming cells.

The effects of thymopoietin pentapeptide (TP5) and levamisole on human peripheral T lymphocytes were investigated by means of the E-rosette formation. Different kinds of E-rosette forming cells (RFC) were measured, i.e. active RFC (RFCa), total RFC (RFCt) and azathioprine-inhibited RFCt. The effects of TP5 and levamisole on RFC were very similar. Azathioprine inhibition of RFCt was restored completely by levamisole and partially by TP5. Both substances enhanced RFCa of healthy subjects and RFCt of patients in which these were low. TP5 and levamisole may act via a common cyclic nucleotide second signal.

Animals↗
PubMed1979

Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression.

The nature of Ia antigens which appear on human T cells after activation and the stimuli required for their expression was examined utilizing a monoclonal antibody reactive with the Ia antigen framework. T cells were purified using monoclonal antibodies directed either at the entire T-cell population (OKT3) or the T-cell inducer subset (OKT4). By indirect immunofluorescence, it was shown that the human T-cell population contains no detectable Ia+ cells in the resting state. In contrast, in excess of 60% of the T-cell population expresses Ia antigen after alloactivation in the mixed lymphocyte culture. Moreover, these Ia antigens are expressed within both the OKT4+ and OKT4- subsets. Similarly, phytohemagglutinin and concanavalin A induced approximately 20% of peripheral T cells to express Ia antigen and the expression of these antigens is not restricted to either OKT4 subset. In contrast, only the inducer T-cell population which proliferates maximally to soluble antigen expresses Ia antigens after activation by tetanus toxoid. Thus, the expression of human Ia antigens on unique T-cell subsets depends upon the activation stimuli utilized and ability of the individual subset to respond to a given stimulus. Additional studies indicated that Ia antigens appear on previously Ia- T cells after activation and do not result from clonal expansion of a small subset of Ia+ T cells.

Antigen-Antibody Reactions↗
PubMed1979

Monoclonal antibodies defining distinctive human T cell surface antigens.

Three novel nonoclonal antibodies (designed OKT1, OKT3, and OKT4) were generated against surface determinants of human peripheral T cells. Both OKT1 and OKT3 reacted with all human peripheral T cells and 5 to 10 percent of thymocytes but differed in their reactivities with T cel- lines. By contrast, OKT4 reacted with 55 percent of human peripheral T cells and 80 percent of thymocyted in that they did not react with normal B cells, null cells, monocytes, or granulocytes.

Animals↗
PubMed1979

Clinical evaluation of computed tomographic scanning.

Computed tomographic (CT) head scans were performed on 100 patients in a neurology ward. The CT scan was diagnostic in 67 patients and suggestive in a further three patients. Computed tomographic scans were most likely to be diagnostic in patients whose symptoms at presentation could be classified as "traumatic intracranial lesion", "space-occupying lesion", "acute cerebrovascular lesion", "dementia", and "epileptic disorder", and much less likely to be diagnostic if a patient presented differently. In all cases where the CT scan was diagnostic. It was considered that, had a CT scan not been available, alternative tests such as nuclear scan, cerebral angiography or pneumoencephalogram (PEG) would have been performed and would also have been diagnostic; no impact of the CT scan on diagnosis, therapy or patient outcomes was documented. However, in patients who received a CT scan, there was a 91% reduction in the PEGs, 85% reduction in cerebral angiograms, a reduction of 73% in nuclear scans and 31% in electroencephalograms. Computed tomographic scanning costs no more than the tests it replaces in the clinical setting studied, and offers significant advantages in patient comfort and safety.

Brain Diseases↗