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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 289 records · Page 16Linked to original sources
PubMed1982

Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody.

The anti-pan T cell monoclonal antibody OKT3 was administered daily for 2 weeks in four human renal allograft recipients. The antibody induced a dramatic and immediate depletion of peripheral T cells followed by an in vivo antigenic modulation of the OKT3-defined membrane antigen: after three injections, OKT3-treated patients showed a limited but significant number of OKT3- cells of T cell nature (as defined by OKT4 and OKT8) which recovered the OKT3 receptor after an overnight in vitro incubation in the absence of the monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1982

A multivariate neuropsychological approach to brain lesion localization in alcoholism.

The study involved a comparison of the neuropsychological test performance of chronic alcoholic patients with that of patients with localized and nonalcoholic diffuse brain damage. It was hypothesized that if the "right hemisphere" or "frontal lobe" theories of brain localization in alcoholism were correct, the profile obtained by the alcoholic patients would either resemble the profile obtained by the right hemisphere brain damaged patients more than the left hemisphere brain damaged patients. Or alternatively, it would resemble the profile obtained by the patients with frontal lobe brain damage more than the one obtained by the patients with posterior brain damage. In the case of the "right hemisphere" hypothesis, the role of sensory-motor as well as cognitive hemisphere asymmetries was evaluated. The results of the study did not provide strong support for either of the above mentioned hypotheses, but were supportive of the view that brain damage in chronic alcoholism is diffuse, and may reflect premature aging of the brain as a whole.

Adult↗
PubMed1982

Isopeptidase: a novel eukaryotic enzyme that cleaves isopeptide bonds.

In an attempt to clarify the regulatory mechanism that accounts for the shift of protein A24 in the mitotic cycle, we demonstrated the existence of an enzyme, provisionally termed isopeptidase, that cleaves A24 stoichiometrically into histone H2A and ubiquitin. Properties of this enzyme are (i) most eukaryotes, including mammals, amphibia, chicken, and yeast, contain isopeptidase in the cytoplasm; (ii) a significant increase in enzyme binding to chromatin occurs when cells enter mitosis; (iii) Escherichia coli does not contain isopeptidase; (iv) isopeptidase has a molecular weight of 38,000; (v) at an ionic strength that induces globular conformation of H2A, isopeptidase activity is repressed; (vi) a SH group is an essential cofactor; and (vii) most divalent cations (except Mg2+ and Ca2+) are inhibitory. In view of the stoichiometric conversion of A24 into H2A and ubiquitin by isopeptidase in vitro, A24 probably contains a Gly-Gly dipeptide in isopeptide linkage but no other intervening polypeptides. Since ubiquitin in various eukaryotes binds to protein other than H2A, and is proteolytically released, isopeptidase probably acts on isopeptide bonds in general and not uniquely on those of A24. Inasmuch as isopeptidase is present throughout the cell cycle, the level of A24 in chromatin appears to be controlled by a balance between isopeptidase and an as yet unestablished H2A-ubiquitin ligase.

Animals↗
PubMed1982

The relationship between T lymphocyte subsets and Ia-like antigen positive nonlymphoid cells in early stages of cutaneous T cell lymphoma.

Immunofluorescence studies were carried out in cutaneous T cell lymphoma (mycosis fungoides) in order to analyse the microanatomical relationship of the different T lymphocyte subsets (inducer and suppressor/cytotoxic cell populations) to large nonlymphoid Langerhans-type and so-called "indeterminate" or interdigitating cells. The conventional and mouse (monoclonal) antibodies were used in various combinations using fluorescein and rhodamine labeled second layers. In 5 of the 7 cases studied the dermal infiltrate consisted of numerous T (HuTLA+) lymphocytes, 80-90% of which expressed the inducer phenotype (HuTLA+,OKT4+). Most of these cells formed close contact with large cells exhibiting large amounts of Ia-like antigens. These cells corresponded to the interdigitating and indeterminate cells in the sections. By contrast, only small numbers (10-20%) of T cells of suppressor/cytotoxic type (HuTLA+,OKT8+) were seen. These did not show a close affinity to the Ia-like antigen positive nonlymphoid component but appeared to have a predilection for the epidermis. Epidermal Langerhans cells, also strongly Ia-like antigen positive, were further defined by 2 monoclonal antibodies reacting with a cortical thymocyte antigen HTA-1. Although Langerhans cells are probably related to the Ia-like antigen positive dermal cells only a few of the abundant latter population were HTA-1+. In the remaining 2 cases, larger populations of OKT8+ (suppressor/cytotoxic) cells were seen and could be heralding a particularly benign course. These observations indicate a close functional relationship between the lymphoid and Ia-like antigen positive dermal cells during the pre-malignant phase of cutaneous T cell lymphoma.

Aged↗
PubMed1982

Development of a shaker culture of Buffalo green monkey kidney cells: potential use for detection of enteroviruses.

Buffalo green monkey kidney cells were adapted to grow as shaker cultures. Replication of environmental and clinical isolates of poliovirus, coxsackievirus, and echovirus in these cultures was analyzed by plaque assay and compared with replication in Buffalo green monkey kidney cell monolayers and HEp-2 cell shaker cultures. Dose-response tests with various concentrations of Mahoney type 1 poliovirus indicated that Buffalo green monkey kidney cell shaker cultures could detect as little as 1 PFU in an inoculum of 0.2 ml. These data suggest that Buffalo green monkey kidney cell shaker cultures can be effectively used for the detection of small quantities of enteroviruses from environmental sources.

Animals↗
PubMed1982

T-lymphocyte subsets in smoking and lung cancer: Analysis of monoclonal antibodies and flow cytometry.

In order to determine whether abnormalities of immunoregulatory T-cells occur in patients with lung cancer, we characterized peripheral T-lymphocytes in 26 patients with untreated lung cancer. The results in patients with primary squamous cancer (SC) (n = 10), primary adenocarcinoma (AC) (n = 7), and secondary lung metastases (M) (n = 9) were compared with each other and to subjects without cancer (n = 48), including nonsmokers (n = 29) and smokers (n = 19). We found that OKT3+ (mature, peripheral (T-lymphocytes, including both OkT4+ (inducer/helper) and OKT8+ (cytotoxic/suppressor) lymphocytes, were increased in light-to-moderate smokers, but that OKT4+ cells were decreased n heavy smokers (p less than 0.05). The ratio of OKT4+ to OKT8+ (4/8) lymphocytes, reflecting the balance of immunoregulatory cells, was normal in light-to-moderate smokers, but was decreased in heavy smokers (p less than 0.05). The profile of circulating T-cells in patients with SC was similar to the smokers. In contrast, in patients with AC, we found a decreased percentage of OKT8+ cells (p less than 0.05). The 4/8 ratio was elevated in patients with AC (p less than 0.05). In patients with M, there was a decreased percentage of OKT3+ cells reflected in both OKT4+ and OKT8+ subsets. The 4/8 ratio in patients with M was low. Thus, a number of abnormalities in circulating T-cells was found both in smokers and in patients with lung cancer. These results suggest that immunoregulatory abnormalities contribute to the pathogenesis of lung cancer.

Adenocarcinoma↗
PubMed1982

Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry.

We characterized T-lymphocyte subsets in peripheral blood of smokers (N = 60) and nonsmokers (N = 35). Total T-lymphocytes and T cell subsets were similar to nonsmokers in light and moderate smokers. In heavy smokers, total OKT3+ cells were increased, the percentage of OKT4+ cells was decreased, and percentage and total number of OKT8+ cells were increased. The ratio of OKT4+ to OKT8+ lymphocytes was decreased in heavy smokers. The percentage of OKT8+ cells and the OKT4+/OKT8+ ratio returned to normal in heavy smokers six weeks after they stopped smoking. These findings suggest that cigarette smoking causes reversible alterations in immunoregulatory T cells.

Adult↗
PubMed1982

Cellular origin and interactions involved in gamma-interferon production induced by OKt3 monoclonal antibody.

OKT3 monoclonal antibody, a human T cell mitogen, induced interferon production by cultured mononuclear cells at 10(-11) M concentrations. Interferon was secreted only under conditions wherein OKT3 was mitogenic, and production was correlated with cell proliferation. Thus, like mitogenesis, interferon secretion reached a peak 3 days after OKT3 stimulation, was inhibited by a factor(s) in human serum, and required 1000 times higher concentrations of Fab and F(ab')2 fragments of OKT3 for induction. The interferon was most likely of "gamma" (immune) type, because pH 2 and 56 degrees C treatments denatured it, whereas anti-alpha or -beta interferon antibodies did not. Mononuclear cells were fractionated into subpopulations that contained OKT4+ cells (helper/inducer T cells), OKT8+ cells (cytotoxic/suppressor T cells), and OKM1+ cells (monocytes) by combining sheep red blood cell rosetting and complement-mediated lysis using monoclonal antibodies against specific cell types. Both OKT4+ and OKT8+ cells proliferated upon OKT3 stimulation with the absolute requirement of OKM1+ cells. However, OKT4+ cells plus OKM1+ cells were necessary for the secretion of interferon. Studies with selective pretreatments with mitomycin C suggested that gamma-interferon was secreted by the OKT4+ cells and that the OKM1+ population subserved an accessory function.

Animals↗
PubMed1982

T-cell subpopulations identified by monoclonal antibodies after human marrow transplantation. I. Helper-inducer and cytotoxic-suppressor subsets.

Peripheral blood helper-inducer and cytotoxic-suppressor T-cell subpopulations in patients receiving marrow transplants for the treatment of acute leukemia or severe aplastic anemia were quantitated on the fluorescence-activated cell sorter (FACS) using the monoclonal antibodies OKT4 and OKT8, respectively. The relative (percent) and absolute number of OKT4+ cells were severely and persistently depleted for up to 2.7 yr posttransplant. In contrast, the percent and absolute number of OKT8+ cells began to recover within the first 60 days of transplant and subsequently remained at normal or high levels for periods of up to 7.3 yr. There was no significant difference in percent or absolute numbers of OKT8+ cells for patients with or without acute graft-versus-host disease (GVHD). The reversal of the normal OKT4:OKT8 ratio (2:1) occurred regardless of whether the recipient was given an allogeneic, syngeneic, or autologous transplant and regardless of whether or not acute or chronic GVHD developed. The reversed ratio was due in the first 3 mo posttransplant to low numbers of OKT4+ cells and later to a combination of low numbers of OKT4+ and high numbers of OKT8+ cells. Normalization and then an increase in the number of OKT8+ cells correlated with increasing time posttransplant and not with resolution of acute GVHD.

Adult↗
PubMed1982

Monoclonal antibodies to human T cell subsets: use for immunological monitoring and immunosuppression in renal transplantation.

Sequential monitoring of peripheral blood T cell populations was performed in normal control individuals and in 55 renal allograft recipients. In addition, 66 patients exhibiting prolonged renal allograft survival were each evaluated at least once with the same monoclonal antibodies. A normal or elevated OKT4:OKT8 ratio, especially in the presence of rising numbers of OKT4+ cells was predictive of possible future graft rejection. This observation, when followed by rising serum creatinine values coupled with biopsy evidence of glomerulopathy, was found in at least 15% of graft recipients. In a small number of patients, graft rejection episodes were successfully suppressed by administration of therapeutic doses of OKT3 antibody. However, production of anti-OKT3 antibodies was observed and may be expected to limit administration of this agent to a single short course in each patient.

Acute Disease↗
PubMed1982

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗
PubMed1982

Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset.

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.

Antibodies, Monoclonal↗
PubMed1982

Treatment of donor bone marrow with OKT3 (PAN-T monoclonal antibody) for prophylaxis of graft-vs.-host disease (GvHD) in histocompatible allogeneic bone marrow transplantation (BMT): a pilot study.

Ten consecutive patients ranging in age from seven to 34 years undergoing bone marrow transplantation from histocompatible siblings for treatment of hematologic malignancy were entered into a pilot study designed to test the safety of OKT3 pretreatment of donor bone marrow for prevention of graft-vs.-host disease. Concentrated donor bone marrow specimens containing a mean of 6.5 X 10(8) nucleated cells/kg recipient weight were treated with 1 mg of OKT3 at 4 degrees C for 30 min prior to administration to the recipient. In vitro immunofluorescent studies confirmed that all OKT3+ cells in bone marrow had effectively bound antibody. Furthermore the addition of neonatal rabbit complement in vitro decreased the proliferative responses of donor bone marrow cells to phytohemagglutinin and concanavalin A (Con A) to less than or equal to 4% of untreated bone marrow. No significant complications resulted from the administration of OKT3 and all recipients engrafted after a mean duration of 22 days. Nine of the 10 patients survived for more than 100 days after marrow transplantation. However, five of the 10 patients developed acute graft-vs.-host disease and required steroid therapy. While this pilot study suggests that OKT3 can be used safely in the bone marrow transplantation setting, further modification of our OKT3 treatment procedure will be necessary to completely eradicate graft-vs.-host disease in histocompatible bone marrow transplantation.

Acute Disease↗