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Biomedical subjects

R H Stevens

Publications and source records attributed to R H Stevens.

At least 109 records · Page 6Linked to original sources
PubMed1980

Subpopulations of circulating B cells and regulatory T cells involved in in vitro immunoglobulin E production in atopic patients with elevted serum immunoglobulin E.

The B lymphocyte subpopulations producing immunoglobulin (Ig)E and the regulatory T cells modulating this IgE production in normals, and in atopic patients with respiratory allergy, atopic dermatitis, and markedly elevated serum IgE levels (>5,000 ng/ml), were investigated. Peripheral blood lymphocytes (PBL) were separated into T and B cell fractions and the ability of B cells to produce IgE in the presence or absence of pokeweed mitogen (PWM) and/or T cells ws determined. The patients had a circulating population of cells which spontaneously produced up to 6 ng of IgE in vitro (per 4 X 10(5) non-E-rosetting cells) in the absence of T lymphocytes and PWM. PBL from normals did not possess such cells. This IgE synthesis occurred primarily (>75%) over the first 72 h of culture. There was a wide range in their activity between patients and from the same patient studied on repeated occasions (from <300 to 6,000 pg per culture). This spontaneous IgE production was inhibited by PWM (mean inhibition, 37%) or normal T lymphocytes (mean inhibition, 42%). The patients lacked T lymphocytes capable of inhibiting this spontaneous IgE synthesis in 7 of 13 experiments. Functionally distinct B cells were identified in the patients and normals that responded to PWM with IgE production in vitro and required T-helper cell activity. Patients had normal PWM-responsive B cell IgE biosynthetic activity and T-helper function for these B cells. Suppressor T cell activity for PWM-driven IgE synthesis was also evaluated. Both the normals' and the patients' T lymphocytes provided similar levels of T cell suppressor function for PWM-driven IgE production. Patients with elevated serum IgE possessed these inhibitory T cells at times when the T lymphocytes which suppressed spontaneous igE production were absent from their PBL.

Adult↗
PubMed1980

Methyl 5'-(6-aminopurin-9-yl)-5'-deoxy-beta-D-ribofuranoside 2',3'-cyclic monophosphate: a novel, biologically active, structural analogue of cyclic AMP.

A novel structural analogue of cyclic AMP has been synthesized. This compound has been found to activate protein kinase from skeletal muscle (Ka 5.0 microM). It is virtually resistant to degradation by beef heart cAMP phosphodiesterase. It is an inhibitor of this enzyme with an [I]50 of 47.0 microM. The proliferation of cancer cells (HT-29) is inhibited by this compound. It represents the first example of a 2',3'-cyclic nucleotide with marked biological activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Abnormal B cell differentiation and variable increased T cell suppression in immunodeficiency with hyper-IgM.

In vitro immunoglobulin (Ig) synthesis was evaluated in three young men having immunodeficiency with hyper-IgM. Patient and normal T and B cells were separated and cultured in various combinations. 35S-methionine incorporation into Ig was measured using immunoprecipitation, and Ig classes were determined by SDS-polyacrylamide gel electrophoresis with autoradiography. The patient B cells were able to produce only IgM in culture with either autologous or allogeneic T cells. Normal B cells produced IgM, G and A when cultured with normal T cells. T cells from two of the patients suppressed the Ig synthesis of normal B cells; irradiation of these T cells allowed them to provide T helper function. T cells from the third patient expressed normal T suppressor/helper activity. This implies that defective differentiation of B cells into IgG- and IgA-producing plasma cells may be a constant feature of immunodeficiency with hyper-IgM, and that excessive T suppressor activity is a variable accompanying abnormality.

Adult↗
PubMed1980

Normal T cell regulation of IgG synthesis in systemic lupus erythematosus.

The regulation of pokeweed mitogen (PWM) stimulated IgG synthesis by peripheral blood mononuclear cells (PBL) was studied in patients with systemic lupus erythematosus (SLE) and controls. The helper-T, suppressor-T and B cell functions of SLE-PBL were separately evaluated and compared to the functions of control lymphocyte populations. SLE-T cells function normally both in helper and suppressor modulation of PWM-stimulated IgG secretion by control or autologous B cells. The SLE-B cell, however, fails to synthesize normal quantities of IgG when cultured under conditions that induce maximal stimulation. While other studies document abnormal Con A induced suppressor cell function in SLE, this study shows that normal functioning populations of SLE-suppressor T cells exist in the peripheral blood.

Adolescent↗
PubMed1980

Antibody potential of human peripheral blood lymphocytes differentially expressing surface membrane IgM.

The appearance of circulating pokeweed mitogen-reactive B lymphocyte subpopulations responsible for the synthesis of IgM and IgG anti-tetanus toxoid antibody after in vivo booster immunization has been analyzed for differential expression of surface membrane IgM. B cells were rosetted with human mu-chain specific antiglobulin-coupled ox red blood cells and separated by density centrifugation into mu+ and mu- populations. After 8 days in vitro culture with irradiated T cells and pokeweed mitogen, antibody synthesis was assessed by quantitative radioimmunoassay. Mu+ cells synthesized both IgG and IgM anti-tetanus toxoid antibodies, whereas mu- cells predominantly synthesized IgG anti-tetanus toxoid antibodies. Limiting dilution analysis revealed a greater number of IgG anti-tetanus toxoid precursors in the mu+ population at all times after immunization compared with mu- cells. However, the activity, as measured by the amount of antibody produced per IgG anti-tetanus toxoid antibody precursor, was 2 to 4 times greater in the mu- population than that in the mu+ population. These results indicate that functionally distinct human circulating B lymphocytes can be identified by their differential expression of surface membrane IgM.

Animals↗
PubMed1980

Superoxide dismutase activity in 1,2-dimethylhydrazine-induced rat colon adenocarcinoma.

1,2-Dimethylhydrazine-induced large bowel tumors in adult male noninbred Holtzman rats contained greatly elevated levels of copper-zinc-containing superoxide dismutase (Cu-Zn SD) activity when compared to levels in normal intestinal tissue but nearly equal levels of manganese-containing superoxide dismutase (Mn SD) activity. Inasmuch as normal intestinal tissue contains many cell types, SD activities were also measured and compared in isolated intestinal epithelial cells. When compared to the activities in villus cells, Cu-Zn SD activity was greatly increased, whereas Mn SD activity was greatly reduced in tumor cells. The SD activity of tumor cells most nearly resembled that of isolated intestinal crypt cells.

Adenocarcinoma↗
PubMed1980

A restricted component of T cell help in pokeweed mitogen-stimulated humans peripheral blood cell cultures.

Limiting dilution analyses using human T and B cells from the peripheral blood of individuals recently (2 to 5 weeks) boosted with tetanus toxoid or a combination of diphtheria and tetanus toxoids were performed in order to investigate the specificity of T cell help during in vitro pokeweed mitogen (PWM) stimulation. Limiting numbers of irradiated T cells were added to an excess of B cells and their ability to help 1) IgG anti-tetanus toxoid antibody or 2) IgG anti-tetanus toxoid and IgG antidiphtheria toxoid antibody production were compared. The helper activity for anti-tetanus toxoid antibody production did not dilute out at the same point as help for total IgG production. Cultures were observed at limiting dilutions of added helper T cells that produced anti-tetanus toxoid IgG or anti-diphtheria toxoid IgG but not both even though a sufficient number of potential specific IgG-producing B cells were present. A distribution analysis of the IgG anti-tetanus and IgG anti-diphtheria helper T cells indicated that the two subpopulations did not segregate together. Thus in the presence of PWM, individual helper T cells appeared capable of supplying help for a restricted number of B cells.

Antibodies, Bacterial↗
PubMed1979

Helper and suppressor t-lymphocyte leukemia in ataxia telangiectasia.

We investigated the nature of the lymphoid leukemia that developed in one of two siblings with ataxia telangiectasia. The leukemic cells were shown to be T lymphocytes. Furthermore, the neoplastic cells carried a characteristic 14q+ chromosome tandem translocation. This chromosome abnormality had been identified 11 years earlier among the patient's "normal" lymphocytes. The patient's neoplastic T lymphocytes in vitro provided helper and suppressor T-lymphocyte activity equivalent to that of normal T lymphocytes. Some neoplastic T lymphocytes bore a receptor for the Fc portion of IgM (45 per cent Tmu) whereas other carried receptors for the Fc portion of IgG (10 per cent Tgamma). All the Tmu and Tgamma lymphocytes possessed the chromosome 14 abnormality. These data suggest that neoplastic transformation occurred in an uncommitted T lymphocyte that was capable of further differentiation into the distinct pathways for help and suppression, in a lymphoid analogy of chronic myelogenous leukemia.

Ataxia Telangiectasia↗
PubMed1979

Retinoblastoma Y79 cell line: a study of membrane structures.

The continuous retinoblastoma cell line Y79, grown in suspension culture, has been examined by transmission and scanning electron microscopy, including freeze-fracture replica preparations. Four classes of cells were distinguishable by their size and surface characteristics. The surface structures included blebs, filopodia, lamellipodia, microvilli, and microplicae. The possible origin of a most unusual type of cell, apparently forming natural clones, is discussed.

Cell Line↗
PubMed1979

Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate phosphodiesterase activities in 1,2-dimethylhydrazine induced colon adenocarcinoma.

The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in 1,2-dimethylhydrazine (DMH) induced rat colon tumors were previously reported to be one-half and twice, respectively, that measured in normal rat colon tissue. The results of this present study indicate that the total amount of cyclic nucleotide hydrolysis by the phosphodiesterase enzymes (PDE) could account for the lower cAMP and elevated cGMP noted in cancer tissue. PDE activities in homogenates prepared from normal and neoplastic tissue showed general similarities in both their hydrogen and metal ion dependencies with optimum degradation of nucleotides occurring at pH 7.2-7.8 in the presence of either Mg2+ or Mn2+ ions. The enzymes from both tissue types were inhibited to a similar extent by papaverine and theophylline. Distribution studies indicated PDE activities were similar throughout the entire length of the normal colon; consequently, the anomalous activities measured in the tumors were attributable to the specific cell population and not to the particular site at which malignancy arose. Thus, the findings of this study suggest that one cause for lowered cAMP and elevated cGMP levels in DMH induced colon adenocarcinomas was the amount of cyclic nucleotide hydrolysis by PDE in the malignant tissue.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Group and type antigens of Capnocytophaga.

Group-specific and type-specific antigens have been identified and purified from sonic extracts of Capnocytophaga. The group-specific antigen, which was purified by affinity chromatography, was found to be identical to an antigen present in all 26 strains tested. The antigen is sensitive to trypsin, sodium dodecyl sulfate and heat labile, and composed predominantly (55%) of protein. The type-specific antigen, which was obtained by preparative immunoelectrophoresis, was found to be present in only 3 of the 26 strains tested. This antigen was resistant to heat, trypsin, and sodium dodecyl sulfate and was primarily composed of carbohydrate (47% phenol-sulfuric acid-positive material, 8% amino sugar). Agglutination and fluorescent antibody data suggest that both the group- and type-specific antigens reside on the cell surface.

Antigens, Bacterial↗
PubMed1979

Lymphocyte cytotoxicity in X-irradiation induced rat small bowel adenocarcinoma. IV. Activation of cellular immunity by X irradiation.

Exposure of only the ileum and jejunum of Holtzman male rats to 100--2000 R resulted in almost immediate and dose-dependent activation of anti-tumor cellular immune mechanisms, as measured in vitro by the cytotoxicity of the animals' peripheral blood lymphoid cells to allogeneic cultured cells from an x-irradiation induced Holtzman rat small bowel adenocarcinoma. These cytotoxic responses were somewhat specific; the lymphoid cells did not kill prostatic adenocarcinoma target cells and cytotoxicity could not be induced by x-irradiation of some tissues other than the small bowel. Results suggest that exposure of an organ to ionizing radiation results in changes which sensitize the lymphoid cells in the animal to recognize and kill cancer cells of the particular tissue. Immunologic suppression by ionizing radiation presumably did not occur because only a small portion of the body was exposed.

Adenocarcinoma↗