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Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 199 records · Page 11Linked to original sources

Immunosuppression associated with SJL/J murine lymphoma. I. Suppression of cell-mediated immune responses after tumor transplantation.

The proliferative responses of peripheral blood lymphocytes of inbred SJL/J mice to the mitogens phytohemagglutinin and concanavalin A were evaluated serially in individual animals before and after induction of lymphomas by transplantation. Tumor-bearing mice exhibited marked suppression of mitogen responsiveness. Proliferative responses in mixed lymphocyte-tumor cell culture and mixed lymphocyte culture were also suppressed. Suppression of responses was tumor related, and responsiveness was restored in animals whose tumors regressed. There was no deficiency of responder T-cells in the peripheral blood of tumor-bearing animals, and suppressor cell activity was not demonstrable in a number of in vitro assays. However, plasma from tumor-bearing animals exhibited potent immunosuppressive activity. The presence of plasma suppressive activity was similarly tumor related. Thus this study demonstrates nonspecific suppression of cell-mediated immune responses following tumor induction, apparently mediated by a plasma suppressor factor.

Animals↗

Immunosuppression associated with SJL/J murine lymphoma. II. Characterization of a plasma suppressor factor in tumor-bearing mice.

The properties of a factor responsible for immunosuppressive activity in the plasma of inbred SJL/J mice bearing transplanted lymphomas were investigated. Suppressive activity was not due to an intact virus but resided in a soluble molecule characterized as a nonimmunoglobulin protein of molecular weight 68,000-88,000. The plasma suppressor factor was relatively stable and was neither directly cytotoxic nor complement-dependent. The degree of suppression of in vitro lymphocyte proliferative responses depended on the time of addition of plasma to cultures. Suppression was reversible if cells exposed to plasma were washed before mitogen stimulation, but stimulated cells exposed to the suppressor factor were irreversibly inhibited. The suppressor factor was partially species-specific. Supernatants from short-term cultures of tumor cells from lymph nodes of SJL/L mice contained a similar suppressor factor, indicating that the plasma factor was probably a product of tumor cells.

Animals↗

Glucocorticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes.

We studied the role of the T lymphocyte in GCS enhancement of PWM-stimulated IgG synthesis by human peripheral blood mononuclear cells. Purified T or B lymphocyte subpopulations were pretreated with 10(-6) M prednisolone or recombined at various T:B ratios and 10(-6) M prednisolone was added. PWM-stimulated IgG synthesis was measured in the culture supernatants at 8 days by radioimmunoassay. Addition of prednisolone to cultures of autologous and allogeneic reconstituted mixtures of T and B lymphocytes resulted in enhancement of PWM-stimulated IgG synthesis. This effect was observed with constant and increasing numbers of lymphocytes in culture, independent of T:B ratio and occurred with purified B lymphocytes containing monocytes. Pretreatment of purified B lymphocytes containing monocytes but not purified T lymphocytes with prednisolone enhanced PWM-stimulated IgG synthesis in reconstituted mixtures of T and B lymphocytes. We propose that GCS enhancement of PWM-stimulated IgG synthesis by human mononuclear cells is independent of T lymphocyte regulation.

B-Lymphocytes↗

Glucocorticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes. III. Common variable immunodeficiency.

We studied the effect of glucocorticosteroids (GCS) on IgG synthesis by peripheral blood mononuclear cells from 19 patients with common variable immunodeficiency (CVID). Purified T and B lymphocyte subpopulations from patients and normal subjects were recombined at various T : B ratios and cultured for 8 days unstimulated, stimulated with pokeweed mitogen (PWM) and in the presence of prednisolone. IgG synthesis was measured in the culture supernatants by radioimmunoassay. Enhancement of PWM-stimulated IgG synthesis by prednisolone at high T : B ratios was found in nine patients, four of whom produced negligible amounts of IgG with PWM alone. In four patients, enhancement by prednisolone of IgG synthesis by purified B lymphocytes was noted. In three out of eight patients whose IgG synthesis was increased by normal allogeneic T lymphocytes with PWM and prednisolone, negligible amounts of IgG were produced by similarly treated autologous combinations. T lymphocytes from CVID patients provided less help compared with normal T lymphocytes for IgG synthesis by normal B lymphocytes at high T : B ratios even in the presence of prednisolone. GCS in vitro enhance IgG synthesis by lymphocytes from some but not all patients with CVID by a mechanism which appears independent of GCS action on regulatory T lymphocytes.

Adolescent↗

Vasculitis: an approach for physicians.

In the absence of a satisfactory classification, a sequential approach to the problems of vasculitis is recommended to the clinician. Clinical recognition will result from a presentation of: i. a well-defined syndrome; ii. a visually identifiable vasculitis (cutaneous or retina); iii--vasculitis-associated disease (connective tissue disease, infectious and neoplastic diseases); iv. multisystem syndrome. Aetiology will be sought from infectious, drug, autoimmune or tumour origin in the main. Helpful pathological features include vessel size, cellular infiltrate, granulomata, necrosis and immune deposits. Immunopathogenesis must clearly distinguish initiators (e.g. immune complexes) from amplifiers and regulators (e.g. fibrin, complement, protease inhibitors, phagocytes). Sites of pathology may be determined by such localising mechanisms as cryoglobulins, immune complex receptors and rheological factors. A rational approach to management dependent on awareness of immunopathology includes inflammatory mediator inhibitors, immunosuppression or plasmapheresis.

Antigen-Antibody Complex↗

Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid.

Serum concentrations of thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured for 14 hypothyroid patients while they were receiving USP desiccated thyroid and after six weeks of therapy with comparable doses of levothyroxine sodium (Na-l-thyroxine). Therapy with USP thyroid caused supraphysiologic elevations in the concentration of T3 in 13 patients. Treatment with levothyroxine resulted in serum concentrations of T3 that were within the range of normal. We believe the preferable therapy for hypothyroidism is levothyroxine.

Adolescent↗

The role of alpha 1 protease inhibitor (alpha 1 antitrypsin) in the regulation of immunologic and inflammatory reactions.

Twenty-six different alleles have been identified for alpha 1 protease inhibitor (alpha 1 antitrypsin), each designated by a letter of the alphabet. In any individual two alleles codominantly determine the characteristics of alpha 1 protease inhibitor (Pi), including mobility on electrophoresis, serum concentration and acute phase response. Recent evidence has linked some mildly deficient phenotypes of Pi with a variety of chronic immunologic and inflammatory disorders, such as rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, asthma and fibrosing alveolitis, in addition to the well recognised association of severe deficiency with emphysema and chronic liver disease. This disease susceptibility in phenotypes associated with reduced serum levels may be due to alteration in lymphocyte responses, complement activation and leukocyte migration. Pi can also influence the autolytic effects of leukocytic enzymes on tissues and may inhibit some aspects of coagulation and fibrinolysis. Therefore patients with deficient Pi phenotypes are likely to have exaggerated immunologic and inflammatory responses.

Asthma↗

HLA-DRw antigens in Mexican-American and Black-American diabetic patients.

HLA-A, - B, and -C antigens were studied in 67 Mexican-American and 38 black-American diabetic patients who had the onset of their disease before age 31 yr. Control populations consisted of 322 Mexican-American and 367 black-American subjects for HLA-A, -B, and -C antigens. In addition, HLA-DRw antigens were studied in 60 Mexican-American and 34 black-American diabetic patients. Control populations for HLA-DRw antigens consisted of 189 Mexican-American and 145 black-American subjects. We found that juvenile-onset--diabetic patients of Mexican-American origin who had the onset of their disease before age 19 demonstrated a significant increase in HLA-DRw4. HLA-DRw4 was also significantly increased in black-American patients with juvenile-onset diabetes mellitus. HLA-DRw2 was not detected in any patient with juvenile-onset diabetes in either ethnic group. A significant association was found between HLA-B18 and HLA-DRw3 in Mexican-American juvenile-diabetic patients. These findings, which are comparable to those in similar Caucasian patients, provide additional information to support the hypothesis that HLA-DRw antigens play a major role in determining the susceptibility to juvenile-onset diabetes mellitus.

Adult↗

The testis.

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Adolescent↗

Circulating immune complexes in acute uveitis: a possible association with the histocompatibility complex locus antigen B27.

39 patients with acute anterior uveitis were investigated for the presence of circulating immune complex (IC) and correlation with the major histocompatibility complex antigen B27 (HLA-B27). ICs were demonstrated by a number of techniques including rheumatoid factor, complement (C) activation, anticomplementary activity, cryoglobulins, inhibition of IgG-EA rosette formation and neutrophil chemotactic index (NCI) in plasma. ICs were most frequently detected in HLA-B27-negative patients. These results indicate that deposition of circulating ICs may be involved in the pathogenesis of acute anterior uveitis, especially in HLA-B27-negative patients.

Acute Disease↗

Corticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes.

The effects of the addition in vitro of corticosteroid on pokeweed mitogen (PWM) induced Ig synthesis by human peripheral blood lymphocytes were studied. IgG in supernatants produced under standardized culture conditions was measured by double antibody radioimmunoassay. The addition of 10(-6)M prednisolone caused a remarkable enhancement of PWM-stimulated IgG synthesis beginning at day 4 of culture and increasing at a faster rate than that in cultures with PWM alone. 10(-6)M prednisolone resulted in a geometric mean enhancement of 5.6-fold of PWM-stimulated IgG synthesis in all twenty-five normal controls studied. This enhancement occurred up to 3 days after the addition of PWM. 10(-6)M and 10(-5)M prednisolone resulted in significantly greater enhancement of PWM-stimulated IgG synthesis than 10(-7)M prednisolone. Hydrocortisone, prednisolone, methylprednisolone, betamethasone and dexamethasone at 10(-6)M were all equally effective in the enhancement of PWM-induced IgG synthesis.

Adrenal Cortex Hormones↗

Testosterone and estradiol concentrations in paired maternal and cord sera and their correlation with the concentration of chorionic gonadotropin.

Testosterone (T) and estradiol (E2) concentrations were determined and correlated with beta human chorionic gonadotropin (beta-HCG) concentrations in 43 paired maternal and cord sera (22 female and 21 male infants). Mean (+/- SD) maternal E2 concentrations were significantly (P less than .005) higher when the sex of the fetus was male than when the sex of the fetus was female (20.6 +/- 3.9 vs 13.5 +/- 3.2 ng/ml). Maternal T concentrations were not significantly different when related to the sex of the fetus (males, 114.8 +/- 60.7 vs females, 113.8 +/- 54.5 ng/100 ml, P greater than .1). Regression analysis did not show a significant correlation between maternal T or E2 concentrations and maternal beta-HCG concentrations. Mean cord serum T and E2 concentrations of male infants were significantly greater than that of female infants (T, 38.8 +/- 8.5 vs 25.8 +/- 7.1 ng/100 ml, P less than .005; E2, 9.1 +/- 3.3 vs 6.6 +/- 2.0 ng/ml, P less than .005). Regression analysis showed a significant (P less than .005) correlation between cord beta-HCG concentrations and E2 concentrations for male infants (r = .7) and female infants (r = .6). A significant correlation between cord beta-HCG concentrations and T concentrations was found for male infants (r = .5; P less than .01) but not for female infants (r = .3; P greater than .05). There was no correlation between maternal and infant E2 concentrations (males, r = .3, P greater than .05; females, r = .3, P greater than .2) or T concentrations (males, r = .02, P greater than 0.4; females, r = .06, P greater than .3). These data (1) confirm the sex difference in cord serum T and E2 concentrations, (2) indicate that the lower beta-HCG concentrations in mothers of male infants are associated with E2 concentrations which are greater than those in mothers of female infants, and (3) are consistent with an influence of beta-HCG on fetal T and E2 secretion.

Chorionic Gonadotropin↗

Tissue C3b receptors.

Using fluorescein-labelled S. typhi coated with C3b (FBC) the presence of a receptor for C3b in normal human glomeruli has been confirmed. A quantitative system, counting the number of FBC bound per unit area of glomerulus, has been developed. Experimental variables have been studied to determine optimal conditions for FBC binding. Glomerular FBC binding has been shown to be dependent on FBC concentration, temperature and time of tissue incubation. A standardized procedure has been adopted. Using this technique we have examined a number of target tissues, including synovium, skin, lung, choroid plexus and uveal tract, which are frequently affected in systemic immune complex diseases. No evidence of this receptor has been found in these tissues. These results suggest a mechanism different from the C3b receptor operating to localise immune complexes in these non-renal sites.

Choroid Plexus↗

Lymphoproliferative disease with IgM lambda monoclonal protein and autoimmune hemolytic anemia. A report of four cases and a review of the literature.

Four patients with lymphoproliferative disease with immunoglobulin M lambda (IgMlambda) monoclonal proteins and severe autoimmune hemolytic anemia are described. These patients had many features in common that may warrant their recognition as a specific entity within the lymphoproliferative spectrum. In each case, a wide thermal range low titer cold agglutinin was present. The association of cold autoimmune hemolytic anemia with IgMlambda monoclonal protein and lymphoproliferative disease is unusual. The literature on IgM monoclonal proteins associated with lymphoproliferative disease is reviewed with emphasis on the presence of direct antiglobulin test positive autoimmune hemolytic anemia.

Adult↗