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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 397 records · Page 22Linked to original sources
PubMed1982

Immunoregulation by blasts from null cell and T-cell leukemias: help and suppression of T-cell proliferative responses to mitogens.

The immunoregulatory activity of bone marrow leukemic blasts from five patients with null-cell acute lymphoblastic leukemia (ALL) and two children with T-cell ALL was evaluated. Blasts were studied in co-culture for their effects on the proliferative responses of normal allogeneic peripheral blood lymphocytes to phytohemagglutinin. Mitomycin C-treated null cell ALL blasts from two of five children suppressed the proliferative responses of normal responder cells by 80% and 58% whereas those from two other children enhanced the responses by 118% and 31%. T-cell leukemic blasts from one patient with T-cell ALL exhibited helper cell activity (26%) and T-leukemic blasts from the other demonstrated suppressor cell activity (53%). The helper cell activity of leukemic blasts was associated with stimulating capacity of null blasts in one-way mixed lymphocyte reactions. In six of seven cases, incubation of blast cells with concanavalin A (20 microgram/ml) for 48 hours prior to co-culture with responder cells did not result in the generation of significant suppressor cell activity. Our study suggests that leukemic blasts from certain patients with 'null' and T-cell ALL may possess spontaneous helper or suppressor cell immunoregulatory activity. This functional heterogeneity of leukemic blasts may help in subclassifying the ALL.

Adolescent↗
PubMed1982

Polyclonal and antigen-specific B-cell responses in patients with common variable immunodeficiency.

Antigen-specific antibody responses were investigated in 32 hypogammaglobulinemic patients with common variable immunodeficiency following in vitro sensitization of their peripheral blood lymphocyte cultures with sheep red blood-cell determinants. Anti-sheep red blood-cell antibody-secreting cells were quantitated in a hemolytic plaque assay. Amplification of T-cell help was achieved with the use of the T-cell mitogen concanavalin A or allogeneic irradiated T cells. Four patients groups, A through D, were identified. Group A was comprised of 10 patients whose cultured lymphocyte readily developed into antibody secreting cells. Cultures of 9 patients (Group B) responded suboptimally, but were enhanced following mitogen activation of autologous or exogenous T cells, and those of 7 patients (Group C) responded only when help was amplified. In 7 patients (Group D), no responses were elicited. On the simultaneous assessment of pokeweed mitogen-driven polyclonal generation of immunoglobulin-secreting cells, only 10 responders, all from groups A and B, were identified. Our observations indicate that the majority of patients with common variable immunodeficiency possesses B cells capable of producing antibody in vitro. The ability of some patients' B cells to respond only in the antigen-specific assay while failing to do so in pokeweed mitogen-stimulated cultures suggests that these two reactions are not identical in their activation pathways.

Adolescent↗
PubMed1982

Immunoregulatory properties of childhood leukemias.

Investigation of in vitro humoral immune responses and immunoregulatory properties of leukemic cell was carried out in 17 children with acute leukemia prior to therapy. Leukemias were of the non-T, non-B-cell type in 13 patients and of T-cell origin in four. Bone marrow and peripheral blood cells consisted of 24-96% lymphoblasts and were generally deficient in surface Ig-positive cells. Induction of Ig secreting cells in response to pokeweed mitogen was markedly decreased in marrow and peripheral mononuclear cell cultures of leukemic patients. Co-culture of leukemic cells with normal lymphocytes led to marked deviations from the expected Ig secreting-cell response of the cell mixtures. The predominant effect was enhancement, as was the case with eight non-T, non-B-cell and one T-cell leukemia samples. Suppression of the Ig secreting-cell response was observed in only three instances, two with non-T, non-B-cell and one with T-cell leukemia samples. These findings implicate non-T, non-B as well as more differentiated leukemic cells in having the potential for modifying Ig production by B cells.

Adolescent↗
PubMed1982

In vitro assessment of immune function in adrenalectomized rats.

Spleen and lymph node cells from normal or adrenalectomized (Adx) rats were assessed for a variety of in vitro immunological measures, including mitogen responsiveness, antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Proliferation in response to mitogens was evaluated with or without 2-mercaptoethanol (2-ME) in the culture media. Compared to spleen cells from normal rats, those from Adx rats demonstrated enhanced responsiveness to all mitogens tested. 2-ME increased proliferation of spleen cells from both normal and Adx rats, and the effect was additive to that of adrenalectomy. In contrast, lymph node cells from Adx rats manifested decreased mitogenic responsiveness compared to those of control rats and, with the addition of 2-ME, this difference disappeared for one of the mitogens tested (phytohemagglutinin). Compared to unoperated rats, ADCC and NK activities were significantly decreased in both the spleen and lymph nodes of the Adx rats. Alteration of normal leukocyte circulatory and homing patterns are suggested as a likely means by which adrenalectomy produces differential effects on lymphoid cells in various organs of the immune system.

Adrenal Cortex Hormones↗
PubMed1982

Prostaglandin regulation of murine mammary tumor virus production: a basis for some of the glucocorticoid and prolactin actions on mammary tumor cell cultures.

Hormonal regulation of mouse mammary tumor virus (MuMTV) production has been studied in cell cultures derived from mammary carcinomas of GR mice. The purpose of this study was to define the role of prolactin in dexamethasone-induced MuMTV production and to evaluate the mechanism(s) of action of these hormones. Results of our investigations in vitro establish a central role for prostaglandins, in particular PGF2 alpha. Prolactin treatment up to 1000 ng/ml increased the MuMTV production only slightly when added alone but a maximal stimulatory response was expressed when prolactin was added simultaneously with dexamethasone 2 micrograms/ml. This prolactin-related enhancement of MuMTV production was probably mediated by PGs since it was inhibited by indomethacin, an inhibitor of prostaglandin synthesis. When higher concentrations of indomethacin were used in dexamethasone-treated cultures, MuMTV production, although inhibited, was restored in part by addition of exogeneous PGF2 alpha. PGF2 alpha added alone stimulated the MuMTV production and, in combination with dexamethasone, showed a synergistic effect on stimulation of MuMTV production. Two compounds, PGF2 alpha and TXA2 (measured as TXB2), were produced in significant concentrations by these cultures. These findings suggest that PGF2 alpha exerts a regulating role on production of MuMTV in GR cells and indicate that the actions of both dexamethasone and prolactin are mediated at least in part by prostaglandins.

Animals↗
PubMed1982

Three distinct stages of B-cell defects in common varied immunodeficiency.

B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG, and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig mu chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG, and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into three approximately equal groups based on their responses. The first group showed normal proliferation in response to the two B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the second group showed proliferative responses to Cowan I or anti-mu, but no differentiation to Ig-secreting cells. The third group had no B-cell proliferative responses or differentiation in our assays. In several patients from each group, (i) helper T cells were functional in Ig-secreting-cell responses with purified normal B cells, (ii) patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture, and (iii) removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. These studies show that primary B-cell defects in common varied immunodeficiency occur at several levels, probably representing blocks at different stages of differentiation.

Adolescent↗
PubMed1982

Low-calorie diet prevents the development of mammary tumors in C3H mice and reduces circulating prolactin level, murine mammary tumor virus expression, and proliferation of mammary alveolar cells.

The effect of carlorie intake on the development of spontaneous mammary tumors in virgin C3H mice was studied. Only about 10% of the mice fed a low-calorie diet [10 kcal/day (1 kcal = 4.184 kJ)] since weaning developed mammary tumors, compared to about 60% of those mice that were reared on high-calorie diets (16 kcal/day or lab chow ad lib). In order to understand the mechanism by which a low-calorie diet decreases the occurrence of mammary tumors in mice, we compared the sex cycle, the amounts of circulating thyroid-stimulating hormone (thyrotropin), growth hormone, and prolactin, the production of type A and B virus particles in the mammary glands, and the morphology of the mammary glands of mice fed low- and high-calorie diets. The amount of serum prolactin and the synthesis of type A and B particles in mammary tissues of mice fed a low-calorie diet was markedly decreased compared to those of age-matched mice fed high-calorie diets. In addition, in young mice fed a low-calorie diet, there were fewer mammary alveolar lesions than in mice fed a high-calorie diet, although the size of the lesions was similar. However, in older mice fed the high-calorie diet, the number and size of these lesions were greater than in the mice raised on the low-calorie diet. The other factors that we studied were not affected by calorie restriction. Our findings suggest that the reduction in serum prolactin level, mammary tumor virus production, and proliferation of mammary alveolar lesions associated with dietary calorie restriction is responsible for lowering the incidence of mammary tumors in mice.

Animals↗
PubMed1982

Abnormal humoral immune responses in peripheral blood lymphocyte cultures of bone marrow transplant recipients.

The present study was aimed at investigating recovery of humoral immunity in vitro after bone marrow transplantation in patients with acute leukemia and severe aplastic anemia. Hemolytic plaque assays were utilized to quantitate pokeweed mitogen-stimulated polyclonal immunoglobulin production and sheep erythrocyte antigen-specific antibody responses in cultures of peripheral blood mononuclear cells of 39 patients beginning at 1 month, for variable periods up to a maximum of 4 years after marrow transplantation. Three phases were identified: an early period of primary B cell dysfunction with concomitant immunoregulatory T cell abnormalities--i.e., decreased helper and increased suppressor activities; an intermediate phase in which B cell dysfunction could be attributed in large measure to immunoregulatory T cell abnormalities; and a late phase of normal B and T lymphocyte functions. Patients with graft-versus-host disease differed from those without it in that they often did not manifest increased T cell suppressor activity in the early period, and they were noted to have prolonged and profound B and T cell abnormalities in the chronic phase of their disease. In selected patients, simultaneous assessment of ratios of Leu-2 to Leu-3 antigens on T cells by monoclonal antibodies and of immunoregulatory T cell functions revealed a correlation between the two only late in the post-transplant period. These studies provide an insight into the ontogeny of B cell function in the post-transplant period and indicate that in certain situations phenotypic alterations in T cell subsets cannot reliably be used to predict abnormalities in their function in recipients of marrow transplantation.

Acute Disease↗
PubMed1982

Impaired proliferative response to B-lymphocyte activators in common variable immunodeficiency.

The cell-mediated immune responses of 39 patients with common variable immunodeficiency (CVI) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators wee found to require intact B-lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared wit those of controls studied in parallel (P less than 0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients' lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG less than 125 mg/dl had markedly lower (P less than 0.01) lymphocyte responses than those with serum IgG greater than 300 mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B-cell number in these patients, intrinsic B-lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases.

Adolescent↗
PubMed1982

The platelet factor 3 assay and circulating immune complexes as studied on non-thrombocytopenic patients with systemic lupus erythematosus.

Sera from 21 patients with systemic lupus erythematosus (SLE) were tested with a platelet factor 3 (PF3) assay. A control serum (pooled blood group AB serum) was always run in parallel with the test sera. The test and control sera were run in duplicate and for each patient the mean recalcification time was used for the calculation of the test serum: AB serum ratio. Concomitantly, the patients' serum concentrations of circulating immune complexes (CIC) were measured by using the Raji cell radioimmunoassay. 20 healthy hospital employees served as controls. In the latter subjects the mean test serum: AB serum ratio was 0.99 (range 0.92-1.09), their CIC concentrations being less than or equal to 16 micrograms/ml. 7 of the SLE patients had CIC values less than or equal to 16 micrograms/ml, and their test serum: AB serum ratios ranged 0.95-1.09. All the remaining SLE patients had elevated values for CIC. In the total material of SLE there was a highly significant (r = -0.87; P less than 0.001) negative correlation between the test serum: AB serum ratios and the values for CIC. It is widely held that the so-called PF3 immunoinjury test detects circulating antiplatelet antibodies. The present results, however, strongly suggest that the assay rather or also detects CIC which like antiplatelet antibodies may damage platelets as we and others have shown in prior publications.

ABO Blood-Group System↗
PubMed1982

Nutrition and immunity: the influence of diet on autoimmunity and the role of zinc in the immune response.

Nutrition exerts profound influence on immunological functions effecting both cell-mediated (humoral) and T cell-mediated (cellular) immune functions. Even the interaction of the immune systems can be profoundly influenced by restrictions or excesses of dietary constituents. In experimental systems where it is possible to control precisely the influence of specific nutriments, development and expression of autoimmune diseases and the associated immunodeficiencies of aging can be delayed by restrictions of dietary protein, protein and calories, fat, zinc, or even essential fatty acids. Tumor immunities likewise can be affected and sometimes even enhanced by restriction of protein, calories, or protein and calories, an influence associated with major delay in development of the experimental cancers--e.g. breast cancer. T cell-mediated immunodeficiencies associated with clinically apparent protein or protein calorie malnutrition are often attributable not to the major nutriment deficiencies per se but to accompanying zinc deficiency, a finding reflecting the vital role of zinc in many immunological functions. Dietary zinc deficiency appears to be responsible, at least in part, for the immunodeficiency that is so regularly associated with certain human cancers, such as epidermoid cancers of the head and neck region.

Animals↗