Degeneracy and race in the nineteenth century: the impact of clinical medicine.
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History, Modern 1601-↗
Biomedical subjects
S C Gilman
Publications and source records attributed to S C Gilman.
Failure of naloxone or beta-endorphin to affect pressure-induced tremor in guinea pig.
Naloxone in doses up to 2 mg/kg and beta-endorphin in doses up to 1 mg/kg had no suppressive effect on pressure-induced tremor or cortical EEG activity in the guinea pig. The lack of effect of either naloxone or beta-endorphin on the HPNS provides evidence that opiate receptor mechanisms are not significantly involved in this syndrome.
Animals↗
Effects of aging on cell cooperation and lymphocyte responsiveness to cytokines.
Functional activities and cell cooperation of macrophages (Mphi), T cells, and B cells of young and old Lewis rats were compared. Splenic M phi from young and old rats provided accessory help for T cell mitogenesis and B cell mitogenesis, provided accessory help for generation of PFC, and produced IL 1 equally well as measured in costimulator assays. Splenic T cells of aged Lewis rats, however, were poorly responsive in mitogen assays and did not respond to supplemental IL 2 and antigen with blast transformation and with increased help for B cells to produce PFC. "Old" B cells did not respond in vitro to mitogens with help from M phi and T cells, nor did they respond to B cell helper factor with increased PFC. The data indicate that hyporesponsiveness of the immune system, especially of B cells, in aged rats is due in part to defective reactivity to interleukins and cytokine(s) and to defective cell-cell cooperation.
Aging↗
Inhibition of interleukin synthesis and T cell proliferation by a monoclonal anti-Ia antibody.
The proliferative response in vitro of Lewis rat spleen cells to Con A was inhibited by a monoclonal antibody, OX4, with specificity for a public rat la antigen. Inhibition was dose-dependent and was observed only if the antibody was present during the first 48 hr of culture. OX4 anti-la antibody inhibited production of IL 1 by peritoneal exudate cells activated by lipopolysaccharide and inhibited the production of IL 2 by spleen cells activated by Con A. Addition of exogenous IL 1 to spleen cell cultures inhibited by OX4 anti-la antibody augmented production of IL 2 and returned the proliferative response of T cells to levels observed in Con A-stimulated cultures. We suggest that OX4 anti-la antibody reacts with la+ accessory cells to inhibit production of IL 1, which in turn limits production of IL 2 and finally T cell proliferation.
Animals↗
Fetal development: effects of decompression sickness and treatment.
Pregnant hamsters were exposed to 7.1 ATA (200 fsw) of compressed air breathing for 40 min. Comparisons were made between three groups of pregnant hamsters: (a) those that developed decompression sickness (DCS); (b) those that did not; and (c) a control (non-divided) group. As reported previously, maternal DCS if untreated resulted in frequent and severe teratogenic effects. Furthermore, fetuses from those females who apparently did not develop DCS were significantly smaller at term than fetuses from the control animals. However, fetuses from females that were treated for DCS did not differ from controls. This suggests that 40-min, 200-fsw dives per se are detrimental to fetal development in hamsters.
Animals↗
beta-Endorphin enhances lymphocyte proliferative responses.
The opioid peptides alpha- and beta-endorphin and [D-Ala2, Met5]enkephalin were investigated for their effect on the proliferation of resting and activated rat splenic lymphocytes in vitro. beta-Endorphin enhanced the proliferative response of spleen cells to the T cell mitogens concanavalin A and phytohemagglutinin. The effect of beta-endorphin was dose dependent and occurred at peptide concentrations similar to those found in rat plasma. alpha-Endorphin and [D-Ala2, Met5]enkephalin did not affect the proliferative responses to any mitogen tested. Furthermore, the potentiating effect of beta-endorphin was not reversed by treatment with 10 microM naloxone. None of the peptides had any effect on resting, unstimulated spleen cells or on the response to a mixture of lipopolysaccharide and dextran sulfate, which is specifically mitogenic for B lymphocytes. The pharmacological properties of the beta-endorphin potentiation indicate that the effect may be mediated by a nonopiate but beta-endorphin-specific mechanism. These results suggest a possible role for peripheral beta-endorphin and may provide a link between stress and disease susceptibility.
Analgesics↗
Activation of rat B lymphocytes. II. Functional and structural changes in "aged" rat B lymphocytes.
Anti-mu, anti-gamma, and anti-delta antibodies induce proliferation of splenic B lymphocytes from young Lewis rats, measured by 3H-TdR uptake. In contrast, splenic B cells of aged Lewis rats respond poorly or not at all to these reagents. T lymphocytes or interleukin 2 (IL-2) of young or aged rats augment the uptake of 3H-TdR in cultures of "young" B cells responding to anti-Ig reagents or LPS and DxS, but have no significant effect on the responses of "old" B cells. Analysis of spleen cells of young and aged rats in a fluorescence-activated cell sorter indicates the density of mu, gamma, and delta isotypes is reduced in "old" B cells, and that B cells of aged rats are significantly larger than those of young rats. These results delineate anatomic and structural changes in B lymphocytes of aged rats.
Aging↗
Altered levels of mononuclear leukocytes in tumor-bearing rats: decrease of helper T lymphocytes and increase of suppressor cells.
In the spleen and peripheral blood of BN rats with progressive tumors, W3/25+ T helper cells were significantly reduced and OX8+ T suppressor/cytotoxic cells were significantly increased. The ratio of helper to suppressor elements was decreased to 1.6 from a ratio of 3 in normal BN rats without tumors, and this decreased ratio correlated with tumor growth. When tumors were eliminated in vivo by infusion of effector cells (W3/25+ T lymphocytes), the levels of W3/25+ and OX8+ T cells returned to normal and the ratio of helper to suppressor/cytotoxic cells in the spleen and peripheral blood reverted to 3.0 or higher. Macrophages and null cells, T-sIg-, were also elevated in the spleen and peripheral blood of rats bearing expanding tumors and returned to normal levels after cure. Assays of spleen cells for cell-mediated cytotoxicity in rats with large tumors revealed little or no specific cytotoxicity. Cytotoxic activity was high in spleen of rats cured of their neoplasms by infusion of helper cells.
Animals↗
T lymphocytes of young and aged rats. II. Functional defects and the role of interleukin-2.
Splenic T lymphocytes of aged Lewis rats respond to Con A and PHA with diminished 3H-TdR uptake compared with splenic T lymphocytes of young Lewis rats. After immunization with allogeneic tumor cells, uptake of 3H-TdR in mixed lymphocyte-tumor cultures and T cell cytotoxicity against tumor target cells are significantly lower with spleen cells of aged rats compared with those of young rats. The culture of spleen cells of aged rats with Con A results in a diminished conversion of Ia-positive T cells from Ia-negative precursors compared with similar cultures of spleen cells of young rats. Spleen cells of both young and aged rats produce high amounts of IL-2 in response to Con A stimulation. "Old" T cells, however, bind relatively little IL-2, do not utilize it in culture, and do not respond to exogenous IL-2 with enhanced 3H-TdR uptake as do "young" T cells. In allogeneic MLTC, "old" T lymphocytes produce little IL-2 compared with "young" cells, and both "young" and "old" cells respond to exogenous IL-2 with enhanced 3H-TdR uptake and increased cytotoxic activity. The data suggest defects in the synthesis and/or recognition of IL-2 as well as defects in the regulation of Ia antigen expression may be responsible, in part, for the reduced T cell function in aged animals.
Aging↗
Immunotherapy of a chemically-induced sarcoma in rats: characterization of the effector T cell subset and nature of suppression.
Chemically-induced sarcomas (BC5), established subcutaneously and growing progressively in BN rats, were completely eliminated by i.v. infusion of syngeneic effector cells. The effector cells were generated from BN spleen cells immune to BC5 in a mixed lymphocyte-tumor cell culture (MLTC). Generation of a high yield of effector cells that were efficacious in eliminating BC5 in vivo necessitated: depletion of macrophages from immune spleen populations, before preparation of MLTC; addition back to MLTC of a small number of macrophages from normal spleens to attain a level of 0.5% of the spleen cells in culture; and addition of T cell growth factor on day 5 of MLTC. With these conditions a subset of T cells was expanded. They were blast cells with surface markers W3/25 and Ia, which exhibited no cytotoxic activity in vitro, and probably functioned as a helper or amplifier element in the tumor-bearing host. Effector cells generated in MLTC with BC5, treated with mitomycin C, were specific for BC5 in vivo and did not affect growth of a viral-induced BN tumor.
Animals↗
Regulation of rat B cell responses by T cell subsets and interleukin 2.
T cell and interleukin 2 (IL 2) regulation of two phases of B cell activation, 3H-TdR uptake and differentiation to antibody-forming cells, were examined. Monoclonal antibody specific for rat kappa light chains (Mab alpha K) stimulated 3H-TdR uptake in vitro in B cell fractions of Lewis spleen cell populations in the presence of T cells and macrophages (M phi); IL 2 reconstituted the response in enriched B cell cultures depleted of T cells and M phi. When IL 2 was added to primary in vitro cultures, spleen cells yielded 100 to 400 anti-SRBC PFC/culture; no PFC were recorded in the absence of IL 2. These results suggested that IL 2 served as a " second signal" for activation in responsive B cell populations. When monoclonal antibody specific for the W3/25+ T cell subset (Mab W3/25) was incorporated into the assay system, both 3H-TdR uptake and PFC responses were inhibited. IL 2 enhancement of B cell responses or responses of reconstituted B cell and T cell fractions was eliminated in the presence of Mab W3/25, indicating that IL 2 mediation of B cell responses was due in part to participation of W3/25+ T cell helper function. In contrast, monoclonal antibody directed to the OX8-bearing T cells (Mab OX8) had no effect on B cell responses. W3/25+ T cells provided helper activity in the generation of a PFC response, whereas OX8+ cells suppressed the antibody response. W3/25+ T cells responded to antigenic stimuli in the presence of IL 2 by undergoing increased blast transformation. OX8+ cells did not exhibit any response. These data define a regulatory network by which T cells, IL 2, and B cells interact to produce in vitro DNA synthesis and antibody formation in activated rat B cells.
Animals↗
Membrane phenotype of the rat cytotoxic T lymphocyte.
We have examined rat cytotoxic T lymphocytes for expression of W3/25, OX8, Ia, Thy-1 antigens, and Fc gamma receptors using an effector cell-target cell conjugate formation assay in conjunction with immunofluorescence techniques. Lymph node, spleen, and peritoneal exudate T cells from Lewis rats immunized with allogeneic BN tumor cells specifically bound to and lysed BN tumor targets and BN blast cells, but did not bind or lyse syngeneic Lewis sarcoma cells, Lewis blast cells, or Lou/M blast cells. The numbers of binding and cytotoxic T lymphocytes were greatest in peritoneal exudate cells of immunized rats, less in spleens, and least in lymph nodes. Seventy to 80% of the lymphocytes bound to tumor targets were OX8+ T lymphocytes; less than 12% expressed W3/25, Ia, Thy-1, or Fc gamma R. Moreover, only OX8+ T cells efficiently lysed the target cells to which they were bound. The membrane phenotype of rat cytotoxic T lymphocytes was: OX8+, W3/25-, Ia-, Thy-1, and Fc gamma R-. Monoclonal OX8 antibody did not inhibit target cell binding or subsequent lysis by effector T cells, and there was no diminution of target cell binding or cytotoxic activity when the OX8 antigen was shed from the cell surface before interaction with target cells. There was no preferential association of OX8 antigen at the interface between the effector and target cell. Thus, OX8 antigen marks a subset of rat T lymphocytes that are cytotoxic but the molecule appears not to play a functional role in the cytotoxic process.
Animals↗
Effect of a 68-day submarine patrol on serum 25-hydroxyvitamin D levels in healthy men.
Serum 25-OH-D levels were determined for 30 submariners prior to, and near the end (day 63), of a patrol lasting 68 d. A significant reduction occurred in serum 25-OH-D levels during the patrol compared to levels obtained before the patrol. Nearly one-third of the sample has serum 25-OH-D levels that were below the minimum normal levels. The late-patrol depletion of serum 25-OH-D was not associated with lower levels of calcium. On the contrary, serum calcium levels were found to be significantly elevated during the late-patrol period compared to pre-patrol levels, even among those submariners who had serum 25-OH-D levels in the low normal or below normal range. This calcium effect may be mediated by the high levels of carbon dioxide maintained in the submarine breathing atmosphere.
Adult↗
Serum ferritin increases during deep saturation dives.
Serum ferritin levels were determined in six U.S. Navy divers during a 29d helium-oxygen saturation dive. Progressive increases in serum ferritin were observed during compression. These increases were maintained during decompression and for 1 week postdive. No relationship was found between serum ferritin increases and the development of decompression sickness (DCS). However, the two divers who subsequently developed DCS had significantly higher serum ferritin levels than those divers who remained free of DCS. These findings indicate that DCS does not result in differential serum ferritin variability and may, therefore, not be involved directly in aseptic bone necrosis (ABN) as postulated earlier by others. However, high baseline levels of serum ferritin may be involved in both DCS and ABN.
Adult↗
Fetal development: effects of stimulated diving and hyperbaric oxygen treatment.
Fetuses from hamsters exposed to repetitive 5.2-ATA (140 fsw) air dives during early pregnancy showed no significant differences from the control group in birth weight, frequency of malformation, or death. Also, exposure of mothers to hyperbaric oxygen as required for treatment of decompression sickness (DCS) has no adverse effect on fetal development or survival. Although the number of females who suffered and survived DCS in this study was small (n = 3), teratogenic effects were nevertheless found among the fetuses of this group. In fact, at least one fetus from each female undergoing DCS was found to have serious malformations. These results suggest that DCS during early organogenesis may have significant deleterious effects on fetal development.
Animals↗
A comparison of utilization of community primary health care and school health services by urban Mexican-American and Anglo elementary school children.
The health care utilization of urban Mexican-American and Anglo elementary school children was recorded at school and community primary-care sites over a 1-year period. No significant differences were found between the two groups with respect to visiting/nonvisiting behavior or frequency of visits. Two unobtrusive measures were used to ascertain the degree of acculturation of the Mexican-American children and their parents: return of Spanish-language questionnaire and enrollment of the child in bilingual classes. No significant differences were found in the proportion of visitors/nonvisitors in each group or the total number of visits for health services among these children. Mexican-American and Anglo children did not differ in the type of health problems presented, except that fewer Mexican-American than Anglo children had visits for emotional, behavioral or learning problems. Results indicate that when health services are available and accessible, and when the barriers of language and income are minimized, Mexican-American and Anglo children do not differ in their use of health services in the community.
Child↗
Antibody responses in humans to individual proteins of herpes simplex viruses.
Sera from 231 women were used to examine their frequency of precipitation of various herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) proteins and to determine if there was a rank order of immune responsiveness of humans to these HSV antigens. Radiolabeled viral proteins were reacted with serum and immune complexes isolated with staphylococcal protein A. Individual antigens were resolved by polyacrylamide gel electrophoresis and visualized by fluorography. As a group, these sera precipitated 31 HSV-1 and 27 HSV-2 proteins. HSV-1 polypeptides with molecular weights of 133,000, 99,000, and 82,000, as well as HSV-2 polypeptides with molecular weights of 131,000 and 101,000, were precipitated by essentially all sera that contained antibodies to HSV-1 and HSV-2. When attempts were made to order the viral proteins by constructing precipitation profiles ranking the antigens in patterns according to their frequency of precipitation, it was observed that the antigens were generally not ordered. Demographic analysis of the sera suggested that the differences in the number of proteins precipitated were associated with differences in age, education, age at first marriage, and income, which collectively may reflect the frequency of exposure to the virus.
Adult↗
T lymphocytes of young and aged rats. I. Distribution, density, and capping of T antigens.
The distribution, density, and capping of the T cell antigens W3/13, W3/25, and Thy-1 were studied in lymphocytes of young (3 to 4 mo) and aged (greater than or equal to 27 mo) Brown Norway (BN) rats. The total number of W3/13, W3/25, and Thy-1 positive cells and the percentage of Thy-1 positive cells are reduced in the spleens and lymph nodes of aged rats. Analysis of spleen and lymph node cells in a fluorescence-activated cell sorter indicated that with ageing there is a loss of moderately and brightly stained W3/13 and W3/25 positive cells. The density of W3/13, W3/25, and Thy-1 is reduced on spleen and lymph node cells of old rats. The rate of capping of all 3 molecules is diminished on "old" cells. Colchicine treatment of young cells enhanced capping of all 3 molecules and allowed capping of W3/13 by a single ligand. However, capping on "old" lymphocytes was not affected by colchicine treatment. Cytochalasin D inhibited capping to the same extent on young and "old" cells. These results suggest that the membrane composition and cytoskeleton are altered in T lymphocytes of aged rats.
Aging↗