Biomedical subjects
J S Goodwin
Publications and source records attributed to J S Goodwin.
Relationship between zinc intake, physical activity, and blood levels of high-density lipoprotein cholesterol in a healthy elderly population.
We investigated the relationship between level of exercise, ingestion of zinc supplements, and serum high-density lipoprotein (HDL) cholesterol levels in 270 healthy men and women over age 60. After controlling for sex, alcohol intake, and body mass, there was a significant positive correlation between level of exercise and serum HDL cholesterol in the 180 subjects not taking supplemental zinc (r = 0.26, P = .005) but not for those subjects taking supplemental zinc (r = -0.18, P = .14). Multiple regression analysis showed a significant interaction of zinc intake and activity level on HDL cholesterol (P = .04). In 22 subjects who were ingesting greater than 15 mg of supplemental, elemental zinc daily, cessation of zinc supplements for 8 weeks was associated with a significant increase in HDL cholesterol levels (2.0 mg/dL; P = .04). The change in HDL after stopping zinc was positively correlated with the level of exercise of the subjects (r = .41, P = .05). Thus supplemental zinc ingestion appears to block the exercise-induced increase in serum HDL cholesterol in a healthy population.
Discrepancy in the expression of autoantibodies in healthy aged individuals.
Sera from 50 healthy old subjects and from 51 young controls were tested by ELISA assays for a panel of autoantibodies, including IgM RF, anti-DNA, anti-F(ab')2, antithyroglobulin, anti-human albumin, anti-human hemoglobin, anti-secretory component from human IgA, and anti-gliadin. In vitro production of anti-DNA as well as anti-F(ab')2 antibodies were measured after stimulation of PBMC by pokeweed mitogen (PWM) in 12 healthy elderly subjects and 11 young controls. Sera from elderly donors contained threefold higher amounts of IgM RF than young controls (P less than 0.001). On the contrary, the levels of anti-DNA as well as anti-F(ab')2 antibodies were similar in both groups (P less than 0.3 for the two determinations). Anti-DNA and anti-F(ab')2 antibodies were also measured in supernates of PWM-stimulated glass nonadherent PBMC cultures from both old and young healthy donors without finding any significant difference between the two groups. Additional ELISA tests were also performed in both elderly and young control sera to detect antibodies against six other different antigens. No significant difference was found in the percentages of positive sera between the two groups. This discrepancy in production of IgM RF compared to other autoantibodies in healthy elderly subjects does not provide support for a general increase of autoantibodies with aging. The biological significance of an increase in IgM RF with aging remains to be determined.
Social bonds in a healthy elderly sample: characteristics and associated variables.
Social bonds were examined in 256 healthy, independent-living elderly men and women using the Interview Schedule for Social Interaction (ISSI). Multivariate techniques were used to test for relationships between six dimensions of social bonds, as measured by the ISSI, and demographic characteristics as well as scores from the Kellner-Sheffield Symptom Questionnaire, the Jacobs Cognitive Screening Exam, the Halstead Category Test and the Wechsler Memory Scale. The study participants reported involvement in a range of satisfying, supportive, interpersonal relationships. Significant associations were found between social bonds and income, marital status, work status and health status. Emotional status, cognitive functioning, and memory were found to be independent of social bonds in our statistical model.
Immunologic effects of nonsteroidal anti-inflammatory agents.
The author discusses the evidence that PGE is an immunomodulator and addresses the thesis that nonsteroidal anti-inflammatory agents, by blocking endogenous PGE production, act to partially correct the immunologic aberrations involved in the pathogenesis of rheumatoid arthritis.
Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis.
Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.
Comparison of admission and discharge medications in two geriatric populations.
Drug usage patterns were determined from a chart review of two groups of the elderly upon admission to and discharge from the hospital. A comparison was made between a United States group (N = 60) and a Scotland group (N = 60). The most common drugs noted in both groups were cardiovascular drugs (primarily diuretics) and vitamins and minerals. The mean number of drugs per patient in both groups was approximately four, with minimal change in number between admission and discharge. The number of drugs decreased with male sex and increasing age in the United States group and increased with male sex and increasing age in the Scotland group. The Scotland group was on more short-acting benzodiazepines, more bowel medications, more antidepressants, more antiparkinson agents, and fewer respiratory drugs than the United States group. Although both groups tended to have certain drugs deleted, Scotland patients were more likely to have narcotics discontinued and bowel medications added before discharge. These drug usage patterns demonstrate substantial polypharmacy in the elderly and the importance of selecting appropriate drugs in the elderly.
Effect of social support on stress-related changes in cholesterol level, uric acid level, and immune function in an elderly sample.
Strong social support systems, which in epidemiologic studies are associated with decreased morbidity and mortality, have been hypothesized to mitigate the harmful effects of stressful stimuli on the individual. The authors found that, among 256 healthy elderly adults, individuals with good social support systems tended to have lower serum cholesterol and uric acid levels and higher indices of immune function; these correlations were independent of age, body mass, tobacco use, alcohol intake, and degree of perceived psychological distress. Thus, social support systems may intervene between the stressful stimulus and the physiologic response to that stimulus.
Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit.
Human infection with the rickettsia Coxiella burnetii presents as an acute flulike primary Q fever, as a subacute granulomatous hepatitis, or, rarely, as chronic endocarditis. We have previously described lymphocyte unresponsiveness to Coxiella antigen in patients with Q fever endocarditis. This unresponsiveness was antigen specific and was mediated in part by adherent suppressor cells. In this report we show that the adherent suppressor cells work via prostaglandin E2 (PGE2)4 production. Addition of the cyclooxygenase inhibitor indomethacin to cultures of PBMC from patients with endocarditis or chronic laboratory exposure resulted in consistent increases in Coxiella-specific lymphocyte proliferation. The degree of increase in proliferation induced by indomethacin correlated strongly with the amount of PGE2 produced in a 4-hr culture stimulated by Coxiella antigen, but it also correlated with the sensitivity to inhibition of mitogenesis by PGE2. The suppressor mechanism was antigen nonspecific, because induction of suppression in vitro by Coxiella antigen also suppressed Candida-induced proliferation when both antigens were present in the same culture. Addition of indomethacin to these antigen cocultures totally reversed the Coxiella-induced suppression, confirming the evidence above that the nonspecific effector mechanism of suppression was prostaglandin (PG)-mediated. Elicitation of suppression, however, was antigen specific and involved a T cell-monocyte suppressor circuit. Supernatants from Coxiella-stimulated immune T cells and from the suppressor subset (OKT8+-enriched) of those T cells, but not unstimulated immune cells, induced augmented PGE2 production by unrelated nonimmune PBMC. We conclude that the lymphocyte unresponsiveness characterizing patients with Q fever endocarditis is modulated in part by an antigen-specific T suppressor cell which secretes a lymphokine to stimulate PGE2 production by adherent cells.
Induction of suppressor cells from peripheral blood T cells by 15-hydroperoxyeicosatetraenoic acid (15-HPETE).
15-hydroperoxyeicosetetraenoic acid (15-HPETE), a lipoxygenase metabolite of arachidonic acid, inhibited polyclonal IgG and IgM production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood mononuclear cells, whereas 15-hydroxyeicosetetraenoic acid (15-HETE) had little effect in this system. T cells preincubated for 18 hr with 15-HPETE caused substantial inhibition of IgG and IgM production of fresh, autologous B and T cells stimulated by PWM. The suppressive effect of the 15-HPETE-treated cells was lost if the cells were irradiated before the PWM culture, but not by treatment with mitomycin C. The suppressive effect was also lost if OKT8+ T cells were removed after, but not before, preincubation of the T cells with 15-HPETE. OKT8- T cells incubated with 15-HPETE for 18 hr showed a large increase in the percentage of cells staining with directly fluoresceinated Leu-2, another marker for suppressor cells. Thus, 15-HPETE induces functional and phenotypic suppressor cells from resting human peripheral blood T cells.
Effect of lipoxygenase metabolites of arachidonic acid on proliferation of human T cells and T cell subsets.
The lipoxygenase products LTB4 and 15 HPETE have been reported to stimulate T suppressor cell function and also to inhibit [3H]thymidine incorporation into mitogen-stimulated T cells. This present report documents that although these compounds do indeed inhibit [3H]thymidine incorporation into unfractionated T cells, they significantly enhance [3H]thymidine incorporation into T cell preparation enriched for cells bearing the cytotoxic suppressor cell phenotype identified by the OKT8 monoclonal antibody. The mitogen response of T cells enriched for OKT4+ helper-inducer cells is inhibited in manner similar to the response of unfractionated T cells. Thus, LTB4 and 15 HPETE stimulate both the function and the proliferation of the cytotoxic-suppressor T cell subset.
A case of hyperthyroidism presenting as recurrent pneumonia.
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Immunologic effects of nonsteroidal anti-inflammatory drugs.
Recent studies of the immunoregulatory effects of prostaglandin and the immunomodulating actions of nonsteroidal anti-inflammatory drugs reveal that earlier reports of inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs cannot alone fully explain the anti-inflammatory properties of these agents. Data defining the complex inter-relationship of prostaglandin, the immune response, and nonsteroidal anti-inflammatory drugs are reviewed, and possible mechanisms of anti-inflammatory action of these agents are considered. The effects of nonsteroidal anti-inflammatory drugs on cellular immune function and humoral immune response suggest that anti-inflammatory activity may be related to altered suppressor cell function, inhibition of monocyte collagenase release, or inhibition of neutrophil migration and activation. Further elucidation is awaited.
Mechanism of action of nonsteroidal anti-inflammatory agents.
Recent data from several laboratories, which suggest that generally accepted concepts relating to the mechanism of action of nonsteroidal, anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis may be incorrect, are reviewed. Over the past decade, most researchers have espoused the idea that NSAIDs act by inhibiting cyclooxygenase, thereby removing prostaglandins, which are thought to be responsible for pain and inflammation. Recent studies demonstrating that prostaglandins have important immunomodulating properties and that NSAIDs actually provide partial correction of several immunoregulatory dysfunctions in patients with rheumatoid arthritis are described. In addition, some NSAIDs inhibit migration along with other monocyte and polymorphonuclear leukocyte functions. Data suggest that these actions are not related to inhibition of cyclooxygenase.
The tomato effect. Rejection of highly efficacious therapies.
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Effect of irradiation on human T-cell proliferation: low dose irradiation stimulates mitogen-induced proliferation and function of the suppressor/cytotoxic T-cell subset.
Unfractionated human T cells exposed to 10-50 rad of X irradiation incorporated less [3H]thymidine than nonirradiated T cells when subsequently cultured with PHA or Con A. The cytotoxic/suppressor T-cell subset, isolated as either OKT8(+) or OKT4(-) cells, demonstrated significantly enhanced [3H]thymidine incorporation in PHA- or Con A-stimulated cultures after exposure to 10-50 rad, compared to unirradiated cells, while the proliferation of the OKT4(+) helper/inducer subset was inhibited by low dose irradiation. It has been previously reported that approximately 30% of the cytotoxic/suppressor subset also stains with OKM1. When the cytotoxic/suppressor subset was further subdivided into OKT4(-), OKM1(+), and OKT4(-), OKM1(-) cells, proliferation of the OKT4(-), OKM1(+) population was inhibited by exposure to 25 rad while proliferation of the OKT4(-), OKM1(-) population was stimulated. The increase in proliferation of the cytotoxic/suppressor T-cell subset after low dose irradiation is paralleled by an increase in suppressor activity of these cells. T cells exposed to 25 rad and then cultured with Con A for 48 hr caused greater inhibition of IgG production when added to fresh autologous lymphocytes stimulated by pokeweed mitogen than did unirradiated cells. Thus, low dose irradiation enhances both the proliferation and function of the human suppressor T-cell subset.
Inhibition of rheumatoid factor production by non-steroidal anti-inflammatory drugs.
The effects of NSAIDs on IgM rheumatoid factor production in vitro and on serum rheumatoid factor concentration in vivo were investigated using indomethacin (5.0 micrograms/ml), carprofen (10 micrograms/ml). IgM rheumatoid factor was isolated from lymphocytes of patients suffering from rheumatoid arthritis. NSAIDs inhibited IgM rheumatoid factor production in vitro. Furthermore, serum IgM rheumatoid factor was reduced when NSAIDs were administered in vivo. It is thought that NSAIDs effectively remove suppressor T-cells from the tonic inhibitory action of PGE2. This previously unrecognized action of NSAIDs may be a factor in their efficacy in rheumatoid arthritis.
Modulation of Fc gamma receptors on I cells and monocytes by 15 hydroperoxyeicosatetranoic acid.
We investigated the effects of the 15-lipoxygenase products, 15 hydroperoxyeicosatetranoic acid (15 HPETE) and 15 hydroxyeicosatetranoic acid (15 HETE) on Fc gamma receptor expression on human T cells and monocytes. Incubation of these cells with 15 HPETE but not 15 HETE results in a shift to decreased density of Fc gamma receptors on the cell surface.