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Biomedical subjects

J S Goodwin

Publications and source records attributed to J S Goodwin.

At least 127 records · Page 7Linked to original sources

Wisconsin Card Sort Test performance in a healthy elderly population.

A 64-card version of the Wisconsin Card Sort Test (WCST) was administered to 5 groups (n = 95), aged 17 to 25, 64 to 69, 70 to 74, 75 to 79 and 80 to 87 years. The elderly groups were chosen for their lack of medical problems in order to determine if previously reported age-related deficits were due to chronic medical problems or to aging per se. The resulting pattern of means showed statistically significant differences only for number of categories attained and total number of errors. For both variables, the 80- to 87-year-old group performed more poorly than the 64- to 69-year-old group. These results, although consistent with previous findings suggestive of frontal lobe vulnerability in old age, indicate that deterioration is less marked for a healthy elderly population.

Adolescent↗

A prospective study of response to stressful life events in initially healthy elders.

Behavioral and physiological reactions to the stress of a major life crisis were studied prospectively in a group of healthy elderly individuals. Significant decreases in caloric intake, body weight, and lymphocyte count were found following the stressful event with a return toward baseline levels after a recovery period. Significant increases were found for psychological distress and serum cortisol. The results support the thesis that behavioral and physiological changes occur during an event perceived by an elderly person to be stressful and that such changes can have adverse effects on health.

Aged↗

Daily multivitamin supplementation and vitamin blood levels in the elderly: a randomized, double-blind, placebo-controlled trial.

Despite the many questions being raised about multivitamin use by the elderly, it has not been proven that consuming an oral multivitamin alters vitamin blood levels in the aged. To address this question, we performed a randomized, prospective, placebo-controlled study of daily multivitamin supplementation in 101 noninstitutionalized ambulatory elderly persons (median age, 64 years). Vitamin levels were assayed at baseline, and at two and four months of supplementation. At four months, those taking multivitamins had statistically significant increased levels of water soluble vitamins (C, B2, B12, plasma, and erythrocyte folate) that were greater than changes noted for the placebo group. This was not true for fat soluble vitamins A and E. Greater storage pools of fat soluble vitamins help explain this discrepancy. We conclude that in the ambulatory elderly, oral multivitamins can raise levels of water soluble vitamins but the effect on fat soluble vitamins remains uncertain.

Administration, Oral↗

Alcohol intake in a healthy elderly population.

The relationship between amount of alcohol consumption and social, psychological, and cognitive status was examined in 270 healthy, independently living men and women over age 65. Forty-eight per cent of the sample recorded some alcohol intake during a three-day diet record, with 8 per cent drinking 30 or more grams of alcohol daily. Alcohol intake was positively associated with male gender, income, and amount of education and negatively associated with age. Alcohol intake was not associated with any changes in social or psychological status, but was positively associated with several measurements of cognitive status. These correlations were weak, however, and tended to disappear after controlling for income, education, gender, and age. Past alcohol intake was not associated with any indicators of present social, psychological, or cognitive functioning.

Age Factors↗

Survival of American Indian and Hispanic cancer patients in New Mexico and Arizona, 1969-82.

Survival was examined by ethnic group for 31,465 incident cancer cases diagnosed from 1969 through 1982 in Hispanic and non-Hispanic whites residing in New Mexico and in American Indians residing in New Mexico and Arizona. In comparison with the 1- and 5-year survival rates following the diagnosis of cancer for non-Hispanic whites, those for American Indians were generally poorer and, to a lesser extent, those for Hispanics were also poorer. The American Indian and Hispanic patients tended to have more advanced disease at the time of diagnosis, although this pattern was not consistent across all sites. For many primary cancer sites, American Indian patients were less likely to receive treatment for their cancer than were non-Hispanic whites. Hispanics were also less likely to be treated for cancers of some sites, although the differences were not as large as for American Indians. However, after adjustment for stage and treatment, American Indians demonstrated significantly poorer survival than non-Hispanic whites for cancers of many sites. After adjustment for stage and treatment, survival in Hispanics was generally comparable to that in non-Hispanic whites.

Age Factors↗

Choice of cancer therapy varies with age of patient.

We used data on 22,899 cancer cases collected by the New Mexico Tumor Registry to examine the relationship between patient age and the use of potentially curative therapy for cancers of selected sites and acute leukemias. For cancers of most sites, either local or regional stage, the proportion of cases receiving potentially curative therapy declined with age. For local-stage cancers, the proportion not given any treatment increased with age. Overall mortality rates during the first year after diagnosis were much higher for local-stage cases without treatment than for those who received treatment. These data show that cancer therapy varies with age and suggest that decision making regarding therapy is influenced by the presence of other diseases.

Adult↗

Mechanism of action of glucocorticoid-induced immunoglobulin production: role of lipoxygenase metabolites of arachidonic acid.

Glucocorticoids stimulate polyclonal immunoglobulin (Ig) production in cultures of human peripheral blood lymphocytes. The mechanism of action of glucocorticoids in this system, and indeed in any physiologic system, is unknown. Because glucocorticoids stimulate the production of phospholipase A2-inhibitory glycoproteins, we investigated whether glucocorticoids stimulate polyclonal Ig production by inhibition of arachidonic acid metabolism. Nonspecific lipoxygenase/cyclooxygenase inhibitors stimulate polyclonal Ig production in a manner similar to the effect of glucocorticoids, whereas specific cyclooxygenase inhibitors actually inhibit Ig production. Two specific 5-lipoxygenase inhibitors, with little or no activity against cyclooxygenase or other lipoxygenases, also stimulate Ig production. The dose-response effect of all of these drugs on Ig production was similar to the dose response of inhibition of 5-lipoxygenase. Leukotriene B4 (LTB4) added in low concentrations (10(-10)M) on days 1, 2, and 3 of a culture eliminated the stimulatory effect of glucocorticoids or 5-lipoxygenase inhibitors, whereas LTC4, LTD4, prostaglandin E, or 5-hydroxyeicosatetraenoic acid had no effect. These results suggest that the relevant action of glucocorticoids in stimulating Ig production might be in preventing endogenous arachidonic acid metabolism, perhaps the endogenous production of LTB4.

Arachidonic Acid↗

Arachidonic acid inhibits 5-lipoxygenase in human T cells.

The data on whether T cells produce leukotrienes or other 5-lipoxygenase metabolites of arachidonic acid is conflicting. We report that exogenous arachidonic acid added to phytohemagglutin-stimulated human T cells profoundly inhibits leukotriene B4 production, with 90% inhibition caused by 10(-6) M arachidonic acid. The 12- and 15-lipoxygenase pathways were also inhibited by arachidonic acid. Recent reports that human T cells produce no 5-lipoxygenase metabolites of arachidonic acid might be explained by the fact that the studies used greater than or equal to 10(-5)M arachidonic acid in the incubation media.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Leukotriene B4 causes proliferation of interleukin 2-dependent T cells in the presence of suboptimal levels of interleukin 2.

We have recently found that endogenous leukotriene B4 (LTB4) production is a necessary component of mitogen-stimulated T-cell proliferation. In this report, we address the relationship between LTB4 and interleukin 2 (IL-2) in stimulating proliferation of IL-2 responsive T cells. We employed an IL-2 responsive T-cell line, HT-2 and also human peripheral blood T cells rendered IL-2 responsive by culture with phytohemagglutinin (PHA). In the presence of concentrations of IL-2 that resulted in suboptimal stimulation of HT-2 cells (5-20% of maximum proliferation), LTB4 at 10(-8) or 10(-10) M produced a several-fold increase in [3H]thymidine incorporation, resulting in levels of [3H]thymidine incorporation that were comparable to those produced by HT-2 cells stimulated with optimal concentrations of IL-2. Similar results were obtained with the peripheral blood T cells. Leukotriene C4, prostaglandin E2 (PGE2), and arachidonic acid did not share with LTB4 the ability to stimulate proliferation of HT-2 cells. Hydrocortisone and nordihydroguairetic acid (NDGA), drugs which block endogenous LTB4 production in cell cultures inhibited [3H]thymidine incorporation of HT-2 cells stimulated by suboptimal but not optimal levels of IL-2. This inhibition could be overcome by the readdition of LTB4 to the cultures. Thus, LTB4 in physiologic concentrations (10(-10) M) can substitute for IL-2 in stimulating proliferation of IL-2 responsive T cells, provided that some IL-2 is present in the culture. Endogenous LTB4 may act synergistically with endogenous IL-2 in promoting T-cell proliferation.

Cell Line↗

Effect of chronic ingestion of a prostaglandin E analogue on immunologic function in healthy elderly subjects.

The immunologic effects of an oral prostaglandin E1 (PGE1) analogue were tested in 25 individuals over age 65, compared to 25 individuals given placebo. Elderly subjects were chosen because previous in vitro studies had found an increased sensitivity to PGE of lymphocytes in older subjects. After 2 weeks of ingestion of PGE analogue or placebo, there was a small but statistically significant decrease in IgM-rheumatoid factor in the PGE analogue group compared to control and a significant decrease in the in vitro sensitivity of lymphocytes from the PGE analogue group to inhibition by PGE. There were no differences in total lymphocyte count, T cell or T cell subset count, delayed hypersensitivity skin test reactivity, serum immunoglobulins, or response to mitogens between the two groups. Administration of an oral PGE analogue to normal elderly individuals is not associated with any detrimental effects on immunologic function after 2 weeks.

Aged↗

Morbidity and mortality in an initially healthy elderly sample: findings after five years of follow-up.

This report summarizes morbidity and mortality data for 263 initially healthy elderly men and women from the beginning of this study through five years of follow-up. The mortality rate for this sample averaged approximately 1.8% per year and the duration of terminal illness averaged 4.9 months. The cancer incidence rate has increased whereas new diagnoses of cardiovascular disease and degenerative conditions have declined. The data support the potential for maximizing vigour and health well into the seventh and eighth decades of life.

Aged↗

Stage at diagnosis of cancer varies with the age of the patient.

The stage of a cancer at diagnosis is multiply determined, theoretically depending on such disparate factors as tumor biology, patient education, and physician behaviors. Data from all Hispanic and non-Hispanic white residents of New Mexico diagnosed with a malignancy from 1969 through 1982 were analyzed to determine the relationship between the age of the patient and the stage of cancer at the time of diagnosis. Three general patterns were apparent. For cancers of the bladder, breast, cervix, ovary, thyroid, and uterus, and for melanoma, there were significant linear trends for the cancers to be diagnosed at more advanced stages in older patients. For cancers of the lung, pancreas, rectum, and stomach, there were significant linear trends for cancers to be diagnosed at an earlier stage in older patients. For cancers of the colon, kidney, liver, and prostate, there were no significant linear trends in stage at diagnosis versus age of the patient.

Age Factors↗

Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

The mechanism whereby glucocorticosteroids are immunosuppressive is unknown. One potential mechanism of action of these compounds is inhibition of arachidonic acid metabolism. We found that the inhibition of lymphocyte proliferation by hydrocortisone or dexamethasone was mimicked by nonspecific lipoxygenase inhibitors and also by a specific 5-lipoxygenase inhibitor, but not by a specific cyclooxygenase inhibitor. Mitogen-stimulated cultures of T cells produce approximately 5 X 10(-9) M leukotriene B4 (LTB4) in 24 h. This production of LTB4 is completely inhibited by concentrations of hydrocortisone or lipoxygenase inhibitors that inhibit mitogen-induced [3H]thymidine incorporation. The inhibition of lymphocyte proliferation by either hydrocortisone or by the 5-lipoxygenase inhibitor was totally reversed by LTB4 but not by leukotriene C4 or leukotriene D4. LTB4 had no effect on the inhibition of lymphocyte proliferation by noncorticosteroids such as prostaglandin E2, histamine, or gamma-interferon. The inhibition of interleukin 2 (IL-2) production by hydrocortisone or dexamethasone was also completely reversed by exogenous LTB4. LTB4 alone did not cause IL-2 production or cell proliferation when added to resting lymphocytes. Thus, endogenous LTB4 production appears to be necessary but not sufficient for phytohemagglutinin-induced IL-2 production and lymphocyte proliferation. Glucocorticosteroids inhibit IL-2 production and lymphocyte proliferation by inhibiting endogenous LTB4 production.

Arachidonate Lipoxygenases↗

Regulation of phytohemagglutinin-induced bovine lymphocyte blastogenesis by leukotrienes.

Leukotriene (LT) B4, a 5-lipoxygenase metabolite of arachidonic acid, is a potent inducer of suppressor cells in phytohemagglutinin-stimulated cultures of bovine peripheral blood mononuclear cells. In contrast, LTC4 and LTD4 have little activity. Incubation of T lymphocytes with LTB4 at concentrations as low as 1 X 10(-12)M rendered these lymphocytes suppressive of [3H]thymidine incorporation in subsequent phytohemagglutinin-stimulated cultures of fresh autologous lymphocytes. This LTB4-induced cell was radiosensitive to irradiation at 2,000 rads. Leukotriene B4 may have an important part in immunoregulation during hypersensitivity reactions.

Animals↗

Cognitive effects of nutritional deficiency.

Deficiencies of various nutrients, primarily vitamins, impair cognition. The link is strongest for vitamin B12, thiamine, and niacin. Yet even for these, the role of mild "subclinical" or multiple deficiencies in the genesis of mental dysfunction is unclear. Most information in this field is based on animal studies often poorly applicable to the human condition or on clinical pathology complicated by advanced age, alcoholism, and intercurrent disease. There is a need for well controlled, double-blind, prospective trials to elucidate the cognitive effects of malnutrition.

Adult↗

IgM, IgA and IgG rheumatoid factors in patients with rheumatoid arthritis and normal donors.

IgM, IgA, and IgG Rheumatoid Factors (RF) were measured by ELISA assay in serum from 26 patients with definite rheumatoid arthritis (RA) and 11 normal controls. IgM-RF was assayed by ELISA, radioimmunoassay, and also by the standard latex fixation test in all sera from RA patients. In patients with RA quantitative amounts of IgM, IgA, and IgG-RF as estimated by ELISA were highly correlated. Significant correlations were found between a physician's rating of disease activity and IgG-RF (r = 0.44; p less than .02) and IgA-RF (r = 0.38; p = .06 but not for IgM-RF as measured in any of the three assays.

Adult↗