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T Harris

Publications and source records attributed to T Harris.

At least 163 records · Page 9Linked to original sources
PubMed1993

Adenosine inhibits platelet-activating factor, but not tumour necrosis factor-alpha-induced priming of human neutrophils.

Regulation of the respiratory burst and its priming by recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and platelet-activating factor (PAF) were investigated in human polymorphonuclear leucocytes (PMN). Adenosine (0.1-10 microM) pretreatment of PMN concentration-dependently inhibited the superoxide anion generation (O2-) in response to formyl-methionyl-leucyl-phenylalanine (FMLP). The priming by PAF (1 microM) for an increased O2- generation by FMLP-stimulated PMN was completely blocked by adenosine pretreatment. In contrast, rhTNF-alpha-induced priming was unaffected by adenosine. In addition, the direct stimulation of PMN O2- by rhTNF-alpha was also unaffected by adenosine as was rhTNF-alpha-induced PAF synthesis. FMLP-induced PAF synthesis was reduced by adenosine to a similar extent as the inhibition of the respiratory burst. Adenosine also inhibited PAF-, but not FMLP-induced increases in intracellular calcium in PMN. These findings indicate that short-term, direct stimulants (FMLP) or priming agents (PAF) are subject to modulation by the endothelial product adenosine, whereas the priming and direct stimulation of the respiratory burst by the longer-acting agent, rhTNF-alpha is unaffected. Moreover, differential inhibition of PMN activation by adenosine reveals important functional differences in the signalling mechanisms initiated by PAF, FMLP and rhTNF-alpha.

Adenosine↗
PubMed1993

The National Health and Nutrition Examination Survey III: describing the health and nutritional status of older Americans.

The National Health and Nutrition Examination III will provide important data for examination of the health and nutritional status of persons in the U.S. Innovations in the study, particularly the inclusion of persons over age 74 and the focus of the survey on the major chronic diseases of old age, will enhance the value for older persons. Response rates for phase 1 (1988-1991) show that about 80% of all older subjects agreed to the interview; examination rates declined with age, but the use of a home examination increased the response rate for those aged 75 or older by about 9% to 67% for men and about 62% for women. Analytic plans include examination of the effect of nutrition on health, as well as the effect of health status on the distribution of nutritional risk factors in old age.

Adult↗
PubMed1993

Musculoskeletal disorders: time trends, comorbid conditions, self-assessed health status, and associated activity limitations.

In this report, cases of musculoskeletal disease were identified by a yes response to questions involving joint pain and/or physician-diagnosed arthritis in four national surveys for the following objectives: (a) to assess time trends in case prevalence; (b) to describe respondent health status; (c) to estimate prevalence of joint pain by location; (d) to estimate prevalence of selected comorbid medical conditions; and (e) to estimate among these persons the burden of ADL and IADL disability. These surveys were conducted over a 25-year interval (1960-84). Joint pain is the final common pathway through which a number of these disorders operate and could be expected to identify a subset of persons who have not sought medical consultation. Physician diagnosis of disease is an item that is conceptually a measure of severity. In these samples, there were slightly more persons reporting joint pain than reporting a diagnosis of arthritis in most years. Increases in the prevalence of both joint pain and physician-diagnosed arthritis were noted across survey years and for the cohort aged 65-69 years in NHANES I. Although this analysis is based on national data from persons with arthritis, estimates of disability prevalence from national surveys of the total U.S. population (18,28) are also available for comparison. In this report, persons with arthritis suffer from poorer health status and more disability when compared with U.S. population prevalence. Overall, 14 percent of persons aged 65-74 years reported difficulty walking, and 20 percent of persons with arthritis reported this difficulty. In the U.S. cohort aged 75-84 years, 23 percent reported difficulty walking, compared with 31 percent of those with arthritis. Among persons aged 85 years and over, 40 percent reported difficulty walking, compared with 46 percent of respondents with arthritis. It should be recognized that persons with arthritis are included in the total population estimates and these differences in disability prevalence, therefore, could be much larger. It is important to note, however, that for tasks such as toileting, dressing, and managing money, estimates of disability for the total U.S. and arthritic U.S. populations are similar. These data suggest that arthritis may be a large contributor to certain types of disability.(ABSTRACT TRUNCATED AT 400 WORDS)

Activities of Daily Living↗
PubMed1992

The low cholesterol-mortality association in a national cohort.

The relationship of low serum cholesterol and mortality was examined in data from the NHANES I Epidemiologic Followup Study (NHEFS) for 10,295 persons aged 35-74, 5833 women with 1281 deaths and 4462 men with 1748 deaths (mean (followup = 14.1 years). Serum cholesterol below 4.1 mmol/l was associated with increased risk of death in comparison with serum cholesterol of 4.1-5.1 mmol/l (relative risk (RR) for women = 1.7, 95% confidence interval (CI) = (1.2, 2.3); for men RR = 1.4, CI = (1.1, 1.7)). However, the low serum cholesterol-mortality relationship was modified by time, age, and among older persons, activity level. The low serum cholesterol-mortality association was strongest in the first 10 years of followup. Moreover, this relationship occurred primarily among older persons (RR for low serum cholesterol for women 35-59 = 1.0 (0.6, 1.8), for women 70-74, RR = 2.1 (1.2, 3.7); RR for low serum cholesterol for men 35-59 = 1.2 (0.8, 2.0), for men 70-74, RR = 1.9 (1.3, 2.7)). Among older persons, however, the low serum cholesterol-mortality association was confined only to those with low activity at baseline. Factors related to underlying health status, rather than a mortality-enhancing effect of low cholesterol, likely accounts for the excess risk of death among persons with low cholesterol. The observed low cholesterol-mortality association therefore should not discourage public health programs directed at lowering serum cholesterol.

Adult↗
PubMed1992

Stressful life events and Graves' disease.

"The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease."

Case-Control Studies↗
PubMed1991

Diazepam alters brain-stimulation reward thresholds in seizure-prone sites.

Studies of the effect of diazepam and related compounds on the rewarding properties of brain stimulation as measured by response rates have not yielded clear results, with self-stimulation performance reported to be potentiated, diminished, or unchanged following drug administration. In this study, the effect of two doses of diazepam (2.5 and 5.0 mg/kg) and its vehicle on self-stimulation thresholds was examined in eight rats with electrode placements scattered along a 4 mm length of the medial forebrain bundle. Stimulation of the lateral preoptic area and the anterior and mid-lateral hypothalamus produced overt seizures. Rate-period curves were generated for a wide range of currents and the resulting period-current trade-off functions were compared across doses. In seizure-prone sites upward shifts in period threshold were observed after 2.5 mg/kg of diazepam with little additional increases incurred by the 5.0 mg/kg dose. The majority of non-seizure sites showed no effects of diazepam upon period threshold. The results suggest that diazepam alters brain-stimulation reward thresholds by suppressing competing seizure activity.

Animals↗
PubMed1991

Platelet-activating factor may participate in signal transduction processes in rabbit leukocytes.

The bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), induces the generation of platelet-activating factor (PAF), the mobilization of arachidonic acid and generation of superoxide anion (O2-) in rabbit polymorphonuclear leukocytes (PMNs). The PAF receptor antagonists, WEB 2086 (10-100 microM) and CV 6209 (1-10 microM), reduced the mobilization of arachidonic acid and the O2- generation in response to fMLP but not that in response to A23187. Pretreatment of PMNs with the phospholipase A2 inhibitor, chloroquine, or the serine protease inhibitor, tosyl-phenylalanine chloromethyl ketone, reduced the fMLP-stimulated generation of PAF and also reduced the generation of O2-. The respiratory burst induced by a submaximal concentration of phorbol myristate acetate was not affected by these compounds. These data are consistent with the suggestion that endogenous PAF may contribute to the signal transduction cascade initiated by fMLP.

Animals↗
PubMed1991

Postural change in blood pressure associated with age and systolic blood pressure. The National Health and Nutrition Examination Survey II.

The prevalence of postural change in blood pressure and its association with age and systolic blood pressure were examined in data from 8,574 White nondiabetic persons aged 25-74 who participated in the second National Health and Nutrition Examination Survey (1976-1980). Postural change in blood pressure was defined as a drop of 20 mm Hg or more on change from supine to seated position. In subjects on no antihypertensive medications (n = 7,316), the prevalence of postural change in blood pressure increased with older age and with higher blood pressure levels, regardless of age. However, systolic blood pressure levels also increased with age. In logistic regression models, level of supine systolic blood pressure was strongly related to postural change in blood pressure (Relative odds (RO) = 1.59, 95% confidence interval (CI) = 1.49, 1.70 for a 10 mm Hg increase in systolic blood pressure) whereas age was not related to postural change in blood pressure (RO for age = 1.07, Cl = .89, 1.19 for a 10-year increase in age). Results were similar for those medicated for hypertension. All results were unchanged by addition of health status indicators, including reports of hospitalization and number of medical conditions, to the model. These data suggest that the age-related increase in the prevalence of postural hypotension previously reported may be partially explained by age-associated increases in systolic blood pressure.

Adult↗
PubMed1991

Is sex necessarily a risk factor to depression?

"To isolate and quantify possible determinants of any increased prevalence of depressive disorders in women we studied a select group of men and women, initially similar in terms of a number of putative social determinants of depression, and reviewed the sample five years later when social role diversity was anticipated. We used the Diagnostic Interview Schedule (DIS) to generate DSM-III and RDC diagnoses to estimate lifetime depressive disorders, and established (via corroborative reports) the likely accuracy of those data. Despite lifetime depression being a relatively common experience, no significant sex differences in depressive episodes were demonstrated, suggesting the possible irrelevance of biological factors in determining any sex difference. As there was not major social role divergence over the five year study, we interpret the lack of a sex difference as a consequence, and suggest that findings support the view that social factors are of key relevance in determining any female preponderance in depression described in general population studies."

Cross-Sectional Studies↗
PubMed1991

Involvement of leukotriene B4 and platelet-activating factor in cytokine priming of human polymorphonuclear leucocytes.

Recombinant human (rh) tumour necrosis factor (TNF) alpha and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) prime human polymorphonuclear leucocytes (PMN) for increased superoxide anion (O2-) generation and for increased platelet-activating factor (PAF) biosynthesis and leukotriene B4 (LTB4) release. Both PAF and LTB4 are candidate mediators for the enhanced O2- generation in cytokine-primed PMN, since exogenous PAF or LTB4 primes PMN. We measured the generation and release of these mediators and examined their potential roles in cytokine priming using the PAF receptor antagonist, WEB 2086, and the inhibitor of 5-lipo-oxygenase, CGS 8515.rhTNF-alpha or rhGM-CSF, alone, increased PAF levels in PMN, but did not cause PAF release or LTB4 synthesis. N-formylmethionyl-leucyl-phenylalanine (FMLP) stimulated the release of detectable and biologically active amounts of both LTB4 and PAF in primed, but not in non-primed PMN. However, neither blockade of PAF receptors, nor inhibition of LTB4 synthesis influenced the priming of O2- generation by rhTNF-alpha or rhGM-CSF. Simultaneous pretreatment of PMN with WEB 2086 and CGS 8515 also failed to inhibit priming. Our results do not exclude a role for cell-associated PAF in the priming response, but indicate that the release of PAF and LTB4 do not mediate this phenomenon. The ability of cytokines to amplify the production and release of lipids may represent a mechanism to attract and localize the pro-inflammatory actions of stimulated PMN to regions where cytokine levels are also elevated.

Cells, Cultured↗
PubMed1991

Self-stimulation: a rewarding decade.

In the past decade, there has been considerable emphasis on developing and refining the measurement instruments used to assess the rewarding effect of brain stimulation. These efforts have given rise to quantitative methods aimed at revealing the underlying neurophysiology and neuroanatomy by tracing the trajectories of the relevant neurons. In this paper, we summarize some of the quantitative findings that have resulted from research at the University of Ottawa in the neurobiology of motivated behavior. These include studies using markers to reveal which structures are metabolically activated by rewarding brain stimulation, comprehensive mapping of brain areas for self-stimulation and other stimulation-induced behaviors, and examination of the effects of benzodiazepines on feeding and reward.

Animals↗
PubMed1990

Platelet-activating factor may act as a second messenger in the release of icosanoids and superoxide anions from leukocytes and endothelial cells.

Platelet-activating factor (PAF) is generated by endothelial cells, polymorphonuclear leukocytes, and macrophages after activation by appropriate receptor agonists, but much of the PAF remains intracellular. We have investigated whether PAF formation is important for the subsequent generation of icosanoids and superoxide anions by these cells. The generation of prostacyclin and leukotriene B4 were measured by radioimmunoassay, superoxide anion was measured by reduction of cytochrome c, and PAF was measured by bioassay. In each cell type, PAF formation preceded or accompanied icosanoid generation. Bradykinin-induced prostacyclin generation in endothelial cells was markedly reduced by the PAF receptor antagonists WEB 2086 or CV 6209. In guinea pig adherent macrophages in vitro, basal prostacyclin generation and that induced by endotoxin and fMet-Leu-Phe were inhibited by either WEB 2086 (1-100 microM) or CV 6209 (0.1-10 microM). In isolated rabbit polymorphonuclear leukocytes, fMet-Leu-Phe stimulated the generation of both leukotriene B4 and superoxide anion. WEB 2086 and CV 6209 caused concentration-dependent inhibition of both these markers of leukocyte activation. These observations lead us to suggest that PAF may be a second messenger in leukocytes and endothelial cells.

Animals↗
PubMed1990

Beta-adrenergic receptors in lymphocyte subsets after exercise. Alterations in normal individuals and patients with congestive heart failure.

Dynamic exercise increases the number of beta-adrenergic receptors in mixed lymphocytes by a mechanism that is incompletely understood. In a set of in vivo studies, we have investigated the effects of dynamic exercise on the subset distribution of circulating lymphocytes and on the number of beta-adrenergic receptors in each of these subsets in two groups of patients. In healthy subjects, exercise increased plasma norepinephrine and epinephrine and caused lymphocytosis. Whereas the number of Thelper cells increased only modestly, the number of Tsuppressor/cytotoxic and natural killer cells more than tripled. The number of beta-adrenergic receptors varied among subsets but was not significantly altered by dynamic exercise in any subset except natural killer cells (35% increase, p = 0.0302). In a group of patients with congestive heart failure, dynamic exercise increased plasma norepinephrine but did not alter plasma epinephrine and did not cause significant lymphocytosis. We did not detect any significant alterations of circulating leukocyte subsets or beta-adrenergic receptors in any of these subsets after exercise. A combined analysis of healthy patients and heart failure patients revealed a significant correlation between increases in plasma epinephrine and increases in circulating lymphocytes. We conclude that the exercise-induced increase in beta-adrenergic receptors of mixed lymphocytes is predominantly caused by a redistribution of circulating cell subsets that differ in their beta-adrenergic receptor number. This appears to be mediated by epinephrine rather than norepinephrine.

Adult↗