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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Positive genetic correlation between parasite resistance and body size in a free-living ungulate population.

Parasite resistance and body size are subject to directional natural selection in a population of feral Soay sheep (Ovis aries) on the island of St. Kilda, Scotland. Classical evolutionary theory predicts that directional selection should erode additive genetic variation and favor the maintenance of alleles that have negative pleiotropic effects on other traits associated with fitness. Contrary to these predictions, in this study we show that there is considerable additive genetic variation for both parasite resistance, measured as fecal egg count (FEC), and body size, measured as weight and hindleg length, and that there are positive genetic correlations between parasite resistance and body size in both sexes. Body size traits had higher heritabilities than parasite resistance. This was not due to low levels of additive genetic variation for parasite resistance, but was a consequence of high levels of residual variance in FEC. Measured as coefficients of variation, levels of additive genetic variation for FEC were actually higher than for weight or hindleg length. High levels of additive genetic variation for parasite resistance may be maintained by a number of mechanisms including high mutational input, balancing selection, antagonistic pleiotropy, and host-parasite coevolution. The positive genetic correlation between parasite resistance and body size, a trait also subject to sexual selection in males, suggests that parasite resistance and growth are not traded off in Soay sheep, but rather that genetically resistant individuals also experience superior growth.

Alleles↗
PubMed2001

Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein e knockout mice but not in C57BL/6 mice.

Transgenic mice with macrophage-specific expression of human (hu) lipoprotein lipase (LPL) were generated to determine the contribution of macrophage LPL to atherogenesis. Macrophage specificity was accomplished with the scavenger receptor A promoter. Complete characterization demonstrated that macrophages from these mice expressed huLPL mRNA and secreted enzymatically active huLPL protein. Expression of huLPL was macrophage specific, because total RNA isolated from heart, thymus, lung, liver, muscle, and adipose tissues was devoid of huLPL mRNA. Macrophage-specific expression of huLPL did not exacerbate lesions in aortas of C57BL/6 mice even after 32 weeks on an atherosclerotic diet. However, when expressed in apolipoprotein E knockout background, the extent of occlusion in the aortic sinus region of male huLPL+ mice increased 51% (n=9 to 11, P<0.002) compared with huLPL- mice after they had been fed a Western diet for 8 weeks. The proatherogenic effect of macrophage LPL was confirmed in serial sections of the aorta obtained after mice had been fed a Western diet for 3 weeks. By immunohistochemical analysis, huLPL protein was detected in the lesions of huLPL+ mice but not in huLPL- mice. Our results establish that macrophage LPL accelerates atherosclerosis in male apolipoprotein E knockout mice.

Animals↗
PubMed2001

Pulmonary tumor embolism as a presenting feature of cavoatrial hepatocellular carcinoma.

Pulmonary tumor embolism as a presenting feature of hepatocellular carcinoma is rare. It has been reported only once previously. In that case, other signs and symptoms of liver disease were present. We report the case of a patient with cavoatrial hepatocellular carcinoma presenting with isolated pulmonary tumor embolism, without any clinical or laboratory evidence of liver disease. Hepatocellular carcinoma should be included in the differential diagnosis as a rare cause of pulmonary tumor embolism.

Aged↗
PubMed2001

Testing relationships among determinants of health, health policy, and self-assessed health status in Quebec.

By removing financial barriers, the Canada Health Act (1984) equalized access to health care services in Canada. Yet class, educational, and geographical disparities in individual and population health status persist. Recent health reform policies in Quebec assert that health and well-being are a function of income, educational level, housing conditions, employment, and other socioeconomic factors. They suggest that health policy should encompass social policies that influence individual and community socioeconomic factors which in turn affect health. Against the backdrop of these reforms, this study tests the importance of socioeconomic factors as a determinant of health--while controlling for other known determinants through a logistic regression model--with data from the Santé Quebec health surveys 1987 and 1992-93. The results confirm the importance of economic security as a determinant of individual health. This effect appears to operate through an individual income variable and through the community-level variable of regional unemployment. The importance of the income effect declined between 1987 and 1992-93. This may indicate that an increased focus on the socioeconomic determinants of health has reduced inequalities in health. It may also mean that health inequalities appear inevitable until health care policy merges completely with broader health and social policies. But such integration may well conflict with economic (and political) imperatives of the post-Fordist capitalist system.

Adolescent↗
PubMed2001

Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti-TNF-alpha agent thalidomide.

The tumor necrosis factor-alpha (TNF-alpha) inhibitor thalidomide is known to be a potent modulator of host immunity, a potential treatment for autoimmune disorders such as rheumatoid arthritis (RA) and a treatment for complications of HIV-1 infection. RA is an autoimmune disease of the joints that has been associated with hyperactivity of lymphocytes and other leukocytes, over-expression of pro-inflammatory cytokines (TNF-alpha and IL-1) and chronic debilitating inflammation. Thalidomide may play a role in RA treatment by altering leukocyte function through down-modulation of cell adhesion molecules necessary for leukocyte migration to inflammatory sites. The present study investigates down-regulation of cell adhesion molecules (ICAM-1 and LFA-1) and decreases in cell-cell contacts between human T leukemic (CEM) cells and human umbilical vein endothelial cells (HUVEC) after thalidomide exposure. CEM cells were cultured in RPMI 1640 medium with 0, 10 or 50 microg/ml thalidomide, stained with fluorescent monoclonal antibodies specific to ICAM-1 and LFA-1 and expression was measured with flow cytometry. For cell-cell adhesion measurements, monolayers of HUVEC cultured in Kaign's F-12 medium were incubated with thalidomide treated CEM cells stained with calcein AM. Specific cell adhesion between the two cell types was visualized with fluorescence microscopy. Thalidomide treatment significantly reduced cell adhesion molecule expression in a dose-dependent fashion and inhibited HUVEC/CEM cell adhesion. These data support the hypothesis that thalidomide has modulatory actions on leukocyte functions through expression of cell adhesion molecules.

Cell Adhesion↗
PubMed2000

Risk of acquiring Creutzfeldt-Jakob disease from blood transfusions: systematic review of case-control studies.

OBJECTIVE: To determine the strength of association between history of blood transfusion and development of Creutzfeldt-Jakob disease. DATA SOURCES: English and non-English language articles published from January 1966 to January 1999 were retrieved using a keyword search of Medline and Embase. These were supplemented by handsearching key journals and searching bibliographies of reviews. STUDY SELECTION: Two independent reviewers selected the relevant abstracts and articles. Articles were chosen that reported the results of case-control studies trying to identify rates of prior blood transfusion in patients with Creutzfeldt-Jakob disease and in controls. DATA EXTRACTION: Odds ratios and information on study quality were extracted from the selected articles by two independent reviewers. DATA SYNTHESIS: Five studies containing data on 2479 patients were included. Three of the five studies used medical or neurological patients as controls, the other two used population controls. Odds ratios for developing Creutzfeldt-Jakob disease from blood transfusion ranged from 0.54 to 0.89. Four of the five studies had confidence intervals that crossed 1.0. The combined odds ratio was 0.70 (95% confidence interval 0.54 to 0.89). CONCLUSIONS: Case-control studies do not suggest a risk of developing Creutzfeldt-Jakob disease from blood transfusion. Rather, a trend seems to exist towards a lower frequency of previous blood transfusion in patients with Creutzfeldt-Jakob disease than in controls. However, it is important to be aware of these studies' methodological limitations-primarily the choice of control population and reliability of recall of transfusion status.

Case-Control Studies↗
PubMed2000

Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes.

Contrary to the general precepts of the clonal selection theory, several recent studies have provided evidence for the secondary rearrangement of immunoglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typically used transgenic mouse models and have only detected secondary recombination of Ig light chain genes. Although Ig heavy chain variable region (V(H)) genes encode a substantial element of antibody combining site specificity, there is scant evidence for V(H) gene rearrangement in the periphery, leaving the physiological importance of peripheral recombination questionable. The extensive somatic mutations and clonality of the IgD(+)Strictly-IgM(-)CD38(+) human tonsillar B cell subpopulation have now allowed detection of the first clear examples of receptor revision of human V(H) genes. The revised VDJ genes contain "hybrid" V(H) gene segments consisting of portions from two separate germline V(H) genes, a phenomenon previously only detected due to the pressures of a transgenic system.

Base Sequence↗
PubMed2000

Health care, federalism and the new Social Union.

The Social Union framework agreement and the Health Accord provide examples of the close relationship that exists between federalism and the delivery of health care. These recent agreements represent a move from a federal-unilateral style of federalism to a more collaborative model. This shift will potentially affect federal funding for health care, interpretation of the Canada Health Act and the development of new health care initiatives. The primary advantage of the new collaborative model is protection of jurisdictional autonomy. Its primary disadvantages are blurring of accountability and potential for exclusion of the public from decision-making.

Canada↗
PubMed2000

Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.

OBJECTIVE: To determine the effect of smoking cessation on mortality after myocardial infarction. DATA SOURCES: English- and non-English-language articles published from 1966 through 1996 retrieved using keyword searches of MEDLINE and EMBASE supplemented by letters to authors and searching bibliographies of reviews. STUDY SELECTION: Selection of relevant abstracts and articles was performed by 2 independent reviewers. Articles were chosen that reported the results of cohort studies examining mortality in patients who quit vs continued smoking after myocardial infarction. DATA EXTRACTION: Mortality data were extracted from the selected articles by 2 independent reviewers. DATA SYNTHESIS: Twelve studies were included containing data on 5878 patients. The studies took place in 6 countries between 1949 and 1988. Duration of follow-up ranged from 2 to 10 years. All studies showed a mortality benefit associated with smoking cessation. The combined odds ratio based on a random effects model for death after myocardial infarction in those who quit smoking was 0.54 (95% confidence interval, 0.46-0.62). Relative risk reductions across studies ranged from 15% to 61%. The number needed to quit smoking to save 1 life is 13 assuming a mortality rate of 20% in continuing smokers. The mortality benefit was consistent regardless of sex, duration of follow-up, study site, and time period. CONCLUSION: Results of several cohort studies suggest that smoking cessation after myocardial infarction is associated with a significant decrease in mortality.

Age Factors↗
PubMed2000

Validation of the Hamilton Depression Rating Scale and Montgommery and Asberg Rating Scales in terms of AGECAT depression cases.

OBJECTIVE: To validate the Hamilton Depression (17) and Montgommery and Asberg Depression Scales as research instruments in older depressed community residents. DESIGN: External validation against GMS/AGECAT case level in the recruitment of older community residents for an antidepressant trial. ANALYSES: Receiver operator curves were generated for each rating scale, using GMS/AGECAT case level in external criterion. The sensitivity, specificity, positive and negative predictive values of both rating instruments were examined in the whole sample and age and gender subgroups. MADRS and HAM-D cut-off scores differentiating GMS/AGECAT cases from subcases were identified. RESULTS: HAM-D cut-off score of 16 and MADRS score of 21 were identified as differentiating case from sub-case. Diagnostic accuracy of both instruments was good, reflecting good sensitivity and specificity across both genders and sub-age groups. CONCLUSIONS: Both scales performed well in this population. These scores provide researchers with externally validated and clinically relevant cut-off scores in designing trials in the management of older depressed community residents.

Aged↗
PubMed2000

Effects of L-dopa treatment on methylation in mouse brain: implications for the side effects of L-dopa.

The effects of L-dopa on methylation process in the mouse brain were investigated. The study is based on recent findings that methylation may play an important role in Parkinson's disease (PD) and in the actions of L-dopa. The methyl donor, S-adenosylmethionine (SAM) and a product of SAM, methyl beta-carboline, were shown to cause PD-like symptoms, when injected into the brain of animals. Furthermore, large amounts of 3-O-methyl dopa, the methyl product of L-dopa, are produced in PD patients receiving L-dopa treatment, and L-dopa induces methionine adenosyl transferase, the enzyme that produces SAM. The results show that, at 0.5 hr, L-dopa (100 mg/kg) decreased the methyl donor, S-adenosylmethionine (SAM) by 36%, increased its metabolite S-adenosylhomocysteine (SAH) by 89% and increased methylation (SAH/SAM) by about 200%. All parameters returned to control values within 4 hr. But 2, 3 and 4 consecutive injections of L-dopa, given at 45 min intervals, depleted SAM by 60, 64 and 76% and increased SAM/SAH to 818, 896, and 1524%. L-dopa (50, 100 and 200 mg/kg) dose-dependently depleted SAM from 24.9 +/- 1.7 nmol/g to 13.0 +/- 0.8, 14.7 +/- 0.8 and 7.7 +/- 0.7 nmol/g, and increased SAH from 1.88 +/- 0.14 to 3.43 +/- 0.26, 4.22 +/- 0.32 and 6.21 +/- 0.40 nmol/g. Brain L-dopa was increased to 326, 335 and 779%, dopamine to 138, 116 and 217% and SAH/SAM to 354, 392 and 1101%. The data show that L-dopa depletes SAM, and increases methylation 4-5 times more than dopamine, therefore, methylation may play a role in the actions of L-dopa. This and other studies suggest that the high level of utilization of methyl group by L-dopa leads to the induction of enzymes to replenish SAM and to increase the methylation of L-dopa as well as DA. These changes may be involved in the side effects of L-dopa.

Animals↗
PubMed2000

Gender, poverty and location: how much difference do they make in the geography of health inequalities?

It is often said that women live longer than men, but suffer more illnesses throughout their lives. It has also been demonstrated in various studies of women's health that measures of health and health behaviour vary over different geographic scales. Added into this mix is the fact that historically more women than men in relative terms are found on the lower rungs of the socio-economic ladder. What has not been so well-developed is our understanding of the connections among health, gender, poverty and especially location. In 1998, Statistics Canada released the second wave of the National Population Health Survey (NPHS-2). Included with the NPHS-2 public use microdata file are measures of health status, gender, income and location which can be analyzed in the form of logistic regression models. Results are reported which provide a better understanding of the relative roles that gender, poverty and location play in the geography of inequalities.

Adult↗