Energy cannot be created nor destroyed.
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Animals↗
Biomedical subjects
Michelle A Miller
Publications and source records attributed to Michelle A Miller.
Circulating soluble E-selectin levels and the Ser 128Arg polymorphism in individuals from different ethnic groups.
BACKGROUND AND AIM: An association between the Ser128 Arg polymorphism and coronary heart disease (CHD) has been previously demonstrated in a white population. The aim of this study was to investigate whether the Ser128 Arg polymorphism of the E-selectin gene is associated with soluble E-selectin levels in individuals from a multiethnic population. METHODS AND RESULTS: Plasma sE-selectin levels and the Ser128 Arg E-selectin gene polymorphism were determined in 244 white (109 females), 176 of African origin (90 females) and 208 South Asian (95 females) healthy individuals living in England selected from the Wandsworth Heart and Stroke Study (WHSS). The substitution of serine for arginine (A to C mutation) was more common in whites (9.6%) and South Asians (7.9%) compared to the people of African origin (3.7%); p=0.005. The C mutation had no effect on sE-selectin levels in any ethnic group. CONCLUSIONS: We found a lower frequency of this polymorphism in the people of African origin who have a low CHD risk. However, in this study the polymorphism was not associated with circulating sE-selectin levels. Whether it plays a role in determining ethnic differences in vascular disease via a mechanism affecting leukocyte recruitment remains to be determined.
Age Factors↗
Cellular adhesion molecules and blood pressure: interaction with sex in a multi-ethnic population.
OBJECTIVE: To clarify the association between blood pressure and four different adhesion molecules, adjusting for potential confounders, in men and women from different ethnic origins. DESIGN AND METHODS: The soluble (s) plasma adhesion molecules sP-selectin, sE-selectin, intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured in 261 white (120 women), 188 African origin (99 women) and 215 South Asian (99 women) individuals living in England. All were free from coronary heart disease, stroke, other cardiovascular disease and diabetes, and were not receiving drug treatment for hypertension or high lipids, hormone replacement therapy or oral contraceptives. RESULTS: After adjustment for age, only sE-selectin concentrations were significantly associated with blood pressure. There was a significant interaction of sex with systolic (P = 0.013), diastolic (P = 0.042) and pulse (P = 0.015) pressures. After adjustment for age, ethnicity, body mass index and smoking, the significant interaction of sex persisted and in women the associations with systolic (P < 0.001), diastolic (P < 0.001) or pulse (P = 0.004) pressure were unchanged, but in men the association with diastolic blood pressure was abolished. Finally, the association appeared to be present in women younger than 50 years, who were likely to be premenopausal. CONCLUSIONS: The relationship between adhesion molecules and blood pressure is adhesion molecule specific and varies with sex and age, which may partially explain previous inconsistencies in the literature. The mechanisms relating blood pressure to adhesion molecule concentrations are unknown, but they are likely to be modified by the menopause. These differences may relate to the production, clearance or cell-surface shedding of the adhesion molecules.
Asian People↗
Aldosterone synthase gene (CYP11B2) C-344T polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population.
BACKGROUND: The aldosterone synthase gene (CYP1B2) locus is a candidate region involved in the development of hypertension. OBJECTIVE: To study the relationship between the C-344T CYP1B2 polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population. DESIGN: Population-based, cross-sectional study of 1313 middle-aged men and women (456 white, 441 of African origin and 416 South Asian). Anthropometry, blood pressure, biochemistry, questionnaire data and timed urine collections were taken with standardized techniques. All were genotyped for the C-344T CYP11B2 polymorphism. RESULTS: The frequency of the C allele was significantly lower in people of African origin (0.21) than in white (0.46) and South Asian (0.43) (P < 0.001). After adjustment for age, sex and ethnicity the TT genotype was associated with 14% higher plasma aldosterone levels, 3.7 mmHg higher systolic and 2.1 mmHg higher diastolic blood pressure than CC (P for linear trend < 0.05). No significant interactions with age, sex, ethnicity, body mass index (BMI) and fractional excretion of sodium were found in the associations between genotype and both blood pressure and aldosterone levels. In a sub-sample of participants in which plasma renin activity was measured (n = 457), a significant excess of T alleles was found in those with a raised (>/= 750) aldosterone-to-renin ratio (ARR). CONCLUSION: In this multi-ethnic population, the C-344T CYP1B2 polymorphism is associated with blood pressure, plasma aldosterone levels and ARR. Although significant differences in allele frequencies were found between groups, ethnicity does not explain the results.
Adult↗
Molecular variants of the sodium/hydrogen exchanger type 3 gene and essential hypertension.
OBJECTIVES: The objectives of this study were to identify polymorphic variants within the gene coding for the sodium/hydrogen exchanger type 3 (NHE3) and to examine their relationship with hypertension and biochemical indices of sodium balance. DESIGN AND METHODS: Case-control comparisons on a total of 691 subjects of which 399 (68% with essential hypertension) were of African or Afro-Caribbean origin (blacks) and 292 (50% with essential hypertension) were of Caucasian origin (whites). RESULTS: Eight exons of the C terminus of the NHE3 gene were screened systematically. A total of six variants were identified: (G1579A, G1709A, G1867A, C1945T, A2041G and C2405T). Further analyses in relation to essential hypertension and phenotypic characteristics were confined to the more frequent A2041G and the C2405T polymorphisms. The genotype frequencies of the A2041G polymorphism were significantly different between the whites and blacks, with the A allele being more frequent in the white population (0.43 for the whites and 0.14 for the blacks, respectively; P < 0.001). In contrast, there was no significant difference in the C2405T polymorphism between whites and blacks (C allele frequency: 0.86 for the whites and 0.88 for the blacks, respectively). In both the white and the black groups, there were no significant associations between these variants and essential hypertension (P > 0.05) or with serum electrolytes, creatinine or plasma renin activity (PRA) (ANOVA P > 0.05). CONCLUSIONS: These results suggest a high degree of structural conservation of the NHE3 gene; however, the lack of association between these polymorphisms and blood pressure status does not necessarily eliminate the participation of this important sodium/hydrogen exchanger in the pathophysiology of essential hypertension, as we cannot exclude the existence of functionally important genetic variants in other sequences within the NEH3 gene.
Adult↗
Association between the Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in a multiethnic population in South London.
The aim was to investigate whether the Thr715Pro P-selectin polymorphism is associated with soluble P-selectin (sP-selectin) levels in individuals from different ethnic groups. Plasma sP-selectin and Thr715Pro (A/C) P-selectin gene polymorphism were measured in 237 white (106 females), 177 black African origin (92 females) and 201 South Asian (94 females) individuals living in England. All were free from coronary heart disease (CHD), stroke and other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone replacement therapy or oral contraceptive pill. The Thr715Pro C allele was rare in blacks (0.8%) and intermediate in South Asians (3.0%) compared to whites (11.2%; p <0.001). sP-selectin levels were significantly lower in the individuals with the AC or CC compared to the AA genotype in both whites (-25% (95% C.I. -33.3 to -16.9); p <0.001) and South Asians (-25.2% (-40.5 to -6.1); p <0.012). There was insufficient power for this analysis in blacks. In conclusion, in whites and South Asians the C allele of the Thr715Pro P-selectin polymorphism is associated with lower sP-selectin levels. Lower levels of sP-selectin were not accounted for by this polymorphism in blacks, in whom the C allele was very rare.
Age Factors↗
Ethnic differences in circulating soluble adhesion molecules: the Wandsworth Heart and Stroke Study.
The aim of this study was to investigate whether soluble adhesion molecule levels differ by ethnic group. Soluble plasma adhesion molecules [soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1)] were measured in 261 white (120 females), 188 African origin (99 females) and 215 South Asian (99 females) individuals living in England. All were free from coronary heart disease, stroke and other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone-replacement therapy or oral contraceptive pill. The results of the study indicated that there were important differences in the levels of adhesion molecules by sex and smoking. However, when adjusting for these and other potential confounders, there were no differences in levels between white subjects and individuals of South Asian origin. In contrast, people of African origin had significantly lower levels of sICAM-1 [Caribbean -30% (-36 to -23%); West African -22% (-29 to -15%), values are means (95% confidence intervals)], sVCAM-1 [Caribbean -14% (-19 to -8%); West African -10% (-17 to -3%)] and sP-selectin [Caribbean -10% (-17 to -2%); West African -24% (-31 to -16%)] than white individuals. In conclusion, circulating levels of some soluble adhesion molecules are lower in individuals of Caribbean or West African origin compared with white or South Asian individuals. These relationships may contribute to the low risk of coronary heart disease seen in people of African origin living in England.
Adult↗
Congenital and acquired brain injury. 3. Rehabilitation interventions: cognitive, behavioral, and community reentry.
UNLABELLED: This self-directed learning module highlights the cognitive and psychosocial adjustment aspects of brain injury. It is part of the chapter on congenital and acquired brain injury in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article focuses specifically on evaluation and treatment of mood and behavioral impairments after brain injury, treatment of cognitive impairments, efficacy of cognitive rehabilitation, psychosocial impact of a traumatic brain injury on families, and resources available for community reintegration. OVERALL ARTICLE OBJECTIVE: To summarize the psychosocial and cognitive impact of brain injury in children and adults.
Activities of Daily Living↗
Congenital and acquired brain injury. 5. Outcomes after acquired brain injury.
UNLABELLED: This self-directed learning module highlights several aspects of outcome after acquired brain injury rehabilitation. It is part of the chapter on brain injury rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. In this article, functional measures commonly used in rehabilitation are described, and their potential uses for various populations are discussed. Key physiologic factors that predict outcome for persons with different acquired brain injuries are identified. Variables that affect return to school and work are described, and the studies evaluating the effectiveness of brain injury rehabilitation programs in general, as well as their subcomponents, are also reviewed. OVERALL ARTICLE OBJECTIVES: (a) To describe variables that affect outcome after acquired brain injury and (b) to identify the outcome tools most appropriate for the patient populations and outcomes to be studied.
Brain Injuries↗
Contrasting associations between aldosterone synthase gene polymorphisms and essential hypertension in blacks and in whites.
BACKGROUND: Genetic variability in the gene for aldosterone synthase--a key enzyme in the production of aldosterone--can affect sodium homeostasis and thereby blood pressure. The possibility of impaired aldosterone production for the development of hypertension is of particular relevance in black Afro-Caribbeans exposed to a high dietary sodium intake. OBJECTIVES: To compare the frequency of three variants (-344C/T, intron 2 conversion, and the K173R polymorphism) of the aldosterone synthase gene in blacks and whites, and to determine any association of the variants with hypertension. DESIGN AND METHODS: We made case-control comparisons of the three gene variants in relation to ethnic background and to essential hypertension in 193 white (51% hypertensive) and 245 black individuals (59% hypertensive) living in south London. RESULTS: The frequency of each of the variants was significantly different between the two ethnic groups. The T and the K alleles were more frequent in the black participants (79 compared with 50% for the -344T allele and 81 compared with 50% for K173 allele), whereas the frequency of the intron 2 conversion allele was much lower in that group (8 compared with 38%). None of these variants was associated with essential hypertension in the black participants. In contrast, in the white participants there was a significant and graded association between the intron 2 conversion allele and essential hypertension (odds ratio 1.86, 95% confidence interval 1.16 to 2.98; = 0.01). Moreover, among the white population, the presence of homozygosity both of the T allele and of the intron 2 conversion alleles was associated with a much greater frequency of hypertension (71 compared with 43%; chi(2) = 0.03). CONCLUSIONS: The contrasting associations between these variants and essential hypertension do not necessarily exclude the possibility that other, as yet undefined, variants of the aldosterone synthase gene could be linked with hypertension in black people. Nonetheless, the strong association between the intron 2 conversion allele and essential hypertension in the white population reinforces the view that the increased blood pressure may be due, at least in part, to abnormal expression of enzymes involved in the metabolism of adrenal mineralocorticoids.
Adenine↗
Congenital and acquired brain injury. 1. Brain injury: epidemiology and pathophysiology.
UNLABELLED: This self-directed learning module highlights recent advances in the understanding of brain injury pathophysiology, epidemiology. severity scales, and treatment interventions to minimize brain injury in adults and children. It is part of the chapter on congenital and acquired brain injury in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. In this article, brain injury epidemiology is summarized, and differences in between brain injury in pediatric and elderly persons are highlighted. Underlying physiologic and chemical mechanisms for secondary brain injury are reviewed, along with strategies and research to minimize this injury. Contemporary understanding of the mechanisms and treatments of brain injury in preterm infants is also discussed. Classification of brain injury severity provides a way to stratify this heterogeneous group. OVERALL ARTICLE OBJECTIVE: (a) To summarize brain injury epidemiology and prevention strategies across the age spectrum, (b) to review the pathophysiology of pediatric and adult brain injury, and (c) to classify brain injury by severity scales.
Aged↗
Soluble adhesion molecules and coronary heart disease.
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Cell Adhesion Molecules↗