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Biomedical subjects

A Clark

Publications and source records attributed to A Clark.

At least 55 records · Page 3Linked to original sources

Do facial averageness and symmetry signal health?

We investigated whether the attractive facial traits of averageness and symmetry signal health, examining two aspects of signalling: whether these traits are perceived as healthy, and whether they provide accurate health information. In Study 1, we used morphing techniques to alter the averageness and symmetry of individual faces. Increases in both traits increased perceived health, and perceived health correlated negatively with rated distinctiveness (a converse measure of averageness) and positively with rated symmetry of the images. In Study 2, we examined whether these traits signal real, as well as perceived, health, in a sample of individuals for whom health scores, based on detailed medical records, were available. Perceived health correlated negatively with distinctiveness and asymmetry, replicating Study 1. Facial distinctiveness ratings of 17-year-olds were associated with poor childhood health in males, and poor current and adolescent health in females, although the last association was only marginally significant. Facial asymmetry of 17-year-olds was not associated with actual health. We discuss the implications of these results for a good genes account of facial preferences.

Journal Article↗

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.

Adrenergic beta-Antagonists↗

Possible association but no linkage of the HSD11B2 gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase to hypertension in Black people.

OBJECTIVE: The HSD11B2 (HSD11K) gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase is mutated in the syndrome of apparent mineralocorticoid excess, an autosomal recessive form of salt-sensitive hypertension. This gene is thus a logical candidate locus for risk of essential hypertension. DESIGN AND METHODS: Because hypertension in Black people tends to be of the low-renin, salt sensitive type, we genotyped independent sets of hypertensives of Afro-American (59 kindreds) and Afro-Caribbean (66 kindreds) origin using a highly polymorphic (heterozygosity index 0.84) CA repeat polymorphism in the first intron of HSD11B2. Linkage was assessed by the affected pedigree member method. RESULTS: No linkage of hypertension to this locus could be demonstrated, but statistically significant allelic associations were noted. CONCLUSIONS: HSD11B2 does not have a strong influence on the development of essential hypertension in Black people, but weaker effects on blood pressure cannot be ruled out.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Attractiveness of facial averageness and symmetry in non-western cultures: in search of biologically based standards of beauty.

Averageness and symmetry are attractive in Western faces and are good candidates for biologically based standards of beauty. A hallmark of such standards is that they are shared across cultures. We examined whether facial averageness and symmetry are attractive in non-Western cultures. Increasing the averageness of individual faces, by warping those faces towards an averaged composite of the same race and sex, increased the attractiveness of both Chinese (experiment 1) and Japanese (experiment 2) faces, for Chinese and Japanese participants, respectively. Decreasing averageness by moving the faces away from an average shape decreased attractiveness. We also manipulated the symmetry of Japanese faces by blending each original face with its mirror image to create perfectly symmetric versions. Japanese raters preferred the perfectly symmetric versions to the original faces (experiment 2). These findings show that preferences for facial averageness and symmetry are not restricted to Western cultures, consistent with the view that they are biologically based. Interestingly, it made little difference whether averageness was manipulated by using own-race or other-race averaged composites and there was no preference for own-race averaged composites over other-race or mixed-race composites (experiment 1). We discuss the implications of these results for understanding what makes average faces attractive. We also discuss some limitations of our studies, and consider other lines of converging evidence that may help determine whether preferences for average and symmetric faces are biologically based.

Adolescent↗

What is the optimal medical management of ischaemic heart failure?

Ischaemic heart disease is probably the most important cause of heart failure. All patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with heart failure due to ischaemic heart disease may also, theoretically, benefit from treatments designed to relieve ischaemia and prevent coronary occlusion and from revascularisation. However, there is little evidence to show that effective treatments, such as angiotensin converting enzyme (ACE) inhibitors and beta-blockers, exert different effects in patients with heart failure with or without coronary disease. Moreover, there is no evidence that treatment directed specifically at myocardial ischaemia, whether or not symptomatic, or coronary disease alters outcome in patients with heart failure. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion appear ineffective or harmful in patients with heart failure. There is no evidence, yet, that revascularisation improves prognosis in patients with heart failure, even in patients who are demonstrated to have extensive myocardial hibernation. On current evidence, revascularisation should be reserved for the relief of angina. Large-scale, randomised controlled trials are currently underway investigating the role of specific treatments targeted at coronary syndromes in patients who have heart failure. The CHRISTMAS study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The WATCH study is comparing the efficacy of aspirin, clopidogrel and warfarin. The HEART-UK study is assessing the effect of revascularisation on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are currently assessing the safety and efficacy of statin therapy in patients with heart failure. Only when the results of these and other studies are known will it be possible to come to firm conclusions about whether patients with heart failure and coronary disease should be treated differently from other patients with heart failure due to left ventricular systolic dysfunction.

Adrenergic beta-Antagonists↗

Urine-based screening for Chlamydia trachomatis in men attending sexually transmitted disease clinics.

BACKGROUND: Nucleic acid-amplified tests for Chlamydia trachomatis are accurate but costly. Screening strategies for asymptomatic men are needed. GOAL: To assess C trachomatis screening strategies for asymptomatic males. STUDY DESIGN: Men attending a sexually transmitted disease clinic were tested for C trachomatis with ligase chain reaction and culture, and for urethral inflammation with urine leukocyte esterase and urethral Gram stain. RESULTS: C trachomatis prevalence was 5.5% among 1,625 asymptomatic men. Ligase chain reaction increased detection by 49% among men without urethral inflammation. An age of younger than 25 years and urethral inflammation were associated with positive ligase chain reaction results. The negative predictive value of urine leukocyte esterase was highest among older men, but urethral Gram stain was equally sensitive in predicting infection regardless of age. An age of younger than 30 years or urethral inflammation identified the highest proportion of infections (92%) and reduced the percentage of men screened by 43%. CONCLUSIONS: Urine ligase chain reaction increased C trachomatis detection, particularly among men without urethral inflammation. Testing all asymptomatic men younger than 30 years is optimal, whereas negative urine leukocyte esterase or urethral Gram stain results in men 30 years or older support no testing.

Adult↗

Partner management for gonococcal and chlamydial infection: expansion of public health services to the private sector and expedited sex partner treatment through a partnership with commercial pharmacies.

BACKGROUND: Public health partner notification (PN) services currently affect only a small minority of patients with gonorrhea or chlamydial infection and new approaches to PN are needed. OBJECTIVES: To expand PN for gonorrhea and chlamydial infection to private sector patients and to assess the feasibility of treating sex partners through commercial pharmacies. METHODS: Selected patients were offered PN assistance and were randomly offered medication to deliver to their partners. RESULTS: Providers permitted the health department to contact 3613 (91%) of 3972 potentially eligible patients, and 1693 (67%) of 2531 successfully contacted patients consented to interview. Of these, 1095 (65%) reported at least one untreated partner. Most patients (90%) wished to notify partners themselves. Patients were more likely to have partners who had not yet been treated and to request PN assistance if they had more than one sex partner in the preceding 60 days or a partner they did not anticipate having sex with in the future. These two factors characterized 49% of all patients interviewed, 70% of those with a partner that was untreated 7 or more days after index patient treatment, and 83% of those accepting PN assistance. Among 458 randomly selected patients with untreated partners at time of study interview, 346 (76%) agreed to deliver treatment to a partner. Of these, most (266) chose to obtain medication for a partner at a pharmacy, of whom 223 (84%) successfully did so. CONCLUSION: A substantial minority of private sector patients have untreated partners more than 7 days after their own treatment; some need help with PN, but most will agree to deliver medication to partners themselves.

Adolescent↗

Expression of the protein tyrosine phosphatase-like protein IA-2 during pancreatic islet development.

A tyrosine phosphatase-like protein, IA-2, is a major autoantigen in Type 1 diabetes but its role in islet function is unclear. Tyrosine phosphorylation mediates regulation of cellular processes such as exocytosis, cell growth, and cell differentiation. To investigate the potential involvement of IA-2 in islet differentiation and insulin secretion, we analyzed by immunohistochemistry expression of IA-2 during islet development in fetal rats and during the maturation of insulin secretory responses after birth. In the fetus, IA-2 immunoreactivity was detected in primitive islets positive for insulin and glucagon at 12 days' gestation. Subsequently, IA-2 was only weakly detectable in the fetal pancreas. In neonatal rat, a progressive increase in IA-2 immunoreactivity was observed in islets from very low levels at 1 day of age to moderate labeling at 10 days. In the adult, relatively high levels of IA-2 were detected in islets, with heterogeneous expression in individual cells within each islet. IA-2 marks a population of endocrine cells that transiently appear early in pancreatic ontogeny. Islet IA-2 expression reappears after birth concomitant with the development of mature insulin secretory responses, consistent with a role for this protein in regulated hormone secretion.

Animals↗

Decreased insulin secretion in type 2 diabetes: a problem of cellular mass or function?

Type 2 diabetes is characterized by diminished or inappropriate secretion of insulin, which could be a defect of either islet cell function or beta-cell mass. Quantitation of islet cell populations in postmortem pancreas demonstrates little change of beta-cell mass in type 2 diabetes. Reduction of islet cell mass (up to 30%) is associated largely with islet amyloid deposition, and the degree of amyloidosis is independent of the duration of the disease. Insulin secretory capacity is dependent on both function and mass of cells. beta-Cell secretion is heterogeneous; increasing glucose concentrations result in recruitment of beta-cells into the secretory pool, indicating a large reserve of secretory capacity that can be recruited in insulin resistant conditions. The Starling curve of islet function describes the relationship of insulin secretion to increasing levels of insulin resistance and hyperglycemia in type 2 diabetes. Longitudinal studies in Macaca mulatta monkeys show that insulin resistance is accompanied by increased islet mass and onset of diabetes is associated with deposition of amyloid and reduction of beta-cells. Increasing the function of unresponsive beta-cells rather than the mass of cells may be a more effective therapeutic target for type 2 diabetes.

Amyloid↗

Data-driven recognition memory: a new technique and some data on age differences.

In this study, we investigate the effect on recognition memory of having target and distractor stimuli consisting of different combinations of low-level elements (letters), relative to when targets and distractors consist of combinations of the same elements (nonoverlap and overlap conditions, respectively). It was found that recognition memory was enhanced in the nonoverlap condition, even though subjects reported being unaware of this experimental manipulation. This confirms the importance of perceptually driven processing in the implicit memory component of recognition memory. The extent to which this effect occurs is found to be age dependent, with elderly subjects benefiting more from having targets and distractors consisting of nonoverlapping elements. This is consistent with the notion that elderly subjects show less reliance on item-specific/contextual detail to support recognition memory.

Adult↗

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes.

PURPOSE: The gut inhabiting bacterium Oxalobacter formigenes may be a negative risk factor in recurrent calcium oxalate kidney stone disease that apparently maintains oxalic acid homeostasis in its host via the degradation of dietary oxalate. The possibility of using this bacterium as probiotic treatment to reduce urinary oxalate was investigated in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were placed on a diet supplemented with ammonium oxalate to induce a state of severe hyperoxaluria. Subgroups of these rats received an esophageal gavage of 1 x 10(3), 10(5), 10(7) or 10(9) O. formigenes per feeding for a 2-week period. Each rat was followed for general health and changes in urinary oxalate. RESULTS: Rats with chronic hyperoxaluria resulting from high dietary oxalate that were treated with O. formigenes showed decreased urinary oxalate within 2 days of initiating probiotic supplementation. The amount of the decrease in a 2-week period proved directly proportional to the dose of bacteria. Urinary oxalate in rats receiving higher amounts of O. formigenes returned to almost normal. Throughout the study the rats remained healthy with no signs of toxicity, antibody development or a histopathological condition. CONCLUSIONS: Probiotic treatment of hyperoxaluric rats with O. formigenes may significantly and rapidly reduce the level of oxalate in the urine. This probiotic treatment appears to be safe and well tolerated. The approach may be feasible for treating calcium oxalate kidney stone disease.

Animals↗

Differentiating embryonal stem cells are a rich source of haemopoietic gene products and suggest erythroid preconditioning of primitive haemopoietic stem cells.

The difficulties associated with studying molecular mechanisms important in hemopoietic stem cell (HSC) function such as the problems of purifying homogeneous stem cell populations, have prompted us to adapt the murine ES cell system as an in vitro model of HSC generation and function. We now report that careful analysis of the time course of HSC generation in differentiating ES cells allows them to be used as a source of known and novel hemopoietic gene products. We have generated a subtracted library using cDNA from ES cells collected just prior to and just following the emergence of HSCs. Analysis of this library shows it to be a rich source of known hemopoietic and hemopoietic related gene products with 44% of identifiable cDNAs falling into these camps. We have demonstrated the value of this system as a source of novel genes of relevance to HSC function by characterizing a novel membrane protein encoding cDNA that is preferentially expressed in primitive hemopoietic cells. Intriguingly, further analysis of the known components of the subtracted library is suggestive of erythroid preconditioning of the ES cell-derived HSC. We have used dot-blot and in situ analysis to indicate that this erythroid preconditioning is probably restricted to primitive but not definitive HSC.

Amino Acid Sequence↗

An F-Box/WD40 repeat-containing protein important for Dictyostelium cell-type proportioning, slug behaviour, and culmination.

FbxA is a novel member of a family of proteins that contain an F-box and WD40 repeats and that target specific proteins for degradation via proteasomes. In fruiting bodies formed from cells where the fbxA gene is disrupted (fbxA(-) cells), the spore mass fails to fully ascend the stalk. In addition, fbxA(-) slugs continue to migrate under environmental conditions where the parental strain immediately forms fruiting bodies. Consistent with this latter behaviour, the development of fbxA(-) cells is hypersensitive to ammonia, the signaling molecule that regulates the transition from the slug stage to terminal differentiation. The slug comprises an anterior prestalk region and a posterior prespore region and the fbxA mRNA is highly enriched in the prestalk cells. The prestalk zone of the slug is further subdivided into an anterior pstA region and a posterior pstO region. In fbxA(-) slugs the pstO region is reduced in size and the prespore region is proportionately expanded. Our results indicate that FbxA is part of a regulatory pathway that controls cell fate decisions and spatial patterning via regulated protein degradation.

Amino Acid Motifs↗