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The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.  相似文献   
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The G of the CHARGE association represents genital hypoplasia, which is typically recognized only in males (micropenis/cryptorchidism). The cause of genital hypoplasia in this disorder has not been determined. We now report the cases of nine individuals with CHARGE association and hypogonadotropic hypogonadism, manifested by hypogenitalism and gonadotropins at or below minimal detectable levels at ages when these hormones should be readily measurable. We suggest that central hypogonadism is responsible not only for the genital hypoplasia in male patients but also for the lack of secondary sexual development in patients of both sexes. Since hypogonadotropic hypogonadism appears to be the usual cause of genital and pubertal abnormalities in CHARGE association, measurement of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations in infants up to 2-3 months of age who are suspected of having this disorder could help establish the diagnosis. Determination of serum LH and FSH concentrations in teenagers with CHARGE association could result in early diagnosis of hypogonadotropic hypogonadism, allowing for treatment of hormonal deficiencies and minimization of potential secondary psychosocial and medical problems.  相似文献   
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There is growing epidemiological evidence from sub-Saharan Africa that male circumcision reduces the risk of HIV acquisition. We review the recent evidence of the protective effect on HIV and other sexually transmitted diseases, including discussion of possible biological mechanisms and highlighting the limitations of the observational studies on which these findings are based. We conclude by discussing the public health implications of these findings, including issues such as safety, acceptability, feasibility and cost-effectiveness of promoting male circumcision in African populations.  相似文献   
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We evaluated the reliability of optic disk area and disk rim area measurements obtained with the Humphrey Retinal Analyzer from ten repeat fundus images each of one eye of ten normal subjects and ten subjects with increased intraocular pressure. Variability of rim and disk areas was not significantly different between these two groups (P greater than .05), nor was it significantly different between images acquired during the same session and those acquired during different sessions (P greater than .05). Variability was significantly different between subject groups based on the distinctness of the disk edge and the slope of the cup wall (P less than .01). The average minimum change in the measurements on the same eye that would exceed variability of the technique at the 95% confidence level was 0.20 mm2 and 0.47 mm2 for rim area for the least variable and most variable subject groups based on optic nerve head characteristics, and 0.09 mm2 and 0.32 mm2 for disk area for the corresponding subject groups. Operator input contributed significantly to overall variability. Reliability of rim and disk areas in this study was comparable to that reported for other computerized image analyzers.  相似文献   
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M G Quigley 《Ophthalmology》1999,106(5):856; author reply 856-856; author reply 857
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