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Biomedical subjects

R Olshen

Publications and source records attributed to R Olshen.

11 recordsLinked to original sources
PubMed2001

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Blood Pressure↗
PubMed2001

The glycine allele of a glycine/arginine polymorphism in the beta2-adrenergic receptor gene is associated with essential hypertension in a population of Chinese origin.

BACKGROUND: Several studies implicate polymorphisms in the human beta-adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 (Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95% CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population. There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2-adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin.

Arginine↗
PubMed2001

High-throughput genotyping with single nucleotide polymorphisms.

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11-beta hydroxylase gene. The genotyping method is accurate-we estimate an error rate of fewer than 1 in 2000 genotypes, rapid-with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible-a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three "pseudo-SNPs" (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.

Alleles↗
PubMed2000

Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations.

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.

Adult↗
PubMed1990

The predictive value of needle localization mammographically assisted biopsy of the breast.

This study was done to review critically the experience at the University of California at San Diego in needle localization mammographic biopsy of the breast with regard to use and accuracy in identifying early carcinoma of the breast. Ninety-seven patients underwent needle localization mammographic biopsy of the breast between 1985 and 1987. Indications for this procedure included the presence of microcalcifications or a mass shown on mammographic examination, or both, in conjunction with physical examination which did not define a discrete abnormality in the area. Mammographic, demographic, pathologic, hormone receptor data and staging information were recorded and processed on the MicroVax II computer (Digital Equipment Corporation). Twenty-four per cent of lesions with needle localization mammographic assisted biopsy proved to be malignant. Sixteen lesions were diagnosed as an infiltrating ductal carcinoma and ten of these had an accompanying intraductal carcinoma. Over-all, intraductal carcinoma was present in 16 of the 23 specimens diagnosed as malignant. At biopsy, the margins were clear in 17 of 23, and vascular invasion was present in only one patient with an infiltrating lobular carcinoma. Five were tumor in situ, 12 were stage 1 and five were stage 2 (staging information was not available in one instance). Hormone receptor data were available in 17 of 23 specimens. Estrogen receptors were positive in 13 and progesterone receptors were positive in six. The smallest preinvasive malignant lesion was 4 millimeters, as seen on the mammogram, and the smallest free-standing invasive lesion was 8 millimeters. Preinvasive lesions (intraductal) presented as microcalcifications in 80 per cent. Invasive lesions presented as either a mass (n = 9) or as a mass and microcalcifications (n = 5) in 81 per cent. All five lesions presenting as both a mass and microcalcifications on mammogram proved to be malignant. Multifocal lesions on mammographic examination which proved to be malignant were multifocal pathologically in only 50 per cent. Needle localization mammographic biopsy is useful in detecting early carcinoma of the breast. Biopsy should be done on lesions presenting on mammogram as both a mass and microcalcifications and not observed. Focality of lesions on mammogram does not correlate with focality on biopsy and may be misleading as criteria for operative planning.

Adenofibroma↗
PubMed1987

Life events do not predict symptoms: symptoms predict symptoms.

The effects of life events and previous symptoms on current symptom levels were examined in a model using data from a 3-year prospective study. Male psychiatric patients and nonpatients reported on life events and symptoms every 2 months on 18 occasions. Logistic regression analysis of these data revealed little dependence of psychiatric symptoms on preceding life events as measured by the Holmes and Rahe Schedule of Recent Experiences (SRE). The best predictor of the current symptom level was the level of previous symptoms. It is concluded that efforts to relate changes in the social environment to health must first consider the possible contribution of the antecedent symptom level to the variability in health outcome.

Adult↗
PubMed1983

Risk prediction after myocardial infarction. Comparison of three multivariate methodologies.

We predicted 30-day mortality and survival following acute myocardial infarction in two different hospital populations utilizing several multivariate statistical methodologies [linear discriminant analysis (LDA), logistic regression (LR), recursive partitioning (RP), and nearest neighbor]. Variables used were identified as predictive univariately from the base hospital and were obtained during the first 24 h after admission. LDA, LR, or RP all performed similarly within a given population; although each used the information contained in the prognostic variables differently. Application between different populations of prediction schemes based on LDA and LR was shown to be feasible but prior validation is essential.

Aged↗
PubMed1982

A computer-derived protocol to aid in the diagnosis of emergency room patients with acute chest pain.

To determine whether data available to physicians in the emergency room can accurately identify which patients with acute chest pain are having myocardial infarctions, we analyzed 482 patients at one hospital. Using recursive partitioning analysis, we constructed a decision protocol in the format of a simple flow chart to identify infarction on the basis of nine clinical factors. In prospective testing on 468 other patients at a second hospital, the protocol performed as well as the physicians. Moreover, an integration of the protocol with the physicians' judgments resulted in a classification system that preserved sensitivity for detecting infarctions, significantly improved the specificity (from 67 per cent to 77 per cent, P less than 0.01) and positive predictive value (from 34 per cent to 42 per cent, P = 0.016) of admission to an intensive-care area. The protocol identified a subgroup of 107 patients among whom only 5 per cent had infarctions and for whom admission to non-intensive-care areas might be appropriate. This decision protocol warrants further wide-scale prospective testing but is not ready for routine clinical use.

Adult↗
PubMed1982

Life events and symptoms: Fourier analysis of time series from a three-year prospective inquiry.

In a three-year prospective study in which life events and psychiatric symptoms were assessed every two months, Fourier analyses led to the classification of event-symptom relationships into five typologies. Only one event-symptom typology, representing 9% of subjects, was consistent with the commonly held causal model. The results indicate that further progress in life-events research will require prospective designs, more sophisticated methods for gathering life-events data than the Schedule of Recent Experiences, focus on qualitative features of events (eg, undesirability or threat), and identification of personal characteristics and coping styles that might augment or attenuate the health impacts of life happenings.

Adult↗
PubMed1981

The pathomechanics of gait in Duchenne muscular dystrophy.

Forty-six separate gait studies were analysed for 21 ambulatory patients with Duchenne muscular dystrophy. Three groups were defined on the basis of significant gait variables: early, transitional and late. Disease progression can be predicted with 91 per cent accuracy by three gait variables: cadence, dorsiflexion in swing, and anterior pelvic tilt. The patients in the early group manifested a positive Gower's sign but gait changes were subtle, being principally slightly increased hip flexion in swing, decreased dorsiflexion in swing and reduction in cadence. The force line moved in front of the knee center early in single-limb support. In the transitional stage, anterior pelvic tilt was exaggerated, cadence was further reduced, and foot drop in swing phase was increased. Shoulder sway was noted as a compensation for gluteus medius weakness. The base of support widened. The force line remained behind the hip joint and in front of the knee joint throughout single-limb support. In the late stage, work output increased, cadence continued to drop, shoulder sway increased further, and there was a wider base of support. The force line remained very close to the center of the hip and in front of the knee at all times during single-limb support. The authors' conclusions are: (1) the earliest postural change in gait is increased lumbar lordosis secondary to gluteus maximus weakness, and at this time the quadriceps are relatively competent; (2) quadriceps insufficiency was the key factor in gait deterioration. It appeared in the transitional stage and was characterized by exaggerated anterior pelvic tilt, restricted hip extension in stance phase, equinus posturing, and maintenance of the force line in front of the knee throughout single-limb support. Long-leg bracing is indicated when these signs of quadriceps insufficiency are noted.

Biomechanical Phenomena↗