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Biomedical subjects

R A Price

Publications and source records attributed to R A Price.

At least 37 records · Page 2Linked to original sources
PubMed2001

Choroid plexus carcinoma in an adult.

Choroid plexus carcinomas are rare in adults. They can behave aggressively and their optimal management is uncertain. An adult patient with choroid plexus carcinoma who was treated with an incomplete surgical resection and postoperative radiotherapy is reported. Despite an identifiable local response to radiotherapy, disease progression resulted in death 4 years after presentation. This report reviews the current literature and discusses the management issues regarding this uncommon adult malignancy.

Adult↗
PubMed2001

Risk ratios for obesity in families of obese African-American and Caucasian women.

We examined age- and sex-standardized risk ratios (SRRs) in matched samples of 1,185 families of obese African-American and Caucasian women. Familial risk ratios increased with body mass index (BMI) of proband and BMI thresholds of relative. Ratios were higher in Caucasian than African-American families, apparently because Caucasian probands were more extreme relative to their population mean. Risk ratios for moderate obesity (BMI >/= 30) were around 2 for African-Americans and were a little higher in Caucasians. Ratios for extreme obesity (BMI >/= 40) ranged from 3 to 5 in African-Americans and from about 5 to 9 in Caucasians. Thin relatives were rare in families of both races. Risk ratios appear high enough in both racial groups to facilitate the identification of quantitative trait loci underlying common obesity phenotypes. The high population prevalence of obesity in African-American women will require particularly high selection thresholds to achieve risk ratios comparable to those for Caucasians. The scarcity of thin siblings in both groups will greatly increase the effort required in sample recruitment for discordant pair designs.

Black or African American↗
PubMed2000

X-linkage does not account for the absence of father-son similarity in plasma uric acid concentrations.

Plasma uric acid concentration aggregates in families, and this similarity has been suggested to be due, in part, to multiple shared genes. Men have higher plasma uric acid concentrations than women and are affected with gout nine times more frequently. Rare forms of hyperuricemia and gout are due to mutations of X-linked genes (HPRT1 and PRPS1). Given these observations, we tested the hypothesis that normal variation in plasma uric acid levels would display a pattern of familial similarity consistent with X-linkage in 892 individuals from 196 obese but otherwise healthy families. As predicted by X-linked inheritance, fathers and sons showed no resemblance in plasma uric acid concentration (r = 0.013, NS), while all other pairings showed moderate-to-strong familial resemblance (ranging from 0.167, P < 0.01, parent-offspring to 0.415, sister-sister, P < 0.01). We then tested the hypothesis that loci along the X chromosome would influence plasma uric acid concentration. We conducted both single-point and multipoint linkage analyses using 17 X-linked markers spaced at approximately 9 cm intervals to determine whether allele sharing among sibs was related to sib similarity in plasma uric acid concentrations (n = 1,100 sib pairs). We found no regions of the X chromosome that cosegregated with plasma uric acid concentrations (P > 0.05). We conclude that variation in genes on the X chromosome contribute little to normal variation in plasma uric acid concentrations.

Adolescent↗
PubMed2000

Dose selection for prostate cancer patients based on dose comparison and dose response studies.

PURPOSE: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). METHODS AND MATERIALS: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score < or =6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. RESULTS: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable > or =20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable > or =20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. CONCLUSIONS: Dose response varies by patient subgroup, and appropriate dose can be estimated for up to six subdivisions of prostate cancer patients. The appropriate use of high dose with 3D CRT results in 5-year cure rates that equal or exceed other treatments. The national practice must be upgraded to allow the safe administration of 75-80 Gy with 3D CRT.

Dose-Response Relationship, Radiation↗
PubMed2000

The peroxisome proliferator-activated receptor gamma 2 Pro12Ala mutation is associated with early onset extreme obesity and reduced fasting glucose.

We screened the peroxisome proliferator activated receptor gamma 2 (PPAR gamma 2) for sequence variants in 165 unrelated obese (BMI >/= 30 kg/m(2)) Caucasian women, and 49 normal weight Caucasian female controls (BMI < 27 kg/m(2)). The allele frequency of the Pro12Ala mutation was higher in obese(18.18%) than in normal weight women (8. 16%) (chi(2)((1)) = 5.68, P = 0.017). Among obese women, the Pro12Ala mutation lowered age of obesity onset (Pro/Pro, 13.2 +/- 9. 4 years; Pro/Ala+Ala/Ala 8.6 +/- 7.1 years, P = 0.005), was associated with lower fasting glucose and was protective against type II diabetes.

Adult↗
PubMed2000

Resemblance for body mass index in families of obese African American and European American women.

OBJECTIVE: We determined the levels of resemblance in body mass index (BMI) in large samples of families selected through obese African American and European American women. RESEARCH METHODS AND PROCEDURES: We examined correlations among relatives in 1,185 European American and African American families ascertained through age-matched obese women (BMI > or = 30 kg/m2). A subset of 801 families were ascertained through extremely obese women (BMI > or = 40 kg/m2). RESULTS: Parent-offspring and sibling correlations ranged from 0.19 to 0.15, suggesting a moderate level of heritability in both groups. Mean BMI values for female relatives were lower for European Americans than for African Americans even though probands were matched, perhaps because the European American relatives regress to a lower population mean. We found significantly higher family correlations for height in European Americans, suggesting greater environmental variability among African Americans for factors affecting growth and physical development. DISCUSSION: Our results suggest a similar level of heritability of BMI in families of obese African American and European American women. Other genetic studies will be needed to determine the extent to which the same or different genes and environmental conditions contribute to an overall similar heritability in the two racial groups.

Adolescent↗
PubMed2000

Melanocortin 3 receptor (MC3R) gene variants in extremely obese women.

OBJECTIVE: Following several reports of linkage of obesity related phenotypes to human chromosome 20q we sought to determine whether variations of the melanocortin 3 receptor (MC3R) gene are associated with obesity. DESIGN: We screened the MC3R gene coding region and approximately 2 kb of 5' and 3' flanking sequences for DNA variants in unrelated extremely obese women and average weight controls using polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) analysis and DNA sequencing. SUBJECTS: 124 unrelated extremely obese women (body mass index, (BMI)>/=40 kg/m2) and 85 average weight controls (BMI<27 kg/m2). MEASUREMENTS: Radiation hybrid (RH) mapping was performed to localize the MC3R gene. 5' and 3' flanking sequences of MC3R gene were cloned. PCR-SSCP and DNA sequencing were used to detect mutations in the MC3R gene coding region and flanking sequences. RESULTS: RH mapping localized the MC3R gene to 20q13, between markers D20S100 and D20S149. 1083 bp 5' and 653 bp 3' flanking region of the MC3R gene were cloned. A missense mutation (+241, codon 81 ATT/GTT, Ile-->Val) was found in the MC3R coding region. Four more variants were detected in the 5' flanking sequence: -201(C-->G), -239 (A-->G), -762(A-->T) and -769(T-->C). Compared with controls, no significant allele frequency differences were found. Racial differences were found for the +241, -201, -239 and -762 polymorphisms. CONCLUSIONS: Several sequence variants were found in the MC3R gene coding region and in 5' flanking sequences. However, none of the variants were associated with obesity phenotypes. The linkage of extreme human obesity on 20q13 is likely caused by genes other than MC3R. International Journal of Obesity (2000) 24, 206-210

Adult↗
PubMed2000

IORT apparatus design improvement through the evaluation of electron spectral distributions using Monte Carlo methods.

Clinically used IORT electron beam characteristics may vary with respect to typical external beams due to the decrease of lateral scatter equilibrium and the addition of the IORT apparatus itself. Additionally, chamber size effects may lead to inaccurate measurements of the changes in electron beam characteristics. The causal components of these beam characteristics are often difficult or impossible to measure using experimental techniques. For this reason, and for potential design improvement, the electron beams were modeled using the OMEGA/BEAM Monte Carlo software for radiation transport. The IORT electron beam characteristics of the Varian Clinac 1800 were studied for 6, 12, and 20 MeV electrons and 1-4 in. diameter flat-end applicators. The characteristics studied include electron energy spectra, percentage depth dose, and cross-plane profiles. It was found that by increasing the thickness of the aluminum base plate of the main attachment, the dose at d(max) outside the primary field could be reduced from approximately 9% to 1% of maximum.

Biophysical Phenomena↗
PubMed2000

Reduced mortality associated with body mass index (BMI) in African Americans relative to Caucasians.

Although obesity is especially common in African-American women, the relationship between body mass index (BMI, kg/m2) and mortality primarily has been studied in Caucasians, and almost exclusively in average weight populations. In order to examine the relationship between race and mortality in a predominately overweight population, we assessed mortality in 6,602 parents of obese African-American and Caucasian subjects. Most parents of both races were overweight or obese: 87.8% of African-American mothers (mean BMI = 37.7) and 78.6% of Caucasian mothers (mean BMI = 34.9) had a BMI > or =27.3; 61.9% of African-American fathers (mean BMI = 31.5) and 63.6% of Caucasian fathers (mean BMI = 31.8) had a BMI > or =27.8. Even though African Americans had equivalent (fathers) or higher (mothers) average BMI and percentage overweight or obesity than Caucasians, unadjusted mortality rates were consistently lower in African Americans than in Caucasians. In a combined sample, income, age (linear, quadratic and cubic effects), gender, BMI (linear and quadratic), and race were significant predictors of mortality. Linear and quadratic effects of BMI were significant within race and in the combined sample, after controlling for the effects of all other predictor variables. Therefore, the mortality differences cannot be due to differences in age, income, BMI, or gender distributions. In addition, there was significant heterogeneity between races for all models examined, suggesting interactions between race and all other predictor variables. Moreover, there was a strong residual effect for race after accounting for the other variables. The highly selective and cross-sectional nature of this sample limits our ability to make specific BMI-associated risk estimates. However, the consistent differences between comparably ascertained racial groups sampled from the upper extreme of the BMI distribution provide support for a lower BMI-associated mortality rate in African Americans relative to Caucasians.

Adult↗
PubMed1999

Sequence variants in the 5' flanking region of the leptin gene are associated with obesity in women.

Few mutations have been found in the human leptin gene and the relationship between leptin gene sequence variation and human overweight is uncertain. To determine whether sequence variation within the leptin gene and its regulatory elements contribute to extreme obesity, we screened approximately 3 kb of the 5' flanking region and the three exons in 125 unrelated extremely obese (BMI > or = 40 kg/m2) and 86 average weight women (BMI < 27 kg/m2). Within the protein coding regions only one heterozygous silent mutation was found (codon 102; AAC/AAT). Within the 5' flanking region, six frequent sequence variants were detected (q > 0.10), and the allele frequencies of three of these variants differed between obese and average weight Caucasian women (+19, chi 2 = 4.46, p = 0.035; -1823, chi 2 = 4.36, p = 0.037; -2548, chi 2 = 5.73, p = 0.017). Nine infrequent sequence variants were detected (q < 0.05) but they did not occur more often among obese women compared with those of average-weight. For extremely obese women, three polymorphisms (+19, -188, and -633) predicted the degree of obesity. Allelic variants may influence the regulation of the leptin gene and thereby influence body weight, particularly among extremely obese women. However, given the low variability in coding regions and the high variability in the 5' flanking region, discerning the functional significance of each variant is likely to be difficult.

Adolescent↗
PubMed1999

Genome scan for human obesity and linkage to markers in 20q13.

Obesity is a highly prevalent, multigenic trait that predicts increased morbidity and mortality. Here we report results from a genome scan based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity and normal body weight. The average marker interval was approximately 10 cM. We examined four correlated obesity phenotypes, including the body-mass index (BMI) (both as a quantitative trait and as a discrete trait with a threshold of BMI > or /=30 kg/m2) and percentage of fat (both as a quantitative trait and as a discrete trait with a threshold of 40%) as assessed by bioelectrical impedance. In the initial stage of the genome scan, four markers in 20q gave positive evidence for linkage, which was consistent across most obesity phenotypes and analytic methods. After saturating 20q with additional markers (25 markers total) in an augmented sample of 713 members from 124 families, we found linkage to several markers in a region, 20q13, previously implicated in both human and animal studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P values (based on Monte Carlo simulations, which controlled for multiple testing) < or /=. 01 for single-point analysis. In addition, the parametric, affecteds-only analysis for D20S476 yielded a LOD score of 3.06 (P=. 00009), and the affected-sib-pair test yielded a LOD score of 3.17 (P=.000067). Multipoint analyses further strengthened and localized these findings. This region includes several plausible candidate genes for obesity. Our results suggest that one or more genes affecting obesity are located in 20q13.

Black People↗
PubMed1999

Possible association between schizophrenia and a CAG repeat polymorphism in the spinocerebellar ataxia type 1 (SCA1) gene on human chromosome 6p23.

The gene for spinocerebellar ataxia type 1 (SCA1) is a potential candidate gene for schizophrenia because of previous positive linkage findings in this region (6p22-24), and because the reported correlation between SCA1 onset and the number of CAG repeats suggests anticipation. To test the involvement of this gene in the development of schizophrenia, we examined genotypes of the SCA1 CAG repeat polymorphism for 49 Caucasian patients with schizophrenia, and 88 Caucasian controls. We found a significant association between the frequencies of alleles of this gene and schizophrenia (chi 2 = 18.40, df = 8, P = 0.018). Among 13 alleles, one allele (31 trinucleotide repeat) was significantly more frequent in patients with schizophrenia than in controls (chi 2 = 9.57, df = 1, P = 0.002). This association was sustained after applying a Bonferroni correction for multiple testing (P = 0.05/13 = 0.004), and the chi-square results were shown to be robust through Monte Carlo simulation. We observed no allelic association with three flanking microsatellite markers (D6S288, D6S1605, and D6S337), suggesting that our result was not due to population stratification. Further studies of this locus are needed to confirm this finding, and to determine a potential role for this gene in the development of schizophrenia.

Ataxin-1↗
PubMed1998

Dieting, exercise, or disordered eating does not account for extremes of body weight within families.

OBJECTIVE: Families having both members with obesity and thin members should contain substantial information for genetics studies, provided measured phenotype is an accurate indicator of genetic predisposition. We assessed the impact of potentially complicating behavioral factors on obesity phenotypes of family members selected for a long-term project to identify genes for human obesity. RESEARCH METHODS AND PROCEDURES: Ninety-nine Caucasian families were selected for study because they contained both extremely obese and average-weight family members. Family members (n=492) were queried about their diet and exercise habits, their psychiatric histories as they pertained to eating disorders, and for a subset of subjects (n=329), a lifetime dieting history and a lifetime maximum weight were recorded. RESULTS: Subjects with average body weights in these families did not appear to be maintaining their weight by dieting and <4% of the average-weight subjects had ever been obese in the past. DISCUSSION: Although dieting and other weight loss practices potentially could either mask or complicate the genotype-phenotype relationship, we found little evidence for this possibility in the families studied.

Adolescent↗
PubMed1998

Obesity related phenotypes in families selected for extreme obesity and leanness.

BACKGROUND: Obesity is a multigenic trait, and special methods and sampling designs are needed for gene identification. OBJECTIVE: To describe characteristics of families selected to increase information for genetic linkage studies of obesity. DESIGN: Families having extremely obese siblings with a lean parent and sibling. SUBJECTS: 594 members of 94 Caucasian families. MEASUREMENTS: Measured height and weight, bioelectric impedance, skinfolds, circumferences and questionnaires. RESULTS: Families have an extreme range of obesity phenotypes, which are bimodally distributed. The obese individuals are predominantly women with an onset of obesity early in life. Obesity onset age was negatively correlated with level of obesity, and onset ages were correlated among family members. Individual obesity measures were highly correlated. The extreme range of phenotypes within families increases family variability and presumably gene segregation. CONCLUSION: Sampling families through extremely obese sibling pairs with a lean parent and sibling results in families with an extreme range of obesity and leanness. The large within-family variance and early age of onset should make these families highly informative for gene mapping and gene identification studies.

Adolescent↗
PubMed1998

Estimates of the heights and weights of family members: accuracy of informant reports.

OBJECTIVE: Information about the accuracy of family informant estimates of height and weight should assist investigators in evaluating the costs and benefits of using this type of data in genetic study designs. DESIGN AND METHOD: To assess the accuracy of family informant estimates, 374 first-degree relatives from 94 Caucasian families, gave estimates about the heights and weights of their first degree relatives. These estimates were compared with measured heights and weights to determine their accuracy. RESULTS: Informant estimates were highly predictive of measured heights (r=0.95), and weights (r=0.94), but informants systematically overestimated heights (mean=1.4 cm) and underestimated weights of their family members (mean=4.1 kg). CONCLUSIONS: On average, height estimates were generally within 1% of the measured height and weight estimates were within 3-5% of the measured weight. Therefore, these proxy measures can provide useful data, when measured or self-reported heights and weights are not available.

Bias↗
PubMed1998

Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae.

Arginine decarboxylase (ADC) is an important enzyme in the production of putrescine and polyamines in plants. It is encoded by a single or low-copy nuclear gene that lacks introns in sequences studied to date. The rate of Adc amino acid sequence evolution is similar to that of ndhF for the angiosperm family studied. Highly conserved regions provide several target sites for PCR priming and sequencing and aid in nucleotide and amino acid sequence alignment across a range of taxonomic levels, while a variable region provides an increased number of potentially informative characters relative to ndhF for the taxa surveyed. The utility of the Adc gene in plant molecular systematic studies is demonstrated by analysis of its partial nucleotide sequences obtained from 13 representatives of Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order Capparales) and 1 from the related order Malvales. Two copies of the Adc gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied to data except the basal genus Aethionema. The resulting Adc gene tree provides robust phylogenetic data regarding relationships within the complex mustard family, as well as independent support for proposed tribal realignments based on other molecular data sets such as those from chloroplast DNA.

Arabidopsis↗