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Biomedical subjects

R A Price

Publications and source records attributed to R A Price.

At least 91 records · Page 5Linked to original sources
PubMed1989

Genetics of obesity in adult adoptees and their biological siblings.

An adoption study of genetic effects on obesity in adulthood was carried out in which adoptees separated from their natural parents very early in life were compared with their biological full and half siblings reared by their natural parents. The adoptees represented four groups who by sampling from a larger population were categorised as either thin, medium weight, overweight, or obese. Weight and height were obtained for 115 full siblings of 57 adoptees and for 850 half siblings of 341 adoptees. In full siblings body mass index (kg/m2) significantly increased with weight of the adoptees. Body mass index of the half siblings showed a steady but weaker increase across the four weight groups of adoptees. There were no significant interactions with sex of the adoptees, sex of the siblings, or (for the half siblings) sex of the common parent. In contrast with the findings in half siblings and (previously) the natural parents there was a striking, significant increase in body mass index between full siblings of overweight and obese adoptees. The degree of fatness in adults living in the same environment appears to be influenced by genetic factors independent of sex, which may include polygenic as well as major gene effects on obesity.

Adoption↗
PubMed1989

Affective disorder not linked to HLA.

These analyses focused on the relationship of affective disorders to HLA. The sample of 86 previously unpublished families from Ontario and 10 unpublished pedigrees from Newfoundland, as well as the original Weitkamp et al. [1981] sample of 20 families, the samples provided by NIMH [Goldin et al., 1982] (18 families), and Egeland et al. [1987] (2 large pedigrees), were examined using sib pair methods as well as standard linkage analysis of the full pedigrees. A variety of genetic models were examined. There was no evidence for linkage from any of the samples based on either analytic approach or for any genetic model. Groups of sibling pairs concordant for affective illness, concordant for being well, or discordant for affective illness did not differ in the proportion of genes identical by descent. No group differed significantly from 50%. From the analysis of full pedigrees, linkage to HLA could be excluded to a distance of approximately 20 to 25 centimorgans. There was no evidence for linkage heterogeneity. These results argue against linkage of affective disorder to HLA.

Affective Disorders, Psychotic↗
PubMed1989

Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT).

Thiol S-methylation is an important pathway in the metabolism of many sulfhydryl compounds including the antihypertensive drug captopril and the antirheumatic medication D-penicillamine. Erythrocyte (RBC) thiol methyltransferase (TMT) activity was measured in blood samples from 237 individuals from 49 nuclear families. Earlier studies have demonstrated familial aggregation of RBC TMT activity, suggesting a role for genetic determinants. Our study indicates the specific mode of inheritance and gives relative contributions of a major locus and background genotype. We found evidence for a major locus, TMT. The allele frequencies for low enzyme activity, TMTL, and high activity TMTH, estimated from a power transformed scale were 0.58 and 0.42, respectively. The high activity allele, TMTH, appears to have reduced expression in heterozygous individuals (d = 0.21) and to act in concert with a strong influence from polygenic genotype (H = 0.75) to produce a highly heritable phenotype. This major gene polymorphism may now be studied using biochemical and molecular genetic techniques.

Adolescent↗
PubMed1989

Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity.

Platelet TS PST basal activity and thermal stability were measured in blood samples from 237 individuals in 50 nuclear families. Significant correlations were found among first degree relatives, confirming the previously reported familial aggregation of TS PST basal activity and thermal stability. Commingling analysis of basal TS PST activity provided evidence for multiple component distributions, and after transformation to remove skewness, segregation analysis supported a major gene hypothesis. For TS PST thermal stability, commingling analysis also provided evidence for multiple component distributions. However, segregation analyses were equivocal with regard to the presence of a major gene for thermal stability, since support for a major gene model depended on skewness. Bivariate commingling analysis, which examined thermal stability by simultaneously considering basal activity and activity after heating, suggested that genotypes, as defined by the inferred component distributions for TS PST activity, differ in thermal stability. A three-allele model is proposed as one hypothesis that may account for the combined results of basal activity and thermal stability. The results of this study indicate that a major gene polymorphism in conjunction with polygenic inheritance plays an important role in the regulation of both level of activity and thermal stability of this important drug-metabolizing enzyme in humans.

Adolescent↗
PubMed1989

Component distributions of body mass index defining moderate and extreme overweight in Danish women and men.

Skewness in the distribution of body mass index in a population of Danish men (n = 1,589) and women (n = 1,988) adopted in Copenhagen between 1923 and 1947 can be explained by mixture of three component distributions, after removing age and sex effects. Even when residual skewness was allowed for in component distributions, similar results were obtained. The upper component distributions corresponded to extreme overweight in both women and men. The results indicate that while there are differences in the means and ranges of body mass index in men and women, the component distributions are similar. Both genetic and environmental factors can produce such component distributions. The authors speculate that the underlying predisposition to obesity is distributed similarly in women and men. Finally, on the basis of the component distributions, the authors propose thresholds of body mass index which allow for 85-98 per cent separation of moderate and extreme overweight groups in men and women.

Adult↗
PubMed1989

Commingling analysis of obesity in twins.

Evidence is presented for multiple components in the distribution of human fatness across several large twin samples, after removing age effects and allowing for residual skewness in component distributions. The upper component distributions corresponded to overweight or obesity in samples of middle-aged or older individuals. A bivariate analysis demonstrated that, while monozygotic co-twins appeared to be drawn from the same component distributions (normal or overweight), the twin correlations varied across components, with the lowest correlation in the overweight group. While these analyses cannot provide a definitive test of competing genetic and environmental hypotheses, this approach is useful for generating hypotheses about the causes of obesity. When combined with other published literature, our results suggest that the genetic background largely determines the propensity to become obese. Whether a predisposed person becomes obese and the extent of obesity depend on environmental exposures that are largely independent of early family experience. Both genes and environment appear to be important in obesity, but it appears that some genotypes may be much more sensitive to the environment than are others.

Body Composition↗
PubMed1989

HLA associations with obesity.

A subgroup of 351 subjects with human leukocyte antigen (HLA) typing were available from the Framingham Heart Study for analyses to identify associations with obesity. The subjects consisted of 143 males and 208 females aged 58-88 years at the 15th biennial examination in 1978. The obese classification was based on maximum body mass index (BMI) over the 16 available biennial examinations of the Framingham Heart Study. The subjects were classified as obese if they exceeded the 95th percentile of BMI for 20- to 29-year-old subjects as described in the NHANES II study; males were obese if BMI greater than 31.1 and females were obese if BMI greater than 32.3. There were 27 obese males (18.9%) and 44 obese females (21.2%) in the sample. Gene frequencies were compared between the nonobese and obese groups for the pooled sample as well as by sex. Among alleles previously shown to be related to obesity, HLA Bw35 appeared to be more frequent in obese females but these data did not confirm a difference for the B18 or Cw4 alleles. More importantly, HLA Aw30 was found to be significantly higher among the obese subjects in both males and females. Further analyses adjusting for potential confounding variables reduced the estimated relative risk for obesity for subjects with the Bw35 allele to approximately 1.30 and no longer significant for this sample size. In contrast, the relative risk for Aw30, while reduced, remained significant after adjustment for confounding variables. Based on these data, individuals with the Aw30 allele have a relative risk of 2.61 for obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Congenital myopathy with progressive external ophthalmoplegia.

Progressive external ophthalmoplegia is associated with an increasingly heterogeneous group of neuromuscular disorders. We describe a 16-year-old girl with delayed motor milestones and onset of progressive external ophthalmoplegia at age 3 years and proximal muscle weakness at age 10 years. Muscle biopsy specimen demonstrated type I myofiber predominance and type II myofiber atrophy. Although the pathological features of this congenital myopathy are quite nonspecific, the case further illustrates the pathogenetic heterogeneity of the progressive external ophthalmoplegia phenotype.

Adolescent↗
PubMed1989

Estimation of segregation and linkage parameters in simulated data. I. Segregation analyses with different ascertainment schemes.

We report the results of a simulation study designed to assess the capability of segregation analysis to detect Mendelian transmission and to estimate genetic model parameters for complex qualitative traits, characterized by heritability in the range 0.20-0.45 and low heterozygote penetrance. The pedigree analysis package, PAP, was used to perform the analyses. For all data sets, models of no transmission could be rejected. In most cases, models of Mendelian transmission could not be rejected; however, several samples approached significance levels. When Mendelian transmission was assumed, reasonably good parameter estimates were obtained, although heterozygote penetrances were often overestimated. Different sampling schemes were imposed on the simulated data in order to examine the extent of information loss with the reduction in sample size. One of these strategies (a sequential sampling scheme) appears to have resulted in critical loss of information in some cases.

Alleles↗
PubMed1989

Estimation of segregation and linkage parameters in simulated data. II. Simultaneous estimation with one linked marker.

This study examined the method of simultaneous estimation of recombination frequency and parameters for a qualitative trait locus and compared the results with those of standard methods of linkage analysis. With both approaches we were able to detect linkage of an incompletely penetrant qualitative trait to highly polymorphic markers with recombination frequencies in the range of .00-.05. Our results suggest that detecting linkage at larger recombination frequencies may require larger data sets or large high-density families. When applied to all families without regard to informativeness of the family structure for linkage, analyses of simulated data could detect no advantage of simultaneous estimation over more traditional and much less time-consuming methods, either in detecting linkage, estimating frequency, refining estimates of parameters for the qualitative trait locus, or avoiding false evidence for linkage. However, the method of sampling affected results.

Alleles↗
PubMed1988

Inheritance of human platelet thermolabile phenol sulfotransferase (TL PST) activity.

Sulfate conjugation is an important pathway in the biotransformation of drugs and neurotransmitters. The thermolabile (TL) form of the enzyme phenol sulfotransferase (PST) catalyzes the sulfation of catecholamine neurotransmitters and drugs such as methyldopa and acetaminophen. Platelet TL PST activity was measured in blood samples from 232 individuals in 49 nuclear families. Correlations ranged from 0.43 to 0.45 for parent-offspring pairs and from 0.44 to 0.47 for siblings. Mother-father correlations were not significantly different from zero. Although evidence was not unequivocal, both segregation and commingling analyses provided some support for a major gene influence on TL PST activity, with other variation due to polygenic background. In both sets of analyses, however, support for a major gene hypothesis depended upon skewness in the TL PST activity distribution. A polygenic model with high heritability (0.77) was most strongly supported with the log transformed data. These results confirm and extend a previous report of high heritability of TL PST based on a study of twins. In addition, our results raise the possibility of a major gene effect on this important catecholamine- and drug-metabolizing enzyme--a possibility that can now be evaluated using biochemical techniques.

Adolescent↗
PubMed1988

Family data support a dominant major gene for Tourette syndrome.

A dominant major gene was supported by analyses of 50 large extended Tourette syndrome (TS) pedigrees and by a subset of families defined by proband's clinical response to the neuroleptic drug haloperidol. Relatives were defined as affected if they ever had tics or TS. Assuming a nearly even sex ratio for TS and related symptoms resulted in the best fit of the genetic model to observed rates in families.

Chromosome Mapping↗
PubMed1987

Early onset (under age 30 years) and panic disorder as markers for etiologic homogeneity in major depression.

Early onset of major depression (age, less than 30 years) in probands confers high risk to relatives, whereas late-onset depression (age, greater than 40 years) involves no elevation of risk over population rates. Analyses of data from families of probands with early onset from the Yale Family Study (47 three generation and 17 two generation) favored a major gene effect over polygenic inheritance. However, no genetic model was supported unambiguously. The increase in prevalence of depression over the past several decades complicates the genetic interpretation of results. Restriction of analyses to older (age, greater than 18 years) age cohorts appeared to simplify the pattern of transmission, but a consequent reduction of sample size provided only limited power for tests of competing genetic hypotheses. In a subgroup of 28 families in which the proband had both depression and panic disorder, a major gene mode of inheritance was not supported.

Adolescent↗
PubMed1987

Diagnosis and treatment of intrapericardial teratoma.

Intrapericardial teratoma is a rare mediastinal tumor that originates from aberrant clusters of multipotential cells from three germinal layers. Previous reports have used the combination of cardiac angiography, CT scan, and echocardiogram to establish the diagnosis prior to surgery. We report a case of intrapericardial teratoma diagnosed noninvasively and removed surgically within the first three days of life. Furthermore, we compare the diagnostic accuracy of echocardiography and computerized tomography (CT), and discuss the superiority of noninvasive evaluation in the management of these critically ill infants.

Echocardiography↗
PubMed1987

The first component of complement as a constituent of human salivary sediment.

The sediment from human saliva is complement-reactive. Evidence presented shows that C1 (first component of complement) is a constituent of sediment from healthy human donors. Sediment (Sed) inactivated functionally pure C4 (fourth component of complement), and this action on C4 was inhibited by EDTA, phenylmethylsulphonylfluoride (PMSF, a serine-esterase inhibitor) and C1-inhibitor (C1-In). When Sed was incubated with 0.15 ionic strength buffer and separated by centrifugation, C1 haemolytic activity was found in the supernatant. By incubating Sed with EAC4 cells (sheep erythrocytes sensitized with rabbit antibody to which C4 has been fixed), transfer was shown of C1 from the Sed to the cells, resulting in the formation of EAC14; this transfer was inhibited by IgG directed against a subunit of C1 (anti-C1s).

Adult↗