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R R Williams

Publications and source records attributed to R R Williams.

At least 199 records · Page 11Linked to original sources

The role of genetic analyses in characterizing obesity.

To understand how genetic and environmental factors could interact to lead to different types of obesity, a simple hypothetical model is examined involving two genes and one environmental factor. Separate and interactive effects are illustrated. The confounded expression of distant phenotypes and advantages of studying phenotypes close to immediate gene products are explained. The appearance of population frequency distribution curves for level of obesity are illustrated for five different situations simulating actual data behaving according to the hypothetical model. Six suggestions are given as a practical approach to characterizing morbid obesity: (1) describe the frequency distribution of morbid obesity by age and sex in the general population; (2) obtain accurate family history data from obese probands, spouses, and controls; (3) contrast results of metabolic studies between obese probands with and without a family history of obesity; (4) obtain metabolic screening data from close relatives of selected obese probands and controls; (5) study special settings (twins, adoption, migration, race); (6) when justified, perform extensive pedigree studies using metabolic evaluations, linkage markers, and carefully prepared computer model testing. Careful collection of family history data is explained in detail and is proposed as an important and relatively inexpensive tool that should be part of any study of human obesity.

Energy Intake↗

Understanding genetic and environmental risk factors in susceptible persons.

Most major chronic diseases probably result from environmental factors accumulating over time in genetically susceptible persons. A detailed family history assessment can help identify the subset of the general population with a strong predisposition to certain major diseases. An understanding of the environmental factors promoting disease development will facilitate more effective prevention or delay disease in a targeted susceptible population. To effectively use this growing knowledge in genetics and epidemiology, health professionals need to motivate people to follow sound recommendations for preventing and delaying disease.To increase the efficiency and effectiveness of strategies for health promotion and disease prevention, family history data can help determine those diseases for which persons have the greatest risk. They can then concentrate their primary efforts on those preventive measures that will most likely benefit them.

Chronic Disease↗

Lack of association of diagonal earlobe crease with other cardiovascular risk factors.

The relationship between diagonal earlobe crease and coronary risk factors, controlling for age and sex effects, was tested in 686 persons. A positive correlation (rho=.86, P<.001) is obtained between age and percentage of persons with earlobe creases in each one-year age interval; no sex difference is seen. To test for associations between cardiovascular risk factors and earlobe creases, 67 persons with creases are compared with 67 controls (matched by age and sex) without creases, using the following variables: diastolic and systolic blood pressures, cigarette smoking, weight, height, scapular skinfold thickness, serum cholesterol level, high-density lipoprotein level, intracellular sodium, sodium-lithium countertransport, plasma renin level and the presence of diabetes and hypertension. None of these variables differs significantly between cases and controls, indicating that the previously documented association between earlobe crease and coronary heart disease may be independent of these risk factors. Although coronary heart disease has often been shown to aggregate in families, no familial aggregation is found for earlobe creases.

Adolescent↗

Structural analysis of the C-terminal region of chicken gizzard desmin.

The C-terminal sequence of chicken gizzard desmin has been examined by computer programs based on Chou-Fasman prediction of secondary structure, auto-correlation and Fourier analysis of hydrophobic residue distribution, and cross-correlation analysis of acidic and basic residues. These analyses indicate that, although parts of the desmin sequence are alpha-helical, the helical regions may not be as extensive as predicted previously. Detailed analysis of the distribution of the charged residues in the desmin sequence strongly suggests that it cannot form a tropomyosin-like coiled-coil double-helix because of the almost complete absence of stabilizing salt-bridge interactions between proximal pairs of acidic and basic residues. Although the desmin sequence does contain the tropomyosin-like hydrophobic residue distribution, differences exist in the overall distributions of hydrophobes, with clusters of these residues being found in certain regions of the desmin sequence. Analyses of the sequences of porcine desmin and vimentin reveal very similar structural characteristics for these molecules, although vimentin is predicted to have a different structure at its C-terminus.

Amino Acid Sequence↗

High-performance liquid chromatography of staphylococcal enterotoxin B.

Size-exclusion, ion-exchange, and reversed-phase chromatography were investigated for use in purification and characterization of Staphylococcal enterotoxin B (SEB), a 28,000 Mr protein associated with Staphylococcal food-borne intoxication. In all approaches chromatography of crude or purified SEB yielded one or more components which displayed toxin activity and contained the 28,000 Mr SEB protein plus other lower-molecular-weight protein species. Reversed-phase chromatography of detergent-treated SEB permitted resolution of the 28,000 Mr protein from lower-molecular-weight components.

Bacterial Proteins↗

The genetics of quantitative plasma Lp(a): analysis of a large pedigree.

Likelihood analysis using the mixed model of quantitative plasma Lp(a) measurements on members of a large pedigree provided evidence that high levels of Lp(a) are inherited as a dominant major gene with polygenic background. The dominant allele frequency was estimated as 0.10. The major gene and polygenic components together accounted for 95% of the variation seen in the measurements. The major gene index and OBP plots, methods that do not allow for the presence of both components, favored the polygenic model over the major gene model as the mode of inheritance. No association was found with any of the lipids, lipoproteins or apolipoproteins considered.

Female↗

Sodium-lithium countertransport in erythrocytes of hypertension prone families in Utah.

Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.

Adolescent↗

The effect of diet on ouabain binding to erythrocytes from obese subjects.

Ouabain binding to erythrocyte membranes is increased in obese subjects. Three study groups are compared: 14 reference subjects, 102 +/- 16% of ideal weight; 9 obese on unrestricted diets, 207 +/- 16% of ideal weight; 11 obese on restricted diets, 202 +/- 35% of ideal weight. A reproducible (CV = 11.3%) ouabain-binding assay is used to measure Na+-K+ ATPase sites in erythrocyte membranes. The number of binding sites per red blood cell for obese subjects on unrestricted diets, 431 +/- 30, is greater than for the reference group, 346 +/- 66 (p less than 0.01), or for obese subjects on restricted diets, 371 +/- 68 (p less than 0.05). These data suggest that caloric intake influences the number of Na+-K+ ATPase sites. Scatchard plots indicate only one type of binding site for ouabain with an affinity constant of about 3 X 10(8) M-1.

Adolescent↗

A reproducible sodium-lithium countertransport assay: the outcome of changing key laboratory parameters.

This paper describes experimental conditions for reproducible measurement of sodium-lithium countertransport in red blood cells. The assay is sensitive to temperature (10% per degree C) and the condition of the red cells; it is affected little by changes in intracellular lithium over the range 2-7 mmol/1 or by red cell concentrations with laboratory hematocrits of 0.03 to 0.07. Repeated measurements of the same subjects give day-to-day coefficients of variation of 10% or less. The mean difference for interlaboratory comparisons is 11%.

Biological Transport↗

A kinetic expression for sodium-lithium countertransport in human red cells.

Sodium-lithium counter-transport in human red blood cells may be a potentially useful measurement in studies of hypertension. A kinetic expression describing this counter-transport was derived and evaluated using red cells from nine subjects at various concentrations of intracellular and extracellular Li+ and Na+. The countertransport is dependent upon all four concentrations, intracellular Li+ and Na+ as well as extracellular Li+ and Na+. We confirm that the maximum Na+-Li+ counter-transport (Vmax) is a property of the individual cells while the half-maximal saturating concentrations (K 1/2) for Li+ and Na+ are the same for all subjects. This expression permits a more thorough understanding of conditions affecting Na+-Li+ countertransport measurement.

Biological Transport↗

Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat.

Complete neonatal thymectomy reduced the frequency of spontaneous diabetes mellitus in BioBreeding/Worcester rats from 27 to 3 percent. Incomplete thymectomy also significantly reduced the frequency of diabetes (to 9 percent). These findings strengthen the hypothesis that thymus-dependent, cell-mediated autoimmune destruction of pancreatic B cells is responsible for the pathogenesis of diabetes in this experimental animal.

Animals↗

Contrasting patterns of familiality for cholesterol and triglyceride in Finland according to type of coronary manifestations and locations.

A descriptive genetic analysis (offspring between parent plot) was applied to serum cholesterol and triglyceride levels of 1044 Finnish subjects who were parents, siblings, spouses, and offspring of 204 male probands with angina pectoris or nonfatal myocardial infarction before age 55 years. The same analysis was also applied to 511 relatives of 106 control men matched to the probands for age and location (northeastern Finland or southern Finland). Striking differences in the plot results for triglyceride data suggest that male probands with angina pectoris as first evidence of coronary disease had different familial characteristics than those with nonfatal myocardial infarction at the onset. Further plot contrasts suggest stronger major gene effects for cholesterol and triglyceride levels in northeastern Finland, both in case and control families. Genetic makeup may help explain why men in northeastern Finland have the world's highest rate of early coronary heart disease.

Adult↗

Toxicity of aflatoxin B1 to penaeid shrimp.

Single intramuscular injections of aflatoxin B1 into the tail muscle of Penaeus stylirostris produced 24- and 96-h median lethal doses of 100.5 (78.3 to 129.0) and 49.5 (29.8 to 82.3) mg/kg, respectively. A toxicity curve showed no threshold at the levels tested. The mortality response in a feeding study with P. vannamei was not dose dependent, but tissue and organ damage were similar to that seen in injected animals.

Administration, Oral↗

Quantitative estimates of beta-lactam residues in raw milk around a reference standard: collaborative study.

A collaborative study was conducted to determine the reliability of a Bacillus stearothermophilus disc assay method for differentiating various concentrations of penicillin in raw milk. Participating laboratories tested 10 different samples (including one negative) in blind duplicate. Triplicate standards were alternated with triplicate unknowns around the periphery of each of 5 different plates. Zone diameters were measured and the difference in zone size of pairs of adjacent standard and unknown samples were analyzed by a paired t-test. Penicillin concentrations 0.003 IU/mL different from the reference concentrations were consistently distinguishable at a 95% confidence level. Such discriminatory power was determined to be possible with as few as 3 plates (9 replicates) per unknown. The method has been adopted official first action.

Animals↗