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C F Sing

Publications and source records attributed to C F Sing.

154 records · Page 9Linked to original sources
PubMed1968

Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a Negro family.

Detailed clinical and genetic studies have been performed in a Negro family, which segregated for sex-linked sideroblastic anemia and glucose-6-phosphate dehydrogenase (G-6-DP) deficiency. This is the first such pedigree reported. Males affected with sideroblastic anemia had growth retardation, hypochromic microcytic anemia, elevated serum iron, decreased unsaturated iron-binding capacity, increased (59)Fe clearance, low (59)Fe incorporation into erythrocytes, normal erythrocyte survival ((51)Cr), normal hemoglobin electrophoretic pattern, erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts, particularly ringed sideroblasts. Perinuclear deposition of ferric aggregates was demonstrated to be intramitochondrial by electron microscopy. Female carriers of the sideroblastic gene were normal but exhibited a dimorphic population of erythrocytes including normocytic and microcytic cells. The bone marrow studies in the female (mother) showed ringed marrow sideroblasts. Studies of G-6-PD involved the methemoglobin elution test for G-6-PD activity of individual erythrocytes, quantitative G-6-PD assay, and electrophoresis. In the pedigree, linkage information was obtained from a doubly heterozygous woman, four of her sons, and five of her daughters. Three sons were doubly affected, and one was normal. One daughter appeared to be a recombinant. The genes appeared to be linked in the coupling phase in the mother. The maximum likelihood estimate of the recombination value was 0.14. By means of Price-Jones curves, the microcytic red cells in peripheral blood were quantitated in female carriers. The sideroblast count in the bone marrow in the mother corresponded closely to the percentage of microcytic cells in peripheral blood. This is the second example in which the cellular expression of a sex-linked trait has been documented in the human red cells, the first one being G-6-PD deficiency. The coexistence of the two genes in doubly heterozygous females has made it possible to study correlations in cell counts; our studies showed a strong positive correlation except in the probable recombinant in which a reciprocal relation held which indicated that X-inactivation was at least regional, rather than locus by locus.

Anemia, Hypochromic↗
PubMedDate not supplied

Analysis of systems influencing renal hemodynamics and sodium excretion. I. Biochemical systems theory.

In this article we present a new methodology--Biochemical Systems Theory and Analysis--as an alternative to traditional parametric statistical procedures for investigating differences between risk groups in a population. We review the systems theory and how it can be used to represent a model of processes influencing renal hemodynamics and sodium (Na+) excretion. We also discuss the potential for new measures of the biology of common diseases that can emerge from a synergism between systems theory and population-based statistical approaches.

Blood Pressure↗
PubMedDate not supplied

Failure to detect association of isolated cleft palate with HLA antigens.

HLA antigen frequencies have been determined in 282 controls and in 33 individuals with isolated cleft palate or the related birth defect velopharyngeal incompetence. No association of particular HLA antigens with this birth defect was found. A previously reported association of HLA A2 with cleft palate, in males, was not confirmed.

Cleft Palate↗
PubMedDate not supplied

Influences of common variants of apolipoprotein E on measures of lipid metabolism in a sample selected for health.

Five-hundred seventy-five white-collar workers (374 men; 99% Caucasians) aged 20-59 years were selected on the basis of their being healthy and clinically free from cardiovascular risk factors (except smoking and family history). We have observed a higher relative frequency of the epsilon 3 allele in this population, as is true of populations with a low prevalence of coronary heart disease. Each of the 11 plasma lipid and lipoprotein traits studied was adjusted for age, weight, height, body mass index, plasma glucose, and uric acid in men and women separately. The influence of each of the three common apo E alleles on each adjusted trait was evaluated by use of the average excess statistic. We established that in a population selected for health, the epsilon 2 allele is associated with lower plasma levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B associated with LDL cholesterol in both men and women. Conversely, the epsilon 4 allele is associated with higher levels of these traits in women only. In contrast to the findings in populations not selected for health, the presence of the epsilon 2 allele in our subjects tended to be associated with lower and the epsilon 4 allele with higher plasma triglyceride levels. Finally and of particular note, the influence of the apolipoprotein E polymorphism on plasma measures of LDL metabolism is different in men and women. Specifically, the influence of the epsilon 4 allele is of greater magnitude in women. A part of this gender difference in allele effects on LDL metabolism in women is associated with the use of oral contraceptives and postmenopausal hormone replacement therapy.

Adult↗
PubMedDate not supplied

Effects of polymorphisms in apolipoproteins E, A-IV, and H on quantitative traits related to risk for cardiovascular disease.

The impact of the common alleles at structural loci coding for apolipoprotein (apos) A-IV, E, and H on 12 quantitative risk factors for cardiovascular disease (apos A-I, A-II, B, C-II, C-III, and E; total cholesterol; triglycerides; high density lipoprotein cholesterol; systolic blood pressure; diastolic blood pressure; and red blood cell sodium-lithium countertransport) was estimated in 453 unrelated individuals (227 men and 226 women) aged 26-63 years from the Rochester Family Heart Study, who were not using medications affecting lipid levels or blood pressure. Each risk factor was adjusted for concomitants (assay date, age, age, squared, height, weight and smoking status) before the genotypic effects on mean levels and variances were estimated. Allele frequencies were the same in men and women and were similar to those observed in other studies of US Caucasians. There were very different gender-specific estimates of the relative contribution of concomitants, measured genetic effects, and residual unexplained effects to the interindividual variation of particular traits. Allelic variation in apo E had effects on the greatest number of traits, namely apo E, apo B, apo C-II, and total cholesterol. An effect on triglycerides was dependent on the inclusion of hypertriglyceridemic subjects. Allelic effects of apo A-IV and apo H were much less than those estimated for the apo E polymorphism. A possible role for apo H in high density lipoprotein metabolism is suggested. This study indicates that variation in many genes may influence variation in a particular trait and that a particular gene may have pleiotropic effects on several traits.

Adult↗
PubMedDate not supplied

Interaction of two lipid disorders in a large French-Canadian kindred.

This study investigates the pedigree of 508 individuals over five generations identified by an individual with hypertriglyceridemia, familial hypercholesterolemia, and a IIb lipoprotein electrophoretic phenotype. The sample of 378 living individuals studied extensively for risk factors and disease status was distributed among maternal (170) and paternal (176) relatives and the codescendants (32) of the index case. It was found that the distributions of the plasma lipid and lipoprotein abnormalities in the different subsets of the kindred were consistent with the presence of two separate hereditary lipid disorders: familial hypercholesterolemia on the paternal side and familial hyperprebetalipoproteinemia on the maternal side. This combination of disorders with a possible contribution from factors influencing glucose metabolism was associated with high frequency of hypercholesterolemia and its clinical manifestations and of cardiovascular morbidity among the codescendants. An interaction effect is suggested as an explanation for the unusually high prevalence of hyperlipidemia among the codescendants and for the presence of a IIb phenotype in the index case.

Canada↗
PubMedDate not supplied

Apolipoprotein E polymorphism and atherosclerosis.

The apo E locus contributes to determining the variation in plasma cholesterol levels of healthy and diseased populations. It also influences the expression of hyperlipidemia and appears to modulate the susceptibility to atherosclerosis in a complex multifactorial interaction. There is evidence that the presence of apo E2 is protective, whereas that of apo E4 predisposes to coronary artery disease. The burden of proof, however, lies on future, well-designed clinical trials and prospective studies. The study of the biological significance of the apo E polymorphism in humans has emphasized the importance of gene-gene and gene-environment interactions in the pathogenesis of hyperlipidemia and atherosclerosis. The apo E polymorphism involves the coding region of the apo E gene and results in alterations of the gene product which, in turn, either directly or secondarily affect the metabolic fate of the lipoprotein particles. Rapid advances in knowledge over the last decade have provided a metabolic explanation for the observation of the opposite effects of the epsilon 4 and the epsilon 2 alleles on lipoprotein levels. Apo E2 has lower receptor binding affinity which results in delayed clearance of apo E2-bearing lipoprotein particles from plasma. Apo E4 is distributed differently from apo E3 between VLDL and HDL, is degraded more rapidly than apo E3, and may enhance the catabolism of E4-bearing particles, leading to other alterations in lipoprotein metabolism which result in elevated levels of LDL. In view of the significant opposite impacts of the epsilon 4 and the epsilon 2 alleles on plasma LDL cholesterol concentrations, it is evident that determination of the apo E phenotype will become a useful adjunct to the assessment of the cardiovascular risk profile of an individual. In addition, the relationship between the epsilon 2 allele and type III hyperlipoproteinemia provides a valuable model for the study of complex genetic interactions in the pathogenesis of hyperlipidemia. The further study of apo E and its interactions shows great promise for a deeper comprehension of the pathogenesis of atherosclerosis.

Alleles↗
PubMedDate not supplied

Sodium-lithium countertransport and blood pressure in healthy blood donors.

Studies finding an increased maximal rate of Na-Li countertransport in red blood cells from persons with essential hypertension and their normotensive offspring have raised the possibility that Na-Li countertransport may serve as a marker for the genetic predisposition to hypertension. We studied Na-Li countertransport in 238 randomly selected blood donors representative of the population of Rochester, Minnesota. The mean value (+/- SD) for Na-Li countertransport in units of mmoles of lithium efflux per liter of red blood cells per hour was 0.29 +/- 0.12. The distribution of Na-Li countertransport values among the donors was continuous. An analysis for multimodality, however, detected significant evidence of bimodality with 72% of the population predicted to belong to the lower mode with a mean of 0.24 mmol/L red blood cells per hour and 28% of the population to belong to the upper mode with a mean of 0.42 mmol/L red blood cells per hour. There was a positive association between Na-Li countertransport and blood pressure; after adjustment for weight and age, Na-Li countertransport predicted approximately 3% of the variation in blood pressure. Persons belonging to the upper mode of the Na-Li countertransport distribution may be at increased risk of acquiring elevated blood pressure as they age.

Adult↗
PubMedDate not supplied

Cerebral infarction after middle cerebral artery occlusion in progenies of spontaneously stroke-prone and normal rats.

A differential outcome results from rapid middle cerebral artery (MCA) occlusion in young normotensive Wistar (NW) rats as compared to the spontaneously hypertensive stroke-prone (SHRSP) rat. The SHRSP invariably infarcts; the NW usually does not. To determine if segregation at a single autosomal locus explains the difference between strains, a NW male was crossed with several SHRSP females to produce F1 rats. The segregation of the strain difference was studied in the F2 and backcrosses to the NW and SHRSP parental strains. The relative frequency of infarcting and noninfarcting animals in the segregating progenies supported a single locus recessive model of inheritance for susceptibility to infarction after sudden occlusion of the MCA. Mean infarct size was largest for SHRSP and proportional to the SHRSP gene dosage in the segregating progenies. Variation in the size of the infarct within segregating classes may be attributable to the segregation of polygenes and/or environmental influences during the initial formation of the cerebral anastomoses.

Animals↗