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Biomedical subjects

S Whitehouse

Publications and source records attributed to S Whitehouse.

13 recordsLinked to original sources
PubMed1979

Possibility of shape conformers of the protein inhibitor of the cyclic adenosine monophosphate dependent protein kinase.

The heat-stable, protein inhibitor of the cyclic adenosine monophosphate (cAMP) dependent protein kinase [Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E., & Krebs, E (1971a) J. Biol. Chem. 246, 1977-1985] has been purified to homogeneity from rabbit skeletal muscle by preparative electrophoresis. Employing a more sensitive assay system, we detected multiple charged forms of the inhibitor on diethylaminoethyl chromatography; the form that has been further characterized is the predominant species in skeletal muscle comprising greater than 70% of the total. The apparent molecular weight of the protein inhibitor, as determined by Sephadex G-75 gel exclusion chromatography, is 22 000 in initial cellular extracts and at all stages during the purification prior to the final purification step of preparative gel electrophoresis, after which the homogeneous protein exhibits a molecular weight of 11 000. These two forms are designated I and I', respectively. The I form migrates with an apparent molecular weight of 10 000 on nondenaturing gel electrophoresis and of 10 500-11 500 on sodium dodecyl sulfate (NaDodSO4) gel electrophoresis; the I' form migrates with an apparent molecular weight of 6500-8300 on NaDodSO4 electrophoresis and has a minimum molecular weight of 10 400 by amino acid analysis. Taking into account the anomalous behavior displayed by low molecular weight proteins with the various techniques employed, we suggest that the I and I' forms of the protein inhibitor may represent shape conformers.

Amino Acids↗
PubMed1979

Genetic susceptibility to diabetes mellitus: the distribution of properdin factor B (Bf) and glyoxalase (GLO) phenotypes.

The distribution of phenotypes controlled by two loci on chromosome 6 has been studied in a series of 239 patients with type 1 (insulin-dependent) and 297 patients with type 2 (non-insulin-dependent) diabetes mellitus. At the properdin factor B (Bf) locus there is a significant increase in the frequency of the BfSu and BfF1 alleles for type 1 patients, and the combined inc;rease in frequency of BfS1 and BfF1 in those patients is highly significant. The relative risk for F1 is 6.2 and for F1 and S1 combined is 5.3. These results confirm the association with F1 reported recently by Raum and co-workers in Boston. The two rare alleles BfS1 and BfF1 are in significant negative disequilibrium with HLA B8. For the glyoxalase (GLO) locus there is a slight but nonsignificant increase in the frequency of the GLO2 allele, but a significant disturbance in the distribution of the GLO phenotypes for type 2 patients. These results for the GLO alleles may be due to stratification in our series of type 2 patients. Further studies are in progress to test this hypothesis.

Alleles↗
PubMed1979

Ethnic variability in the plasma insulin response to oral glucose in Polynesian and Micronesian subjects.

The pattern of insulin response to oral glucose over a wide range of glucose tolerance has been studied in two separate ethnic groups--Polynesians and Micronesians. Fasting insulin concentrations were relatively unchanged over the entire range of glucose tolerance in both populations, irrespective of whether comparable lean or obese samples of both groups were studied. The patterns of 2-h plasma insulins were similar over the whole range of glucose tolerance in Polynesians and Micronesians. However, in the comparisons of all subjects, or lean or obese groups of these populations, the plasma insulin concentrations of the Micronesians were both consistently and significantly higher. As the data analysis was arranged to take into account groups with identical 2-h plasma glucose concentrations and comparable degrees of obesity, the differences cannot be attributed to differences in the glucose levels or in obesity. In the presence of similar fasting insulin concentrations, these findings imply an ethnic variability in the pancreatic beta-cell response to oral glucose.

Adolescent↗
PubMed1978

High prevalence of hyperuricaemia and gout in an urbanised Micronesian population.

The prevalence of hyperuricaemia and gout was investigated in the Micronesian inhabitants of the highly urbanised central Pacific island of Nauru. Sixty-four per cent of men and 60% of women aged 20 years and over had hyperuricaemia--the highest prevalence rates yet reported for a population. The hyperuricaemia in men was accompanied by a high prevalence of clinical gout (6.9%). While the hyperuricaemia is probably genetic, the high prevalence of gout may be related to the environmental change from the traditional island style of living to one of almost complete Westernisation.

Adult↗
PubMed1978

Bimodality of fasting and two-hour glucose tolerance distributions in a Micronesian population.

While frequency distributions of glucose concentrations in Caucasian populations are unimodal, bimodality has been described in the Pima Indians, a population with an extremely high prevalence of diabetes. Venous plasma glucose concentrations at fasting and after a 75-gm. oral glucose load were determined in 596 Nauruans, a Micronesian population with a diabetes prevalence of the same order as the Pima Indians. In both sexes and in subjects 10 to 19 years, the frequency distributions of the logarithms of the fasting and two-hour glucose values were clearly unimodal. In most sex and age groups of 20 years and older, the frequency distributions of fasting and two-hour glucose values were bimodal and consistent with a model of two overlapping Gaussian distributions. This population is characterized by marked obesity. However, there was no significant difference in the degree of obesity between subjects in the first and second curves of the bimodal distribution. This makes it unlikely that the bimodality is a consequence of the marked obesity seen in both the Pima and Nauru populations. The data show that among Nauruans, as with the Pimas, the frequency distribution of glucose concentrations can be used to separate the population into normal and hyperglycemic groups.

Adolescent↗
PubMed1978

The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

Animals↗
PubMed1976

Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide.

The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mM) or dichloroacetate (1mM) increased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart, presumably by inhibiting the pyruvate dehydrogenase kinase reaction. Alloxan-diabetes markedly decreased the proportion of active dehydrogenase in hearts perfused with pyruvate or dichloroacetate. 3. The total activity of pyruvate dehydrogenase in mitochondria prepared from rat heart was unchanged by diabetes. Incubation of mitochondria with 2-oxo-glutarate plus malate increased ATP and NADH concentrations and decreased the proportion of active pyruvate dehydrogenase. The decrease in active dehydrogenase was somewhat greater in mitochondria prepared from hearts of diabetic rats than in those from hearts of non-diabetic rats. Pyruvate (0.1-10 mM) or dichloroacetate (4-50 muM) increased the proportion of active dehydrogenase in isolated mitochondria presumably by inhibition of the pyruvate dehydrogenase kinase reaction. They were much less effective in mitochondria from the hearts of diabetic rats than in those of non-diabetic rats. 4. The matrix water space was increased in preparations of mitochondria from hearts of diabetic rats. Dichloroacetate was concentrated in the matrix water of mitochondria of non-diabetic rats (approx. 16-fold at 10 muM); mitochondria from hearts of diabetic rats concentrated dichloroacetate less effectively. 5. The pyruvate dehydrogenase phosphate phosphatase activity of rat hearts and of rat heart mitochondria (approx. 1-2 munit/unit of pyruvate dehydrogenase) was not affected by diabetes. 6. The rate of oxidation of [1-14C]pyruvate by rat heart mitochondria (6.85 nmol/min per mg of protein with 50 muM-pyruvate) was approx. 46% of the Vmax. value of extracted pyruvate dehydrogenase (active form). Palmitoyl-L-carnitine, which increased the ratio of [acetyl-CoA]/[CoA] 16-fold, inhibited oxidation of pyruvate by about 90% without changing the proportion of active pyruvate dehydrogenase.

Acetates↗
PubMed1975

Regulation of mammalian pyruvate dehydrogenase.

In mammalian tissues, two types of regulation of the pyruvate dehydrogenase complex have been described: end product inhibition by acetyl CoA and NADH: and the interconversion of an inactive phosphorylated form and an active nonphosphorylated form by an ATP requiring kinase and a specific phosphatase. This article is largely concerned with the latter type of regulation of the complex in adipose tissue by insulin (and other hormones) and in heart muscle by lipid fuels. Effectors of the two interconverting enzymes include pyruvate and ADP which inhibit the kinase, acetoin which activates the kinase and Ca2+ and Mg2+ which both activate the phosphatase and inhibit the kinase. Evidence is presented that all components of the pyruvate dehydrogenase complex including the phosphatase and kinase are located within the inner mitochondrial membrane. Direct measurements of the matrix concentration of substrates and effectors is not possible by techniques presently available. This is the key problem in the identification of the mechansims involved in the alterations in pyruvate dehydrogenase activity observed in adipose tissue and muscle. A number of indirect approaches have been used and these are reviewed. Most hopeful is the recent finding in this laboratory that in both adipose tissue and heart muscle, differences in activity of pyruvate dehydrogenase in the intact tissue persist during preparation and subsequent incubation of mitochondria.

Acetates↗
PubMed1975

Histidines and renal function.

The results of endogenous renal clearances of 3-methylhistidine and histidine in twelve patients with normal and decreased renal functions are reported. Differences in the renal handling of the amino acids have been established. 3-methylhistidine showed a hyperbolic relationship between serum concentration and inulin clearance: histidine a linear relationship. The percentage tubular reabsorption of 3-methylhistidine was found to be about half that of histidine. The possible use of the measurement of serum 3-methylhistidine concentration as an index of renal insufficiency is discussed.

Adult↗
PubMedDate not supplied

An unanticipated increase in patient visits to a pediatric emergency department.

This study was conducted to explain a more than threefold increase in anticipated patient visits associated with the opening of a separate pediatric emergency department (PED) 2 miles from the nearest general emergency department. Population demographics and data pertaining to visits to other emergency departments were obtained. Parents visiting the new PED were surveyed using a standardized questionnaire. Over the study period (1984-1989), the city population increased by 7%; school population increased by 17%, with no increase in birth rate. Total patient visits to the other city hospitals increased by less than 10%, while the number of visits to the PED increased 250% over anticipated visits. Of children visiting the PED, 48% were less than 5 years old, 30% had lived at their current address less than 2 years, and 80% came from the geographic area close to the PED. Parental decision to bring the child to the PED was as follows: a service perceived to be "for kids" (47%), previous visit (42%), closest facility (33%), better service (20%), referred (12%), and pediatrician availability (10%). The PED is staffed by licensed pediatricians, whereas the general emergency departments are staffed by emergency physicians. We conclude that the increase in visits cannot be accounted for by increases in regional population base only. Anticipated patient volume to a new health care facility should not be based on population demographics only, but on other factors such as user perception of facility. Patient or parent preference should also be considered.

Birth Rate↗