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Biomedical subjects

W H Peters

Publications and source records attributed to W H Peters.

At least 127 records · Page 7Linked to original sources
PubMed1987

Serum free amino acids of healthy males and pregnant women from Ethiopia.

Several clinical, anthropometric and biochemical parameters have been used for the evaluation of the nutritional status and diagnosis of protein-energy malnutrition [1]. Analysis of the complete serum amino-acid spectrum by ion-exchange chromatography provides valuable information on the adequacy of protein intake and on the metabolic response to protein depletion in undernourished subjects. However, the serum aminogram is quite differently affected by acute or chronic starvation or the great variety of starchy but low-protein foods and further toxic factors (e.g. mycotoxins) leading to kwashiorkor. Thus, very complex alterations of the serum amino-acid spectrum had to be expected [5, 9] and stimulated the present investigation for reference purposes. We report the results of amino acid determinations in apparently healthy adult males and pregnant women taking the traditional Ethiopian diet. For want of a better evaluation of the specific nutritional influence, we also collected data on serum amino acids of healthy Ethiopians consuming an average European diet.

Amino Acids↗
PubMed1987

Characterization and tissue specificity of a monoclonal antibody against human uridine 5'-diphosphate-glucuronosyltransferase.

A monoclonal antibody against human liver uridine 5'-diphosphate-glucuronosyltransferase (UDPGTase) was developed. Enzyme inhibition studies with this monoclonal antibody showed inhibition of human liver UDPGTase activity with bilirubin, 4-methylumbelliferone, and 4-nitrophenol as substrates. Testosterone, estrone, and phenolphthalein UDPGTase activity was not inhibited. The monoclonal antibody probably recognizes the uridine 5'-diphosphate-glucuronic acid binding site at 4-nitrophenol UDPGTase. Proteins with a molecular mass of 54,000 daltons were immunopurified from solubilized human liver using the monoclonal antibody as ligand coupled to Sepharose 4B beads. The distribution of UDPGTase isoforms in various human tissues was studied by immunofluorescence. The enzyme could be detected in liver, kidney, stomach, small intestine, colon, and skin. In liver, only hepatocytes contain UDPGTase. In kidney, the enzyme was localized exclusively in proximal tubuli and in stomach in epithelial mucous cells. In small intestinal epithelium, maximal fluorescence was seen at the villous tip. In colon, all lining epithelial cells were stained. In colon polyps, staining for UDPGTase was clearly decreased, and in colon carcinoma it was undetectable. In skin, the stratum corneum was intensely stained, whereas the stratum basale showed no fluorescence.

Animals↗
PubMed1987

Hepatobiliary excretion of organic anions in double-mutant rats with a combination of defective canalicular transport and uridine 5'-diphosphate-glucuronyltransferase deficiency.

Mutant rats with a selective defect for the hepatobiliary excretion of organic anions (GT+TR- rats) are valuable models to study hepatic transport processes. However, retained conjugates in the livers of these rats may secondarily affect hepatic uptake, metabolism, and excretion of other compounds and this may confound the interpretation of test results. We have developed double mutants (GT-TR-) rats with both a conjugation and an excretion defect by cross-breeding uridine 5'-diphosphate-glucuronyl-transferase-deficient GT-TR+ Gunn rats with transport-deficient GT+TR- rats. Phenotypically, GT-TR- rats and Gunn rats are alike in that both have unconjugated hyperbilirubinemia. Intravenous administration of tetrabromosulphthalein, bilirubin diglucuronide, and bilirubin monoglucuronide revealed a significant difference in that the clearance of these compounds was reduced to 10%, 10%, and 20%, respectively, in GT-TR- rats when compared with Gunn rats. The hepatic elimination of tetrabromosulphthalein in GT-TR- rats and in GT+TR- rats is impaired to the same extent. Thus, both have a similar hepatic excretion defect. However, bile flow and bile acid excretion in GT+TR- rats are more depressed than in GT-TR- rats: bile flow, 88 +/- 3 vs. 36 +/- 1 microliters/min.kg and bile acid excretion, 3.4 +/- 0.2 vs. 1.5 +/- 0.1 mumol/min.kg in GT-TR- and GT+TR- rats, respectively. This suggests that accumulated glucuronides in the liver inhibit bile flow and bile acid excretion. To test whether conjugated bilirubin and the photoisomers of unconjugated bilirubin are excreted via the same transport pathways, the effect of phototherapy was studied in GT-TR- rats and in Gunn rats. Photoexposure caused a 120% increase in biliary excretion of bilirubin isomers in Gunn rats and only 40% in GT-TR- rats. This shows that the biliary excretion of bilirubin photoisomers is indeed affected by the hepatic excretion defect of GT-TR- rats and suggests that hepatic excretion of bilirubin photoisomers proceeds via the same route as other organic anions such as conjugated bilirubin and tetrabromosulphthalein.

Animals↗
PubMed1987

Buffering substances of human semen.

The quantitative contribution of several components to the BC of human semen has been investigated. The role of spermatozoa is negligible (less than 2%). Both the high-molecular components (proteins) and the HCO3-/CO2 system contribute about 25% to the BC. Therefore, about 50% of the BC of semen must be due to low molecular weight components other than HCO3-/CO2.

Bicarbonates↗
PubMed1987

Ketosis, serum carnitine and its precursor amino acids in normal and diabetic ethiopians.

In a hospital-based study in northwestern Ethiopia some clinical and biochemical features of diabetes mellitus have been assessed to contribute to the problem of classification of diabetes in a tropical country. Diabetes requiring primary insulin treatment is presented by unequivocally elevated blood glucose levels and the classic symptoms of the disease. Newly discovered cases and readmitted rural diabetics show significantly lower body mass indices and 31% have been classified as underweight. The overall frequency of ketonuria at (re)admission was 45% together with moderately elevated or high 3-hydroxybutyrate serum concentrations. The hormonal status is characterized by a reduced beta-cell function. Serum concentrations of all carnitine fractions are lower in both normal and diabetic Ethiopians when compared with Caucasoids. Carnitine precursor amino acids are normal and the complete amino acid spectrum reveales no clear-cut pattern related to protein-energy malnutrition.

Acidosis↗
PubMed1986

Deconjugation of glucuronides catalysed by UDPglucuronyltransferase.

Evidence was found for UDPglucuronyltransferase-catalysed deconjugation of p-nitrophenol-, 4-methylumbelliferone- and phenolphthalein-glucuronides. The evidence is based on the following observations: 1, deconjugation is UDP-dependent and the reactions show Michaels-Menten kinetics with respect to UDP and glucuronide saturability; 2, UDP-glucuronic acid was identified as reaction product; 3, all studies were done in the presence of a beta-glucuronidase inhibitor; 4, induction profiles, using 3-methylcholanthrene and phenobarbital as inducing agents, were identical for conjugation and deconjugation reactions. Optimal deconjugation rates for p-nitrophenol- and 4-methylumbelliferone-glucuronides were at pH 5.1 and for phenolphthalein-glucuronide at pH 6.5. Only conjugation reactions showed latency; the corresponding deconjugation reactions were not latent. UDPglucuronyltransferase is a group of oligomeric isoenzymes with different molecular masses. The molecular masses of the isoenzyme species catalysing the forward and reverse reactions were determined by radiation-inactivation analysis. The molecular masses of the isoenzyme species mediating the catalyses of deconjugation reactions were significantly smaller than those mediating catalyses of conjugation reactions: 66 +/- 4 kDa vs. 109 +/- 7 kDa for p-nitrophenol; 82 +/- 8 kDa vs. 105 +/- 6 kDa for 4-methylumbelliferone; and 74 +/- 8 kDa vs. 159 +/- 14 kDa for phenolphthalein. This suggests that for catalyses of deconjugation reactions only part of a UDPglucuronyltransferase isoenzyme is needed, whereas for forward reactions the complete isoenzymes are required.

Animals↗
PubMed1986

[Population genetic studies in Ethiopia: distribution of blood group polymorphisms in Amhara/Tigrai ethnic groups].

During 1981-1982 and 1983-1984 a population-genetic study has been performed in the Amhara/Tigrai ethnic groups of Northwestern Ethiopia (Gondar). Blood group frequencies are reported for 6 systems (AB0, MNSs, Rh, P, Kell, Kidd), secretor status, haptoglobin, Gc, Gm/Km, HLA-A and -B as well as for the erythrocytic enzyme polymorphisms AcP, PGM1, ADA, EsD, GPT, AK and GLO I. The results are compared with other reports from East Africa and the Arabian peninsula. The mixed caucasoid-negroid gene pool of the Amhara/Tigrai as well as their relations with Arabia are confirmed.

ABO Blood-Group System↗
PubMed1986

Clinical value of serum bilirubin subfractionation by high-performance liquid chromatography and conventional methods in patients with primary biliary cirrhosis.

The clinical value of serum bilirubin subfractionation, using high-performance liquid chromatography (HPLC), was studied in 26 patients with primary biliary cirrhosis (PBC) from whom 59 serum samples were obtained. Total bilirubin (TB) levels were determined by alkaline methanolysis and HPLC (TBHPLC) as well as by the conventional diazo method (TB diazo). The correlation between TBHPLC and TBdiazo was significant (P less than 0.001) but bilirubin concentrations measured by HPLC amounted to only about 30% of those by diazo method. This difference is probably caused by tightly albumin-bound bilirubin, so called 'delta bilirubin' or 'bilirubin-albumin', which is measured by the diazo but not by the HPLC method. Bilirubin conjugates were present in 16 sera of 26 patients; 14 of these had normal total bilirubin levels. There was an excellent correlation between bilirubin conjugates (BcHPLC) and TB diazo (P less than 0.001). In all conjugate-containing samples, mono- and diconjugates were present in about equal proportions. Our results suggest that the biochemical methods of choice in the follow-up of patients with primary biliary cirrhosis are determination of total serum bilirubin by conventional diazo technique and determination of serum alkaline phosphatase activity. Both are simple methods which correlate well with liver histology. For the detection of patients with liver disease, such as asymptomatic PBC, the more elaborate HPLC technique has the distinct advantage of being a reliable method to detect bilirubin conjugates at normal total bilirubin levels. However, one should realize that with the presently used HPLC method only free conjugates are measured whereas covalently bound 'bilirubin-albumin' may represent up to 70% of all bilirubin species in cholestatic serum. Both free conjugates and 'bilirubin-albumin' start to appear in serum at total bilirubin levels as low as 5 mumol/l. The presence of bilirubin conjugates and 'bilirubin-albumin' in serum suggests liver disease. Reliable methods to quantify 'bilirubin-albumin' are needed.

Adult↗
PubMed1986

Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver.

Human liver microsomal bilirubin UDP-glucuronyltransferase catalyzes formation of bilirubin mono- and diglucuronide. KmUDPGA and Vmax of the enzyme are 0.6 mM and 1.69 nmol/mg protein X min. In vitro, bilirubin readily dissolves in the microsomal lipid phase. Taking this into account a Kmbilirubin of 60.6 microM was found, which is much higher than the in vivo microsomal UCB concentration of human liver (2.9-11.4 microM). The total capacity of human liver to form bilirubin mono- and diglucuronide in vitro exceeds the in vivo mono- and diglucuronide production rates by a factor 8 to 10. Radiation-inactivation studies reveal that human liver microsomal bilirubin UDP-glucuronyltransferase is a tetrameric enzyme with a molecular mass of 209 000 +/- 20 000 Da. The complete tetrameric enzyme catalyzes both glucuronidation steps, formation of bilirubin monoglucuronide and conversion of mono- to diglucuronide. In its monomeric form, the enzyme with molecular mass of 55 000 +/- 1 500 Da catalyzes only the first step of bilirubin glucuronidation, the formation of bilirubin monoglucuronide.

Bilirubin↗
PubMed1986

The frequency of islet cell surface antibodies in newly diagnosed diabetics from Ethiopia.

Forty-three newly diagnosed diabetic patients from Ethiopia were studied for the frequency of islet cell surface antibodies and other clinical features which are relevant to the aetiopathogenesis and classification of diabetes mellitus. In preliminary investigations of a small number of controls and noninsulin-dependent diabetics we found, as expected, no circulating antibodies. Four first-degree relatives of ICSA-positive sibs were negative, too. However, 3 out of 7 known insulin-treated diabetics displayed ICSA in the blood serum. In our study of newly diagnosed diabetics we found ICSA in 39% (17/43). Five patients who were assigned to the NIDDM subclass had no antibodies. 37 diabetics required insulin treatment after clinical diagnosis and 16 (43%) of these were ICSA-positive. There were no differences in the assessed clinical parameters between ICSA-positive and -negative patients. One ICSA-positive patient initially controlled with oral hypoglycaemic agents became insulin-dependent within our study period. Our observations in newly diagnosed diabetics from Ethiopia revealed a lower frequency of ICSA than in Caucasians, however, the results provide evidence for the occurrence of auto-immune phenomena in the aetiopathogenesis of diabetes mellitus in this ethnic group.

Adult↗
PubMed1986

ABH-secretion and Lewis red cell groups in diabetic and normal subjects from Ethiopia.

The possible relationship between Lewis red cell groups and secretor status and diabetes mellitus has been investigated in diabetic patients from Northwestern Ethiopia. The Lewis negative phenotype [Le(a-b-)] showed similar frequencies in diabetics and a control sample. Determination of the secretor status revealed a tendency to higher non-secretor rates in diabetics, particularly of the insulin-dependent type, in comparison with non-diabetic Ethiopians. A lack of effective immune protection from secretory IgA antibodies as a plausible explanation for the relationship between non-secretor status and IDDM is discussed. However, the available data from our study showed no statistically significant association between secretor state and IDDM. Without a detailed genetic characterization of our diabetic patients (HLA association data) it will be difficult to define precisely the postulated contribution of the Se gene to the aetiopathogenesis of IDDM.

ABO Blood-Group System↗
PubMed1984

The molecular weights of UDP-glucuronyltransferase determined with radiation-inactivation analysis. A molecular model of bilirubin UDP-glucuronyltransferase.

The molecular masses of the UDP-glucuronyltransferases were determined by means of radiation-inactivation analysis of sodium dodecyl sulfate-treated lyophilized rat liver microsomal preparations using a calibrated 60Co source. Bilirubin glucuronidation with formation of bilirubin monoglucuronide is catalyzed by a 41,500-Da enzyme; conversion of bilirubin mono- to diglucuronide is catalyzed by a 175,000-Da enzyme. The glucuronidation of estrone and testosterone is mediated by enzymes with molecular masses of 73,500 and 142,000 Da, respectively, and the glucuronidation of p-nitrophenol and phenolphthalein is mediated by enzymes with molecular masses of 109,000 and 159,000 Da, respectively. Our results show that UDP-glucuronyltransferase consists of a heterogenous group of enzymes with strikingly different molecular masses. Our data furthermore suggest that these enzymes may be oligomers composed of one to four subunits with similar molecular masses. Based on these findings, a molecular model of bilirubin UDP-glucuronyltransferase is proposed, consisting of four subunits. For bilirubin diglucuronide formation, the complete tetrameric enzyme is required, whereas formation of monoglucuronide can be mediated by a single subunit. The monomeric monoglucuronide-forming enzyme is resistant to sodium dodecyl sulfate, treatment whereas the tetrameric diglucuronide-forming enzyme is labile, but once inactivated, the diglucuronide-forming enzyme can be reconstituted by decreasing the sodium dodecyl sulfate concentration by means of dialysis.

Animals↗
PubMed1984

Lack of immunological cross reactivity between the transport enzymes (Na+ + K+)-ATPase and (K+ + H+)-ATPase.

Goat antisera against (Na+ + K+)-ATPase and its isolated subunits and against (K+ + H+)-ATPase have been prepared in order to test for immune cross-reactivity between the two enzymes, whose catalytic subunits show great chemical similarity. None of the (Na+ + K+)-ATPase antisera cross-reacted with (K+ + H+)-ATPase or inhibited its enzyme activity. The same was true for the (K+ + H+)-ATPase antiserum with regard to (Na+ + K+)-ATPase and its subunits and its enzyme activity. So notwithstanding the chemical similarity of their subunits, there is no immunological cross-reactivity between these two plasma membrane ATPases.

Adenosine Triphosphatases↗
PubMed1984

Quantitation of bilirubin conjugates with high-performance liquid chromatography in patients with low total serum bilirubin levels.

Bilirubin mono- and diconjugates were determined by alkaline methanolysis and high-performance liquid chromatography (HPLC) in serum from patients with metastatic liver disease and liver cirrhosis. Conjugates could be detected and quantitated at normal or low total bilirubin levels. Comparison with serum alkaline phosphatase activity revealed that in cirrhosis bilirubin conjugates were sometimes detectable at normal or slightly elevated alkaline phosphatase activities. In patients with metastatic liver disease alkaline phosphatase activity was a more sensitive indicator. In normal controls and in patients with Gilbert's syndrome no bilirubin conjugates were detected whereas serum of patients with haemolysis contained conjugated bilirubin. Therefore HPLC appears to be an excellent method to diagnose Gilbert's syndrome. In liver cirrhosis HPLC is a useful liver function test.

Bilirubin↗
PubMed1982

Studies on (K+ + H+)-ATPase V. Chemical composition and molecular weight of the catalytic subunit.

(1) A (K+ + H+)-ATPase preparation from porcine gastric mucosa is solubilized in sodium dodecyl sulfate, and is subjected to gel filtration. (2) A main subunit fraction is obtained, which is a protein carbohydrate lipid complex, containing 88% protein, 7% carbohydrate and 5% phospholipid. The Detailed composition of the protein and carbohydrate moieties are reported. (3) Sedimentation analysis of the subunit preparation, after detergent removal, reveals no heterogeneity, but the subunits readily undergo aggregation. (4) Acylation of the subunit preparation with citraconic anhydride causes a clear shift of the band obtained after SDS gel electrophoresis, but the absence of broadening and splitting of the band pleads against subunit heterogeneity. (5) Treatment of the subunit preparation with dansyl chloride indicates that the NH2 terminus is blocked, which favors the assumption of homogeneity of the protein. (6) Binding studies with concanavalin A indicate that at least 86% of the subunit preparation is composed of glycoprotein. (7) These findings, taken together, strongly suggest that there is a single subunit which is a glycoprotein and which represents the catalytic subunit of the enzyme. From sedimentation equilibrium analysis a molecular mass value of 119 kDa (S.E. 3, n = 6) is calculated for protein + carbohydrate and of 110 kDa (S.E. 3, N = 6) for protein only. (8) In combination with the molecular mass of 444 kDa (S. E. 10, n = 4) obtained for the intact enzyme by radiation inactivation we conclude that the enzyme appears to be composed of a homo-tetramer of catalytic subunits.

Adenosine Triphosphatases↗