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Biomedical subjects

D H Hunneman

Publications and source records attributed to D H Hunneman.

At least 55 records · Page 3Linked to original sources
PubMed1984

Esthesioneuroblastoma: ultrastructural, immunohistological and biochemical investigation of one case.

A case of esthesioneuroblastoma, the pathological diagnosis of which almost always causes great difficulties, was investigated ultrastructurally, biochemically, and immunohistologically, using antibodies against the five known types of intermediate filaments [keratin, vimentin, desmin, glial fibrillary acidic protein (GFAP) and neurofilaments]. The tumour cells did not react with antibodies against any of the five intermediate filament proteins. Ultrastructural investigations showed dense cored secretory granules in the cytoplasm and cell processes. Thus, immunohistology offers by "exclusion" a differential diagnosis to avoid often misdiagnosed tumours (undifferentiated carcinomas, embryonal rhabdomyosarcomas, and malignant lymphomas), since carcinomas react with antikeratin, embryonal rhabdomyosarcomas with antibodies to desmin and malignant lymphomas show immunofluorescence with antibodies to vimentin. The biological behaviour (age distribution, tendency to metastasize), the normal values of biochemical parameters, homovanillic acid and vanilmandelic acid (HVA, VMA), and the absence of neurofilaments distinguish this type of tumour from the peripheral sympathetic neuroblastoma.

Cytoplasmic Granules↗
PubMed1984

Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine].

Potential protective effects of oxfenicine [(S)-4-hydoxyphenylglycine] in ischemic stressed canine myocardium have been studied. This compound is characterized as a drug leading to metabolic inhibition of free fatty acid (FFA) metabolism. The drug (0.06 mmol . kg-1 body weight) caused no changes in hemodynamics or energy demand (Et) but depressed myocardial oxygen consumption (MVO2) by 11% (P less than 0.02). Significant changes in FFA and lactate metabolism were observed: lactate extraction (EX) increased from 22.5-37.1 mumol/Min, extraction ratio (EXR) from 16.5-30% and oxygen extraction ratio (OER) from 24.8-38%; EX of FFA decreased from 6900-5000 nmol/min, EXR from 48.2-31.4% and OER from 59.7-46.6%. Arterial concentrations of FFA and lactate remained unchanged. EX, EXR and OER of glucose were not affected under basic conditions. In the same collective, repeated ischemia (3 min) was produced by proximal occlusion of the left anterior descending artery (LAD). The efficiency of the drug was examined by (a) the amounts of ischemia metabolites released in the early reperfusion and (b) quantification of O2-debt and O2-repayment in the occlusion- and reperfusion periods. Compared to control occlusions, premedication led to a reduced O2-debt (P less than 0.01) combined with a reduced amount of oxygen additionally taken up in the early reperfusion (P less than 0.05). Furthermore, release of potassium increased (+7.1%; P less than 0.05); release of lactate (-32%, P less than 0.001) and inorganic phosphate (-34%, P less than 0.01) decreased. These data give support to the concept that a pharmacologically induced shift of cardiac metabolism with reduction of FFA utilisation may be favourable in circumstances with limited oxygen supply.

Animals↗
PubMed1983

Mass fragmentographic determination of homovanillic and 4-hydroxy-3-methoxy mandelic acids in 50 microliter plasma.

A method is presented for the mass fragmentographic determination of homovanillic and 4-hydroxy-3-methoxy mandelic acids in 50 microliter plasma or serum. The values found in normal, healthy adults agree well with previously published reports which required, however, much larger plasma volumes. The method uses a simple ethyl acetate extraction from acidified plasma and a one-step derivatisation with trifluoroethanol and pentafluoropropionic anhydride. The deuterium-labelled analogues are used as internal standards.

Adult↗
PubMed1983

Plasma levels of catecholamine metabolites in the newborn period.

Plasma levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA) were measured mass fragmentographically in 37 healthy preterm infants and 62 healthy infants born at term during the postnatal period. HVA and VMA levels increased after birth and declined steadily afterwards. Infants with various clinical problems showed marked elevations of HVA and VMA during episodes of clinical deterioration. The results indicate a readily functioning sympathoadrenal system in newborns.

Adrenal Glands↗
PubMed1982

Influence of myocardial substrate utilization on the oxygen consumption of the heart.

The effect of changing myocardial metabolism from predominantly lipid to predominantly carbohydrate utilization on myocardial oxygen consumption (MVO2) was studied in 10 closed-chest dogs. Oxygen saving potency of different metabolic interventions was quantified over a wide hemodynamic range by comparing the directly determined MVO2 with the hemodynamic parameter total left ventricular energy demand (Et), which correlates closely under control conditions with MVO2 (r = 0.98). Stimulation of carbohydrate metabolism by addition of glucose and beta-pyridyl carbinol or by activation of pyruvate dehydrogenase with dichloroacetate (DCA) shifted the cardiac respiratory quotient during beta-stimulation from 0.73 to 1.00 and 0.89, respectively, the nonesterified fatty acid/albumin ratio decreased from 4.0 to 0.5, or remained unchanged with DCA, and MVO2 was reduced by 25 and 16%, respectively. Therapeutic approaches aimed at decreasing MVO2 by changing substrate utilization are discussed.

Animals↗
PubMed1982

A nystatin-resistant mutant of Rhodotorula gracilis. Transport properties and sterol content.

A nystatin-resistant mutant of Rhodotorula gracilis was obtained by treatment of the wild strain cells with N-methyl-N-nitro-N-nitrosoguanidine and selected on agar plates containing 150 micrograms nystatin/ml. Three important transport functions of the plasma membrane of mutant cells: the accumulation of monosaccharides, the generation and maintenance of the pH-gradient and of the membrane potential, as well as the cell respiration were insensitive to at least 10(-5) M nystatin. This concentration of nystatin inhibited completely all these processes in wild strain cells. Analysis of cellular sterols revealed a defect of ergosterol biosynthesis in the mutant, which was localized at the last oxidative step between 5,6-dihydroergosterol and ergosterol.

Biological Transport↗
PubMed1980

Isolation and characterization of an ornithine-containing lipid from Paracoccus denitrificans.

The isolation and characterization of an ornithine-containing lipid from various strains of Paracoccus denitrificans (grown heteretrophically and autotrophically) is reported. The structure of this aminolipid was found to be H2N--CH2--(CH2)2--CH[NH--CO--CH2--CH(O--CO--R1)--R2]--CO2H, where R1 predominantly represents the residue of octadec-11-enoic acid, R2 the residue of a 3-hydroxyeicos-13-enoic acid. In addition, the major phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol) were isolated and characterized.

Fatty Acids↗
PubMed1979

Sensitive in vivo assay of the phenylalanine hydroxylating system with a small intravenous dose of heptadeutero L-phenylalanine using high pressure liquid chromatography and capillary gas chromatography/mass fragmentography.

A method is described which allows the in vivo determination of the phenylalanine hydroxylating system in atypical and classical phenylketonuria. Phenylalanine-d7 is administered i.v. (0.030 g/kg body weight) within 10 min. Tyrosine-d6 in plasma is measured from 30 to 240 min post load by using a computerized capillary gas chromatography/mass fragmentography system. In two patients with hyperphenylalaninemia, the residual activity of the phenylalanine hydroxylating system was 15.7 and 3.7% of the normal, in two phenylketonurics 1.5 and 0.3% respectively. The in vivo figures correspond well to the in vitro assay of the residual activity of the phenylalanine hydroxylase in needle liver biopsy material.

Adult↗
PubMed1979

Stereochemistry of hydrolysis of adenosine 3':5'-cyclic phosphorothioate by the cyclic phosphodiesterase from beef heart.

Adenosine 3':5'-cyclic phosphorothioate, Sp-diastereomer was hydrolyzed by cyclic phosphodiesterase from beef heart in the presence of [18O]water to [18O]adenosine 5'-phosphorothioate. This was phosphorylated by myokinase and pyruvate kinase to [18O]adenosine 5'-(1-thiotriphosphate),Sp-diastereomer. The position of 18O was determined to be in a nonbridging position. This result indicates that the hydrolysis proceeded with inversion of configuration at phosphorus.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Stereochemistry of hydrolysis by snake venom phosphodiesterase.

[18O]Adenosine 5'-O-phosphorothioate-O-p-nitrophenyl ester was prepared by saponification of the bis (-O,O-p-nitrophenyl ester) with K18OH. Only the diastereoisomer with the Rp configuration si a substrate for snake venom phosphodiesterase. The asymmetrically labeled [18O]adenosine 5'-O-phosphorothioate formed in this reaction was converted enzymatically to [18O]adenosine 5'-(1-thiodiphosphate) with the Sp configuration. The position of the 18O label, either bridging [1,2-mu-18O] or nonbridging [1-18O] was then determined. The results show that the reaction catalyzed by snake venom phosphodiesterase takes place with retention of configuration at phosphorus. This indicates that the hydrolysis proceeds via a covalent nucleotide enzyme intermediate.

Crotalid Venoms↗
PubMed1977

[Hyperreninism without hyperaldosteronism in diuretic abuse: a report of a case with identification of mefruside and ethacrynic acid in urine (author's transl)].

A 46-year-old nurse had been hospitalized 16 times during the preceding five years because of episodes of excessive hypokalaemia. On admission to hospital there was hypokalaemia, polyuria, excessive plasma renin activity but no increased aldosterone secretion rate. Diuretic abuse was confirmed by gas-chromatography and mass spectrometry of mefruside and ethacrynic acid in the patient's urine. Apart from other interesting aspects of this case there was the demonstration of hyperreninism without hyperaldo-steronism. The stimulating effect of renin on aldosterone secretion was obviously lower than the inhibiting effect of hypokalaemia. The general term "renin-angiotensin-aldosterone system" is, therefore, misleading because it mentions only one pathway of aldosterone regulation. The combination of hypokalaemia, polyuria, hyperreninism without hyperaldosteronism is apparently the principal but not widely recognised feature of diuretic abuse.

Aldosterone↗
PubMedDate not supplied

Investigation of cardiac metabolism using stable isotopes and mass spectrometry.

The technique described in this communication enables detailed investigations of cardiac metabolism using 13C-labeled substrates and mass spectrometric measurements of 13CO2 in the coronary effluent. To validate this technique for further studies isolated working rat hearts were perfused with 13C-labeled substrates in a bicarbonate-free perfusion fluid. The fraction of CO2 produced by oxidation of labeled substrate was calculated by the 13CO2/CO2 ratio in the coronary perfusate. The oxidation of 13C-acetate showed a linear correlation with 13C-acetate concentrations between 0.015 and 0.16 mmol/l. An inhibitor of acylcarnitine translocase, 2-(3-methylcinnamylhydrazono)-propionate (BM42.304) decreased CO2 production from 13C-palmitate from 48% +/- 4% to 31% +/- 3% (n = 11, SEM). Taking into account considerations of tracer kinetic theory rapidly accessible intracellular palmitate stores were estimated to be less than 900 nmol/g ww. This technique allows specific investigations of the oxidation of labeled substrates in the heart and may be useful for basic research and/or clinical diagnosis, thus avoiding the hazards of radiolabeled substrates.

Acetates↗
PubMedDate not supplied

A new method for studying the incorporation of nonesterified fatty acids into cardiac lipids by using deuterium-labelled palmitate.

A new method for measuring the incorporation of exogenous fatty acids into myocardial lipids of working rat hearts using deuterium-labelled palmitate has been developed. After perfusing isolated hearts, the fatty acid composition of triglycerides, diglycerides, monoglycerides, cholesterol esters, and nonesterified fatty acids (NEFA) was measured by a mass fragmentographic method. Hearts perfused only with 5 mM glucose and 1 mM lactate perfusion as basic substrates showed a significant decrease of triglyceride content, while the other lipids were not found to be significantly reduced. The fatty acid composition of all lipids were not affected. An addition of D31-palmitate complexed to albumin at a molar ratio of 5:1, caused a dose-dependent incorporation into triglycerides and diglycerides which suggested saturation kinetics. The tissue content of nonesterified D31-palmitate was found to be linearly related to its concentration in the perfusate. It may be of note that the concentration of the other NEFA was significantly affected neither by a fatty-acid-free perfusion nor by a perfusion with D31-palmitate. A significant incorporation of the supplied fatty acid into cholesterol esters and monoglycerides could not be detected.

Animals↗