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Biomedical subjects

D G Clark

Publications and source records attributed to D G Clark.

At least 55 records · Page 3Linked to original sources
PubMed1982

Acute inhalation toxicity of some halogenated and non-halogenated hydrocarbons.

1 The relative potency of effect of a wide range of halogenated and unsubstituted hydrocarbons on the central nervous system (CNS) and the heart of experimental animals have been determined. 2 The chemicals used caused either stimulation or depression of the rat CNS after 10 minutes' inhalation of concentrations ranging from 0.24% to greater than 80% (v/v), and cardiac sensitization in dogs after 5 minutes' inhalation of 0.12% to approximately 80% (v/v). 3 The toxicity could not be correlated with chemical structure, molecular weight, the presence or absence of various halogen atoms or the degree of saturation, but it was inversely related to the saturated vapour pressure. When the results were expressed on a thermodynamic scale the chemicals had similar potencies at relative saturations of 0.004 to 0.04 4 It is suggested that the effects of these chemicals on the CNS and the heart are probably structurally non-specific, and the chemicals may be regarded as physical toxicants whose effects are predictable from their physico-chemical properties.

Animals↗
PubMed1981

Preoperative criteria predictive of late survival following valve replacement for severe aortic regurgitation.

Forty-five patients underwent aortic valve replacement (AVR) for severe isolated aortic regurgitation from 1973 to 1979. There were two (4.4%) hospital deaths, both functional class IV. Six patients with mechanical prosthesis not receiving anticoagulants were excluded from further analysis. These data relate to 39 patients; the two operative deaths, 35 patients with mechanical prosthesis receiving anticoagulants, and two with bioprosthesis. There were three late cardiac deaths with 5-year survival 85%; average annual mortality rate of 3%. The 5-year survival with pre-AVR left ventricular (LV) ejection fraction greater than or equal to 0.45 was 87% vs 54% less than 0.45, (p less than 0.04); cardiac index greater than or equal to 2.5 L/min/m2 92% vs 66% less than 2.5 (p less than 0.04); mean VCF greater than or equal to 0.75 vs less than 0.75 circ/sec (p less than 0.09); end-diastolic pressure less than or equal to 20 vs greater than 20 mm Hg (p less than 0.08). Late survival was not significantly different between pre-AVR functional class I and II vs class III and IV; LV end-diastolic volume index greater than or equal to 210 vs less than 210 ml/m2; LV end-systolic volume index greater than or equal to 110 vs less than 110 ml/m2; and LV mass greater than or equal to 240 vs less than 240 gm/m2. With ejection fraction greater than or equal to 0.50 there was only one operative death (functional class IV) and no late cardiac deaths. Thus late survival following aortic valve replacement for severe isolated aortic regurgitation is better predicted preoperatively by the LV systolic pump function variables of ejection fraction and cardiac index than by LV diastolic parameters and clinical status.

Adolescent↗
PubMed1981

Angiography and peritoneal lavage in blunt abdominal trauma.

Records of 123 consecutive patients who underwent abdominal angiography for blunt trauma were reviewed. Twenty-four patients underwent abdominal angiography on the basis of positive physical findings. Seven (29%) required intervention as determined by angiography and the diagnosis was confirmed. Ninety-nine patients had abdominal angiography in association with angiographic evaluation of the chest, pelvis, or extremities. In 14 (14%) the angiogram indicated the need for intervention. In 13 this diagnosis was confirmed at laparotomy. The fourteenth patient was embolized angiographically and did well. Fifty-four patients had peritoneal lavage in addition to their angiograms. Sixteen were positive and 38 were negative. In four patients the lavage was negative and the angiographic findings indicated need for intervention. Three of these four were confirmed at laparotomy and the fourth patient was embolized angiographically. Indications for abdominal angiography in blunt trauma are: 1) incidental to needed thoracic aortography; 2) incidental to angiography when done for pelvic fractures; 3) suspected intra-abdominal injuries when clinical and lavage data are not definitive.

Abdominal Injuries↗
PubMed1980

Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase.

Rats from an inbred strain (NZR/Mh) were found to have high concentrations of glycogen in their livers, even after 24 h of starvation. Despite this, blood glucose concentrations were well maintained on starvation for up to 72 h. The primary defect is a deficiency of liver phosphorylase kinase, causing a lack of active glycogen phosphorylase, although total phosphorylase is normal. The intravenous injection of glucagon caused a rapid activation of cyclic AMP-dependent protein kinase in the liver, but no increase in either phosphorylase kinase or phosphorylase a activity. Although total glycogen synthase activity in the livers of affected rats was higher than normal, glycogen synthase in the active form was very low, presumably as a result of the high liver glycogen content. The condition is transmitted as autosomal recessive and, apart from hepatomegaly, the affected rats appear healthy.

Animals↗
PubMed1980

Use of antibiotics for prevention of Bacteroides fragilis wound sepsis in rats.

A Bacteroides fragilis wound sepsis model was developed in rats. Topical and parenteral administration of clindamycin, chloramphenicol, and carbenicillin were used prophylactically to eradicate bacteria from contaminated wounds. Topical clindamycin prevented bacterial growth in 15 of 34 wounds, while topical chloramphenicol and carbenicillin were not effective. Clindamycin injected into the wound margins or at a distal site prevented bacterial growth in 16 of 18 wounds and in a lower dose prevented growth of 50 per cent of 12 wounds. These results support the clinical use of clindamycin for the prevention of Bacteroides wound infection.

Administration, Topical↗
PubMed1979

Effects of fructose concentration on carbohydrate metabolism, heat production and substrate cycling in isolated rat hepatocytes.

1. Hepatocytes from starved rats were incubated with 5mm-glucose, labelled uniformly with (14)C and specifically with (3)H at positions 1, 2, 3 or 6, and with fructose at concentrations of 2.5, 7.5 or 25mm. 2. In the absence of other substrates only 1% of the radioactivity initially present in [U-(14)C]glucose appeared in the metabolic products, CO(2), lactate, pyruvate, amino acids and glycogen. 3. Fructose at 2.5mm caused a 30% increase in the glucose concentration and a 4-fold increase in the apparent oxidation of [U-(14)C]-glucose. 4. The formation of (3)H(2)O from [1-(3)H]-, [2-(3)H]-, [3-(3)H]- or [6-(3)H]-glucose was 2.4, 4.3, 2.15 or 1.6% respectively in the control incubations and 4.1, 10.4, 7.7 or 5.1% with 2.5mm-fructose. 5. Fructose at 7.5 and 25mm decreased the (3)H(2)O yields to less than the control values, but had no apparent effect on the amount of [U-(14)C]glucose metabolized. 6. In the incubations with 5mm-glucose and 25mm-fructose there were significant decreases in heat production, O(2) consumption and in the ratio of O(2) uptake to heat output. 7. Fructose at 2.5mm caused a 64% increase in heat output, but only a 43% increase in O(2) uptake. 8. The radioisotopic and calorimetric data demonstrate that physiological concentrations of fructose greatly increase metabolism in hepatocytes from starved rats. These data also indicate increased cycling at glucose/glucose 6-phosphate and at fructose 6-phosphate/fructose 1,6-bisphosphate in the presence of 2.5mm-fructose, although the rates of cycling were actually decreased relative to the amount of glucose catabolized. 9. At concentrations of 2.5, 7.5 and 25mm, fructose depressed hepatocyte ATP concentrations by 20, 65 and 80% respectively. Although fructose at 7.5 and 25mm increased glucose and lactate release, O(2) consumption, production of heat and formation of(3)H(2)O from [1-(3)H]-, [2-(3)H]-, [3-(3)H]- or [6-(3)H]-glucose were lowered to values equal to, or less than, controls. These effects probably reflect a severe derangement of hepatic metabolism due to excess phosphorylation of fructose when present at high concentrations.

Adenosine Triphosphate↗
PubMed1979

Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids.

1. Livers from fed rats were perfused in situ with whole rat blood containing glucose labelled uniformly with (14)C and specifically with (3)H at positions 2, 3 or 6. 2. When ethanol was infused at a concentration of 24mumol/ml of blood the rate of utilization was 2.8mumol/min per g of liver. 3. Ethanol infusion raised perfusate glucose concentrations and caused a 2.5-fold increase in hepatic glucose output. 4. Final blood lactate concentrations were decreased in ethanol-infused livers, but the mean uptake of lactate from erythrocyte glycolysis was unaffected. 5. Production of ketone bodies (3-hydroxybutyrate+3-oxobutyrate) and the ratio [3-hydroxybutyrate]/[3-oxobutyrate] were raised by ethanol. 6. Formation of (3)H(2)O from specifically (3)H-labelled glucoses increased in the order [6-(3)H]<[3-(3)H]<[2-(3)H]. Production of (3)H(2)O from [2-(3)H]glucose was significantly greater than that from [3-(3)H]glucose in both control and ethanol-infused livers. Ethanol significantly decreased (3)H(2)O formation from all [(3)H]glucoses. 7. Liver glycogen content was unaffected by ethanol infusion. 8. Production of very-low-density lipoprotein triacylglycerols was inhibited by ethanol and there was a small increase in liver triacylglycerols. Very-low-density-lipoprotein secretion was negatively correlated with the ratio [3-hydroxybutyrate]/[3-oxobutyrate]. Perfusate fatty acid concentrations and molar composition were unaffected by perfusion with ethanol. 9. Ethanol decreased the incorporation of [U-(14)C]glucose into fatty acids and cholesterol. 10. The concentration of total plasma amino acids was unchanged by ethanol, but the concentrations of alanine and glycine were decreased and ([glutamate]+[glutamine]) was raised. 11. It is proposed that the observed effects of ethanol on carbohydrate metabolism are due to an increased conversion of lactate into glucose, possibly by inhibition of pyruvate dehydrogenase. The increase in gluconeogenesis is accompanied by diminished substrate cycling at glucose-glucose 6-phosphate and at fructose 6-phosphate-fructose 1,6-bisphosphate.

Amino Acids↗
PubMed1979

The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes.

1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of O(2) uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of O(2) uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of O(2) uptake to heat output from 1.94+/-0.05 in the controls to 1.52+/-0.04 and 1.54+/-0.01mumol/J respectively. 5. Glucagon (1mum), which slightly increased both O(2) uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NH(4)Cl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of O(2) uptake to heat output from 1.81+/-0.08 to 1.47+/-0.06mumol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of O(2) uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell O(2) uptake to heat output between homozygote Zucker fa/fa obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of O(2) uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling.

Animals↗
PubMed1978

Partial purification and some properties of a cholinesterase from bush bean (Phaseolus vulgaris L.) roots.

A cholinesterase was partially purified from bush bean (Phaseolus vulgaris L.) roots by using acridinium-based ligand affinity chromatography. The procedure gave a 78-fold increase in specific activity, although at least three inactive contaminants remained. The enzyme activity was maximal against acetyl esters of choline and was inhibited by neostigmine. Di-isopropyl phosphorofluoridate completely inhibited activity at concentrations greater than 0.1 mM. The catalytic centre activity was 2 X 10(-4) times that of electric eel acetylcholinesterase. Cholinesterase activity appeared as a peak (s = 4.2 +/- 0.1 S) after isokinetic sedimentation. The Stokes radius was 4.00 nm and the apparent molecular weight was 72700 +/- 1900. The smallest active and native form of the enzyme appeared to be a monomer. This contrasts with animal acetylcholinesterases, in which the smallest active and native forms are multimeric.

Binding Sites↗