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Biomedical subjects

D G Clark

Publications and source records attributed to D G Clark.

At least 37 records · Page 2Linked to original sources

Inhalation hazard test. Interlaboratory trial with OECD method 403.

Six industrial laboratories validated the Inhalation Hazard Test (OECD Method 403) using eight volatile chemicals. The test gave similar results in all laboratories, despite variation in inhalation exposure systems and strain of rat used. Detailed atmosphere analyses are not necessary, since nominal atmosphere concentrations were close to the analysed values. The method gives reproducible results directly applicable to hazard evaluation, and is quicker and cheaper and uses fewer animals than the conventional LC50 test.

Administration, Inhalation↗

Effects of subchronic inhalation of D-D (1,3-dichloropropene/1,2-dichloropropane) on reproduction in male and female rats.

The effects of inhaled D-D (1,3-dichloropropene/1,2-dichloropropane) on reproduction were studied in rats of both sexes. The rats inhaled nominal concentrations of 0, 10, 30, or 90 ppm (v/v) D-D for 6 hr/day, 5 days/week for 10 weeks. Treated males of proven fertility were paired with untreated virgin females at intervals during and after exposure. Treated females were paired with untreated males immediately after the 10-week exposure period. Various aspects of reproductive performance and general toxicity were assessed. Exposure to D-D produced no adverse effects on the libido, fertility, or morphology of the reproductive tracts of rats of either sex; no treatment-related dominant lethal effect was observed in male rats. Slight reductions in body weight gains and slight increases in liver and kidney weights were observed in 90 ppm rats of both sexes.

Allyl Compounds↗

Radiation-induced angiosarcoma.

A 47-year-old woman presented with an angiosarcoma of the terminal ileum 14 years after receiving adjuvant radiation therapy for ovarian dysgerminoma. Her clinical course is described, and the previously reported cases of radiation-induced angiosarcoma are reviewed.

Combined Modality Therapy↗

Age-related augmentation of phosphorylase b kinase in hepatic tissue from the glycogen-storage-disease (gsd/gsd) rat.

The effects of food deprivation on body weight, liver weight, hepatic glycogen content, glycogenolytic enzymes and blood metabolites were compared in young and old phosphorylase b kinase-deficient (gsd/gsd) rats. Although the concentration of glycogen in liver from 9-week-old female gsd/gsd rats (730 mumol of glucose equivalents/g wet wt.) was increased by 7-8% during starvation, total hepatic glycogen was decreased by 12% after 24 h without food. In 12-month-old male gsd/gsd rats the concentration of liver glycogen (585 mumol of glucose equiv./g wet wt.) was decreased by 16% and total hepatic glycogen by nearly 40% after food deprivation for 24 h. Phosphorylase b kinase and phosphorylase a were present at approx. 10% of the control activities in 9-week-old gsd/gsd rats, but both enzyme activities were increased more than 3-fold in 12-month-old affected rodents. It is concluded that the age-related ability to mobilize hepatic glycogen appears to result from the augmentation of phosphorylase b kinase during maturation of the gsd/gsd rat.

Aging↗

Microcalorimetric measurements of heat production in brown adipocytes from control and cafeteria-fed rats.

The effects of the sequential addition of glucose, noradrenaline, propranolol and oleic acid on the rates of O2 consumption and heat production by isolated interscapular brown adipocytes from control and cafeteria-fed rats were compared. Although the chemical agents produced very similar changes in oxidative metabolism, the actual rates of O2 uptake and heat output in adipocytes from the cafeteria-fed rats, when expressed per g dry wt. of cells, were approx. 65% less than those obtained with cells from the control rats. However, when the same results were expressed per 10(8) multiloccular brown adipocytes, rather than gravimetrically, rates of O2 consumption and heat production were equivalent. Further interpretation of these data is complicated, because the average volume of multiloccular brown adipocytes from cafeteria-fed rats was 2.5 times that for multiloccular cells from control animals.

Adipose Tissue, Brown↗

A review of second-look laparotomy for ovarian cancer.

One hundred twenty-seven patients underwent second-look laparotomies from July 1969 to June 1982. To be included in this report they must have met the following criteria: a documented ovarian neoplasm; previous surgery; adequate chemotherapy for cessation if no disease was found; and no X-ray, chemical, or clinical evidence of disease including an exam under anesthesia. Forty-one percent had residual disease at second-look laparotomy. The original stage and the percentage of tumor debulked at initial surgery were inversely related to the likelihood of finding residual disease. Age, histologic type and grade, and type of chemotherapy did not show a significant relationship with the likelihood of disease persisting. Recurrent tumor was subsequently detected in 16% of patients who had been found to be free of disease at second-look laparotomy. Of thirty stage III and IV patients treated with combinations containing cis-platinum, 10 (33%) had recurrences. This rate of recurrence was significantly greater than the 17.6% recurrence rate in 17 patients with Stage III and IV disease whose chemotherapy consisted of single alkylating agents or with combinations without cis-platinum. Twenty patients underwent a third-look laparotomy after completion of additional chemotherapy. Nine were found to have no residual disease. Two of the nine (22%) subsequently had recurrence of disease. Three of the eleven patients with persistent disease at the time of a third-look laparotomy underwent a fourth-look laparotomy. All were found free of disease and none have recurred. Six (55%) of those with persistent disease at the third-look laparotomy have died despite continued therapy. The ability to successfully treat some patients with persistent disease continues to be a justification for the use of a second-look laparotomy. However, the high rate of recurrence after cessation of treatment following the finding of no residual disease raises the question of whether it is appropriate to discontinue all therapy at this time.

Alkylating Agents↗

Effects in vivo of food deprivation and 3-mercaptopicolinate in the glycogen-storage-disease (gsd/gsd) rat.

Intraperitoneal injection of 3-mercaptopicolinate into 24 h-food-deprived 27-week-old female control (GSD/GSD) rats lowered the concentration of circulating glucose by 66%, but glycerol and lactate concentrations were increased up to 3- and 4-fold respectively. In phosphorylase b kinase-deficient (gsd/gsd) rats the corresponding changes for blood glucose, lactate and glycerol were half those observed in the controls. Although the concentration of liver glycogen (approx. 12%, w/w) in the gsd/gsd rats was not altered during food deprivation, total hepatic glycogen was decreased by 17%. It is suggested that the gradual breakdown of the extensive hepatic glycogen stores during starvation assists in the maintenance of normoglycaemia in the gsd/gsd rat.

Animals↗

The contribution of hepatic metabolism to diet-induced thermogenesis.

In order to examine the possible contribution of the liver to diet-induced thermogenesis, we examined the metabolism of hepatocytes from rats that had been fed a varied choice of highly palatable human food items ("cafeteria feeding"). Liver cells derived from cafeteria-fed rats that had been fasted for 20 hours showed marked increases in rates of respiration and gluconeogenesis in the presence of glycerol or sorbitol. These cells were also much less sensitive to the inhibitory effects of rotenone than were hepatocytes of control animals. hepatocytes from fasted cafeteria-fed rats also demonstrated a substantially enhanced rate of fatty acid oxidation and ketogenesis, which did not appear to be correlated with cellular demands for adenosine triphosphate (ATP). This apparent fall in metabolic efficiency was confirmed by calorimetric studies, which indicated augmented cellular heat production. These changes in hepatic metabolism, associated with cafeteria-feeding, suggest that the liver may have a significant role in diet-induced thermogenesis.

Animals↗

Reliability of verbal-manual interference.

Considerable recent research has used unimanual finger tapping with concurrent vocalization to assess hemispheric lateralization for language. This study examined whether an index finger tapping task is a reliable measure in adults and whether the task demonstrates sex differences in hemispheric specialization for language. Thirty right-handed subjects, fifteen male and fifteen female, between the ages of 18 and 25 were tested. The task measured the differences in tapping rate for each hand between tapping with and without a concurrent verbal task. The task was completed once each day for 3 consecutive days to determine reliability. The tapping task was found to be a reliable measure. No significant differences were found between tapping scores of males and females.

Adolescent↗

Hormonal regulation of L-type pyruvate kinase in hepatocytes from phosphorylase kinase-deficient (gsd/gsd) rats.

The hormonal regulation of L-type pyruvate kinase in hepatocytes from phosphorylase b kinase-deficient (gsd/gsd) rats was investigated. Adrenaline (10 microM) and glucagon (10 nM) each led to an inactivation and phosphorylation of pyruvate kinase. Dose-response curves for adrenaline-mediated inactivation of pyruvate kinase, phosphorylation of pyruvate kinase and the stimulation of gluconeogenesis from 1.8 mM-lactate were similar for hepatocytes from control and gsd/gsd rats. Time-course studies indicated that adrenaline-mediated inactivation and phosphorylation of pyruvate kinase proceeded more slowly in phosphorylase kinase-deficient hepatocytes than in control hepatocytes. The age-dependent change in the adrenergic control of pyruvate kinase was similar between control and phosphorylase kinase-deficient hepatocytes. Adrenaline, glucagon and noradrenaline activated the cyclic AMP-dependent protein kinase and inhibited pyruvate kinase in phosphorylase kinase-deficient hepatocytes. Vasopressin (0.2-2 nM), angiotensin (10nM) and A23187 (10 microM) had no effect on the activity ratio of the cyclic AMP-dependent protein kinase or pyruvate kinase in these cells. It is concluded that phosphorylase kinase plays no significant role in the hormonal control of pyruvate kinase and that phosphorylation and inactivation of this enzyme results predominantly from the action of the cyclic AMP-dependent protein kinase.

Animals↗

Colonic complications of acute pancreatitis and pancreatic abscess.

Colonic involvement should be suspected in patients with severe acute pancreatitis, especially in the following clinical settings: plain abdominal radiographs suggesting bowel ischemia, colonic obstruction, acute lower gastrointestinal hemorrhage, gram-negative septicemia, enteric bacteria on Gram stain or culture of peritoneal fluid, and feculent abdominal drainage from a previously drained pancreatic abscess. Intraoperatively, the pancreas should be widely drained and the fecal stream diverted. Colonic hemorrhage and nonviable bowel require immediate resection. Broad-spectrum antibiotic administration and vigorous nutritional support also are required in these critically ill patients. Although proximal diversion and pancreatic diversion alone may suffice, colonic resection may be required later for persistent obstruction or fistulization, but in a more elective setting. Colonic anastomoses should be performed only when pancreatic inflammation and associated sepsis have resolved completely.

Abscess↗

Metabolism of [U-14C, 2-3H] glucose in rat liver during non-recirculating perfusion: effects of insulin.

Livers from fed male rats were perfused in a non-recirculating manner with undiluted blood containing either 6 or 13 mM [U-14C,2-3H] glucose. At the lower concentration there was a small output of glucose which was unaffected by insulin whereas at the high concentration there was a substantial uptake of glucose which was significantly increased by the hormone. The rate of metabolism of [2-3H] glucose was greater than that of [U-14C] glucose in all experiments indicating an active substrate cycle between glucose:glucose 6-phosphate. Cycling was unaffected by insulin at the lower glucose concentration but was increased by perfusion with 13 mM glucose, the latter increase being abolished by insulin. These data show that although the perfused liver acts to autoregulate blood glucose, this is not achieved solely at the substrate cycle glucose:glucose 6-phosphate.

Animals↗

Glycogen metabolism in the liver of the neonatal gsd/gsd and control (GSD/GSD) rat.

1. The metabolism of hepatic glycogen, labelled with [6-3H]glucose at day 19.5 of gestation and with 14C from [U-14C]galactose at delivery, was followed for 10 h in food-deprived gsd/gsd and control (GSD/GSD) neonatal rats. 2. In the affected pups glycogen was maintained at 12% (w/w) and there was no loss of incorporated radioactivity. 3. The 3H and 14C in glycogen from the controls were both decreased by 80%, but 14C was removed at 0--5 h and [6-3H]glucose at 5--10 h. 4. Blood glucose concentrations in the unaffected neonatal rats fell from 5.3 mM at 20 min to 1.7 mM after 10 h. In the gsd/gsd pups blood glucose concentration was decreased from 2 mM at birth to 0.3 mM at 2.5 h: it was maintained at 0.8 mM between 5 and 10 h. 5. In neonatal rats that had been dead for 10 h, hepatic glycogen was decreased by 34% in the controls and by 22% in the gsd/gsd pups. These results demonstrate that liver from the affected rats contains glycogenolytic activity, but that it is not expressed in living tissue.

Animals↗

No major thermogenic role for (Na+ + K+)-dependent adenosine triphosphatase apparent in hepatocytes from hyperthyroid rats.

(Na+ + K+)-dependent ATPase activity, heat production and oxygen consumption were increased by 59%, 62% and 75% respectively in hepatocytes from tri-iodothyronine-treated rats. Ouabain at concentrations of 1 and 10 mM decreased oxygen uptake by 2--8% in hepatocytes from euthyroid rats and by 5--15% in hepatocytes from hyperthyroid animals. Heat output was decreased by 4--9% with the glycoside in isolated liver parenchymal cells from the control animals and by 11% in the cells from the tri-iodothyronine-treated animals. These results do not support the hypothesis that hepatic (Na+ + K+)-ATPase plays a major role in increased heat production in hepatocytes from hyperthyroid rats.

Animals↗

Inhibition by insulin of ethanol-induced hyperglycaemia in perfused livers from fed rats.

Livers from fed male rats were perfused with homologous whole blood and infused with ethanol and insulin. Ethanol raised hepatic glucose output by enhancing gluconeogenesis from perfusate lactate and amino acids. Ketogenesis and the ratio [3-hydroxy butyrate]/[acetoacetate] were also raised. Insulin, infused alone, lowered blood glucose, ketogenesis and total serum amino acids and when added with ethanol opposed the metabolic effects of the latter. Ethanol did not affect serum fatty acids but their concentrations were raised by insulin.

Amino Acids↗