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Biomedical subjects

J C Russell

Publications and source records attributed to J C Russell.

At least 91 records · Page 5Linked to original sources

Beneficial effects of acarbose in the atherosclerosis-prone JCR:LA-corpulent rat.

The JCR:LA-corpulent rat is a strain exhibiting marked obesity and metabolic derangements characterized by hyperlipidemia due to hypersecretion of very-low-density lipoprotein (VLDL) and severe insulin resistance. The corpulent male rats spontaneously develop atherosclerosis and ischemic myocardial lesions. Male corpulent rats were treated with acarbose in the presence and absence of sugar-supplemented diets. The acarbose-treated rats had lower body weights at 3 months of age with unaltered food consumption, and a similar effect was seen with a high-fructose diet. Fasting insulin concentrations were decreased significantly in acarbose-treated animals at both 3 and 9 months of age, and the rate of plasma glucose disappearance increased at 3 months of age. Acarbose treatment did not affect whole-serum triglyceride concentrations, but there were modest decreases in cholesterol levels. Sugar-supplemented diets caused no significant changes in insulin or glucose concentrations, and caused small increases in nonesterified cholesterol only. Fructose- but not sucrose-supplemented diets were associated with a significantly decreased frequency of old scarred myocardial lesions. The frequency of occurrence of such lesions was also decreased by acarbose treatment. This effect of acarbose treatment may reflect improvement in insulin and glucose metabolism in treated rats. The decrease in myocardial lesions in fructose-fed rats may be secondary to increased carbohydrate metabolism via the pathways leading from fructose to triglyceride.

Acarbose↗

Effects of obesity and hypertension on ventricular myocytes: comparison of cells from adult SHHF/Mcc-cp and JCR:LA-cp rats.

OBJECTIVE: The aim was to compare beta adrenergic receptors, cAMP production, and Ca2+ accumulation by the sarcoplasmic reticulum in ventricular cardiomyocytes from female SHHF/Mcc-cp and JCR:LA-cp rats. Whereas rats from both strains exhibit gross obesity when the animals are homozygous for the recessive "corpulent" gene, the SHHF rats, which are hypertensive, all develop heart failure during their second year of life. The normotensive JCR:LA-cp animals do not. METHODS: beta Adrenergic receptor number, ligand affinity, isoprenaline and forskolin stimulated cyclic AMP production, and ATP dependent, phosphate supported 45Ca2+ uptake by the sarcoplasmic reticulum were compared in ventricular cardiomyocytes isolated from 6 months old obese female SHHF/Mcc-cp and obese and lean female JCR:LA-cp rats. RESULTS: Bmax and Kd for (-)-[125iodo]-cyanopindolol (125ICYP) binding were each approximately 50% lower in SHHF/Mcc-cp v JCR:LA-cp myocytes. Cyclic AMP production in response to isoprenaline, isoprenaline plus isobutylmethylxanthine (IBMX), and forskolin plus IBMX was also significantly depressed in the SHHF/Mcc-cp cells. In addition, sarcoplasmic reticular 45Ca2+ uptake by SHHF/Mcc-cp cells was 35% lower than in lean or obese JCR:LA-cp myocytes. Isoprenaline stimulated cAMP production and sarcoplasmic reticular Ca2+ uptake by the lean JCR:LA-cp cells were comparable to that described previously for myocytes from normal Sprague-Dawley rats. By contrast, Bmax and Kd for 125ICYP binding by the JCR myocytes differed substantially from previously described results for normal Sprague-Dawley rats, whereas values for the SHHF cells did not. CONCLUSIONS: Declines in Ca sequestration by the sarcoplasmic reticulum of ventricular cardiomyocytes from obese, hypertensive SHHF rats are not related to their obesity. However, obesity may contribute to the decline in cAMP production. This may account, in part, for the exacerbation by obesity of cardiac dysfunction in essential hypertension.

Animals↗

Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats.

Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30-70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state.

Animals↗

Occupational injury deaths in Alaska's fishing industry, 1980 through 1988.

OBJECTIVES: Studies from other countries have identified fishing as a hazardous industry, but little is known about occupational injury mortality related to fishing in the United States. Alaska was chosen for this study because approximately 45,000 people annually participate in Alaska's fishing industry and fishing is thought to be a major contributor to occupational injury mortality in the state. METHODS: Work-related injury deaths in Alaska's fishing industry were identified by means of death certificates and US Coast Guard mortality data. Fatality rates were calculated by using average annual fishing industry employment estimates. RESULTS: The 5-year average annual fishing-related fatality rate was 414.6 per 100,000 fishermen. The majority of the decedents were Caucasian men who drowned while fishing. CONCLUSIONS: This study emphasizes that fishing is a dangerous industry in Alaska and demonstrates the benefit of using multiple data sources to identify fishing-related deaths in the state.

Accidents, Occupational↗

Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA-corpulent rats treated with D-fenfluramine.

1. The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2. Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3. Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4. Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5. The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis.

Adipose Tissue↗

Phosphatidate phosphohydrolases in liver, heart and adipose tissue of the JCR:LA corpulent rat and the lean genotypes: implications for glycerolipid synthesis and signal transduction.

The activities of two distinct phosphatidate phosphohydrolases (PAP) were measured in livers, hearts and adipose tissues of the JCR:LA corpulent rat which is hyperphagic, hypertriglyceridaemic and insulin resistant. The specific activity of PAP-1, which requires Mg2+, was similar in the livers of lean and corpulent female rats and in male corpulent rats, but these activities were about 1.6-fold higher than in lean males. There was a correlation between the specific activity of PAP-1 and the concentrations of hepatic and serum triacylglycerols in the males, but not in the females. Chronic treatment of the corpulent rats with ethanol did not significantly alter the hepatic activity of PAP-1, or the concentrations of hepatic or serum triacylglycerols. Specific activities of PAP-1 in the heart were higher in the lean compared to the corpulent males. There was no significant difference for the females. Specific activities of PAP-1 were over 5-fold higher in the subcutaneous adipose tissue of the corpulent males and females compared to the lean genotypes. The differences were smaller (1.6-1.9-fold) in the gonadal adipose tissue of both sexes and in the peri-renal depot for the males. PAP-1 activity in the peri-renal depots of corpulent females was 23% lower than in lean females. PAP-2 activity was insensitive to N-ethylmaleimide and did not require Mg2+ for activity. Its activity was 1.5-2.0-fold higher in the livers and hearts of the lean male and female rats than in the corpulent genotypes. Chronic treatment with ethanol increased the activity of PAP-2 in the hearts of the corpulent males, but had no effect in the corpulent females. The specific activity of PAP-2 was higher in subcutaneous, gonadal and peri-renal adipose depots in the females and in the peri-renal depot of the corpulent males compared with the lean genotypes. Lean males had higher specific activities in all three depots compared to lean females. The tissue specificity and the sex differences in the specific activities of PAP-1 and PAP-2 are discussed in terms of their proposed functions in glycerolipid biosynthesis and signal transduction. It is proposed that a decreased activity of PAP-2 could be involved in the insulin insensitivity in the corpulent rats.

Adipose Tissue↗

Cystadenomas of the pancreas.

Five patients with cystadenoma of the pancreas were treated at two Connecticut hospitals between 1981 and 1987. All patients were women, with an average age of 42 (range 29 to 64). Abdominal pain was the most common presenting complaint and was present in four of five patients; two patients had palpable abdominal masses. Four patients had serious cystadenomas; one patient had a mucinous cystadenoma. All patients were treated by resection (four distal pancreatectomies; one pancreaticoduodenectomy). All patients are alive and well 3 to 9 years following surgery. Nonoperative differentiation of benign from premalignant or malignant cystic pancreatic neoplasms can be extremely difficult. Unresected benign cystadenomas may undergo malignant degeneration or cause significant morbidity and mortality as a result of local complications. Complete resection, if possible, is the treatment of choice for these unusual lesions.

Adult↗

Fatal occupational injury related to helicopters in the United States 1980-1985.

This paper discusses characteristics of occupational traumatic deaths, caused by helicopters, during 1980-1985. Death certificate data are used to describe demographic characteristics and causes of death. Information from National Transportation Safety Board (NTSB) investigations is used to describe pilot experience and environmental circumstances surrounding the incident. During 1980-1985, 374 worker deaths involving helicopters were identified in the National Traumatic Occupational Fatality (NTOF) database. The majority of deaths resulted from trauma to body organs (including the brain). According to NTSB investigations, 59% of crashes in this study were attributed to pilot error, compared to 16.5% from mechanical failure of the helicopter. Thirty percent of deaths were related to military use of helicopters. While death due to occupational exposure to helicopters is not common, some workers (e.g., helicopter pilots) appear to be at especially high risk. This group should be studied further to develop better strategies for their protection.

Accidents, Aviation↗

Fatty acid synthase and adipsin mRNA levels in obese and lean JCR:LA-cp rats: effect of diet.

In Sprague-Dawley rats, fatty acid synthase (FAS) activity is suppressed by dietary fat. To test the hypothesis that a defect in regulation of de novo fatty acid synthesis exists in massive obesity, we investigated the effect of diet on FAS mRNA levels in genetically obese JCR:LA-corpulent (cp) rats. We also determined levels of mRNA encoding adipsin, a fat cell-derived protein possibly associated with lipid metabolism. Hepatic FAS mRNA levels were elevated five-fold in obese compared to lean cp rats and were unsuppressed by dietary fat. Dietary sucrose increased FAS mRNA levels in lean cp rats, but, in contrast to Sprague-Dawley rats, little deposition of lipid resulted. Adipsin mRNA levels were fivefold lower in obese cp and Sprague-Dawley rats than in lean cp rats and were unaffected by diet. We conclude that exaggerated de novo fatty acid synthesis may play a major role in the pathogenesis of obesity in obese JCR:LA-corpulent rats.

Adipose Tissue↗

Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex.

Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome.

Adipose Tissue↗

Effect of dietary n-3 fatty acids on atherosclerosis prone JCR:LA-corpulent rats.

Corpulent male rats of the atherosclerosis prone JCR:LA-corpulent strain were fed diets supplemented with 10% by weight of olive oil or red fish oil. These rats are obese, with VLDL hyperlipidemia and marked insulin resistance. The diets were maintained to 9 months of age. Olive oil-fed rats had a 45% reduction in triglyceride concentrations with no significant changes in cholesterol or phospholipids. Red fish oil caused significant reduction in all lipid classes, with a 65% reduction in triglycerides and 35% reduction in cholesterol concentrations. Olive oil caused increases in the relative concentrations of oleic acid-containing triglycerides, while red fish oil preferentially enriched the longer chain fatty acids. There were no significant changes in insulin or glucose metabolism. The incidence of myocardial lesions, characteristic of the JCR:LA-cp strain, was unaltered by either oil-supplemented diet. These results, in a spontaneous animal model for cardiovascular disease, are consistent with other studies showing that diets rich in n-3 fatty acids do not, in themselves, confer protection against cardiovascular disease in animal models with genetically or experimentally induced lipid disorders.

Animals↗

Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat.

The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6-hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat.

Animals↗

Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat.

Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin-dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1-14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Agricultural machine-related deaths.

Analysis of 1980-1985 death certificate data for the United States indicated that an average of 369 occupational deaths per year involved agricultural machinery as the external cause of death. Out of all agricultural machine-related deaths, tractors accounted for 69 percent. Over half of these tractor-related deaths were rollovers. There is a need for public health programs to affect greater use of rollover protective structures (ROPS) on farm tractors.

Accident Prevention↗

Reduction of cold injury by superoxide dismutase and catalase.

The pathophysiology of cold injury was examined by cooling a hind leg of an anesthetized New Zealand white rabbit. A flow probe and a thermocouple were placed in the leg to be cooled to monitor the blood flow and tissue temperature. After baseline measurements, the leg was cooled with a freezing mixture up to 0 degrees C, which was followed by rewarming. The other leg served as control. In the experimental group, liposome-bound superoxide dismutase and catalase were infused through the femoral vein 15 minutes prior to putting the freezing mixture on the leg. Salicylic acid was injected through the femoral vein at the end of some experiments to assay hydroxy radical (OH). Our results demonstrated reduction of local blood flow in cold-exposed leg, indicating development of ischemia. Creatine kinase and lactage dehydrogenase were increased during rewarming in conjunction with hydroxyl radical formation, phospholipid breakdown, and lipid peroxidation. Treatment with superoxide dismutase and catalase reduced OH formation, prevented phospholipid degradation, and decreased creatine kinase, lactate dehydrogenase, and malonaldehyde formation. These results indicate that rewarming of cooled tissue is associated with "rewarming injury" similar to "reperfusion injury", and that oxygen-derived free radicals play a significant role in the pathophysiology of such injury.

Animals↗

Influence of occupational therapy curricula on students' attitudes toward persons with disabilities.

The influence of occupational therapy curricula on students' attitudes toward persons with disabilities was studied. Twenty-six female students in either their first or fourth (i.e, final) semester of the occupational therapy curriculum were assessed with the Attitudes Toward Disabled Persons Scale (ATDP) (Yukor, Block, & Younng, 1966). A comparison group, 26 female students in either their first or fourth semester of the medical technology program, was also assessed with this scale. As hypothesized, the fourth-semester occupational therapy students showed significantly higher scores than did the other three groups of subjects. Also as predicted, this same group showed significantly higher scores than their first-semester counterparts and the fourth-semester medical technology students. No significant difference was found between first-semester and fourth-semester medical technology students. The occupational therapy curriculum appears to positively influence students' attitudes toward persons with disabilities.

Attitude of Health Personnel↗

Independence of myocardial disease in the JCR:LA-corpulent rat on plasma cholesterol concentration.

The JCR:LA-corpulent rat is one of the strains incorporating the corpulent (cp) gene. Animals homozygous for the cp gene are obese, insulin-resistant and hyperlipidemic. Corpulent males, but not females or lean rats, spontaneously develop atherosclerotic and ischemic myocardial lesions. Administration of clofibrate to corpulent male rats reduced the plasma cholesterol ester concentration by 50% to that of lean controls rats. Unesterified cholesterol was slightly raised by the treatment. The markedly raised triglyceride concentrations were lowered modestly (from 282 to 220 mg/100 ml), but significantly in young rats and more markedly (from 305 to 136 mg/100 ml) in 9-month-old chronically treated rats. Apolipoproteins A-1 and E were reduced and Apo B increased by clofibrate treatment. Fasting plasma glucose and insulin concentrations were not altered nor was there any change in the impaired glucose tolerance in clofibrate-treated rats. Myocardial lesion frequency was also not reduced by clofibrate treatment. These results are consistent with others that showed inhibition of myocardial lesion formation only when the plasma insulin levels were reduced. Thus myocardial lesion formation in this strain of rats, while probably dependent upon the presence of hypertriglyceridemia, is most critically dependent upon hyperinsulinemia.

Animals↗