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Biomedical subjects

J C Russell

Publications and source records attributed to J C Russell.

At least 109 records · Page 6Linked to original sources
PubMed1991

Comparison of the enteroinsular axis in two strains of obese rat, the fatty Zucker and the JCR:LA-corpulent.

The 'fatty' Zucker and more recently the JCR:LA-cp 'corpulent' have been studied extensively as genetic models of the hyperinsulinemia, insulin resistance and abnormal fat metabolism of obesity. It has been hypothesized that an abnormal enteroinsular axis leading to hypersecretion of the insulin releasing hormone gastric inhibitory polypeptide (GIP) could contribute to the hyperinsulinemia of obesity, although this has been controversial. The present study was undertaken to compare the enteroinsular axis in fatty Zucker and JCR:LA-cp rats. The in vivo GIP and insulin responses to an oral glucose challenge, as well as glucose tolerance, were compared in lean and obese phenotypes of both strains as well as the sensitivity of the perfused pancreas to the secretagogues glucose, arginine and GIP. In addition, the effect of perfusate glucose concentration on the beta cell response to GIP was assessed in both strains. Tissue samples from the pancreas were taken for immunocytochemical analysis of comparative size and composition of pancreatic islets. Our results indicate that corpulent rats are hyperGIPemic when compared to fatty Zuckers and that hyperinsulinemia (both in vivo and in vitro) is more severe in the JCR:LA-cp than in the fatty Zucker, as is the degree of insulin resistance (as evidenced by glucose intolerance). Islets of corpulent rats were found to be larger than those of fa/fa rats as well as having a larger area occupied by beta cells. It was concluded that GIP may contribute to fasting hyperinsulinemia in the Zucker rat (as a result of a defective glucose threshold for the insulinotropic action of GIP), whereas the hyperGIPemia of the JCR:LA-cp rat may contribute to the massive nutrient-stimulated hyperinsulinemia observed in the male phenotype of this strain.

Administration, Oral↗
PubMed1990

Effect of age on serum lipids and lipoproteins of male and female JCR:LA-corpulent rats.

The JCR:LA-cp rat is a strain incorporating the corpulent (cp) gene. When homozygous for the cp gene, the rats are hyperphagous, hyperinsulinemic, hyperlipidemic and obese. The corpulent male rats develop atherosclerotic and myocardial lesions from an early age, while corpulent female and lean rats do not develop lesions. The hyperlipidemia is due to elevated levels of VLDL resulting in moderately raised cholesterol levels and markedly elevated triacylglycerol levels. The VLDL concentrations are similar in corpulent male and female rats at an early age with both having much higher levels than lean rats. As the animals age, the VLDL hyperlipidemia in the corpulent male increases at 3 months and then decreases slowly and rises again at 12 months of age. The corpulent female rats show higher triacylglycerol and phospholipid concentrations than the males at 3 months age and reach values over 1000 mg/100 ml by 9 months of age, then decrease at 12 months of age. The cholesterol concentrations of the corpulent females are greater than those of the males from 9 months of age. Thus, in the period of life up to middle age, the cardiovascular disease incidence does not correlate with the degree of hyperlipidemia. The disease progression does correlate with the severity of insulin resistance and glucose intolerance, which is more severe in the corpulent male than female rats. The results suggest that the hyperlipidemia must be a necessary condition for development of atherosclerotic disease in this strain of rats, but it is not a sufficient condition.

Aging↗
PubMed1990

Suppression of food deprivation-induced high-rate wheel running in rats.

To test for involvement of endogenous opioids in the maintenance of high-rate running we have administered naloxone, a specific opioid antagonist, to rats. The animals were stabilized voluntarily running 6000 to 8000 m/day through a standard protocol and maintained in this state on approximately 18 g of food per day. Naloxone (50 mg/kg in saline) or saline alone was injected intraperitoneally on alternate days for 20 days. All rats ran less on days when naloxone was administered. The mean distance run for the group (N = 6, mean +/- SE) was: saline: 6401 +/- 985; naloxone: 5344 +/- 805 m/day. This difference was highly significant (p less than 0.001). In the 4-hour period immediately following the naloxone injection there was no inhibition of running. The second four-hour period showed a nonsignificant (p greater than 0.05) decrease in running. Inhibition of running was highly significant after eight hours (30%, p less than 0.001). The results demonstrate a clear inhibition of the high-rate running by naloxone and imply a significant role by endogenous opioids in the maintenance of running. The time course of the inhibition is consistent with the relatively high initial concentrations of naloxone exerting an agonist action and the subsequent lower levels having an antagonist effect.

Animals↗
PubMed1990

Paradoxically slow preadipocyte replication and differentiation in corpulent rats.

We have investigated the in vitro rate of replication and differentiation of preadipocytes derived from lean (+/+) and obese (cp/cp) male JCR:LA-corpulent (cp) rats in an attempt to identify mechanisms that regulate adipose tissue growth. Cp/cp rats were twofold heavier than age-matched lean rats by 9-10 mo. Cp/cp-derived preadipocytes demonstrated an inherently slower rate of replication than +/+ preadipocytes (population doubling time: cp/cp 52.3 +/- 9.6 h vs. +/+ 19.7 +/- 1.6 h), although the preadipocyte pool in the cp/cp was significantly greater. Cp/cp preadipocytes were resistant to hormonally induced differentiation (19.9 +/- 9.4% of cells accumulated lipid) but differentiated when cocultured with mature adipocytes to the same extent as preadipocytes derived from Sprague-Dawley (SD) rats (cp/cp 48.4 +/- 15.2% vs. SD 52.2 +/- 11.9%). In contrast, SD preadipocytes did not differentiate in response to mature adipocytes from +/+ rats (13.8 +/- 5.2%). Our observations suggest that preadipocyte replication and maturation may not be controlled in a coordinated manner.

Adipose Tissue↗
PubMed1990

Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat.

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.

Animals↗
PubMed1990

Influence of paracrine factors on preadipocyte replication and differentiation.

Regional adipose tissue growth may be modulated by paracrine factors that influence preadipocyte replication and/or differentiation. To investigate this hypothesis, we have studied the effects of culture media conditioned by adipose microvascular endothelial cells, preadipocytes, or mature fat cells, on rat preadipocyte replication and differentiation in vitro. Endothelial cell-conditioned medium (ECCM) stimulated preadipocyte replication while medium conditioned by mature fat or preadipocytes had little effect. ECCM contained heat and trypsin sensitive polypeptides, with molecular masses in the 18-35 kDa range. Mature fat-conditioned medium, but not medium enriched with triacylglycerols, induced differentiation in about 50 percent of preadipocytes. This effect was greatly reduced in cells derived from genetically obese JCR:LA-corpulent (cp) rats compared to those derived from lean JCR:LA-cp or Sprague-Dawley rats. The present studies demonstrate the presence of paracrine factors which may play a role in regulating regional adipose tissue growth.

Adipose Tissue↗
PubMed1990

Effects of advancing age and severe food restriction on pathological processes in the insulin resistant JCR:LA-corpulent rat.

Corpulent rats of the JCR:LA-corpulent strain spontaneously develop atherosclerotic lesions, occlusive thrombi and myocardial lesions. In addition to exhibiting a VLDL hyperlipidemia they are insulin resistant. Young male corpulent rats have significantly impaired rates of clearance of plasma glucose on an intravenous glucose tolerance test in comparison to lean rats (k = 0.94 +/- 0.69 vs 2.06 +/- 0.64 x 10(-2) min-1, p less than 0.01). Food restriction to 60% of the spontaneous intake of lean controls (12 g/day) for 10 days raised the rate of glucose clearance to that of the lean rats (k = 3.01 +/- 0.40 x 10(-2) min-1) and this was highly significant compared to the rate at three months of age (p less than 0.0005). Food restriction significantly lowered the elevated insulin levels of corpulent rats at 3 and 12 months of age. It inhibited, but did not prevent, the development of hyperplasia of the islets of Langerhans. The hypertriglyceridemia was less severe in 12 month old rats (214 +/- 52 vs 282 +/- 19 mg/100 ml while total cholesterol was increased (129 +/- 20 vs 85 +/- 5.5 mg/100 ml). Severe food restriction halved the triglyceride concentration at both 3 and 12 months of age while total cholesterol was unaffected. The food restriction throughout life up to 12 months of age, however, did inhibit the development of advanced myocardial lesions.

Aging↗
PubMed1990

The effects of an iron chelator on cellular injury induced by vascular stasis caused by hypothermia.

Rewarming of a cooled rabbit leg was associated with the generation of oxygen-derived free radicals, shown to be instrumental for tissue injury occurring during rewarming. The present study used a compound that, by its ability to bind with free iron, can remove hydroxyl radical (OH.) from tissue. Deferoxamine reduced tissue injury during cooling and rewarming, as evidenced by its ability to decrease tissue release of lactic acid dehydrogenase and creatine kinase. Deferoxamine also reduced the formation of OH. and lipid peroxidation during the rewarming phase. This compound did not have any effect on the arterial blood flow pattern, which uniformly decreased during cooling and was restored during rewarming. The results of this study indicate the efficacy of deferoxamine in reducing cellular injury associated with cold and rewarming and further suggest a role for oxygen-derived free radicals in the pathophysiology of cold-rewarming injury.

Animals↗
PubMed1990

Hypersecretion of VLDL, but not HDL, by hepatocytes from the JCR:LA-corpulent rat.

The JCR:LA-corpulent male rat, when homozygous for the cp gene (cp/cp) is hyperlipidemic and prone to atherosclerosis. Both male and female cp/cp rats have markedly elevated serum levels of triacylglycerols and phospholipids [Dolphin, P.J. et al. 1987. Biochim. Biophys. Acta. 919: 140-148]. In the present study, monolayer cultures of hepatocytes were prepared from male and female, corpulent and lean, rats. There was a marked hypersecretion of all very low density lipoprotein (VLDL) lipid and apoprotein components from corpulent-derived cells. The increased secretion most likely accounts for the increased levels of VLDL lipids and apoproteins previously observed in serum. In contrast, there was no difference between the corpulent and lean hepatocytes in their secretion of high density lipoprotein (HDL) lipids and apoproteins. The difference in triacylglycerol secretion between the lean and corpulent cells was sustained even when the cells were cultured for 24, 48, and 72 h prior to the experiment, by which time the hormonal differences between the corpulent and lean animals would have been largely eliminated. The magnitude of the difference in triacyglycerol secretion did not diminish with increasing time in culture. The biochemical basis responsible for the hypersecretion of VLDL has not yet been established. However, preliminary results suggest that there is an inherent difference in glycerolipid metabolism in the two types of hepatocytes.

Animals↗
PubMed1990

Endometriosis of the colon. Its diagnosis and management.

Cases of endometriosis of the colon were examined in a retrospective fashion to illustrate the problems in diagnosis and management of this disease entity. Nine patients were identified from 1956 to 1988; their average age was 41 years. Common presenting symptoms were abdominal pain, diarrhea, constipation, tenesmus, small caliber stools, abdominal distention, and blood per rectum. Bowel symptoms were cyclic in four of the nine patients, and seven had a history of gynecologic complaints. Barium enema was performed in six patients and endoscopy in five patients. All cases involved the sigmoid or rectosigmoid colon. In no case was the diagnosis established endoscopically. Surgical procedures included resection with primary anastomosis (6 patients), and resection with sigmoid endcolostomy and Hartmann's pouch (3 patients). In only one case was full-thickness colonic wall involvement noted. One patient had an adenocarcinoma of the colon adjacent to the area of endometriosis. Our data indicate that the diagnosis of endometriosis of the colon should be considered in women with colonic symptoms, especially with an associated history of dysmenorrhea or cyclic changes in bowel habits. Surgical resection offers the best chance for relief of symptoms.

Adult↗
PubMed1990

Medical examiner/coroner records: uses and limitations in occupational injury epidemiologic research.

Epidemiologic research often relies on existing data, collected for nonepidemiologic reasons, to support studies. Data are obtained from hospital records, police reports, labor reports, death certificates, or other sources. Medical examiner/coroner records are, however, not often used in epidemiologic studies. The National Institute for Occupational Safety and Health's Division of Safety Research has begun using these records in its research program on work-related trauma. Because medical examiners and coroners have the legal authority and responsibility to investigate all externally caused deaths, these records can be used in surveillance of these deaths. Another use of these records is to validate cases identified by other case ascertainment methods, such as death certificates. Using medical examiner/coroner records also allows rapid identification of work-related deaths without waiting several years for mortality data from state offices of vital statistics. Finally, the records are an invaluable data source since they contain detailed information on the nature of the injury, external cause of death, and results of toxicologic testing, which is often not available from other sources. This paper illustrates some of the ways that medical examiner/coroner records are a valuable source of information for epidemiologic studies and makes recommendations to improve their usefulness.

Accidents, Occupational↗
PubMed1989

Evidence of free radical (FR) involvement in ischemic colitis.

Early ischemic colitis was induced in rats to evaluate the roles of FRs and intraluminal content. After 30 minutes of ischemia, biopsies for histology, conjugated dienes (CD) and malonaldehyde (M), presumptive marker of lipid peroxidation, were obtained at 0, 30, and 60 minutes reperfusion. Histology was unchanged. CD and M were elevated in ischemic and saline controls, and rose progressively during reperfusion; CD and M were essentially the same as non-ischemic controls during reperfusion with intraluminal corticosteroid (c) and Alcide (A). These agents may be beneficial in early ischemic colitis.

Adrenal Cortex Hormones↗
PubMed1989

Prevention of myocardial disease in JCR:LA-corpulent rats by running.

The JCR:LA-corpulent rat is a congenic strain that, if homozygous for the cp gene, is obese with a very low-density lipoprotein hyperlipidemia and is insulin resistant. The male corpulent rats develop atherosclerotic lesions of the major arteries and myocardial lesions. Corpulent and lean male rats were induced through mild food restriction to run intensively (approximately 6,000 m/day) from 6 wk to 6 mo of age. Food restriction, especially when coupled with running, lowered all classes of lipids in the whole serum of corpulent rats. The principal changes in lipid concentrations were in the very low-density lipoprotein fraction. Food restriction caused a significant drop in fasting insulin levels of corpulent rats and decreased beta-cell hyperplasia. Both effects were more marked in the running animals. There was a significant decrease in myocardial lesion frequency in the food-restricted corpulent rats and an absence of lesions in the running rats. The results indicate that intensive physical activity can largely correct the lipid abnormalities and insulin resistance of this atherosclerosis-prone strain, and these changes are associated with inhibition of the disease process. However, moderate food restriction has similar effects, and the greater effects seen with intensive running may simply reflect an effectively more severe metabolic restriction in the presence of the exercise.

Animals↗
PubMed1989

Surgery by non-surgeons: podiatric surgery in Connecticut.

In order to determine the standards for credentialing, privilege delineation, and quality assurance of podiatric surgery in Connecticut, a questionnaire was mailed to all acute care hospitals, with a 100% institutional response. Of 38 hospitals, 25 currently have granted clinical privileges to podiatrists. Full podiatric surgical programs exist in 12 hospitals; multitiered privileges in seven hospitals differentiate podiatrists with and without postgraduate surgical residency training. Credentialing, privilege delineation, and quality assurance generally is conducted through the chief of surgery or chief of orthopedics, with participation of staff podiatrists. Based on the Connecticut experience, recommendations are made regarding establishment of new podiatric surgical programs.

Connecticut↗
PubMed1989

Multicenter evaluation of TDx test for assessing fetal lung maturity.

"TDx Fetal Lung Maturity," an automated assay that measures the relative concentrations of surfactant and albumin in amniotic fluid, was compared with the lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol determination at five clinical sites. A total of 695 amniotic fluid samples were analyzed, of which 312 were followed by delivery of the infant within three days of sample collection. Of these 312, 24 developed respiratory distress syndrome and seven developed transient tachypnea. With the cutoff for maturity set at a surfactant/albumin value of 50 mg/g, the assay showed a sensitivity of 0.96 and a specificity of 0.88 for all samples, compared with a sensitivity of 0.96 and a specificity of 0.83 for the L/S ratio. The combination of rapid assay (30 min), accurate results, and uniformity among testing centers makes the TDx assay a very promising method.

Albumins↗
PubMed1988

Reduction of hyperlipidemia in the LA/N-corpulent rat by dietary fish oil containing n-3 fatty acids.

The LA/N rat, when homozygous for the corpulent gene (cp/cp), is obese, hyperphageous, hyperinsulinemic, hypertriglyceridemic and prone to the development of vascular and myocardial lesions. The hypertriglyceridemia, which in 3-month-old cp/cp males is 282 +/- 42 mg/dl and in females, 512 +/- 83 mg/dl, results from the presence of a large triacylglycerol-rich VLDL. The moderate hypercholesterolemia in these animals is largely due to markedly elevated HDL levels, which reach 172 +/- 21 mg total lipid/dl in males and 154 +/- 22 mg total lipid/dl in females. The LA/N-cp rat is thus an interesting animal model of endogenous hypertriglyceridemia in which to examine the hypolipidemic effects of pharmacological agents and also dietary oil supplements containing the n-3 fatty acids. In this study, 1-month-old male and female cp/cp rats were fed a normal low fat laboratory chow supplemented with either 10% olive oil or 10% redfish (Sebastes marinus) oil ad libitum for a period of 2 months. The redfish oil contained 4.9 +/- 0.1% of its total fatty acids as eicosapentaenoic (20:5(n-3)) and 2.3 +/- 0.5% as docosahexaenoic acid (22:6(n-3)), the predominant fatty acids being gondoic (20:1(n-3)), 21.9 +/- 0.9% and cetoleic acid (22:1(n-11)), 21.7 +/- 1.7%, which are of dietary origin. Daily caloric intake was similar to the oil-fed versus control rats. However, the oil-fed animals weighed significantly more than the controls after 2 months of oil supplementation. Redfish oil reduced serum triacylglycerols by 54% in males and 45% in females after 2 months. VLDL levels, after the same time period, were reduced by 44% in males and 39% in females. HDL lipid mass was significantly reduced in both sexes (by 27% in males and 49% in females). However, the levels remained above those of male LA/N +/+ rats of the same age and Long-Evens rats. Olive oil feeding significantly reduced serum cholesterol, triacyglycerols and phospholipids in male but only cholesterol and phospholipids in female animals. This oil had no significant effect upon VLDL total lipid levels in either sex, but significantly increased the particle diameter with a concomitant reduction in the cholesterol and phospholipid content. HDL total lipid levels were unaffected: However, HDL total cholesterol increased significantly in males only. Both oils markedly reduced serum LDL levels in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Atherogenesis in two strains of obese rats. The fatty Zucker and LA/N-corpulent.

Two strains of obese rats, the fatty Zucker and the LA/N-corpulent have been compared at 6 months age for the presence of vascular and myocardial disease. Both strains, when obese, exhibit a VLDL hyperlipidemia with elevated triglycerides and moderate elevations of plasma cholesterol concentrations compared to the lean rats of the same strain. The hyperlipidemia is more modest in the fatty Zucker than the corpulent LA/N, and the serum lipid concentrations of the lean Zucker are lower than those of the lean LA/N. Apolipoprotein concentrations were similar and elevated in the two obese genotypes compared to the lean genotypes which were also similar to each other. Male and female obese animals of both strains exhibited hyperinsulinemia under fasting conditions and after oral glucose, with obese male LA/N rats exhibiting the most severe hyperinsulinemia. Glucose tolerance was impaired in obese LA/N animals but was normal in lean rats of both strains and fatty Zucker rats of both sexes. The glucose intolerance observed in obese LA/N animals was more severe in the male than in the female rats. Unlike the corpulent rat, which develops atherosclerotic lesions, the fatty Zucker shows no evidence of advanced vascular lesions on scanning electron microscopy. The fatty Zucker also does not develop the myocardial lesions that are frequent in the male corpulent LA/N rat. It is suggested that the initiation of the atherogenic process is dependent upon elevated insulin levels or transient hyperglycemia. Development of the advanced lesions appears to require the presence of hyperlipidemia.

Animals↗