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Biomedical subjects

J C Russell

Publications and source records attributed to J C Russell.

At least 19 recordsLinked to original sources
PubMed1995

Overexpression of the obese gene in the genetically obese JCR:LA-corpulent rat.

Expression of the obese (ob) gene in JCR:LA-cp rats was examined. A 360 bp fragment of the conserved region of the gene was obtained by RT-PCR using total RNA isolated from adipose tissues of Sprague-Dawley (SD), JCR:LA-cp obese and lean rats. The three gene fragments were sequenced and shown to be identical. They were over 90% identical to the mouse ob gene sequence. The amplified fragments encode for 120 amino acids and have a glutamine residue at position +49. The gene was shown to be expressed only in adipose tissues, both white and brown. A ten-fold increase in ob mRNA was detected in white adipose tissues of obese animals compared to the lean ones of the JCR-LA:cp strain of rat. Ob gene was expressed in adipocytes and preadipocytes from the obese rat whereas in the lean and SD rats, ob gene expression was found in adipocytes only. No ob mRNA was detected in preadipocytes from the lean or SD rats, indicating a differentiation or maturation-dependent expression in normal rats.

Adipocytes↗
PubMed1995

Sexual dimorphism in the metabolic response to the calcium channel antagonists, diltiazem and clentiazem, by hyperlipidemic JCR:LA-cp rats.

The JCR:LA-cp rat is obese, insulin resistant, and hypertriglyceridemic. The obese male rats spontaneously develop atherosclerosis and ischemic myocardial lesions that are prevented by treatment with the calcium channel antagonist, nifedipine. Male and female JCR:LA-cp rats were treated with the calcium channel antagonist, diltiazem, and a closely related compound, clentiazem (at 30 mg/kg). Clentiazem, but not diltiazem, caused a significant increase in body weight of both sexes in the presence of decreased food consumption. Serum triacylglycerols were decreased by half by both drugs in male rats only, reflecting decreased very-low-density lipoprotein (VLDL) secretion. Females did not respond with lower concentrations of triacylglycerol (although VLDL secretion rate was decreased) and showed increased concentrations of cholesterol in the high-density lipoprotein (HDL) fraction. Diltiazem-treated male rats showed decreased VLDL particle size, together with a shift to shorter-chain fatty acids in the triacylglycerols. This effect was not seen with clentiazem treatment. There was no effect on insulin and glucose metabolism in these insulin-resistant animals. Calcium channel antagonists have complex metabolic effects in the hypertriglyceridemic rats, with highly beneficial hypolipidemic effects in the males that are not seen in the females. The sexual dimorphism of these responses is sex linked, but appears not to be due to the steroid sex hormones. These results suggest caution in the chronic treatment of human females with these agents and the importance of detailed human studies in females and individuals with the insulin-resistant/hypertriglyceridemic/obese syndrome.

Animals↗
PubMed1995

Metabolic abnormalities linked to obesity: effects of dexfenfluramine in the corpulent rat.

The JCR:LA-corpulent rat is a useful experimental model for the obese-diabetic-dyslipidemic syndrome that mimics the human condition and exhibits spontaneous development of atherosclerosis and myocardial lesions. A 30-day treatment of 6-month-old rats with dexfenfluramine 1, 2.5, and 5 mg per kilogram decreased body weight through loss of adipose tissue mass. The effect is caused primarily by the ability of dexfenfluramine to reduce food intake. The maximum depression of food intake and greatest weight loss is seen during the first 10 days of treatment in this experimental model; thereafter, body weight stabilizes. However, during this period, there is a marked decrease in serum concentrations of triglycerides, cholesterol, and insulin. Corpulent male rats were also treated from 6 to 37 weeks of age with dexfenfluramine 2.5 mg/kg. This also produces a sustained decrease in body weight and a decrease in circulating insulin concentrations. Preliminary evidence demonstrates a substantial decrease in the incidence of necrotic myocardial lesions produced by ischemic events. This study establishes that dexfenfluramine treatment can decrease the severity of associated risk factors for cardiovascular disease, namely obesity, diabetes, and dyslipidemias. Furthermore, we report the first evidence that long-term treatment with dexfenfluramine can largely prevent the occurrence of myocardial lesions and end-stage cardiovascular disease in this animal model prone to atherosclerosis.

Animals↗
PubMed1995

Increased glucose phosphorylating activity correlates with insulin secretory capacity of male JCR:LA-corpulent rat islets.

In this study the glucose responsiveness of isolated, overnight-cultured islets of obese LA/N-corpulent (cp/cp) rats was compared with glucose phosphorylating activity to determine whether changes in the function of glucokinase could be identified. Islets from both male and female cp/cp rats showed a left-shifted concentration response to glucose, with EC50 values of 1.5 and 4.6 mM, respectively, compared with 9.2 mM for lean control islets. Islets from cp/cp rats were partially resistant to inhibition by mannoheptulose, a glucokinase inhibitor. Minimum inhibitory concentrations were 10 mM in cp/cp vs. 3 mM in lean rat islets. Glucose phosphorylating potential was markedly increased in islets of male cp/cp, but not female cp/cp, compared with lean rats. The maximal velocity (Vmax) of hexokinase was increased 5-fold, while the Km of glucokinase was significantly decreased, in male cp/cp compared with the lean control islets(3.6 vs. 35.2 mM). The Km for glucokinase was also decreased in female cp/cp rat islets (17.2 mM). The data from male cp/cp rat islets are consistent with the idea that increased glucose phosphorylation capacity can contribute to insulin hypersecretion and an extreme leftward shift in the concentration-response curve. However, other factors must also be considered because female cp/cp rats have moderately increased insulin secretory capacity without marked changes in total glucose phosphorylating capacity.

Animals↗
PubMed1995

Inhibition of atherosclerosis and myocardial lesions in the JCR:LA-cp rat by beta, beta'-tetramethylhexadecanedioic acid (MEDICA 16).

Atherosclerosis-prone, insulin-resistant JCR:LA-cp male rats were treated from 6 weeks to 39 weeks of age with beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16). Body weights were reduced (13%, P < .001) at 36 weeks without any accompanying decrease in food consumption. The treatment did not cause any significant change in plasma glucose or fasting insulin concentrations. There was a significant decrease in the extreme hyperplasia of the islets of Langerhans (38%, P < .05). The marked VLDL hypertriglyceridemia was decreased by 70% (P < .001), with an accompanying significant reduction in cholesterol concentrations. The severity of raised atherosclerotic lesions on the aortic arch was very markedly reduced (P < .01) in treated rats. This was accompanied by a reduction (P < .01) in the incidence of ischemic myocardial lesions. We conclude that long-term (33 weeks) MEDICA 16 treatment of an animal model for the obesity/insulin-resistant/hyperlipidemic syndrome not only markedly improved lipid metabolism, but also inhibited the development of advanced cardiovascular disease.

Animals↗
PubMed1994

Effects of obesity on bile formation and biliary lipid secretion in the genetically obese JCR:LA-corpulent rat.

Obesity, a known risk factor in cholesterol gallstone disease, is a favorable factor in the formation of bile supersaturated with cholesterol. Previous studies have been indirect and limited to human beings. To better define the hepatic secretory defect, we directly measured bile secretion and bile salt kinetics in a genetically obese rat. Common bile duct cannulations and 24-hr bile collections were performed on 11 obese (homozygous for the cp gene) and 11 lean (heterozygous cp) female rats of the JCR:LA-cp strain. In absolute terms, obese rats had normal bile salt secretion rates, 28% larger bile salt pools and 45% greater bile salt synthesis than lean controls. Obese rats had twice the total liver DNA content of lean controls, indicating twice the liver cell number. In terms relative to liver cell number, bile salt synthesis per milligram DNA was no different in the obese rats and controls. Biliary secretion under basal conditions, when expressed per total DNA content, was significantly decreased in the obese rats. Bile salt and phospholipid secretion per milligram DNA were decreased 54% and 49%, respectively, whereas a lesser 31% reduction in cholesterol secretion resulted in an increased cholesterol saturation index. The bile salt secretion rate and bile flow per milligram DNA were both decreased by half in obese rats, a cholestatic state likely reflecting the accumulation of intracellular microvesicular fat and mitochondrial damage. The secretory defect in this model of obesity is therefore less bile salt and phospholipid in relation to the cholesterol secreted per liver cell.

Animals↗
PubMed1994

Abnormal insulin and glucose metabolism in the JCR:LA-corpulent rat.

The JCR:LA-corpulent rat, if homozygous for the cp gene, exhibits a syndrome characterized by obesity, hypertriglyceridemia, and hyperinsulinemia with impaired glucose tolerance. The insulin and glucose metabolism of lean and obese rats of this strain have been studied with the euglycemic insulin clamp technique in 3- and 9-month-old rats. Lean rats require a twofold greater glucose infusion rate than obese rats at high plasma insulin concentrations. Glucose turnover was measured using isotope dilution techniques and 1-3H-glucose. Glucose turnover in lean rats of both sexes increases by a factor of 2 to 3 at very high insulin levels. In contrast, obese male rats are unable to respond even to extreme insulin levels with an increase in basal glucose turnover, indicating a profound insulin resistance. The calculated hepatic glucose production is inhibited by high insulin levels in the obese male rats, while lean animals show no inhibition. Thus, the obese male rats have normal basal glucose turnover, but have a profound insulin insensitivity in peripheral tissues. These abnormalities are present at a much reduced level in the obese female rats. These results are consistent with the hypothesis that the hyperinsulinemia, which correlates strongly with cardiovascular disease in this strain of rat, is secondary to a marked peripheral insulin resistance.

Aging↗
PubMed1994

Comparison of mortality rates for open and closed cholecystectomy in the elderly: Connecticut statewide survey.

The objective was to determine the safety of laparoscopic cholecystectomy for patients 65 years of age and older with symptomatic uncomplicated chronic gallbladder disease by comparing the mortality rate with open cholecystectomy. Connecticut Hospital Information Management Exchange and the Connecticut Society of American Board of Surgeons established a Connecticut Laparoscopic Registry made up of 33 acute care hospitals. A cohort longitudinal retrospective statewide registry collected data mortality rates on all 2865 elderly patients undergoing open (OC) or closed (LC) cholecystectomy for uncomplicated chronic cholecystitis. A database was established and continuously monitored from October 1, 1988, to December 31, 1992. Seven hundred sixty-one patients over 65 years of age underwent open cholecystectomy for uncomplicated chronic cholecystectomy during fiscal year 1989, with a mortality rate of 1.4%. The mortality rate of a similar cohort of patients who underwent laparoscopic cholecystectomy during fiscal years 1991 and 1992 was 0.3% and 0.6%, respectively. The mortality rate was further broken down into age subsets 65-69, 70-79, and 80+. The prelaparoscopic era (FY 1989) age subsets were compared with those of the laparoscopic era (FY 1991 and 1992). A statistically significant reduction (p = 0.01) in mortality rate was noted in the 70-79 age group following laparoscopic surgery. Laparoscopic cholecystectomy in the elderly for the treatment of symptomatic, uncomplicated chronic cholecystitis is as safe if not safer than open cholecystectomy as measured by mortality rate.

Aged↗
PubMed1994

Defective endothelium-dependent relaxation in the JCR:LA-corpulent rat.

Endothelium-dependent relaxation of the aorta was assessed in JCR:LA-corpulent rats, which are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese and spontaneously develop atherosclerotic disease and myocardial lesions. The findings in corpulent rats (6 months of age) were compared with those in age-and sex-matched lean rats. Aortic rings were prepared and mounted in Krebs-Henseleit buffer in a conventional organ bath. The tissue was contracted with norepinephrine (10(-6) mol/L), and relaxation was induced using acetylcholine, the calcium ionophore A23187, or bradykinin. The maximum relaxation to acetylcholine was impaired in corpulent male rats compared with lean rats, whereas relaxation in response to the calcium ionophore was similar in the corpulent and lean animals. Aortic rings from corpulent and lean female rats showed no differences in response to acetylcholine or to the calcium ionophore. Removal of endothelium resulted in the loss of relaxant response to acetylcholine and the calcium ionophore. The relaxant responses to sodium nitrite were not significantly different in the corpulent and lean male rats when deendothelialized tissues were examined, but the sensitivity to sodium nitrite was significantly lower in rings from corpulent male rats with intact endothelium. There were no differences in the response to bradykinin between corpulent and lean rats. These findings suggest that there is a specific impairment of endothelium-dependent relaxation in the corpulent male rat that is limited to that mediated by muscarinic receptors. The possibility that endothelium-derived contractile agents are secreted in the vessels of corpulent male rats cannot be excluded.

Animals↗
PubMed1993

Effect of castration on hyperlipidemic, insulin resistant JCR:LA-corpulent rats.

The JCR:LA-cp rat exhibits an obese, insulin resistant, hyperlipidemic syndrome. Obese male rats, only, develop atherosclerosis and ischemic myocardial lesions. The obese males have a greater hyperinsulinemia, but the obese females have a much greater hypertriglyceridemia due to hypersecretion of very low density lipoprotein (VLDL). Obese rats of both sexes were surgically castrated at 6 weeks of age to study the influence of testosterone and estrogen secretion on the sexual dimorphism of metabolism and disease in this strain. Castration had no effect on body weight or food consumption up to 16 weeks of age. Castrated male rats had significantly improved glucose tolerance, but a doubled serum triglyceride concentration. Castrated female rats showed approximately halved triglyceride levels. The distribution of the triglyceride molecular species was altered in the castrated male rats to resemble that of the females in which there was no change with castration. The effects suggest that testosterone may inhibit hepatic triglyceride secretion and promotes insulin insensitivity. Estrogen appears to exacerbate hepatic hypersecretion of VLDL. Castration had no effect on myocardial lesion frequency in 9-month-old rats of either sex. This implies that estrogen does not exert a direct protective effect against cardiovascular disease in this animal model.

Animals↗
PubMed1993

Maxillofacial prosthetics: vital signs.

A maxillofacial prosthetics survey was designed to record the response rate of prosthodontists regarding the frequency of maxillofacial procedures and insurance coverage in 1991. The survey explored variability with respect to membership in professional organizations, region, education, primary activity, and age of the prosthodontist. A total of 342 survey instruments were received from a total of 690 mailed. A total of 18,410 maxillofacial procedures were performed by the survey population. Members of the American Academy of Maxillofacial Prosthetics performed procedures at a significantly higher rate than did the members of the American College of Prosthodontists. A greater procedure rate was observed for prosthodontists in the South Midwest and Southwestern regions; the hospital setting; with 2 plus 1 year additional postgraduate maxillofacial training; and the 45- to 54-year age group. Insurance covered most maxillofacial procedures, but was not uniformly distributed within predictor variables nor between procedures.

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗