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Biomedical subjects

R C Bell

Publications and source records attributed to R C Bell.

At least 37 records · Page 2Linked to original sources

Consequences of high dietary fructose in the islet-transplanted rat with suboptimal beta-cell mass.

Fructose (FR) feeding in rats provides a model of dietary-induced insulin resistance that has been used to examine interactions among the cluster of metabolic disorders including insulin resistance, hyperinsulinemia, hypertension, and dyslipidemia known as Syndrome X. In animals with reduced beta-cell mass, however, insulin resistance may not have similar associated disorders. Therefore this study examined the consequences of FR feeding in rats with a reduced beta-cell mass. Formerly diabetic islet-transplanted (TX) or shamoperated (SHAM) male Wistar Furth rats were fed a purified control (CNTL) diet or a diet containing either 40 or 70% (wt/wt) FR for 3-5 wk. FR feeding in SHAM animals resulted in elevated triglyceride levels but did not affect fed or fasting glucose and insulin concentrations, blood pressure, glucose tolerance, and the acute insulin response to a glucose bolus compared with CNTL-fed animals. Among TX animals, hypertriglyceridemia and fasting hyperglycemia were observed only in those fed FR. Thus the effects of diet-induced insulin resistance are limited to dyslipidemia, if insulin secretory capacity is adequate, but are detrimental to both glucose and lipid metabolism in combination with a reduced beta-cell mass.

Animals↗

Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic islet-transplanted streptozotocin-diabetic rats.

To study the long-term effects of exposure to maternal hyperglycemia and insulin deficiency in utero, we used the syngeneic islet transplanted streptozotocin-diabetic rat model of diabetes in pregnancy and examined insulin secretion and action in 6-month-old offspring. Female rats were rendered diabetic with streptozotocin and then transplanted with 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in either glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animals. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x 100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared to that in the control. There were no differences in insulin sensitivity between male and female animals. In summary, animals displaying maternal insulin deficiency have offspring who are insulin resistant without any evidence of iv glucose intolerance or diminished insulin secretion.

Animals↗

Accuracy and reliability of total body electrical conductivity (TOBEC) for determining body composition of rats in experimental studies.

Total body electrical conductivity (TOBEC) has been promoted as a noninvasive method to estimate body composition in small mammals. Validation of this method has primarily been under normative conditions and has generally been inadequate. This article reports on the reliability and accuracy of TOBEC methodology to assess gradual, physiologically induced changes in body composition in rats under different experimental conditions. Reliability of the index of electrical conductivity (EM number) was assessed by analyzing components of variance. Accuracy was assessed by comparing EM number to actual lean body mass (LBM, from carcass analysis), across different experimental conditions, within a particular experimental condition, and over time for a given set of animals. Reliable measurements were obtained by strictly adhering to a standard protocol. TOBEC was inaccurate across experimental conditions, within experimental conditions, and within a single experimental condition during the course of an experiment. This inaccuracy apparently stemmed from the lack of a direct relationship between EM number and LBM; EM number was more strongly correlated with body weight than with LBM. At the present time, TOBEC cannot be used in place of carcass analysis to accurately predict the body composition of rats during or following the administration of a variety of experimental conditions.

Adipose Tissue↗

Latent trait modelling of symptoms of schizophrenia.

Latent trait models were fitted to data for 149 schizophrenic or schizophreniform inpatients rated on the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) using the Rasch Extended Logistic Model. It was found that a reduction in the numbers of rating categories, from six to three or four led to consistencies in response while deletion of several items led to consistent scales of symptoms that accorded with an item response characterization. Behaviours included in the final scales varied in the numbers of categories, and in the range of symptom level covered by a category. Relationships between scores representing symptoms were found to be modelled better by a factor structure that included a third overlapping 'cognitive' factor in addition to the now traditional positive and negative factors, than by the original positive and negative factors alone.

Adult↗

Long-term intake of a low-casein diet is associated with higher relative NK cell cytotoxic activity in F344 rats.

Earlier studies in our laboratory showed that animals exposed to aflatoxin B1 (AFB1) develop fewer gamma-glutamyl transpeptidase-positive preneoplastic foci and tumors when fed 6% dietary casein than when fed 22% casein during promotion; mechanisms underlying this effect have not been elucidated. We examined natural killer (NK) cell activity, mitogenic responses, and lymphocyte surface antigen profiles in male Fischer 344 rats dosed with AFB1 or dosing vehicle alone and then fed 6% or 22% casein isocaloric diets for one year. Mean body weights and food intake did not differ significantly among the groups during the study. NK cells purified from peripheral blood of rats fed 6% casein mediated higher specific lysis (p < 0.0001) against YAC-1 target cells than cells obtained from animals fed 22% casein. Mitogenic responses of splenic lymphocytes to concanavalin A and lymphocyte subpopulations, identified by flow cytometry, did not differ significantly among dietary groups. Hepatic tumors were detected in 27% of the 22% casein AFB1-treated group and in 6% of animals in the 6% casein AFB1-treated group. The association between long-term intake of a 6% casein diet and higher relative NK cell cytotoxic activity suggests a potentially important mechanism that may help protect against the development of hepatocellular tumors. Further study of this mechanism as a causal factor in limiting tumor development is required.

Aflatoxin B1↗

Gender differences in the metabolic response to graded numbers of transplanted islets of Langerhans.

Gender differences after treatment with streptozotocin (STZ) have been previously reported; however, differences in the glucose response to islet transplantation in STZ-induced diabetes in male and female rats after islet transplantation have not been examined. Male and female Wistar-Furth rats were made diabetic using STZ (55 mg/kg BW) and then given an intraportal islet transplant. Control animals received sham injections and sham transplant surgery; diabetic animals received STZ and sham surgery. In male animals, islet grafts contained 0 (diabetic), 250, 500, 1000, 1500, 2000, and 3000 islets; in female rats, grafts were made up of 0, 500 700, 750, 1000, or 2500 islets. STZ treatment had more dramatic effects on male than female rats. During the diabetic phase, body weights of male rats were significantly reduced compared to those of control male animals; this was not observed among females. Although all STZ-treated animals were hyperglycemic, plasma glucose levels in male diabetic rats were significantly higher than those in females during this phase (29.8 +/- 2.1 vs. 24.6 +/- 0.6 mM). After islet transplantation, body weight gain was positively associated with the number of islets transplanted in male rats (r2 = 0.59; P < 0.01), but not in females (r2 = 0.09; P > 0.8). In both male and female rats, animals that received 1000 islets or more were generally normoglycemic by 3 weeks posttransplant (males, 10.8 +/- 2.2 mM; females, 7.1 +/- 0.2 mM). Approximately 60% of male and female animals that received 500 islets achieved a reduction in plasma glucose levels. Mean plasma glucose levels were 17.2 +/- 2.3 in the females and 22.6 +/- 1.0 mM in males. However, a significantly larger proportion of female 500-islet animals (6 of 16) achieved a plasma glucose level of 9.5 mM or less compared with males receiving 500 islets (2 of 30). Multivariate regression analysis suggests that sex and islet number interact to affect glycemic normalization after islet transplantation. Gender differences appear to influence body weight and plasma glucose responses to islet transplantation. This finding may have particular relevance when a marginal number of functional islets are available.

Animals↗

The effects of D-fenfluramine on the development of aflatoxin-B1 induced GGT+ hepatic foci in F344 rats.

The role of total caloric intake and attained body weight in the carcinogenic process in rodents is controversial. In the present study we examined the development of hepatic pre-neoplastic foci in rats treated with aflatoxin-B1 (AFB) and given the drug D-fenfluramine (FEN). Ingestion of this drug leads to a reduction in body weight by increasing the thermogenic response to a meal and by transiently reducing food intake. Young male rats were dosed with AFB or vehicle alone and were then assigned to receive control diet (NO FEN) or control diet + FEN (FEN; 0.15 g/kg diet) for 12-14 weeks. Body weight gain and food intake were reduced among animals given FEN; brown adipose tissue weight (% body weight) was elevated in these groups. Indices of protein status, and concentrations of T3, T4 and insulin did not differ among the groups. All animals given FEN developed GGT+ hepatic foci. The number and volume fraction of foci were significantly larger in FEN relative to NO FEN animals. The mean diameter of foci was slightly enhanced among FEN animals. These results suggest that FEN promotes the development of AFB-induced hepatocellular foci, despite reduced food intake and lower body weight. Since FEN is widely used as a weight loss aid, these findings deserve further study.

Adipose Tissue↗

Pathologic changes induced by phospholipase A2 isolated from the venom of Collett's snake, Pseudechis colletti: a light and electron microscopic study.

Pseudechis colletti is an Australian elapid snake with a range limited to central Queensland, Australia. The venom of this snake, as well as that of several other Australian elapids, has been shown to contain a phospholipase A2 (PLA2) which can cause a marked myoglobinuria in mice. Few studies have described the histopathologic and ultrastructural changes that result from myotoxic PLA2-induced damage. Our investigation demonstrated that the isolated PLA2 induced myodegeneration and necrosis in myocardium in a dose-related manner, with subsequent myoglobinuria and myoglobinuric nephropathy.

Animals↗

Prediction of employability in schizophrenic patients.

This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview-based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements.

Activities of Daily Living↗

Relative usefulness of the WMS and WMS-R: a comment on D'Elia et al. (1989)

In a previous commentary, D'Elia and colleagues reflected on the relative adequacy of normative data for the original Wechsler Memory Scale (WMS) and the Wechsler Memory Scale-Revised (WMS-R). They concluded that, for some age groups, the original version of the test is preferred. We discuss further the crux of the D'Elia and colleagues criticism of the WMS-R, namely the issue of interpolation in tables of normative data. We also consider two additional criteria: the sampling techniques used to obtain the normative samples, and the respective standard errors of measurement and scaling properties of scores on the two tests. We conclude that on each of these criteria the WMS-R is preferable.

Adolescent↗

The structure of personality disorders in DSM-III.

In DSM-III it is proposed that there are 11 personality disorders (PDs) that fall into 3 superordinate clusters: cluster A, labelled the odd or eccentric; cluster B, labelled the emotional, dramatic or erratic; and cluster C, described as the anxious or fearful. To check this proposal, data were obtained from a sample of 112 state hospital psychiatric inpatients via the Structured Interview for DSM-III Personality (SIDP). Various statistical techniques were applied to the data, ranging from the least constrained method of multidimensional scaling to the most constrained and statistically rigorous approach of confirmatory factor analysis. In the latter approach, the models suggested by the various statistical approaches were contrasted directly. A 3-cluster solution was accepted as the best representation of the data, although PD membership of the 3 clusters varied in some ways from those suggested by DSM-III. An exploratory correlation analysis showed that many of the items were more strongly correlated with PDs other than the ones specified by DSM-III, but generally items clustered within the 3 superordinate clusters. This issue deserves further investigation.

Adult↗

A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery.

Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision.

Adult↗

Lethal potency and fractionation of Duvernoy's secretion from the brown tree snake, Boiga irregularis.

The liquid secretion contained only 15% protein and had relatively low proteolytic activity. The reconstituted crude secretion had a murine i.p. LD50 of 10.33 mg/kg and was not hemorrhagic in doses up to 200 micrograms. Fast Protein Liquid Chromatographic (FPLC) cation exchange analysis of reconstituted crude secretion resulted in resolution of 16 peaks. Lethal activity was identified in three peaks. The major lethal fraction was 12.5% of the secretion protein and had a murine i.p. LD50 of 7.3 mg/kg. A pooled fraction containing two lethal peaks which comprised 9.4% of secretion protein had moderate proteolytic activity and produced myoglobinuria in mice. The fraction had an approximate murine i.p. LD50 of 3.7 mg/kg. Microscopic examination of muscle tissue from mice succumbing to this fraction revealed multifocal myofiber degeneration and necrosis. SDS-PAGE indicated that the major lethal fraction contained three proteins with mol. wts of 12,500, 18,000 and 52,000 and the myotoxic fraction contained two proteins with mol. wts of 14,500 and 17,000. While B. irregularis Duvernoy's secretion has a low lethal index, it does contain a myotoxic fraction with moderate lethal potency. These observations and recent data describing clinical envenomation of several infant patients suggest that large specimens may pose a hazard to infants and small children.

Animals↗

Thermogenesis, low-protein diets, and decreased development of AFB1-induced preneoplastic foci in rat liver.

The development of hepatocellular, putatively preneoplastic, gamma-glutamyl transpeptidase positive (GGT+) foci and tumors induced by aflatoxin B1 (AFB1) has been shown to be reduced in male F344 rats fed a diet containing 6% protein (as casein). This reduction occurs despite increased energy intake, when compared with animals fed a diet containing 22% protein. Among its many effects, low protein intake is known to increase the proportion of energy intake expended in the form of heat (thermogenesis); thus, this investigation examined the association between the development of GGT+ foci and alterations in indices of thermogenesis induced by feeding varying levels of dietary protein. Five days following the completion of AFB1 dosing, animals were assigned to groups fed 4%, 8%, 12%, 16%, or 22% dietary protein for 6 weeks. Foci development (% liver volume occupied) was markedly reduced in animals fed the low-protein diet (4%, 8%), yet calorie consumption per 100 g body wt was greater. A modest negative linear trend was observed in oxygen consumption with increasing levels of dietary protein intake. Urinary norepinephrine levels were elevated in the groups fed 4% and 8% protein; urinary dopamine and norepinephrine turnover rates in brown adipose tissue were highest in animals fed 4% protein. These results suggest that GGT+ foci development occurs when a "critical level" (approx 12%) of dietary protein intake is reached. Inhibition of foci development at lower levels of protein intake is associated with several indicators of increased thermogenesis.

Aflatoxin B1↗

Radiographic findings in a group of elderly patients at a Canadian dental school.

The panoramic and intraoral radiographs of 154 elderly dental patients aged 65 years and older were assessed at the College of Dentistry, University of Saskatchewan, Saskatoon. Thirty-seven per cent of the patients were completely edentulous, and 61% were partially edentulous. In the dentate group, 87% had evidence of at least one carious tooth, and all had radiographic evidence of alveolar bone loss. The incidence of periapical inflammatory lesions and root remnants was relatively high.

Aged↗

Decision for surgical management of perforation following endoscopic sphincterotomy.

Duodenal perforation resulting from endoscopic sphincterotomy (ES) is a serious complication with a high mortality. Diagnosis is often problematic and the optimum treatment is controversial. Eight proven perforations occurred following 441 ES at University of Colorado Hospital, a rate of 1.8 per cent. Physical and laboratory findings were of little diagnostic value, whereas plain abdominal radiographs showed evidence of perforation in 86 per cent. All patients were operated on promptly after diagnosis of perforation. Delay in diagnosis of perforation beyond 24 hours in six patients was associated with a high morbidity and two deaths. Analysis of published series confirmed that delay in diagnosis and delay in operation after perforation were associated with a higher mortality rate than early diagnosis with or without operation. We recommend operative intervention in all patients with clinical evidence of perforation following ES.

Adult↗