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Biomedical subjects

J Stevenson

Publications and source records attributed to J Stevenson.

At least 127 records · Page 7Linked to original sources

Transport of L-lactate by cultured rat brain astrocytes.

Several reports indicate that lactate can serve as an energy substrate for the brain. The rate of oxidation of this substrate by cultured rat brain astrocytes was 3-fold higher than the rate with glucose, suggesting that lactate can serve as an energy source for these cells. Since transport into the astrocytes may play an important role in regulating nutrient use by individuals types of brain cells, we investigated the uptake of L-[U-14C]lactate by primary cultures of rat brain astrocytes. Measurement of the net uptake suggested two carrier-mediated mechanisms and an Eadie-Hofstee type plot of the data supported this conclusion revealing 2 Km values of 0.49 and 11.38 mM and Vmax values of 16.55 and 173.84 nmol/min/mg protein, respectively. The rate of uptake was temperature dependent and was 3-fold higher at pH 6.2 than at 7.4, but was 50% less at pH 8.2. Although the lactate uptake carrier systems in astrocytes appeared to be labile when incubated in phosphate buffered saline for 20 minutes, the uptake process exhibited an accelerative exchange mechanism. In addition, lactate uptake was altered by several metabolic inhibitors and effectors. Potassium cyanide and alpha-cyano-4-hydroxycinnamate inhibited lactate uptake, but mersalyl had little or no effect. Phenylpyruvate, alpha-ketoisocaproate, and 3-hydroxybutyrate at 5 and 10 mM greatly attenuated the rate of lactate uptake. These results suggest that the availability of lactate as an energy source is regulated in part by a biphasic transport system in primary astrocytes.

Animals↗

Multiple binding sites for nicotine receptor antagonists in inhibiting [3H](-)-nicotine binding in rat cortex.

The displacement of [3H](-)-nicotine from its binding site in rat cerebral cortex by a number of antagonists was investigated. [3H](-)-Nicotine appeared to bind to a single site with a dissociation constant (KD) of 5.5 nM; pancuronium, gallamine and trimetaphan displaced [3H](-)-nicotine with inhibition constants (KI) of 57, 99 and 621 microM, respectively, whereas mecamylamine only displaced 50% of nicotine binding in concentration > 1 mM. For hexamethonium and (+)-tubocurarine the displacement of [3H](-)-nicotine binding appeared to involve two sites; the higher affinity site comprising 30% of the total binding for hexamethonium but 76% of the sites for (+)-tubocurarine. In the presence of mecamylamine (100 microM) the displacement of [3H](-)-nicotine binding by (+)-tubocurarine appeared to involve only a single site with an affinity similar to that for the high affinity site in the absence of mecamylamine whereas that for hexamethonium still involved two sites. It is suggested that (+)-tubocurarine may act at both the binding site for [3H](-)-nicotine per se and also at an allosteric site. The failure of mecamylamine to influence the binding of hexamethonium suggests that there may be more than one allosteric site or that hexamethonium may distinguish between subtypes of nicotine receptors in the cortex.

Animals↗

Hand infections: an audit of 160 infections treated in an accident and emergency department.

160 consecutive hand infections presented to an Accident and Emergency department over a four-month period. All but one were treated solely on an out-patient basis. The mean delay to presentation was three days, the mean duration of treatment was six days. Follow-up to complete resolution was achieved in 89% of cases. No patients were treated with parenteral antibiotics. The need for careful assessment, early aggressive surgery, and meticulous attention to the principles of wound care by experienced clinicians is emphasized.

Adult↗

A phase-III study of recombinant interleukin 2 and 5-fluorouracil chemotherapy in patients with metastatic colorectal cancer.

Sixteen patients with metastatic colorectal cancer have been treated with a regimen involving an 120 h continuous infusion of rIL-2, 18 x 10(6) iu m-2 day followed by three injections of 5FU 600 mg m-2 at weekly intervals. Entry criteria included no previous chemotherapy, ambulatory performance status, and a measurable lesion. In most cases side effects were easily manageable and only one patient required transfer to an intensive care unit with the capillary leak syndrome. In three patients persistent hypotension was found to be unrelated to treatment with rIL-2, being caused respectively by a line infection, pulmonary embolus, and bowel perforation. This last proved a fatal complication. Five patients (33%; [95% confidence limits, 11.8%-61.6%]) achieved a partial response, and two non-responders later achieved a partial response when treated with weekly 5FU. This regimen is currently being evaluated in a phase-III randomised controlled trial.

Abdominal Neoplasms↗

Cerebral-palsied children's interactions with siblings--I. Influence of severity of disability, age and birth order.

Sixty-four Greek cerebral-palsied children, aged 2-13, and their siblings were observed in a semi-structured play situation at home. Compared to matched control dyads, disabled children were passive and lacking in assertiveness, while their siblings were correspondingly more directive. Interaction in disabled dyads was predominantly hierarchical in nature with disabled children assuming the role of the younger child regardless of age or birth order. Control dyads were more egalitarian, with members taking turns in initiating the interaction. Maternal intervention was higher in disabled dyads, particularly among younger groups where social skills were poorly developed.

Adolescent↗

Cerebral-palsied children's interactions with siblings--II. Interactional structure.

The interactions between 64 cerebral-palsied children and their siblings were compared to those of matched control dyads. Disabled children displayed pronounced deficits in initiating and directing social interactions. Their siblings, regardless of their age or birth order, took on the leadership role and maintained the positive but controlling stance which was also displayed by mothers of the disabled. Though hierarchical organization allowed the disabled dyads to function effectively, the siblings failed to experience the frequent challenges and the close, reciprocal style of interaction developed by control dyads.

Adolescent↗

Hyperactivity and spelling disability: testing for shared genetic aetiology.

The influence of genetic factors in the comorbidity of spelling disability and hyperactivity was investigated in two samples of 190 and 260 same sex twin pairs. The method of bivariate group heritability was used to estimate the genetic correlation for spelling disability and hyperactivity. A similar though not statistically significant value for the genetic correlation was obtained for the two samples (0.29 and 0.42). It was estimated that approximately 75% of the co-occurrence of these two conditions was due to shared genetic influences.

Adult↗

Diabetic end-stage renal disease among Native Americans.

OBJECTIVE: To examine why ESRD has become a major source of morbidity and mortality for Native Americans with diabetes mellitus. RESEARCH DESIGN AND METHODS: Using data from the Medicare ESRD Program, we examined incidence rates for ESRD among Native Americans for the years 1983-1987. RESULTS: During this period, the annual incidence of total ESRD in Native Americans increased by 18%, from 170.5/million to 200.1/million. The incidence of diabetic ESRD increased by 47%, from 80.6/million to 118.2/million. In 1987, the age-adjusted incidence rate of diabetic ESRD was 6.8 times higher in Native Americans than in whites. CONCLUSIONS: Recommendations for the prevention of diabetic ESRD include early identification of renal disease and improved control of hypertension and blood glucose. The magnitude of diabetic ESRD among Native Americans also underscores the need for primary prevention of non-insulin-dependent diabetes mellitus.

Age Factors↗

Diabetes and associated risk factors among Native Americans.

OBJECTIVES: To estimate the prevalence of diabetes and related risk factors among Native Americans. RESEARCH DESIGN AND METHODS: We used 1988-1989 data from the Behavioral Risk Factor Surveillance System to calculate the overall, age-adjusted prevalence of diabetes, obesity, sedentary life-style, hypertension, and smoking among Native Americans. The SESUDAAN software package was used to derive confidence intervals. RESULTS: The prevalence of diabetes was 11.6% among the 768 Native American Behavioral Risk Factor Surveillance System respondents (95% confidence interval 7.8-15.4) and 4.7% among the 121,986 white respondents (95% confidence interval 4.6-4.8). The age-adjusted prevalence of diabetes was 2.5 times higher among Native Americans than among whites. The prevalence of obesity was higher among Native Americans (34.4; 95% confidence interval 31.7-37.1) than among whites (23.9%; confidence interval 23.7-24.1). The prevalences of sedentary lifestyle (58%), hypertension (16%), and smoking (28%) were similar among both populations. CONCLUSIONS: The Behavioral Risk Factor Surveillance System may prove as a useful tool for surveying Native Americans living on and off reservations for inclusion in national estimates of diabetes prevalences.

Adult↗

Evidence for a genetic etiology in hyperactivity in children.

There has been considerable controversy over the nosology of hyperactivity and attention deficit hyperactivity disorder (ADHD). There have been suggestions that genetic influences may play a role in the origins of individual differences on this dimension or dimensions of behavior and that an understanding of the significance of genetic factors might help to clarify the classification of these disorders. Multiple regression is used to analyze data from a sample of 91 pairs of identical twins and 105 pairs of same sex fraternal twins. The heritability of extreme group membership (h2g = 0.75) was significant for activity rated by the mother. The heritability for one of the measures of attention deficit was also significant (h2g = 0.76). The results are consistent with a significant genetic contribution to individual differences in activity levels and attention abilities.

Adolescent↗

Danazol induces resistance to both insulin and glucagon in young women.

1. Danazol elevates plasma insulin, plasma glucagon and serum low-density lipoprotein concentrations and reduces the serum high-density lipoprotein concentration. 2. Associations between these disturbances were studied in 17 women receiving danazol therapy for endometriosis. Eleven women underwent intravenous glucose tolerance tests with measurement of plasma glucose, insulin, C-peptide and glucagon concentrations and modelling analysis of intravenous glucose tolerance test concentration profiles. Six women underwent glucagon sensitivity tests. Serum concentrations of lipids and lipoproteins were measured in all cases. 3. Danazol reduced the fasting plasma glucose and insulin concentrations, but markedly raised the fasting plasma glucagon concentration. The insulin and C-peptide responses to the intravenous glucose tolerance test were increased twofold and the net decrement in glucagon concentration was increased tenfold. The glucose response to the intravenous glucose tolerance test was unaffected. Insulin sensitivity was reduced by 55%. Both first-phase plasma insulin responsiveness and net first-phase pancreatic insulin secretion were increased; insulin half-life was prolonged. The glucose response to the glucagon sensitivity test was reduced on treatment. The calculated low-density lipoprotein cholesterol level rose by 20%, whereas high-density lipoprotein cholesterol level fell by 47%. None of these changes in serum lipoprotein levels correlated with changes in insulin metabolism. In general, metabolic changes normalized after 3 months. 4. Danazol increases the sensitivity of pancreatic insulin and glucagon secretion to glucose. Danazol-induced insulin and glucagon resistance could be due to receptor down-regulation resulting from hypersecretion of insulin and glucagon.

Adult↗

Fears and fearfulness in children and adolescents: a genetic analysis of twin data.

A sample of 175 same sex dizygotic pairs and 144 monozygotic twin pairs aged between 8:00 and 18:00 completed the Fear Survey Schedule for Children--Revised. The heritabilities were significant for Fear of the Unknown (h2 = 0.46, p less than 0.001), Fear of Injury and Small Animals (h2 = 0.46, p less than 0.001), Fear of Danger (h2 = 0.34, p less than 0.001) and for Total Fear Score (h2 = 0.29, p less than 0.001). Multiple regression was used to estimate the heritability of extreme fearfulness (h2g). For each of the fear factors the values of h2g were of similar magnitude to those of h2 suggesting that there is no evidence of greater genetic influences at more extreme levels of fearfulness.

Adolescent↗

Gender ratios among reading-disabled children and their siblings as a function of parental impairment.

Gender ratios are reported for 374 reading-disabled probands and their 530 siblings included in five independent studies of reading disability. Ratios were tabulated for each study as a function of parental impairment (neither parent affected, mother only affected, father only affected, and both parents affected). Results reveal a small excess of male probands in referred and clinic samples of reading-disabled children, but not in research-identified samples. Gender ratios among siblings of reading-disabled probands are approximately 1:1. In addition, combined results indicate that gender ratios of neither probands nor their siblings vary substantially as a function of parental impairment.

Adult↗