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Biomedical subjects

B Bell

Publications and source records attributed to B Bell.

At least 73 records · Page 4Linked to original sources

GAL4 fusion vectors for expression in yeast or mammalian cells.

We describe two sets of vectors, one for yeast (pY1, pY2 and pY3) and one for mammalian cells (pM1, pM2, and pM3), that simplify the production of fusion proteins containing the DNA-binding domain of GAL4. This protein fragment, consisting of GAL4 amino acid (aa) residues 1-147, binds to a specific 17-bp nucleotide sequence, but is incapable of activating transcription unless fused to a protein that can contribute an activating function. Genetic strategies exploiting this property of GAL4 (aa 1-147) have been developed to characterize transcription factor functional domains, protein-protein interactions, and site-specific proteolysis. The vectors we describe allow fusion to the C terminus of GAL4 (aa 1-147) in any reading frame, and thus facilitate these experimental strategies.

Amino Acid Sequence↗

Alcohol affects rat testicular interstitial fluid volume and testicular secretion of testosterone and beta-endorphin.

The effects of alcohol on testicular interstitial fluid (TIF) volume and the secretion of testosterone and beta-endorphin (beta E) into this important testicular compartment were assessed in the rat. Alcohol time- and dose-response curves were constructed for changes in TIF volume and the bioactive concentrations of testosterone and immunoreactive beta E (i-beta E). Alcohol (3 g/kg) decreased TIF volumes and increased TIF i-beta E secretion 0.5 to 6 hr after injection and decreased TIF testosterone 1 to 6 hr after injection. These effects were dose-related at 2 hr postinjection. The possible role of alcohol-induced reductions in serum luteinizing hormone and testosterone levels in mediating the effects of alcohol on TIF volume was also examined. We found that pretreating rats with human chorionic gonadotropin, which reversed alcohol-induced suppression in levels of serum gonadotropins and testosterone, failed to reverse the effects of alcohol on TIF volume and the secretion of testosterone and i-beta E. These results indicate that alcohol decreases TIF volume, inhibits TIF testosterone secretion and stimulates TIF i-beta E secretion and, furthermore, suggest that these effects are not indirectly mediated by decreased levels of gonadotropins or testosterone, but by direct effects of alcohol on gonadal function. The strong inverse correlation between TIF i-beta E and testosterone secretion after alcohol administration and previous evidence that testicular opioids inhibit the biosynthesis of testosterone suggest that alcohol may act through testicular beta E to suppress the synthesis and release of testosterone in the testes.

Animals↗

Phase I study of a 120-hour continuous intravenous infusion of 5-fluorouracil in pediatric patients with recurrent solid tumors: a Pediatric Oncology Group study.

To determine the maximum tolerated dose of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients, we performed a phase I study using a starting dosage of 900 mg/m2/day. The maximum tolerated dosage (MTD) was 1,100 mg/m2/day. At this dosage level 40% of courses were complicated by grade 3 mucositis. Three additional patients were treated at the dosage level of 1,000 mg/m2/day after the MTD was determined. We recommend the dosage level of 1,000 mg/m2/day for phase II studies of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients.

Adolescent↗

Phase I evaluation of diaziquone in childhood cancer. A Pediatric Oncology Group study.

We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly X 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M2/week X 4 for patients with a solid tumor, and is 30 mg/M2/week X 4 for children with acute leukemia.

Adolescent↗

Response to nondepolarizing muscle relaxants in children with tumours.

The rate of onset of action of d-tubocurarine (64 patients) or alcuronium (36 patients) was studied electromyographically in 100 children who had abdominal, bone or cerebral tumours. It was found that there was a significantly delayed onset (over three times longer than controls) or additional doses were required in patients with malignant liver, renal and bone tumours who received d-tubocurarine. The onset of alcuronium blockade was also prolonged but to a lesser extent. When tumours with an abnormal prolongation of onset of relaxation were successfully treated by chemotherapy and/or surgery, the response reverted to normal. Children with benign tumours or masses had normal responses. In contrast, neuroblastomas were associated with little prolongation of onset. Cerebral tumours showed a variable response, with the observed changes being unreliable indicators of degree of malignancy.

Adolescent↗

Suxamethonium--electromyographic studies in children.

Suxamethonium was administered to 225 children aged from one to sixteen years, in doses varying from 0.1 to 0.5 mg/kg. Dose responses were determined. ED95 was 445 micrograms/kg in one to four year olds, 454 micrograms/kg in the five to ten years group and 270 micrograms/kg in eleven to fifteen year olds (P less than 0.05). There is a wider variability in patient responses to 0.1 and 0.2 mg/kg than to the higher doses. Sixty-two children in the three age groups were given suxamethonium 1 mg/kg. The time from injection to maximum block and to 50% recovery increased with increasing age (P less than 0.05).

Adolescent↗

Does suxamethonium influence the subsequent dose requirements of alcuronium and its reversibility in children?

Suxamethonium is often used for intubation prior to the use of a nondepolarizing muscle relaxant. This study was performed to determine whether suxamethonium altered the dose of alcuronium required to produce neuromuscular block. The findings were that suxamethonium 1.0 mg/kg did not alter the depth, duration or reversibility of block if given before alcuronium 0.3 mg/kg. Reversal with neostigmine was more rapid following 50 micrograms/kg than after 25 micrograms/kg. If recovery from neuromuscular block was greater than 25 per cent, the lower dose produced satisfactory reversal, whether or not suxamethonium had been given previously.

Adolescent↗

Randomized, controlled trial of clonidine for smoking cessation in a primary care setting.

Clonidine hydrochloride has been reported to reduce tobacco withdrawal symptoms and facilitate smoking cessation. We enrolled 185 subjects, 92 receiving clonidine and 93 receiving placebo, in a randomized, double-blind study of clonidine for smoking cessation in a primary care setting. Clonidine had no demonstrable effect on withdrawal (8 of 11 measures favoring placebo). At 4 weeks, 17 (18%) subjects receiving clonidine had quit compared with 13 (14%) receiving placebo (chi 2 = 0.7; 90% confidence interval of benefit from clonidine, -4% to 13%). At 4 weeks, the mean number of cigarettes smoked was 17.7 for those receiving clonidine and 17.5 for those receiving placebo (t = 0.1; 90% confidence interval of benefit from clonidine, -4.1 to 3.7 cigarettes per day). These results provide little support for a beneficial effect of clonidine on tobacco withdrawal symptoms, quitting, or smoking reduction in a primary care setting.

Adolescent↗

Small cell carcinoma of the pleura.

Extrapulmonary small cell carcinoma is uncommon. Small cell carcinoma of pleural primary origin has not, based on a literature review of the past three decades, been reported. We have reported a case of small cell carcinoma of the pleura, discussed its management and significance, and briefly reviewed the pertinent literature.

Aged↗

Long term renal prognosis of Henoch-Schönlein purpura in an unselected childhood population.

All 270 patients presenting with Henoch-Schönlein Purpura over a 13-year period from a total childhood population of 155,000 were studied. This is an incidence of 13.5/100,000 children per year. Fifty-five (20%) were found to have initial evidence of renal involvement, and were re-examined at a mean of 8.3 years later. The 37 with isolated haematuria or haematuria with mild proteinuria (67%) recovered completely. Eighteen (33%) had nephritic or combined nephritic/nephrotic features, of these one died in the acute phase of the illness, only three others have persistent urinary abnormalities but have no biochemical evidence of renal impairment and only minor histological changes. The overall prognosis in this unselected population is therefore good with a mortality less than 1% overall and low long term morbidity of 1.1%. This study indicates a more optimistic outcome in this condition than the majority of published estimates based on more selected groups of patients.

Child↗