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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 577 records · Page 32Linked to original sources

Impotence: treatment by autoinjection of vasoactive drugs.

One hundred and twenty five men with psychogenic or organic impotence used autoinjection of the penile corpora cavernosa with either papaverine or papaverine and phentolamine for a mean period of 10.5 months (range 1-24 months) to achieve penile erection for sexual intercourse. Prolonged (over four hours) painless erection resulted from 34 of the 3513 self administered injections. This seems to be a highly effective approach to treating impotence irrespective of the aetiology.

Adult↗

Provision of the immunoglobulin heavy chain enhancer downstream of a test gene is sufficient to confer lymphoid-specific expression in transgenic mice.

To test whether the immunoglobulin heavy chain enhancer is sufficient to direct lymphoid specific gene expression in vivo, we have incorporated into the mouse germ line a test gene (chloramphenicol-acetyl transferase) whose transcription is potentiated by the enhancer. Analysis of transgenic mice bearing single-copy integrations of the injected DNA indicates that provision of the enhancer downstream of the test gene (beyond the polyadenylation site) is sufficient to direct lymphoid-specific expression. The tissue specificity is considerable as judged by the fact that transgene expression is at least one thousandfold higher in spleen than in liver. Within the lymphoid family, expression of the transgene is much higher in surface IgM+ spleen cells than in thymocytes high in Thy-1 expression, suggesting that the enhancer preferentially directs expression to cells of the B lineage.

Acetyltransferases↗

Carbohydrate residues in non-malignant prostatic epithelium as revealed by lectins.

Non-neoplastic prostatic epithelium from 39 patients obtained at transurethral resection for outflow tract obstruction and 5 normal prostates from men under 35 years of age obtained at postmortem were formalin-fixed and paraffin-embedded. The distribution of 8 lectin receptors were studied using a peroxidase anti-peroxidase method and an avidin-biotin method. Con A, WGA, and PNA bound to most epithelial cells. Con A and WGA also showed major stromal binding. Approximately 5% to 10% of cells bound UEA1, GS1, DBA, SBA and BPA. No major differences in lectin receptor expression were observed between normal and hyperplastic epithelium with either of the immunohistochemical techniques except that hyperplastic cells stained more strongly than normal epithelium.

Adult↗

Massive insulin resistance apparently due to rapid clearance of circulating insulin.

A 23-year-old insulin-dependent diabetic woman demonstrated increasing resistance to insulin administered by all routes, eventually requiring up to 20,000 units per day intravenously. Therapeutic trials of human and chemically modified insulin and of aprotinin were unsuccessful. Inappropriately low plasma free insulin levels (less than 60 mU/liter) during administration of extremely high insulin dosages (300 to 10,000 units per day) suggested that resistance was caused by rapid clearance of circulating insulin. There were several short periods of normal insulin sensitivity with hyperinsulinemia (more than 300 mU/liter) persisting long after intravenous insulin withdrawal, suggesting reentry to the circulation of intact, previously sequestered insulin. For four years, she has been treated with ambulatory continuous intravenous insulin infusion, which has been complicated by septicemia and central venous thrombosis. Her condition remains poorly controlled with documented intravenous insulin requirements of 2 to 20 units/hour.

Adult↗

A protocol and guide for the in vitro rat hepatocyte DNA-repair assay.

The in vitro rat-hepatocyte DNA-repair assay is a valuable tool in assessing the genotoxic activity of chemical agents. An advantage of the assay is that the target cells themselves are metabolically competent, so that the patterns of metabolic activation and detoxification closely reflect those in the whole animal. This article provides a typical procedure and guidelines for conducting the rat in vitro hepatocyte DNA-repair assay.

Animals↗

A protocol and guide for the in vivo rat hepatocyte DNA-repair assay.

The in vivo rat hepatocyte DNA-repair assay is a valuable tool in assessing the genotoxic activity of chemical agents. An advantage of the system is that it reflects the complex patterns of uptake, distribution, metabolism, detoxification and excretion that actually occur in the whole animal. This article provides a typical procedure and guidelines for conducting the rat in vivo hepatocyte DNA-repair assay.

Animals↗

The transfer of radiolabelled n-6 essential fatty acids by the mammary system of the tree-shrew (Tupia tana).

The fatty acid content of tree-shrew milk has been determined from analysis of the stomach content of infants immediately after suckling. Comparison of the n-6 fatty acid composition of the stomach contents, liver and brain demonstrate a striking increment in the ratio of arachidonic to linoleic acid. Feeding radioactively labelled linoleic acid to the mother 24 hr prior to suckling showed that 12-20% was transferred to the milk. Evidence from the appearance of the radioactivity administered as linoleic acid into arachidonic acid indicates that this species is able to desaturate linoleic acid.

Animals↗

Retinyl acetate effects on the life span and the incidence of cryptogenic neoplasms in C3H mice.

The effect of feeding 0.02% retinyl acetate on the development of cryptogenic neoplasms and the life span of C3H/HeJ (+) mice of both sexes was studied. The survival at 105 weeks was 58% in untreated males and 28% in untreated females vs. 39% in treated males and 14% in treated females. The average weight in treated groups was also 10-15% lower. The incidence (percent) of neoplasm-bearing animals and total neoplasms was 87% and 57, respectively, in female controls vs. 93% and 55 in treated females. In male controls, these values were 57% and 39 compared with 50% and 38 in treated males. In treated animals, there was no reduction in the most common neoplasms, that is, neoplasms of the mammary gland and liver. The numbers of ovarian neoplasms and lung adenomas were slightly lower. Therefore, retinyl acetate exerted, at best, only a slight inhibitory effect on development of some types of cryptogenic neoplasms in mice.

Animals↗

The effect of a long-acting somatostatin analogue (SMS 201-995) on intermediary metabolism and gut hormones after a test meal in normal subjects.

SMS 201-995 is an octapeptide analogue of somatostatin. The effect of a single subcutaneous (s.c.) injection of 50 micrograms SMS 201-995 on post-prandial intermediary metabolism was investigated in normal subjects. In spite of a long-lasting post-prandial suppression of insulin secretion, there were no significant changes in the plasma concentration of alanine, glycerol, 3-OH-butyrate or lactate. However, SMS 201-995 impairs carbohydrate tolerance, probably due to inhibition of insulin secretion. Basal and post-prandial plasma concentrations of the gut regulatory peptides pancreatic glucagon, motilin, pancreatic polypeptide, gastric inhibitory polypeptide, enteroglucagon, gastrin and peptide YY were suppressed up to 5 hours after subcutaneous administration of a single dose of SMS 201-995.

3-Hydroxybutyric Acid↗

Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995).

Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201-995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly.

Acromegaly↗

Adrenocortical responsiveness in neonates weaned from the ventilator with dexamethasone.

Adrenocortical responsiveness was assessed in eight very low birthweight neonates who had bronchopulmonary dysplasia and had been weaned from mechanical ventilation using dexamethasone. Three of the eight infants did not respond to ACTH stimulation during the first week after cessation of dexamethasone, but all three responded normally when retested at least 1 month later. The present authors have thus demonstrated that some infants have at least temporary adrenocortical unresponsiveness after prolonged courses of glucocorticoid therapy, and suggest that adrenocortical function should be assessed in all infants who are weaned from mechanical ventilation using dexamethasone.

Adrenal Cortex↗