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Biomedical subjects

R Mitchell

Publications and source records attributed to R Mitchell.

At least 271 records · Page 15Linked to original sources

Ethanol and leucine oxidation--III. Leucine oxidation by rat heart in vitro.

The activities of leucine aminotransferase (BCAT) and 2-oxoisocaproate dehydrogenase (OADH) were measured in rat heart in vitro. The effect upon these enzyme activities of both ethanol and acetaldehyde, administered either acutely or chronically, was determined. Enzyme activities were not significantly altered by either acetaldehyde or ethanol when given chronically. Ethanol administered acutely to rats decreased OADH activity but BCAT was unaffected. Acetaldehyde administered acutely did not alter significantly BCAT activity but significantly increased OADH activity.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Pituitary follicular cells produce basic fibroblast growth factor.

Cultured monolayers of bovine pituitary follicular cells, which transport ions, contain high amounts of mitogenic activity for endothelial cells which, on the basis of gene expression analysis, heparin-Sepharose elution profile, bioassay, immunoblotting, radioimmunoassay, and radioreceptor assay, has been identified as basic fibroblast growth factor (bFGF). These data indicate that follicular cells may be a major source of bFGF in the pituitary gland. Considering that bFGF has been proposed to play a role in paracrine regulation of pituitary hormone secretion, the data also suggest that these cells may exert important local regulatory functions.

Animals↗

Prognostic factors for continued or rebleeding and death from gastrointestinal haemorrhage in the elderly.

We analysed 103 episodes of upper gastrointestinal bleeding in 88 elderly patients (age 76 +/- 7.7 years) to determine which of a group of 52 clinical and laboratory variables, measured on admission, best predicted continued or rebleeding, and death in these patients. Variables which related directly to the size of the bleed (blood urea, haemoglobin, pulse rate, systolic blood pressure) were all strongly predictive of both outcomes (P less than 0.001). Of the variables unrelated to the size of the bleed, prolonged prothrombin time and elevated serum creatinine were most strongly predictive of a poor outcome, suggesting that haemostatic dysfunction may be a major contributor to death from upper gastrointestinal haemorrhage in elderly patients. Other variables with strong predictive potential were age (P less than 0.001), the presence of multiple disease states (P less than 0.01), therapy with multiple drugs (P less than 0.01) and acute stroke or obtundation on admission (P less than 0.01). In general terms the size of the bleed was as significant as the premorbid condition of the patient in predicting the outcome. This, together with the fact that half the patients died of hypovolaemia, suggests that death from upper gastrointestinal bleeding in the elderly is not inevitable and that further reduction in mortality from this cause is attainable.

Aged↗

Serological characterisation of a mouse monoclonal anti-P-like antibody.

An IgM mouse monoclonal antibody, LM 147/328, raised against an Escherichia coli immunogen, was found to possess anti-P-like specificity. It is proposed that this antibody recognises an epitope on a Gal beta 1-3GalNAc disaccharide structure (GalNAc = N-acetyl-D-galactosamine). The haemagglutinating activity of this antibody was consistently strong with adult erythrocytes, but gave significantly weak reactions with about 7% of cord erythrocyte samples.

Animals↗

Passive haemagglutination inhibition for quantitation of red cell associated IgG.

Passive haemagglutination inhibition (PHI) was adapted to quantitate red cell associated IgG. Twenty one patients with autoimmune haemolytic anaemia (AIHA) had a raised red cell associated IgG, mean (SD) = 5.783 (6.183) ng/10(6) red blood cell compared with that of 69 subjects with a red cell associated IgG of 0.433 (0.349) ng/10(6) red blood cell. Thirteen of 14 blood donors with a positive direct antiglobulin test (DAGT) had a normal red cell associated IgG. The only blood donor with positive DAGT and raised red cell associated IgG had AIHA. Studies of red cell associated IgG in other groups of patients were also undertaken. The technique is simple, does not require the use of sophisticated equipment, and is suitable as a routine test in hospital laboratories. The results of red cell associated IgG by PHI are reproducible and clinically relevant.

Agammaglobulinemia↗

Pubic osteomyelitis presenting as irritable hip.

Two cases of pubic osteomyelitis presenting as a painful hip are reported. In both cases the diagnosis was delayed by the unusual presentation and by the limited radiological investigation. Pubic osteomyelitis is rare in childhood but should be considered in the differential diagnosis of the 'irritable hip'.

Adolescent↗

Imaging study of the painful heel syndrome.

A total of 45 patients with the painful heel syndrome without evidence of an associated inflammatory arthritis, seven of whom had pain in both heels, were studied using technetium-99 isotope bone scans and lateral and 45 degrees medial oblique radiographs of both feet. Of the 52 painful heels 31 (59.6%) showed increased uptake of tracer at the calcaneum. Patients with scans showing increased uptake tended to have more severe heel pain and responded more frequently to a local hydrocortisone injection. On plain x-ray, 39 of 52 painful heels (75%) and 24 of the 38 opposite nonpainful heels (63%) showed plantar spurs, compared with five of 63 (7.9%) heels in 59 age- and sex-matched controls. No evidence of stress fractures was seen.

Adult↗

Bovine granulosa cells produce basic fibroblast growth factor.

Cultured bovine granulosa cells express the gene encoding basic fibroblast growth factor (bFGF). The bFGF gene is transcribed into 7.0- and 3.7-kilobase mRNA transcripts which are apparently translated into 16,000 mol wt bFGF-like growth factor. The granulosa cell-derived bFGF is bioactive, i.e. it can stimulate the proliferation of capillary endothelial or granulosa cells. This mitogenic effect is prevented by specific neutralizing anti-bFGF antibodies. Our results indicate that bFGF derived from granulosa cells can act as both autocrine and paracrine growth factor, and they further suggest that the factor may be involved in the development of the rich vasculature of the theca interna of the follicle.

Adrenal Cortex↗

Biopotency and site of action of drugs affecting testicular steroidogenesis.

The effect of etomidate (an anaesthetic), epostane (WIN 32729; an inhibitor of ovarian and adrenal steroidogenesis) and cyproterone acetate (an antiandrogen) on testosterone secretion from mouse Leydig cells stimulated with LH (5 i.u./l) was tested. The concentration of drug which inhibited testosterone secretion by 50% was 11.5 +/- 1.1 (S.E.M.) mumol/l for cyproterone acetate, 1.2 +/- 0.2 mumol/l for etomidate and 0.23 +/- 0.03 mumol/l for epostane. The effect of all three drugs on testicular steroidogenesis was completely reversible. Thus testicular cells which had been washed after exposure to a greater than 95% inhibitory dose of drug responded in a similar manner to hormone stimulation as cells similarly washed and which had not been exposed to the drug. The sites of the antisteroidogenic effect of epostane, etomidate and cyproterone acetate were established using a method based on the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of testosterone. It was concluded that etomidate acts at the sequence between LH binding and pregnenolone production, epostane acts at 3 beta-hydroxysteroid dehydrogenase and cyproterone acetate inhibits 3 beta-hydroxysteroid dehydrogenase and C17,20-lyase.

Androgen Antagonists↗

Solubilization of a large molecular weight form of the rat LHRH receptor.

The LHRH receptor has been solubilized from male rat anterior pituitary glands, using the zwitterionic detergent 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate in the presence of a high concentration of sodium chloride. This method gave high yields (up to greater than 70%) of the LHRH-binding site from the membrane preparation. Ligand binding studies using LHRH analogues were carried out to determine dissociation constants for LHRH receptors both in situ in the membrane preparation and for solubilized LHRH receptors. For all the analogues the binding characteristics were similar in both preparations, suggesting that the solubilization procedure left the LHRH receptor undenatured. Gel filtration revealed an apparent molecular weight for the LHRH receptor of 100,000-160,000, with the mean value being approximately twice that found by others using sodium dodecyl sulphate-polyacrylamide gel electrophoretic techniques. The results indicate that the LHRH receptor probably exists in gonadotroph membranes as a large complex of more than one subunit.

Animals↗

Bone density in generalized osteoarthritis.

The densities of trabecular and cortical bone in the radius were measured by computed tomography in 40 women with generalized osteoarthrosis (osteoarthritis, GOA), and the results were compared to normal values obtained from prediction equations. When age, weight and height were considered, no significant differences were observed between patients with GOA and normal controls. But when age only was considered, trabecular bone density in the distal radius was found to be 7% higher than predicted (p less than 0.05). Increased trabecular bone density is unlikely to be an etiopathogenetic factor in GOA although this cannot be completely excluded from our study.

Absorptiometry, Photon↗

The effect of ketoconazole on adrenal and testicular steroidogenesis in vitro.

The effect of the anti-fungal agent, ketoconazole, on cortisol secretion from adrenal cells stimulated with ACTH (1-24, 50 ng/l) and on testosterone secretion from Leydig cells stimulated with LH (5 i.u./l), has been tested. The concentration of drug which inhibited cortisol and testosterone secretion by 50% (ED50) was 3.6 +/- 0.7 mumol/l and 0.61 +/- 0.03 mumol/l, respectively. The effect of ketoconazole on adrenal and testicular steroidogenesis was completely reversible. Thus, adrenal and testicular cells which had been washed after exposure to greater than 95% inhibitory dose of ketoconazole responded in a similar manner to hormone stimulation as cells similarly washed and which had not been exposed to drug. The sites of the anti-steroidogenic effect of ketoconazole have been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells and testosterone by Leydig cells. We conclude that ketoconazole reversibly inhibits the sequence between ACTH/LH binding and pregnenolone production and also inhibits testicular C-17-C-20, lyase activity.

Adrenal Glands↗