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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,477 records · Page 82Linked to original sources

Treatment of renal bone disease with 1 alpha-hydroxylated derivatives of vitamin D3. Clinical, biochemical, radiographic and histological responses.

Forty patients with severe bone disease and chronic renal failure were treated with 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for 7--49 months (total = 738 patient months). There were symptomatic, biochemical and radiographic improvements in the majority of patients (greater than 70 per cent). Paired bone biopsies, taken before and during treatment in 26 patients, showed no change in bone matrix area, whereas matrix area decreased in a control group of 26 patients over the same period. There were small but consistent decreases in bone marrow fibrosis and in bone cell (osteoblast and osteoclast) counts in treated patients but not in controls. However, the proportion of patients who showed histological 'cure', in the sense of complete reversal of marrow fibrosis or excess osteoid was no greater in the treated than in the control group...

Adolescent↗

Diurnal intraocular pressure in juvenile open-angle glaucoma.

Outpatient diurnal intraocular pressures were obtained on 10 patients with juvenile open-angle glaucoma at approximately 6 hour intervals. There were 8 males and 2 females with an age range of 19 to 38 years. All glaucomatous medications were stopped 24 hours before recording the tensions. The peak intraocular pressure was recorded at the 6 PM interval in 6 of the 10 patients. Three patients recorded their highest pressures at the 12 AM (midnight) interval. Extraordinarily wide angles were observed in all cases and myopia was a common refractive error. Although the family history was not known in 3 patients, there was a positive family history of glaucoma in 7 of the 10 patients, which suggests an autosomal dominant mode of inheritance.

Adult↗

Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man?

Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.

Adult↗

Cross-linking of lipid bilayers by central nervous system myelin basic protein: aggregation of free and vesicle-bound protein.

Central nervous system myelin basic protein binds to the zwitterionic lipid, egg diacylphosphatidylcholine, over a wide range of pH and ionic strength. Lipid vesicles containing the protein have been observed to increase in size and to aggregate. The size increase is most marked at very low ionic strengths whereas aggregation is evident at ionic strengths from 0.001 to 0.35. The pH and ionic-strength dependence of this aggregation closely follows that of the self-association of the protein, suggesting that vesicle association is mediated by binding between polypeptides attached to different vesicles. Basic protein is monomeric at low pH but above pH 6 self-associates yielding primarily small oligomers (probably dimers) and minor amounts of higher species. It is envisaged that each protein molecule possesses two distinct binding sites, one capable of association with lipid bilayers and the second with another protein molecule. Basic protein is found predominantly on the intracellular surface of the myelin membrane. Given the ability of the protein to act as a bridge between lipid bilayer vesicles in vitro it is proposed that it may perform a similar function in vivo, serving to cross-link the inner surfaces of the oligodendroglial cell membrane. This protein function could lead to formation of the long cellular processes which encircle the nerve cell axon and could assist in stabilizing the highly ordered myelin structure which results.

Animals↗

Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.

Bone Development↗

Autotransfusion of blood contaminated by intestinal contents.

In a series of 183 emergency operations in which intraoperative autotransfusion was used, 14 patients received blood contaminated by intestinal contents. Six of the 14 patients died early in the postoperative period, four of whom had received more than 16 liters of blood. Only two of the eight survivors had received comparable amounts of blood (13 and 17.5 liters). All eight received antibiotics upon admission; four had positive blood cultures within 24 hours of operation. Complications included acute tubular necrosis in three patients and bowel obstruction with intra-abdominal abscess in another. One of the patients with acute tubular necrosis died six weeks later; all others recovered. We believe this procedure may be life-saving in some cases.

Blood Transfusion, Autologous↗

Features of children taken to juvenile court for failure to attend school.

The social reports on 84 children taken to court for failure to attend school were studied. Independent raters were able to assess reliably the presence and absence of a variety of variables concerned with the individual's behaviour, school, family, and involvement with social work agencies. In 68 instances teacher's questionnaires measuring psychiatric disturbance had been completed. There was no evidence that truancy in these circumstances is a homogenous condition. At least 3 independent sets of features appear to be involved in most cases. One involves antisocial and educational problems ('clinical truancy'), a second is concerned with adverse social factors and parental complicity ('school withdrawal'), and a third set includes a tendency to social isolation ('school refusal'). There was no evidence that individuals tend to exhibit one of these features to the exclusion of the others.

Absenteeism↗

Extraction and fingerprint analysis of simian virus 40 large and small T-antigens.

A study of simian virus 40 (SV40) T-antigens isolated from productively infected CV1 cells using a variety of different extraction procedures showed that under some conditions the highest molecular weight form of T-Ag (large-T) isolated comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with large-T from SV40-transformed H65-90B cells. Other faster-migrating forms of large-T are probably generated during the extraction procedure by a protease which is active at low pH, and such forms are probably experimental artifacts. After extraction under conditions which minimize proteolytic degradation of large-T, a further form of T-antigen was isolated; this has an apparent molecular weight in the range 15,000 to 20,000 and is referred to as small-t. Fingerprint analysis of [35S]methionine-labeled SV40 proteins showed that small-t has 10 to 12 methionine peptides whereas large-T has 15 to 18 methionine peptides. All but two of the methionine tryptic peptides present in small-t are also present in large-T. The fingerprint data also showed that T-antigens have no peptides in common with SV40 VP1. Experiments using reagents which inhibit posttranslational cleavage of encephalomyocarditis virus polyproteins showed that these reagents do not affect the synthesis of small-t and suggest that it is not made by proteolytic cleavage of large-T in vivo. An alternative model, which proposes that large-T and small-t are synthesized independently, is discussed in terms of the fingerprint data and the number of methionine tryptic peptides predicted from the primary sequence of SV40 DNA.

Antigens, Neoplasm↗