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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,441 records · Page 80Linked to original sources
PubMed1980

An evaluation of 1 alpha-hydroxy-and 1,25-dihydroxyvitamin D3 in the treatment of renal bone disease.

40 patients with bone disease due to chronic renal failure have been treated with 1 alpha-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for a total of 750 patient-months. Both compounds were very effective in relieving bone pain and muscle weakness, and in reversing the radiographic and biochemical indices of disturbed skeletal metabolism. Their effects as judged from bone biopsies were, however, less complete, and histological improvement occurred only in a few patients. Patients with the combination of osteitis fibrosa and osteomalacia responded better than patients with either abnormality alone. Factors of importance in adversely influencing the outcome of treatment included a high pre-treatment level of calcium or immunoreactive parathyroid hormone, and a failure to augment secretion of calcitonin during treatment. It is concluded that a major therapeutic advantage of 1 alpha-OHD3 and 1,25(OH)2D3 over previously available forms of vitamin D is their rapid onset and reversal of action. These drugs do not invariably reverse bone disease and may give rise to unwanted effects. They should therefore only be used with adequate clinical, biochemical and radiographic supervision. They should not be used indiscriminately in all renal patients.

Adolescent↗
PubMed1980

Idiopathic osteoporosis in the young.

Six patients are described with idiopathic osteoporosis which began between the ages of 4 and 16 years. In four children the disorder was mild with pain in the back, vertebral collapse, qualitatively normal iliac bone biopsies, variable calcium balance and spontaneous recovery. The two remaining patients had progressive bone disease with deformity. One with a previously normal skeleton developed changes similar to those of osteogenesis imperfecta; in the other patient, who rapidly developed structural collapse associated with severe metaphysial osteoporosis, treatment was ineffective and the histological appearances of the bone suggested osteoblastic failure. Quantitative bone histology in four patients showed no evidence of excessive active resorption; and the ratio of Type III to Type I collagen in the skin was normal, in contrast to the findings in osteogenesis imperfecta. The significance of this study in relation to previous accounts is reviewed.

Adolescent↗
PubMed1980

A 13C NMR spin-lattice relaxation study of the interaction of myelin proteins with lipid vesicles.

Natural abundance 13C nuclear magnetic spin-lattice relaxation times have been measured for bovine brain phosphatidylserine vesicles with and without bound proteins. The relaxation times were lower than published values for the corresponding nuclei in egg phosphatidylcholine, but showed the same trend, with relaxation times increasing along the acyl chains away from the polar headgroup. These times were inversely related to the degree of saturation of the lipid. Cytochrome c caused insignificant changes in the lipid acyl chain relaxation rates but reduced the resonance intensities, in agreement with Brown and Wüthrich (Biochem. Biophys. Acta 468 (1977) 389). In contrast, the basic protein from bovine myelin did not affect the intensities but reduced the relaxation times for 13C nuclei near the bilayer centre, and for nuclei near carbon-carbon double bonds. These proteins also dramatically broadened the serine headgroup carboxyl resonance. It appears, in accord with other recent evidence, that the basic protein does penetrate the hydrophobic region of the bilayer (possibly to the centre), producing quantitatively similar changes in the relaxation rates to proteolipid protein, an integral membrane protein.

Journal Article↗
PubMed1980

Dog intestinal mucosa contains two vitamin D-stimulating calcium binding proteins.

Dog intestinal mucosa has been found to contain more than one vitamin D-responsive calcium-binding protein (CaBP). Duodenal and upper jejunal mucosa contains a protein that has a mol wt of 19,000 and a Kd of 1.2 microM, and that increases in activity over twofold after administration of 1,25 (OH)2 vitamin D3. This protein could not be demonstrated in ileal tissue. In ileal mucosa all the calcium binding activity resides in fractions that elute from Sephadex G200 with a mol wt of about 57,000. Calcium-binding activity was demonstrated in gel electrophoresis corresponding to a protein with an Rf of about 0.5, unlike the small CaBP, which has an Rf of 1.0. The calcium-binding activity from the ileum was demonstrated to coincide with a protein band on acrylamide gel electrophoresis, and to be destroyed by pronase. This large CaBP responded to 1,25 (OH02 vitamin D3 by increasing activity by about 50%, and was inhibited similarly to the small protein by Sr, Ba, and Mg. Neither fresh tissue homogenates, nor explants cultured up to 20 hr showed any evidence of the small CaBP on disc gel acrylamide electrophoresis. The small CaBP could be demonstrated on gel electrophoresis only in tissue that was partially autolyzed or was treated with a 10% (milligrams per milligram) solution of trypsin. The small CaBP was relatively resistant to trypsin. It is suggested that the small CaBP may be derived at least in part from the large protein.

Animals↗
PubMed1980

Some circulating factors which influence granulocyte-monocyte production in the chick with myeloblastic leukemia.

Soft-agar cloning was used to investigate possible granulopoietic-monopoietic regulatory defects in the chick with myeloblastic leukemia induced by avian myeloblastosis virus. The plasma levels of granulocyte-monocyte colony-stimulating activity (CSA) of normal and leukemic plasmas were the same when undiluted or unfractionated plasmas were tested. However, dilution or fractionation revealed elevations in plasma CSA levels in the leukemic animals. Most of the activity in both normal and leukemic plasma eluted in the void-volume peak during Sephadex G-200 gel filtration, and the CSA levels in the leukemic peak were increased 5- to 10-fold. This increase did not reflect higher levels of an inhibitory lipoprotein eluting in the void volume since the differential between normal and leukemic plasma was present after delipidation. We therefore investigated the possibility that a nonlipoprotein inhibitor was present. Sephadex G-200 chromatography of leukemic plasma revealed that a potent inhibitor of colony formation was present in one of the peaks of material eluting from the column. Eight micrograms of this material inhibited colony formation by 50%. This inhibitory material was not detected in corresponding fractions obtained after chromatography of normal plasma. These data show that plasma from the chick with myeloblastic leukemia has marked elevated levels of CSA and that it also contains an inhibitor of colony formation which is absent or present at very low levels in normal plasma. Finally, leukemic plasma contained abundant amounts of avian myeloblastosis virus polypeptides which are being investigated for possible relationships to the above-described activities.

Animals↗
PubMed1979

Circular dichroic analysis of the secondary structure of myelin basic protein and derived peptides bound to detergents and to lipid vesicles.

In aqueous solution bovine myelin basic protein exhibits no significant alpha-helical or beta-pleated sheet structure. However, in vivo this protein is associated largely with the myelin membrane: experiments have therefore been performed to determine the structure of the protein when bound to lipid bilayers. Circular dichroism spectra show that this protein undergoes a major conformational change on binding to lipid bilayer vesicles formed from diacylphosphatidylserine or diacylphosphatidic acid, and on binding to micelles of several detergents. Association with diacylphosphatidylcholine failed to induce a structural change: this observation is interpreted in terms of an earlier report that lysophosphatidylcholine does increase the alpha-helical content of basic protein. These circular dichroism measurements and studies of the binding to the bilayer-forming lipids appear to provide support for significant hydrophobic lipid-protein interactions. Similar studies using two peptides produced by cleavf basic protein indicate that a major structure-forming region in the middle of the protein has been disrupted by this scission.

Animals↗
PubMed1979

Association of myelin basic protein with detergent micelles.

Equilibrium measurements of the binding of central nervous system myelin basic protein to sodium dodecyl sulphate, sodium deoxycholate and lysophosphatidylcholine have been obtained by gel permeation chromatography and dialysis. This protein associates with large amounts of each of these surfactants: the apparent saturation weight ratios (surfactant/protein) being 3.58 +/- 0.12 and 2.30 +/- 0.15 for dodecyl sulphate at ionic strengths 0.30 and 0.10, respectively 1.34 +/- 0.10 for deoxycholate (at 0.12 ionic strength) and 4.0 +/- 0.5 for lysophosphatidylcholine. Binding to the ionic surfactants increases markedly close to their critical micelle concentrations. Sedimentation analysis shows that at 0.30 ionic strenght in excess dodecyl sulphate the protein is monomeric. It becomes dimeric when the binding ratio falls below 1 at a free detergent concentration of approximately 0.25 mM: below this concentration much of the protein and deterent forms an insoluble complex. The amount of dodecyl sulphate bound at high concentrations and at both above-mentioned ionic strengths corresponds closely to that expected for interaction of a single poly-peptide with two micelles. Variability of deoxycholate micelle size on interaction with other molecules precludes a similar analysis for this surfactant. Association was observed only with single micelles of lysophosphatidylcholine. The results provide strong evidence for dual lipid-binding sites on basic protein and indicate that lipid bilayer cross-linking by this protein may be effected by single molecules.

Animals↗
PubMed1979

Hyperthermia potentiates doxorubicin-related cardiotoxic effects.

The intercurrent administration of doxorubicin hydrochloride to a patient undergoing whole-body hyperthermia for the treatment of metastatic cancer repeatedly produced ventricular irritability and cardiac dysfunction. Individually, doxorubicin and hyperthermia were tolerated by the patient without incident. Catecholamine determinations showed that the administration of doxorubicin under hyperthermic conditions increased the liberation of both epinephrine and norepinephrine. The acute synergistic cardiotoxic effects occurred with doxorubicin dosages that were severalfold less than those associated with only mild and transient ECG disturbances under normothermic conditions.

Arrhythmias, Cardiac↗
PubMed1979

The metabolism of floctafenin in man and rodents.

Floctafenin (FFn), 2,3-dihydroxypropyl--N--(8--trifluoromethyl--4--quinolyl) anthranilate, a new nonnarcotic analgesic drug, was studied in man, mice, and the isolated perfused rat liver. In all species the drug is rapidly hydrolyzed to floctafenic acid (FFa). In seven volunteer subjects who each received a single oral dose of 400 mg floctafenin on an empty stomach, the blood concentration of FFa usually reached a maximum between 1 and 2 hours (mean 1.57 +/- 1.28 microgram/ml at 1.5 hours) and declined over the next 6 hours. Eight hours after drug administration the mean concentration of FFa in the blood of the volunteers was 0.1 +/- .05 microgram/ml. Approximately 25 per cent of the administered dose of floctafenin was recovered as FFa and hydroxy-FFa in the urine collected from each subject for 48 hours after drug administration. In mice each having received a single intraperitoneal dose of floctafenin (2 mg), the concentration of floctafenin declined by about 50 per cent in 15 minutes, and this decline was accompanied by a rise in the concentration of FFa that remained constant for 3 hours. The analgesic effect observed after administration of floctafenin to humans is likely to be mediated by its major metabolite, FFa. In these volunteers no free floctafenin was detected in the blood.

Adult↗
PubMed1979

In vitro studies of gonadal organogenesis in the presence and absence of H-Y antigen.

In a very strict sense, the primary (gonadal) sex of mammals is determined not so much by the presence or absence of the Y but the expression or nonexpression of the evolutionary extremely conserved plasma membrane H-Y antigen. The central somatic blastema of embryonic indifferent gonads contains one cell lineage characterized by the possession of S-F differentiation antigen that differentiates into testicular Sertoli cells in the presence of H-Y and into ovarian follicular (granulosa) cells in its absence. This cell lineage appears to play the most critical role in gonadal differentiation. Whether or not testicular Leydig cells and ovarian theca cells are similarly derived from the common cell lineage has not been determined. Nevertheless, if given H-Y antigen, presumptive theca-cell precursors of the fetal ovary acquire hCG (LH?)-receptors-the characteristic of fetal Leydig cells.

Animals↗