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R Smith

Publications and source records attributed to R Smith.

At least 19 recordsLinked to original sources
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↗
PubMed1979

Characterization of different tumor antigens present in cells transformed by simian virus 40.

In addition to large T and small t antigens, cells transformed by simian virus 40 (SV40) commonly contain other proteins which specifically immunoprecipitate with SV40 anti-T serum and which are not detected in untransformed cells. The additional tumor antigens (T-Ags) fall into two groups: those having a close structural relationship with normal SV40 T-Ags, and those unrelated to large T and small t. The latter are probably nonviral T-Ags (NVT-Ags). The NVT-Ags comprise a family of proteins of molecular weight 50,000-55,000. Fingerprint analysis shows that NVT-Ags have few if any peptides in common with large T or small t, and that they lack the amino terminal tryptic peptide and the peptides unique to small t. NVT-Ags from different species have different fingerprints, but those isolated from different transformants of the same cell line are identical. The size of NVT is unaltered in cells transformed by mutants of SV40 with deletions in the region 0.60-0.55 map units. The mRNA for NVT does not hybridize to SV40 DNA. The other forms of T-Ag isolated from transformed cells fall into three classes: shortened forms of large T (truncated large T); multiple species of T-Ag with molecular weights very similar to, but distinct from, those of normal large T (large T doublets and triplets); and elongated forms of large T (super T). These proteins all contain the normal amino terminus of SV40 T-Ags, and the truncated forms of large T lack peptides from the carboxy terminal half of large T. One species of super T (molecular weight 130,000) contains only those methionine tryptic peptides present in normal large T, although it may contain some peptides in more than one copy.

Animals↗
PubMed1979

Changes in blood glucose and plasma insulin after intravenous galactose in human injury.

1. The increase in blood glucose after intravenous galactose was measured at 6--8 h and 14 days after hip replacement (14 patients) and accidental injury (14 patients). 2. After hip replacement there was a greater rise of glucose after galactose on the day of the operation than on recovery, despite basal hyperglycaemia. This earlier period was also associated with inappropriately low insulin concentrations for the prevailing glucose concentration, and hyperketonaemia (13 out 14 patients). 3. After accidental injury patients with initial hyperketonaemia (nine out of 14) also had a greater rise of blood glucose after galactose than on recovery and had relative insulin deficiency; in contrast those who were initially normoketonaemic (five out of 14) showed a rise in glucose comparable with that after recovery and basal insulin concentrations more appropriate to the existing glucose concentration. 4. It is concluded that in most subjects after injury hepatic glucose release after galactose administration is not suppressed despite hyperglycaemia.

Adolescent↗
PubMed1979

Effect of vitamin D deficiency on sarcoplasmic reticulum function and troponin C concentration of rabbit skeletal muscle.

1. Weanling rabbits were made rachitic either by a vitamin D-deficient diet or by parenteral administration of ethane 1-hydroxy-1,1-diphosphonate (EHDP) in amounts sufficient in other species to block the formation of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. 2. The uptake of calcium into the isolated sarcoplasmic reticulum from mixed striated quadriceps muscle, and the amount of troponin C (the calcium-binding component of the troponin complex) in relation to other proteins from the same muscle, were measured. 3. In muscle from animals made rachitic by a dietary deficiency of vitamin D, the rate of uptake of calcium by the sarcoplasmic reticulum and the troponin C concentration were both significantly less (P less than 0.02) than in control littermates. In EHDP-treated animals no significant differences from controls were found. 4. These results show that dietary deficiency of vitamin D in such animals can affect muscle physiology. Since no changes are found in animals made rachitic with EHDP, who presumably have a selective deficiency of 1,25-(OH)2D3, it is possible that the effect of vitamin D on muscle is mediated through metabolites other than 1,25-(OH)2D3 such as 25-hydroxycholecalciferol.

Animals↗
PubMed1979

The 3-methylhistidine content of human tissues.

1. The amount of 3-methylhistidine (3-MeH) has been measured in eighty-eight samples of tissue taken post-mortem from five adults. 2. The highest concentration (mumol/g fat-free dry weight) of 3-MeH was in skeletal muscle (3.31 +/- 0.05); intermediate values (2-3) were found in cardiac muscle and those tissues containing smooth muscle; and low values (less than 1) occurred in parenchymal tissues such as liver and kidney. 3. There was little variation between the mean 3-MeH content of striated muscles in different individuals, and no significant difference between the 3-MeH concentrations of striated muscles taken from six different sites. 4. The results suggest that it is justifiable to use values obtained from single muscles to calculate the rate of myofibrillar breakdown from urinary 3-MeH excretion.

Adult↗
PubMed1979

Herpes zoster oticus. Uncommon but recognizable cause of facial paralysis.

Three cases of herpes zoster oticus illustrate the manifestations of this relatively uncommon cause of facial paralysis. Topographic analysis, in which functions of facial nerve branches are assessed, helps establish the level of facial nerve involvement. Sequential faradic stimulation testing often is a sensitive prognostic indicator of recovrey of facial nerve function, particularly if nerve excitability persists. A few recent reports support the use of systemic steroid therapy for herpes zoster oticus; opinions vary regarding the efficacy of surgical decompression for facial paralysis. Although general principles cannot be deduced from three cases, each case discussed exemplifies an important aspect of management. The prognostic significance of results of nerve stimulation tests is illustrated by the complete return of facial nerve function in our first patient. Our second patient's response to systemic steroid therapy supports recent reports of the value of such agents in herpes zoster oticus. Partial return of facial nerve function in our third patient two months after onset of paralysis accentuates the importance of a period of observation before a nerve graft or other rehabilitative procedures are undertaken.

Adult↗