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S Smith

Publications and source records attributed to S Smith.

At least 1,027 records · Page 57Linked to original sources
PubMed1976

Lipophosphonoglycan of the plasma membrane of A canthamoeba castellanii. Inositol and phytosphingosine content and general structural features.

Lipophosphonoglycan, a major component of the plasma membrane of Acanthamoeba castellanii, has now been shown to contain 8% inositol and 13% C25- and C24-phytosphingosines in addition to the previously identified content of neutral sugars (26%), amino sugars (3%), aminophosphonates (10%), acidhydrolyzable phosphate (3%), and long chain fatty acids (14%). The fatty acids and phytosphingosines are in ceramide groups. Lipophosphonoglycan can be separated by dodecyl sulfate-polyacrylamide electrophoresis into two major components that are similar in composition except for different oligosaccharide groups. A tentative structural model incorporating these features is proposed in which each of the two components of lipophosphonoglycan is conceived as an oligomeric inositol-containing glycosphingolipid.

Amoeba↗
PubMed1976

Inhibition of platelet aggregation by acyl-CoA thioesters.

The aggregation of platelets induced by ADP, collagen, or epinephrine in human platelet-rich plasma is inhibited by long chain acyl-CoA thioesters. Palmityl-CoA exerts a concentration dependent inhibition of collagen-induced aggregation and of the primary and secondary waves of ADP-induced aggregation. Palmityl-CoA also inhibits the secondary wave of epinephrine-induced aggregation but has no effect on the primary wave. This inhibitory effect of palmityl-CoA can be reversed by addition of excess ADP and cannot be attributed to a detergent action.

Adenosine Diphosphate↗
PubMed1976

T cell requirements for the expression of the lipopolysaccharide adjuvant effect in vivo: evidence for a T cell-dependent and a T cell-independent mode of action.

The in vivo adjuvant effect of lipopolysaccharide (LPS) in mice was investigated with the soluble synthetic polypeptide antigen (T, G)-A--L, the antibody response to which is determined by the Ir-1A gene. With this specific antigen it can be demonstrated that the LPS adjuvant effect has the following modes of action: a) a T cell-dependent enhancement of primary and secondary IgM antibody response; b) a T cell-dependent enhancement of IgG secondary andibody response; and c) a T cell-dependent induction of switchover from IgM to IgG andibody in some strains of Ir-1A low responders. Although T cells are necessary for some aspects of the adjuvant effect, these data do not distinguish between a mechanism involving a direct interaction between LPS and T cells or a direct interaction of LPS and B cells with a general requirement for T cells for expression of IgG antibody.

Adjuvants, Immunologic↗
PubMed1976

Specific release of the thioesterase component of the fatty acid synthetase multienzyme complex by limited trypsinization.

Limited trypsinization of the fatty acid synthetase multienzyme complex from rat mammary gland results in the release of a protein, molecular weight 32,000, with thioesterase activity. The other components of the multienzyme complex--the acyl carrier protein, acetyl and malonyl transferases, condensing enzyme, keto reductase, dehydrase and enoyl reductase--are not affected and remain associated with the complex. The thioesterase can be isolated by ammonium sulfate precipitation and gel filtration. Extensive trypsinization of fatty acid synthetase multienzyme complex results in a loss of thioesterase activity, probably due to cleavage of the thioesterase component into inactive peptides. However, the molecular weight and specific activity of the thioesterase isolated after limited trypsinization is relatively unaffected by the severity of the conditions of proteolysis. Both the thioesterase and the residual trypsinized complex react with antibodies produced against the native multienzyme. The results demonstrate that mild trypsinization can be used to release the thioesterase component of the multienzyme with little perturbation of either the thioesterase or the other components of the complex.

Animals↗
PubMed1976

Therapeutic irradiation of the central nervous system using intrathecal 90Y--DTA.

The erdication of established neuroleukaemia is often difficult, and with subsequent relapses even harder. The use of an intrathecally-injected beta emitting isotope has the advantage of preserving the bone-marrow of the vertebral column and cranium whislt irradiating the meninges. The value of intrathecal 90Y-DTPA(diethylene-triamine penta-acetic acid) has been investigated in nine patients with neuroleukaemia or CNS involvement in malignant lymphoma. Measurements of retention of the isotope in the whole body, spinal, and intracranial subarachnoid spaces have been made, together with blood levels, and are reported. The clinical results are presented. In three out of five evaluable patients 90Y-DTPA failed to maintain a chemotherapy-induced CNS remission and in two out of two evaluable patients malignant cells were not dispersed from the CNS with a single intrathecal injection of 90Y-DTA. It is concluded, therefore, that with this agent and the doses used no useful clinical result is gained.

Adolescent↗
PubMed1976

Acyl specificity in triglyceride synthesis by lactating rat mammary gland.

We have studied the specificity of the acyl-CoA:diglyceride acyltransferase reaction in lactating rat mammary gland to provide a rational explanation at the enzyme level for the nonrandom distribution of fatty acids in milk fat triglycerides. Acyl-CoA:diglyceride acyltransferase activity was measured using various diglyceride and radioactive acyl-CoA substrates; products were identified as triglycerides by thin-layer and gas-liquid chromatography. Most of the enzymatic activity was located in the microsomal fraction and showed a broad specificity for the acyl donors tested C10, C12, C14, C16, C18, and C18:1 CoA esters). The acyltransferase activity was highly specific for sn-1,2-diglyceride enantiomers; rac-1,3- and sn-2,3-diglycerides were relatively inactive. The acyl-CoA specificity was not affected by the type of 1,2-diglyceride acceptor offered, although dilaurin was the best acceptor and sn-1,2-dilaurin greater than sn-1,2-dimyristin greater than sn-1,2-dipalmitin greater than sn-1,2-distearin. We have previously shown that in the microsomal fraction from lactating rat mammary gland, the acyltransferase activities concerned with the conversion of sn-glycero-3-phosphate to diacylglycerophosphate show a very marked specificity for long chain acyl-CoA's. Therefore, we conclude that the predominant localization of long chain fatty acids in the 1 and 2 positions, and of shorter chain fatty acids in the 3 position of the glycerol backbone, results at least in part from the specificities of the mammary gland acyltransferases.

Acyltransferases↗
PubMed1976

IgM-mediated, T cell-independent suppression of humoral immunity.

The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity.

Animals↗
PubMed1976

The use of drug concentration measurements in studies of the therapeutic response to propranolol.

The dose of propranolol which produces the optimal therapeutic effect in patients with angina pectoris has been found to vary widely among patients. Because the plasma concentration of propranolol also differs markedly due to interpatient variability in absorption it seemed possible that this might be the reason for the wide range of effective doses in angina and that plasma propranolol might provide a useful guide to therapeutic response. To examine this possibility we selected ten patients with coronary artery disease complicated by angina and studied them at varying propranolol doses to a maximum of 320 mg/day. Exercise capacity was tested on a treadmill and plasma propranolol concentration was measured by gas liquid chromatography. In seven normal subjects beta-blockade was quantified precisely as inhibition of exercise tachycardia and was related to plasma propranolol levels at various doses. Maximal beta-blockade occurred at 100 ng/ml of plasma propranolol, but the dose response curve of blockade was relatively flat and the ED50 of plasma propranolol was 8+/-1 ng/ml. In the patients maximal therapeutic benefit from propranolol occurred at 30+/-7 ng/ml and at a dose of 144 mg/day. This resulted in an increase in exercise capacity from an estimated 12-7+/-0-8 ml/kg/min of oxygen consumption during control to 17-2+/-1-1 ml/kg/min on the drug. Thus, there was a wide variation of both dose and concentration among these patients at the maximum therapeutic response. However, when plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 and 98% of total blockade. These studies indicated the extent of beta-blockade necessary to produce an effective therapeutic response in angina, but demonstrate that plasma drug levels provide no practical guide to therapy in patients with angina pectoris. A further study was conducted measuring plasma propranolol in twenty hypertensive patients to investigate the fall in blood pressure in relations to the change in plasma renin activity and the inhibition of cardiac adrenergic receptors. The inhibition of plasma renin closely resemble the response seen in heart rate inhibition in that the maximum response is seen at 100 ng/ml and the ED50 was 11 ng/ml. In contrast propranolol is shown only to begin to have a significant effect on blood pressure at a plasma level of 30 ng/ml and the effect becomes progressively greater as the plasma level increases. This suggests that the hypotensive effect of propranolol may be dissociated from the beta-blocking effects of cardiac and renin releasing receptors.

Angina Pectoris↗
PubMed1975

Purification and properties of Escherichia coli dihydrofolate reductase.

Dihydrofolate reductase has been purified 40-fold to apparent homogeneity from a trimethoprim-resistant strain of Escherichia coli (RT 500) using a procedure that includes methotrexate affinity column chromatography. Determinations of the molecular weight of the enzyme based on its amino acid composition, sedimentation velocity, and sodium dodecyl sulfate gel electrophoresis gave values of 17680, 17470 and 18300, respectively. An aggregated form of the enzyme with a low specific activity can be separated from the monomer by gel filtration; treatment of the aggregate with mercaptoethanol or dithiothreitol results in an increase in enzymic activity and a regeneration of the monomer. Also, multiple molecular forms of the monomer have been detected by polyacrylamide gel electrophoresis. The unresolved enzyme exhibits two pH optima (pH 4.5 and pH 7.0) with dihydrofolate as a substrate. Highest activities are observed in buffers containing large organic cations. In 100 mM imidazolium chloride (pH 7), the specific activity is 47 mumol of dihydrofolate reduced per min per mg at 30 degrees. Folic acid also serves as a substrate with a single pH optimum of pH 4.5. At this pH the Km for folate is 16 muM, and the Vmax is 1/1000 of the rate observed with dihydrofolate as the substrate. Monovalent cations (Na+, K+, Rb+, and Cs+) inhibit dihydrofolate reductase; at a given ionic strength the degree of inhibition is a function of the ionic radius of the cation. Divalent cations are more potent inhibitors; the I50 of BaCl2 is 250 muM, as compared to 125 mM for KCl. Anions neither inhibit nor activate the enzyme.

Amino Acids↗