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S Silberstein

Publications and source records attributed to S Silberstein.

31 records · Page 2Linked to original sources

The 48-kDa subunit of the mammalian oligosaccharyltransferase complex is homologous to the essential yeast protein WBP1.

Oligosaccharyltransferase has been purified from canine microsomal membranes as a protein complex with three nonidentical subunits of 66, 63/64, and 48 kDa. The 66- and 63/64-kDa subunits were found to be identical to ribophorins I and II, respectively. The ribophorins are integral membrane glycoproteins that were previously shown to be localized exclusively to the rough endoplasmic reticulum. The 48-kDa subunit (OST48) of the oligosaccharyltransferase complex is not a glycoprotein and is not recognized by antibodies to either ribophorin. Here, we describe the characterization of a cDNA clone that encodes OST48. Like ribophorins I and II, OST48 was found to be an integral membrane protein, with the majority of the polypeptide located within the lumen of the endoplasmic reticulum. OST48 does not show significant amino acid sequence homology to either ribophorin I or II. A 45-kDa integral membrane protein, designated WBP1, from the yeast Saccharomyces cerevisiae was found to be 25% identical in sequence to OST48. Recently, WBP1 was shown to be essential for in vivo and in vitro expression of oligosaccharyltransferase activity in yeast. We conclude that OST48 and WBP1 are homologous gene products.

Amino Acid Sequence↗

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult↗

Isolation and characterization of a dimeric cAMP-dependent protein kinase from the fungus Saccobolus platensis.

A cAMP-dependent protein kinase from mycelia of Saccobolus platensis was characterized. The holoenzyme seems to be a dimer (i.e., regulatory subunit--catalytic subunit) of 78,000 Da, slightly activated by cAMP but susceptible to dissociation into its subunits by cAMP, or by kemptide and protamine, the best substrates for Saccobolus protein kinase. The regulatory subunit was purified to homogeneity by affinity chromatography. It is highly specific for cAMP and has two types of binding sites but failed to inhibit the phosphotransferase activity of the homologous or the heterologous (bovine heart) catalytic components. The activity of the catalytic subunit was completely abolished by the regulatory component of the bovine heart protein kinase as well as by a synthetic peptide corresponding to the active site of the mammalian protein kinase inhibitor. The data suggest that interaction between the subunits of the S. platensis protein kinase is different than that found in cAMP-dependent protein kinases from other sources. Similarities and differences between the Saccobolus protein kinase and enzymes from low eucaryotes and mammalian tissues are discussed.

Ascomycota↗

A radioactive method for the measurement of trypsin and trypsin-like activities.

A simple and highly sensitive method for the assay of trypsin has been developed by making use of the phosphorylated synthetic peptide Leu-Arg-Arg-Ala-Ser-(32P)-Leu-Gly as substrate. The technique has been adapted from the phosphocellulose method of R. Roskoski, Jr. (in Methods in Enzymology (Corbin, J., and Hardman, J., Eds.), Vol. 99, pp. 3-6, Academic Press, New York) used for measuring of protein kinases. In addition to measuring the activity of trypsin at the microgram level, the 32P-labeled peptide method can be used for measuring other trypsin-like enzymes. It has been successfully utilized for the identification of a new peptidase from the fungus Saccobolus platensis.

Adenosine Triphosphate↗

Sympathetic nervous system activity and the thermic effect of feeding in man.

Animal studies have demonstrated an important role for the sympathetic nervous system in food-induced increases in energy expenditure. Despite studies in man showing a rise in plasma norepinephrine after a meal, no relationship has previously been demonstrated between the increment in plasma norepinephrine and the increase in energy expenditure. Because changes in plasma norepinephrine may not always accurately reflect alterations in sympathetic nervous system activity, we investigated the effects of an 800-kcal high-carbohydrate meal on both plasma norepinephrine kinetics and energy expenditure as well as their relationship to each other. A post-cibum increase in both energy expenditure (0.18 +/- 0.09 kcal/min, P less than 0.001) and plasma norepinephrine concentration (44 +/- 39 pg/ml, P less than 0.05) was noted but again no relationship between the two parameters was found. In contrast, the increment in norepinephrine appearance rate after the meal (0.11 +/- 0.09 microgram/min, P less than 0.001) was significantly correlated to the increment in energy expenditure (r = 0.57, n = 20, P less than 0.01). No change was noted in norepinephrine clearance rate after the meal. It is concluded that sympathetic nervous system induced increases in energy expenditure may account for at least part of the thermogenesis that occurs after a high-carbohydrate meal. It is postulated that individual variability in this sympathetic nervous system induced component of the thermic effect of feeding may account for some of the differences in energy expenditure noted between obese or elderly subjects and normal weight young controls after a meal.

Adult↗