Biomedical subjects
S Schorling
Publications and source records attributed to S Schorling.
Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae.
Multiple or pleiotropic drug resistance often occurs in the yeast Saccharomyces cerevisiae through genetic activation of the Cys(6)-Zn(II) transcription factors Pdr1p and Pdr3p. Hyperactive alleles of these proteins cause overproduction of target genes that include drug efflux pumps, which in turn confer high level drug resistance. Here we provide evidence that both Pdr1p and Pdr3p act to regulate production of an enzyme involved in sphingolipid biosynthesis in S. cerevisiae. The last step in formation of the major sphingolipid in the yeast plasma membrane, mannosyldiinositol phosphorylceramide, is catalyzed by the product of the IPT1 gene, inositol phosphotransferase (Ipt1p). Transcription of the IPT1 gene is responsive to changes in activity of Pdr1p and Pdr3p. A single Pdr1p/Pdr3p response element is present in the IPT1 promoter and is required for regulation by these factors. Loss of IPT1 has complex effects on drug resistance of the resulting strain, consistent with an important role for mannosyldiinositol phosphorylceramide in normal plasma membrane function. Direct assay for lipid contents of cells demonstrates that changes in sphingolipid composition correlate with changes in the activity of Pdr3p. These data suggest that Pdr1p and Pdr3p may act to modulate the lipid composition of membranes in S. cerevisiae through activation of sphingolipid biosynthesis along with other target genes.
Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae.
Lag1p and Lac1p are two homologous transmembrane proteins of the endoplasmic reticulum in Saccharomyces cerevisiae. Homologous genes have been found in a wide variety of eukaryotes. In yeast, both genes, LAC1 and LAG1, are required for efficient endoplasmic reticulum-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins. In this study, we show that lag1 Delta lac1 Delta cells have reduced sphingolipid levels due to a block of the fumonisin B1-sensitive and acyl-CoA-dependent ceramide synthase reaction. The sphingolipid synthesis defect in lag1 Delta lac1 Delta cells can be partially corrected by overexpression of YPC1 or YDC1, encoding ceramidases that have been reported to have acyl-CoA-independent ceramide synthesis activity. Quadruple mutant cells (lag1 Delta lac1 Delta ypc1 Delta ydc1 Delta) do not make any sphingolipids, but are still viable probably because they produce novel lipids. Moreover, lag1 Delta lac1 Delta cells are resistant to aureobasidin A, an inhibitor of the inositolphosphorylceramide synthase, suggesting that aureobasidin A may be toxic because it leads to increased ceramide levels. Based on these data, LAG1 and LAC1 are the first genes to be identified that are required for the fumonisin B1-sensitive and acyl-CoA-dependent ceramide synthase reaction.
[Annual Meeting of the German-Speaking Mycology Society and the European Confederation of Medical Mycology in Dresden, June 4-6 1999].
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Selenoprotein synthesis in archaea: identification of an mRNA element of Methanococcus jannaschii probably directing selenocysteine insertion.
Selenocysteine is encoded by a UGA codon in all organisms that synthesise selenoproteins. This codon is specified as a selenocysteine codon by an mRNA secondary structure, which is located immediately 3' of the UGA in the reading frame of selenoprotein genes in Gram-negative bacteria, whereas it is located in the 3' untranslated region of eukaryal selenoprotein genes. The location and the structure of a similar mRNA signal in archaea has so far not been determined. Seven selenoproteins were identified for the archaeon Methanococcus jannaschii by labelling with 75Se and by SDS/polyacrylamide electrophoresis. Their size could be correlated with open reading frames possessing internal UGA codons from the total genomic sequence. One of the open reading frames, that of the VhuD subunit of a hydrogenase, possesses two UGA codons and appears to code for a selenoprotein with two selenocysteine residues. A strongly conserved mRNA element was identified that is exclusively linked to selenoprotein genes. It is located in the 3' untranslated region in six of the mRNAs and in the 5' untranslated region of the fdhA mRNA. This element, which is present in the 3' non-translated region of two selenoprotein mRNAs from Methanococcus voltae, is proposed to act in decoding of the UGA with selenocysteine.
[Experiences with lumbar disc herniations in adolescents].
AIM: Lumbar disc herniation is rare in adolescents and often misread. The difference of etiology, symptoms and therapy in comparison to adults were investigated and the long-term outcome of conservative and surgically treatment evaluated. METHOD: We analysed informations obtained from the medical records of 51 patients younger than 20 years with 79 lumbar disc herniations. For the long-term follow-up we prepared a questionnaire composed of general questions about the patient's lifestyle, pain level and remaining symptoms. RESULTS: The average period from the beginning of the symptoms to the finding of the right diagnosis took about 14,3 months. We compared disc herniations in adolescents with the current literature of disc herniations in adults and found differences in etiology and symptoms. In 16 % of our patients the beginning of the pain was associated with a trauma, in 12 % the pain began during sports activity (microtrauma). In 49 % we found radiological signs of spinal aberrations. Low back pain and monoradicular sciatica were the main complaints, but findings of neurological deficits were rare. 27 patients were managed conservatively and 24 surgically. On the day of discharge 94 % of patients reported excellent or good results. The outcomes of the follow-up period were similar in both treatment groups. Almost all patients were able to attain a normal activity level and few reported restrictions of their daily life. The success rate of the pain frequency was 85 % and pain intensity was 81 %. CONCLUSION: The etiology of lumbal disc herniations in adolescents has a multifactoral basis. Conservative treatment should be pursued as a mainstay of treatment. Only if conservative treatment fails, surgical treatment should be considered.
Provider sponsored organizations: new opportunities for long-term care providers.
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