Deletion of the yeast gene ACB1 encoding Acb1p, the yeast homologue of the acyl-CoA-binding protein (ACBP), resulted in a slower growing phenotype that adapted into a faster growing phenotype with a frequency Ͼ1:10 5 . A conditional knockout strain (Y700pGAL1-ACB1) with the ACB1 gene under control of the GAL1 promoter exhibited an altered acyl-CoA profile with a threefold increase in the relative content of C18:0-CoA, without affecting total acyl-CoA level as previously reported for an adapted acb1⌬ strain. Depletion of Acb1p did not affect the general phospholipid pattern, the rate of phospholipid synthesis, or the turnover of individual phospholipid classes, indicating that Acb1p is not required for general glycerolipid synthesis. In contrast, cells depleted for Acb1p showed a dramatically reduced content of C26:0 in total fatty acids and the sphingolipid synthesis was reduced by 50 -70%. The reduced incorporation of [ 3 H]myo-inositol into sphingolipids was due to a reduced incorporation into inositol-phosphoceramide and mannose-inositol-phosphoceramide only, a pattern that is characteristic for cells with aberrant endoplasmic reticulum to Golgi transport. The plasma membrane of the Acb1p-depleted strain contained increased levels of inositol-phosphoceramide and mannose-inositol-phosphoceramide and lysophospholipids. Acb1p-depleted cells accumulated 50-to 60-nm vesicles and autophagocytotic like bodies and showed strongly perturbed plasma membrane structures. The present results strongly suggest that Acb1p plays an important role in fatty acid elongation and membrane assembly and organization.
Hyperalgesia and allodynia in 4 cancer patients treated with morphine disappeared after discontinuing or substituting morphine with other opioid agonists. The first case describes a young female who developed hyperalgesia and myoclonus during intravenous morphine infusion. The hyperalgesia and myoclonus disappeared when the morphine administration was discontinued and she felt comfortable on small and sporadic oral doses of methadone. The second case describes hyperalgesia occurring after a small dose of sustained-release morphine which disappeared after alternative use of oral ketobemidone. The third case describes hyperalgesia following high doses of intramuscular morphine which disappeared after alternative use of continuous subcutaneous infusion of sufentanil. The fourth case describes a boy developing hyperalgesia after high doses of oral and intramuscular morphine. The hyperalgesia disappeared after discontinuing morphine administration but withdrawal symptoms developed due to too small doses of methadone. Possible mechanisms of morphine-induced hyperalgesia are discussed.
Proteomics1 is an emerging area of research of the post-genomic era that deals with the global analysis of gene expression using a plethora of techniques to resolve (high resolution two-dimensional polyacrylamide gel electrophoresis, 2D PAGE), identify (peptide sequencing by Edman degradation, mass spectrometry, Western immunoblotting, etc.), quantitate and characterize proteins, as well as to store (comprehensive 2D PAGE databases), communicate and interlink protein and DNA sequence and mapping information from genome projects. Here we review the current status as well as applications of human and mouse proteomic 2D PAGE databases that are being systematically constructed for the global analysis of gene expression in both health and disease (http://biobase.dk/cgi-bin/celis). Furthermore, we discuss the problems one faces when using powerful proteomic technology to study heterogeneous tissue and tumor biopsies, and emphasize the importance of building comprehensive databases that contain a critical mass of information for both known and novel proteins in normal and disease conditions. z 1998 Federation of European Biochemical Societies.
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