No abstract

Homopolymers of a-2,8-ketosidically linked sialic acid (polysialic acid) represent a posttranslational modification which, in mammals, appears to be unique for the neural cell adhesion molecule and the a subunit of sodium channels in brain. Under steady-state conditions, polysialic acid is detectable in the plasma membrane of different cell types but not in the cytoplasm. We have studied the site of synthesis and the cell surface re-expression of polysialic acid in a clonal subline of small cell lung carcinoma using the monoclonal antibody 735 and bacteriophage endosialidase, both specific reagents for polysialic acid. After enzymic removal, cell surface polysialic acid re-expression reached control levels only after 5 days. When Golgi to plasma membrane transport of endosialidase-treated cells was blocked by culture at 20°C or in the presence of monensin at 37"C, de-novosynthesized polysialic acid became detectable in the Golgi apparatus. Our data show that synthesis of polysialic acid of the neural cell adhesion molecule with a degree of polymerization of at least nine occurs intracellular in the Golgi apparatus of a human small cell lung carcinoma cell line.Sialic acids are ubiquitous in oligosaccharide side chains of glycoconjugates of a wide variety of phyla [ 11. Homopolymers of a-2,8-ketosidically linked sialic acid (polySia) occur more specifically [2, 31 and, in mammals, have been reported to be associated with only two proteins, the neural cell adhesion molecule (NCAM) [4] and the a subunit of the voltagegated sodium channels in rat brain [5]. PolySia of NCAM modulates the homophilic binding properties of this and other cell-adhesion molecules [6-91 and, thereby, is involved in various cellular phenomena during organogenesis [lo] and regenerative processes [ll], as well as malignant growth [12].The genetics [13, 141 and molecular mechanisms [15, 161 of the synthesis of polySia in bacteria are well known. A multigenic cluster encodes for various proteins required for the synthesis, translocation and export of polySia. Synthesis and activation of sialic acid occurs in the cytosol, followed by the formation of polySia linked to undecaprenol at the cytoplasmic surface of the inner membrane by a membraneassociated polysialyltransferase. Phospholipid substitution at the inner membrane of the polySia is preceding by the translocation of fully assembled polySia across the membranes to the surface. In contrast, little is known about the mechanism and site of polySia biosynthesis in eukaryotes. In brain, the presence of a developmentally regulated sialyltransferase activity, which is required for the polysialylation of exogenous NCAM, has been demonstrated in a smooth membrane fraction containing Golgi membranes . From the results of chemical analysis [20] and overexpression of P-galactoside a-2,6-sialyltransferase during embryogenesis of Xenopus [21], it was suggested the pol- The present study was undertaken to obtain more direct information about the cellular site of synthesis of polySia. For this purpose, w...

No abstract

A series of 417 consecutively admitted psychiatric inpatients were studied with regard to their use of potentially abusive psychotropic substances in the last 3 months preceding admission. In all patients face-to-face interviews were performed; in 354 of them urine specimens could also be tested. Alcohol and benzodiazepines belonged to the most frequently used substances followed by cannabis, opiates and cocaine. Barbiturates, hallucinogens and amphetamine derivatives were only exceptionally reported. The most important finding of the study is that every fifth patient regularly used "hard" drugs (opiates and/or cocaine), every fourth patient illegal drugs and every third patient alcohol. Substances were found in 54% of all urine specimens; methadone, opiates and cocaine were hardly found alone. For the latter substances excellent agreement was found between interview reports and urine exams. Excluding patients diagnosed as substance-use disorders, there were no statistically significant differences between schizophrenic, affective, neurotic/stress/somatoform and other disorders with regard to the use of "hard" drugs and illegal drugs. Regular substance use correlated with much worse psychosocial adjustment. Substance use has to be explored and considered in every individual psychiatric inpatient.

A method which optimizes on global properties of sample recordings is proposed for the definition of and the discrimination between electroencephalogram (EEG) classes. The sample was drawn from students at the University of Heidelberg from 1974 to 1978 and consists of 15 healthy index cases clinically ascertained as belonging to the low voltage EEG group. In addition, the three clinically defined groups: diffuse β (18 index cases), borderline α (12 index cases) and monomorphous α (18 index cases) have been included in the study, as well as the first degree relatives of the index cases, thus providing a clinical classification into four groups. The proposed method provides an automatic and reliable classification algorithm using discriminant and cluster analysis. The relation between such an automatized classification and clinical classification schemes is investigated. In particular, the inheritance of the low voltage, EEG, the question on sex differences and the question of a simple Mendelian mechanism had been examined. The method of random splittings had been applied for discriminant and cluster analysis. Our findings can be summarized as follows: (1) except for the monomorphous α EEG group, the clinical classification shows rather marginal separation (discriminating performance 60% to 75%), while a new and more reliable grouping scheme improves the discriminating performance up to 87% to 91%. The latter scheme leads to the concept of personal channel pattern (PCP) and was compared to the clinical classification scheme by means of contingency tables; (2) only a weak correlation between the clinically and PCP‐based groups could be found (Cramér Index: 0.27). Accordingly, we continued to investigate the extent to which the proposed EEG classification scheme can nevertheless explain the genetic mechanisms apparently involved in the low voltage EEG. We thus considered the role of sex differences manifest in our proposed new grouping scheme; (3) males occurred more frequently in the new group 3 and females more frequently in the new group 1. In this regard, a much better correlation of the new groups between mothers and children than between fathers and children was observed; and (4) with help of our new PCP scheme, we have been able to reproduce a simple two gene Mendelian scheme to explain inheritance of the clinical low voltage EEG group. In this PCP‐based scheme, the low voltage property does not occur when dominance of a certain gene (called gene A) is absent. © 1996 Wiley‐Liss, Inc.