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In a 1 year longitudinal study of twenty-two) patients with multiple sclerosis (MS) and twenty-one normal control subjects, peripheral blood leucocytes were stimulated with lipopolysaccharide (LPS), a B cell mitogen, and phytohaemagglutinin (PHA) a T cell mitogen. EA- and EAC-rosette formation was also performed to assay null and B cells respectively, and the serum concentration of the C3 component of complement was determined. For ten multiple sclerosis (MS) patients with stationary' phases of the disease, percentages of lymphocytes significantly lower than normal were found with normal leucocyte counts in the peripheral blood. Lymphocyte stimulation by PHA was significantly lower than normal in stable MS, while neither LPS stimulation nor EA-and EAC-rosette formation differed significantly from the controls. The C3 serum concentration was found to he significantly higher than normal. For nine out of twelve MS patients with a fluctuating clinical course, the C3 concentration was elevated during remission, but dropped to normal levels during relapse. None of the other parameters studied could be correlated with the clinical course. [ABSTRACT FROM AUTHOR]

Conformational changes in enzymes and their role in their catalytic activity have been thoroughly addressed experimentally and theoretically. There is a vivid discussion in the field of enzyme catalysis on whether conformational changes of the enzyme are coupled to catalysis, or whether transition state stabilization through the preorganized protein and its electrostatic properties govern the catalysis. In this study, an additional contribution to the catalysis of one specific enzyme, Pin1, is proposed, which arises from its conformational selection of the peptide substrate from aqueous solution with the lowest activation barrier. The most stable conformers of the reactant (cis) and product (trans) peptide were identified through molecular dynamics simulations in combination with metadynamics. The cis-trans isomerization reaction was studied with quantum mechanical/molecular mechanical molecular dynamics simulations and density functional theory together with the mean reaction force, which allows us to separate structural and electronic contributions to the activation barrier. Our results show that enzyme Pin1 binds the trans isomer in the conformation of the peptide with the smallest activation barrier and reduces the barrier further through specific substrate-enzyme interactions, as we have shown previously. The activation barrier of the cis peptide is independent of the conformer and remains unchanged in the enzyme.

In the past one possible mechanism of DNA damage in bulk water has been attributed to the presence of hydrated electrons in water. Recently, one important property of hydrated electrons, namely their binding energy, was reported to be smaller at hydrophobic interfaces than in bulk aqueous solution. This possibly opens up new reaction possibilities with different solutes such as the DNA at hydrophobic, aqueous interfaces. Here, we use QM/MM molecular dynamics simulation to study how the molecular environment at the vacuum-water interface and in the bulk alters the electron affinity of cytosine being a characteristic part of the DNA. The electron affinity at the interface is closer to the corresponding binding energy of the partially hydrated electron. The increased energy resonance makes the electron capture process more probable and suggests that hydrated electrons at hydrophobic interfaces may be more reactive than the fully hydrated ones. Additionally, we found that the relaxation of the anionic form after electron attachment also induces a proton transfer from the surrounding solvent that was confirmed by comparison with the experimental reduction potential.

In this study, we describe a two-allelic RsaI restriction fragment length polymorphism identified by Southern blot analysis and by allele-specific polymerase chain reaction amplification for the human beta 2-glycoprotein I (beta 2-I; apolipoprotein H = APOH) gene. This polymorphism, which segregates in a co-dominant fashion, leads to a valine-leucine amino acid exchange at amino acid position 247. The allele frequency has been established in 34 unrelated parents of the Centre d'Etude du Polymorphisme Humain family panel and was found to be 0.76 for valine and 0.23 for leucine. The Val-Leu polymorphism described in this study does not correlate with the four isoelectric focusing alleles previously described, indicating that other variants are responsible for this polymorphism.

A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction.

From anoxic sewage sludge a new strictly anaerobic, spore-forming bacterium was isolated with 2-hydroxybutyrate as sole substrate. 2-, 3-, and 4-hydroxybutyrate, 4-chlorobutyrate, crotonate, vinylacetate, and pyruvate were fermented to acetate and butyrate. Fructose was converted to acetate, butyrate, butanol, and H2. Lactate and acrylate were fermented to acetate and propionate. Cells pregrown with lactate fermented 2-hydroxybutyrate to butyrate, propionate and acetate. No inorganic electron acceptors were reduced. The DNA base ratio was 32.0 +/- 1.0 mol% and was similar to that of Clostridium propionicum, which was determined to be 35.3 +/- 0.5 mol%. Strain LuHBu1 is described as type strain of a new species, Clostridium homopropionicum sp. nov. Another isolate obtained from marine sediment degraded 2- and 3-hydroxybutyrate to acetate and butyrate and was in some respects similar to the known species Ilyobacter polytropus.

Complement-dependent gliotoxic antibody activity was determined in 22 patients with multiple sclerosis (MS) and 19 normal control persons. Peripheral blood serum was collected from MS patients at about 4-week intervals for one year, and the results of cytotoxicity tests correlated with the course of disease. For 10 MS patients with stable disease, complement-dependent cytotoxic antibodies directed against a noncytocidally infected mouse glial cell line (an as yet unidentified virus) were found in significantly higher than normal titer. For 12 MS patients with fluctuating clinical course, the gliotoxic antibody titer remained relatively constant before relapse. During relapse, the titer remained constant or dropped. With remission initially low titers increased appreciably.