Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.     

Identification of syntaxin 1A as a novel binding protein for presenilin-1

Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds syntaxin under physiological conditions.     

A placebo controlled, double-blind study of mecamylamine treatment for cocaine dependence in patients enrolled in an opiate replacement program.

A placebo controlled, double-blind trial of mecamylamine treatment of cocaine dependence was performed in methadone or LAAM maintained subjects who met DSM-IV criteria for cocaine dependence. After an eight-week placebo run-in screening period, 35 subjects were randomly assigned to receive either mecamylamine (6 mg/day) or placebo transdermal patches for a 16-week treatment period. Outcome measures included quantitative urine benzoylecognine (BE) levels, self-report of cocaine use, cocaine craving, global impression scores, mood, retention, and safety. Mecamylamine was well tolerated, and study retention did not differ by treatment group. Evidence for cocaine use, based on urine BE levels and cocaine abstinence rates, did not differ by treatment group. Self reported cocaine use, cocaine craving, and global impression scores showed moderate improvement in both groups, with a significantly greater reduction in cocaine craving (p < 0.05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support the effectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients.     

Expression of integrin adhesion molecules in normal ovary and epithelial ovarian tumors

The metastatic potential of a solid tumor is dependent upon its ability to interact with the extracellular matrix. The integrin superfamily is a group of proteins that are fundamental in such interactions and play a major role in cell-cell and cell-matrix adhesion. Localization of the integrin proteins was performed in normal ovary, primary epithelial ovarian tumors and metastatic tumor cells in ascitic samples. Expression of α₁, α₃, α₆ and β₄ was observed on normal ovarian epithelium with variable expression of α₅. Loss of α₁ expression by malignant cells in the primary tumors was noted. β₄, a component of the laminin receptor which was strongly expressed by both normal ovary and solid tumor, was absent from the ascitic tumor cells in the majority of cases. There was an associated loss of α₆ expression, indicating a deficiency of hemidesmosomes in the ascitic tumor cells. This alteration of integrin expression by metastatic malignant epithelial ovarian tumor cells may therefore represent one important mechanism by which metastatic disease occurs.     

Comparative clinical study of a new 17D thermostable yellow fever vaccine

The immunogenicity and the safety of a new heat-stable 17D yellow fever vaccine have been assessed in a randomized comparative study by reference to a non-stabilized vaccine preparation. Seronegative adults were used and 115 and 143 were given the heat-stable and the non-stabilized vaccine, respectively. Fifty two days after the immunization, haemagglutination inhibiting antibodies were found in 77.6 and 73.9% of the vaccinees, neutralizing antibodies in 99.3 and 100% of them. The percentage of seroconversion and the geometric mean of antibody titres were not significantly different. No complaints or adverse reactions in association with the vaccines were recorded. This study demonstrates the high immunogenicity of this new stabilized vaccine whose stability has already been proven.