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By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them — D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

The effects of a pharmacological blockade of the mu opiate receptors on the manifestation of tonic-clonic seizures were investigated in freely moving animals. 4-aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult rats with 1 mg/kg naltrexone HCl, 3, 5, 7, 9, 14 mg/kg 4-aminopyridine was injected intraperitoneally, and the latencies of the symptoms generated by 4-aminopyridine were measured. Naltrexone HCl decreased these latencies and enhanced the seizures significantly. The experiments provided further evidence for the existence of a tonic anticonvulsant opioid system in the brain.

The diagnostic criteria postulated by Poser necessitate clinical and laboratory CSF analysis for establishment of the diagnosis of definitive multiple sclerosis. The present paper reports methods for CSF examinations relating to multiple sclerosis with regard to the examinations suggested by the Charcot Foundation. In the course of CSF analysis, it is important to discriminate between the immunoglobulins present in normal amounts, those synthesized locally in pathological quantities and those penetrating across the damaged blood-CSF barrier. Normally, a parallel assay of CSF and serum specimens is carried out in the course of quantitative and qualitative protein analysis. In 37 patients with clinical multiple sclerosis, we determined the albumin and the immunoglobulin classes IgG, IgA and IgM, using laser nephelometry. An elevated IgG index was found in 76% of the cases, which points to local IgG snythesis and might be proof of the humoral immune response. The albumin quotient, which is suitable for examination of the integrity of the blood-CSF barrier, was within the reference range. Qualitative protein analysis was performed by means of electrophoresis on agarose-gel and isoelectric focusing. Agarose-gel electrophoresis revealed oligoclonal gammopathy in 68%, in contrast with the 91% demonstrated by isoelectric focusing. Comparison of the two kids of qualitative protein analyses indicated that isoelectric focusing was more sensitive for the detection of oligoclonal bands, in support of the literature finding.

We present a modification of Hansson's method for the demonstration of carbonic anhydrase activity. Using a semipermeable membrane together with a fluid incubation medium, frozen sections of aldehyde-fixed tissue were incubated without floating or dipping. Thin sections (thickness, 20-40 microns) were mounted on the outer surface of a tubular-shaped, semipermeable cellophane dialysis membrane containing the incubation fluid. After incubation for 25-30 min at room temperature, the sections were rinsed in buffer and treated with 0.5% (NH4)2S solution. The histochemical reaction was fully inhibited by 10(-4) M acetazolamide.