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A large German family with "myoclonic dystonia with lightning jerks responsive to alcohol" was identified. Eleven affected pedigree members and six obligate gene carriers from five generations were identified. A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinical syndrome of a nonprogressive movement disorder characterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms (CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for subunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 and rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.

The inhibition of [3H]nitrobenzylthioinosine ([3H]NBI) binding to human parietal cortex membranes by adenosine transport inhibitors, adenosine receptor agonists and antagonists and dihydropyridines was investigated. While the adenosine transport inhibitors inhibited [3H]NBI binding with Ki values in the low nanomolar range and the adenosine A1 receptor agonist, cyclopentyladenosine, with a Ki in the low micromolar range, no IC50 values could be obtained for the adenosine receptor antagonists at concentrations up to 100,000 nM. Among the dihydropyridines (+)-nimodipine was the most potent with a Ki of 201 +/- 55 nM. Inhibition of adenosine transport thus may contribute to the clinical effects of nimodipine in the central nervous system.

We report the results of a screen of 230 European familial index cases of Parkinson's disease for the recently described Ala53Thr mutation in the alpha-synuclein gene in an autosomal dominant Parkinson's disease kindred. No mutations were found from this broad white population, and we therefore conclude that although of great interest, this mutation is a very rare cause of familial Parkinson's disease.

A large German family with "myoclonic dystonia with lightning jerks responsive to alcohol" was identified. Eleven affected pedigree members and six obligate gene carriers from five generations were identified. A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinical syndrome of a nonprogressive movement disorder characterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms (CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for subunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 and rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.

We compared the binding sites of the adenosine transport inhibitors ( 3 H)dipyridamole (DPR) and ( 3 H)nitrobenzylthioinosine (NBI) in human parietal cortex and erythrocytes. In comparison with guinea pig ( 3 H)DPR marked only slightly more binding sites than ( 3 H)NBI with a Bmax of 1080±29 and 780±7 fmol/mg protein respectively in parietal cortex and 24288±2725 and 20875±1905 fmol/mg protein respectively in erythrocytes. NBI displaced ( 3 H)DPR binding completely from its binding sites at about K D /2 concentrations in parietal cortex as well as erythrocytes with inhibition constants comparable to its dissociation constants. Lineweaver-Burke analysis in erythrocytes indicated a competitive inhibition of ( 3 H)DPR binding by NBI. Pharmacological characterization of ( 3 H)DPR binding sites in human erythrocytes is consistent with their localization on adenosine transporters. These findings provide evidence that as opposed to guinea pig ( 3 H)DPR and ( 3 H)NBI largely label binding sites to the same adenosine transporter in human erythrocytes and parietal cortex.

Adenosin ist als hemmender Neuromodulator anerkannt [3], Seine extrazellulare Konzentration wird mittels eines bidirektionalen Transportmechanismus gesteuert [1]. An diesem Transporter wirkt der Transporthemmer Nitrobenzylthioinosin, dessen Bindungsstelle im menschlichen Gehirn biochemisch charakterisiert wurde [2, 9]. Wenig bekannt ist uber die Interaktion anderer pharmakologischer Stoffe mit dieser Bindungsstelle.

Adenosin Transport Hemmer wurden zur Behandlung neuropsychiatrischer Erkrankungen wie Ischamie, Epilepsie, Schlafstorungen und Angsterkrankungen vorgeschlagen [1].