We measured beta-carbolinium cations (BC+s) endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP+), in the lumbar CSF of 22 patients with idiopathic Parkinson's disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC+s, 2,9-diemethylnorharmanium cation (2,9-Me2NH+), the most potent neurotoxicant that mirrors MPP+ in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC+s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC+ content, sum of 2-MeBC+ and 2,9-Me2NH+ levels, was significantly higher in PD patients than in controls. The 2-MeBC+ contents significantly increased with the progression of the PD, but 2,9-Me2NH+ decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that "bioactivated" BC+s, especially 2,9-Me2NH+s, may be the endogenous causative factors underlying PD.
Peptidylarginine deiminase is a protein‐modulating enzyme which converts the arginine residues in proteins to citrulline residues. This study describes the complete primary structure of mouse peptidylarginine deiminase, which was deduced from nucleotide sequence analysis of cDNA clones plus proteochemical analysis of the purified enzyme. The composite cDNA sequence contained a 5′ untranslated region of 7 bases, an open reading frame of 2019 bases that encoded 673 amino acids, a 3′ untranslated region of 2662 bases, and part of a poly(A) tail. The N‐terminal and C‐terminal sequences of the enzyme matched the sequences deduced from nucleotide analysis. Furthermore, we determined that the N‐terminal sequence was Nα‐acetyl‐Met‐Gln‐, a sequence which has never previously been reported among Nα‐acetyl‐Met proteins. The Arg 352 of the enzyme was converted to a citrulline residue and the potential Asn‐linked glycosylation site (Asn542‐Glu543‐Ser544) had no carbohydrate moiety. Thus, mouse peptidylarginine deiminase consists of 673 amino acids with a molecular mass of 76 260. Mouse peptidylarginine deiminase mRNA has two AU‐rich structures in the 3′ untranslated region which exhibit a high degree of similarity to those in lymphokine, cytokine and proto‐oncogene mRNA species. Since the rat enzyme (previously reported) does not possess these characteristic structures, we compared the levels of enzyme activity and mRNA in the mouse and rat uterus at four defined phases of the estrous cycle. The degradation of peptidylarginine deiminase and its mRNA proceeded significantly faster in the mouse than in the rat. We speculate that the unusual structure of the mouse enzyme and its mRNA be involved in this species‐specific rapid degradation.
Summary. Monosomy 7 is the most frequent chromosome abnormality among patients with secondary myelodysplastic syndrome (MDS). We used fluorescence in situ hybridization (FISH) and fluorescence-activated cell sorting (FACS) in order to clarify the lineage involvement. Four patients, three with de novo MDS and one with secondary MDS, were enrolled in this study. Monosomy 7 was observed in pluripotent stem cells (CD34
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