Citrullinated proteins are the products of a posttranslational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner. In our previous report, PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of protein citrullination in human neuronal degeneration, we examined whether citrullinated proteins are produced during Alzheimer's disease (AD). By Western blot analysis with antimodified citrulline antibody, citrullinated proteins of varied molecular weights were detected in hippocampal tissues from patients with AD but not normal humans. Two of the citrullinated proteins were identified as vimentin and glial fibrillary acidic protein (GFAP) by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Interestingly, PAD2 was detected in hippocampal extracts from AD and normal brains, but the amount of PAD2 in the AD tissue was markedly greater. Histochemical analysis revealed citrullinated proteins throughout the hippocampus, especially in the dentate gyrus and stratum radiatum of CA1 and CA2 areas. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also ubiquitous throughout both the AD and the normal hippocampal areas. PAD2 enrichment coincided well with citrullinated protein positivity. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells also coincided with GFAP-positive cells, but not all GFAP-positive cells were positive for PAD2. As with GFAP, which is an astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes. These collective results, the abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 in hippocampi of patients with AD, strongly suggest that PAD has an important role in the onset and progression of AD and that citrullinated proteins may become a useful marker for human neurodegenerative diseases.

We used the enzyme-linked immunosorbent assay to investigate autoantibodies against the gangliosides GM1, GD1a, GD1b, GT1b, GD2, and GQ1b in sera from 16 patients with Fisher's syndrome. We found high anti-GQ1b antibody titers, mainly those of the IgG class, in the sera of 13 of these patients. The titers decreased with the clinical course of the illness. Moreover, anti-GQ1b antibody-positive patients had more severe ataxia of cerebellar type than the antibody-negative patients.

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A minilaparotomy approach is a feasible, minimally invasive, and attractive alternative to conventional laparotomy for selected patients with colonic cancer.

Peptidylarginine deiminases (PADs) are post-translational modification enzymes to convert protein arginine to citrulline residues in a calcium ion-dependent manner. Here, we investigated the tissue specific expression of PAD type I, II, III and IV by using a reverse transcriptionpolymerase chain reaction (RT-PCR) method. The type I mRNA was detected only in the epidermis and stomach, and type III mRNA was detected only in the epidermis and ovary. On the other hand, the type II and type IV mRNAs were found in a variety of tissues such as the epidermis, lung, spleen,