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        Immunohistochemical differentiation between chronic enteropathy associated with SLCO2A1 gene and other inflammatory bowel diseases

        Satoko Yamaguchi,Shunichi Yanai,Shotaro Nakamura,Keisuke Kawasaki,Makoto Eizuka,Noriyuki Uesugi,Tamotsu Sugai,Junji Umeno,Motohiro Esaki,Takayuki Matsumoto 대한장연구학회 2018 Intestinal Research Vol.16 No.3

        Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic enteropathy associated with SLCO2A1 (CEAS). The aim of this study was to evaluate SLCO2A1 protein expression in the intestinal tissues of patients with CEAS, intestinal Behçet’s disease (BD), simple ulcer (SU), and Crohn’s disease (CD). Methods: Immunohistochemical staining using a polyclonal anti-SLCO2A1 antibody was performed on the resected intestinal specimens from 13 cases of CD, 9 cases of intestinal BD/SU, and 3 cases of CEAS. The extent of SLCO2A1 expression was determined by counting positively-staining vascular endothelial cells and scored as 0 (no cells), 1 (1%−30% cells), 2 (31%−60%), or 3 (>60%). The intensity of SLCO2A1 expression was scored either as 0 (negative), 1 (intermediate), or 2 (strong). The extent score and intensity score were summed for the final score of 0, 2, 3, 4, or 5. Results: SLCO2A1 protein expression was observed in 1 of 3 cases of CEAS (33%), all 13 cases of CD (100%), and all 9 cases of BD/SU (100%). The mean final expression scores of CEAS, CD, and BD/SU were 1.6 (range, 0−5), 4.8 (range, 4−5), and 4.3 (range, 4−5), respectively. The final expression score in CEAS was significantly lower than in CD (P=0.03). Conclusions: Immunohistochemical staining of the SLCO2A1 protein is considered useful to distinguish CEAS from other inflammatory bowel diseases.

      • KCI등재

        Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn’s Disease

        Shunichi Yanai,Satoko Yamaguchi,Shotaro Nakamura,Keisuke Kawasaki,Yosuke Toya,Noriyuki Yamada,Makoto Eizuka,Noriyuki Uesugi,Junji Umeno,Motohiro Esaki,Eiko Okimoto,Shunji Ishihara,Tamotsu Sugai,Takayu 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.1

        Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1 ) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn’s disease (CD). Methods: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. Results: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (p<0.001). The three patients with CEAS without SLCO2A1 expression had a homozygous splice-site mutation in SLCO2A1, c.1461+1G>C (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. Conclusions: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.

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        Reduction of L-Type Amino Acid Transporter 1 mRNA Expression in Brain Capillaries in a Mouse Model of Parkinson's Disease

        Ohtsuki, Sumio,Yamaguchi, Hirofumi,Kang, Young-Sook,Hori, Satoko,Terasaki, Tetsuya Pharmaceutical Society of Japan 2010 Biological & pharmaceutical bulletin Vol.33 No.7

        <P>The blood–brain barrier (BBB) expresses transporters that influence both dopaminergic neuronal function and drug therapy for Parkinson's disease (PD). The purpose of the present study was to clarify changes of transporter mRNA expression at the BBB in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model of PD, in order to understand the pathophysiological role of BBB transport function in PD. At 7 d after MPTP treatment, mice showed a motor deficit and a loss of dopaminergic neurons. At the same time, L-type amino acid transporter 1 (LAT1) mRNA expression in the brain capillary fraction of the MPTP-treated mice was significantly reduced by 62.6% compared with saline-treated mice, while no significant change was observed in the expression of glucose transporter 1, creatine transporter 1, taurine transporter, organic cation transporter 2, serotonin transporter, norepinephrine transporter and dopamine transporter. LAT1 mRNA expression in whole brain was not affected at 1, 3 and 5 d after the treatment, but was reduced by 46.3% at 7 d. LAT1 mediates the transport of large neutral amino acids, including tyrosine, as well as the PD-therapeutic drug levodopa, across the BBB. Our findings indicate that decreased LAT1 expression at the BBB in PD patients may adversely affect amino acid supply from the circulating blood and levodopa distribution into the brain.</P>

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