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Ohkubo K Nagashima M Naito Y Taguchi T Suita S Okamoto N Fujinaga H Tsumura K Kikuchi K Ono J 《Clinical endocrinology》2005,62(4):458-465
OBJECTIVE: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic beta-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic beta-cell ATP-sensitive potassium channel. PATIENTS AND METHODS: In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. RESULTS: We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). CONCLUSION: The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations. 相似文献
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Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis
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Yuka Terada Mayuko Fujimura Sachiyo Nishimura Maho Tsubota Fumiko Sekiguchi Atsufumi Kawabata 《Journal of neuroscience research》2015,93(2):361-369
Hydrogen sulfide (H2S), formed by multiple enzymes, including cystathionine‐γ‐lyase (CSE), targets Cav3.2 T‐type Ca2+ channels (T channels) and transient receptor potential ankyrin‐1 (TRPA1), facilitating somatic pain. Pancreatitis‐related pain also appears to involve activation of T channels by H2S formed by the upregulated CSE. Therefore, this study investigates the roles of the Cav3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T‐channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H2S donor. In the mice with cerulein‐induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55‐0396 (NNC), a selective T‐channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Cav3.2 selectively among three T‐channel isoforms; and knockdown of Cav3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein‐induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Cav3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein‐induced pancreatitis. The data indicate that TRPA1 and Cav3.2 mediate the exogenous H2S‐induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Cav3.2 targeted by H2S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. © 2014 Wiley Periodicals, Inc. 相似文献
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Tetsuji Sawada Masakazu Yashiro Kazuhiro Sentani Naohide Oue Wataru Yasui Kohji Miyazaki Keita Kai Sachio Fushida Takashi Fujimura Masaichi Ohira Yoshihiro Kakeji Shoji Natsugoe Ken Shirabe Sachiyo Nomura Yutaka Shimada Naohiro Tomita Kosei Hirakawa Yoshihiko Maehara 《Gastric cancer》2015,18(1):119-128
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Purpose
Commercially available mechanical devices for gastrointestinal anastomosis are mostly made in overseas. Japanese female surgeons have described these devices as being too large and difficult to handle. This study investigated the degree of satisfaction and problems experienced by Japanese surgeons in using various staplers for mechanical anastomosis.Methods
A questionnaire was prepared and sent via email to 5,537 members of the Japanese Society of Gastroenterological Surgery. The questionnaire included sex, age, surgical glove size, degree of satisfaction with various mechanical staplers, stress felt when using the staplers in anastomosis, and problems regarding the devices.Results
Valid responses were received from 241 respondents (167 males, 74 females, response rate 4.9 %). The satisfaction rate ranged from 0 to 100 %. The average glove size in males was significantly larger than that in females (median: 7.0 versus 6.0; P < 0.0001). Surgeons with glove size 6.0 or smaller felt stress more frequently than those with size 6.5 or larger (median: 40 vs. 20 %; P < 0.0001). Surgeons with glove size 6.0 and smaller experienced more difficulties during firing and releasing.Conclusion
The satisfaction rates with currently available mechanical staplers were low. Japanese surgeons with small hands felt more stress when using the staplers. Ergonometric consideration is necessary in stapler design. 相似文献100.