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61.
Tsuyoshi Ozawa MD Shinsuke Kazama MD PhD Takashi Akiyoshi MD PhD Koji Murono MD Satomi Yoneyama MD PhD Toshiaki Tanaka MD PhD Junichiro Tanaka MD PhD Tomomichi Kiyomatsu MD PhD Kazushige Kawai MD PhD Hiroaki Nozawa MD PhD Takamitsu Kanazawa MD PhD Hironori Yamaguchi MD PhD Soichiro Ishihara MD PhD Eiji Sunami MD PhD Joji Kitayama MD PhD Teppei Morikawa MD PhD Masashi Fukayama MD PhD Toshiaki Watanabe MD PhD 《Annals of surgical oncology》2014,21(8):2650-2658
Background
The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.Methods
The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.Results
Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).Conclusions
Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC. 相似文献62.
A new class of synthetic hallucinogens called NBOMe has emerged, and reports of adverse effects are beginning to appear. We report on a case of a suicide attempt after LSD ingestion which was analytically determined to be 25I-NBOMe instead. Clinicians need to have a high index of suspicion for possible NBOMe ingestion in patients reporting the recent use of LSD or other hallucinogens. 相似文献
63.
64.
Masahiko Noguchi MD Minoru Tabata MD Kotaro Obunai MD Kentaro Shibayama MD Joji Ito MD Hiroyuki Watanabe MD Fumiaki Yashima MD Yusuke Watanabe MD Toru Naganuma MD Motoharu Araki MD Futoshi Yamanaka MD Shinichi Shirai MD Hiroshi Ueno MD Kazuki Mizutani MD Akihiro Higashimori MD Kensuke Takagi MD Norio Tada MD Masanori Yamamoto MD Kentaro Hayashida MD 《Catheterization and cardiovascular interventions》2021,97(1):E113-E120
65.
Dr. Kenji Fujiward MD PhD Satoshi Mochida MD Akihiko Ohno MD Masahiro Arai MD Atsushi Matsui MD Naohiko Masaki MD Keiichi Hirata MD Tomoaki Tomiya MD Miho Yamaoka MD Sumiko Nagoshi MD Yasuhiko Ohta MD Itsuro Ogata MD Antonio Francavilla MD David H. Van Thiel MD Thomas E. Starzl MD PhD 《Digestive diseases and sciences》1995,40(1):41-47
Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin followingCorynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed totert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearning action. 相似文献
66.
Shuichi Ishiyama Akira Fuse Hiroshi Kuzu Joji Tanaka Masahiro Urayama Yukio Igarashi Fumiaki Sakurai Kiyoshi Kawaguchi Masaru Tsukamoto Tadashi Nakamura Shuji Koike 《Journal of hepato-biliary-pancreatic sciences》1997,4(4):417-422
A microsurgical technique was used in performing anterior hepatic segmentectomy and pancreatoduodenectomy with reconstruction of the posterior hepatic artery in a 64-year-old man with widespread bile duct cancer from the intrapancreatic bile duct over the hepatic hilus. The anterior hepatic artery was obviously involved and the posterior hepatic artery just behind common hepatic duct was very close to the cancer. Microsurgical anastomosis between the remnant gastroduodenal artery and the posterior hepatic artery at the hepatic hilus made it possible to preserve the posterior segment of the liver and to perform a curative resection of the cancer. The patient had pyrexia because of suprahepatic abscess after the operation, but the abscess drained spontaneously. Postoperative arteriogram showed neither obstruction nor kinking of the reconstructed artery. He was discharged 2 months after surgery and has been enjoying a normal quality of life for 10 months since, with no signs of recurrence. It is suggested that a microsurgical technique is useful for performing an accurate anastomosis with good patency that allows not only a safe but also a highly curative operation for advanced bile duct cancer. 相似文献
67.
Mild hypothermia in neurologic emergency: an update 总被引:6,自引:0,他引:6
Induced hypothermia to treat various neurologic emergencies, which had initially been introduced into clinical practice in the 1940s and 1950s, had become obsolete by the 1980s. In the early 1990s, however, it made a comeback in the treatment of severe traumatic brain injury. The success of mild hypothermia led to the broadening of its application to many other neurologic emergencies. We sought to summarize recent developments in mild hypothermia, as well as its therapeutic potential and limitations. Mild hypothermia has been applied with varying degrees of success in many neurologic emergencies, including traumatic brain injury, spinal cord injury, ischemic stroke, subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepatic encephalopathy, perinatal asphyxia (hypoxic-anoxic encephalopathy), and infantile viral encephalopathy. At present, the efficacy and safety of mild hypothermia remain unproved. Although the preliminary clinical studies have shown that mild hypothermia can be a feasible and relatively safe treatment, multicenter randomized, controlled trials are warranted to define the indications for induced hypothermia in an evidence-based fashion. 相似文献
68.
Nobuyoshi Takasaki Kouichi Tachibana Satoshi Ogasawara Hideki Matsuzaki Jun Hagiuda Hiromichi Ishikawa Keiji Mochida Kimiko Inoue Narumi Ogonuki Atsuo Ogura Toshiaki Noce Chizuru Ito Kiyotaka Toshimori Hisashi Narimatsu 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(3):1120-1125
For normal fertilization in mammals, it is important that functionally mature sperm are motile and have a fully formed acrosome. The glycosyltransferase-like gene, human polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5), belongs to the polypeptide N-acetylgalactosamine-transferase (pp-GalNAc-T) gene family because of its conserved glycosyltransferase domains, but it uniquely truncates the C-terminal domain and is expressed exclusively in human testis. However, glycosyltransferase activity of the human GALNTL5 protein has not been identified by in vitro assay thus far. Using mouse Galntl5 ortholog, we have examined whether GALNTL5 is a functional molecule in spermatogenesis. It was observed that mouse GALNTL5 localizes in the cytoplasm of round spermatids in the region around the acrosome of elongating spermatids, and finally in the neck region of spermatozoa. We attempted to establish Galntl5-deficient mutant mice to investigate the role of Galntl5 in spermiogenesis and found that the heterozygous mutation affected male fertility due to immotile sperm, which is diagnosed as asthenozoospermia, an infertility syndrome in humans. Furthermore, the heterozygous mutation of Galntl5 attenuated glycolytic enzymes required for motility, disrupted protein loading into acrosomes, and caused aberrant localization of the ubiquitin–proteasome system. By comparing the protein compositions of sperm from infertile males, we found a deletion mutation of the exon of human GALNTL5 gene in a patient with asthenozoospermia. This strongly suggests that the genetic mutation of human GALNTL5 results in male infertility with the reduction of sperm motility and that GALNTL5 is a functional molecule essential for mammalian sperm formation.O-glycosylation begins by the addition of N-acetylgalactosamine to the serine or threonine residues in the target protein. This first step occurs in the Golgi apparatus, and is mediated by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-T; EC 2.4.1.41), which transfer GalNAc from the nucleotide sugar to the acceptor residues (1). Polypeptide N-acetylgalactosaminyltransferase-like protein 5 [GALNTL5, also described as pp-GalNac-T19 (2) or GalNac-T20 (3); Refseq accession no.: ] is classified as a member of the pp-GalNAc-T family because GALNTL5 possesses highly conserved catalytic domains of pp-GalNAc-T, whereas it uniquely lacks the conserved lectin domain at the C terminus. Thus far, 20 distinct pp-GalNAc-T genes have been identified in the human genome ( NP_660335.22, 4–6). The in vitro enzymatic activities as a glycosyltransferase have been confirmed for 14 members of this family using acceptor peptide substrates (2, 7), but not identified for the other 6 members, including GALNTL5. During the preparation of this paper, it was reported that the transferase activity of GALNTL5 (GalNAc-T20) could not be detected using in vitro assays (3). The in vivo functions of these isoforms are poorly understood because of the absence of specific enzymatic activity. Meanwhile, O-fucosyltransferase 1, a member of a fucosyltransferase family, exhibits chaperon activity specific to Notch folding in Drosophila (8). One possibility is that the isoforms lacking enzymatic activities may have functions other than characteristics of glycosyltransferases, despite having typical glycosyltransferase motifs.Spermatogenesis is a complex process in which spermatogonial stem cells form spermatozoa through the proliferative phase (spermatogonia), the meiotic phase (spermatocytes), and the differentiation or spermiogenic phase (spermatids). Spermatids are connected by intercellular bridges, through which cytoplasmic constituents are shared among haploid spermatids (9). In the last spermiogenic phase, the round haploid spermatids differentiate into spermatozoa where acrosomes and tails unique and necessary for fertilization are developed. Spermatozoa are released through the seminiferous lumen into the epididymis, where they undergo further maturation and acquire motility. Sperm motility is an important factor in normal fertilization, whereas over 80% of sperm samples from infertile men demonstrate asthenozoospermia, poor sperm motility (10). Although defects of many potential genes are reported in mouse models exhibiting asthenozoospermia (11), it is rare that mutations in these genes are identified in human patients with asthenozoospermia.To investigate the biochemical machineries and biological functions of glycosylation, we performed comprehensive identification of the mammalian glycosyltransferase genes using various approaches and confirmed their enzymatic activity in vitro using biochemical methods (12). During these studies, we identified a unique isoform of the human GALNTL5 gene restricted to the human testis. However, we could not confirm the glycosyltransferase activity of GALNTL5, including whether it is a functional molecule in spermatogenesis. Therefore, using the mouse Galntl5 gene, we attempted to elucidate the biological role of GALNTL5 in spermatogenesis and found that the heterozygous mutation of Galntl5 causes male infertility by reducing sperm motility, which highly resembles human asthenozoospermia. In reference to the aberrant protein compositions of sperm from the Galntl5 heterozygous mutant mice (Ht mice), we found a patient with asthenozoospermia carrying one heterozygous nucleotide deletion at the sixth exon of the human GALNTL5 gene. Together with these data, we speculate that the function of GALNTL5 is indispensable for mature sperm formation and that GALNTL5 might have a unique role in mammalian spermiogenesis. 相似文献
69.
Kayoko Sugawara Mie Inao Nobuaki Nakayama Satoshi Mochida 《Journal of gastroenterology》2014,49(2):363-368
Background
The significance of retinopathy during triple therapy with telaprevir is uncertain.Methods
Ophthalmologic examination was done prospectively before and every month during the therapy in 95 CHC patients.Results
Retinopathy was found in 46 (48.4 %), and the specialists recommended discontinuation of the therapy in 9 (9.5 %). Such lesions may develop as adverse effects by telaprevir, since the lesions disappeared following discontinuation of telaprevir in a 65-year-old man, in whom both pegylated-interferon (Peg-IFN) and ribavirin were continued, and reappeared when he took telaprevir again by his decision. Multivariate analysis revealed that interleukin 28B single-nucleotide polymorphism (IL28B SNP) and anemia development during the therapy were independent factors associating retinopathy.Conclusion
Ophthalmologic examinations should be done carefully during triple therapy, since the incidence was higher than that in previous Peg-IFN therapy, and lesions may develop as adverse effects by telaprevir, but not by Peg-IFN, especially in those showing preferable IL28B SNPs allele and/or anemia during the therapy. 相似文献70.
Yoshihito Uchida Masamitsu Nakao Shohei Tsuji Hayato Uemura Jun-ichi Kouyama Kayoko Naiki Daisuke Motoya Kayoko Sugawara Nobuaki Nakayama Yukinori Imai Tomoaki Tomiya Satoshi Mochida 《Journal of medical virology》2020,92(3):329-338
The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching. Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance. 相似文献