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Shiraki M Aihara H Kinouchi Y Takahashi S Oki M Noguchi M Takahashi K Miyazaki J Shimosegawa T 《Laboratory investigation; a journal of technical methods and pathology》2004,84(11):1491-1500
T-helper-1 (Th1) cytokines play an important role in Crohn's disease, and interleukin-12 (IL-12), which is composed of two subunits, p40 and p35, drives Th1 differentiation. In previous reports, IL-12 p40 was shown to prevent IL-12 from binding to the receptor. We demonstrate here the effect of IL-12 p40 overexpression in intestinal epithelia on enterocolitis mediated by Th1 cells in IL-10-deficient (IL-10(-/-)) mice on a C57BL/6J background. IL-10 deficient (IL-10(-/-))/T3b-IL-12 p40+ (IL-12 p40+) mice and IL-10(-/-)/T3b-IL-12 p40- (IL-12 p40-) mice were generated by crossing T3b-IL-12 p40 transgenic mice and IL-10(-/-) mice. At 8 weeks of age, IL-12 p40+ mice did not show any clinical manifestations of colitis. The colon length of IL-12 p40- mice became shorter than that of IL-12 p40+ mice. The histological score of IL-12 p40+ mice was lower. Interferon-gamma (IFN-gamma) production was suppressed in both the mesenteric lymph node cell culture and colon tissue culture of IL-12 p40+ mice. There was no significant difference in IL-4 production and tumor necrosis factor-alpha (TNF-alpha) production between the two groups. These results show that overexpression of IL-12 p40 in intestinal epithelia prevents enterocolitis in IL-10(-/-) mice by suppressing IFN-gamma production, and suggest a potential clinical application of IL-12 p40 for Crohn's disease. Furthermore, these results also suggest that local gene transduction in the intestinal epithelium may be a potent therapeutic approach for Crohn's disease. 相似文献
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Hoshi T Sasano H Kato K Ohara S Shimosegawa T Toyota T Nagura H 《Human pathology》1999,30(12):1412-1417
Helicobacter pylori (HP) is believed to be involved in the transition from normal gastric mucosa to atrophic gastritis and intestinal metaplasia. Infection with the organism is one of the risk factors for development of intestinal-type gastric adenocarcinoma, possibly through altered cell turnover. Medical eradication of HP is widely performed for the treatment of peptic ulcers and other upper gastrointestinal disorders. Eradication of HP may affect altered cell turnover of the gastric mucosa caused by the infection, but there are few reports comparing sterilized mucosa with HP-infected and non-infected mucosa. In this study, we examined cell damage using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), in situ nick translation (ISNT), and cell proliferation by Ki 67 immunohistochemistry staining in gastric mucosa before and after HP eradication and in non-infected gastric mucosa. We then compared these findings using endoscopic gastric biopsy specimens. Labeling indices of TUNEL (2.46 +/- 1.22), ISNT (1.13 +/- 0.42), and Ki67 (21.8 +/- 6.14) in tissue from which HP had been eradicated were significantly lower than those of HP-infected mucosa (6.36 +/- 2.26, 4.00 +/- 1.62, 45.8 +/- 5.35, for TUNEL, ISNT, and Ki67, respectively). There were no significant differences between formerly infected and non-infected mucosa (TUNEL: 2.26 +/- 0.69, ISNT: 1.29 +/- 0.63, Ki67: 23.5 +/- 8.20). These results indicate that medical HP eradication results in decreased cell proliferation and damage, restoring the condition seen in non-infected mucosa. Thus, HP eradication may be effective, not only in the treatment of gastric ulcers or gastric symptoms, but also in the prevention of gastric carcinoma. 相似文献
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Keiichi Tamai Masafumi Toyoshima Nobuyuki Tanaka Noriko Yamamoto Yuji Owada Hiroshi Kiyonari Kazuko Murata Yoshiyuki Ueno Masao Ono Tooru Shimosegawa Nobuo Yaegashi Masahiko Watanabe Kazuo Sugamura 《The American journal of pathology》2008,173(6):1806-1817
The endosomal sorting complex required for transport (ESCRT) proteins form multimolecular complexes that control multivesicular body formation, endosomal sorting, and transport ubiquitinated membrane proteins (including cell-surface receptors) to the endosomes for degradation. There is accumulating evidence that endosomal dysfunction is linked to neural cell degeneration in vitro, but little is known about the relationship between neural disorders and ESCRT proteins in vivo. Here we specifically deleted the hrs gene, ESCRT-0, in the neurons of mice by crossing loxP-flanked hrs mice with transgenic mice expressing the synapsin-I Cre protein (SynI-cre). Histological analyses revealed that both apoptosis and a loss of hippocampal CA3 pyramidal neurons occurred in the hrsflox/flox;SynI-cre mice. Notably, the hrsflox/flox;SynI-cre mice accumulated ubiquitinated proteins, such as glutamate receptors and an autophagy-regulating protein, p62. These molecules are particularly prominent in the hippocampal CA3 neurons and cerebral cortex with advancing age. Accordingly, we found that both locomotor activity and learning ability were severely reduced in the hrsflox/flox;SynI-cre mice. These data suggest that Hrs plays an important role in neural cell survival in vivo and provide an animal model for neurodegenerative diseases that are known to be commonly affected by the generation of proteinaceous aggregates. 相似文献
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Amadou Kane Edmond Ekué Creppy Angelika Roth Robert Röschenthaler Guy Dirheimer 《Archives of toxicology》1986,58(4):219-224
The distribution of a single low dose of [3H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA. 相似文献
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Jun Hatazawa Hiroshi Itoh Eku Shimosegawa Iwao Kanno Matsutaroh Murakami Shuichi Miura Hidehiro Iida Toshio Okudera Atsushi Inugami Toshihide Ogawa Hideaki Fujita Yuichi Satoh Ken Nagata Yutaka Hirata Kazuo Uemura 《Annals of nuclear medicine》1994,8(3):213-217
We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain. 相似文献
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Xiaoyi Jin Tomoyuki Koike Takashi Chiba Yutaka Kondo Nobuyuki Ara Kaname Uno Naoki Asano Katsunori Iijima Akira Imatani Mika Watanabe Akio Shirane Tooru Shimosegawa 《Digestive endoscopy》2013,25(5):547-549
In the present paper, we report a case of rare collagenous gastritis. The patient was a 25‐year‐old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis. 相似文献
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F. A. Cissé M. M. Konaté W. A. Ekué M. Cissé N. Camara B. S. Djigué A. O. M. Baldé I. A. Camara F. L. Y. Diallo B. S. Diallo F. Konaté L. F. Barry I. Diakhaté A. Cissé 《Bulletin de la Societe de pathologie exotique (1990)》2016,109(2):70-76
Cardiovascular and neurological manifestations associated with thiamine deficiency in Guinean prisons are common but not reported.We performed a prospective study of 38 cases related to vitamin B1 deficiency over a period of 4 years. In this population, the literature of traditional data gathered: frequency peak after thirty (92.6%) and clear representation male (sex ratio M/F: 18/1). The clinical symptomatology remains essentially dominated by sensorimotor polyneuropathy and pure sensory (52.2%), overall heart failure (31.5%) and to a lesser degree by Gayet Wernicke’s encephalopathy (7.8%) and shoshin beriberi with severe evolution (5.2%). The study of nutritional status by body mass index (BMI) of the World Health Organization, by the criteria of Detsky and biological markers including albumin, shows that these patients are severely malnourished. 相似文献