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71.
72.
Takafumi Sai Kazuyuki Uchida Hiroyuki Nakayama 《Experimental and toxicologic pathology》2013,65(4):365-373
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces damage to the nigrostriatal system and subventricular zone (SVZ) of mice. While there have been many researches on the neurotoxicity of MPTP in adult mice, there have been few reports concerning that in embryonic and newborn mice. Very recently, we revealed that such neurotoxicity of MPTP and 1-methyl-4-phenylpyridinium (MPP+), a metabolite of MPTP, is observed not only in adult mice but also in embryonic and newborn mice; however, the mechanism of acute toxicity is not well elucidated. In the present study, we attempted to reveal the involvement of monoamine oxidase B (MAO-B) in the metabolism of MPTP to MPP+ and dopamine transporter (DAT) in the neuronal cellular uptake of MPP+ during the acute toxicity of MPTP in both embryonic and newborn mice. Immunohistochemistry and double-labeling immunofluorescent staining demonstrated an increase of MAO-B-positive glial cells in the brain only in MPTP-treated mice, indicating the involvement of MAO-B in the metabolism of MPTP to MPP+ during the acute neurotoxicity of MPTP in both embryonic and newborn mice. The expression of DAT was not observed in the nigrostriatal zone of embryonic mice and in the zone and SVZ of newborn mice. The mechanism of how MPP+ is taken up into those neuronal cells remains unknown. In conclusion, MAO-B is involved in the acute neurotoxicity of MPTP in embryonic and newborn mice. 相似文献
73.
Tomoyuki Nakamura Ryosuke Yamaguchi Akifusa Wada Kazuyuki Takamura Haruhisa Yanagida Toru Yamaguchi 《Journal of orthopaedic science》2021,26(4):644-649
BackgroundAlthough acetabular dysplasia is a common etiology of osteoarthritis of the hip regardless of the history of developmental dysplasia of the hip (DDH), whether or not corrective surgeries are beneficial for the childhood asymptomatic acetabular dysplasia remains controversial due to a lack of evidence. We conducted a longitudinal study to compare the cartilaginous morphology on childhood magnetic resonance imaging (MRI) and the mature hip morphology of the same patient and to assess the predictive indicators for future acetabular dysplasia.MethodsA total of 92 unaffected hips (47 unilateral DDH and 45 unilateral Legg-Calvé-Perthes disease) were reviewed for X-ray and MRI findings on childhood (mean age: 6.0 years) and X-ray findings from a skeletally mature age with a mean follow-up period of 15.1 years. The following parameters were measured and compared: the immature-acetabular index (AI) and center edge angle (CE) on immature X-ray; the cartilage- and bone- AI, CE, Sharp and acetabular head index (AHI) on childhood MRI; and the mature-acetabular roof obliquity (ARO), CE, Sharp and AHI on skeletally mature X-ray. The prognostic factors on childhood MRI for acetabular dysplasia, defined by a CE of <20° on skeletally mature X-ray were also assessed.ResultsPositive correlations were shown between the cartilage-AI and mature-ARO (7.6°/6.3°; r = 0.44), the cartilage-CE and mature-CE (27.8°/28.0°; r = 0.62), the cartilage-Sharp and mature-Sharp (44.4°/41.8°; r = 0.52) and the cartilage-AHI and mature-AHI (78.7%/80.3%; r = 0.46). A multivariate analysis indicated cartilage-CE to be an independent predictor for acetabular dysplasia with a cut-off value of 22°. Children with a cartilage-CE <22° developed more frequently acetabular dysplasia compared to the others (52.4% vs. 1.4%).ConclusionsChildhood MRI findings are useful for the prediction of acetabular dysplasia without a DDH history. Children with a cartilage-CE ≥23° are likely to achieve a non-dysplastic hip without the need for surgical intervention. 相似文献
74.
Tsuyoshi Ito Kazuhiko Suzuki Kazuyuki Uchida Hiroyuki Nakayama 《Experimental and toxicologic pathology》2012,64(7-8):761-765
Intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration induces apoptosis of subventricular zone (SVZ) doublecortin (Dcx)-positive neural progenitor cells (migrating neuroblasts, A cells). Actually, a metabolite of MPTP, 1-methy-4-phenylpiridinium (MPP+), is responsible for neural progenitor cell toxicity. In the present study, to examine whether the MPTP-induced SVZ cell apoptosis is caused directly by MPP+ metabolized through monoamine oxidase B (MAO-B), MPTP or MPP+ was intracerebroventricularly (icv) injected into C57BL/6 mice. At Day 1 postinjection, many terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were observed in the SVZ of both low (36 μg) and high (162 μg) dose MPTP- and MPP+-injected mice. The number of Dcx-positive A cells showed a significant decrease following high dose of MPTP- or MPP+-injection on Days 1 and 3, respectively, whereas that of EGFR-positive C cells showed no change in mice with any treatment. In addition, prior icv injection of a MAO-B inhibitor, R(?)-deprenyl (deprenyl), inhibited MPTP-induced apoptosis, but not MPP+-induced apoptosis. MAO-B- and GFAP-double positive cells were detected in the ependyma and SVZ in all mice. It is revealed from these results that icv injection of MPTP induces apoptosis of neural progenitor cells (A cells) in the SVZ via MPP+ toxicity. In addition, it is suggested that the conversion from MPTP to MPP+ is caused mainly by MAO-B located in ependymal cells and GFAP-positive cells in the SVZ. 相似文献
75.
76.
Hideaki Hozumi Ryota Hokari Motonori Shimizu Koji Maruta Kazuyuki Narimatsu Hirokazu Sato Shingo Sato Toshihide Ueda Masaaki Higashiyama Chikako Watanabe Shunsuke Komoto Kengo Tomita Atsushi Kawaguchi Shigeaki Nagao Soichiro Miura 《Digestive endoscopy》2014,26(4):594-598
Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease. 相似文献
77.
Healing of two‐wall intra‐bony defects treated with a novel EMD‐liquid—A pre‐clinical study in monkeys
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78.
79.
Kazuyuki Hanajiri Hiroshi Mitsui Toshiyuki Maruyama Naoaki Hashimoto Masataka Sata Masao Omata 《Journal of gastroenterology and hepatology》2009,24(5):866-871
Background and Aim: There have so far been few reports describing echographic studies of chemically-induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine-induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c-Jun N-terminal kinase.
Methods: Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results: The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions: Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms. 相似文献
Methods: Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results: The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions: Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms. 相似文献
80.
Nakamura S Nakamura R Shibata K Kobayashi M Sahara N Shigeno K Shinjo K Naito K Ohnishi K Kasahara N Iwaki Y 《European journal of haematology》2004,73(4):285-294
Adeno-associated virus (AAV) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. However, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. To overcome limitations in AAV production, in this report, we explored the possibility of generating AAV packaging cell line, 293T R/C.VA.E2A.E4. cells, by using lentivirus-mediated transduction of Rep/Cap gene of AAV-2, VA RNA, E2A, and E4 genes of Ad5 into 293T cells. In packaging cell lines, it is important that supply of the AAV vector can be stably performed for long time. We showed that the 293T R/C.VA.E2A.E4. cells have stably maintained the transduced components after more than 10 passages and yielded high-titer AAV vectors, and the titer of AAV vectors did not decline even if culture of the packaging cells was continued for long time. The Rep/Cap and E4 gene products caused no remarkable cytotoxicity. The 293T R/C.VA.E2A.E4. cells might be able to tolerate the Rep/Cap and E4 gene products, or have less copy numbers of the Rep/Cap and E4 genes than the traditional method. Moreover, we showed that the AAV vectors derived from 293T R/C.VA.E2A.E4. cells infected the primary human CD34+ haematopoietic progenitor cells with high efficiency (50-70%). In the 293T R/C.VA.E2A.E4. cells, the AAV vectors can be generated by the transfection of one AAV vector plasmid, and large-scale AAV production can be easily achieved. It is important that cumbersome, variable, and costly transfection is avoided. 相似文献