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81.
Hamada K Sasaki T Koni PA Natsui M Kishimoto H Sasaki J Yajima N Horie Y Hasegawa G Naito M Miyazaki J Suda T Itoh H Nakao K Mak TW Nakano T Suzuki A 《Genes & development》2005,19(17):2054-2065
PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice. Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85alpha and p110gamma. In vitro, Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration. Tie2CrePten(flox/flox) mice died before embryonic day 11.5 (E11.5) due to bleeding and cardiac failure caused by impaired recruitment of pericytes and vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the endocardium. These phenotypes depend strongly on p110gamma rather than on p85alpha and were associated with decreased expression of Ang-1, VCAM-1, connexin 40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2. Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis. 相似文献
82.
Ikegawa S Ohashi H Ogata T Honda A Tsukahara M Kubo T Kimizuka M Shimode M Hasegawa T Nishimura G Nakamura Y 《American journal of medical genetics》2000,94(4):300-305
Chondrodysplasia punctata (CDP) is a heterogeneous group of skeletal dysplasias characterized by stippled epiphyses. A subtype of CDP, X-linked dominant chondrodysplasia punctata (CDPX2), known also as Conradi-Hünermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. The cause of CDPX2 was unknown until recent identification of mutations in the gene encoding Delta(8),Delta(7) sterol isomerase emopamil-binding protein (EBP). Twelve different EBP mutations have been reported in 14 patients with CDPX2 or unclassified CDP, but with no evidence of correlation between phenotype and nature of the mutation. To characterize additional mutations and investigate possible phenotype-genotype correlation, we sequenced the entire EBP gene in 8 Japanese individuals with CDP; 5 of them presented with a CDPX2 phenotypes. We found EBP mutations in all 5 CDPX2 individuals, but none in non-CDPX2 individuals. Three of these CDPX2 individuals carried novel nonsense mutations in EBPand the other two, separate missense mutations that had been reported also in different ethnic groups. Our results, combined with previous information, suggest all EBP mutations that produce truncated proteins result in typical CDPX2, whereas the phenotypes resulted from missense mutations are not always typical for CDPX2. Patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Delta(8), Delta(7) sterol isomerase. X-inactivation patterns of the patients showed no skewing, an observation that supports the assumption that inactivation of the EBP gene occurs at random in affected individuals. 相似文献
83.
Akitaka Nonomura Yuji Mizukami Toru Hasegawa Mitsuo Ohkawa Masumi Kadoya 《Pathology international》1995,45(2):160-164
A case of a rare renal tumor showing characteristic histo-logic features is presented. The patient was a 54 year old female, whose renal tumor was incidentally detected on abdominal ultrasound (US) examination. Ultrasound, computed tomography and angiography findings were consistent with a diagnosis of renal cell carcinoma of the hypovascular type. Left nephrectomy was performed. The tumor, which measured 2.6 times2.6 times 2.5 cm, was located in the left renal cortex, and had a uniformly whitish-yellow cut surface and well-defined margin. Histologically, the tumor was characterlzed by its monomorphous growth pattern and was composed of uniformly small cells arranged in a tubular or rosette-like pattern. The tumor cells had scant cytoplasm and the nuclei were small, round and regular. These histo-logic features resembled the epithelial elements of a metanephric hamartoma in the nephroblastomatosis complex in infants. However, there was no mitosis and cellular atypia was minimal, suggesting benignity. According to these his-tologic features, the diagnosis of metanephric adenoma was made. Its clinicopathologic features are discussed. 相似文献
84.
Circadian rhythms of pineal melatonin release were measured in freely moving pigeons (Columba livia) by in vivo microdialysis. The birds were placed in light-dark cycles with 12 h of light and 12 h of darkness (LD 12:12) or continuous dim light (LLdim) after LD 12:12. Although the level of melatonin was various, daily changes of melatonin with higher levels during the dark and lower levels during the light were observed in all of the birds examined. The daily changes of melatonin persisted in LLdim, indicating circadian nature of pineal melatonin release. Moreover pineal melatonin release was inhibited by acute exposure of light during the dark. These results indicate that microdialysis is useful for studying circadian pineal melatonin rhythms of birds. 相似文献
85.
Okamoto N Toribe Y Nakajima T Okinaga T Kurosawa K Nonaka I Shimokawa O Matsumoto N 《Journal of human genetics》2002,47(10):0556-0559
Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation,
and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of
the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber
type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association
may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome.
Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.
Received: March 4, 2002 / Accepted: July 7, 2002 相似文献
86.
Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis. 总被引:4,自引:1,他引:4 下载免费PDF全文
A. Nomura Y. Morita S. Maruyama N. Hotta M. Nadai L. Wang T. Hasegawa S. Matsuo 《The American journal of pathology》1997,151(2):539-547
The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage. 相似文献
87.
IgA plasma cells in biliary mucosa: a likely source of locally synthesized IgA in human hepatic bile 总被引:2,自引:0,他引:2 下载免费PDF全文
H Nagura Y Tsutsumi H Hasegawa K Watanabe P K Nakane W R Brown 《Clinical and experimental immunology》1983,54(3):671-680
IgA synthesized in hepatobiliary tissues accounts for about one-half of the IgA present in human hepatic bile, but the location of the IgA synthesizing cells has been in doubt because few plasma cells are present in normal liver. Therefore, we immunocytochemically localized IgA, J chain and secretory component in bile duct tissues of six patients operated upon for biliary duct obstruction. Numerous plasma cells containing IgA and J chain were found surrounding the accessory glands of the major bile ducts and in the area just beneath the surface epithelium of the ducts. At the ultrastructural level, IgA and SC in the epithelial cells had the features characteristic of secretory component-mediated endocytic translocation of IgA. We conclude that plasma cells in biliary duct mucosa are the likely source of much of the locally synthesized IgA that is secreted into human hepatic bile. The IgA probably reaches the bile by direct transfer across biliary epithelium. 相似文献
88.
Photon attenuation in small animal nuclear medicine scans can be significant when using isotopes that emit lower energy photons such as iodine-125. We have developed a method to use microCT data to perform attenuation corrected small animal single-photon emission computed tomography (SPECT). A microCT calibration phantom was first imaged, and the resulting calibration curve was used to convert microCT image values to linear attenuation coefficient values that were then used in an iterative SPECT reconstruction algorithm. This method was applied to reconstruct a SPECT image of a uniform phantom filled with 125I-NaI. Without attenuation correction, the image suffered a 30% decrease in intensity in the center of the image, which was removed with the addition of attenuation correction. This reduced the relative standard deviation in the region of interest from 10% to 6%. 相似文献
89.
CD10 is a cell surface metalloprotease expressed by a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes, and some epithelial cells. We noticed that stromal cells of some cancers are positive for CD10. In this study, we investigated the role of CD10 produced by the stromal cells of colorectal neoplasms in the progression of colorectal neoplasms. Immunohistochemical examination of CD10 and p53 was performed in 169 colorectal epithelial neoplasms representing various stages of carcinogenesis. The results were correlated with the morphologic characteristics of the neoplasms. There was no expression of CD10 in the stromal cells of normal colorectal tissue. CD10-positive stromal cells were present adjacent to the tumor cells in 16 of 73 adenomas with mild or moderate dysplasia. More frequent expression of CD10 by the stromal cells was detected in adenomas with severe dysplasia (12 of 17), intramucosal carcinomas (10 of 16), and invasive carcinomas (50 of 63) than in adenomas with mild or moderate dysplasia (P < 0.0001). Expression of CD10 by > 10% of the stromal cells was detected only within the area of the invasive growth front of invasive carcinomas, not in adenomas and in only 1 of the intramucosal carcinomas. The difference between invasive and non invasive tumors was significant (P < 0.0001). The stromal expression of CD10 was significantly associated with the accumulation of p53 and a larger tumor size. These results indicate that CD10 expression is an integral part of colorectal carcinogenesis. CD10 expression seems to contribute to the invasion and thus probably facilitates metastasis. 相似文献
90.
Host resistance to Listeria monocytogenes infection is enhanced but resistance to Staphylococcus aureus infection is reduced in acute graft-versus-host disease in mice 下载免费PDF全文
Miura T Mizuki D Sasaki S Hasegawa S Sashinami H Nakane A 《Infection and immunity》2000,68(7):4340-4343
Acute graft-versus-host disease (GVHD) is characterized by the production of high levels of T helper 1 (Th1)-type cytokines. Bone marrow transplantation from allogeneic C57BL/6 cells to CBF(1) mice produced acute GVHD. Host resistance to Th1-driven Listeria monocytogenes was enhanced, whereas host resistance to Th2-driven Staphylococcus aureus was reduced during acute GVHD. These results suggest that opposite host responses are observed between Th1-driven and Th2-driven bacterial infections in acute GVHD. 相似文献