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51.
Cultured epidermal keratinocytes and dermal fibroblasts derived from porokeratosis (PK) patients' skin lesions or normal-appearing skin had numerical and sometimes structural chromosomal abnormalities. Such abnormal cells were seen in 4.08% and 0.375% of all the studied epidermal keratinocytes derived from affected skin and normal-appearing skin, respectively. Similar abnormalities were present in 1.70% and 3.67% of the dermal fibroblasts from the patients' affected skin and normal-appearing skin, respectively. Chromosomal abnormalities were more frequent in keratinocytes and fibroblasts from the patients' skin than in keratinocytes (0.429%) or in fibroblasts (1.22%) derived from normal control donors. Clonal proliferation of such abnormal cells was frequently seen in keratinocytes from the patients' affected skin. The frequent appearance of chromosomal abnormalities and clonal proliferation in epidermal keratinocytes may explain skin lesion formation and skin cancer development in PK patients. 相似文献
52.
Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer 总被引:5,自引:0,他引:5
Ito R Oue N Yoshida K Kunimitsu K Nakayama H Nakachi K Yasui W 《Virchows Archiv : an international journal of pathology》2005,447(4):717-722
Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our
serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas.
CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric
carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics
and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal
metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression
was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive
CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases
that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression
of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. 相似文献
53.
ABC proteins: key molecules for lipid homeostasis 总被引:2,自引:0,他引:2
Takahashi K Kimura Y Nagata K Yamamoto A Matsuo M Ueda K 《Medical molecular morphology》2005,38(1):2-12
Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures. 相似文献
54.
Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry 总被引:3,自引:0,他引:3
Yu P Constien R Dear N Katan M Hanke P Bunney TD Kunder S Quintanilla-Martinez L Huffstadt U Schröder A Jones NP Peters T Fuchs H de Angelis MH Nehls M Grosse J Wabnitz P Meyer TP Yasuda K Schiemann M Schneider-Fresenius C Jagla W Russ A Popp A Josephs M Marquardt A Laufs J Schmittwolf C Wagner H Pfeffer K Mudde GC 《Immunity》2005,22(4):451-465
The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype. 相似文献
55.
Yasuhiko Hirata Hiromi Ishibashi Harumichi Kimura Kazuhiro Hayashida Masanori Nagano Hideo Okubo 《Inflammation》1985,9(2):201-209
Isolated rat Kupffer cells produced a factor which stimulated the synthesis of
2-macroglobulin (2M) in primary cultured rat hepatocytes. Although Kupffer cells placed in culture produced the factor without stimulation by lipopolysaccharide (LPS), the LPS-stimulated cells produced larger amounts of the factor. On the other hand, the production of the factor was inhibited by addition of actinomycin D. The induction of2M synthesis by cultured hepatocytes was enhanced in the presence of dexamethasone (Dex), in that hepatic synthesis of2M increased by addition of the factor alone and with Dex 1.5 and three- to four-fold, respectively. The factor was nondialyzable and stable at 60°C for 30 min. When the factor was fractionated using the molecular sieve method, the activity recovered in the fraction had a molecular weight of over 30,000. 相似文献
56.
T cell immunity and primary biliary cirrhosis 总被引:4,自引:0,他引:4
T lymphocytes play a pivotal role in the autoimmune response in primary biliary cirrhosis (PBC). Recent studies have shown that there is overlapping in the PDC-E2-specific T and B cell epitopes. In addition, helper T and cytotoxic T cell epitopes all contain a shared peptide sequence. In addition, recognition of exogenous antigens including bacterial antigens by autoantigen-specific T cell and the mechanism of molecular mimicry provide a clue to clarifying the pathogenesis of PBC. Furthermore, the findings that autoantigen-immune complexes cross present and also that the presentation of autoantigen is of a higher relative efficiency, define a unique role of autoantibodies in the pathogenesis of the autoimmune disease. The mechanism of immune-mediated bile duct damage in PBC, including the possible role of T cell-mediated cytotoxicity and molecular mimicry is discussed. 相似文献
57.
ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats 总被引:28,自引:1,他引:28
Nishitoh H Matsuzawa A Tobiume K Saegusa K Takeda K Inoue K Hori S Kakizuka A Ichijo H 《Genes & development》2002,16(11):1345-1355
Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce neuronal cell death. However, the molecular mechanism of polyQ-induced cell death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and cell death. These findings suggest that ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases. 相似文献
58.
Emergence of a unique O3:K6 clone of Vibrio parahaemolyticus in Calcutta, India, and isolation of strains from the same clonal group from Southeast Asian travelers arriving in Japan. 总被引:4,自引:0,他引:4 下载免费PDF全文
J Okuda M Ishibashi E Hayakawa T Nishino Y Takeda A K Mukhopadhyay S Garg S K Bhattacharya G B Nair M Nishibuchi 《Journal of clinical microbiology》1997,35(12):3150-3155
Active surveillance of Vibrio parahaemolyticus infection among hospitalized patients in Calcutta, India, was initiated in January 1994. The incidence of cases of V. parahaemolyticus infection suddenly increased in February 1996 and has remained high since then. One hundred thirty-four strains of V. parahaemolyticus isolated from January 1994 to August 1996 were examined for serovar, the presence of the thermostable direct hemolysin gene (tdh) and tdh-related hemolysin genes (trh1 and trh2), production of urease, and antibiogram. Strains of the O3:K6 serovar appeared for the first time in February 1996. The O3:K6 serovar strains accounted for 50 to 80% of the strains isolated during the high-incidence period (February to August 1996). All of the serovar O3:K6 strains carried the tdh gene but not the trh genes and did not produce urease. All of the isolates except two were sensitive to all of the antibiotics tested. These and the results of analysis by an arbitrarily primed PCR method indicated that the O3:K6 serovar strains belong to a unique clone. When the O3:K6 serovar strains, isolated from travelers arriving in Japan from Southeast Asian countries, were compared by the arbitrarily primed PCR method, the strains isolated between 1982 and 1993 were distinct from Calcutta O3:K6 while the strains isolated in 1995 and 1996 were indistinguishable from the Calcutta O3:K6 strains. The results suggest that this unique O3:K6 clone may have become prevalent not only in Calcutta but also in Southeast Asian countries very recently. Not only the O3:K6 strains but also the non-O3:K6, tdh-bearing strains isolated in 1996 produced thermostable direct hemolysin at high levels, and thus the level of hemolysin produced does not appear to have influenced the high incidence of serovar O3:K6 strains. 相似文献
59.
The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization 总被引:9,自引:0,他引:9
Tsutsumi C Sonoda KH Egashira K Qiao H Hisatomi T Nakao S Ishibashi M Charo IF Sakamoto T Murata T Ishibashi T 《Journal of leukocyte biology》2003,74(1):25-32
Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation. 相似文献
60.
The stereoregularity of poly(methyl vinyl ketone) (PMVK) was determined by NMR spectra of the polymers. Isotactic and atactic PMVK's were thermally degraded, and thermogravimetric analysis, IR and visible and UV spectroscopy were applied to elucidate the mechanism of the degradation. It was found that the isotactic polymer begins to degrade at lower temperature than the atactic polymer, but its rate becomes lower than that of the atactic polymer at temperatures higher than 320°C. If the two types of polymers were treated at a constant temperature (200°C) for varying times under N2 atmosphere, the isotactic polymer showed a higher degradation rate as determined by thermogravimetric analysis and IR spectroscopy. The isotactic polymer shows a higher tendency to form a monocyclic structure in the heat treatment than the atactic polymer. This is similar to poly(isopropenyl methyl ketone). 相似文献