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991.
Hahn S Cho K Ryu K Kim J Pai K Kim M Park H Yoo O 《Molecular genetics and metabolism》2001,73(1):86-90
Menkes disease is an X-linked recessive disorder of the copper metabolism and affected males suffer a systemic copper deficiency due to malabsorption and defective distribution of dietary copper. It is caused by a defect in the Menkes (ATP7A) gene, which encodes a transmembrane copper-transporting P-type ATPase. A variety of mutations were reported; however, only a few mutations were reported in Asian patients. We identified four novel mutations and one known mutation in five Korean patients. Arg646Ter in exon 8, a novel mutation transmitted from his carrier mother, was identified in one patient. Prenatal DNA diagnosis on an unaffected fetus in this carrier mother was successfully accomplished. An additional three novel mutations, Leu706Arg in exon 9, Gly1118Asp in exon 17, and Gly1255Arg in exon 19, were identified. Splicing mutation was not identified. Menkes disease in Korean patients appears to be caused by heterogeneous mutations with different spectrums from Caucasian patients. 相似文献
992.
Mashimo T Goodarzi G Watabe M Cuthbert AP Newbold RF Pai SK Hirota S Hosobe S Miura K Bandyopadhyay S Gross SC Watabe K 《Genes, chromosomes & cancer》2000,28(3):285-293
Much of the lethality of malignant neoplasms is attributable directly to their ability to develop secondary growths in organs at a distance from the primary tumor mass, whereas few patients die from their primary neoplasm. Little is known about the molecular mechanism of tumor metastasis, however, which is controlled by a variety of positive and negative factors. In the search for metastasis suppressor genes, we have used the microcell-mediated chromosome transfer method and a rat prostate tumor model in SCID mice. When human chromosome 2 was introduced into the highly metastatic rat prostatic tumor cell, AT6.1, the metastatic ability of this cell was significantly (>99%) decreased in animals. An STS-based PCR analysis for 8 hybrid clones indicates that the suppressor activity is located in the p25-22 region of the chromosome. Furthermore, the AT6.1 cell with human chromosome 2 showed a reduced ability to invade Matrigel, suggesting that the suppressor activity is involved in the step of tumor invasion during the progression of prostate cancer. We have also examined the status of the suppressor region on chromosome 2 in human prostate cancer specimens and found that this region was often lost in high-grade tumors. These results suggest that the putative suppressor gene on chromosome 2 is functionally involved in the progression of human prostate cancer. Genes Chromosomes Cancer 28:285-293, 2000. 相似文献
993.
Results of our previous studies have shown that the chemiluminescence response of human neutrophils (polymorphonuclear leukocytes [PMNs]) is inhibited by plasmid-mediated cell surface components from Yersinia enterocolitica. In this study we examined the susceptibility to phagocytosis of Y. enterocolitica cells with or without plasmid-mediated surface structure and the effect of isolated outer membrane fragments on phagocytosis of Escherichia coli by PMNs in vitro. Y. enterocolitica cells with expressed plasmid-mediated surface structure were much less sensitive to ingestion by PMNs than those without it, and the resistance to phagocytosis was readily eliminated in a dose-dependent fashion by pronase treatment of whole cells, which was shown to remove plasmid-encoded outer membrane proteins. Ingestion and intracellular killing of E. coli were inhibited significantly in the presence of isolated outer membrane fragments derived from plasmid-bearing Y. enterocolitica cells. To assess the interaction of Y. enterocolitica with phagocytic cells in vivo, two isogenic strains of Y. enterocolitica, differing only in the presence or absence of the virulence plasmid, were inoculated intradermally into the backs of rabbits; and tissue sections obtained at 12 h postinoculation were examined by light and electron microscopy. The plasmidless strain was found almost entirely in PMNs or mononuclear cells. In contrast, the plasmid-bearing strain was found to be surrounded by, or interspersed with, PMNs and mononuclear cells; but most bacteria were extracellular, with little evidence of phagocytosis. These results suggest that plasmid-mediated cell surface components of Y. enterocolitica act as antiphagocytic factors, thus facilitating the survival and proliferation of the organism in the host tissue. 相似文献
994.
Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats 总被引:7,自引:9,他引:7
Huntington's disease (HD) is caused by expansion of a glutamine repeat in
huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients
and >60 repeats in juvenile HD patients. An N-terminal fragment of
mutant huntingtin forms aggregates in neuronal nuclei in the brains of
transgenic mice and HD patients. Aggregation of expanded polyglutamine is
thought to be a common pathological mechanism in HD and other glutamine
repeat diseases. It is not clear how the length of the repeats is
correlated with formation of protein aggregates. By expressing a series of
huntingtin constructs encoding various glutamine repeats (23-150 units) in
cultured cells we observed N-terminal fragments of huntingtin (amino acids
1-67 and 1-212), but not full- length huntingtins, with glutamine repeats
>/=66 units formed protein aggregates. Huntingtin aggregation was not
induced when the repeat was </=49 units and was markedly promoted by
very long repeats >/=120 units. This study suggests that various
N-terminal fragments of mutant huntingtin can form aggregates and that
aggregation is prompted by lengthening the glutamine repeat.
相似文献
995.
Helicobacter pylori culture supernatant interferes with epidermal growth factor-activated signal transduction in human gastric KATO III cells. 总被引:1,自引:0,他引:1 下载免费PDF全文
R. Pai F. A. Wyle T. L. Cover R. M. Itani M. J. Domek A. S. Tarnawski 《The American journal of pathology》1998,152(6):1617-1624
The mechanisms by which Helicobacter pylori infection leads to gastroduodenal ulceration remain poorly understood. Previous studies have shown that H. pylori vacuolating cytotoxin (VacA) inhibits proliferation of gastric epithelial cells, which suggests that H pylori may interfere with gastric mucosal repair mechanisms. In this study, we investigated the effects of H. pylori broth culture supernatants on epidermal growth factor (EGF)-mediated signal transduction pathways in a gastric carcinoma cell line (KATO III). Exposure of these cells to EGF resulted in increased expression and phosphorylation of the EGF receptor (EGF-R), increased ERK2 activity and phosphorylation, and increased c-fos protein levels. Preincubation of cells with broth culture supernatant from VacA (+) H. pylori strain 60190 inhibited the capacity of EGF to induce each of these effects. In contrast, preincubation of cells with broth culture supernatant from an isogenic VacA-mutant strain (H. pylori 60190-v1) failed to inhibit the effects of EGF. These results suggest that the H. pylori vacuolating cytotoxin interferes with EGF-activated signal transduction pathways, which are known to be essential for cell proliferation and ulcer healing. 相似文献
996.
Inhibition of major histocompatibility complex II expression and antigen processing in murine alveolar macrophages by Mycobacterium bovis BCG and the 19-kilodalton mycobacterial lipoprotein 下载免费PDF全文
Fulton SA Reba SM Pai RK Pennini M Torres M Harding CV Boom WH 《Infection and immunity》2004,72(4):2101-2110
Alveolar macrophages constitute a primary defense against Mycobacterium tuberculosis, but they are unable to control M. tuberculosis without acquired T-cell immunity. This study determined the antigen-presenting cell function of murine alveolar macrophages and the ability of the model mycobacterium, Mycobacterium bovis BCG, to modulate it. The majority (80 to 85%) of alveolar macrophages expressed both CD80 (B7.1) and CD11c, and 20 to 30% coexpressed major histocompatibility complex II (MHC-II). Gamma interferon (IFN-gamma) enhanced MHC-II but not B7.1 expression. Naive or IFN-gamma-treated alveolar macrophages did not express CD86 (B7.2), CD11b, Mac-3, CD40, or F4/80. M. bovis BCG and the 19-kDa mycobacterial lipoprotein inhibited IFN-gamma-regulated MHC-II expression on alveolar macrophages, and inhibition was dependent on Toll-like receptor 2. The inhibition of MHC-II expression by the 19-kDa lipoprotein was associated with decreased presentation of soluble antigen to T cells. Thus, susceptibility to tuberculosis may result from the ability of mycobacteria to interfere with MHC-II expression and antigen presentation by alveolar macrophages. 相似文献
997.
Kao PC van Heerden JA Farley DR Thompson GB Taylor RL 《Annals of clinical and laboratory science》2002,32(3):244-251
The Mayo Clinic was one of the first institutions to develop an in-house rapid parathyroid hormone (PTH) assay that used homegrown antibodies to monitor plasma PTH levels during parathyroidectomy. This PTH assay is economical, but it requires highly trained technologists and an experienced laboratory director and it is difficult to perform in the operating suite. We sought a fully automated multipurpose autoanalyzer with bar code reader to identify different patients' names and capacity to manage specimens from several patients who are having simultaneous operations. In addition, after complete tumor removal, the plasma PTH level should decrease to < 25% of the baseline level; otherwise, it may indicate that the antibodies used in the assay have cross-reacted with long half-life fragments other than intact PTH, which has a half-life of only approximately 2 min. An automated multipurpose analyzer, the Immulite 1000 with a Turbo PTH kit (DPC), fits these criteria and has replaced our in-house rapid assay. Of 47 patients who had parathyroidectomy for primary hyperparathyroidism and were tested with the new equipment, 45 (96%) had their plasma PTH levels decrease to < 25% of the baseline levels. In 41 of 47 patients (87%), the PTH value decreased to < 5 pmol/L (provisional reference range) within 20 min after tumor excision. The usefulness of the PTH assay extends from the traditional diagnosis of parathyroid disease to intraoperative monitoring, helping to ensure a higher cure rate. 相似文献
998.
Goodarzi G Mashimo T Watabe M Cuthbert AP Newbold RF Pai SK Hirota S Hosobe S Miura K Bandyopadhyay S Gross SC Balaji KC Watabe K 《Genes, chromosomes & cancer》2001,32(1):33-42
Acquisition of metastatic ability by prostate cancer cells is the hallmark of their lethal trait and outcome. However, the genetic alterations underlying the clinical progression and pathogenesis of prostate cancer are not well understood. Several studies involving loss of heterozygosity (LOH) and comparative genomic hybridization analysis have identified distinctively altered regions on various human chromosomes, and genomic imbalance of chromosome 20 was implicated in progression and recurrence of prostate tumors. To examine the role of chromosome 20 in prostate neoplasms, we introduced this chromosome into highly metastatic rat prostate cancer cells using the microcell-mediated chromosome transfer technique. Introduction of the chromosome resulted in significant suppression of the metastatic ability of the hybrid cells, by as much as 98%, without any interference with the in vivo growth rate or tumorigenicity of primary tumor in SCID mice. Our STS-PCR analysis on 10 hybrid clones indicates that the suppressor activity of chromosome 20 is located in the p11.23-12 region. Further examination of the hybrid clones by experimental metastasis assay and histologic analysis as well as Matrigel invasion assay suggests the involvement of the suppressor region at an early stage of invasion and extravasation. We also investigated the status of the chromosome 20 suppressor region in pathology specimens from human prostate cancer patients and detected the frequent loss of this region in high-grade tumors. These results suggest the presence of a putative suppressor gene on human chromosome 20 that is functionally involved in development of prostate cancer metastases. 相似文献
999.
Kumar P Pai K Tripathi K Pandey HP Sundar S 《Clinical and diagnostic laboratory immunology》2002,9(5):1119-1123
Sera from Indian patients with parasitologically confirmed visceral leishmaniasis were studied by immunoblot analysis in order to identify a specific pattern for Leishmania infection. A soluble extract of Leishmania donovani was used as antigen. At diagnosis the sera from patients with visceral leishmaniasis specifically recognized fractions represented by bands of 201 kDa (50% of serum samples), 193 kDa (60%), 147 kDa (50%), 120 kDa (60%), 100 kDa (50%), 80 kDa (80%), 70 kDa (70%), 65 kDa (100%), 50 kDa (50%), 36 kDa (50%), 20 kDa (70%), and 18 kDa (50%). The 65-kDa band, common to all patients infected with Leishmania parasites, was found at the time of diagnosis. However, the immunoblot pattern changed after patients were treated and cured with sodium antimony gluconate (SAG; n =10) or miltefosine (n =10), as was evident from blots of sera obtained pretreatment and at 1, 3, and 6 months posttreatment. At 6 months posttreatment, immunoblots of sera from patients on the SAG regimen showed the disappearance of all bands except the 70-kDa band. Similarly, sera from those on the miltefosine regimen showed the disappearance of all bands except the 65- and 70-kDa bands. This study shows that Western blot analysis is a sensitive test for detection of anti-Leishmania antibodies. Moreover, the persistence of reactivity with the 65- and 70-kDa bands in the sera of all groups shows its promise as a diagnostic and prognostic tool. 相似文献
1000.
Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study 总被引:3,自引:0,他引:3
Hadfield RM; Yudkin PL; Coe CL; Schefler J; Uno H; Barlow DH; Kemnitz JW; Kennedy SH 《Human reproduction update》1997,3(2):109-115
The autopsy records between 1980 and 1995 of 399 female rhesusmonkeys (Macaca mulatta) at the Wisconsin Regional Primate ResearchCenter were examined. Spontaneous endometriosis was found in81 (20%) of the animals. The mean (±SD) ages at deathfor animals with and without endometriosis were 20.7±5.5(range 10-35) and 13.4±7.7 (range 4-37) years respectively.Many of the animals had been exposed to experimental procedures,including laparoscopies, hysterotomies and oestradiol implants,and these were examined as possible risk factors for endometriosis.Of the 81 affected animals, 62 were matched to unaffected controlsfor age at death (to within 1 year) and year of death (to within2 years) and the effect of various factors on the developmentof endometriosis was determined using conditional logistic regression.Exposure to three or more oestradiol implants or one or morehysterotomies were both significant risk factors, with estimatedrelative risks of 9.7 (95% confidence interval 2.5-37.2) and5.8 (95% confidence interval 1.6-20.2) respectively. Animalsthat had been exposed to one or more laparoscopies showed noincreased risk for developing endometriosis. These findingsprovide insight into the aetiology of the disease in women. 相似文献