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41.
Kazi A Urbizu DA Kuhn DJ Acebo AL Jackson ER Greenfelder GP Kumar NB Dou QP 《International journal of molecular medicine》2003,12(6):879-887
Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers. Most recently, we have reported that TA and ester-bond containing green tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We hypothesize that CellQuest, a patented formula which contains high level of TA obtained from a musaceas (plantain) plant extract, will inhibit the tumor cell proteasome activity. Here, we report that a partially purified CellQuest fraction, S3, potently inhibits the proteasomal chymotrypsin-like activity of Jurkat T cell extracts in a concentration-dependent manner. Inhibition of the proteasome by S3 in leukemia Jurkat T, simian virus 40-transformed and prostate cancer LNCaP cells results in accumulation of ubiquitinated proteins and the natural proteasome substrate p27Kip1, followed by induction of apoptosis. In contrast, non-transformed, immortalized human natural killer cells and normal human fibroblasts are resistant to S3-mediated proteasome inhibition and apoptosis induction. Our present study suggests that CellQuest targets and inhibits the proteasome selectively in tumor cells, which may contribute to the claimed anticancer activity. 相似文献
42.
Neutrophils and other phagocytic cells support host defense by ingesting microbes and destroying them with reactive oxygen species or oxygen independent mechanisms. Production of ROS is initiated by the phagocyte NADPH oxidase (phox), an enzyme system composed of several constituents. During activation of the cell cytosolic phox proteins (p47phox, p67phox, p40phox, and Rac2) translocate to the plasma membrane and specific granules fuse with the plasma membrane increasing the amount of flavocytochrome b(558). The resultant assembly of phox components results in formation of a complete complex and expression of activity. In this study, we evaluated the oxidase activity of specific granules. In the SDS cell-free system, specific granules expressed oxidase activity in the presence of cytosol in a manner similar to plasma membrane. In contrast to plasma membrane, activity of specific granules was latent, diminishing rapidly over time. In addition, this subcellular fraction contained an inhibitor, possibly related to contamination with azurophilic granules explaining previously published discrepant results. Experiments with recombinant p47phox, p67phox, and dilute cytosol or fractionated cytosol as a source of Rac demonstrated that specific granules have requirements identical to specific granules for oxidase activity. Finally, analysis of neutrophils stimulated with PMA demonstrated translocation of p47phox and to p67phox to specific granules as well as plasma membrane. Both plasma membrane and specific granules from PMA stimulated cells expressed oxidase activity with addition of NADPH demonstrating an assembled oxidase complex. These studies establish a critical role for specific granules as a site for assembly and activation of the oxidase enzyme system and an important constituent for the microbicidal activity of the neutrophil. 相似文献
43.
44.
A gene from the locus of enterocyte effacement that is required for enteropathogenic Escherichia coli to increase tight-junction permeability encodes a chaperone for EspF 总被引:5,自引:0,他引:5
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Elliott SJ O'Connell CB Koutsouris A Brinkley C Donnenberg MS Hecht G Kaper JB 《Infection and immunity》2002,70(5):2271-2277
Disruption of the barrier properties of the enterocyte tight junction is believed to be important in the pathogenesis of diarrhea caused by enteropathogenic Escherichia coli (EPEC). This phenotype can be measured in vitro as the ability of EPEC to reduce transepithelial resistance (TER) across enterocyte monolayers and requires the products of the locus of enterocyte effacement (LEE) and, in particular, the type III secreted effector protein EspF. We report a second LEE-encoded gene that is also necessary for EPEC to fully reduce TER. rorf10 is not necessary for EPEC adherence, EspADB secretion, or formation of attaching and effacing lesions. However, rorf10 mutants have a diminished TER phenotype, reduced intracellular levels of EspF, and a reduced ability to translocate EspF into epithelial cells. The product of rorf10 is a 14-kDa intracellular protein rich in alpha-helices that specifically interacts with EspF but not with Tir or other EPEC secreted proteins. These properties are consistent with the hypothesis that rorf10 encodes a type III secretion chaperone for EspF, and we rename this protein CesF, the chaperone for EPEC secreted protein F. 相似文献
45.
Berka N Nunlee-Bland G Erabhaoui E Belmamoun M Dunston GM 《Journal of the National Medical Association》2004,96(8):1042-1046
In this study, we investigate the polymorphic microsatellite repeat (TCAT)n, in the insulin gene region that has been associated with susceptibility to type-1 diabetes in some Caucasian populations. The microsatellite repeat polymorphism begins at base pair 1,170 in intron 1 of the hTH gene, which is located on the short arm of chromosome 11. This study is the first to investigate the association of this microsatellite repeat polymorphism in African-American type-1 diabetes patients and controls. The predicted amplified sequence was 254 bp. We found five alleles among African Americans in the Washington, DC area. The alleles were labeled K5 (244 bp), K4 (248 bp), K3 (252 bp), K2 (256 bp), and K1 (260 bp), and heterozygosity was greater than 0.75. The most frequent allele of the hTH microsatellite repeats was K5 (248 bp) with a frequency 0.62 in controls and 0.66 in type-1 diabetes patients, which did not differ significantly. Although the largest allele was more frequent in controls, the difference was not statistically significant. The five alleles of the hTH microsatellite generated 15 different genotypes. The most frequent genotype in controls and patients was K5/K4, whose frequencies were 0.19 and 0.17, respectively. No significant differences in genotype frequencies were found between type-1 diabetes patients and controls. This data shifts the focus from hTH to the VNTR at the insulin gene for IDDM2, the second major candidate gene for type-1 diabetes. 相似文献
46.
Bastien N Ward D Van Caeseele P Brandt K Lee SH McNabb G Klisko B Chan E Li Y 《Journal of clinical microbiology》2003,41(10):4642-4646
47.
Shor-Posner G Miguez MJ Pineda LM Rodriguez A Ruiz P Castillo G Burbano X Lecusay R Baum M 《Journal of acquired immune deficiency syndromes (1999)》2002,29(2):169-173
The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV-1-infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV-1-seropositive drug users was investigated over a 2-year period (1999-2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of 相似文献
48.
Genetic Pathways of Colorectal Carcinogenesis Rarely Involve the PTEN and LKB1 Genes Outside the Inherited Hamartoma Syndromes 总被引:9,自引:3,他引:9
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Zhen-Jung Wang Fleur Taylor Michael Churchman Gail Norbury Ian Tomlinson 《The American journal of pathology》1998,153(2):363-366
Germline mutations of the PTEN/MMAC1/TEP and LKB1 genes cause hamartomas to develop in the gastrointestinal tracts of patients with Cowden syndrome and Peutz-Jeghers syndrome, respectively. PTEN mutations may also be responsible for some cases of juvenile polyposis. Histologically, hamartomas appear benign, but there is good evidence that in these syndromes, the hamartomas can progress to colorectal carcinoma. It remains unknown whether or not cancers that develop from hamartomas acquire a spectrum of mutations similar to those in sporadic colon cancers. PTEN and LKB1 are candidate genes for mutations in sporadic colon cancers, either as initiating events in tumorigenesis or providing a selective advantage during tumor growth. Using single-strand conformational polymorphism analysis, we have screened a set of sporadic colon cancers for somatic mutations in PTEN and LKB1. No variants predicted to alter protein function were detected in LKB1, but 1 of 72 cancers showed a somatic mutation in PTEN, together with allele loss. This cancer did not have a detectable APC mutation or allele loss at APC. It remains possible that PTEN and LKB1 are inactivated in other sporadic colon cancers by means such as deletion or promoter methylation. Like BRCA1 and BRCA2, however, it appears that PTEN and LKB1 mutations can cause cancers when present in the germline, but occur rarely in the soma. 相似文献
49.
Stunz LL Busch LK Munroe ME Sigmund CD Tygrett LT Waldschmidt TJ Bishop GA 《Immunity》2004,21(2):255-266
The oncogenic EBV protein LMP1 mimics a dysregulated CD40 receptor in vitro. To compare CD40 and LMP1-mediated events in vivo, transgenic mice were engineered to express mouse CD40 (mCD40tg) or a protein with extracellular mCD40 and cytoplasmic LMP1 (mCD40-LMP1tg). Transgenic and CD40(-/-) mice were bred so that only the transgenic CD40 molecule is expressed in B cells, macrophages, and dendritic cells. mCD40-LMP1tg mice had normal lymphocyte subsets, and immunization elicited an antibody response featuring normal isotype switching, affinity maturation, and germinal center (GC) formation. However, unimmunized mCD40-LMP1tg mice had expanded immature and germinal center B cells, produced autoantibodies, exhibited marked splenomegaly and lymphadenopathy, and elevated serum IL-6. Thus, signaling through the LMP1 cytoplasmic tail results in amplified and abnormal mimicry of CD40 functions in vivo, indicating possible ways in which LMP1 contributes to the pathogenesis of EBV-associated human disease. 相似文献
50.
Marc Gellman Susan Spitzer Gail Ironson Maria Llabre Patrice Saab Rosemary De Carlo Pasin Donald J. Weidler Neil Schneiderman 《Psychophysiology》1990,27(5):544-551
Ambulatory blood pressure was studied as a function of posture, place, and mood in 131 subjects classified according to race, gender, and hypertensive status. The effect of posture was significant and explained a substantial proportion of within-subject variability. After controlling for posture, significant place and mood effects were observed when subjects were sitting but not when they were standing. Home vs. work differences in both systolic and diastolic blood pressure were significantly greater in Whites than in Blacks. Similar differences in systolic blood pressure were greater in mild hypertensive than in normotensive subjects. The results of this study underscore the need to control for effects of posture when interpreting ambulatory blood pressure readings. 相似文献