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1Contribution of oxidative stress to pulmonary arterial hypertension显示文摘Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.Vincent G DeMarco Adam T Whaley-Connell James R Sowers Javad Habibi Kevin C Dellsperger 2010World Journal of Cardiology2010,2,10:21
2Calcium signaling and T-type calcium channels in cancer cell cycling显示文摘Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers.James T Taylor Xiang-Bin Zeng Jonathan E Pottle Kevin Lee Alun R Wang Stephenie G Yi lennifer A S Scruggs Suresh S Sikka Ming Li 2008World Journal of Gastroenterology2008,14,32:12
3World Review of Laparoscopic Liver Resection—2,804 Patients显示文摘Kevin Tri Nguyen T Clark Gamblin David A. Geller 2009Annals of Surgery2009,,5:8
4Microscopic colitis:A large retrospective analysis from a health maintenance organization experience显示文摘AIM:To examine the demographic data on a large multi-ethnic population of patients with microscopic colitis (MC) in Southern California and to determine the association of MC with inflammatory bowel disease (IBD) and colorectal cancer.METHODS: All patients diagnosed with MC by colonic biopsy from 1996-2005 were identified utilizing a pathology database. All biopsies were reviewed by experienced pathologists utilizing standard histologic criteria. Patients' medical records were reviewed and data regarding patient age, co-morbidities, sex, ethnicity, and medications were analyzed. An age-and sexmatched standard control group was also generated. Chi-square test was used to evaluate the associations of co-morbidities between lymphocytic colitis (LC), collagenous colitis (CC) and the control group.RESULTS: A total of 547 cases of MC were identif ied,376 patients with LC and 171 patients with CC. The female/male ratio was 3:1 in CC and 2.7:1 in LC patients. Celiac disease (P<0.001), irritable bowel syndrome (IBS) (P<0.001), and thyroid diseases (P<0.001) were found to have a higher occurrence in MC compared to the control group. No statistical differences in the occurrence of colorectal cancer, diabetes and IBD were found between the MC group and the control group.CONCLUSION: This is the largest group of patients with MC known to the authors that has been studied to date. Conditions such as celiac disease, IBS, and thyroid diseases were found to be related to MC. Furthermore, neither an increased risk of colorectal cancer nor IBD was associated with MC in this study.Kevin T Kao Benito A Pedraza Amy C McClune David A Rios Yi-Qiong Mao Robert H Zuch Michael H Kanter Sony Wirio Chris N Conteas 2009World Journal of Gastroenterology2009,15,25:5
5Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2显示文摘We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2.杨建民 Michael S FRIEDMAN Christopher M REYNOLDS Marianne T HUBEN Lee WILKE Jennifer FULLER 李桥 Zelig ESHHAR James J MULE Kevin T MCDONAGH 2004Journal of Microbiology and Immunology2004,2,4:5
6In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene显示文摘We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells.JIAN MIN YANG MICHAEL S FRIEDMAN MARIANNE T HUBEN JENNIFER FULLER QIAO LI ALFRED E CHANG JAMES J MULE KEVIN T MCDONAGH 2006Journal of Microbiology and Immunology2006,4,2:3
7转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用显示文摘目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(SK-OV-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。杨建民 Michael S Friedman 李峤 James J Mule Alfred E Chang Kevin T McDonagh 2006中国肿瘤生物治疗杂志2006,13,4:2
8The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men显示文摘Chris J. Malkin Peter J. Pugh Richard D. Jones Dheeraj Kapoor Kevin S. Channer T Hugh Jones 2004The Journal of Clinical Endocrinology & Metabolism2004,,7:2
9Spatially continuous six degree of freedom position and orientation sensor 显示文摘LEE D KEVIN E ANDREW T 1999Sensors Review1999,19,2:1
10Marketing on the Internet- Who Can Benefit from an Online Marketing Approach显示文摘Melidy Y Kiang T S Raghu Kevin Huei-MinShang 2000Decision Support System2000,27,:1
11Reconstructing the Key Stream from a Chaotic Encryption Scheme 显示文摘Andrew T Kevin M 2001IEEE Transactions on Circuits and Systems I : Fundamental Theory and Applications2001,48,5:1
12Role of Spl,C/EBPα, HNF3 and PXR in the basal- and xenobiotic-mediated regulation of the CYP3A4 gene 显示文摘Vicent B Kevin T Gordon G 2004Drug Metab Dispos2004,32,:1
13Comparison of ABTS, DPPH, FRAP,and ORAC assays for estimating antioxidant activity from guava fruit extracts显示文摘Kriengsak T Unaroj B Kevin C 2006Journal of Food Composition and Analysis2006,19,67:1
14Comparison of Micro-PinFin and Micro-channel Heat Sinks Considering Thermal-Hydraulic Performanceand Manufacturability显示文摘Benjamin A J Yongho J Kevin T 2010IEEE Transactions on Components and Packaging Technology2010,33,1:1
15Spatially Continuous Six Degree of Fleedom Position and Orientation Sensor显示文摘LEE D KEVIN E ANDREW T 1999Sensor Review1999,19,2:1
16Seismic refraction at Horse Mesa Dam: an application of the generalized reciprocal method 显示文摘Kevin T K Reger A N W R McLamore 1986Geophysics1986,51,:1
17Backscatter coeffi- cient as an attribute for the classification of full-wave- form airborne laser scanning data in urban areas显示文摘CICI A KEVIN T JORG K 2010ISPRS Journal of Photogrammetry and Remote2010,65,:1
18Microendoscoplc lumbar discectomy: technical note显示文摘MICK J KEVIN T 2002Neurosurgery2002,51,:1
19The Joint polarization experiment:Polarirnetric Radar in forecasting and warning decision making显示文摘KEVIN A S DANIEL J M SCHUUR T J 2005Wea Force2005,20,5:1
20Conductive poly- mer composite materials and their utility in electromagneticshielding applications显示文摘Richard T F Vijay W Kevin E H 2008Journal of Applied Polymer Sci- ence2008,107,4:1
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