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91.
Pilot Study Evaluating Regulatory T Cell–Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model 下载免费PDF全文
J. Lei J. I. Kim S. Shi X. Zhang Z. Machaidze S. Lee C. Schuetz P. N. Martins T. Oura E. A. Farkash I. A. Rosales R. N. Smith R. Stott K. M. Lee J. Soohoo S. Boskovic K. Cappetta O. M. Nadazdin Y. Yamada H. Yeh T. Kawai D. H. Sachs G. Benichou J. F. Markmann 《American journal of transplantation》2015,15(10):2739-2749
The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1‐ethyl‐3‐(3′‐dimethylaminopropyl)‐carbodiimide (ECDI)‐treated donor lymphoid cell infusion (ECDI‐DLI) with thymoglobulin, anti‐interleukin‐6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor‐specific T cell hyporesponsiveness and a transient absence of donor‐specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation. 相似文献
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Yung-Pin Lin Li-Yun Lin Hsiang-Yu Yeh Cheng-Hung Chuang Sheng-Wen Tseng Yue-Horng Yen 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2016,24(3):516
Allium chinense is a medicinal plant and nutritional food commonly used in Eastern Asia. In this study, we investigated the in vitro antioxidant activity (scavenging of α,α-diphenyl-β-picrylhydrazyl free radical, total phenol content, reducing power, and total antioxidant activity) and constituents of various extracts from A. chinense. Moreover, we also studied the in vivo hypolipidemic effects of extracts on high-fat-diet Wistar rats. Ethanol extracts from A. chinense showed notable antioxidant activity, and its high-dose essential-oil extract both significantly reduced serum and hepatic total cholesterol, triglyceride, and low-density lipoprotein levels and increased serum high-density lipoprotein levels in high-fat-diet Wistar rats compared with those observed following treatment with the control drug probucol. Additionally, visceral fat in high-fat-diet Wistar rats was reduced. Furthermore, groups with high doses of essential-oil and residue extracts showed protective effects associated with histopathological liver alteration. These results suggested that A. chinense is a valuable plant worthy of further investigation as a potential dietary supplement or botanical drug. 相似文献
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Rong Liu Stephanie Curry Patricia McMonagle Wendy W. Yeh Steven W. Ludmerer Patricia A. Jumes William L. Marshall Stephanie Kong Paul Ingravallo Stuart Black Irene Pak Mark J. DiNubile Anita Y. M. Howe 《Antimicrobial agents and chemotherapy》2015,59(11):6922-6929
Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier .) NCT01532973相似文献
96.
Procedural variation in the performance of primary percutaneous coronary intervention for ST‐elevation myocardial infarction: A SCAI‐based survey study of US interventional cardiologists 下载免费PDF全文
Austin Chiang MD Hemal Gada MD MBA Susheel K. Kodali MD Michael S. Lee MD Allen Jeremias MD Duane S. Pinto MD MPH Sripal Bangalore MD MHA Robert W. Yeh MD MSc Timothy D. Henry MD Georgina Lopez‐Cruz BS MSHA Roxana Mehran MD Ajay J. Kirtane MD SM 《Catheterization and cardiovascular interventions》2014,83(5):721-726
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Huy Tran Ming-Lung Yu Chia-Yen Dai I-Ling Lin Ming-Lun Yeh Wan-Long Chuang Kenji Abe 《Virus genes》2014,49(1):30-37
The hepatitis B virus (HBV) genomes in Taiwanese aborigines, whose ancestors have lived in Taiwan for over 10,000 years, have not been characterized. In order to characterize of HBV in this special population, serum samples were obtained from serologically HBsAg-positive 27 Taiwanese aborigines. The pre-S1/S2 region and the full-length 3.2 kb of the HBV genome were amplified by PCR. Obtained amplicons were sequenced and confirmed the HBV genotypes by phylogenetic analysis. By phylogenetic analysis of the sequence of pre-S1/pre-S2 region, HBV/B2 (21/27: 78 %) was the most prevalent followed by genotype D (6/27: 22 %). Two strains of HBV/B2, each having 3,215 bp genomes, had recombination with genotype C in the pre-C/C gene which is characteristic of subgenotype B2 circulating in Southeast Asia. Interestingly, six strains of genotype D formed a distinct cluster between subgenotypes D1 and D2 suggesting a novel group of HBV. A similar finding could also be confirmed based on the entire 3,182 bp genome from four strains of HBV/D. This new cluster was supported by a branch with 99 % bootstrap value and 3.4–5.8 % nucleotide divergence over the entire genome from other known subgenotypes D1 to D9. Four strains of the new D subgenotype showed serotype ayw2, but had unique amino acid sequences consisting of N115 in the preS/S gene; P41 in the X gene; S239, K/E295, V567, and P708 in the P gene, respectively. From the above results, we provisionally proposed to designate it as novel quasi-subgenotype D2 identified in Taiwanese aborigines. 相似文献
100.
Yi-Tsung Lin Kai-Yu Tseng Yi-Chen Yeh Fu-Chen Yang Chang-Phone Fung Nien-Jung Chen 《Infection and immunity》2014,82(3):1335-1342
Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation of K. pneumoniae from a patient''s bowel into the liver via the portal circulation. TREM-1 (triggering receptor expressed on myeloid cells 1) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type and Trem-1 knockout (KO) mice after oral inoculation of capsular type K1 K. pneumoniae. Translocation of K. pneumoniae to mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance of K. pneumoniae in the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increased K. pneumoniae dissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhanced K. pneumoniae translocation, which renders Trem-1 KO mice more susceptible to K. pneumoniae oral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response against K. pneumoniae. TREM-1 deficiency enhances K. pneumoniae translocation in the small intestine and increases mortality rates in mice with KPLA. 相似文献