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991.
Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date 下载免费PDF全文
Martin Wijkstrom Huidong Zhou Jagjit Singh Hidetaka Hara Mohamed Ezzelarab Cassandra Long Edwin Klein Robert Wagner Carol Phelps David Ayares Ron Shapiro Abhinav Humar David K. C. Cooper 《Xenotransplantation》2015,22(4):302-309
The longest survival of a non‐human primate with a life‐supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an α‐1,3‐galactosyltransferase gene‐knockout pig transgenic for two human complement‐regulatory proteins and three human coagulation‐regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti‐CD20mAb (induction) and anti‐CD40mAb+rapamycin+corticosteroids (maintenance). Anti‐TNF‐α and anti‐IL‐6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein‐losing nephropathy were observed. There was no evidence of an elicited anti‐pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti‐inflammatory agents prevented immune injury and a protein‐losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality. 相似文献
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Kushaljit Singh Sodhi Vivek Virmani M. S. Sandhu N. Khandelwal 《The Indian journal of surgery》2015,77(2):104-110
Diagnosis of abdominal wall hernia is often a clinical problem, especially in occult or in obese patients. Multidetector CT is an accurate method of detecting various types of abdominal and diaphragmatic hernias. It clearly demonstrates the anatomical sites of hernial sac, its contents and possible complications. 相似文献
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Aditya Aggarwal Hardeep Singh Sanjay Mahendru Vimalendu Brajesh Sukhdeep Singh Ashish Khare Umang Kothari Rakesh Kumar Khazanchi 《Indian Journal of Plastic Surgery》2015,48(3):274-277
Introduction:The pedicle positioning in free tissue transfer is critical to its success. Long thin pedicles are especially prone to this complication where even a slight twist in the perforator can result in flap loss. Pedicles passing through the long tunnels are similarly at risk. Streaking the pedicle with methylene blue is a simple and safe method which increases the safety of free tissue transfer.Conclusion:This simple and novel method is very reliable for pedicle positioning avoiding any twist necessary for successful free tissue transfer.KEY WORDS: Free flaps, pedicle, perforator 相似文献
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J G Hunsberger F L Chibane A G Elkahloun R Henderson R Singh J Lawson C Cruceanu V Nagarajan G Turecki A Squassina C D Medeiros M Del Zompo G A Rouleau M Alda D-M Chuang 《Translational psychiatry》2015,5(2):e504
We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery. 相似文献
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Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. 总被引:7,自引:0,他引:7 下载免费PDF全文
L Singh A S Lewis M J Field J Hughes G N Woodruff 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(4):1130-1133
The effect of neuropeptide cholecystokinin (CCK) receptor agonists and antagonists was examined in the rat elevated X-maze model of anxiety. The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200. The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to pentagastrin but not that induced by pentylenetetrazol. These results strongly suggest that activation of the brain CCK-B receptor induces anxiety and that selective antagonists of this receptor represent a separate class of anxiolytic agents. 相似文献
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