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31.
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
32.
Michelle K. York Deepak K. Gupta Cassandra F. Reynolds Eric Farber-Eger Quinn S. Wells Katherine N. Bachmann Meng Xu Frank E. Harrell Thomas J. Wang 《Journal of the American College of Cardiology》2018,71(19):2079-2088
Background
Circulating B-type natriuretic peptide (BNP) concentrations strongly predict mortality in patients with heart failure (HF). Both cardiac and extracardiac stimuli influence BNP levels, suggesting that BNP might have similar prognostic value in patients without HF.Objectives
The aim of this study was to compare the prognostic value of BNP between patients with and those without HF.Methods
Using the Vanderbilt University Medical Center electronic health record, 30,487 patients (median age 63 years, 50% men, 17% black, 38% with HF) who had a first plasma BNP measurement between 2002 and 2013, with follow-up through 2015, were studied. The risk for death according to BNP level was quantified using multivariate Cox proportional hazards models.Results
BNP levels were lower in patients without HF (median 89 pg/ml; interquartile range: 34 to 238 pg/ml) compared with those with HF (median 388 pg/ml; interquartile range: 150 to 940 pg/ml) (p < 0.0001). Over 90,898 person-years of follow-up, 5,903 patients without HF (31%) and 6,181 patients with HF (53%) died. In multivariate models including demographic and clinical characteristics, BNP and age were the strongest predictors of death in both patients with and those without HF. In acute care settings and even among outpatients with modestly elevated BNP, the risk for death according to BNP was similar between patients with and those without HF. For instance, a BNP level of 400 pg/ml was associated with a 3-year risk for death of 21% (95% confidence interval: 20% to 23%) and 19% (95% confidence interval: 17% to 20%) in patients with and those without HF, respectively.Conclusions
Among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting. 相似文献33.
Suzannah M. Schmidt-Malan Melissa J. Karau Julia Cede Kerryl E. Greenwood-Quaintance Cassandra L. Brinkman Jayawant N. Mandrekar Robin Patel 《Antimicrobial agents and chemotherapy》2015,59(8):4610-4615
Bacterial biofilms are difficult to treat using available antimicrobial agents, so new antibiofilm strategies are needed. We previously showed that 20, 200, and 2,000 μA of electrical current reduced bacterial biofilms of Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Here, we tested continuous direct current at lower amperages, intermittent direct current, and combinations of surface materials (Teflon or titanium) and electrode compositions (stainless steel, graphite, titanium, or platinum) against S. aureus, S. epidermidis, and P. aeruginosa biofilms. In addition, we tested 200 or 2,000 μA for 1 and 4 days against biofilms of 33 strains representing 13 species of microorganisms. The logarithmic reduction factor was used to measure treatment effects. Using continuous current delivery, the lowest active amperage was 2 μA for 1, 4, or 7 days against P. aeruginosa and 5 μA for 7 days against S. epidermidis and S. aureus biofilms. Delivery of 200 μA for 4 h a day over 4 days reduced P. aeruginosa, S. aureus, and S. epidermidis biofilms on Teflon or titanium discs. A reduction of P. aeruginosa, S. aureus, and S. epidermidis biofilms was measured for 23 of 24 combinations of surface materials and electrode compositions tested. Four days of direct current delivery reduced biofilms of 25 of 33 strains studied. In conclusion, low-amperage current or 4 h a day of intermittent current delivered using a variety of electrode compositions reduced P. aeruginosa, S. aureus, and S. epidermidis biofilms on a variety of surface materials. The electricidal effect was observed against a majority of bacterial species studied. 相似文献
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Differences in the morphology of spinal V2a neurons reflect their recruitment order during swimming in larval zebrafish 下载免费PDF全文
Evdokia Menelaou Cassandra VanDunk David L. McLean 《The Journal of comparative neurology》2014,522(6):1232-1248
Networks of neurons in spinal cord generate locomotion. However, little is known about potential differences in network architecture that underlie the production of varying speeds of movement. In larval zebrafish, as swimming speed increases, Chx10‐positive V2a excitatory premotor interneurons are activated from ventral to dorsal in a topographic pattern that parallels axial motoneuron recruitment. Here, we examined whether differences in the morphology and synaptic output of V2a neurons reflect their recruitment order during swimming. To do so, we used in vivo single‐cell labeling approaches to quantify the dorsoventral distribution of V2a axonal projections and synapses. Two different classes of V2a neurons are described, cells with ascending and descending axons and cells that are only descending. Among the purely descending V2a cells, more dorsal cells project longer distances than ventral ones. Proximally, all V2a neurons have axonal distributions that suggest potential connections to cells at and below their own soma positions. At more distal locations, V2a axons project dorsally, which creates a cumulative intersegmental bias to dorsally located spinal neurons. Assessments of the synapse distribution of V2a cells, reported by synaptophysin expression, support the morphological observations and also demonstrate that dorsal V2a cells have higher synapse densities proximally. Our results suggest that V2a cells with more potential output to spinal neurons are systematically engaged during increases in swimming frequency. The findings help explain patterns of axial motoneuron recruitment and set up clear predictions for future physiological studies examining the nature of spinal excitatory network connectivity as it relates to movement intensity. J. Comp. Neurol. 522:1232–1248, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
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Mérino D Khaw SL Glaser SP Anderson DJ Belmont LD Wong C Yue P Robati M Phipson B Fairlie WD Lee EF Campbell KJ Vandenberg CJ Cory S Roberts AW Ludlam MJ Huang DC Bouillet P 《Blood》2012,119(24):5807-5816
The BH3-mimetic ABT-737 and an orally bioavailable compound of the same class, navitoclax (ABT-263), have shown promising antitumor efficacy in preclinical and early clinical studies. Although both drugs avidly bind Bcl-2, Bcl-x(L), and Bcl-w in vitro, we find that Bcl-2 is the critical target in vivo, suggesting that patients with tumors overexpressing Bcl-2 will probably benefit. In human non-Hodgkin lymphomas, high expression of Bcl-2 but not Bcl-x(L) predicted sensitivity to ABT-263. Moreover, we show that increasing Bcl-2 sensitized normal and transformed lymphoid cells to ABT-737 by elevating proapoptotic Bim. In striking contrast, increasing Bcl-x(L) or Bcl-w conferred robust resistance to ABT-737, despite also increasing Bim. Cell-based protein redistribution assays unexpectedly revealed that ABT-737 disrupts Bcl-2/Bim complexes more readily than Bcl-x(L)/Bim or Bcl-w/Bim complexes. These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies. 相似文献
38.
Schmidt MG Anderson T Attaway HH Fairey S Kennedy C Salgado CD 《American journal of infection control》2012,40(6):559-561
Effective cleaning of the patient environment has been advocated to reduce the risk for nosocomial infection. This pilot study compared 2 terminal cleaning methods, a traditional method in which a disinfectant was applied with a wetted cloth and an alternative method in which the disinfectant was applied using the PureMist system (PureCart Systems, Green Bay, WI). There was no difference in effectiveness, with a mean relative reduction of microbial burden of 84% for the traditional method versus 88% for the PureMist method. 相似文献
39.
Wannan Cassandra M. J. Bartholomeusz Cali F. Pantelis Christos Di Biase Maria A. Syeda Warda T. Chakravarty M. Mallar Bousman Chad A. Everall Ian P. McGorry Patrick D. Zalesky Andrew Cropley Vanessa L. 《European archives of psychiatry and clinical neuroscience》2022,272(6):971-983
European Archives of Psychiatry and Clinical Neuroscience - Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory... 相似文献
40.
Jason R. Stubbs John A. House A. Jacob Ocque Shiqin Zhang Cassandra Johnson Cassandra Kimber Kyle Schmidt Aditi Gupta James B. Wetmore Thomas D. Nolin John A. Spertus Alan S. Yu 《Journal of the American Society of Nephrology : JASN》2016,27(1):305-313
Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r2=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography. 相似文献