University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Use of an Intrapericardial, Continuous-Flow, Centrifugal Pump in Patients Awaiting Heart Transplantation

Abstract: Background—Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. Methods and Results—We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events i...

Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18).

Abstract: Zymosan, the cell wall from Saccharomyces cerevisiae, was reported to be a macrophage activator through its beta-glucan over 30 yr ago. Nevertheless, the identity of the beta-glucan receptor has been controversial. This study showed that the alpha M beta 2-integrin, CR3 (Mac-1, CD11b/CD18) served as the beta-glucan receptor through one or more lectin sites located outside of the CD11b I-domain that contains the binding sites for iC3b, ICAM-1, and fibrinogen. Sugar specificity, analyzed with FITC-labeled soluble polysaccharides and flow cytometry, showed CR3-specific staining with several pure beta-glucans but not with alpha-mannan. However, a 10-kDa soluble zymosan polysaccharide (SZP) with high affinity (6.7 x 10(-8) M) for CR3 consisted largely of mannose and approximately 5% glucose. Binding of either SZP-FITC or beta-glucan-FITC to CR3 was blocked not only by pure beta-glucans from yeast, mushroom, seaweed, or barley, but also by N-acetyl-D-glucosamine (NADG), alpha- or beta-methylmannoside, and alpha- or beta-methyl-glucoside. SZP-FITC and beta-glucan-FITC stained all leukocyte types similarly to anti-CR3-FITC, and polysaccharide-FITC staining was inhibited > or = 95% by unlabeled anti-CR3. SZP-FITC staining of cells expressing recombinant chimeras between CR3 and CR4 (p150,95, CD11c/CD18) suggested that both the divalent cation-binding region of CD11b and the region C-terminal to it may regulate binding of polysaccharides to CR3. Unlabeled SZP or beta-glucan also blocked CR3 staining by 11 mAb to C-terminal domain epitopes of CD11b but had no effect on staining by mAb directed to the I-domain. In conclusion, CR3 serves as the leukocyte beta-glucan receptor through a cation-independent lectin site located C-terminal to the I-domain of CD11b. Its sugar specificity is broader than originally appreciated, allowing it to react with certain polysaccharides containing mannose or NADG, as well as glucose.

Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71.

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control brain, suggesting a possible role for oxidation-related decrease in protein function in the process of neurodegeneration. Oxidative damage to proteins, assessed by measuring the protein carbonyl content, is involved in several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, neuronal death. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. Previously, we used our proteomics approach, which successfully substitutes for labor-intensive immunochemical analysis, to detect proteins and identified creatine kinase, glutamine synthase and ubiquitin carboxy-terminal hydrolase L-1 as specifically oxidized proteins in AD brain. In this report we again applied our proteomics approach to identify new targets of protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase related protein 2 (DRP-2), which is involved in the axonal growth and guidance, showed significantly increased level in protein carbonyls in AD brain, suggesting a role for impaired mechanism of neural network formation in AD. Additionally, the cytosolic enzyme alpha-enolase was identified as a target of protein oxidation and is involved the glycolytic pathway in the pathological events of AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not significant, oxidation in AD brain. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD brain.