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Institution

University of Louisville

EducationLouisville, Kentucky, United States
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.


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Journal ArticleDOI
L.Z. Bito1, H. Davson1, E. Levin1, M. Murray1, N. Snider1 
TL;DR: The concentrations of free amino acids in plasma, CSF and in vivo dialysates of peripheral blood (neck sac fluid) and central nervous tissue (brain sac fluid), from each of five dogs, were determined by ion‐exchange chromatography.
Abstract: SUMMARY The concentrations of free amino acids in plasma, CSF and in vivo dialysates of peripheral blood (neck sac fluid) and central nervous tissue (brain sac fluid) from each of five dogs (neck sac fluid from four of five dogs) were determined by ion-exchange chromatography. Dialysates were obtained by implanting small dialysis sacs filled with a dextran-saline solution into the subcutaneous tissue of the neck or the parenchyma of the brain at least 10 weeks before sample collection. The mean plasma concentration of most amino acids was within the range of values reported in the literature for human or dog plasma. The concentrations of most amino acids were higher in the neck sac fluid than in plasma; this discrepancy, however, was, for the most part, small and could most likely be accounted for by falling plasma free amino acid levels prior to sample taking. Previous conclusions that the CSF concentrations of most amino acids are lower than plasma concentrations are confirmed, although the present work indicates that there may be considerable individual variation in the CSF/plasma distribution ratio with respect to most amino acids. In the brain sac fluid the concentration of nearly every amino acid was consistently higher than that in CSF and lower than that in the neck sac fluid. The potassium concentration in the brain sac fluid was significantly higher than, and the total osmolality significantly lower than, those in the neck sac fluid. On the assumption that the brain sac fluid represents a dialysate of the brain extracellular fluid, these results contradict recent findings (Bito and Davson, 1965; 1966) indicating that the potassium concentration of the cortex extracellular fluid is lower than that of ventricular or cisterna magna CSF and certainly lower than that of plasma. Because of this and on the basis of consideration of the reaction of the brain to a foreign body, the possibility that the implanted brain sac lay on the‘blood side’of the bloodbrain barrier was suggested. Some implications of this possibility are discussed.

344 citations

Journal ArticleDOI
TL;DR: ZEB1 is identified as an ATM substrate linking ATM to CHK1 and the mechanism underlying the association between EMT and radioresistance, which promotes homologous recombination-dependent DNA repair and resistance to radiation.
Abstract: Epithelial-mesenchymal transition (EMT) is associated with characteristics of breast cancer stem cells, including chemoresistance and radioresistance. However, it is unclear whether EMT itself or specific EMT regulators play causal roles in these properties. Here we identify an EMT-inducing transcription factor, zinc finger E-box binding homeobox 1 (ZEB1), as a regulator of radiosensitivity and DNA damage response. Radioresistant subpopulations of breast cancer cells derived from ionizing radiation exhibit hyperactivation of the kinase ATM and upregulation of ZEB1, and the latter promotes tumour cell radioresistance in vitro and in vivo. Mechanistically, ATM phosphorylates and stabilizes ZEB1 in response to DNA damage, ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitylate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation. These findings identify ZEB1 as an ATM substrate linking ATM to CHK1 and the mechanism underlying the association between EMT and radioresistance.

344 citations

Journal ArticleDOI
TL;DR: Functional neuroimaging found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls, suggesting a genetically controlled neural circuitry for regulating human social behavior.
Abstract: Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

342 citations

Journal ArticleDOI
TL;DR: It is concluded that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.
Abstract: There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles. Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P less than 0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ("dominant protection"). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/DQw8 haplotype ("dominant susceptibility"). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8. We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.

342 citations

Journal ArticleDOI
TL;DR: A review of animal models that are appropriate for examining components of host-bacteria interactions that can lead to breakdown of hard and soft connective tissue or conditions that limit its repair can be found in this article.
Abstract: Even though animal models have limitations, they are often superior to in vitro or clinical studies in addressing mechanistic questions and serve as an essential link between hypotheses and human patients. Periodontal disease can be viewed as a process that involves four major stages: bacterial colonization, invasion, induction of a destructive host response in connective tissue and a repair process that reduces the extent of tissue breakdown. Animal studies should be evaluated in terms of their capacity to test specific hypotheses rather than their fidelity to all aspects of periodontal disease initiation and progression. Thus, each of the models described below can be adapted to test discrete components of these four major steps, but not all of them. This review describes five different animal models that are appropriate for examining components of host-bacteria interactions that can lead to breakdown of hard and soft connective tissue or conditions that limit its repair as follows: the mouse calvarial model, murine oral gavage models with or without adoptive transfer of human lymphocytes, rat ligature model and rat Aggregatibacter actinomycetemcomitans feeding model.

342 citations


Authors

Showing all 24802 results

NameH-indexPapersCitations
Robert M. Califf1961561167961
Aaron R. Folsom1811118134044
Yang Gao1682047146301
Stephen J. O'Brien153106293025
James J. Collins15166989476
Anthony E. Lang149102895630
Sw. Banerjee1461906124364
Hermann Kolanoski145127996152
Ferenc A. Jolesz14363166198
Daniel S. Berman141136386136
Aaron T. Beck139536170816
Kevin J. Tracey13856182791
C. Dallapiccola1361717101947
Michael I. Posner134414104201
Alan Sher13248668128
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202373
2022249
20212,489
20202,234
20192,193
20182,153