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.

The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype.

Abstract: Inferring CYP2D6 phenotype from genotype is increasingly challenging, considering the growing number of alleles and their range of activity. This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy. To simplify genotype interpretation and improve phenotype prediction, we evaluated the utility of an "activity score" (AS) system. Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African-American heritage. The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods. Phenotype prediction, given as a probability for each AS group, was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP2D6 activity was significantly slower in African Americans compared to Caucasians. The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations.

A population of very small embryonic-like (VSEL) CXCR4 + SSEA-1 + Oct-4 + stem cells identified in adult bone marrow

Abstract: By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (approximately 0.02% of BMMNC) Sca-1(+)lin(-)CD45- cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (approximately 2-4 microm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (approximately 1-month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1(+)lin(-)CD45- very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/organ regeneration.

National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases

Abstract: The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL. An expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases. The NACB Committee prepared a preliminary draft of the guidelines, made them available on the World Wide Web (www.nacb.org), and distributed them before the presentations. The recommendations were divided into four areas: the use of markers in the triage of patients with chest pain, acute coronary syndromes, clinical applications other than acute myocardial infarction and research, and assay platforms and markers of acute myocardial infarction. The recommendations were revised and subsequently re-presented in part at the "Biomarkers in Acute Cardiac Syndromes Conference", sponsored by the Jewish Hospital Heart and Lung Institute, Louisville KY, on October 16-17, 1998. This report lists each recommendation, its scientific justification, and a summary of discussions from conference participants and reviewers. Approximately 100 individuals responded to various versions of these recommendations via direct correspondences, telephone calls to Committee members, electronic mail correspondence to the Committee Chairman, or oral questions and comments raised during one of the two conference presentations. Some of the recommendations were changed to reflect the consensus opinion. In cases in which there was no consensus, the Committee included pertinent discussion without necessarily changing the original recommendations. At times, the Committee members felt that although a particular recommendation might not be the current standard of care today, they anticipate that it likely will be adopted in the near future.

Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria.

Abstract: Summary To date, there have been few systematic attempts to provide a standard operating procedure for the neuropathological diagnosis of Parkinson's disease (PD). Pathological examination cannot classify the clinical syndrome with certainty; therefore, the neuropathological diagnosis is, at best, a probability statement. The neuropathological diagnosis of parkinsonism has become increasingly based on fundamental molecular underpinnings, with recognition that the genetics of parkinsonism is heterogeneous and includes disorders that are associated with and without Lewy bodies. The advent of α-synuclein immunohistochemistry has substantially improved the ability to identify Lewy pathology, particularly cortical Lewy bodies and smaller aggregates within processes and the neuropil. In this Review we discuss the diagnostic criteria for the neuropathological assessment of PD. These criteria are provisional and need to be validated through an iterative process that could help with their refinement. Additionally, we suggest future directions for neuropathology research on PD.

Understanding the Search for Meaning in Life: Personality, Cognitive Style, and the Dynamic Between Seeking and Experiencing Meaning

Abstract: Although several theories assert that understanding the search for meaning in life is important, empirical research on this construct is sparse. Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program. Assessed were relations between search for meaning and well-being, cognitive style, and the Big Five, Big Three, Approach/Avoidance, and Interest models of personality, with a particular emphasis on understanding the correlates of search for meaning that are independent of presence of meaning. Conceptual models of the relation between search and presence were tested. Findings suggest that people lacking meaning search for it; the search for meaning did not appear to lead to its presence. Study 3 found that basic motive dispositions moderated relations between search for meaning and its presence. Results highlight the importance of basic personality dispositions in understanding the search for meaning and its correlates.