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At least 379 records · Page 21Linked to original sources
PubMed1987

Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile.

Kinetics of 5-fluorouracil (FUra) and FUra metabolites in plasma and urine were investigated in 10 cancer patients following i.v. bolus administration of 500 mg/m2 FUra with 600 microCi of [6-3H]FUra. Biliary excretion was examined in two patients with external biliary catheters. Quantitation of unchanged drug and metabolites was assessed by a highly specific high-performance liquid chromatographic method. FUra plasma levels declined rapidly with an apparent elimination half-life of 12.9 +/- 7.3 min. Dihydrofluorouracil was detected within 5 min in most patients, demonstrating rapid catabolism and reached maximum peak levels of 23.7 +/- 9.9 microM at approximately 60 min. The apparent elimination half-life of dihydrofluorouracil (61.9 +/- 39.0 min) was consistently greater than that of the unchanged drug. The apparent elimination half-lives of the subsequent metabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine were prolonged with values of 238.9 +/- 175.4 min and 1976 +/- 358 min, respectively. Approximately 60-90% of the administered dose was excreted in urine within 24 h, primarily as alpha-fluoro-beta-alanine. Biliary excretion accounted for 2-3% of total administered radioactivity. The major fraction of this radioactivity eluted on high-performance liquid chromatography as a previously unrecognized FUra metabolite. Analysis of its structure is currently ongoing in our laboratory. In conclusion, this study provides the first comprehensive analysis of the formation and excretion of FUra metabolites in plasma, urine, and bile following i.v. bolus administration of FUra in humans.

Adult↗
PubMed2000

A large scale analysis of cDNA in Arabidopsis thaliana: generation of 12,028 non-redundant expressed sequence tags from normalized and size-selected cDNA libraries.

For comprehensive analysis of genes expressed in the model dicotyledonous plant, Arabidopsis thaliana, expressed sequence tags (ESTs) were accumulated. Normalized and size-selected cDNA libraries were constructed from aboveground organs, flower buds, roots, green siliques and liquid-cultured seedlings, respectively, and a total of 14,026 5'-end ESTs and 39,207 3'-end ESTs were obtained. The 3'-end ESTs could be clustered into 12,028 non-redundant groups. Similarity search of the non-redundant ESTs against the public non-redundant protein database indicated that 4816 groups show similarity to genes of known function, 1864 to hypothetical genes, and the remaining 5348 are novel sequences. Gene coverage by the non-redundant ESTs was analyzed using the annotated genomic sequences of approximately 10 Mb on chromosomes 3 and 5. A total of 923 regions were hit by at least one EST, among which only 499 regions were hit by the ESTs deposited in the public database. The result indicates that the EST source generated in this project complements the EST data in the public database and facilitates new gene discovery.

Arabidopsis↗
PubMed1999

Report of the International Equine Gene Mapping Workshop: male linkage map.

The goal of the First International Equine Gene Mapping Workshop, held in 1995, was the construction of a low density, male linkage map for the horse. For this purpose, the International Horse Reference Family Panel (IHRFP) was established, consisting of 12 paternal half-sib families with 448 half-sib offspring provided by 10 laboratories. Blood samples were collected and DNA extracted in each laboratory and sent to the Lexington laboratory (KY, USA) for dispatch in aliquots to 14 typing laboratories. In total, 161 markers (144 microsatellites, seven blood groups and 10 proteins) were tested for all families for which the sire was heterozygous. Genealogies and typing data were sent for analysis to the INRA laboratory (Jouy-en-Josas, France) according to a specific format and entered into a database with input verification and output processes. Linkage analysis was performed with the CRIMAP program. Significant linkage was detected for 124 loci, of which 95 were unambiguously ordered using a multipoint analysis with an average spacing of 14.2 CM. These loci were distributed among 29 linkage groups. A more comprehensive analysis including synteny group data and FISH data suggested that 26 autosomes out of 31 are covered. The complete map spans 936 CM.

Animals↗
PubMed1991

The WAMI Rural Hospital Project. Part 1: Historical and theoretical underpinnings.

This set of six manuscripts describes the content and impact of the WAMI Rural Hospital Project (RHP), a research and development effort supported by the W.K. Kellogg Foundation, designed to improve the delivery of health services in six rural communities in the Pacific Northwest and Alaska. The major objective of the RHP--an activity which spanned a four-year period from 1985 through 1988--was to assist the project communities in improving the financial stability and quality of care of their local health care systems. Special attention was directed at helping the communities determine and implement an appropriate scope of health services, improve management and governance of the local health care enterprise, recruit and retain additional health personnel, and increase the extent to which community residents used local health services. In this first section we discuss the historical antecedents and conceptual underpinnings of the RHP and describe the five principal phases of the project. These include: (1) selection of communities for participation in the RHP, (2) comprehensive analysis of the health care system in each community, (3) community health services planning, including the development of comprehensive strategic plans, (4) implementation of techniques to improve local health services, and (5) project dissemination and evaluation. A pre-test, post-test model was employed to assess qualitative and quantitative changes in a variety of key measures of health system performance, including organization and management, scope of services, fiscal viability of the rural hospital, and utilization and patient satisfaction with health services in each community. The results of this evaluation constitute the balance of this report.

Alaska↗
PubMed1999

Amino acid neighbours and detailed conformational analysis of cysteines in proteins.

Here we present an investigation of the contacts that cysteines make with residues in their three-dimensional environment and a comprehensive analysis of the conformational features of 351 disulphide bridges in 131 non-homologous single-chain protein structures. Upstream half-cystines preferentially have downstream neighbours, whereas downstream half-cystines have mainly upstream neighbours. Non-disulphide bridged cysteines (free cysteines) have no preference for upstream or downstream neighbours. Free cysteines have more contacts to non-polar residues and fewer contacts to polar/charged residues than half-cystines, which correlates with our observation that free cysteines are more buried than half-cystines. Free cysteines prefer to be located in alpha-helices while no clear preference is observed for half-cystines. Histidine and methionine are preferentially seen nearby free cysteines. Tryptophan is found preferentially nearby half-cystines. We have merged sequential and spatial information, and highly interesting novel patterns have been discovered. The number of cysteines per protein is typically an even number, peaking at four. The number of residues separating two half-cystines is preferentially 11 and 16. Left-handed and right-handed disulphide bridges display different conformational parameters. Here we present side chain torsion angle information based on a 5-12 times larger number of disulphide bridges than has previously been published. Considering the importance of cysteines for maintaining the 3D-structural scaffold of proteins, it is essential to have as accurate information as possible concerning the packing and conformational preferences. The present work may provide key information for engineering the protein environment around cysteines.

Amino Acids↗
PubMed1984

Competitor analysis in health care marketing.

Health care providers increasingly are relying upon marketing as a means of overcoming growing competition. Competition-oriented marketing necessitates a comprehensive analysis of the competitive setting, a task which the health care marketing literature has generally given little attention. Herein the concept, perspective and tools of competitor analysis are borrowed from strategic planning and adapted for use in health care marketing.

Economic Competition↗
PubMed1994

The graphical analysis of tooth width discrepancy.

The standard tooth width ratio tables currently do not provide an overall indication of the final interdigitation of teeth. To provide a comprehensive analysis of inter-arch tooth width discrepancy, this study has developed a combination of cumulative percentage tooth width ratios and a method to visually determine the harmony between maxillary and mandibular tooth widths. Mesiodistal tooth widths from the first permanent molar to the corresponding first permanent molar were measured from 60 sets of pretreatment study models which were selected consecutively. Cumulative percentage ratios relating mandibular teeth to maxillary teeth were calculated utilising the mesiodistal tooth width measurements. The 13 mean cumulative percentage ratios developed in this study were plotted on graph paper showing plus and minus two standard deviations from the mean. These ratios provide a standard from which cumulative percentage ratios obtained from any new case may be compared graphically. Deviations from the mean cumulative percentage ratios are immediately recognised. No simple graphical method of assessment on the final interdigitation of anterior and posterior teeth has previously been devised. The graphical analysis of tooth width discrepancy is invaluable as an aid in localising any tooth width discrepancy and ensuring that incompatible maxillary-to-mandibular tooth widths are recognised prior to orthodontic treatment.

Humans↗
PubMed2026

Machine learning-based integration develops a novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in acute myeloid leukemia.

BACKGROUND: Lysosomes are essential for intracellular degradation and recycling, and changes in their function significantly contribute to tumor growth. Nonetheless, the exact role of lysosome-related genes (LRGs) in the pathogenesis of acute myeloid leukemia (AML) is still inadequately comprehended. METHODS: Differentially expressed LRGs (DE-LRGs) between AML and control groups were identified using AML-related data extracted from the Gene Expression Omnibus (GEO). The LRGs-related prognostic genes were identified and the risk model was established using univariate COX regression analysis and machine learning algorithms, based on the data obtained from The Cancer Genome Atlas (TCGA). Subsequently, we performed comprehensive analyses regarding clinical features, functional pathways, immune microenvironment, and chemotherapeutic drugs sensitivity between the high- and low-risk groups. Reverse transcription Quantitative polymerase chain reaction (RT-qPCR) and western blot were adopted to validate the expression of prognostic genes in human bone marrow-derived cell line HS-27 A and human AML cell line MOLM-13. RESULTS: Through comprehensive analysis, a risk model was developed utilizing ten LRGs (ATP6V0E2, CALCRL, TMEM165, GZMB, HCK, TCIRG1, CD1D, GPRASP1, ABCA1, and NAGA), and this model was further validated using GEO datasets. Significant differences in clinical characteristics, functional pathways, immune microenvironment characteristics, and chemotherapeutic drug sensitivity were observed between the two risk groups In vitro validation experiment illustrated that the expression trends of ATP6V0E2, TMEM165, and ABCA1 were consistent with our bioinformatics analysis. CONCLUSION: Our study demonstrates that lysosome-associated signature might forecast the prognosis of AML patients and offer guidance for subsequent immunotherapy and chemotherapy strategies.

Acute myeloid leukemia↗
PubMed1994

The comparison of limited resection to lobectomy for T1N0 non-small cell lung cancer. LCSG 821.

The Lung Cancer Study Group, in order to investigate lesser resection within the community as definitive management for T1N0 lung cancers, in 1982 began a prospective trial of limited resection compared to lobectomy for these patients. First reported results demonstrated no significant differences for stratification and other prognostic variables, and no differences in postoperative complication rates. Interim analysis 3 years later suggested a higher local recurrence rate in the limited resection arm of the study. Further comprehensive analysis will be forthcoming.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Establishing a physician incentive system.

The increasing complexity of managed care is changing the need for better information on medical costs and utilization. Because most claims systems have limited reporting and analysis capabilities, a better alternative is to transfer the data into the reporting systems described herein, in which a comprehensive analysis is conducted faster and at a lower cost. Virtually any type of analysis is possible.

Adult↗
PubMed2002

MIPS: a database for genomes and protein sequences.

The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) continues to provide genome-related information in a systematic way. MIPS supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the databases for the comprehensive set of genomes (PEDANT genomes), the database of annotated human EST clusters (HIB), the database of complete cDNAs from the DHGP (German Human Genome Project), as well as the project specific databases for the GABI (Genome Analysis in Plants) and HNB (Helmholtz-Netzwerk Bioinformatik) networks. The Arabidospsis thaliana database (MATDB), the database of mitochondrial proteins (MITOP) and our contribution to the PIR International Protein Sequence Database have been described elsewhere [Schoof et al. (2002) Nucleic Acids Res., 30, 91-93; Scharfe et al. (2000) Nucleic Acids Res., 28, 155-158; Barker et al. (2001) Nucleic Acids Res., 29, 29-32]. All databases described, the protein analysis tools provided and the detailed descriptions of our projects can be accessed through the MIPS World Wide Web server (http://mips.gsf.de).

Amino Acid Sequence↗
PubMed1999

Design and analysis issues in case-control studies addressing genetic susceptibility.

Case-control studies are among the main study designs for investigating the effect of environmental exposures on disease etiology and are now becoming more frequently used to examine the influence of genetic susceptibility. Incorporating a case-control design to examine genetic exposure would seem appropriate as the main problems of case-control studies, those of bias and confounding, are more easily avoided. However, they do not have a strong image and are thought to provide too many spurious findings as a result of chance, bias or confounding. This criticism has often been valid, especially for many early studies based on small numbers of poorly defined cases that were compared to convenient groups of local controls. New family-based study designs that account for these problems have been suggested, including the transmission disequilibrium test. However, the traditional format of case-control studies may be improved by incorporating methodological refinements developed over the past 30 years in environmental epidemiology. The present chapter attempts to outline these issues and to provide guidelines for the selection of cases and controls and for the analysis of genetic data from case-control studies. Alternative, family-based study designs will also be discussed. Finally, a comprehensive analysis approach to gene-environment and gene-gene interaction is proposed.

Bias↗
PubMed1992

[A frontal cephalometric analysis].

A comprehensive frontal cephalometric analysis was developed and its normal values for Chinese adults were established in this study. This analysis includes two parts: width proportional analysis and symmetry analysis. Most linear width values of males were significantly greater than those of females as expected. However, there were no significant sex differentials in the most width ratios. Among these, the ratio Go/Z reached ca. 75%, Mx/Zy ca. 50%, L6/Go ca. 50% and the Mx/Go ca. 66.6% (2/3). Width problems and possible expansion at canine and molar areas could be evaluated through proportional analysis. To determine the locations as well as extents of dentofacial asymmetry is of great clinical value especially in orthodontic treatment. In symmetry analysis, linear differences between both side structures in vertical and horizontal directions could be calculated.

Adult↗
PubMed1996

Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas.

Only one oncogene, cyclin D1/PRAD1, has an established role in parathyroid tumorigenesis, and parathyroid tumor suppressor genes on chromosome arms 1p and 11q, which still have not been identified, have also been implicated by loss of heterozygosity analysis. To investigate whether other putative tumor suppressor genes are involved in the pathogenesis of parathyroid adenomas, we performed a more comprehensive analysis of allelic losses in these tumors. Using 39 polymorphic markers, we examined each chromosome arm, excluding the short arms of the acrocentric chromosomes. In 25 parathyroid adenomas, frequent loss of heterozygosity, in > 25% of the informative cases, was observed on chromosome arms 6q (30%), 11p (27%), and 15q (35%), in addition to previously reported 1p (30%) and 11q (38%) allelic losses. To more specifically localize the smallest shared regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 6 (9 additional markers), chromosome 11 (8 additional markers), and chromosome 15 (15 additional markers). The regions most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and 15q26-qter. All tumors with 11p loss had patterns consistent with monosomy for chromosome 11. These findings provide novel evidence for the existence of tumor suppressor genes on chromosome arms 6q and 15q that contribute commonly to the pathogenesis of parathyroid adenomas.

Adenoma↗
PubMed1994

Integrin expression by human articular chondrocytes.

OBJECTIVE: To perform a comprehensive analysis of the integrin forms expressed by normal human articular chondrocytes. METHODS: Cartilage sections and collagenase-released chondrocytes were probed with a comprehensive panel of integrin isoform-specific monoclonal antibodies (MAb), using in situ immunohistochemistry techniques, indirect immunofluorescence and flow cytometry, and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Chondrocytes in cartilage sections reacted with MAb specific for the alpha 5, alpha v, and beta 1 integrin subunits and the alpha v beta 3 and alpha v beta 5 heterodimers. They also reacted with a polyclonal antibody specific for the intracytoplasmic portion of the alpha 1 subunit. MAb specific for the alpha v subunit reacted more strongly with chondrocytes near the articular surface than with those in deeper layers of cartilage, and the alpha v beta 3-specific MAb reacted exclusively with chondrocytes within the most superficial 30 microns of cartilage. Flow cytometric analysis and SDS-PAGE analysis of immunoprecipitates prepared from extracts of cell-surface radioiodinated chondrocytes confirmed the above observations, and additionally revealed the presence of the alpha 3 beta 1 integrin. CONCLUSION: Normal human articular chondrocytes prominently display substantial quantities of the alpha 1 beta 1, alpha 5 beta 1, and alpha v beta 5 integrin heterodimers, as well as lesser quantities of the alpha 3 beta 1 and alpha v beta 3 heterodimers. The alpha v subunit-containing integrins are detected more readily on the more superficial chondrocytes than on chondrocytes deep within cartilage. These observations provide the basis for analysis of the role of chondrocyte integrins in cartilage homeostasis and in the pathogenesis of joint diseases.

Adult↗
PubMed2002

Analysis of the proteome in the human pituitary.

The pituitary is the master endocrine gland responsible for the regulation of various physiologic and metabolic processes. Proteomics offers an efficient means for a comprehensive analysis of pituitary protein expression. This paper reports on the application of proteomics for the mapping of major proteins in a normal (control) pituitary. Pituitary proteins were separated by two-dimensional gel electrophoresis with immobilized pH 3-10 gradient strips. Major protein spots that were visualized in the two-dimensional gel by silver staining were excised, and the proteins in these spots were digested with trypsin. The tryptic digests were analyzed by mass spectrometry, and the mass spectrometric data were used to identify the proteins through searches of the SWISS-PROT or NCBInr protein sequence databases. The majority of the proteins were identified on the basis of peptide mass fingerprinting data obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Several proteins were also characterized based on product-ion spectra measured by post-source decay analysis and/or liquid chromatography-electrospray-quadrupole ion trap mass spectrometry. To date, 62 prominent protein spots, corresponding to 38 different proteins, were identified. The identified proteins include important pituitary hormones, structural proteins, enzymes, and other proteins. The protein identification data were used to establish a two-dimensional reference database of the human pituitary, which can be accessed over the Internet (http://www.utmem.edu/proteomics). This database will serve as a tool for further proteomics studies of pituitary protein expression in health and disease.

Computational Biology↗
PubMed2024

Exploring Regulatory Roles of Transposable Elements in EMT and MET through Data-Driven Analysis: Insights from regulaTER.

Gene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in a given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded from https://github.com/karakulahg/regulaTER.

DNA Transposable Elements↗
PubMed2002

Tools for comparative analysis of alternatives: competing or complementary perspectives?

A third generation of environmental policy making and risk management will increasingly impose environmental measures, which may give rise to analyzing countervailing risks. Therefore, a comprehensive analysis of all risks associated with the decision alternatives will aid decision-makers in prioritizing alternatives that effectively reduce both target and countervailing risks. Starting with the metaphor of the ripples caused by a stone that is thrown into a pond, we identify 10 types of ripples that symbolize, in our case, risks that deserve closer examination: direct, upstream, downstream, accidental risks, occupational risks, risks due to offsetting behavior, change in disposable income, macro-economic changes, depletion of natural resources, and risks to the manmade environment. Tools to analyze these risks were developed independently and recently have been applied to overlapping fields of application. This suggests that either the tools should be linked in a unified framework for comparative analysis or that the appropriate field of application for single tools should be better understood. The goals of this article are to create a better foundation for the understanding of the nature and coverage of available tools and to identify the remaining gaps. None of the tools is designed to deal with all 10 types of risk. Provided data suggest that, of the 10 types of identified risks, those associated with changes in disposable income may be particularly significant when decision alternatives differ with respect to their effects on disposable income. Finally, the present analysis was limited to analytical questions and did not capture the important role of the decision-making process itself.

Cost-Benefit Analysis↗