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At least 613 records · Page 34Linked to original sources
PubMed2000

Structural and functional properties of membrane and secreted IgD.

More than 35 years ago, study of an unknown immunoglobulin (Ig) in the serum from a myeloma patient led to the discovery of IgD. Subsequently, the finding that it also exists as a membrane-bound Ig stimulated a large number of studies during the 70s. Then, the interest on IgD shrank, largely because of the lack of known function of secretory IgD (secIgD) and of a stagnating knowledge of the functions of surface IgD. In the recent years, very significant advances followed the tremendous accumulation of data on the physiology of the B cell receptor, of which IgD is the major component, on the role of secIgD in normal and diseased individuals. This review, which is focused on human IgD but integrates data in the mouse and other species when needed, summarizes present data on the structure, synthesis and functions of both membrane and secIgD, IgD receptors and the involvement of IgD in various diseases, especially the hyperIgD syndrome.

Animals↗
PubMed1985

Automated data processing for chromatographic assay method validations.

A set of computer programs has been developed for the automated transfer, storage, and processing of data related to chromatographic pharmaceutical assay method validations. These programs calculate and report statistical parameters relating to the resolution, linearity of response, and precision of an assay method based upon peak width, retention time, and integration data provided by a commercial chromatographic data system. Utilization of an interface between the data system and a microcomputer minimizes manual handling of all data. Techniques and equations used in the development of the software are described, and an application to the validation of a high performance liquid chromatographic assay method for a bulk drug substance is demonstrated.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

New topographic mapping of temporal lobe seizures.

A unique topographic map has been developed based on EEG data of ictal events originating from the basal/mesiotemporal lobe regions. This technique involves a new mapping method of temporal lobe seizures as opposed to the interictal activity maps of most commercially available software. The map integrates data from sphenoidal electrodes as well as the standard 10-20 surface electrodes recorded with bipolar montages. A basal view is ideal for visualization of onset of temporal lobe ictal discharges recorded with chronic sphenoidal electrodes. We used the last 150 ictal events from 40 patients with basal/mediotemporal lobe epilepsy to develop this technique. Results indicate that a topographic view incorporating sphenoidal and scalp electrodes may provide a useful adjunct for interpretation of EEG recordings and a basis for comparison between and among patient groups for both ictal and interictal epileptic discharges.

Brain Mapping↗
PubMed2001

PIES, a protein interaction extraction system.

We consider the problem of extracting, manipulating, and managing biological pathways, especially protein-protein interaction pathways. We discuss here the Protein Interaction Extraction System (PIES). PIES is contructed on top of three main technologies: Kleisli, BioNLP, and Graphviz. Kleisli is a broad-scale data integration system that we use for downloading Medline abstracts and for general manipulation and management of pathway/interaction databases. BioNLP is a natural language-based information extraction module that we use for analysing Medline abstracts and to extract precise protein-protein and other interaction information. Graphviz is a graphical layout package developed for directed graphs that we use for visualization of the extracted pathways. PIES can be augmented with various means for extracting protein interaction information from sequence databases, for example, by using Kleisli's power to integrate sequence comparison tools to detect gene fusion events in sequence databases.

Abstracting and Indexing↗
PubMed2000

The hindsight gene is required for epithelial maintenance and differentiation of the tracheal system in Drosophila.

During animal development, morphogenesis of tissues and organs requires dynamic cell shape changes and movements that are accomplished without loss of epithelial integrity. Data from vertebrate and invertebrate systems have implicated several cell surface and cytoskeleton-associated molecules in the establishment and maintenance of epithelial architecture, but there has been little analysis of the genetic regulatory hierarchies that control epithelial morphogenesis in specific tissues. Here we show that the Drosophila Hindsight nuclear zinc-finger protein is required during tracheal morphogenesis for the maintenance of epithelial integrity and assembly of apical extracellular structures known as taenidia. In hindsight (hnt) mutants tracheal placodes form, invaginate, and undergo primary branching as well as early fusion events. Starting at midembryogenesis, however, the tracheal epithelium collapses or expands to give rise to sacs of tissue. While a subset of hnt mutant tracheal cells enters the apoptotic pathway, genetic suppression of apoptosis indicates that this is not the cause of the epithelial defects. Surviving hnt mutant tracheal cells retain cell-cell junctions and a normal subcellular distribution of apical markers such as Crumbs and DE-Cadherin. However, taenidia do not form on the lumenal surface of tracheal cells. While loss of epithelial integrity is a common feature of crumbs, stardust, and hnt mutants, defective assembly of taenidia is unique to hnt mutants. These data suggest that HNT is a tissue-specific factor that regulates maintenance of the tracheal epithelium as well as differentiation of taenidia.

Animals↗
PubMed2002

Prediction of intestinal absorption: comparative assessment of GASTROPLUS and IDEA.

We have assessed two commercial software tools employing physiologically based models for prediction of intestinal absorption in human. IDEA 2.0 and GASTROPLUS 3.1.0 were compared both in their ability to predict fraction absorbed for a set of 28 drugs and in terms of the functionality offered. The emphasis was placed on the practical usefulness to pharmaceutical drug discovery. Predictions were assessed for three levels of input data (i) pure in silico input, (ii) thermodynamic solubility and in silico permeability, (iii) thermodynamic solubility and human colon carcinoma cell line (CACO-2) permeability. We found the pure in silico prediction ability of the tools to be comparable with 70% correct classification rate. With measured input data the IDEA prediction rate improved to 79% while GASTROPLUS stayed at 70%. In terms of functionality GASTROPLUS is a powerful system for the trained user. Open access to model parameters, diagnostic tools and the ability to integrate data make it particularly suitable for the later stages of discovery and development. IDEA is web based and presents a simple interface suitable for widespread use with minimal training. However the limited functionality and inconvenient handling of multiple compound batches currently restrict the usefulness of version 2.0 for drug discovery.

Intestinal Absorption↗
PubMed1992

Techniques for dataset design: a utilization management system model.

Designing a clinical information system offers a sense of accomplishment similar to that of a dramatic performance. The development of the data dictionary and proposed system description requires the same attention to detail as stage directions in a script. The people involved in daily system operation are of key importance in developing a clear understanding of how things actually happen in the information flow and decision process. Once the business rules are defined and edits and conditions are developed to ensure data integrity, it is time to step back and let the performance begin. The real power of the user-designed system, like that of a performance before a live audience, comes with the ability to query the data for answers to issues and problems decision makers did not face at the time of the initial system design.

Clinical Medicine↗
PubMed1988

[Transmission of Dusseldorf Integrated Medical Documentation data by a personal computer. A new concept in the flexibility of the Dusseldorf Integrated Medical Documentation system].

The software package HOST PC was created as an important expansion of the oncological aftercare program INMEDD (Integrated Medical Documentation Düsseldorf). INMEDD itself provides only small evaluation capabilities. HOST PC is able to transmit data from INMEDD on a host computer to a personal computer. This transmission is fully automated. On the personal computer the data is stored in a database, which is completely compatible with the standards of dBase III. These created databases can be evaluated and analyzed by a lot of standard software packages. Therefore a wide range of individual statistical evaluation, analyzing with optional criteria and graphic presentation can be realized with small expenses of time and money. HOST PC increases the attractiveness of INMEDD and therefore improves the aftercare of cancer patients.

Aftercare↗
PubMed1987

Normal sleep: patterns and mechanisms.

In the last three decades, research in the sleep laboratory has decisively contributed to a much deeper knowledge of sleep physiologic and pathologic states. Parallel to clinical research related to sleep disorders, multifaceted basic research has greatly contributed to a better understanding of the mechanisms underlying sleep and wakefulness. This basic research in the realm of the neurosciences integrates data derived from the application of various methodologic approaches. Currently, the prevailing concepts about sleep mechanisms generally favor the idea of a dynamic interaction among systems rather than that of a unidimensional explanation for sleep generation. Examples of these integrative concepts in current sleep research are the revised model of reciprocal interaction for the control of REM sleep and the two-process model comprising the seemingly incompatible homeostatic and circadian sleep mechanisms. In sleep disorders medicine, the prevailing approach is also integrative: findings from the sleep laboratory are considered in conjunction with those from clinical experience in understanding the nature of sleep disorders. Applying this integrative model, physicians in sleep disorders medicine are able to manage patients with sleep disorders comprehensively. Based on an understanding of sleep physiology, clinicians can make the diagnosis of most sleep disorders in the office setting.

Adolescent↗
PubMedDate not supplied

Estimating the frequency of tap-water exposures to Mycobacterium avium complex in the U.S. population with advanced AIDS.

Mycobacterium avium complex (MAC) is a group of ubiquitous and opportunistic bacterial pathogens included on the U.S. Environmental Protection Agency Drinking Water Contaminant Candidate List. The risk of contracting a disseminated MAC infection is primarily limited to the immunocompromised, including those with advanced acquired immunodeficiency syndrome (AIDS). These infections likely result from exposures to MAC-contaminated tap water, food, or soil, although the epidemiologic evidence is insufficient to implicate a specific medium. The objective of this study was to assess tap water exposure to MAC in the U.S. population with advanced AIDS, defined here as having fewer than 100 CD4(+) cells/mm(3) of blood. Using limited data on the detection of MAC and self-reported post-tap treatment practices, two exposure models were developed to simulate the likelihood of exposure to MAC via tap water consumption in this sensitive population. The first model integrated data from studies that described sources of water for consumption and post-tap treatment rates in cohorts infected with human immunodeficiency virus (HIV(+)). The second model used data from a study that categorized the fraction of water intake consisting of tap water that was not further treated. Approximately 1500 individuals with advanced AIDS were estimated to ingest tap water with detectable concentrations of MAC organisms daily. Additional studies on tap-water use in U.S. HIV(+) populations are needed to confirm these findings. Longitudinal and cross-sectional studies on the occurrence of MAC in tap water, particularly in regions with large HIV(+)/AIDS populations, would help address some of the uncertainty in these exposure estimates.

AIDS-Related Opportunistic Infections↗
PubMed2026

Genetic architecture of endometriosis: risk factors, comorbidities and clinical implications.

BACKGROUND: In 1999, Dr Susan Treloar and colleagues conducted a landmark twin study in Australia and reported their estimate of 51% for the heritability of endometriosis. This important result led several groups to begin mapping genetic factors contributing to increased endometriosis risk. Despite early challenges, advances in genome-wide association studies (GWAS) have identified multiple genetic risk factors and some target genes implicated in follow-up studies on genetic regulation of transcription. Access to large publicly available genetic datasets and analysis with endometriosis GWAS results is also providing new opportunities to answer important questions about comorbid conditions associated with endometriosis and their implications for clinical practice. OBJECTIVE AND RATIONALE: The objective of the review is to summarize the last 25 years of genetic studies in endometriosis, outline contributions to our understanding of the disease, and suggest future directions to accelerate biological insights from genetic studies to improve clinical outcomes. SEARCH METHODS: A comprehensive review of scientific literature on the genetics of endometriosis was conducted through searches in PubMed and Google Scholar up to June 2026. Search terms included "endometriosis AND (genetics OR GWAS OR genetic risk factors)", For studies addressing the functional characterization of genetic risk loci, additional searches employed the terms "endometriosis AND (genotype-phenotype associations OR colocalization OR eQTL OR mQTL OR multi omics methods)". To identify studies examining shared genetic risk between endometriosis and comorbid conditions, the search strategy included "endometriosis AND (genetic correlation OR colocalization OR Mendelian randomisation)". Publications reporting discoveries related to genetic risk factors for endometriosis and studies interpreting their biological and clinical significance were critically evaluated, and 144 publications were discussed in the review. OUTCOMES: Discovery of genetic risk factors started slowly and has accelerated in recent years with developments in technology and international collaborations to combine data and increase statistical power. GWAS have mapped 80 genetic risk factors that implicate gene regulation of hormonal targets, development of the reproductive tract, regulation of cell proliferation, and regulation of epithelial cell differentiation. In common with most other complex diseases, effects of individual common genetic risk factors are small. However, several examples demonstrate that small effect sizes are not a good predictor for the impact of drugs developed against genetically validated targets. Genetic risk factors implicate five genes regulating gonadotrophin release and oestrogen action, the major target pathway of current drugs for treatment of endometriosis demonstrating proof-of-principal for biologically meaningful results. Genetic correlation and Mendelian Randomization studies highlight important causal relationships between endometriosis and comorbid conditions including a possible role for testosterone during development and shared genetic risk factors for gynaecological, gastrointestinal, pain, psychiatric, and inflammatory conditions. Understanding causal relationships between endometriosis and related conditions will aid clinical management and more personalized treatments. WIDER IMPLICATIONS: Genetic studies provide novel insights into endometriosis pathogenesis and associations with related comorbid conditions. Genetic factors modifying gene regulation and disease risk likely act in specific cell types, and access to datasets from genetically informed cell-based models, single-cell and spatial omics data are needed to accelerate progress. Future studies should address critical questions of heterogeneity and disease subtypes, expand the search for genetic risk factors to non-European populations, evaluate the role of rare and structural variants, and better integrate data from functional, genomics, genetics, and clinical studies to reduce diagnostic delay, develop novel treatment strategies, and translate discoveries into personalized management strategies for affected individuals. REGISTRATION NUMBER: N/A.

comorbid conditions↗
PubMed2001

Correlates of depression in older Latinos.

OBJECTIVE: To report the rates of depressive disorders--i.e., major and subthreshold depression--as well as the correlates of depression in a sample of older Latino primary care consumers. The study addresses the gap in the literature concerning depression and older Latinos residing in the U.S. DATA SOURCES AND STUDY SETTING: Data were collected from 150 Latino primary care consumers (50+ years-old) in Los Angeles County. Depression was measured using the depression module of the PRIME-MD Patient Health Questionnaire. Demographic, stress-related, health, and social integration data were also collected. STUDY DESIGN: A cross sectional design was employed vis-à-vis face-to-face interviews of respondents at the clinic sites or in their homes. Descriptive analyses and logistic regression modeling were used to describe the sample and to examine the correlates of depression. PRINCIPLE FINDINGS: Rates of depression indicate that 24.1% of the sample reported symptoms sufficient to meet the criteria for a PHQ depression diagnosis. Only social functioning and income were associated with the presence of a depressive disorder. Interference with social activities with family and friends as a result of physical and emotional problems was associated with a 1.86-fold increase risk of being depressed. CONCLUSIONS: Although most of the cases were classified as subthreshold, prior work has shown that subthreshold depression can be clinically significant and debilitating. Using brief screening instruments such as the PHQ, practitioners can identify cases needing further assessment and treatment.

Acculturation↗
PubMed1991

Work experiences of minority managers and professionals: individual and organizational costs of perceived bias.

The present study examined the relations of the way minority managers and professionals described their treatment within their organizations, and their organizations' acceptance and openness to minorities within measures of satisfaction, commitment, skill utilization, and integration. Data were collected from 81 minority managers and professionals in early career stages using questionnaires completed anonymously. Minority managers experiencing more positive treatment in their organization, and employed in organizations more accepting of minorities, were more satisfied, committed, and integrated.

Achievement↗
PubMed1997

Effect of prosthetic superstructure accuracy on the osteointegrated implant bone interface.

OBJECTIVE: This study evaluated the biologic result of forces induced by a misfitting prosthetic superstructure on implants placed in a New Zealand white rabbit tibia model. STUDY DESIGN: Nine rabbits had two dental implants placed in both right and left proximal tibias. After 6 weeks, one animal was sacrificed for baseline integration data, and the remaining animals had fitting or misfitting prosthetic superstructures attached to the implants for 12 weeks. Implants were evaluated clinically, radiographically, and histomorphometrically at the scanning electron microscopic level. RESULTS: No clinical, radiographic, or histomorphometric evidence exists of integration failure with implants subjected to superstructure strain, although bone remodeling is noted. CONCLUSIONS: Given the limitations of sample size, animal model used, duration of prosthetic superstructure attachment, and loading confounders possible, the study of prosthetic framework misfit must be evaluated with another animal model, such as an intraoral primate model, to determine the relationship between clinical performance and histologic findings.

Adaptation, Physiological↗
PubMed2003

Effective integration of protein data through better data modeling.

Protein data, from sequence and structure to interaction, is being generated through many diverse methodologies; it is stored and reported in numerous forms and multiple places. The magnitude of the data limits researchers abilities to utilize all information generated. Effective integration of protein data can be accomplished through better data modeling. We demonstrate this through the MIPD project.

Models, Molecular↗
PubMed2003

The UCSC Genome Browser Database.

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.

Animals↗
PubMed2004

Noise filtering and nonparametric analysis of microarray data underscores discriminating markers of oral, prostate, lung, ovarian and breast cancer.

BACKGROUND: A major goal of cancer research is to identify discrete biomarkers that specifically characterize a given malignancy. These markers are useful in diagnosis, may identify potential targets for drug development, and can aid in evaluating treatment efficacy and predicting patient outcome. Microarray technology has enabled marker discovery from human cells by permitting measurement of steady-state mRNA levels derived from thousands of genes. However many challenging and unresolved issues regarding the acquisition and analysis of microarray data remain, such as accounting for both experimental and biological noise, transcripts whose expression profiles are not normally distributed, guidelines for statistical assessment of false positive/negative rates and comparing data derived from different research groups. This study addresses these issues using Affymetrix HG-U95A and HG-U133 GeneChip data derived from different research groups. RESULTS: We present here a simple non parametric approach coupled with noise filtering to identify sets of genes differentially expressed between the normal and cancer states in oral, breast, lung, prostate and ovarian tumors. An important feature of this study is the ability to integrate data from different laboratories, improving the analytical power of the individual results. One of the most interesting findings is the down regulation of genes involved in tissue differentiation. CONCLUSIONS: This study presents the development and application of a noise model that suppresses noise, limits false positives in the results, and allows integration of results from individual studies derived from different research groups.

Algorithms↗
PubMed1997

Foot pressure distribution: methodology and clinical application for children with ankle rheumatoid arthritis.

INTRODUCTION:: Foot pressure measurements furnish information about distribution of pressures, forces, time and contact areas under the foot during standing and walking. Foot pressure measurement has been used in a number of rehabilitation and athletic applications in adults, however, little has been published regarding the clinical usefulness of this technology for children with disabilities. Children with juvenile rheumatoid arthritis (JRA) are reported to have various foot deformities and gait deviations and clinicians report that the children may have foot pain such as metatarsalgia. These may be treated with specially fitted shoes, shoe modifications or ankle foot orthoses. The purpose of this preliminary study was to describe the methodology used to quantify foot pressure distribution patterns and, further, to describe the patterns seen in individual children with JRA compared to aged matched typical children without JRA. METHODS:: Pressure, area and force were measured using the EMED-F system including a platform with 2048 capacitive pressure sensors and a computerized data collection and analysis system. Children were asked to walk comfortably and normally across the platform while time, pressure and area measurements were automatically taken. Other data collected were height and weight, observational gait analysis and lower extremity range of motion measurements. Data are reported for the entire foot, as well as particular areas of the foot that are of interest. For this study, eight discrete areas or masks were identified (medial and lateral heel, medial and lateral midfoot, first metatarsal, lateral four metatarsals, great toes and four lateral toes) for description. Information reported for each area and the total foot included force, peak pressure, total area, pressure time integral and force time integral. Data from three pairs of children were analysed and differences were described. RESULTS:: Several differences in the descriptive data were noted and will be highlighted. Children with JRA had striking asymmetries in several variables, higher peak pressures and in increased total foot pressure time integrals and force time integrals. This information is presented to improve our understanding of the patterns under the foot so that (1) appropriate treatment strategies for foot impairments may be better prescribed for children with JRA and (2) to assist in planning for treatment of gait abnormalities. This preliminary work will also form the basis for determining the clinically meaningful variables to consider in a larger study and statistical analysis.

Journal Article↗