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At least 1,603 records · Page 89Linked to original sources
PubMed2006

Ages of onset suggestive of genetic anticipation in rheumatoid arthritis multicase sibships can be explained by observational bias.

OBJECTIVES: Previous work has suggested that features of genetic anticipation might be present in familial rheumatoid arthritis (RA), but bias is difficult to exclude when looking at disease in two consecutive generations. We used data from the North American Rheumatoid Arthritis Consortium (NARAC) and the Arthritis Research Campaign National repository for RA multicase pedigrees to determine whether differences in age of onset within multicase sibships were supportive of genetic anticipation. METHOD: RA sibling pairs were identified from both data sets. The period of observation was defined as the time between the first sibling developing RA and the time that the sibship was ascertained for the study. A paired t-test for the difference in ages of RA onset within the pairs was calculated. Ages of conception of the parent were correlated with the age of RA onset. RESULTS: Information was available for 743 sibships in the NARAC data set and 396 sibships in the Arthritis Research Campaign (ARC) data set. In both data sets, the older siblings had an older age of onset than their younger siblings (39.3 vs 36.9 in the NARAC, and 43.8 vs 40.1 in the ARC data set, both P < 0.001). The two data sets were then stratified into tertiles by a period of observation. In both data sets, there was a progressive decline in the sibling age of onset differences. For the first tertile (shortest observation period), the older sibling had a significantly older age of onset than the younger. This difference decreased in the second tertile, and was not significant in the third tertile (longest observation period). There was no significant correlation between the age of RA onset and the maternal or paternal ages of conception in either data set. CONCLUSION: Features compatible with genetic anticipation in RA multicase sibships are subject to observational bias. This does not support a role for genetic anticipation in familial RA.

Adult↗
PubMed2006

Thermal stability of the thermoluminescence trap structure of bentonite.

This work reports about the thermal stability of the blue thermoluminescence (TL) of a well-characterised natural bentonite from Almeria (Spain). The main interest of this clay, mainly composed of montmorillonite, is because of its application in the field of high-level radioactive waste (HLW) repository in deep-lying rocks. As observed in other aluminosilicates, bentonite exhibits a very complex structure of the emission spectra based on a wide broad maximum peaked at approximately 265 degrees C that can be associated to physico-chemical processes such as dehydroxylation processes, consecutive breaking linking of bonds, formation of hydrolysed ions and redox reactions. The thermal stability tests performed at different temperatures confirm a continuum in the distribution of traps. Hence, the glow curve analysis methods commonly used for synthetic materials based on single discrete traps cannot be applied for this material and the kinetic parameters were fitted assuming an exponential distribution of trapped electrons.

Bentonite↗
PubMed2026

Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders (SSDs) produce severe symptoms, disability, and premature mortality, but only partially effective symptomatic treatments exist. Treatment development is impeded by lack of insight into disease mechanisms or objective biomarkers for clinical trials. Advances in genetics and neurobiology have converged on strong pathogenic hypotheses for SSDs centered on synapse dysfunction and excessive pruning, pathogenic processes that may produce measurable proteomic evidence in cerebrospinal fluid (CSF). Leveraging design precedents from successful fluid biomarkers discovery for Alzheimer's disease, we undertook a pilot study to test the feasibility of repeated CSF and blood samples collection from individuals with SSDs. Here we report on successful implementation of longitudinal bio-behavioral phenotyping in SSDs and establishment of a repository to permit broad sample and data sharing. STUDY DESIGN: The Schizophrenia Spectrum Biomarkers Consortium (SSBC) study principles included longitudinal study design, paired CSF and plasma collection associated with robust phenotypic characterization, at 3 academic sites and the establishment of a biorepository. Participants underwent clinical and cognitive assessments, neuroimaging, blood draws, and CSF collection via lumbar puncture (LP) every 6&#xa0;months. STUDY RESULTS: SSBC successfully enrolled 48 SSD and 41 Healthy Controls with a 73% longitudinal retention. Clinical, cognitive, and neuroimaging results were consistent across sites and with existing studies. Study procedures were well tolerated, and almost all LPs (99%) resulted in either no or minor headache/backache that resolved without medical interventions. CONCLUSIONS: The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.

Humans↗
PubMed1990

Late-season changes in allocation of starch and sugar to shoots, coarse roots, and fine roots in two hybrid poplar clones.

Two hybrid Populus clones, Tristis and Eugenei, which had been grown from cuttings in 114-liter pots sunk in the ground, were sequentially harvested during the latter part of the first growing season. Pots were supplied with water and nitrogen at two different rates. Starch and sugar concentrations were determined in samples taken from stems, branches, cuttings, and five diameter classes of roots. Concentrations of starch and sugar in all components of the trees were significantly affected by time of harvest and clone. Water and nitrogen treatments, however, did not significantly affect carbohydrate concentrations. From August to November, as plants developed cold hardiness, starch concentrations declined and sugar concentrations increased in stems and branches, especially in Tristis. In both clones, the large roots (> 1 mm diameter) were major repositories of starch and sugar late in the season. By the end of September, 80% of total-tree nonstructural carbohydrates in Eugenei were located in the roots. Even the fine-root fraction (< 0.5 mm diameter) showed substantial carbohydrate loading in late season, contradicting the hypothesis that starch deposition in fine roots occurs only when they are being formed.

Journal Article↗
PubMed2006

MGOS: A resource for studying Magnaporthe grisea and Oryza sativa interactions.

The MGOS (Magnaporthe grisea Oryza sativa) web-based database contains data from Oryza sativa and Magnaporthe grisea interaction experiments in which M. grisea is the fungal pathogen that causes the rice blast disease. In order to study the interactions, a consortium of fungal and rice geneticists was formed to construct a comprehensive set of experiments that would elucidate information about the gene expression of both rice and M. grisea during the infection cycle. These experiments included constructing and sequencing cDNA and robust long-serial analysis gene expression libraries from both host and pathogen during different stages of infection in both resistant and susceptible interactions, generating >50,000 M. grisea mutants and applying them to susceptible rice strains to test for pathogenicity, and constructing a dual O. sativa-M. grisea microarray. MGOS was developed as a central web-based repository for all the experimental data along with the rice and M. grisea genomic sequence. Community-based annotation is available for the M. grisea genes to aid in the study of the interactions.

Computational Biology↗
PubMed2026

Integrated Genomics and Transcriptomics Reveal Stable Resistance Loci and Candidate Genes for Powdery Mildew in Wheat.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), poses a substantial threat to global wheat production. Enhancing resistance through molecular breeding necessitates a comprehensive understanding of its genetic and molecular underpinnings. This study leveraged a 2-year phenotypic evaluation of 283 diverse wheat accessions combined with genome-wide association studies (GWAS) to pinpoint stable quantitative trait loci for powdery mildew resistance. We identified 52 robust resistance loci across the wheat genome, including seven novel loci consistently detected across four environments. Comparative transcriptome profiling of resistant and susceptible wheat lines revealed 95 differentially expressed genes, predominantly enriched in defense response, signal transduction, and transcription regulation pathways. By integrating the GWAS and transcriptomic data, we precisely identified three compelling candidate genes (TaPIP5K, TaPKG, and TaORR6) on chromosome 2A, which are implicated in cell wall reinforcement, jasmonic acid signaling, and reactive oxygen species scavenging, respectively. Further validation using expression analysis corroborated their pivotal roles in resistance. Our findings provide a rich repository of validated genetic markers, promising candidate genes, and superior resistant germplasms, offering critical resources to accelerate targeted molecular breeding efforts for durable powdery mildew resistance in wheat.

Blumeria graminis f. sp. tritici↗
PubMed2000

Live rhesus offspring by artificial insemination using fresh sperm and cryopreserved sperm.

Artificial insemination (AI) and the cryopreservation of sperm with full reproductive capabilities are vital in the armamentarium of infertility clinics and reproductive laboratories. Notwithstanding the fantastic successes with AI and sperm cryopreservation in numerous species, including humans and cattle, these assisted reproductive technologies are less well developed in other species of importance for biomedical research, such as genetically modified mice and nonhuman primates. To that end, AI at high efficiency in the rhesus macaque (Macaca mullata) and the successful cryopreservation of rhesus sperm is presented here, as are the complexities of this primate model due to differences in reproductive tract anatomy and gamete physiology. Cryopreservation had no effect on the ability of sperm to fertilize oocytes in vitro or in vivo. Post-thaw progressive motility was not affected by cryopreservation; however, acrosome integrity was lower for cryopreserved (74.1%) than for fresh sperm (92.7%). Fertilization rates did not differ when fresh (58.1%; n = 32/55) or cryopreserved sperm (63.8%; n = 23/36) were used for in vitro fertilization. Similarly, pregnancy rates did not differ significantly after AI with fresh (57.1%; n = 8/14) or cryopreserved sperm (62.5%; n = 5/8). Seven live rhesus macaques were born following AI with fresh sperm, and three live offspring and two ongoing pregnancies were obtained when cryopreserved sperm were used. Cryopreservation of rhesus sperm as presented here would allow for the cost-effective storage of lineages of nonhuman primates with known genotypes. These results suggest that either national or international centers could be established as repositories to fill the global needs of sperm for nonhuman primate research and to provide the experimental foundation on which to explore and perfect the preservation of sperm from endangered nonhuman primates.

Acrosome Reaction↗
PubMed1999

History of medicine: the metamorphosis of scientific medicine in the ever-present past.

Hippocrates (460-370 BCE), the father of medicine, developed principles for medical diagnosis and treatment together with a code of ethics. When the first Ptolemy ruled Egypt, he created a great library of 700,000 rolls at Alexandria, which became a repository for the works of Socrates, Plato, Aristotle, Hippocrates, and all the writings of the known world, but it was destroyed by a great fire. Galen of Pergamum (129-216), who lived 500 years after Hippocrates, was well educated and studied anatomy, surgery, drugs and Hippocratic medicine. His ideas influenced medical thinking for the next 1500 years. The Arabic physician Ibn Sina (Avicenna) wrote a great medical work entitled Canon of Medicine. After the Dark Ages (500 to 1050), academic medicine was reestablished in Europe, especially at Salerno, Bologna, Padua, Paris, Montpellier, and Oxford. The greatest medical disaster of the Middle Ages was the Black Death. Other diseases of note were leprosy, smallpox, tuberculosis, typhus, measles, diarrhea, meningitis, and colic. As interest in human dissection increased, the study of anatomy became popular. With development of the printing press, medical knowledge became more widely disseminated and technical advances in science flourished. Advances in medicine occurred in concert with developments in technology. These included the microscope, the stethoscope, anesthetic agents, discoveries in bacteriology, a carbolic acid spray to reduce infection during surgery, the clinical thermometer, blood transfusions, electrocardiography, X-rays, and the sphygmomanometer. Johns Hopkins University was established at the end of the 19th century to train scientifically knowledgeable physicians. The first faculty included Welch, Osler, Halstead, Kelly, Mall, and Abel. Graduates of the new school carried scientific medicine to universities throughout America. More medical advances have been made during the 20th century than in all the other centuries combined. Advances in medical knowledge have resulted not only from developments in technology but from increased access to current information provided through libraries such as the National Library of Medicine in Bethesda, Maryland.

Clinical Medicine↗
PubMed2001

Thymidylate synthase as a molecular target for drug discovery using the National Cancer Institute's Anticancer Drug Screen.

Thymidylate synthase (TS) is a critical cellular target for cancer chemotherapeutics, particularly the fluoropyrimidine and antifolate classes of antineoplastic agents. One of the primary mechanisms of clinical insensitivity to these agents is through the overexpression of the target enzyme, TS. Thus, there is a need for the development of agents which selectively target TS-overexpressing malignant cells. To this end, we conducted a search for agents which potentially selectively target TS-overexpressing cells using two separate algorithms for identifying such compounds in the NCI Drug Repository by comparing cytotoxicity profiles of 30000 compounds with the TS expression levels measured by Western blot analysis in 53 cell lines. Using the traditional COMPARE analysis we were unable to identify compounds which maintain a selective ability to kill high TS-expressing cells in a subsequent four cell line validation assay. A new algorithm, termed COMPARE Effect Clusters analysis, enabled the identification of a particular drug cluster which contained compounds that maintained a selective ability to kill TS-overexpressing cell lines in the validation assay. While the identified compounds were selectively cytotoxic to TS-overexpressing cells, we found that they were not specifically targeting TS as a mechanism of action. Apparently, the overexpression of TS was providing a marker for sensitivity. This identified class of compounds which appears to be selectively cytotoxic against cells which overexpress TS may be useful for the development of therapeutics for those whose cancers overexpress TS de novo.

Antineoplastic Agents↗
PubMed1998

Education in ambulatory settings: developing valid measures of educational outcomes, and other research priorities.

Efforts to redesign education in ambulatory settings are hampered by a lack of rigorous and coherent research on the learning process in these settings and the desired outcomes of the educational experiences. The authors present 13 priority research topics and 51 important research questions concerning education in ambulatory settings that were defined by a distinguished group of medical educators, clinicians, and policymakers who attended an invitational conference on education in ambulatory settings in 1996. The need to establish valid and reliable measures of quality and outcomes of educational programs and instructional interventions stood out as the major prerequisite for conducting research on education in ambulatory settings. Issues of theory building, research priorities, and research design are discussed, and policy recommendations are made for the development of valid measures of educational outcomes. The creation of a "Medical Education Outcomes Commission" is proposed to act as a repository for measures and instruments, and to provide the field with mechanism to validate instruments and uniform recommendations to conduct studies of quality. The authors urge funding agencies with missions that support medical education to invest in basic research on the outcomes of education in ambulatory settings.

Ambulatory Care↗
PubMed2003

Tufts Health Sciences Database: lessons, issues, and opportunities.

The authors present their seven-year experience with developing the Tufts Health Sciences Database (Tufts HSDB), a database-driven information management system that combines the strengths of a digital library, content delivery tools, and curriculum management. They describe a future where online tools will provide a health sciences learning infrastructure that fosters the work of an increasingly interdisciplinary community of learners and allows content to be shared across institutions as well as with academic and commercial information repositories. The authors note the key partners in Tufts HSDB's success--the close collaboration of the health sciences library, educational affairs, and information technology staff. Tufts HSDB moved quickly from serving the medical curriculum to supporting Tufts' veterinary, dental, biomedical sciences, and nutrition schools, thus leveraging Tufts HSDB research and development with university-wide efforts including Internet2 middleware, wireless access, information security, and digital libraries. The authors identify major effects on teaching and learning, e.g., what is better taught with multimedia, how faculty preparation and student learning time can be more efficient and effective, how content integration for interdisciplinary teaching and learning is promoted, and how continuous improvement methods can be integrated. Also addressed are issues of faculty development, copyright and intellectual property, budgetary concerns, and coordinating IT across schools and hospitals. The authors describe Tufts' recent experience with sharing its infrastructure with other schools, and welcome inquiries from those wishing to explore national and international partnerships to create a truly open and integrated infrastructure for education across the health sciences.

Academic Medical Centers↗
PubMed2005

Managing knowledge and technology to foster innovation at the Ohio State University Medical Center.

Biomedical knowledge is expanding at an unprecedented rate-one that is unlikely to slow anytime in the future. While the volume and scope of this new knowledge poses significant organizational challenges, it creates tremendous opportunities to release and direct its power to the service of significant goals. The authors explain how the Center for Knowledge Management at The Ohio State University Medical Center, created during the academic year 2003-04, is doing just that by integrating numerous resource-intensive, technology-based initiatives-including personnel, services and infrastructure, digital repositories, data sets, mobile computing devices, high-tech patient simulators, computerized testing, and interactive multimedia-in a way that enables the center to provide information tailored to the needs of students, faculty and staff on the medical center campus and its surrounding health sciences colleges. The authors discuss how discovering, applying, and sharing new knowledge, information assets, and technologies in this way is a collaborative process. This process creates open-ended opportunities for innovation and a roadmap for working toward seamless integration, synergy, and substantial enhancement of the academic medical center's research, educational, and clinical mission areas.

Academic Medical Centers↗
PubMed2006

The impact of E-learning in medical education.

The authors provide an introduction to e-learning and its role in medical education by outlining key terms, the components of e-learning, the evidence for its effectiveness, faculty development needs for implementation, evaluation strategies for e-learning and its technology, and how e-learning might be considered evidence of academic scholarship. E-learning is the use of Internet technologies to enhance knowledge and performance. E-learning technologies offer learners control over content, learning sequence, pace of learning, time, and often media, allowing them to tailor their experiences to meet their personal learning objectives. In diverse medical education contexts, e-learning appears to be at least as effective as traditional instructor-led methods such as lectures. Students do not see e-learning as replacing traditional instructor-led training but as a complement to it, forming part of a blended-learning strategy. A developing infrastructure to support e-learning within medical education includes repositories, or digital libraries, to manage access to e-learning materials, consensus on technical standardization, and methods for peer review of these resources. E-learning presents numerous research opportunities for faculty, along with continuing challenges for documenting scholarship. Innovations in e-learning technologies point toward a revolution in education, allowing learning to be individualized (adaptive learning), enhancing learners' interactions with others (collaborative learning), and transforming the role of the teacher. The integration of e-learning into medical education can catalyze the shift toward applying adult learning theory, where educators will no longer serve mainly as the distributors of content, but will become more involved as facilitators of learning and assessors of competency.

Competency-Based Education↗
PubMed1991

Quantitative assessment of HIV-1 DNA load by coamplification of HIV-1 gag and HLA-DQ-alpha genes.

We developed an assay for simultaneous amplification, detection and quantitation of HIV-1 gag gene and the DQ-alpha locus of the histocompatibility (HLA) region of the human genome by polymerase chain reaction (PCR). Crude cell lysates from control cell lines and peripheral blood mononuclear cells (PBMC) from HIV-1-infected and control individuals were coamplified using optimized concentrations of primers directed at both loci, followed by simultaneous hybridization with radioactively labeled HIV-1-gag and HLA-DQ-alpha probes. Simultaneous quantitation of the 242-base-pair HLA and 115-base-pair HIV products was accomplished by both end-point dilution analysis and image analysis of autoradiographs relative to standard curves derived from infected cell lines. We observed good agreement between input cell counts on fresh samples and the HLA-DQ-alpha target copy number values determined by both end-point dilution analysis and comparison of band intensities with standard curves. HIV-1 proviral load in symptomatic patients ranged from 200 to 4000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 1245 copies), whereas asymptomatic patients had levels ranging from two to 1000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 213 copies). This HIV/HLA coamplification approach should be particularly useful for analysis of frozen repository samples from natural history studies, and may facilitate wider application of quantitative PCR analysis.

Base Sequence↗
PubMedDate not supplied

Establishment and characterization of a bank of cytotoxic T lymphocytes for immunotherapy of epstein-barr virus-associated diseases.

Adoptive immunotherapy using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) generated ex vivo can be an effective treatment of EBV-positive posttransplantation lymphoproliferative disease (PTLD). We describe the establishment of a cryopreserved repository of allogeneic virus-specific CTL lines, to our knowledge the first of its kind in the world. CTL lines were grown by weekly stimulation with autologous EBV immortalized lymphoblastoid cell lines (LCLs) from 96 EBV-seropositive blood donors. Analysis of 60 CTL lines grown continuously for 7 to 10 weeks showed an average proportional weekly increase in cell numbers of 1.4, with an overall increase ranging from 1.1 to 83.4. The greatest increase occurred during the early culture period. After four rounds of stimulation, killing of autologous LCLs was generally high (mean 48%); however, most lines required 9 or 10 stimulations to reduce the killing of nonspecific targets. Overall, 79% of CTLs generated showed acceptable levels of specific killing. Phenotypically, the CTL lines consisted of TCRalpha beta+, CD8+ T cells (medians 97% and 90% respectively) with a minority population of CD4+ T cells (median 2%). Most cells expressed the activation and differentiation markers, HLA-DR, CD26, CD45RO, CD69, and CD150. Favorable results have been obtained in an open trial using partially HLA-matched, allogeneic CTLs from this bank to treat PTLD patients. This now represents a single resource that can provide therapeutic CTLs rapidly on a countrywide basis, superseding the time-consuming, expensive practice of generating autologous CTLs from each patient requiring treatment. Additionally, other patient groups, such as those with EBV-positive Hodgkin disease, may benefit from CTL treatment.

Blood Banking↗
PubMed2003

Impact of intensive care unit (ICU) drug use on hospital costs: a descriptive analysis, with recommendations for optimizing ICU pharmacotherapy.

OBJECTIVE: To determine the cost impact of intensive care unit (ICU) drug use on a hospital's total drug expense and to compare ICU pharmacy resource utilization with resource utilization of other hospital departments that provided services to the ICU. Additionally, to suggest strategies, based on these methods and results, to optimize ICU drug use. METHODS: Financial transactions for all ICU patients (n = 23,107) treated during fiscal years 1999-2002 were retrieved from the hospital's data repository. ICU drug costs were calculated both as the percentage of total drug costs for each fiscal year and adjusted for hospital volume (ICU patient days). ICU department charges were calculated as a percentage of total ICU charges and analyzed by simple descriptive statistics (mean +/- sd). Drug utilization was retrieved for those patients accounting for the highest percentage of ICU pharmacy charges. MAIN RESULTS: ICU drug costs accounted for 38.4% (+/-4.1% sd) of the total drug costs and have increased at a rate greater than non-ICU drug costs (12% vs. 6%). ICU pharmacy charges accounted for an average of 11.1% (+/-9.2% sd) of the total ICU charges, ranking as the fourth most costly of ICU charges. Both costly and highly used ICU therapies were identified for focus on cost-effectiveness analyses or application of an evidence-based drug use and disease state management program model to ICU pharmacotherapy. CONCLUSIONS: ICU drug therapies have a significant impact on hospital costs, and effective clinical informatics services and multidisciplinary collaboration programs are necessary to optimize ICU pharmacotherapy.

Academic Medical Centers↗
PubMed1991

Monitoring underground radiation fields using powdered calcium sulfate thermoluminescent dosimeters.

Powered thermoluminescent dosimeters, CaSO4:Dy, were used to monitor underground radiation fields. Methods of monitoring at selected sites in Taiwan are described; exposure rates above ground at the monitoring sites are also included for comparison. Differences in exposure rates between above ground at 1 m and underground at -2 m may reach 0.516 nC kg-1 h-1. The key factor affecting exposure rates underground is the water content in soil or precipitation that may reduce the diffusion of Rn. The difference in exposure rates between rainy days and sunny days may reach 0.774 nC kg-1 h-1. An example of applying this monitoring technique at a radwaste repository is given.

Calcium Sulfate↗
PubMed1993

The scientific base for the disposal of spent nuclear fuel.

The main objectives of the Swedish expert seminar on spent nuclear fuel disposal were to identify those safety questions for which there is, or will be, a definitive answer, and to establish the degree of uncertainty surrounding those questions which still cannot be satisfactorily answered. The opinion was that the geological environment of the repository can be defined and its behavior predicted with much confidence, assuming the existing environment remains stable. Thus in the short term (a few hundred to thousands of years), the situation is favorable for safe disposal of spent fuel. In the longer term perspective, it was considered necessary to further investigate the evidence of the geologically recent past to predict future changes.

Nuclear Energy↗