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[Surgical treatment of coxitis tuberculosa (author's transl)].

Statistical data on the proportionate share of tuberculosis of the skeleton in tuberculotic diseases, vary between 1% and 4%, according to the Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose, 1977 Hamburg; Kaster 1964. This type of tuberculosis mainly affects relatively young people up to 20 years of age and elderly people who are around 50. Tuberculosis of the skeleton is a secondary tuberculosis and usually has its primary focus in the lung or in the mediastinal lymph nodes. Spreading is effected via the blood stream. Infection of the bones and joints depends on the number and virulence of the pathogens and on the cellular defence reaction of the patient. Tuberculosis of the joints is a combination of arthritis and osteomyelitis. Modern chemotherapy enables healing of early stages of the infection, whereas late stages can be arrested in combination with surgery. Principally speaking, tuberculosis is on the retreat, although it is still the most frequent of all bacterial infectious diseases. The share of coxitis tubrculosa in the overall total of tuberculosis of the joints is 25%.

Abscess↗

Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis.

Mitochondrial DNA samples from each of 21 humans of diverse racial and geographic origin were digested with each of 18 restriction endonucleases. The sizes of the resulting DNA fragments were compared after gel electrophoresis. No differences among the samples were detected in digest with 7 of the enzymes. Analysis of digests with the remaining enzymes showed one or more differences. Each of the 21 samples could be characterized individually on the basis of these digests. All between-sample differences could be explained by single base substitutions. No evidence for sequence rearrangements (inversions, transpositions) was obtained. Fourteen of the site alterations were shared by two or more samples; six of these were shared between races. The data indicate that individuals differ from a postulated ancestral mtDNA sequence at 0.18% of their base pairs. On the basis of an estimated rate for base substitution of 1% per 10(6) years [Brown, W. M., George, M., Jr. & Wilson, A. C. (1979) Proc. Natl. Acad. Sci. USA 76, 1967-1971], Homo sapiens could have speciated or passed through a severe population constriction as recently as 180,000 years ago. The data suggest that group-specific patterns of cleavage exist. The high resolution and precision afforded by this method of analysis makes possible the investigation of many questions concerning human population genetics, evolution, and recent history.

Asia↗

Low major histocompatibility complex class II diversity in European and North American moose.

Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphism was restricted to six amino acid substitutions, all in the peptide binding site, and four of these were shared between continents. The data imply that the moose have lost MHC diversity in a population bottleneck, prior to the divergence of the Old and New World subspecies. Sequence analysis of mtDNA showed that the two subspecies diverged at least 100,000 years ago. Thus, viable moose populations with very restricted MHC diversity have been maintained for a long period of time. Both positive selection for polymorphism and intraexonic recombination have contributed to the generation of MHC diversity after the putative bottleneck.

Alleles↗

The Rho-deamidating cytotoxic necrotizing factor 1 from Escherichia coli possesses transglutaminase activity. Cysteine 866 and histidine 881 are essential for enzyme activity.

Recently, it has been reported that cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli induces formation of stress fibers by deamidation of glutamine 63 of RhoA (Schmidt, G., Sehr, P., Wilm, M., Selzer, J., Mann, M., and Aktories, K. (1997) Nature 387, 725-729); Flatau, G., Lemichez, E., Gauthier, M., Chardin, P., Paris, S., Fiorentini, C., and Boquet, P. (1997) Nature 387, 729-733). By using mass spectrometric analysis, we show now that the toxin transfers ethylenediamine, putrescine, and dansylcadaverine specifically onto glutamine 63 of RhoA. RhoA was also a substrate for guinea pig liver transglutaminase, which modified not only glutamine 63, but also glutamine residues at positions 52 and 136. Treatment of the fully active N-terminal fragment of CNF1 (amino acid residues 709-1014) with iodoacetamide inhibited both deamidation and transglutamination activities. Moreover, exchange of cysteine 866 with serine blocked the enzyme activity of the N-terminal CNF1 fragment. In addition, we identified histidine 881 to be essential for the enzyme activity of CNF1. The data indicate that CNF1 shares a catalytic dyad of cysteine and histidine residues with eukaryotic transglutaminases and cysteine proteases.

Amides↗

Antigen discovery and tuberculosis vaccine development in the post-genomic era.

For a number of years, a major effort has been put into the identification of candidate molecules for inclusion in a novel vaccine against tuberculosis. Various techniques have been exploited and have resulted in the identification of immunologically important antigens such as the immunodominant antigens ESAT-6 and antigen 85A/B. Today, the availability of the total nucleotide sequence of the Mycobacterium tuberculosis genome enables a post-genomic antigen discovery approach based on denotation and screening of complete protein families containing immunodominant molecules. One group of genes sharing properties with ESAT-6 constitute what has been called the esat-6 gene family. The genes have 10-35% homology to esat-6, are approximately the same size and share genomic organization. The data accumulated so far demonstrate that these molecules are immunodominant antigens strongly recognized in human TB patients and with the potential for a novel TB vaccine.

Antigens, Bacterial↗

The significance of the placenta in assessment of the newborn.

The placenta may harbor many diagnostic tools available for the care of ill neonates. Such tools enable fine-tuning of diagnoses or even the establishment of diagnoses not considered during the investigation and care of the newborn. For this reason, obstetricians, pediatricians, and pathologists should all be familiar with common placental diagnoses so that sharing of the available data among these specialists may, in many cases, provide supportive and diagnostic information critical to the management of the newborn.

Female↗

A semantic-based kernel for advanced health information systems.

This paper reports on the design and development of an infrastructure allowing one to share and exchange multimedia data in the context of a health network. A single technology exploiting a semantic model of the hospital universe provides users with information and data of diverse origins, generated by the various actors or departments of the health organization. Functions provided include act management and patient record management governed by domain semantics. The functionality has been validated through laboratory experiments against the requirements of protocol directed care and health networks. The functionality is integrated into a clinician workstation exploited in the Internet/Intranet environment thanks to a commercial browser. These results have been obtained with the support of several projects in the frame of the Health-Care Telematics Applications Programme of the European Community and of the Eurêka Programme.

Artificial Intelligence↗

Observations of ethical misconduct among industrial hygienists in England.

Industrial hygienists are uniquely situated to help solve problems in the working environment, and failure to behave ethically might have serious and possibly fatal consequences. A survey was conducted to estimate the prevalence and nature of ethical misconduct within the UK occupational hygiene profession during the past 5 years. A postal questionnaire was sent to 50 professional industrial/occupational hygienists. Of the 43 respondents, 33 (77%) had witnessed activities of potential ethical misconduct in at least one of nine questionnaire categories. Additionally, greater than 20% of the hygienists had witnessed at least one incident of data fabrication, failure to share credit on work, failure to protect confidentiality, criticizing the integrity of another hygienist for one's own gain, and plagiarism. The investigation also asked hygienists for their opinions on the reasons for breaches as well as potential methods of improvement.

Confidentiality↗

Presence of human immunodeficiency virus (HIV) type 1, group M, non-B subtypes, Bronx, New York: a sentinel site for monitoring HIV genetic diversity in the United States.

In the United States, human immunodeficiency virus (HIV) type 1, group M, subtype B is the predominant subtype. A cross-sectional study of HIV-infected patients at the Bronx-Lebanon Hospital Center, Bronx, NY, between September 1997 and February 1998 identified 3 (1. 2%) of 252 persons infected with non-B subtypes: subtypes A and F, 1 each, and 1 potential recombinant subtype B(env)/F(prt). All 3 persons were born in the United States and tested positive for HIV antibodies between 1988 and 1997 while living in the Bronx. None reported travel to other countries, receipt of blood products, or drug injection. This study is among the first to indicate probable transmission of non-B HIV-1 subtypes in the United States. The occurrence of non-B HIV-1 subtypes in long-term US residents without a history of foreign travel may have implications for the evaluation and development of antiretroviral drugs, vaccines, and tests intended for use in the United States to diagnose HIV infection and screen blood.

Adolescent↗

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Aged↗

Tele-diagnostic and therapeutic guidance in urology.

PURPOSE: To design a Web-based network for diagnostic and therapeutic guidance in urology. MATERIALS AND METHODS: We designed an architectural model of a low-cost multimedia Web platform that runs on a collection of distributed collaborative network nodes to provide a set of urologist-oriented Web-enabled services. Any node of the platform was able to share patient-oriented data via automated processes with appropriate authorization, confidentiality, and high-security protocols. The urologist can show the details of the records of patients and additionally enrich the world experience with his or her own cases. Video clips maintained locally at the nodes will be accessible by clinicians in a trouble-free way with MS Windows Media player and a relatively small amount of source code. RESULTS AND CONCLUSIONS: The primary advantage of this architectural model is that it provides Web-enabled integrated urologic services while using a distributed storage scheme for urological video files (AVI format) and a global repository of laboratory results using Extensible Markup Language (XML) and Data Grid technologies. In addition, this model provides decision-support services (knowledge from a global database and predefined procedures). The architecture model is based entirely on HTTP, XML, GRID-like environment and DotNet technologies. Finally, the platform provides extensibility and scalability targeted to large-scale Web-enabled global urologic databases.

Decision Support Techniques↗

Human airspace macrophage signatures are conserved during sterile lung injury and repair.

RATIONALE: Airspace macrophages (AM) are implicated in both persistent inflammation and tissue repair following acute lung injury. Distinct subsets of AM are associated with lung pathology in humans but whether unique AM signatures are specific to disease states or represent a conserved response to lung inflammation is unknown. OBJECTIVES: We sought to test the hypothesis that conserved subsets of inflammatory and reparative AM could be identified by transcriptional programing in a human model of self-resolving acute lung injury. METHODS: Fifteen subjects underwent bronchoscopic lavage (BAL) before and at a pre-assigned time point after endobronchial exposure to bacterial endotoxin. BAL cells were subjected to single cell RNA sequencing and longitudinal assessment of AM programing during resolution of inflammation and lung repair was performed. MEASUREMENTS AND MAIN RESULTS: We identify transcriptionally distinct subsets of tissue resident and recruited AM present at all time points, in all subjects. Two recruited AM populations increase following inflammation, one which aligns with classical monocytes (MoAM) and one with interstitial macrophages (IAM). AM subsets display unique patterns of gene expression throughout the time course. Comparison of subset-specific markers to those identified in disease states reveals that IAM express many so-called "pathogenic" markers during normal lung repair. CONCLUSIONS: By applying a uniform inflammatory stimulus to healthy adults and examining BAL cells obtained at precise time points thereafter, we construct a time-resolved kinetic of AM transcriptional programing during typical lung repair. Our data demonstrate that IAM share transcriptional similarity to AM identified in disease states and suggest they may reflect a conserved cellular response to tissue injury.

Journal Article↗

An extended region of biallelic gene expression and rodent-human synteny downstream of the imprinted H19 gene on chromosome 11p15.5.

There is increasing evidence for chromosomal domains containing multiple imprinted genes and for domain-wide disruption of imprinting in certain diseases. In a majority of Wilms' tumors (WTs) there is an abnormal bipaternal pattern of expression at three imprinted loci, H19, IGF2 and KIP2, clustered on chromosome 11p15.5. We previously described biallelic expression of L23MRP, 40 kb downstream of H19. Here we map two additional genes, the first encoding a ubiquitously expressed RNA, 2G7, and the second encoding the fast isoform of skeletal muscle troponin-T (TNNT3), in the 55 kb of DNA downstream of L23MRP. 2G7 RNA is spliced and polyadenylated but lacks long open reading frames. 2G7 and TNNT3 are biallelically expressed in mid-fetal and adult human tissues and 2G7 shows persistent expression in WTs. The rat homologue of L23MRP is highly conserved and lies within 85 kb of H19 in a region of rat chromosome 1 which also contains IGF2 and TNNT3. Parallel expression of H19 and TNNT3 in different adult skeletal muscle types suggests that these genes may share an enhancer. These data outline multiple contiguous loci downstream of H19 which escape functional imprinting in humans. The rodent-human synteny of this region may facilitate a search for an imprinting domain boundary.

Adult↗

Poststreptococcal anti-myosin antibody idiotype associated with systemic lupus erythematosus and Sjögren's syndrome.

Anti-myosin antibodies are found in acute rheumatic fever (ARF), a sequela of group A streptococcal infection. An antiidiotypic serum was produced that was specific for idiotopes expressed by anti-myosin antibodies in ARF (anti-My1). Studies indicated that idiotypic determinants detected with this serum were present in anti-myosin antibodies and absent from normal human immunoglobulins that lacked specificity for myosin. Anti-My1 was tested against sera from patients with other types of autoimmune diseases as well as uncomplicated streptococcal infections. Sera from systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and poststreptococcal acute glomerulonephritis patients demonstrated idiotypic reactivity with anti-My1. Affinity-purified anti-myosin antibodies from SLE, SS, and ARF sera also reacted strongly with anti-My1, indicating that immunoglobulins produced in these diseases share idiotypic determinants. The data demonstrated an association of the My1 idiotype with poststreptococcal sequelae and the two autoimmune diseases SLE and SS.

Autoantibodies↗

Partnering with communities to improve health: the New York City Turning Point experience.

Concurrent with the New York City Department of Health's reorganization efforts, the Robert Wood Johnson and W.K. Kellogg Foundations launched Turning Point, a national initiative designed to strengthen the nation's public health system. The Turning Point initiative has emphasized broad-based partnership building and planning as key prerequisites for improving public health practice. In response to the foundations' request for proposals, the department formed a New York City Public Health Partnership, which in turn applied for and was granted a Turning Point planning grant. This funding allowed New York City Turning Point to initiate a public health planning process, part of which involved convening forums in each of the five boroughs. With over 1,100 community participants, these forums provided both a starting point for establishing public health priorities and an interactive setting for sharing health and demographic data. Included among the issues that emerged as priorities were: access to care, environmental health, mental health, housing, asthma, education, and dietary issues. Building on the forum outcomes, the New York City Public Health Partnership developed a public health system improvement plan. The goals delineated in this plan are: (1) to create and support public health partnerships at the community, borough, and citywide levels; (2) to identify community health concerns and develop strategies responsive to these concerns; and (3) to develop policies to support and sustain a community health approach to improve health status. This article also discusses possible roles for local health departments in promoting a community health approach to address public health concerns.

Community Health Planning↗

NASCArrays: a repository for microarray data generated by NASC's transcriptomics service.

NASC operates an Affymetrix 'GeneChip' (microarray) service for the Arabidopsis thaliana community. All data produced by the service are publicly available through our microarray data base 'NASCArrays' published at http://affymetrix. arabidopsis.info. The data are accessible through text searching and a series of data mining tools. All data are annotated with sample preparation details, and the original Affymetrix data are available for download. The database aims to be MIAME supportive and provide a coordinated resource for re searchers interested in the transcriptome of Arabidopsis. Using this database, data produced will be shared with other databases worldwide.

Arabidopsis↗

Sex differences in the risks of hormone-dependent cancers.

There are marked variations in the risk of hormone-dependent cancers between males and females, and these are likely to reflect sex differences in endogenous hormone profiles. The authors examined sex differences in the risk of hormone-dependent cancers of sex-shared sites by using data from the England and Wales national cancer registry for 1962-1984. Both breast and thyroid cancers showed marked excesses in risk for women, but the female: male ratio peaked around menopause for breast cancer and a puberty for thyroid cancer, suggesting that although female sex hormones may influence the risk of these two cancers, the mechanisms involved are probably different. In the descending colon, the risk of cancer was greater in females than in males at ages under 60 years, but greatest in males at ages above this, whereas in the ascending colon there were no age-specific differences in risk between the sexes. This is consistent with the hypothesis that female reproductive events may decrease a woman's risk of cancer in the descending but not in the ascending colon. Sex differences in bone cancer risk at puberty, particularly for osteosarcomas and Ewing's sarcomas, paralleled known sex differences in skeletal growth; there was a peak in age-specific rates earlier and lower in girls than in boys. Rhabdomyosarcoma, a soft tissue cancer, also showed a rise in risk at puberty with age differences between boys and girls that correlated with sex differences in muscle growth patterns; this suggests that its etiology may be hormonally related as well.

Adolescent↗

Texas Consortium for Physical Therapy Clinical Education. A model for Interinstitutional Consortium arrangements.

This article describes the Texas Consortium for Physical Therapy Clinical Education, which exemplifies one type of collaborative arrangement among universities. Coordination of physical therapy clinical education among five Texas universities is the major function of the Texas Consortium. Although originally developed from a federally funded project (1977-1980), it currently functions with sole financial support from the participating universities. The collaborative efforts of the Texas Consortium have resulted in 1) developing and implementing a common evaluation tool for students' clinical performance; 2) coordinating development of new clinical education centers, development of clinical instructors, and visits to students at clinical education centers; and 3) developing and using a shared computer program for data on clinical education centers. The successful functioning of the Texas Consortium with a resultant decrease in duplication of time, effort, and costs of clinical education demonstrates that this type of arrangement is feasible and beneficial.

Costs and Cost Analysis↗