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Biomedical subjects

L D Stein

Publications and source records attributed to L D Stein.

At least 19 recordsLinked to original sources
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

JADE: an approach for interconnecting bioinformatics databases.

To achieve the integration of biological data available on the World Wide Web and maintained in diverse sources such as GDB, Genbank or Acedb, we have developed a software called Jade. Jade allows programmers to create analytic tools and graphical user interfaces for one or more existing bioinformatics data sources. These tools can then be interchanged, compared and reused without making modifications in the data sources themselves. The system is implemented in the Java programming language and will run equally well on Macintosh, Windows or Unix workstations. Jade is free and can be used immediately by all interested parties.

Computational Biology↗
PubMed1998

The LabBase system for data management in large scale biology research laboratories.

MOTIVATION: The development of laboratory information management systems (LIMSs) for large scale biology research projects can be a challenging problem. Many such projects generate complex datasets via complex procedures that undergo continuous refinement. A key software challenge is to simplify the database-development task so that databases can be built and modified quickly enough to keep pace with changing project-requirements. RESULTS: LabBase extends the facilities offered by relational database systems to simplify the task of creating databases for large scale biology research projects. LabBase provides a structural object data model, similar to ACEDB, and adds to this the concepts of Materials, Steps, and States: Materials are objects representing the identifiable things that participate in a laboratory protocol; Steps are objects reporting the results of a laboratory or analytical procedure; and States are objects denoting places in a laboratory protocol. The system provides a data definition language for succinctly defining laboratory databases, and operations for conveniently storing and retrieving data in such databases. The system also provides support for workflow management. LabBase is implemented in Perl5 and provides a natural interface for laboratory application programs written in Perl. AVAILABILITY: The software is freely available. Contact the authors. CONTACT: nat@jax.org

Computational Biology↗
PubMed1998

Scriptable access to the Caenorhabditis elegans genome sequence and other ACEDB databases.

Much of the world's genomic data are available to the community through networked databases that are accessed via Web interfaces. Although this paradigm provides browse-level access and has greatly facilitated linking between databases, it does not provide any convenient mechanism for programmatically fetching and integrating data from diverse databases. We have created a library and an application programming interface (API) named AcePerl that provides simple, direct access to ACEDB databases from the Perl programming language. With this library, programmers and computer-savvy biologists can write software to pose complex queries on local and remote ACEDB databases, retrieve the data, integrate the results, and move data objects from one database to another. In addition, a set of Web scripts running on top of AcePerl provides Web-based browsing of any local or remote ACEDB database. AcePerl and the AceBrowser Web browser run on Unix systems and are available under a license that allows for unrestricted use and redistribution. Both packages can be downloaded from URL. A Microsoft Windows port of AcePerl is in the planning stages.

Animals↗
PubMed1998

Training pediatricians for the evolving generalist-specialist interface in the managed care era.

Managed care involves the linkage of service delivery and financing. One of the outgrowths of the rapid expansion of managed care over the past decade has been an increasing consensus that the generalist of the future will need to manage more of the patients traditionally cared for by subspecialists. Subspecialty education for pediatric residents becomes increasingly important as the role of the pediatric generalist enlarges to include independent outpatient management of some less complex but traditional subspecialty patients as well as collaborative management of more complex patients. To prepare for this role, a balanced exposure to subspecialty problems in outpatient as well as inpatient settings is required. At the same time, however, the growth of managed care has led to certain barriers for providing this enhanced training. This article describes the effects of managed care on the role and scope of the pediatric subspecialist as well as on educational strategies for coping with these changes while reshaping the roles of both generalists and subspecialists for maximal effectiveness in meeting the health care needs of children.

Academic Medical Centers↗
PubMed1998

The LabFlow system for workflow management in large scale biology research laboratories.

LabFlow is a workflow management system designed for large scale biology research laboratories. It provides a workflow model in which objects flow from task to task under programmatic control. The model supports parallelism, meaning that an object can flow down several paths simultaneously, and sub-workflows which can be invoked subroutine-style from a task. The system allocates tasks to Unix processes to achieve requisite levels of multiprocessing. The system uses the LabBase data management system to store workflow-state and laboratory results. LabFlow provides a Per15 object-oriented framework for defining workflows, and an engine for executing these. The software is freely available.

Artificial Intelligence↗
PubMed1997

Genomewide scan of multiple sclerosis in Finnish multiplex families.

Multiple sclerosis (MS) is a neurological, demyelinating disorder with a putative autoimmune etiology. It is thought to be a multifactorial disease with a complex mode of inheritance. Here we report the results of a two-stage genomewide scan for loci predisposing to MS. The first stage of the screen, with a low-resolution map, was performed in a selection of 16 pedigrees collected from an isolated Finnish population. Multipoint, non-parametric linkage analysis of the 328 markers did not reveal statistically significant results. However, 10 slightly interesting regions (P = .1-.15) emerged, including our previous findings of the HLA complex on 6p21 and a putative locus on 5p14-p12. Eight of these novel regions were further analyzed by use of denser marker maps, in the second stage of the scan. For the chromosomal regions 4cen, 11tel, and 17q, the statistical significance increased, but not conclusively; for 2q32 and 10q21, the statistical significance did not change. Accordingly, genotyping of the high-density markers in these regions was performed, and the data were analyzed by use of two-point, parametric linkage analysis using the complete pedigree information of the 21 Finnish multiplex families. We detected suggestive evidence for a predisposing locus on chromosomal region 17q22-q24. Several markers on 17q22-q24 yielded positive LOD scores, with the maximum LOD score (Zmax) occurring with D17S807 (Zmax = 2.8, theta = .04; dominant model). Interestingly, a suggestive linkage between MS and the markers on 17q22-q24 was also revealed by a recent genomewide scan in MS families from the United Kingdom.

Autoimmune Diseases↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

OBJECTIVE: To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). METHODS: The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. RESULTS: Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. CONCLUSION: Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

Adolescent↗
PubMed1995

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Animals↗
PubMed1995

Breast feeding and the development of juvenile rheumatoid arthritis.

OBJECTIVE: To determine if children with juvenile rheumatoid arthritis (JRA) are less likely to have been breast fed than controls. METHODS: Case-control study of data obtained from a survey of mothers 54 children with JRA and 79 playmates regarding breast feeding. Duration of breast feeding was tabulated and odds ratios (OR) with 95% confidence intervals (CI) were determined. RESULTS: OR for breast feeding in children with JRA was 0.40 (0.20-0.81, 95% CI) compared to playmates. For pauciarticular JRA (N = 28) OR was 0.31 (0.10-0.93); in polyarticular JRA (N = 24) OR was 0.60 (0.21-1.70). Lower OR for increased durations of breast feeding were noted in children with JRA. CONCLUSION: Children who have had JRA, especially pauciarticular JRA, are less likely to have been breast fed than controls, suggesting that breast feeding may have a protective effect on the development of JRA.

Adolescent↗
PubMed1993

Expression of Schistosoma mansoni genes involved in anaerobic and oxidative glucose metabolism during the cercaria to adult transformation.

Schistosomes switch rapidly from the use of stored glycogen to a reliance on host glucose during the transformation from free-living cercariae to parasitic schistosomula. We have cloned a set of cDNAs encoding proteins involved in glucose metabolism to allow us to examine the expression of these genes during this transformation. We first obtained and characterized Schistosoma mansoni cDNA clones encoding the tricarboxylic acid cycle enzyme, mitochondrial malate dehydrogenase (SMDH) and the mitochondrial encoded electron transport protein, cytochrome oxidase subunit 1 (SCOX1). Northern blots were then prepared using mRNA isolated from whole cercariae, cercarial tails, schistosomula, adult males and adult females. The Northern blots were successively hybridized with a variety of probes including those for SMDH, SCOX, the glycolytic enzymes, hexokinase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase and several control probes. Probes were additionally hybridized to mRNA dot blots and the signals were quantified using storage phosphor technology. These studies reveal that transcripts encoding these metabolic enzymes are localized at much higher levels in cercarial tails than in whole cercariae or transformed schistosomula, and support the notion of a dominant aerobic metabolism in tails. Male and female adult worms express each of the mRNAs at roughly equal levels. Adults express the metabolic mRNAs, including those involved in oxidative glucose metabolism, at relatively high levels suggesting that adult schistosomes retain a significant capacity to produce energy through aerobic metabolism.

Amino Acid Sequence↗
PubMed1992

Alternative splicing of the Schistosoma mansoni gene encoding a homologue of epidermal growth factor receptor.

The complete coding DNA for a Schistosoma mansoni homologue of the epidermal growth factor receptor (SER) was characterized from cDNA clones obtained by homology to the tyrosine kinase domain of erbB. The DNA sequence predicts a 200-kDa translation product that contains a secretory leader, a cysteine-rich extracellular domain, a hydrophobic transmembrane sequence, and an intracellular tyrosine kinase domain. The SER transcript is present in cercariae and adult schistosomes. In addition to SER transcripts, schistosomes produce at least 3 variant transcripts encoding truncated SER products that include the secretory leader and a small portion of the extracellular domain followed by short sequences of unrelated, C-terminal amino acids. Based on these sequences, 2 of the variant mRNAs (class 2 and 5) appear to encode soluble, secreted proteins while one (class 4) encodes an SER variant protein with a hydrophobic C-terminus that may serve as a membrane anchor. Class 2 SER variant transcripts are present at levels comparable to SER transcripts in adult worms but are not detected in cercariae. Class 4 and 5 SER variant transcripts are also found within adult worms but at lower levels. Genomic cloning and characterization demonstrate that the variant SER transcripts arise through alternative splicing of the SER gene.

Amino Acid Sequence↗
PubMed1991

Realistic viewing and manipulation of radiographic images on a personal computer--a user interface for educational applications.

The authors have designed a user interface for the display and manipulation of radiographic images that is intended for use in digitized teaching files and computer-aided instruction (CAI) applications. By making the way the viewer interacts with a set of digitized images on the computer screen as similar as possible to the interaction with conventional films on a view-box the authors have tried to create a system that combines the directness of the conventional teaching file with the power and flexibility of CAI. This is accomplished on readily available personal computer workstations.

Computer-Assisted Instruction↗
PubMed1990

Expression of IgE from a nonrearranged epsilon locus in cloned B-lymphoblastoid cells that also express IgM.

During development, B lymphocytes have the ability to switch from synthesis of IgM to immunoglobulins of another isotype such as IgG, IgA, or IgE. This class switching mechanism has been shown to involve DNA rearrangement and concomitant deletion of intervening CH genes. In our report, an EBV-transformed B lymphoblastoid cloned cell line is described that simultaneously expressed and secreted both IgM and IgE. DNA analysis showed the (nonproductive) rearrangement of one allele to gamma and (productive) rearrangement of the other allele to mu. Germ-line arrangement of the C epsilon gene was preserved on both alleles.

B-Lymphocytes↗