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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

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

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↗
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↗
PubMed1990

A cloned ATP:guanidino kinase in the trematode Schistosoma mansoni has a novel duplicated structure.

Creatine kinase (CK) is part of a conserved family of ATP:guanidino phosphotransferases whose members play important roles in intracellular energy flow. Previously characterized members of this family are approximately 80-kDa dimers of two related 40-kDa subunits. We have cloned a gene from the parasitic trematode Schistosoma mansoni which has substantial amino acid sequence similarities to CK. Like the genes for vertebrate CKs, this gene is developmentally regulated; mRNA levels are high in the infective cercarial stage but rapidly decrease upon transformation to the parasitic schistosomulum stage. In contrast to members of the guanidino phosphotransferase family characterized previously, however, the schistosome gene appears to be a direct fusion of two CK-like domains that encode a single 74-kDa polypeptide. Correlative evidence from enzyme assays of crude parasite homogenates suggests that the cloned gene is a creatine kinase. This represents the first molecular cloning of an invertebrate ATP:guanidino phosphotransferase.

Amino Acid Sequence↗
PubMed1990

Intravenous gamma globulin therapy in systemic juvenile rheumatoid arthritis.

Intravenous (IV) gamma globulin has been successfully used as replacement therapy for antibody-deficient patients and, more recently, in the treatment of autoimmune diseases such as idiopathic thrombocytopenic purpura, myasthenia gravis, and Kawasaki disease. In view of the successful treatment of these diseases, we initiated a pilot study of the effect of IV gamma globulin in systemic juvenile rheumatoid arthritis (JRA). Eight patients with active systemic JRA that was unresponsive to first-line agents, second-line agents, and/or corticosteroids received this therapy monthly for 6 months. Outcome measures included changes in articular and extraarticular features, steroid dosage, and laboratory parameters. Following IV gamma globulin therapy, there was significant improvement in arthritis and/or morning stiffness in 5 of 8 patients, while extraarticular features significantly improved in 7 of 8 patients. At study entry, 6 of 8 patients were receiving prednisone; at study end, prednisone was discontinued in 3 patients and decreased by more than 50% in the other 3. Overall, there was an 80% reduction in the prednisone dosage. Initially, all patients had anemia, low levels of serum albumin, and an elevated erythrocyte sedimentation rate, while a thrombocytosis was seen in 7 of 8 patients. Serum IgG was initially elevated in 6 patients. IV gamma globulin therapy resulted in a significant increase in hemoglobin and albumin levels and a significant decrease in the mean serum IgG level, platelet count, and erythrocyte sedimentation rate. In only 1 patient did IV gamma globulin fail to significantly improve the clinical or laboratory features of the disease. We suggest that this therapy may be beneficial in the treatment of systemic JRA.

Arthritis, Rheumatoid↗
PubMed1989

Schistosoma mansoni: increasing saline concentration signals cercariae to transform to schistosomula.

Cercariae of S. mansoni shed the surface glycocalyx, form a double lipid bilayer on their surface, and transform to schistosomula when tails are removed and parasites are transferred from pond water to 300 mOsm phosphate-buffered saline. To determine whether the absolute concentration of saline or the relative change in saline concentration was the signal for surface transformation, cercariae were isolated from the snail hepatopancreas, sheared to remove the tails, and incubated in defined media for 3 hr at 37 degrees C. Surface transformation was assayed using the binding of the fluorescein-conjugated lectin concanavalin A to the schistosomular double unit membrane but not to the cercarial glycocalyx. An increase in salinity either from 18 mOsm (artificial pond water) to 120 mOsm (the snail osmolarity) or from 120 to 300 mOsm (the mammalian osmolarity) triggered transformation to schistosomula. Organisms constantly exposed to 120 mOsm or shifted from 120 mOsm to pond water did not transform their surfaces. The signal for transformation appeared to be increasing salinity rather than increasing osmolarity because cercarial bodies did not become schistosomula in 300 mOsm mannitol. Surface transformation was inhibited when cercariae were incubated with the acetylcholinesterase inhibitor eserine sulfate during a 10 min time when the osmolarity was raised. We conclude that increasing salinity rather than the absolute saline concentration is the signal for surface transformation and that eserine sulfate may inhibit the receipt of this signal.

Animals↗
PubMed1987

IgE-enhancing activity directly and selectively affects activated B cells: evidence for a human IgE differentiation factor.

T cells from highly atopic individuals spontaneously secrete in vitro a factor that specifically induces IgE synthesis from normal human B cells. We investigated the effects of such T cell supernatants derived from atopic individuals (TCSN-A) on functionally distinct B cell subsets to determine at what developmental stage B cells become responsive to this IgE-enhancing activity. B cells from normal and allergic donors were separated into subsets of small resting and large activated cells by density centrifugation or unit gravity sedimentation. When stimulated by TCSN-A, large activated B cells made more IgE than small resting B cells. The difference was as much as 3300% in comparing these subsets from allergic donors. Similarly, resting B cells stimulated by Staphylococcus aureus Cowan I (SAC) made 52 to 125% more IgE in response to TCSN-A than unstimulated small resting B cells. However, IgE production from large B cells, already activated in vivo, was not enhanced by the addition of SAC. Notably, the IgE level synthesized by in vivo large activated B cells from allergic persons was markedly greater than that seen with similar cells from normal donors, whereas resting B cells purified from allergic and normal donors produced comparable levels of IgE in response to TCSN-A. These results suggest that this enhancing activity functions as an IgE differentiation factor for activated B cells. This was further confirmed by the effects of TCSN-A on the IgM- and IgE-secreting EBV-transformed human B cell line K1D5. TCSN-A specifically enhanced IgE synthesis from these cells; TCSN from normal donors, IL 2, IFN-gamma, and BCGF did not. These results confirm that this activity functions as an IgE-specific differentiation factor, directly influencing activated B cells to synthesize IgE.

B-Lymphocytes↗
PubMed1987

Intravenous pulse methylprednisolone treatment of juvenile dermatomyositis.

Recent observations that juvenile dermatomyositis (JDMS) may be a heterogenous disorder, in both its clinical course and prognosis, suggest that subgroups of patients with this disease may respond to various modes of therapy. Therefore, current treatment recommendations of daily, long-term oral corticosteroid treatment, with its attendant side effects, may not be necessary for all children with JDMS. We report the results of treatment with high-dose, pulse intravenous methylprednisolone in 7 children with JDMS, 3 of whom had an excellent response with complete remission and no need for daily steroid therapy. We suggest that patients with early, mild JDMS may be candidates for therapy with intravenous methylprednisolone.

Adolescent↗