Search PubMed⌕ Search

Biomedical subjects

M Snyder

Publications and source records attributed to M Snyder.

At least 37 records · Page 2Linked to original sources
PubMed2001

A metadata framework for interoperating heterogeneous genome data using XML.

The rapid advances in the Human Genome Project and genomic technologies have produced massive amounts of data populated in a large number of network-accessible databases. These technological advances and the associated data can have a great impact on biomedicine and healthcare. To answer many of the biologically or medically important questions, researchers often need to integrate data from a number of independent but related genome databases. One common practice is to download data sets (text files) from various genome Web sites and process them by some local programs. One main problem with this approach is that these programs are written on a case-by-case basis because the data sets involved are heterogeneous in structure. To address this problem, we define metadata that maps these heterogeneously structured files into a common eXtensible Markup Language (XML) structure to facilitate data interoperation. We illustrate this approach by interoperating two sets of essential yeast genes that are stored in two yeast genome databases (MIPS and YPD).

Databases, Genetic↗
PubMed2000

Pleiotropic syndrome of dehydrated hereditary stomatocytosis, pseudohyperkalemia, and perinatal edema maps to 16q23-q24.

Dehydrated hereditary stomatocytosis (DHS) is a rare genetic disorder of red cell permeability to cations, leading to a well-compensated hemolytic anemia. DHS was shown previously to be associated in some families with a particular form of perinatal edema, which resolves in the weeks following birth and, in addition, with pseudohyperkalemia in one kindred. The latter condition was hitherto regarded as the separate entity, "familial pseudohyperkalemia." DHS and familial pseudohyperkalemia are thought to stem from the same gene, mapping to 16q23-q24. This study screened 8 French and 2 American families with DHS. DHS appeared to be part of a pleiotropic syndrome in some families: DHS + perinatal edema, DHS + pseudohyperkalemia, or DHS + perinatal edema + pseudohyperkalemia. If adequately attended to, the perinatal edema resolved spontaneously after birth. Logistic regression showed that increased mean corpuscular volume and mean corpuscular hemoglobin concentration were the parameters best related to DHS. In patients in whom cation fluxes were investigated, the temperature dependence of the monovalent cation leak exhibited comparable curves. Specific recombination events consistently suggested that the responsible gene lies between markers D16S402 and D16S3037 (16q23-q24). The 95% confidence limits (Z(max) >/= 3.02) spanned almost the complete 9-cM interval between these 2 markers.

Adolescent↗
PubMed2000

Mutagenesis of murine cytomegalovirus using a Tn3-based transposon.

A transposon derived from Escherichia coli Tn3 was introduced into the genome of murine cytomegalovirus (MCMV) to generate a pool of viral mutants. We analyzed three of the constructed recombinant viruses that contained the transposon within the M25, M27, and m155 open reading frames. Our studies provide the first direct evidence to suggest that M25 and M27 are not essential for viral replication in mouse NIH 3T3 cells. Studies in cultured cells and Balb/c mice indicated that the transposon insertion is stable during viral propagation both in vitro and in vivo. Moreover the virus that contained the insertion mutation in M25 exhibited a titer similar to that of the wild-type virus in the salivary glands, lungs, livers, spleens, and kidneys of the Balb/c mice that were intraperitoneally infected with these viruses. These results suggest that M25 is dispensable for viral growth in these organs and the presence of the transposon sequence in the viral genome does not significantly affect viral replication in vivo. The Tn3-based system can be used as a mutagenesis approach for studying the function of MCMV genes in both tissue culture and in animals.

3T3 Cells↗
PubMed2000

TRIPLES: a database of gene function in Saccharomyces cerevisiae.

Using a novel multipurpose mini-transposon, we have generated a collection of defined mutant alleles for the analysis of disruption phenotypes, protein localization, and gene expression in Saccharomyces cerevisiae. To catalog this unique data set, we have developed TRIPLES, a Web-accessible database of TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces. Encompassing over 250 000 data points, TRIPLES provides convenient access to information from nearly 7800 transposon-mutagenized yeast strains; within TRIPLES, complete data reports of each strain may be viewed in table format, or if desired, downloaded as tab-delimited text files. Each report contains external links to corresponding entries within the Saccharomyces Genome Database and International Nucleic Acid Sequence Data Library (GenBank). Unlike other yeast databases, TRIPLES also provides on-line order forms linked to each clone report; users may immediately request any desired strain free-of-charge by submitting a completed form. In addition to presenting a wealth of information for over 2300 open reading frames, TRIPLES constitutes an important medium for the distribution of useful reagents throughout the yeast scientific community. Maintained by the Yale Genome Analysis Center, TRIPLES may be accessed at http://ycmi.med.yale.edu/ygac/triples.htm

DNA Transposable Elements↗
PubMed2000

Development of a measure of resident satisfaction with the nursing home.

A satisfaction instrument specifically designed for use with nursing home residents, the Satisfaction with the Nursing Home Instrument (SNHI), was developed and tested with a sample of 110 nursing home residents from three proprietary facilities in Minnesota. As hypothesized, significant relationships were found between SNHI scores and measures of affect (negatively associated with depression and positively associated with morale), providing support for the construct validity of the scale. The lack of a significant relationship between SNHI scores and both age and mental status confirmed the predicted divergent validity of the instrument. The alpha coefficient for the 29-item scale was 0.81.

Adult↗
PubMed2000

Probe-guided surgery for colorectal cancer.

Anti-CEA-scintigraphy turned out to be very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90%. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we launched the following feasibility study the results of which are compared to those reported in the recent literature. We investigated 20 patients, six with rectum and 14 with colon cancer. 24 hours before surgery they were intravenously given 1 ml of a fab'-fragment-antibody to CEA, labeled with 25 mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regional to the tumors was measured and compared to the much lower activity in healthy nodes. For this we used a scintillation probe (C-Trak, Care Wise, Inc., Morgan Hill, CA). All lymph nodes of interest were then excised and submitted to frozen section pathology. In 7 out of 20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regional to the primary tumor (retroperitoneum, renal hilum etc.). Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging while surgery is still ongoing. In a further step the concept of sentinel node diagnosis, which is right now being clinically evaluated, may some day be applied in colorectal surgical oncology.

Adenocarcinoma↗
PubMed2000

An integrated web interface for large-scale characterization of sequence data.

Large-scale genome projects require the analysis of large amounts of raw data. This analysis often involves the application of a chain of biology-based programs. Many of these programs are difficult to operate because they are non-integrated, command-line driven, and platform-dependent. The problem is compounded when the number of data files involved is large, making navigation and status-tracking difficult. To demonstrate how this problem can be addressed, we have created a platform-independent Web front end that integrates a set of programs used in a genomic project analyzing gene function by transposon mutagenesis in Saccharomyces cerevisiae. In particular, these programs help define a large number of transposon insertion events within the yeast genome, identifying both the precise site of transposon insertion as well as potential open reading frames disrupted by this insertion event. Our Web interface facilitates this analysis by performing the following tasks. Firstly, it allows each of the analysis programs to be launched against multiple directories of data files. Secondly, it allows the user to view, download, and upload files generated by the programs. Thirdly, it indicates which sets of data directories have been processed by each program. Although designed specifically to aid in this project, our interface exemplifies a general approach by which independent software programs may be integrated into an efficient protocol for large-scale genomic data processing.

Clinical Laboratory Information Systems↗
PubMed2000

Drivers and passengers wanted! the role of kinesin-associated proteins.

Members of the kinesin superfamily of proteins participate in a wide variety of cellular processes. Although much attention has been devoted to the structural and biophysical properties of the force-generating motor domain of kinesins, the factors controlling the functional specificity of each kinesin have only recently been examined. Genetic and biochemical approaches have identified two classes of proteins that associate physically with the diverse non-motor domains of kinesins. These proteins can be divided into two general classes: first, those that form tight complexes with the kinesin and are instrumental in directing the distinct function of the motor (i.e. drivers) and, second, those proteins that might transiently interact with the motor or be an integral part of the motor's cargo (i.e. passengers). Here, we discuss known kinesin-binding proteins, and how they might participate in the activity of their motor partners.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Screening females for chlamydia trachomatis (CT) In a large managed care organization (Mco). A new hedis measure

Background: Since CT testing for females is a new Health Plan Employer Data and Information Set (HEDIS) measure to assess MCO quality of care, we determined the proportion of females enrolled in a large closed panel vertically integrated MCO serving a demographically diverse population who were tested for CT at least once during 1998 and resulting CT prevalences.Methods: A data base with MCO members >/= 12 yrs old tested with CT DNA probes (GenProbe) from 1/1/98-12/30/98 was examined. Only females 12-24 yrs old and enrolled at least 11 continuous months in 1998 were included in the analysis.Results: In 1998, 5425 (13.1%) of 41,566 females 12-24 yrs were CT tested and 849 (2.0%) tested positive at least once. Proportion of females tested and proportion of females testing positive at least once varied by age and clinic location. Among 11, 562 12-14 yr females, 277 (2.4%) were CT tested and 48 (0.4%) tested positive; among 18,155 15-19 yr females, 2,424 (13.4%) were tested and 572 (3.2%) tested positive; and among 11,849 20-24 yr females, 2, 724 (23.0%) were tested and 229 (1.9%) tested positive. The proportion 12-24 yr females tested was 579/3,945 (14.7%) with 92/3, 945 (2.3%) testing positive in the Baltimore area; in Washington, DC/Maryland area 2,999/21,085 (14.2%) were tested with 601/21,085 (2. 9%) testing positive; in Northern Virginia 1,847/16,536 (11.2%) were tested with 156/16,536 (0.9%) testing positive.Proportion of females with at least one positive test among those females who were tested for CT also varied by age and clinic location. Among 277 of 12-14 yr females tested 48 (17.3%) tested positive at least once; among 2,424 of 15-19 yr females tested, 572 (23.6%) tested positive at least once; and among 2,724 of 20-24 yr females tested, 229 (8.4%) tested positive at least once. The proportion of females tested with at least one positive test among 12-24 yr females was 92/579 (15.9%) in the Baltimore area, 601/2,999 (20.0%) in Washington DC/Maryland area, and 156/1,847 (8.4%) in Northern Virginia.Conclusion: CT testing of adolescent females 12-19 yrs revealed a high proportion of positive tests. The lower proportion of positive tests in young adults 20-24 yrs may be due to differences in prevalence and increased number of tests performed. CT testing practices and rates varied by location. Therefore, in a large MCO, a uniform system wide approach in identifying and screening sexually active adolescent females may identify a large reservoir or asymptomatic infection.

Journal Article↗
PubMed2000

Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast.

Formation and maintenance of specialized plasma membrane domains are crucial for many biological processes, such as cell polarization and signaling. During isotropic bud growth, the yeast cell periphery is divided into two domains: the bud surface, an active site of exocytosis and growth, and the relatively quiescent surface of the mother cell. We found that cells lacking septins at the bud neck failed to maintain the exocytosis and morphogenesis factors Spa2, Sec3, Sec5, and Myo2 in the bud during isotropic growth. Furthermore, we found that septins were required for proper regulation of actin patch stability; septin-defective cells permitted to enter isotropic growth lost actin and growth polarity. We propose that septins maintain cell polarity by specifying a boundary between cortical domains.

Actins↗
PubMed2000

Genome-wide mutant collections: toolboxes for functional genomics.

The sequencing of entire genomes has led to the identification of many genes. A future challenge will be to determine the function of all of the genes of an organism. One of the best ways to ascertain function is to disrupt genes and determine the phenotype of the resulting organism. Novel large-scale approaches for generating gene disruptions and analyzing the resulting phenotype are underway in the budding yeast Saccharomyces cerevisiae and other organisms including flies, Mycoplasma, worms, plants and mice. These approaches and mutant collections will be extremely valuable to the scientific community and will dramatically alter the manner in which science is performed in the future.

Animals↗
PubMed2000

Self-monitoring: appraisal and reappraisal.

Theory and research on self-monitoring have accumulated into a sizable literature on the impact of variation in the extent to which people cultivate public appearances in diverse domains of social functioning. Yet self-monitoring and its measure, the Self-Monitoring Scale, are surrounded by controversy generated by conflicting answers to the critical question, Is self-monitoring a unitary phenomenon? A primary source of answers to this question has been largely neglected--the Self-Monitoring Scale's relations with external criteria. We propose a quantitative method to examine the self-monitoring literature and thereby address major issues of the controversy. Application of this method reveals that, with important exceptions, a wide range of external criteria tap a dimension directly measured by the Self-Monitoring Scale. We discuss what this appraisal reveals about with self-monitoring is and is not.

Humans↗
PubMed2000

Analysis of yeast protein kinases using protein chips.

We have developed a novel protein chip technology that allows the high-throughput analysis of biochemical activities, and used this approach to analyse nearly all of the protein kinases from Saccharomyces cerevisiae. Protein chips are disposable arrays of microwells in silicone elastomer sheets placed on top of microscope slides. The high density and small size of the wells allows for high-throughput batch processing and simultaneous analysis of many individual samples. Only small amounts of protein are required. Of 122 known and predicted yeast protein kinases, 119 were overexpressed and analysed using 17 different substrates and protein chips. We found many novel activities and that a large number of protein kinases are capable of phosphorylating tyrosine. The tyrosine phosphorylating enzymes often share common amino acid residues that lie near the catalytic region. Thus, our study identified a number of novel features of protein kinases and demonstrates that protein chip technology is useful for high-throughput screening of protein biochemical activity.

Adenosine Triphosphate↗
PubMed2000

Sbe2p and sbe22p, two homologous Golgi proteins involved in yeast cell wall formation.

The cell wall of fungal cells is important for cell integrity and cell morphogenesis and protects against harmful environmental conditions. The yeast cell wall is a complex structure consisting mainly of mannoproteins, glucan, and chitin. The molecular mechanisms by which the cell wall components are synthesized and transported to the cell surface are poorly understood. We have identified and characterized two homologous yeast proteins, Sbe2p and Sbe22p, through their suppression of a chs5 spa2 mutant strain defective in chitin synthesis and cell morphogenesis. Although sbe2 and sbe22 null mutants are viable, sbe2 sbe22 cells display several phenotypes indicative of defects in cell integrity and cell wall structure. First, sbe2 sbe22 cells display a sorbitol-remediable lysis defect at 37 degrees C and are hypersensitive to SDS and calcofluor. Second, electron microscopic analysis reveals that sbe2 sbe22 cells have an aberrant cell wall structure with a reduced mannoprotein layer. Finally, immunofluorescence experiments reveal that in small-budded cells, sbe2 sbe22 mutants mislocalize Chs3p, a protein involved in chitin synthesis. In addition, sbe2 sbe22 diploids have a bud-site selection defect, displaying a random budding pattern. A Sbe2p-GFP fusion protein localizes to cytoplasmic patches, and Sbe2p cofractionates with Golgi proteins. Deletion of CHS5, which encodes a Golgi protein involved in the transport of Chs3p to the cell periphery, is lethal in combination with disruption of SBE2 and SBE22. Thus, we suggest a model in which Sbe2p and Sbe22p are involved in the transport of cell wall components from the Golgi apparatus to the cell surface periphery in a pathway independent of Chs5p.

Amino Acid Sequence↗
PubMed2000

The Kar3p kinesin-related protein forms a novel heterodimeric structure with its associated protein Cik1p.

Proteins that physically associate with members of the kinesin superfamily are critical for the functional diversity observed for these microtubule motor proteins. However, quaternary structures of complexes between kinesins and kinesin-associated proteins are poorly defined. We have analyzed the nature of the interaction between the Kar3 motor protein, a minus-end-directed kinesin from yeast, and its associated protein Cik1. Extraction experiments demonstrate that Kar3p and Cik1p are tightly associated. Mapping of the interaction domains of the two proteins by two-hybrid analyses indicates that Kar3p and Cik1p associate in a highly specific manner along the lengths of their respective coiled-coil domains. Sucrose gradient velocity centrifugation and gel filtration experiments were used to determine the size of the Kar3-Cik1 complex from both mating pheromone-treated cells and vegetatively growing cells. These experiments predict a size for this complex that is consistent with that of a heterodimer containing one Kar3p subunit and one Cik1p subunit. Finally, immunoprecipitation of epitope-tagged and untagged proteins confirms that only one subunit of Kar3p and Cik1p are present in the Kar3-Cik1 complex. These findings demonstrate that the Kar3-Cik1 complex has a novel heterodimeric structure not observed previously for kinesin complexes.

Amino Acid Sequence↗