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Biomedical subjects

S Sims

Publications and source records attributed to S Sims.

At least 19 recordsLinked to original sources
PubMed2006

The genomic sequence and analysis of the swine major histocompatibility complex.

We describe the generation and analysis of an integrated sequence map of a 2.4-Mb region of pig chromosome 7, comprising the classical class I region, the extended and classical class II regions, and the class III region of the major histocompatibility complex (MHC), also known as swine leukocyte antigen (SLA) complex. We have identified and manually annotated 151 loci, of which 121 are known genes (predicted to be functional), 18 are pseudogenes, 8 are novel CDS loci, 3 are novel transcripts, and 1 is a putative gene. Nearly all of these loci have homologues in other mammalian genomes but orthologues could be identified with confidence for only 123 genes. The 28 genes (including all the SLA class I genes) for which unambiguous orthology to genes within the human reference MHC could not be established are of particular interest with respect to porcine-specific MHC function and evolution. We have compared the porcine MHC to other mammalian MHC regions and identified the differences between them. In comparison to the human MHC, the main differences include the absence of HLA-A and other class I-like loci, the absence of HLA-DP-like loci, and the separation of the extended and classical class II regions from the rest of the MHC by insertion of the centromere. We show that the centromere insertion has occurred within a cluster of BTNL genes located at the boundary of the class II and III regions, which might have resulted in the loss of an orthologue to human C6orf10 from this region.

Animals↗
PubMed2006

The LRC haplotype project: a resource for killer immunoglobulin-like receptor-linked association studies.

There is increasing evidence for epistatic interactions between gene products (e.g. KIR) encoded within the Leukocyte Receptor Complex (LRC) with those (e.g. HLA) of the Major Histocompatibility Complex (MHC), resulting in susceptibility to disease. Identification of such associations at the DNA level requires comprehensive knowledge of the genetic variation and haplotype structure of the underlying loci. The LRC haplotype project aims to provide this knowledge by sequencing common LRC haplotypes.

Chromosome Mapping↗
PubMed2005

Analysis of the genomic region containing the tammar wallaby (Macropus eugenii) orthologues of MHC class III genes.

Major histocompatibility complex (MHC) molecules are central to development and regulation of the immune system in all jawed vertebrates. MHC class III cytokine genes from the tumor necrosis factor core family, including tumor necrosis factor (TNF) and lymphotoxin alpha and beta (LTA, LTB), are well studied in human and mouse. Orthologues have been identified in several other eutherian species and the cDNA sequences have been reported for a model marsupial, the tammar wallaby. Comparative genomics can help to determine gene function, to understand the evolution of a gene or gene family, and to identify potential regulatory regions. We therefore cloned the genomic region containing the tammar LTB, TNF, and LTA orthologues by "genome walking", using primers designed from known tammar sequences and regions conserved in other species. We isolated two tammar BAC clones containing all three genes. These tammar genes show similar intergenic distances and the same transcriptional orientation as in human and mouse. Gene structures and sequences are also very conserved. By comparing the tammar, human and mouse genomic sequences we were able to identify candidate regulatory regions for these genes in mammals. Full length sequencing of BACs containing the three genes has been partially completed, and reveals the presence of a number of other tammar MHC III orthologues in this region.

Animals↗
PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗
PubMed1999

Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes.

Smooth muscle cells (SMCs) perform diverse functions that can be categorized as contractile and synthetic. A traditional model holds that these distinct functions are performed by the same cell, by virtue of its capacity for bidirectional modulation of phenotype. However, this model has been challenged, in part because there is no physiological evidence that an adult synthetic SMC can acquire the ability to contract. We sought evidence for this by cloning adult SMCs from human internal thoracic artery. One clone, HITB5, expressed smooth muscle alpha-actin, smooth myosin heavy chains, heavy caldesmon, and calponin and showed robust calcium transients in response to histamine and angiotensin II, which confirmed intact transmembrane signaling cascades. On serum withdrawal, these cells adopted an elongated and spindle-shaped morphology, random migration slowed, extracellular matrix protein production fell, and cell proliferation and [(3)H]thymidine incorporation fell to near 0. Cell viability was not compromised, however; in fact, apoptosis rate fell significantly. In this state, agonist-induced elevation of cytoplasmic calcium was even more pronounced and was accompanied by SMC contraction. Readdition of 10% serum completely returned HITB5 cells to a noncontractile, proliferative phenotype. Contractile protein expression increased after serum withdrawal, although modestly, which suggested that the switch to contractile function involved reorganization or sensitization of existing contractile structures. To our knowledge, the physiological properties of HITB5 SMCs provide the first direct demonstration that cultured human adult SMCs can convert between a synthetic, noncontracting state and a contracting state. HITB5 cells should be valuable for characterizing the basis of this critical transition.

Adult↗
PubMed1999

Does a year make a difference? Changes in physician satisfaction and perception in an increasingly capitated environment.

BACKGROUND: Although capitation has become an increasingly common method of payment for heath care, little is known about changes in physician satisfaction as they become more experienced working in a capitated environment. METHODS: We surveyed the members of a physician hospital organization at an urban teaching hospital in the summers of 1996 and 1997. In 1996, fully capitated contracts covered <5% of patients under 65 years of age, but that figure increased to nearly 25% by 1997. We assessed physicians' satisfaction with their practice, compared satisfaction under fee-for-service and capitated payment, and evaluated ethical issues related to capitation. RESULTS: In 1996, we surveyed 587 physicians with direct patient care responsibilities, of whom 62% responded; 51% of 520 physicians responded in 1997. Overall satisfaction was 57% in 1996 and 71% in 1997. Among physicians who responded in both years, overall satisfaction was unchanged, but increases in satisfaction were noted for patient load (an increase of 0.5 points on a five-point scale, P <0.01), time to discuss patient needs (an increase of 0.3 points, P <0.01), and helpfulness of care coordination (an increase of 0.5 points, P = 0.02). In a direct comparison between fee-for-service and capitation, physicians were more satisfied with both methods of payment in 1997 than they were in 1996, but they were much more satisfied with fee-for-service in both years. For many individual indicators, the difference in satisfaction between fee-for-service and capitation increased between 1996 and 1997. CONCLUSION: When introduced to capitation, physicians had strong negative perceptions about it. After a year's experience, satisfaction with capitation improved, but perceived differences between capitation and fee-for-service grew even larger. Thus, physicians have serious concerns about capitation that may not be alleviated by experience with it.

Attitude of Health Personnel↗
PubMed1999

Capitation and its effects on physician satisfaction.

OBJECTIVE: Capitation is an increasingly common method of paying physicians, but few data exist on its impact on physician satisfaction. This study examines the perceived effects of capitation on physician satisfaction at a large, academic medical center. STUDY DESIGN: Survey of physicians at a single, tertiary care hospital. METHODS: Physicians in a physician hospital organization were surveyed at an urban teaching hospital which received capitation for 5% of patients at the time of the survey but was preparing for a sharp increase in capitation. We used a 5-point Likert scale to assess physicians' satisfaction with their practice, and to compare satisfaction under fee-for-service and expected satisfaction under capitation. RESULTS: Of the 734 physicians surveyed, 147 were excluded because they had no direct patient care responsibilities. Of the remaining 587 physicians, 363 replied, giving a response rate of 62%. Overall, 57% of physicians were satisfied with their practice. Compared to their satisfaction under fee-for-service reimbursement, they were much less satisfied with their ability to care for capitated patients (17 of 19 questions, p < 0.05). The greatest differences were for freedom to order necessary tests and freedom to obtain referrals (0.9 and 0.8 on the 5-point scale, respectively, both p < 0.0001). Multiple logistic regression analyses revealed four independent predictors of overall satisfaction: patient load (OR = 2.7, 95% CI = 1.9-3.9), efficiency in resource utilization (OR = 1.5, 95% CI = 1.1-2.1), perceived employment stability (OR = 1.7, 95% CI = 1.3-2.2), and control over clinical time schedule (OR = 1.6, 95% CI = 1.2-2.0). CONCLUSIONS: Physicians initially encountering capitation payment have strong negative perceptions about it, even for areas in which some policy experts expect capitation to benefit patient care. Physician education and focusing on management relations may help smooth the transition to capitated reimbursement.

Academic Medical Centers↗
PubMed1997

Immobilization of calcium phosphate nano-clusters into alkoxy-derived porous TiO2 coatings.

Alkoxy-derived porous coatings of titanium oxide were fabricated on commercially pure titanium substrates by an electrochemical method in methanolic electrolytes. Nano-clusters of brushite (CaHPO4. 2H2O) were immobilized into the pores of the oxide network by reacting these coatings in acidic calcium phosphate solutions at 50 degrees C. The acid-base reaction between calcium phosphate solutions and the hydroxyl groups of the oxide network resulted in the formation of nano-clusters of brushite crystals immobilized inside the oxide pores. This treatment resulted in the conversion of the porous oxide network into a coherent mass with improved physical integrity. Nano-clusters of brushite crystals immobilized in the oxide matrix were converted into amorphous calcium phosphate (ACP) and poorly crystallized hydroxyapatite (HA) by further treatment of the oxide in alkaline solutions. The porous oxide coating also reacted strongly with concentrated phosphoric acid. The phosphate-modified oxide resulting from this reaction was further treated in calcium hydroxide solution to form nano-clusters of poorly crystallized HA within the oxide network.

Journal Article↗
PubMed1995

Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor.

How does the nervous system encode environmental stimuli as sensory experiences? Both the type (visual, olfactory, gustatory, mechanical or auditory) and the quality of a stimulus (spatial position, intensity or frequency) are represented as a neural code. Here we undertake a genetic analysis of sensory modality coding in Caenorhabditis elegans. The ASH sensory neurons respond to two distinct sensory stimuli (nose touch and osmotic stimuli). A mutation in the glr-1 (glutamate receptor) gene eliminates the response to nose touch but not to osmotic repellents. The predicted GLR-1 protein is roughly 40% identical to mammalian AMPA-class glutamate receptor (GluR) subunits. Analysis of glr-1 expression and genetic mosaics indicates that GLR-1 receptors act in synaptic targets of the ASH neurons. We propose that discrimination between the ASH sensory modalities arises from differential release of ASH neurotransmitters in response to different stimuli.

Animals↗
PubMed1993

Roles of catalase and cytochrome c in hydroperoxide-dependent lipid peroxidation and chemiluminescence in rat heart and kidney mitochondria.

A recent report (Radi et al., J. Biol. Chem. 266:22028-22034, 1991) showed that rat heart mitochondria contain catalase. The protective role of mitochondrial catalase was tested by exposing heart or kidney mitochondria and mitoplasts to two oxidants (H2O2) or tert-butyl hydroperoxide, t-BOOH), estimating lipid peroxidation (as thiobarbituric acid-reactive substances, TBARS) and overall oxidative stress (as chemiluminescence). Additional controls included heart and kidney preparations from aminotriazole-treated (catalase-depleted) rats. Both oxidants increased TBARS in catalase-free preparations to similar extents over their respective controls (between 200 to 350%). In catalase-containing preparations, H2O2 lipid peroxidation increased by only 40 to 96% over controls. Similar qualitative results were obtained when measuring chemiluminescence. The catalytic role of cytochrome c in mitochondrial lipid peroxidation was investigated by exposing either control or cytochrome-c-depleted kidney mitoplasts (catalase free) to either H2O2 or t-BOOH. Hydrogen-peroxide-dependent mitochondrial lipid peroxidation varied with cytochrome c concentration, remaining close to controls when cytochrome c concentration decreased by 66%, even though there was no catalase present. Tert-butyl hydroperoxide-dependent lipid peroxidation was less affected by cytochrome c remaining 2.3-fold above controls under the same conditions, suggesting that organic peroxides are more likely to remain in the less polar membrane environment being decomposed by heme or nonheme iron imbedded in the inner mitochondrial membrane. Chemiluminescence was less affected by cytochrome c depletion. Comparing control and cytochrome-c-deficient mitochondria, chemiluminescence was 1.7-fold and 2.8-fold higher when control preparations were challenged with t-BOOH or H2O2, respectively.

Animals↗
PubMed1992

Identification of a complex formed between nuclear proteins and the transcriptional enhancer of interferon-inducible genes that is present in the peripheral blood myeloid cells of CML but not normal individuals.

Interferon-alpha (INF-alpha) induces cytogenetic remissions in 20% of chronic myelogenous leukemia (CML) patients. To clarify the mechanisms through which this antiproliferative action of IFN is mediated in the CML cell, a modification of the mobility-shift assay was used to follow the formation of complexes between nuclear proteins and IFN-inducible transcriptional enhancers involved in mediating the cellular effects of IFN-alpha. These studies identified a complex that was present in the myeloid cells of 18/24 (75%) of chronic-phase CML patients tested whose cells contained 100% Philadelphia chromosome positive (Ph+) cells, while the proteins of none of the samples tested from normal peripheral blood samples and only 22% (2/9) of the CML patients in an IFN-induced major cytogenetic remission (less than 30% Ph+ cells) contained these complexes. These studies suggest that the mobility-shift assay detects changes in the CML myeloid cell that distinguish it from the normal myeloid cell.

Base Sequence↗