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At least 1,243 records · Page 69Linked to original sources
PubMed2006

Selective deficits in the expression of striatal-enriched mRNAs in Huntington's disease.

We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is that such mRNA molecules are likely to encode proteins that are preferentially associated with particular physiological processes intrinsic to striatal neurons, and therefore might contribute to the regional specificity of neurodegeneration observed in striatal disorders such as Huntington's disease (HD). Expression of these genes was measured simultaneously in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD transgenic mice. Changes in expression of genes associated with G-protein signaling and calcium homeostasis were highlighted. The most striking decrement was observed for a newly identified subunit of the sodium channel, beta 4, with dramatic decreases in expression beginning at 8 weeks of age. A subset of striatal genes was tested by real-time PCR in caudate samples from human HD patients. Similar alterations in expression were observed in human HD and the R6/1 model for the striatal genes tested. Expression of 15 of the striatum-enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their dependence on dopamine innervation. No changes in expression were observed for any of these genes. These findings demonstrate that mutant huntingtin protein causes selective deficits in the expression of mRNAs responsible for striatum-specific physiology and these may contribute to the regional specificity of degeneration observed in HD.

Analysis of Variance↗
PubMed2006

State-mandated benefit review laws.

OBJECTIVE: To determine which states have laws that require the review of mandated health insurance benefits and describe the various approaches states take in reviewing mandated benefits, as stated in the mandated benefit review (MBR) laws. DATA SOURCES: We queried online databases of the individual state statutes and reviewed the state statutes and state legislative agendas for all 50 states and Washington, DC to identify those states with active MBR laws as of September 2004. STUDY DESIGN: We reviewed the identified MBR laws to catalog their various components. The components chosen for this analysis include: general review strategy, designated reviewers, time frame for conducting reviews, criteria used in the review, requirements to use actuaries, sources of funding, and state data collection systems. Two of the authors independently created analysis categories and coded the MBR laws to document details on the major components of the laws. PRINCIPAL FINDINGS: We identified 26 state MBR laws active as of September 2004. A majority of the MBR laws specified a prospective review approach and only one law used an exclusively retrospective review approach. A substantial amount of variation was found with regards to the designated reviewers, time frames for conducting reviews, and criteria used in the review. Few states specified the use of actuaries, sources of funding, and state data collection systems. CONCLUSIONS: The number of states that have enacted MBR laws has increased substantially in recent years, however, different states have structured the review of mandated benefits differently, according to the values and perceived needs of the state legislatures. It is important that states increasingly consider a broader scope of review criteria so state decision makers can position themselves to mandate only those benefits that add real value to the state's health care system.

Insurance Benefits↗
PubMed2006

Use of handheld computers in medical education. A systematic review.

BACKGROUND: Over the past decade, handheld computers (or personal digital assistants [PDAs]) have become a popular tool among medical trainees and physicians. Few comprehensive reviews of PDA use in medicine have been published. OBJECTIVE: We systematically reviewed the literature to (1) describe medical trainees' use of PDAs for education or patient care, (2) catalog popular software applications, and (3) evaluate the impact of PDA use on patient care. DATA SOURCES: MEDLINE (1993 to 2004), medical education-related conference proceedings, and hand search of article bibliographies. REVIEW METHODS: We identified articles and abstracts that described the use of PDAs in medical education by trainees or educators. Reports presenting a qualitative or quantitative evaluation were included. RESULTS: Sixty-seven studies met inclusion criteria. Approximately 60% to 70% of medical students and residents use PDAs for educational purposes or patient care. Satisfaction was generally high and correlated with the level of handheld computer experience. Most of the studies included described PDA use for patient tracking and documentation. By contrast, trainees rated medical textbooks, medication references, and medical calculators as the most useful applications. Only 1 randomized trial with educational outcomes was found, demonstrating improved learning and application of evidence-based medicine with use of PDA-based decision support software. No articles reported the impact of PDA use on patient outcomes. CONCLUSION: Most medical trainees find handhelds useful in their medical education and patient care. Further studies are needed to evaluate how PDAs impact learning and clinical outcomes.

Attitude of Health Personnel↗
PubMed2003

U.S. allopathic emergency medicine residency programs: a descriptive review.

OBJECTIVE: To use collected data from all 124 allopathic emergency medicine residency (EMR) programs in existence in 2001 to describe allopathic EMR training programs in the United States. METHODS: The authors performed a cross-sectional review of all 124 EMRs using self-reported, standardized data from regularly updated sources: the SAEM Residency Catalog and the AMA's FREIDA (Fellowship and Residency Electronic Interactive Database Access). The authors report median values, ranges, and interquartile ranges (IQRs) on a variety of variables. RESULTS: Median values for EMR programs included a class size of 10 per year; a total faculty-to-resident ratio of 0.78 (1:1.29); an annual primary emergency department (ED) census of 66,000 (IQR = 53,000 to 80,000), with an annual combined primary and secondary ED census of 95,500 (IQR = 75,000 to 126,000); a combined pediatric census of 20,000 (IQR = 15,000 to 32,500) at the primary and secondary sites; an annual combined ED visit per resident of 3,181 (IQR = 2,542 to 3,949), including 733 pediatric visits per resident, at the primary and secondary sites; an admission rate of 20% (IQR = 17% to 23%); and an intensive care unit admission rate of 13% (IQR = 5% to 20%). Despite a wide variability in ranges and IQR in most characteristics pertaining to training setting, the overall reported completion rate of training for residents was high (99%). CONCLUSIONS: This summary description provides median values and ranges for important components of the emergency medicine training environment and provides a basis of comparison for medical students and graduate medical educators.

Cross-Sectional Studies↗
PubMed2006

Using the yeast two-hybrid assay to discover protein partners for the leucine-rich amelogenin peptide and for tuftelin-interacting protein 11.

The established structural proteins of the enamel matrix are amelogenin, ameloblastin, and enamelin. Historically, tuftelin and tuftelin-interacting protein 11 (TFIP11) have also been discussed as possible enamel proteins. Protein complexes are achieved by protein-protein interactions, and it is protein complexes that control biomineralization. The purpose of our recent studies was to catalog protein partners for these proteins that are, or have been, implicated in tooth formation. We used the sensitive yeast two-hybrid assay to identify proteins that interact directly with amelogenin, ameloblastin, enamelin, the leucine-rich amelogenin peptide (LRAP) and TFIP11. In this manuscript we refer to, or document, potential protein partners for the proteins listed above. The yeast two-hybrid assay may ultimately prove to be a valuable proteomics methodology for using to decipher molecular events that ultimately result in enamel biomineralization.

Amelogenin↗
PubMed2005

Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations.

The structure of the complex between the minor groove binder netropsin and d(GGCCAATTGG) was determined via single-crystal X-ray techniques. The structure was refined to completion using refmac5.1.24, resulting in a residual R-factor of 20.0% (including 68 water molecules). Using crystal engineering and cryocooling techniques, the resolution could be enhanced to 1.75 A, resulting in an unambiguous determination of the drug conformation and orientation. As previously noticed, bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug and the N3 and O2 atoms of A and T base pairs, respectively, clearly cataloging the structure to class I. As the bulky NH2 group on guanine was believed to prevent binding of the drug in the minor groove, the detailed nature of several of the amidinium and guanidinium end contacts were further investigated by ab initio quantum chemical methods.

Base Sequence↗
PubMed2005

Kinetic mechanism for p38 MAP kinase alpha. A partial rapid-equilibrium random-order ternary-complex mechanism for the phosphorylation of a protein substrate.

p38 Mitogen-activated protein kinase alpha (p38 MAPKalpha) is a member of the MAPK family. It is activated by cellular stresses and has a number of cellular substrates whose coordinated regulation mediates inflammatory responses. In addition, it is a useful anti-inflammatory drug target that has a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a number of transcription factors as well as protein kinases in its catalog of known substrates. Fundamental to signal transduction research is the understanding of the kinetic mechanisms of protein kinases and other protein modifying enzymes. To achieve this end, because peptides often make only a subset of the full range of interactions made by proteins, protein substrates must be utilized to fully elucidate kinetic mechanisms. We show using an untagged highly active form of p38 MAPKalpha, expressed and purified from Escherichia coli[Szafranska AE, Luo X & Dalby KN (2005) Anal Biochem336, 1-10) that at pH 7.5, 10 mm Mg2+ and 27 degrees C p38 MAPKalpha phosphorylates ATF2Delta115 through a partial rapid-equilibrium random-order ternary-complex mechanism. This mechanism is supported by a combination of steady-state substrate and inhibition kinetics, as well as microcalorimetry and published structural studies. The steady-state kinetic experiments suggest that magnesium adenosine triphosphate (MgATP), adenylyl (beta,gamma-methylene) diphosphonic acid (MgAMP-PCP) and magnesium adenosine diphosphate (MgADP) bind p38 MAPKalpha with dissociation constants of KA = 360 microm, KI = 240 microm, and KI > 2000 microm, respectively. Calorimetry experiments suggest that MgAMP-PCP and MgADP bind the p38 MAPKalpha-ATF2Delta115 binary complex slightly more tightly than they do the free enzyme, with a dissociation constant of Kd approximately 70 microm. Interestingly, MgAMP-PCP exhibits a mixed inhibition pattern with respect to ATF2Delta115, whereas MgADP exhibits an uncompetitive-like pattern. This discrepancy occurs because MgADP, unlike MgAMP-PCP, binds the free enzyme weakly. Intriguingly, no inhibition by 2 mm adenine or 2 mm MgAMP was detected, suggesting that the presence of a beta-phosphate is essential for significant binding of an ATP analog to the enzyme. Surprisingly, we found that inhibition by the well-known p38 MAPKalpha inhibitor SB 203580 does not follow classical linear inhibition kinetics at concentrations > 100 nm, as previously suggested, demonstrating that caution must be used when interpreting kinetic experiments using this inhibitor.

Activating Transcription Factor 2↗
PubMed1997

Managed care organizations and public health: exploring collaboration on adolescent immunizations.

Managed care organizations (MCOs) joined local and state public health agencies in a pilot effort to improve hepatitis B immunization rates of adolescents in an urban and a suburban/rural school district. The pilot also explored issues inherent in public and private collaboration on population health improvement. Local public health agencies provided links to schools in their communities, took the lead in implementing school-based immunization programs, and provided health education materials. MCOs contributed financial support necessary for the project. The final cost per fully vaccinated student, not taking into account the work group's planning and coordination time, was little more than the catalog price of the vaccine alone. Managed care organizations face challenges that complicate their participation and funding of school-based vaccinations: 1) Limited data on health plans of participating students complicate allocation of costs to each MCO; 2) Double-paying occurs for MCOs paying clinics a monthly, per-member rate that already includes adolescent immunizations; 3) When schools provide adolescent immunizations, MCOs lose the "hook" that draws adolescents to clinics for comprehensive health services. When self-consenting is permitted, schools can achieve a high consent and completion rates for multi-dose adolescent immunizations such as hepatitis B. At the same time, MCOs have the responsibility to provide members with comprehensive care and should continue to examine both internal modifications and external partnerships as opportunities to improve their services to adolescents.

Adolescent↗
PubMed1986

Membrane cholesterol and tumor bioenergetics.

We have established that a preferential export of pyruvate-generated citrate occurs from cholesterol-rich tumor mitochondria, with both isolated mitochondrial systems as well as with viable tumor tissue slices (i.e., with whole tumors cells). Furthermore, we have demonstrated that the more rapid citrate efflux kinetics (catalyzed by the tricarboxylate exchange carrier) of isolated tumor mitochondria is completely inhibited upon addition of 1,2,3-benzenetricarboxylate (BTC) and have shown that this inhibition is apparently also obtained in viable tumor tissue when the inhibitor is added to the tissue incubation. Upon BTC inhibition of tumor mitochondrial citrate export in viable tumor tissue incubations, the incorporation of [14C]pyruvate into newly synthesized cholesterol is severely inhibited as well. Among the most interesting conclusions drawn from our results, we catalog the following. The preferential export of citrate from isolated tumor mitochondria appears to be coupled, functionally, to a high linear rate of incorporation of 14C from pyruvate to cholesterol in viable tumor tissue slices, simultaneously supporting the postulate of a truncated Krebs cycle and corroborating the well-established deregulated and continuous cholesterogenesis pathway in tumors, especially hepatomas. The extent of [14C]pyruvate flux to newly generated cholesterol in either tumor or normal liver tissue is inversely related to the extent of 14CO2 production. Despite the evolution of some CO2 during cholesterogenesis, the predominant portion presumably arises via metabolic processing of pyruvate-generated citrate during Krebs cycle-linked respiration. Isolated tumor mitochondrial systems, as well as viable tumor tissue incubations, can manifest a reversal in the pattern of enhanced mitochondrial citrate efflux coupled to increased cholesterogenesis, when BTC is added to the system. This implies that BTC, a hydrophobic but negatively charged moiety at pH 7, can indeed penetrate the plasma membrane of cells. Upon entry into the cell, BTC apparently blocks the tricarboxylate carrier of tumor tissue mitochondria, thus forcing the mitochondrial citrate into Krebs cycle-linked respiration rather than permitting it to serve as the predominant provider of an increased supply of cytosolic acetyl CoA precursor required for deregulated cholesterogenesis during the development of the tumor.

Animals↗
PubMed1998

Behavioral and electrophysiological analysis of Ca-activated K-channel transgenes in Drosophila.

The slowpoke gene of Drosophila melanogaster encodes a Ca-activated K channel. This gene is expressed in neurons, muscles, tracheal cells, and the copper and iron cells of the midgut. The gene produces a large number of alternative products using tissue-specific transcriptional promoters and alternative mRNA splicing. We have described in great depth how transcription is regulated and are now cataloging the tissue-specificity of different splice variants. It is believed that the diversity of products serves to tailor channel attributes to the needs of specific tissues. Electrophysiological and behavioral assays indicate that at least some of these products produce channels with distinct properties.

Animals↗
PubMed1997

Determination of the energy fluence of diagnostic x-ray beams from field measurements of attenuation curves.

The use of field measurements of attenuation curves of low-energy x-ray beams as a functional description of the beams is presented in this work. The energy fluence carried by diagnostic x-ray beams has been determined from A1 attenuation measurements made with a quality control ionization chamber for diagnostic x-ray equipment and with a low-volume ionization chamber. The obtained values are compared with those obtained from a catalog of spectral data for diagnostic x rays.

Humans↗
PubMed2003

The cosmic production of helium.

We estimate the cosmic production rate of helium relative to metals (DeltaY/DeltaZ) using K dwarf stars in the Hipparcos catalog with accurate spectroscopic metallicities. The best fitting value is DeltaY/DeltaZ = 2.1 +/- 0.4 at the 68% confidence level. Our derived value agrees with determinations from H II regions and with theoretical predictions from stellar yields with standard assumptions for the initial mass function. The amount of helium in stars determines how long they live and therefore how fast they will enrich the interstellar medium with fresh material.

Journal Article↗
PubMed2003

Finding functional features in Saccharomyces genomes by phylogenetic footprinting.

The sifting and winnowing of DNA sequence that occur during evolution cause nonfunctional sequences to diverge, leaving phylogenetic footprints of functional sequence elements in comparisons of genome sequences. We searched for such footprints among the genome sequences of six Saccharomyces species and identified potentially functional sequences. Comparison of these sequences allowed us to revise the catalog of yeast genes and identify sequence motifs that may be targets of transcriptional regulatory proteins. Some of these conserved sequence motifs reside upstream of genes with similar functional annotations or similar expression patterns or those bound by the same transcription factor and are thus good candidates for functional regulatory sequences.

Algorithms↗
PubMed1995

Serial analysis of gene expression.

The characteristics of an organism are determined by the genes expressed within it. A method was developed, called serial analysis of gene expression (SAGE), that allows the quantitative and simultaneous analysis of a large number of transcripts. To demonstrate this strategy, short diagnostic sequence tags were isolated from pancreas, concatenated, and cloned. Manual sequencing of 1000 tags revealed a gene expression pattern characteristic of pancreatic function. New pancreatic transcripts corresponding to novel tags were identified. SAGE should provide a broadly applicable means for the quantitative cataloging and comparison of expressed genes in a variety of normal, developmental, and disease states.

Base Sequence↗
PubMed2000

Heightened odds of large earthquakes near istanbul: An interaction-based probability calculation

We calculate the probability of strong shaking in Istanbul, an urban center of 10 million people, from the description of earthquakes on the North Anatolian fault system in the Marmara Sea during the past 500 years and test the resulting catalog against the frequency of damage in Istanbul during the preceding millennium. Departing from current practice, we include the time-dependent effect of stress transferred by the 1999 moment magnitude M = 7.4 Izmit earthquake to faults nearer to Istanbul. We find a 62 +/- 15% probability (one standard deviation) of strong shaking during the next 30 years and 32 +/- 12% during the next decade.

Journal Article↗
PubMed2000

Interoperability of biodiversity databases: biodiversity information on every desktop.

Data about biodiversity are either scattered in many databases or reside on paper or other media not amenable to interactive searching. The Global Biodiversity Information Facility (GBIF) is a framework for facilitating the digitization of biodiversity data and for making interoperable an as-yet-unknown number of biodiversity databases that are distributed around the globe. In concert with other existing efforts, GBIF will catalyze the completion of a Catalog of the Names of Known Organisms and will develop search engines to mine the vast quantities of biodiversity data. It will be an outstanding tool for scientists, natural resource managers, and policy-makers.

Animals↗
PubMed2001

A progress report on translational control in eukaryotes.

An extraordinary amount of regulation goes into making sure that protein expression is controlled correctly. Several layers of regulation function to achieve the proper levels and proper timing of protein expression. Much is known about the protein machinery involved in translation, but we are lagging behind in understanding the mechanisms of control in eukaryotes. Kozak reviews the new second edition of Translational Control of Gene Expression, which attempts to catalog the mechanisms used by prokaryotes and eukaryotes, and the viruses that infect them and subvert their translational machinery.

Animals↗
PubMed2006

Bacillus endospores isolated from granite: close molecular relationships to globally distributed Bacillus spp. from endolithic and extreme environments.

As part of an ongoing effort to catalog spore-forming bacterial populations in environments conducive to interplanetary transfer by natural impacts or by human spaceflight activities, spores of Bacillus spp. were isolated and characterized from the interior of near-subsurface granite rock collected from the Santa Catalina Mountains, AZ. Granite was found to contain approximately 500 cultivable Bacillus spores and approximately 10(4) total cultivable bacteria per gram. Many of the Bacillus isolates produced a previously unreported diffusible blue fluorescent compound. Two strains of eight tested exhibited increased spore UV resistance relative to a standard Bacillus subtilis UV biodosimetry strain. Fifty-six isolates were identified by repetitive extragenic palindromic PCR (rep-PCR) and 16S rRNA gene analysis as most closely related to B. megaterium (15 isolates), B. simplex (23 isolates), B. drentensis (6 isolates), B. niacini (7 isolates), and, likely, a new species related to B. barbaricus (5 isolates). Granite isolates were very closely related to a limited number of Bacillus spp. previously found to inhabit (i) globally distributed endolithic sites such as biodeteriorated murals, stone tombs, underground caverns, and rock concretions and (ii) extreme environments such as Antarctic soils, deep sea floor sediments, and spacecraft assembly facilities. Thus, it appears that the occurrence of Bacillus spp. in endolithic or extreme environments is not accidental but that these environments create unique niches excluding most Bacillus spp. but to which a limited number of Bacillus spp. are specifically adapted.

Bacillus↗