Search PubMed⌕ Search

Biomedical subjects

J Pierce

Publications and source records attributed to J Pierce.

At least 19 recordsLinked to original sources

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families.

Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.

Asthma↗

Initiator and upstream elements in the alpha2-tubulin promoter of Giardia lamblia.

Giardia lamblia, one of the earliest diverging eukaryotes and a major cause of diarrhea world-wide, has unusually short intergenic regions, raising questions concerning its regulation of gene expression. We have approached this issue through examination of the alpha2-tubulin promoter and in particular investigated the function of an AT-rich element surrounding the transcription start site. Its placement and the ability of this sequence to direct transcription initiation in the absence of any other promoter elements is similar to the initiator element in higher eukaryotes. However, the sequence diversity of extremely short (8-10 bp) initiator elements is surprising, as is their ability to independently direct substantial levels of transcription. We also identified a large AT-rich element located between -64 and -29 bp upstream of the transcriptional start site and show using both deletions and site-specific mutations of this region that sequences between -60 and the start of transcription are important for promoter strength; interestingly this AT-rich sequence is not highly conserved among different Giardia promoters. These data suggest that while the overall structure of the core promoter has been conserved throughout eukaryotic evolution, significant variation and flexibility is allowed in element consensus sequences and roles in transcription. In particular, the short and diverse sequences that function in transcription initiation in Giardia suggest the potential for relaxed transcriptional regulation.

Animals↗

Motor vehicle occupant crashes among teens: impact of the graduated licensing law in San Diego.

To assess the effect of California's graduated driver's license (GDL) law in San Diego County, we compared motor vehicle crash and passenger injury rates involving 16-year-old drivers for 1999 and 2000, the first two years of the law, against 1997, using data from a statewide database of all injury crashes. While the crash rate per 1,000 drivers did not change following GDL, a significant decline in the percentage of 16-year-olds with a driver's license corresponded with large decreases in population-based crash and injury rates.

Accidents, Traffic↗

Intrapartum amnioinfusion for meconium-stained fluid: meta-analysis of prospective clinical trials.

OBJECTIVE: To evaluate the effectiveness of intrapartum prophylactic amnioinfusion in pregnancies complicated by meconium-stained amniotic fluid. DATA SOURCES: We identified prospective clinical trials of amnioinfusion in pregnancies complicated by meconium-stained amniotic fluid (AF) published in English by using computerized databases, references in published studies, and index reviews. METHODS OF STUDY SELECTION: We analyzed prospective studies of intrapartum amnioinfusion for meconium-stained AF. In every case, group allocation was based exclusively on meconium in AF. Only published studies with clearly documented outcome data were included. The trials were evaluated for meconium below the vocal cords, meconium aspiration syndrome, fetal acidemia, cesarean delivery, and postpartum endometritis. Each trial was evaluated for the quality of its methodology, inclusion and exclusion criteria, adequacy of randomization, amnioinfusion protocols, definition of outcomes, and statistical analyses. TABULATION, INTEGRATION, AND RESULTS: Thirteen studies met inclusion criteria for our systematic review. Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated for each outcome. Estimates of ORs and risk differences for dichotomous outcomes were calculated using random and fixed-effects models. We tested for homogeneity across the studies. We found that intrapartum amnioinfusion significantly reduced the frequency of meconium aspiration syndrome (OR 0.30; 95% CI 0.19, 0. 46), of meconium below the vocal cords, and neonatal acidemia. Subjects allocated to receive amnioinfusion also had a significantly lower overall cesarean rate (OR 0.74, 95% CI 0.59, 0.93) without increased postpartum endometritis. CONCLUSION: Amnioinfusion in cases of meconium-stained fluid significantly improves neonatal outcome, lowers the cesarean delivery rate, and does not increase the postpartum endometritis rate.

Amnion↗

Defining and measuring fatigue.

In response to a long history of problems with defining and measuring fatigue, the University of Kansas School of Nursing established a Center for Biobehavioral Studies of Fatigue Management to facilitate the study of fatigue in diverse populations. The purpose of this article is to review past efforts to define and measure fatigue and the conceptual problems relevant to currently used measures of fatigue. Several distinct characteristics and corresponding measures of fatigue are identified and a definition and framework for the study of fatigue are discussed. Future research on fatigue must attend to the conceptual distinctions among various measures and the measures of fatigue most appropriate to the goals of a study.

Diagnosis, Differential↗

Use of the School Performance Rating Scale with children treated for attention deficit hyperactivity disorder.

The School Performance Rating Scale was developed to assess academic performance of children diagnosed with attention deficit hyperactivity disorder. The most frequent concern of professionals, parents, and teachers is the child's performance and achievement in school; however, assessments are seldom obtained pretest and posttest. The scale has yet to be standardized so its association with academic behavior was estimated with the ADD-H Comprehensive Teachers' Rating Scale. 24 elementary-school children were given both scales after being diagnosed and treated for ADHD, following evaluation by a multidisciplinary team at a medical university's child-development clinic. A positive correlation of .8 was found between scores on the School Performance Rating Scale and .6 with Attention and Social Skills from the ADD-H Comprehensive Teachers' Rating Scale. Standardization of the scale would allow clinicians more specific identifications.

Achievement↗

Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Trial of Nonpharmacologic Interventions in the Elderly (TONE) Cooperative Research Group.

The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure (BP) has been controlled for 1 year. However, discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events. The Trial of Nonpharmacologic Interventions in the Elderly (TONE) was a clinical trial of the efficacy of weight loss and/or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP< 145/85 mm Hg on 1 antihypertensive medication. Of 975 participants, 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications. Thirty-three events (stroke, transient ischemic attack, myocardial infarction, arrhythmia, congestive heart failure, angina, other) occurred between randomization and the onset of drug withdrawal (median time 3.6 months), 57 events occurred either during or after drug withdrawal (14.0 months), and 36 events occurred after resumption of antihypertensive therapy (15.9 months). Event rates per 100 person-years were 5.5, 5.5, and 6.8 for the 3 time periods (p=0.84) in the nonoverweight group and 7.2, 5.2, and 5.6 (p=0.08) in the overweight group. The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal, providing that good BP control can be maintained with nonpharmacologic therapy.

Aged↗

2,3-Dihydro-2,5-dihydroxy-4H-benzopyran-4-one: a nonphysiological substrate for fungal melanin biosynthetic enzymes.

We have synthesized an alternate substrate for trihydroxynaphthalene reductase (3HNR) and scytalone dehydratase (SD), two enzymes in the fungal melanin biosynthetic pathway. The oxidation of 2,3-dihydro-2,5-dihydroxy-4H-benzopyran-4-one (DDBO) to 4,5-dihydroxy-2H-benzopyran-2-one (DBO) with concomitant reduction of NADP+ is catalyzed by 3HNR. DDBO is dehydrated by SD to 5-hydroxy-4H-1-benzopyran-4-one (HBO). These reactions can be monitored using continuous spectrophotometric assays. DDBO race-mizes rapidly, so chiral synthesis to mimic the natural substrate is not required. DDBO, DBO, and HBO are stable in aerated aqueous solution, in contrast to the rapidly autooxidizing trihydroxynaphthalene, a physiological substrate for 3HNR and product of SD. Unlike the natural substrates, DDBO, DBO, and HBO do not change protonation state between pH's 4 and 9. Oxidation of DDBO is effectively irreversible at pH 7, as DBO deprotonates with a pKa of 2.5. At pH 7.0 and 25 degrees C, the kcat for 3HNR catalyzed DDBO oxidation is 14 s-1 and the K(m) is 5 microM; the kcat for SD catalyzed DDBO dehydration is 400 s-1 and the K(m) is 15 microM. Based on these kinetic constants, DDBO is a better substrate than the natural substrate scytalone for both 3HNR and SD at neutral pH. An explanation for the preference of DDBO over scytalone in the oxidation and dehydration reactions is offered.

Ascomycota↗

Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent.

Signal transduction through the interferongamma (IFNgamma) receptor involves the formation of a ligand-dependent multimolecular association of receptor chains (alpha and beta), Janus tyrosine kinases (Jak1 and Jak2), and the transcription factor (signal transducers and activators of transcription 1alpha (STAT1alpha)) in addition to activation of mitogen-activated protein kinases (MAPK). Interactions between components of the Jak/STAT cascade and the p21(ras)/Raf-1/MAPK cascade are unexplored. Treatment of HeLa cells with IFNgamma resulted in the rapid and transient activation of Raf-1 and MAPK. Parallel activation of cells resulted in essentially no enhancement of p21(ras) activation despite marked enhancement after treatment with epidermal growth factor. In HeLa (E1C3) and fibrosarcoma (U4A) cell lines, both of which are deficient in Jak1 kinase, Raf-1 activation by IFNgamma was absent. Reconstitution of Raf-1 activity was observed only with kinase active Jak1 in both cell lines. In COS cells, transient expression of wild type or kinase-inactive Jak1 coimmunoprecipitated with Raf-1, but activation of Raf-1 activity was only observed in cells expressing kinase-active Jak1. These observations suggest that a kinase-active Jak1 is required for IFNgamma activation of Raf-1 that is p21(ras)-independent.

Calcium-Calmodulin-Dependent Protein Kinases↗

Biosynthesis and metabolism of native and oxidized neuropeptide Y in the hippocampal mossy fiber system.

Neuropeptide Y (NPY) gene expression is known to be modulated in the mossy fiber projection of hippocampal granule cells following seizure. We investigated NPY biosynthesis and metabolism in an attempt to characterize NPY biochemically as a neurotransmitter in the granule cell mossy fiber projection. NPY biosynthesis was compared in normal control animals and in animals that had experienced a single pentylenetetrazole-induced seizure. In situ hybridization analysis established the postseizure time course of preproNPY mRNA expression in the hippocampal formation, localizing the majority of increased preproNPY mRNA content to the hilus of the dentate gyrus. Radioimmunoassay analysis of the CA3/mossy fiber terminal subfield confirmed a subsequent increase in NPY peptide content. Biosynthesis of NPY peptide by granule cells and transport to the CA3/mossy fiber subfield was demonstrated by in vivo radiolabel infusion to the dentate gyrus/hilus followed by sequential HPLC purification of identified radiolabeled peptide from the CA3/mossy fiber terminal subfield. Additional in vivo radiolabeling studies revealed a postseizure increase in an unidentified NPY-like immunoreactive (NPY-LI) species. HPLC/radioimmunoassay analyses of CA3 subfield tissue extracts comparing normal control animals and pentylenetetrazole-treated animals confirmed the increased total NPY-LI, and demonstrated that the increased NPY-LI was comprised of a minor increase in native NPY and a major increase in the unknown NPY-LI. Data from subsequent and separate analyses incorporating immunoprecipitation with anti-C-terminal flanking peptide of NPY, further HPLC purification, and matrix-assisted laser desorption/ionization mass spectrometry support the conclusion that the unknown NPY-LI is methionine sulfoxide NPY. NPY and NPY-sulfoxide displayed differential calcium sensitivity for release from mossy fiber synaptosomes. Similar to NPY, NPY sulfoxide displayed high-affinity binding to each of the cloned Y1, Y2, Y4, and Y5 receptor subtypes. Postrelease inactivation of NPY was demonstrated in a mossy fiber synaptosomal preparation. Thus, the present study in combination with previously reported electrophysiological activity of NPY in the CA3 subfield demonstrates that NPY fulfills the classical criteria for a neurotransmitter in the hippocampal granule cell mossy fiber projection, and reveals the presence of two molecular forms of NPY that display differential mechanisms of release while maintaining similar receptor potencies.

Amino Acid Sequence↗

Crystallization and characterization of bovine liver glutamate dehydrogenase.

Bovine liver glutamate dehydrogenase has been crystallized as an abortive complex with glutamic acid, NADH, and an inhibitor, GTP. Crystals of this complex were grown using the sitting drop vapor diffusion method with PEG 8000 as the precipitant and diffract to better than 2.5 A resolution. The crystals belong to the space group P2(1) with an entire enzyme hexamer in the crystallographic asymmetric unit. Self-rotation and self-Patterson functions clearly define the orientation and position of this hexameric enzyme.

Animals↗

Confidentiality and privacy breaches in a university hospital emergency department.

OBJECTIVE: To determine the frequency of visual and auditory confidentiality and privacy breaches in a university ED. METHODS: A prospective, observational study of medical personnel behavior was performed using participant and direct observation techniques. Observations were made in a university tertiary referral and trauma center emergency facility. Observers recorded auditory and visual confidentiality and privacy breaches in various patient care areas during 1-hour periods. Information collected included patient name or room number, complaint/diagnosis, diagnostic tests, past medical history, and personal information. It was then determined whether a clear identification of the patient's name or face and/or an association to his or her clinical course could be made. RESULTS: All members of the health care team committed confidentiality and privacy breaches. Frequency of breaches was dependent on room location and design. Breaches in the triage/waiting area occurred for > 53% of the patients. Breaches near the physician/nursing station ranged from 3 to 24 per hour and 1.5 to 3.4 per patient hour. Other inappropriate comments also were noted. One hundred consecutive patients and family members were interviewed at ED release, with only 2/100 having noticed the status board, although neither could recall any specific details. CONCLUSION: Confidentiality and privacy breaches occur in a university ED by all members of the health care team. The ED architecture and floor plan affect patient confidentiality and privacy.

Attitude to Health↗

Beta interferon and oncostatin M activate Raf-1 and mitogen-activated protein kinase through a JAK1-dependent pathway.

Activation of early response genes by interferons (IFNs) and other cytokines requires tyrosine phosphorylation of a family of transcription factors termed signal transducers and activators of transcription (Stats). The Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) is required for cytokine-induced tyrosine phosphorylation and dimerization of the Stat proteins. In order for IFNs to stimulate maximal expression of Stat1alpha-regulated genes, phosphorylation of a serine residue in the carboxy terminus by mitogen-activated protein kinase (MAPK) is also required. In HeLa cells, both IFN-beta and oncostatin M (OSM) stimulated MAPK and Raf-1 enzyme activity, in addition to Stat1 and Stat3 tyrosine phosphorylation. OSM stimulation of Raf-1 correlated with GTP loading of Ras, whereas IFN-beta activation of Raf-1 was Ras independent. IFN-beta- and OSM-induced Raf-1 activity could be coimmunoprecipitated with either Jak1 or Tyk2. Furthermore, HeLa cells lacking Jak1 displayed no activation of STAT1alpha, STAT3, and Raf-1 by IFN-beta or OSM and also demonstrated no increase in the relative level of GTP-bound p21ras in response to OSM. The requirement for Jak1 for IFN-beta- and OSM-induced activation of Raf-1 was also seen in Jak1-deficient U4A fibrosarcoma cells. Interestingly, basal MAPK, but not Raf-1, activity was constitutively enhanced in Jak1-deficient HeLa cells. Transient expression of Jak1 in both Jak-deficient HeLa cells and U4A cells reconstituted the ability of IFN-beta and OSM to activate Raf-1 and decreased the basal activity of MAPK, while expression of a kinase-inactive form of the protein showed no effect. Moreover, U4A cells selected for stable expression of Jak1, or COS cells transiently expressing Jak1 or Tyk2 but not Jak3, exhibited enhanced Raf-1 activity. Therefore, it appears that Jak1 is required for Raf-1 activation by both IFN-beta and OSM. These results provide evidence for a link between the Jaks and the Raf/MAPK signaling pathways.

Animals↗