Seeking Athena.
Explore the source record for details and available documents.
Education, Nursing, Continuing↗
Biomedical subjects
E Hayes
Publications and source records attributed to E Hayes.
Myosin conformational states determined by single fluorophore polarization.
Muscle contraction is powered by the interaction of the molecular motor myosin with actin. With new techniques for single molecule manipulation and fluorescence detection, it is now possible to correlate, within the same molecule and in real time, conformational states and mechanical function of myosin. A spot-confocal microscope, capable of detecting single fluorophore polarization, was developed to measure orientational states in the smooth muscle myosin light chain domain during the process of motion generation. Fluorescently labeled turkey gizzard smooth muscle myosin was prepared by removal of endogenous regulatory light chain and re-addition of the light chain labeled at cysteine-108 with the 6-isomer of iodoacetamidotetramethylrhodamine (6-IATR). Single myosin molecule fluorescence polarization data, obtained in a motility assay, provide direct evidence that the myosin light chain domain adopts at least two orientational states during the cyclic interaction of myosin with actin, a randomly disordered state, most likely associated with myosin whereas weakly bound to actin, and an ordered state in which the light chain domain adopts a finite angular orientation whereas strongly bound after the powerstroke.
Animals↗
Functional significance of cardiac myosin essential light chain isoform switching in transgenic mice.
The different functions of the ventricular- and atrial-specific essential myosin light chains are unknown. Using transgenesis, cardiac-specific overexpression of proteins can be accomplished. The transgenic paradigm is more useful than originally expected, in that the mammalian heart rigorously controls sarcomeric protein stoichiometries. In a clinical subpopulation suffering from heart disease caused by congenital malformations of the outflow tract, an ELC1v-->ELC1a isoform shift correlated with increases in cross-bridge cycling kinetics as measured in skinned fibers derived from the diseased muscle. We have used transgenesis to replace the ventricular isoform of the essential myosin light chain with the atrial isoform. The ELC1v--> ELC1a shift in the ventricle resulted in similar functional alterations. Unloaded velocities as measured by the ability of the myosin to translocate actin filaments in the in vitro motility assay were significantly increased as a result of the isoform substitution. Unloaded shortening velocity was also increased in skinned muscle fibers, and at the whole organ level, both contractility and relaxation were significantly increased. This increase in cardiac function occurred in the absence of a hypertrophic response. Thus, ELC1a expression in the ventricle appears to be advantageous to the heart, resulting in increased cardiac function.
Amino Acid Sequence↗
The presence of transcription factors in fetal bovine sera.
Three sources of fetal bovine serum (FBS) were fractionated by ammonium sulfate precipitation and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transferred to Immobilon-P membranes, immunoblotted with a panel of transcription factor antibodies, and detected by enhanced chemiluminescence. Nine transcription factors were detected--ATF-2, SRE-ZBP, GATA-2, TFIID, Ets-1/Ets-2, E2F-1, Oct-2, p53, and AP-2; four transcription factors were not detected--Myo D, CREB, Sp2, and Wilms' tumor. The results indicated the presence of varying amounts of several transcription factors in three commercial sources and may represent heretofore unrecognized factors influencing cell culture.
Animals↗
Mentoring and self-efficacy for advanced nursing practice: a philosophical approach for nurse practitioner preceptors.
Nurse practitioners (NPs), frequently called upon by graduate schools of nursing to be preceptors for NP students, are asked to play an active role in the socialization of these students as capable primary care providers. Much is expected of the preceptor in the typical short-term clinical preceptorship with little guidance available to her or him. A mentoring model of clinical education, while representing a longer-term commitment for preceptors than usual precepting arrangements, may ultimately be a more effective model for student learning and more satisfying for the preceptor than currently practiced models. Eastern philosophical principles, very much in harmony with valued nursing approaches to relationships, can provide a framework for examining mentoring as a strategy for promotion of self-efficacy for advanced practice that can be of benefit to both the NP preceptor and the NP neophyte.
Clinical Competence↗
Cell specific expression of the sst2A and sst5 somatostatin receptors in the rat anterior pituitary.
Somatostatin (SRIF), originally described as a hypothalamic hormone that inhibits the release of growth hormone was subsequently shown to inhibit the secretion of multiple pituitary hormones. Five genes encoding six different SRIF receptors (sst1, 2A, 2B, 3, 4 and 5) have been cloned and mRNAs for all five are expressed in the anterior pituitary. We used double immunostaining to determine which cells in the anterior pituitary bear sst2A and sst5 receptors. Our results show that these two receptors are widely distributed in the pituitary gland and are both present in a large percentage of GH cells. In addition, sst5 occurs in a small population of corticotrophs and a large percentage of lactotrophs whereas sst2A is found in only a few lactotrophs but a large number of corticotrophs. The sst2A receptor is also expressed in about a third of the gonadotrophs and thyrotrophs. Interestingly, sst2A and sst5 receptors colocalize in a small percentage of cells, most likely somatotrophs demonstrating that the same cells can contain multiple sst receptor subtypes. These results indicate that sst subtype specific analogs are likely to be useful for the selective regulation of individual pituitary hormones.
Animals↗
Paediatric HIV infection in the Republic of Ireland and the need for antenatal screening.
Thirty-seven HIV-infected children have been identified in the Republic of Ireland since 1985. Only 12 (32%) of 37 were followed prospectively from birth. Median age at diagnosis was 18 months (4 weeks to 8 years). In 32 (86%) of 37 cases, HIV infection was acquired as a result of transmission from mother to infant with intravenous drug use (IVDU) the most frequent risk factor for maternal acquisition of HIV. Of these 32 children, median maternal age at delivery was 24 (interquartile range (IQR) 23-26) years with median gestation at delivery 40 (IQR 38-40) weeks. Mode of delivery was by vaginal delivery in all 29 (91%) cases where mode of delivery is known. Only 2 infants were breastfed. Seven children have died at a median age of 9 (0.8-9.6) years. As of July 1997, 12 children have AIDS, 14 have symptomatic disease without AIDS and 3 are asymptomatic. Median age at AIDS diagnosis was 2.6 (0.1-6.5) years. Median survival time post-AIDS diagnosis was 6.5 (1.8-8.3) years. Of 29 living children, 24 mothers and 14 fathers are HIV infected and only 14 children live with both parents. Childhood HIV infection has had a significant personal, social and financial impact on both Irish families and society in general. More effective measures to control HIV infection among intravenous drug users are needed. Antenatal detection of HIV-infected mothers is paramount as vertical transmission can be successfully prevented and morbidity and death can be prevented in the infected infant.
Child↗
First-time mothers' perceptions of prenatal care services.
This study sought to uncover information regarding prenatal care services as reported by primiparas. Inadequate prenatal care has been linked with the delivery of low birth weight (LBW) infants and infant mortality. This secondary analysis of a larger study (N = 426) examined the need for and availability, accessibility, and use of prenatal care services by primiparas (n = 141). Results indicated that primiparas delivering LBW infants reported less satisfaction with information on birth control and less information on infant feeding. In addition, mothers of LBW infants reported more often than mothers of normal birthweight infants that transportation and finances were barriers to prenatal care. Childbirth preparation class was the only predictor variable for birth weight in this study.
Adult↗
Who's leading radiology--and where is it headed?
Explore the source record for details and available documents.
Leadership↗
Characterization of a non-human primate model of drug-induced torsades de pointes.
Explore the source record for details and available documents.
Animals↗
Cellular actions of etretinate in psoriasis: enhanced epidermal differentiation and reduced cell-mediated inflammation are unexpected outcomes.
Retinoids are potent cell growth and differentiation modulators, but cellular effects of therapeutic retinoids in psoriasis are unknown. We studied the effects of etretinate on pathological activation of keratinocytes and lymphocytes in patients treated systemically with this agent for 8 weeks. Ten patients with extensive psoriasis vulgaris were treated with etretinate at 0.75 mg/kg for 8 weeks. Skin biopsies obtained before and at 8 weeks of treatment were studied using immunohistochemical markers for keratinocyte proliferation or differentiation and for the presence of T-lymphocyte subsets or associated inflammatory proteins. During 8 weeks of treatment, the clinical severity decreased by a mean of 64% (p < 0.001). Compared to a similar group of patients treated with bath PUVA, psoriatic plaque erythema resolved more slowly and less completely (p < 0.05), but improvements in plaque thickness and scale were not significantly different between etretinate and PUVA treatments. Etretinate produced a 44% decrease in epidermal thickness (p < 0.001) and a 62% reduction in keratinocyte proliferation (p < 0.001) after 8 weeks of treatment. Unexpectedly, keratinocyte differentiation was enhanced following etretinate treatment as indicated by increased filaggrin production, increased number and size of keratohyaline granules, greater abundance of keratin filaments, and increased secretion of intercellular lipids from Odland bodies. The stratum corneum in resolving psoriatic lesions was unusually thin, probably caused by retinoid-induced shedding of corneocytes. "Regenerative" epidermal growth was maintained during etretinate treatment, as marked by continued expression of keratin 16 and alpha 3-integrin by suprabasal keratinocytes. Surprisingly the inflammation-associated proteins HLA-DR and ICAM-1 were no longer produced by epidermal keratinocytes following etretinate treatment, and CD3+, CD8+, and CD25+ T-lymphocyte subsets were reduced by 50-65% in lesional tissue (p < 0.01). Etretinate shows unexpected anti-inflammatory and pro-differentiation actions in psoriasis. Etretinate appears to function as a disease suppressive agent which improves hyperplasia, keratinocyte differentiation and tissue inflammation mediated by cellular immune elements.
Cell Differentiation↗
Maximal actomyosin ATPase activity and in vitro myosin motility are unaltered in human mitral regurgitation heart failure.
Myofibrillar but not actomyosin ATPase is depressed in failing myocardium from patients with dilated cardiomyopathy. Since there is a similar depression of myofibrillar ATPase in mitral regurgitation myocardium, we investigated whether or not the hydrolytic and mechanical performances of myosin are altered by comparing the maximal actomyosin ATPase activity and the in vitro myosin motility of myocardial myosin from patients with mitral regurgitation heart failure with that of patients with normal ventricular function. The results show that there is no significant difference (P > .05) between nonfailing and failing values for either the maximal actomyosin ATPase activity (0.3 s-1.head-1) or the myosin motility (1 micron/s). These observations suggest that changes, other than in the myosin heavy chain, contribute to the altered myocardial performance in mitral regurgitation myocardium.
Actins↗
Managed-care inpatients receive fewer imaging tests. Discrepancy may be linked to length of stay.
Explore the source record for details and available documents.
Diagnostic Imaging↗
The cardiac electrophysiological effects of sparteine and its analogue BRB-I-28 in the rat.
This study compares the cardiovascular and antiarrhythmic effects of sparteine and a 3,7-diheterobicyclo[3.3.1]nonane analogue of sparteine, BRB-I-28, in pentobarbitone-anaesthetized rats subjected to left-ventricle electrical stimulation and occlusion of the left anterior descending coronary artery. Sparteine and BRB-I-28 produced a dose-dependent reduction in heart rate and blood pressure over the dose range 1-64 mumol/kg/min. As well, the P-R and Q-aT intervals of the electrocardiogram (ECG) were prolonged. The thresholds for induction of premature beats and ventricular fibrillation were dose-dependently increased and both drugs increased refractoriness. While sparteine and BRB-I-28 (at 16 and 64 mumol/kg/min, respectively) did not change the incidence of premature beats or ventricular tachycardia with coronary occlusion, both drugs equally reduced the incidence of ventricular fibrillation. We characterized the actions of sparteine and BRB-I-28 on cardiac Na+, transient outward and sustained outward plateau K+ currents of rat myocytes using the whole-cell patch-clamp. Sparteine and BRB-I-28 produced a concentration-dependent reduction in Na+ current with EC50 values of 110 and 230 microM, respectively. Both drugs produced hyperpolarizing shifts of 8 and 11 mV, respectively, for Na+ channel inactivation while neither produced a change in channel activation. Both drugs produced a concentration-dependent block of the sustained plateau K+ current and increased the rate of decay of the transient outward K+ current. Thus, sparteine and BRB-I-28 possess Na+ and K+ channel blocking properties which may account for their antiarrhythmic actions against electrical and ischaemic arrhythmias.
Animals↗
Thiophosphorylation independently activates each head of smooth muscle myosin in vitro.
To determine whether thiophosphorylation of the 20-kDa myosin light chain activates each head of smooth muscle myosin independently of the head with which it is paired, chicken gizzard smooth muscle myosin was randomly thiophosphorylated, producing a mixture of unphosphorylated and singly and doubly thiophosphorylated myosin. Thiophosphorylation levels were measured by glycerol-urea gels, and the activity of this myosin was determined by actin-activated adenosinetriphosphatase measurements and in an in vitro motility assay, where the velocity of actin filaments moving over a myosin-coated surface is measured. Activity at each thiophosphorylation level was similar to that previously observed for mixtures of unphosphorylated and doubly thiophosphorylated myosin (D. E. Harris, S. S. Work, R. K. Wright, N. R. Alpert, and D. M. Warshaw. J. Muscle Res. Cell Motil. 15: 11-19, 1994). All doubly thiophosphorylated myosin was then formed into filaments and removed from randomly thiophosphorylated myosin by centrifugation. The remaining myosin (mixture of unphosphorylated and singly phosphorylated myosin), which could not polymerize because of their conformation, retained approximately 70% activity compared with mixtures of unphosphorylated and doubly thiophosphorylated myosin. Thus a thiophosphorylated smooth muscle myosin head can produce substantial biochemical and mechanical activity, even when it is paired with an unphosphorylated partner.
Actins↗
Policy on MR angio mystifies radiologists.
Explore the source record for details and available documents.
Carotid Artery Diseases↗
A membrane-mediated catalytic event in prothrombin activation.
Prothrombinase assembly takes place on the surface of unsaturated phosphatidylcholine (PC), phosphatidylserine (PS) membranes in the presence of Ca2+, through the rapid association of membrane-bound factor Va and factor Xa. The present study uses saturated PCPS (75:25, w/w) vesicles to study prothrombinase assembly and catalytic properties in order to differentiate the influences of the membrane upon catalyst assembly, substrate delivery, and peptide bond cleavage. In contrast to studies using unsaturated phospholipid, prothrombin activation studies using saturated PCPS (75:25, w/w) (C14:0, C16:0, and C18:0) revealed up to a 20-fold decrease in prothrombinase activity. C18:0 membranes support at least 50% of the prothrombinase binding capacity (KdVa-Xa = 1 nM and nVa-Xa = 1.1) of C18:1 PCPS (75:25, w/w). Thus, the 95% loss in activity cannot be explained by gross alterations in catalyst concentration or assembly. Stopped-flow studies with saturated lipids demonstrate that factor Va, factor Xa, and prothrombin have decreased kon values. Compensatory changes in koff leave the Kd values for these protein-lipid interactions almost unchanged relative to unsaturated PCPS. The profoundly decreased activation rate on saturated phospholipid membranes as compared to unsaturated phospholipids is in part due to slowed substrate/enzyme delivery caused by the saturated lipids. However, studies using prethrombin-1 and C18:0 PCPS (75:25, w/w) also revealed a 15-fold decrease in activity for preassembled prothrombinase. Although there was a slight change in Km (+2-fold), the major cause of the decrease is an 18-fold decrease in kcat. Similar differences for Km and kcat values were obtained for prothrombin. Substrate delivery is thus only partially responsible for the diminished prothrombinase activity observed with saturated phospholipids. Since the activity of prothrombinase is decreased for both prothrombin and prethrombin-1 principally by reducing kcat, it appears that catalyst formation on saturated phospholipids somehow compromises the proteolytic activity of the enzyme complex. This implies that the phospholipid bilayer serves not merely as a surface for condensing the proteins but also as a functional element of the prothrombinase enzyme.
Amino Acid Sequence↗
Relationship between QaT and RR intervals in rats, guinea pigs, rabbits, and primates.
The ECG is routinely used in many species to monitor effects of drugs. While it is relatively easy to measure both PR and QRS, measurement of QT is complicated by the fact that this interval can change with heart rate. In order to compensate for variations in QT due to variations in heart rate, various correction factors have been used, including those of Bazett and Hodges. Such corrections were devised for humans and may have limited applicability in other species. We have systematically varied heart rate in anesthetized rats, guinea pigs, rabbits, and primates using procedures such as vagal stimulation, direct atrial stimulation, injection of cold saline and drugs, including anesthetics, and measured the resulting QT (as QaT and related measures). Over a wide range of heart rates we tested various formulas for their value in correcting for the variation in QT interval associated with changes in heart rate. In rats the "QT" interval did not change appreciably with heart rate. In the other species QaT intervals varied in the expected manner with heart rate in that they decreased with tachycardia and increased with bradycardia. Various formulas were tested for their utility in correcting measures of the QaT interval (QaTc) for changes in heart rate in guinea pigs, rabbits, and primates. In species other than rats, there was little difference between the various formulas in their ability to increase the precision of QaTc and the normality of its distribution, although the best correction is that derived from the regression (either linear, square root, or polynomial) equation relating RR and QaT.
Animals↗