Distribution by Scientific Domains
Distribution within Medical Sciences

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  • Selected Abstracts

    The effects of acute and chronic exercise on the vasculature

    ACTA PHYSIOLOGICA, Issue 4 2010
    J. J. Whyte
    Abstract Regular physical activity (endurance training, ET) has a strong positive link with cardiovascular health. The aim of this review is to draw together the current knowledge on gene expression in different cell types comprising the vessels of the circulatory system, with special emphasis on the endothelium, and how these gene products interact to influence vascular health. The effect beneficial effects of ET on the endothelium are believed to result from increased vascular shear stress during ET bouts. A number of mechanosensory mechanisms have been elucidated that may contribute to the effects of ET on vascular function, but there are questions regarding interactions among molecular pathways. For instance, increases in flow brought on by ET can reduce circulating levels of viscosity and haemostatic and inflammatory variables that may interact with increased shear stress, releasing vasoactive substances such as nitric oxide and prostacyclin, decreasing permeability to plasma lipoproteins as well as the adhesion of leucocytes. At this time the optimal rate-of-flow and rate-of-change in flow for determining whether anti-atherogenic or pro-atherogenic processes proceed remain unknown. In addition, the impact of haemodynamic variables differs with vessel size and tissue type in which arteries are located. While the hurdles to understanding the mechanism responsible for ET-induced alterations in vascular cell gene expression are significant, they in no way undermine the established benefits of regular physical activity to the cardiovascular system and to general overall health. This review summarizes current understanding of control of vascular cell gene expression by exercise and how these processes lead to improved cardiovascular health. [source]

    EndothelinA (ETA) and ETB receptor-mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla

    ACTA PHYSIOLOGICA, Issue 4 2007
    J. C. Sullivan
    Abstract Aim:, Our laboratory and others have shown that endothelin (ET)-1 directly stimulates nitric oxide (NO) production in inner medullary collecting duct (IMCD) cells. The goal of this study was to determine which NO synthase (NOS) isoforms in IMCD are sensitive to ET-1, and the role of ETA and ETB receptor activation in vivo and in vitro. Methods:, NOS enzymatic activity and NOS isoform protein expression were examined in cultured IMCD-3 cells and isolated renal inner medulla. ETB receptor-deficient homozygous rats (sl/sl) have elevated levels of circulating ET-1 and lack a functional ETB signalling pathway in kidneys, and furthermore provides a unique model to study ETA receptor signalling in the renal inner medulla in vivo. Results:, Incubation of IMCD-3 cells with exogenous ET-1 (50 nm) resulted in ETA -dependent increased NOS1 protein expression in IMCD-3 cells with no effect on NOS2 or NOS3 expression. ETB receptor antagonism has no effect on NOS expression in IMCD-3 cells. Consistent with in vitro results, cytosolic NOS1 protein expression was significantly greater in the renal inner medulla of sl/sl rats compared with heterozygous (sl/+) controls, with no alteration in NOS3 expression. In contrast to protein expression data, NOS1- and NOS3-specific enzymatic activities decreased in the cytosolic fraction from the renal inner medulla of sl/sl compared with sl/+. Conclusion:, These results provide evidence that both ETA and ETB receptors regulate NOS isoform activity in the renal inner medulla and specifically support the hypothesis that ETA receptor activation increases NOS1 expression. [source]

    Kinetic studies on the influence of temperature and growth rate history on crystal growth

    P. M. Martins
    Abstract Crystallization experiments of sucrose were performed in a batch crystallizer to study the effect of temperature and growth rate history on the crystal growth kinetics. In one of the growth methods adopted, the isothermal volumetric growth rate (RV) is determined as a function of supersaturation (S) at 35, 40 and 45 şC. In the other, crystals are allowed to grow at constant supersaturation by automatically controlling the solution temperature as the solute concentration decreased. Using the latter method RV is calculated as the solution is cooled. The obtained results are interpreted using empirical, engineering and fundamental perspectives of crystal growth. Firstly, the overall activation energy (EA) is determined from the empirical growth constants obtained in the isothermal method. The concept of falsified kinetics, widely used in chemical reaction engineering, is then extended to the crystal growth of sucrose in order to estimate the true activation energy (ET) from the diffusion-affected constant, EA. The differences found in the isothermal and constant supersaturation methods are explained from the viewpoint of the spiral nucleation mechanism, taking into account different crystal surface properties caused by the growth rate history in each method. Finally, the crystal growth curve obtained in the batch crystallizer at 40 şC is compared with the one obtained in a fluidized bed crystallizer at the same temperature. Apparently divergent results are explained by the effects of crystal size, hydrodynamic conditions and growth rate history on the crystallization kinetics of sucrose. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

    Cardiac expression patterns of endothelin-converting enzyme (ECE): Implications for conduction system development

    David Sedmera
    Abstract The spatiotemporal distribution of the endothelin-converting enzyme (ECE) protein in the embryonic chick heart and the association of this polypeptide with the developing cardiac conduction system is described here for the first time. Further, we show how cardiac hemodynamic load directly affects ECE level and distribution. Endothelin (ET) is a cytokine involved in the inductive recruitment of Purkinje fibers. ET is produced by proteolytic cleavage of Big-ET by ECE. We generated an antibody against chick ECE recognizing a single band at ,70 kD to correlate the cardiac expression of this protein with that reported previously for its mRNA. ECE protein expression was more widespread compared to its mRNA, being present in endothelial cells, mesenchymal cells, and myocytes, and particularly enriched in the trabeculae and nascent ventricular conduction system. The myocardial expression was significantly modified under experimentally altered hemodynamic loading. In vivo, ET receptor blockade with bosentan delayed activation sequence maturation. These data support a role for ECE in avian cardiac conduction system differentiation and maturation. Developmental Dynamics 237:1746,1753, 2008. © 2008 Wiley-Liss, Inc. [source]

    Endoscopic Injection Sclerotherapy for the Treatment of Recurrent Esophageal Varices after Esophageal Transection

    Hiroshi Yoshida
    Background: ,We examined the hemodynamic changes associated with recurrent esophageal varices after esophageal transection (ET) and evaluated the effectiveness of endoscopic injection sclerotherapy (EIS) as the treatment for these varices. Methods: ,Nineteen patients with recurrent esophageal varices after ET were treated by EIS. Endoscopic varicealography during injection sclerotherapy, following oral blockage of flow by a balloon, identified three patterns: (i) type 1: common type, continuous filling by the feeder vessel of the varix; (ii) type 2: retrograde-disappearing type, confirmed hepatofugal flow; and (iii) type 3: immediate washout type, immediate washout of contrast medium. Results: ,Angiography revealed that the hepatofugal feeder vessel was the right gastric vein in all cases. Fourteen patients (73.7%) were classified as type 1, 4 patients (21.1%) as type 2, and 1 patient (5.3%) as type 3. Fewer treatment sessions were required in type 1 than in type 2 (P < 0.005). Recurrent varices were completely eradicated in all patients except the patient with type 3 disease. Cumulative re-recurrence rates at 5 and 10 years were similar for types 1 and 2 (28.6 and 71.4%vs 25 and 25%, respectively). The cumulative survival rates after EIS at 5 and 10 years were also similar for types 1 and 2 (77.1 and 66.1%vs 66.7 and 66.7%). Conclusion: ,Endoscopic injection sclerotherapy is an effective treatment for recurrent esophageal varices after ET, except in type 3 disease. Our classification based on endoscopic varicealography during injection sclerotherapy provides knowledge of blood flow within the varices that helps to inform the treatment strategy. [source]

    Original article: Quality of life after esophagectomy and endoscopic therapy for Barrett's esophagus with dysplasia

    D. Schembre
    SUMMARY Esophagectomy (EG) and endoscopic therapy (ET) can eradicate Barrett's esophagus with early neoplasia. Their relative effect on quality of life is unknown. The 36-item Short Form Health Survey (SF-36) and Gastrointestinal Quality of Life Index (GIQLI) questionnaires were sent to all patients who underwent either EG or ET at our institution over the last 9 years. Groups were stratified by age and American Society of Anesthesia (ASA) class. Surveys were sent to 77 patients and completed by 14 EG (50%) and by 28 ET patients (57%). The average time between treatment and survey was 4 years in the ET group and 5 years in the EG group. There were no significant differences in SF-36 scores between EG and ET patients except for superior physical functioning among EG patients 65 and older QOL scores among EG and ET groups were not significantly different than sex age-matched controls. GIQLI scores were similar between ET and EG patients of all ages (P= 0.60). GIQLI scores were higher among younger ET patients than young EG patients (P= 0.049). GIQLI scores also tended to be higher among ASA 1 and 2 ET patients than ASA 1 and 2 EG patients, but this did not reach statistical significance (P= 0.09). EG and ET for early Barrett's neoplasia appear to have similar impact on QOL 1 year or more after treatment compared with age-matched controls. Negative QOL impact appears to be greater for younger patients undergoing EG than for ET. [source]

    Ecohydrology of a semi-arid forest: partitioning among water balance components and its implications for predicted precipitation changes

    ECOHYDROLOGY, Issue 2 2010
    Naama Raz Yaseef
    Abstract The distribution of precipitation inputs into different hydrological components of water-limited forest ecosystems determines water availability to trees and consequently forest productivity. We constructed a complete hydrological budget of a semi-arid pine forest (285 mm annual precipitation) by directly measuring its main components: precipitation (P), soil water content, evapotranspiration (ET, eddy covariance), tree transpiration (sap flux), soil evaporation (soil chambers), and intercepted precipitation (calculated). Our results indicated that on average for the 4-year study period, ET accounted for 94% of P, varying between 100% when P < 250 mm and 85% when P > 300 mm (with indications for losses to subsurface flow and soil moisture storage in wetter years). Direct measurements of the components of the ET flux demonstrated that both transpiration and soil evaporation were significant in this dry forest (45% and 36% of ET, respectively). Comparison between ecosystem ET (eddy covariance measurements) and the sum of its measured components showed good agreement on annual scales, but up to 30% discrepancies (in both directions) on shorter timescales. The pulsed storm pattern, characteristics of semi-arid climates, was sufficient to maintain the topsoil layer wet during the whole wet season. Only less often and intensive storms resulted in infiltration to the root zone, increasing water availability for uptake by deeper roots. Our results indicate that climate change predictions that link reduced precipitation with increased storm intensity may have a smaller effect on water availability to forest ecosystems than reduced precipitation alone, which could help forests' survival and maintain productivity even under drier conditions. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Comparison of soil moisture and meteorological controls on pine and spruce transpiration

    ECOHYDROLOGY, Issue 3 2008
    Eric E. Small
    Abstract Transpiration is an important component of the water balance in the high elevation headwaters of semi-arid drainage basins. We compare the importance of soil moisture and meteorological controls on transpiration and quantify how these controls are different at a ponderosa pine site and a spruce site in the Jemez river drainage basin of northern New Mexico, a sub-basin of the Rio Grande. If only soil moisture controls fluctuations in transpiration, then simple hydrologic models focussed only on soil moisture limitations are reasonable for water balance studies. If meteorological controls are also critical, then more complex models are required. We measured volumetric water content in the soil and sap velocity, and assumed that transpiration is proportional to sap velocity. Ponderosa sap velocity varies with root zone soil moisture. Nearly all of the scatter in the ponderosa sap velocity,soil moisture relationship can be predicted using a simple model of potential evapotranspiration (ET), which depends only on measured incident radiation and air temperature. Therefore, simple hydrologic models of ponderosa pine transpiration are warranted. In contrast, spruce sap velocity does not clearly covary with soil moisture. Including variations in potential evapotranspiration does not clarify the relationship between sap velocity and soil moisture. Likewise, variations in radiation, air temperature, and vapour pressure do not explain the observed fluctuations in sap velocity, at least according to the standard models and parameters for meteorological restrictions on transpiration. Both the simple and more complex models commonly used to predict transpiration are not adequate to model the water balance in the spruce forest studied here. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    An Evaluation of a Blind Rotational Technique for Selective Mainstem Intubation

    Aaron E. Bair MD
    Abstract Objectives: Although rare, massive hemoptysis and major bronchial disruptions are associated with high mortality. Selective ventilation of the uninvolved lung can increase the likelihood of survival. Specialized devices used for single lung ventilation are often not readily available and can be difficult to place in the emergency department. The authors evaluated a blind rotational technique for selective mainstem intubation using either a standard endotracheal tube (ET) or a directional-tip endotracheal tube (DTET). Methods: This was a prospective, randomized trial on 25 human cadavers. The desired side of mainstem intubation was determined by randomization. Each cadaver was used for four ET, four DTET, and four control intubations. In the ET group, the trachea was intubated. The tube was then rotated 90° in the direction of the desired placement and advanced until resistance was met. In the DTET group, the technique was identical, except the trigger was activated to flex the tip during advancement. In the control group, an ET was advanced in neutral alignment until resistance was met. A bronchoscopist blinded to the desired placement determined tube position. Comparison testing was performed using Pearson's chi-square test. Results: When attempting to intubate the left mainstem, use of the ET with the rotational technique was successful 72.3% of the time (95% confidence interval [95% CI] = 57% to 84%). Intubation of the left mainstem using the DTET was successful 68.5% of the time (95% CI = 54% to 81%; p = 0.67). Attempts to selectively intubate the right mainstem using the rotational technique were highly successful in both groups: 94% for the ET (95% CI = 84% to 99%) versus 97.8% for the DTET (95% CI = 89% to 100%). Among controls, the right mainstem was intubated 93% of the time (95% CI = 86% to 97%). Conclusions: In a cadaveric model, the left mainstem bronchus can be selectively intubated with moderate reliability using this rotational technique. Use of a DTET confers no significant advantage. The ability to generalize these findings to living subjects is unknown. [source]

    Use of a Voltammetric Electronic Tongue for Detection and Classification of Nerve Agent Mimics

    ELECTROANALYSIS, Issue 14 2010
    Inmaculada Campos
    Abstract An electronic tongue (ET) based on pulse voltammetry has been used to predict the presence of nerve agent mimics in aqueous environments. The electronic tongue array consists of eight working electrodes (Au, Pt, Ir, Rh, Cu, Co, Ni and Ag) encapsulated on a stainless steel cylinder. Studies including principal component analysis (PCA), artificial neural networks (fuzzy ARTMAP) and partial least square techniques (PLS) have been applied for data management and prediction models. For instance the electronic tongue is able to discriminate the presence of the nerve agent simulants diethyl chlorophosphate (DCP) and diethyl cyanophosphate (DCNP) from the presence of other organophosphorous derivatives in water. Finally, PLS data analysis using a system of 3 compounds and 3 concentration levels shows a good accuracy in concentration prediction for DCP and DCNP in aqueous environments. [source]

    Gold Nanoparticle-Based Mediatorless Biosensor Prepared on Microporous Electrode

    ELECTROANALYSIS, Issue 3 2006
    Fenghua Zhang
    Abstract A mediatorless biosensor was fabricated with a double-sided microporous gold electrode by successively immobilizing a mixed self-assembled monolayer (SAM) comprising carboxylic-acid- and thiol-terminated thiolate (dl -thiorphan and 1,8-octanedithiol), glucose oxidase (GOx) and finally gold nanoparticle (Au NP) on one working side. The double-sided microporous gold electrodes were formed by plasma sputtering of gold on a porous nylon substrate, yielding a face-to-face type two-electrode electrochemical cell. While the straight chain molecule 1,8-octanedithiol forms a dense insulating monolayer, the side armed dl -thiorphan forms a low density layer for the diffusion of redox couples to the electrode surface. The mixed SAM not only provided the linking functional groups for both enzyme and Au NP but also resulted in the appropriately spaced monolayer for direct electron tansfer (ET) process from the center of the redox enzyme to the electrode surface. After covalently immobilizing GOx onto the carboxylic-acid-terminated monolayer, Au NP was easily immobilized to both enzyme and nearby thiols by simple dispensing of the colloidal gold solution. It was observed that the resulting amperometric biosensor exhibited quantitatively the same response to glucose in the presence and in the absence of dissolved oxygen, which evidence that the Au NPs immobilized on and around the GOx promote direct ET from the enzymes to the electrode, assuming the role of a common redox mediator. [source]

    Electrohydrodynamic-mediated dielectrophoretic separation and transport based on asymmetric electrode pairs

    ELECTROPHORESIS, Issue 24 2008
    E. Du
    Abstract This paper presents a system for continuous separation and transport of micron and submicron particles in fluidic environment based on dielectrophoretic fractionation in concert with AC electrothermal (AC ET)-induced fluidic pumping action. In this system, high frequency AC signals are used to energize asymmetric electrode pairs. AC ET-driven fluidic pumping is utilized as an alternative to the commonly used external pressure-driven fluid flow. Distinct collection sites for negative-dielectrophoretic and positive-dielectrophoretic particle populations are identified. The coupling effects of dielectrophoretic force and viscous drag from AC ET fluid flow on particle motions are investigated theoretically and numerically. We demonstrate that these two forces can be efficiently coupled to achieve continuous separation and transport of particle mixture in a fluidic medium when the dielectric properties of the particles and the fluidic environment are different. The combination of dielectrophoretic separation and AC ET pumping function provides a promising approach to further miniaturize and integrate these mechanisms into lab-on-chip devices. [source]

    Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a selective ETA receptor antagonist

    Summary Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ETA receptors. Pulmonary and systemic haemodynamic responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET-1 (0.1, 0.2 and 0.4 ,g/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respectively. The effect of ET-1 on PAP and CAP was rapid and transient for PAP (,10 min) but prolonged for CAP (up to 60 min). ET-1 significantly decreased cardiac output by up to 35% and significantly increased systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 ,g/kg bwt ET-1. Infusion of a selective ETA receptor antagonist (TBC11251) completely inhibited the responses to a subsequent bolus of 0.2 ,g/kg bwt ET-1. We conclude that exogenous ET-1 exerts a potent vasoconstrictive action on the pulmonary and systemic circulations of the horse. These effects appear to be mediated largely through ETA receptors in both circulations. Endothelin may play a role in hypertensive conditions in the horse. [source]

    The science of endothelin-1 and endothelin receptor antagonists in the management of pulmonary arterial hypertension: current understanding and future studies

    N. J. Davie
    Abstract Pathological vascular remodelling is a key contributor to the symptomatology of pulmonary arterial hypertension (PAH), and reversing this process may offer the best hope for improving this debilitating condition. The vascular remodelling process is believed to be due to endothelial cell dysfunction and to involve altered production of endothelial cell-derived vasoactive mediators. The observation that circulating plasma levels of the vasoactive peptide endothelin (ET)-1 are raised in patients with PAH, and that ET-1 production is increased in the pulmonary tissue of affected individuals, makes it a particularly interesting target for a therapeutic intervention in PAH. Clinical trials with ET receptor antagonists (ETRAs) show that they provide symptomatic benefit in patients with PAH, thereby proving the clinical relevance of the ET system as a therapeutic target. In this paper, we review the role of ET-1 together with the available data on the roles of the specific ET receptors and ETRAs in PAH. In particular, we discuss the possible role of ET receptor selectivity in the vascular remodelling process in PAH and whether selective ETA or nonselective ETA/ETB blockade offers the greatest potential to improve symptoms and alter the clinical course of the disease. [source]

    Endothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidence

    W. Neuhofer
    Abstract Endothelin (ET) is a potent vasoconstrictory peptide with proinflammatory and profibrotic properties that exerts its biological effects through two pharmacologically distinct receptor subtypes, namely ETA and ETB. In addition to its substantial contribution to normal renal function, a large body of evidence suggests that derangement of the renal ET system is involved in the initiation and progression of chronic kidney disease (CKD) in diabetes, hypertension and glomerulonephritis. Thus, the use of ET receptor antagonists (ERAs) may offer potential novel treatment strategies in CKD. Recent literature on the role of the renal ET system in the healthy kidney was reviewed. In addition, an unbiased PubMed search was performed for studies published during the last 5 years that addressed the effects of ERAs in CKD. A particular objective was to extract information regarding whether selective or nonselective ERAs may have therapeutic potential in humans. ET-1 acts primarily as an autocrine or paracrine factor in the kidney. In normal physiology, ET-1 promotes diuresis and natriuresis by local production and action through ETB receptors in the renal medulla. In pathology, ET-1 mediates vasoconstriction, mesangial-cell proliferation, extracellular matrix production and inflammation, effects that are primarily conveyed by ETA receptors. Results obtained in animal models and in humans with the use of ERAs in CKD are encouraging; nevertheless, it is still under debate which receptor subtype should be targeted. According to most studies, selective inhibition of ETA receptors appears superior compared with nonselective ERAs because this approach does not interfere with the natriuretic, antihypertensive and ET clearance effects of ETB receptors. Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials. [source]

    Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis C

    W. Grander
    Abstract Pulmonary arterial hypertension (PAH) with coexisting portal hypertension has been defined as portopulmonary hypertension (PPHTN). It is often related to liver cirrhosis of various aetiologies and is associated with a high mortality rate. Endothelin-1 (ET) is supposed to play an important role in the pathogenesis of PAH as well as portal hypertension. Therefore, therapy with an ETA/ETB receptor antagonist might be of use in the treatment of PPHTN. We report the case of a 76-year-old male with liver cirrhosis owing to chronic hepatitis C virus infection and PPHTN who was treated with the dual ETA/ETB receptor antagonist bosentan. The patient showed remarkable improvement of 6-min walking distance from 300 to 480 m after 2 weeks and to 540 m after 14 weeks, respectively. In addition, a significant decline of N-terminal pro B-type natriuretic peptide fraction (NT-proBNP) from 4928 ng mL,1 to 640 ng mL,1 was observed. Bosentan might be a promising new therapeutical option for patients suffering from PPHTN. [source]

    Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype,phenotype associations

    Domenica Caramazza
    Abstract Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype,phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL -negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12,1q32 in PV, 1q21,32,1q32,44 in post-PV MF or PMF), deletions (e.g. 1p13,36,pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21,25;p21.3,23), and other partner chromosomes involving 1q10/1p11 and 1q21,25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21,1q32 and 1p11,13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. [source]

    Cytogenetic abnormalities in essential thrombocythemia: prevalence and prognostic significance

    Naseema Gangat
    Abstract Objectives:, In the current study we describe cytogenetic findings as well as clinical correlates and long-term prognostic relevance of abnormal cytogenetics at the time of diagnosis of essential thrombocythemia (ET). Patients and methods:, The study cohort consisted of a consecutive group of patients with ET who fulfilled the World Health Organization diagnostic criteria, and in whom cytogenetic analysis was performed at diagnosis. Results:, A total of 402 patients were studied (median age, 56 yrs; median follow-up 70 months). The prevalence of abnormal cytogenetics at diagnosis was 7% (28 of 402). The most common cytogenetic anomalies were trisomy 9 (four patients), abnormal chromosome 1 (three patients) and trisomy 8 (two patients). Parameters at diagnosis that were significantly associated with abnormal cytogenetics included palpable splenomegaly (P = 0.03), current tobacco use (P = 0.04); venous thrombosis (P = 0.02), and anemia with a hemoglobin of <10 g/dL (P = 0.02); but did not include JAK2V617F mutation status, or advanced age. During follow up, patients with abnormal cytogenetics did not have shorter survival, or increased transformation to acute leukemia or myelofibrosis. Conclusion:, Cytogenetic anomalies at diagnosis are relatively uncommon in ET, and do not predict evolution into more aggressive myeloid disorders, or inferior survival. [source]

    Transcription factor Fli-1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation

    Oliver Bock
    Abstract:,Objectives:,Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph, CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. Methods:,Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph, CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. Results:,Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph, CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph, CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph, CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. Conclusion:,Fli-1 is rather constitutively expressed by bone marrow cells in Ph, CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph, CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded. [source]

    Acute myeloid leukaemia arising from a patient with untreated essential thrombocythaemia

    Javier Bolańos-Meade
    Abstract:, Acute myeloid leukaemia (AML) is an uncommon complication of patients with essential thrombocythaemia (ET). We report a patient with ET which progressed into AML and who had only received a few days of therapy with hydroxyurea (HU) when diagnosed with ET. This is extremely rare, as in large series no patients who were left untreated for their ET developed this complication. This case supports the theory that AML transformation can be part of the natural history of ET in some cases. [source]

    A single institutional experience with 43 pregnancies in essential thrombocythemia

    Curtis A. Wright
    Abstract: Objectives: We describe the periconception circumstances and outcome of 43 consecutive pregnancies in an unselected group of young women with essential thrombocythemia (ET). Patients and methods: We retrospectively studied 74 consecutive cases of young women with ET seen at our institution, among whom 43 pregnancies occurred in 20 patients. Results: Of the 43 pregnancies, 22 (51%) were successful (21 term and 1 preterm live births) and 21 (49%) ended in miscarriages (1 ectopic pregnancy, 2 elective abortions, 16 first-trimester spontaneous abortions, 1 stillbirth at 22 wk, and 1 abruptio placentae at 33 wk). Management of ET at the time of conception included either no specific therapy (16 cases) or the use of aspirin alone (24 cases), a cytoreductive agent (2 cases), or heparin (1 case). There were no significant differences with respect to platelet count or the effect of treatment with aspirin, either at the time of conception or during the first trimester, among cases of successful pregnancies (22), all miscarriages (21), or first-trimester spontaneous abortions (16). The findings were similar when the analysis was restricted to only first-time pregnancies. In patients with multiple pregnancies, the outcome of a subsequent pregnancy was not predicted by the outcome of the first. In general, in successful cases the last two trimesters were mostly uneventful, with healthy offspring being reported in all cases. Conclusions: Pregnant patients with ET have an increased risk of first-trimester abortion which is not predictable by preconception platelet count or aspirin therapy. In addition, our experience does not support the use of prophylactic platelet apheresis during delivery. [source]

    Orbital Splitting and Pairing Energy in Open-Shell Organometallics: A Study of Two Families of 16-Electron Complexes [Cp2M] (M = Cr, Mo, W) and [CpM(PH3)] (M = Co, Rh, Ir)

    Rinaldo Poli
    Abstract The singlet,triplet gap for two families of 16-electron organometallic complexes has been examined in detail by DFT calculations at the B3LYP level with polarized basis sets on both metal and ligands. For the first family, the group 6 metallocenes (Cp2M with Cp = ,5 -C5H5 and M = Cr, Mo, W), the singlet,triplet gap (ES , ET) is always positive and decreases continuously on going from Cr to Mo to W. For the family of group 9 CpM(PH3), on the other hand, there is a decrease on going from Co to Rh, followed by a slight increase on going further to Ir. These trends have been analyzed in qualitative monoelectronic terms as a function of the competition between the pairing energy and the orbital gap. While the pairing energy decreases as expected in the order 3d >> 4d > 5d, the orbital gap varies in a different way for the two families and, though quantitatively less important, is responsible for the different trends. It is argued that changes in orbital gap are system-dependent for open-shell organometallic systems, thus it is not possible to establish a universal trend of singlet,triplet gaps for a homologous series of complexes with a group of transition metals. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

    Paraoxonase 1 (PON1) polymorphisms and risk for essential tremor

    E. García-Martín
    Background:, The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3), plays a major role in the metabolism of organophosphorus compounds. We investigated the possible association between the PON1 genotype and allelic variants of the polymorphisms Leu55Met and Glu192Arg, and the risk for essential tremor (ET). Methods:, We studied the frequency of the PON1 genotypes and allelic variants in 201 patients with ET and 220 healthy controls using a PCR-RLFP method. Results:, The frequencies of the PON1 genotypes and allelic variants of the polymorphisms Leu55Met and Gln192Arg did not differ significantly between patients with ET and controls. These polymorphisms were unrelated with the age of onset of ET. Conclusions:,PON1 polymorphisms are not related with the risk for ET. [source]

    How are we doing with the treatment of essential tremor (ET)?

    Persistence of patients with ET on medication: data from 528 patients in three settings
    Background:, The pharmacological treatment of essential tremor (ET) is not optimal. There are only two first-line medications and troublesome side effects are common. It is not uncommon for patients to simply stop taking medication. Yet, no published data substantiate or quantify this anecdotal impression. Objectives:, To determine, amongst patients with ET who were prescribed medication for tremor, what proportion are still taking medication and what proportion have stopped? Methods:, Five hundred and twenty-eight patients with ET from three distinct study settings (clinical, brain donors, population) were interviewed. Results:, A clear pattern that emerged across settings was that the proportion of patients with ET who had stopped medication was sizable and consistently similar (nearly one-third): 31.4% (clinical), 24.3% (brain donors), 30.0% (population), 29.8% (overall). A similarly high proportion of cases with severe tremor had stopped their medication: 31.9% (clinical), 36.4% (brain donors). For the four most commonly used medications (propranolol, primidone, diazepam, topiramate), one-half or more of the treated patients had stopped the medication; amongst the less commonly used medications, the proportion who stopped was even higher. Conclusions:, Nearly one of every three patients with ET who had been prescribed medication for tremor had discontinued pharmacotherapy. Even more revealing was that a similar proportion of cases with severe tremor had stopped medication. These data make tangibly evident that there is a sizable population of patients with ET who are untreated and disabled, and underscore the inadequacy of current pharmacotherapeutic options for this common neurological disease. [source]

    DRD3 Ser9Gly variant is not associated with essential tremor in a series of Italian patients

    C. Vitale
    Background: Essential tremor (ET) is the most common movement disorder worldwide. Three susceptibility loci on chromosomes 3q13, 2p24.1, and 6p23 have been reported, but no causative genes were found. The Ser9Gly variant of dopamine D3 receptor (DRD3) receptor was found associated to ET in a French and US population. Methods: A case,control study to evaluate the association between the Ser9Gly variant and ET was performed in a cohort of 116 Italian patients with familial ET and in 158 normal controls. Results: No significant difference in allele and genotype frequencies was found between the two groups. Conclusions: These results do not support an association between DRD3 Ser9Gly and susceptibility to ET in Italian patients. [source]

    Reductive Coupling of Aromatic Aldehydes Promoted by an Aqueous TiCl3/tBuOOH System in Alcoholic Cosolvents

    Angelo Clerici
    Abstract The tert -butoxyl radical, generated by the aqueous TiIII/TBHP system, abstracts an H atom from alcoholic cosolvents (EtOH, iPrOH), leading to ,-hydroxyalkyl radicals thatreduce aromatic aldehydes to the corresponding 1,2-diols. The reactivities observed are explained by resonance stabilization of the ,-hydroxybenzyl radicals formed in the electron-transfer (ET) process. Good Hammett-type correlations are obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

    Exercise training attenuates ageing-induced BKCa channel downregulation in rat coronary arteries

    Sulayma Albarwani
    Physical inactivity and ageing are widely recognized as risk factors for development of coronary artery disease. One of the characteristic changes that occurs in aged coronary artery is downregulation of their large-conductance voltage- and calcium-activated K+ (BKCa) channels. In this study, we investigated the effects of moderate exercise training (ET) on the activity of BKCa channels in coronary arteries of aged rats. Old Fischer 344 rats (23,26 months old) were randomly assigned to sedentary (O-SED, n= 24) or exercise-trained groups (O-ET, n= 28). The O-ET rats underwent a progressive treadmill exercise-training programme for 60 min day,1, 5 days week,1 for 12 weeks. Young animals were used for comparison. Coronary arteries were mounted on a wire myograph, and contractions in response to 1, 10, 30, 50 and 100 nmol l,1 iberiotoxin were compared. Iberiotoxin (100 nmol l,1) contracted coronary arteries of young, O-SED and O-ET rats by 115 ± 14, 36 ± 5.6 and 61 ± 5% of 5-hydroxytryptamine-induced contractions, respectively. Patch-clamp studies revealed a larger magnitude of BKCa current in young (104 ± 15.6 pA pF,1) compared with O-ET (44 ± 9 pA pF,1) and least in O-SED coronary smooth muscle cells (8.6 ± 2 pA pF,1). Western immunoblotting was performed to study expression levels of BKCa channel proteins. The , and ,1 subunits of the BKCa channel were reduced by 40 ± 3.5 and 30 ± 2.6%, respectively, in coronary arteries of old compared with young rats, and ET attenuated this reduction in expression level to 28 ± 2 and 12 ± 4%, respectively. Our results showed that ageing was associated with a reduction in BKCa channels, and ET partly reversed this reduction. We conclude that low-intensity ET may be beneficial in restoring age-related decline in coronary vasodilatory properties mediated by BKCa channels. [source]

    Isolation and structural characterization of the Ndh complex from mesophyll and bundle sheath chloroplasts of Zea mays

    FEBS JOURNAL, Issue 11 2005
    Costel C. Darie
    Complex I (NADH: ubiquinone oxidoreductase) is the first complex in the respiratory electron transport chain. Homologs of this complex exist in bacteria, mitochondria and chloroplasts. The minimal complex I from mitochondria and bacteria contains 14 different subunits grouped into three modules: membrane, connecting, and soluble subcomplexes. The complex I homolog (NADH dehydrogenase or Ndh complex) from chloroplasts from higher plants contains genes for two out of three modules: the membrane and connecting subcomplexes. However, there is not much information about the existence of the soluble subcomplex (which is the electron input device in bacterial complex I) in the composition of the Ndh complex. Furthermore, there are contrasting reports regarding the subunit composition of the Ndh complex and its molecular mass. By using blue native (BN)/PAGE and Tricine/PAGE or colorless-native (CN)/PAGE, BN/PAGE and Tricine/PAGE, combined with mass spectrometry, we attempted to obtain more information about the plastidal Ndh complex from maize (Zea mays). Using antibodies, we detected the expression of a new ndh gene (ndhE) in mesophyll (MS) and bundle sheath (BS) chloroplasts and in ethioplasts (ET). We determined the molecular mass of the Ndh complex (550 kDa) and observed that it splits into a 300 kDa membrane subcomplex (containing NdhE) and a 250 kDa subcomplex (containing NdhH, -J and -K). The Ndh complex forms dimers at 1000,1100 kDa in both MS and BS chloroplasts. Native/PAGE of the MS and BS chloroplasts allowed us to determine that the Ndh complex contains at least 14 different subunits. The native gel electrophoresis, western blotting and mass spectrometry allowed us to identify five of the Ndh subunits. We also provide a method that allows the purification of large amounts of Ndh complex for further structural, as well as functional studies. [source]

    The influence of temperature and osmolyte on the catalytic cycle of cytochrome c oxidase

    FEBS JOURNAL, Issue 2 2003
    Jack A. Kornblatt
    The influence of temperature on cytochrome c oxidase (CCO) catalytic activity was studied in the temperature range 240,308 K. Temperatures below 273 K required the inclusion of the osmolyte ethylene glycol. For steady-state activity between 278 and 308 K the activation energy was 12 kcal·mol,1; the molecular activity or turnover number was 12 s,1 at 280 K in the absence of ethylene glycol. CCO activity was studied between 240 and 277 K in the presence of ethylene glycol. The activation energy was 30 kcal·mol,1; the molecular activity was 1 s,1 at 280 K. Ethylene glycol inhibits CCO by lowering the activity of water. The rate limitation in electron transfer (ET) was not associated with ET into the CCO as cytochrome a was predominantly reduced in the aerobic steady state. The activity of CCO in flash-induced oxidation experiments was studied in the low temperature range in the presence of ethylene glycol. Flash photolysis of the reduced CO complex in the presence of oxygen resulted in three discernable processes. At 273 K the rate constants were 1500 s,1, 150 s,1 and 30 s,1 and these dropped to 220 s,1, 27 s,1 and 3 s,1 at 240 K. The activation energies were 5 kcal·mol,1, 7 kcal·mol,1, and 8 kcal·mol,1, respectively. The fastest rate we ascribe to the oxidation of cytochrome a3, the intermediate rate to cytochrome a oxidation and the slowest rate to the re-reduction of cytochrome a followed by its oxidation. There are two comparisons that are important: (a) with vs. without ethylene glycol and (b) steady state vs. flash-induced oxidation. When one makes these two comparisons it is clear that the CCO only senses the presence of osmolyte during the reductive portion of the catalytic cycle. In the present work that would mean after a flash-induced oxidation and the start of the next reduction/oxidation cycle. [source]

    C3,C4 composition and prior carbon dioxide treatment regulate the response of grassland carbon and water fluxes to carbon dioxide

    FUNCTIONAL ECOLOGY, Issue 1 2007
    H. W. POLLEY
    Summary 1Plants usually respond to carbon dioxide (CO2) enrichment by increasing photosynthesis and reducing transpiration, but these initial responses to CO2 may not be sustained. 2During May, July and October 2000, we measured the effects of temporarily increasing or decreasing CO2 concentration by 150,200 µmol mol,1 on daytime net ecosystem CO2 exchange (NEE) and water flux (evapotranspiration, ET) of C3,C4 grassland in central Texas, USA that had been exposed for three growing seasons to a CO2 gradient from 200 to 560 µmol mol,1. Grassland grown at subambient CO2 (< 365 µmol mol,1) was exposed for 2 days to an elevated CO2 gradient (> 365 µmol mol,1). Grassland grown at elevated CO2 was exposed for 2 days to a subambient gradient. Our objective was to determine whether growth CO2 affected the amount by which grassland NEE and ET responded to CO2 switching (sensitivity to CO2). 3The NEE per unit of leaf area was greater (16,20%) and ET was smaller (9,20%), on average, at the higher CO2 concentration during CO2 switching in May and July. The amount by which NEE increased at the higher CO2 level was smaller at elevated than subambient growth concentrations on both dates, but relationships between NEE response and growth CO2 were weak. Conversely, the effect of temporary CO2 change on ET did not depend on growth CO2. 4The ratio of NEE at high CO2 to NEE at low CO2 during CO2 change in July increased from 1·0 to 1·26 as the contribution of C3 cover to total cover increased from 26% to 96%. Conversely, in May, temporary CO2 enrichment reduced ET more in C4 - than C3 -dominated grassland. 5For this mesic grassland, sensitivity of NEE and ET to brief change in CO2 depended as much on the C3,C4 composition of vegetation as on physiological adjustments related to prior CO2 exposure. [source]