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Kinds of pH Terms modified by pH Selected AbstractsGreater Prevalence and Incidence of Dementia in Older Veterans with Posttraumatic Stress DisorderJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2010[See editorial comments by Dr. Soo Borson, pp 1797-1798] OBJECTIVES: To explore the association between posttraumatic stress disorder (PTSD) and dementia in older veterans. DESIGN: Administrative database study of individuals seen within one regional division of the Veterans Affairs healthcare network. SETTING: Veterans Integrated Service Network 16. PARTICIPANTS: Veterans aged 65 and older who had a diagnosis of PTSD or who were recipients of a Purple Heart (PH) and a comparison group of the same age with no PTSD diagnosis or PH were divided into four groups: those with PTSD and no PH (PTSD+/PH,, n=3,660), those with PH and no PTSD (PTSD,/PH+, n=1,503), those with PTSD and a PH (PTSD+/PH+, n=153), and those without PTSD or a PH (PTSD,/PH,, n=5,165). MEASUREMENTS: Incidence and prevalence of dementia after controlling for confounding factors in multivariate logistic regression. RESULTS: The PTSD+/PH, group had a significantly higher incidence and prevalence of dementia than the groups without PTSD with or without a PH. The prevalence and incidence of a dementia diagnosis remained two times as high in the PTSD+/PH, group as in the PTSD,/PH+ or PTSD,/PH, group after adjusting for the confounding factors. There were no statistically significant differences between the other groups. CONCLUSION: The incidence and prevalence of dementia is greater in veterans with PTSD. It is unclear whether this is due to a common risk factor underlying PTSD and dementia or to PTSD being a risk factor for dementia. Regardless, this study suggests that veterans with PTSD should be screened more closely for dementia. Because PTSD is so common in veterans, this association has important implications for veteran care. [source] Novel hepatic progenitor cell surface markers in the adult rat liver,HEPATOLOGY, Issue 1 2007Mladen I. Yovchev Hepatic progenitor/oval cells appear in injured livers when hepatocyte proliferation is impaired. These cells can differentiate into hepatocytes and cholangiocytes and could be useful for cell and gene therapy applications. In this work, we studied progenitor/oval cell surface markers in the liver of rats subjected to 2-acetylaminofluorene treatment followed by partial hepatectomy (2-AAF/PH) by using rat genome 230 2.0 Array chips and subsequent RT-PCR, immunofluorescent (IF), immunohistochemical (IHC) and in situ hybridization (ISH) analyses. We also studied expression of the identified novel cell surface markers in fetal rat liver progenitor cells and FAO-1 hepatoma cells. Novel cell surface markers in adult progenitor cells included tight junction proteins, integrins, cadherins, cell adhesion molecules, receptors, membrane channels and other transmembrane proteins. From the panel of 21 cell surface markers, 9 were overexpressed in fetal progenitor cells, 6 in FAO-1 cells and 6 are unique for the adult progenitors (CD133, claudin-7, cadherin 22, mucin-1, ros-1, Gabrp). The specificity of progenitor/oval cell surface markers was confirmed by ISH and double IF analyses. Moreover, study of progenitor cells purified with Ep-CAM antibodies from D-galactosamine injured rat liver, a noncarcinogenic model of progenitor cell activation, verified that progenitor cells expressed these markers. Conclusion: We identified novel cell surface markers specific for hepatic progenitor/oval cells, which offers powerful tool for their identification, isolation and studies of their physiology and pathophysiology. Our studies also reveal the mesenchymal/epithelial phenotype of these cells and the existence of species diversity in the hepatic progenitor cell identity. (HEPATOLOGY 2007;45:139,149.) [source] The role of p28GANK in rat oval cells activation and proliferationLIVER INTERNATIONAL, Issue 2 2006Yun-Feng Shan Abstract: Background: Human gankyrin gene product (p28GANK) is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma and also plays a role in cell cycle progression in normal hepatocytes and liver regeneration. However, little is known about the physiological role of p28GANK in the liver oval cell activation and proliferation. We investigated the possible involvement of p28GANK in oval cell-mediated liver regeneration and cell cycle progression. Methods: We examined the different p28GANK expression in 2-acetylaminofuorene/partial heptectomy (2-AAF/PH) rats, as a model of oval cell activation, and PH rats by Western blot and immunohistochemistry. Oval cells isolated from 2-AAF/PH rat model were cultured in our study. p28GANK expression was examined in the oval cells after mitogenic stimulation. Results: In 2-AAF/PH rats, p28GANK was expressed in the activated oval cells and located in the nucleus. p28GANK protein expression was increased in 2-AFF/PH rats after hepatectomy lasting for 96 h when retinoblastoma maintained hyperphosphorylation status at Ser-795. The isolated oval cells express AFP, OV6, CK19, CD34, CD45, c-kit and albumin. After epidermal growth factor stimulation, p28GANK protein was up-regulated in oval cells from 24 to 72 h, which coincided with increased expression of CyclinD1, CDK4 and decreased of Rb protein. Conclusions: p28GANK expression was increased in oval cell-mediated liver regeneration and oval cells after mitogenic stimulation. Thus, p28GANK may play a role in oval cell-mediated liver regeneration and liver oval cell cycle progression. [source] Solvent-free route to ,-enamino dichloromethyl ketones and application in the synthesis of novel 5-dichloromethyl-1H -pyrazolesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2009Marcos A. P. Martins An efficient procedure to prepare a series of five 4-amino-1,1-dichloro-3-penten-2-ones [CHCl2C(O)CHC(Me)NR1R2, where R1/R2 = H/Ph, H/Bn, H/CH2CH2OH, (CH2)4,(CH2)2O(CH2)2] from the solvent-free reaction of 1,1-dichloro-4-methoxy-3-penten-2-one with primary and secondary amines is reported. 1,1-Dichloro-4-methoxy-3-penten-2-one was reacted with hydrazine hydrochloride, phenylhydrazine hydrochloride and semicarbazide hydrochloride to obtain 5-dichloromethyl-3-methylpyrazoles. Aminoguanidine hydrochloride and 1,2-dimethylhydrazine dihydrochloride were also reacted with 1,1-dichloro-4-methoxy-3-penten-2-one to obtain 5-dichloromethyl-3-methylpyrazoline and 5-dichloromethyl-1,2,3-trimethyl pyrazolium chloride, respectively. All cyclocondensation reactions were performed in one-pot procedures. J. Heterocyclic Chem., (2009). [source] Downregulation of oxytocin receptors in right ventricle of rats with monocrotaline-induced pulmonary hypertensionACTA PHYSIOLOGICA, Issue 2 2010T. L. Broderick Abstract Aim:, Pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1,, IL-6 and tumour necrosis factor-, in the hypertrophied RV in a model of PH. Methods:, RV hypertrophy was induced in male Sprague,Dawley rats with monocrotaline (MCT; 60 mg kg,1) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. Results:, In the RV of MCT-treated rats, a ,40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1, and IL-6. Conclusion:, Our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1, and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH. [source] Identifying Left Ventricular Dysfunction in Pulmonary HypertensionCONGESTIVE HEART FAILURE, Issue 5 2009Navin Rajagopalan MD The significance of left ventricular (LV) dysfunction in patients with pulmonary hypertension (PH) is unknown. Our purpose was to quantify LV function in PH patients by measuring LV myocardial performance index (MPI) and correlating it with invasively determined hemodynamic variables. The authors prospectively measured LV MPI via transthoracic echocardiography in 50 patients with PH (53±11 years; 35 women) who also underwent right heart catheterization within 1 day of echocardiography. For comparative purposes, LV MPI was also measured in 15 healthy volunteers who served as controls. LV MPI was significantly increased in the PH group compared with controls (0.62±0.27 vs 0.36±0.08; P<.001), indicating worse LV dysfunction despite that LV ejection fraction was not significantly different between the groups (58%±4% vs 60%±3%). LV MPI demonstrated significant correlations with invasively determined mean pulmonary artery pressure (r=.50; P<.001), pulmonary vascular resistance (r=.57; P<.001), and cardiac index (r=,.64; P<.001). By receiver operating characteristic analysis, LV MPI >0.75 predicted cardiac index <2 L/min/m2 with 89% sensitivity and 78% specificity (area under the curve, 0.89). In a multivariate model, LV MPI was independently associated with cardiac index (P<.01). Patients with PH demonstrate abnormal LV function as quantified by elevated LV MPI, which correlates significantly with pulmonary vascular resistance and cardiac index. [source] Metacognition as a mediator of the effects of impairments in neurocognition on social function in schizophrenia spectrum disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010P. H. Lysaker Lysaker PH, Shea AM, Buck KD, Dimaggio G, Nicolò G, Procacci M, Salvatore G, Rand KL. Metacognition as a mediator of the effects of impairments in neurocognition on social function in schizophrenia spectrum disorders. Objective:, This study explored whether Mastery, a domain of metacognition that reflects the ability to use knowledge about mental states to respond to psychological challenges, mediated the effects of neurocognition on the frequency of social contact and persons' capacity for social relatedness. Method:, Participants were 102 adults with schizophrenia or schizoaffective disorder. Neurocognition was represented by a single factor score produced by a principal components analysis of a neurocognitive test battery. Mastery was assessed using the metacognitive assessment scale and social functioning by the quality of life scale. Results:, Using structural equation modeling, specifically measured-variable path analysis, a mediational model consisting of neurocognitive capacity linked to mastery and capacity for social relationships and mastery linked with frequency of social contact and capacity for social relatedness showed acceptable fit to the observed data. This persisted after controlling for negative and cognitive symptoms. Conclusion:, Results suggest that certain forms of metacognition mediate the influence of neurocognition upon function in schizophrenia. [source] Glucometabolic state of in-hospital primary hypertension patients with normal fasting blood glucose in a sub-population of ChinaDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Yang-Xin Chen Abstract Background There is a high prevalence of abnormal glucometabolism (AGM) in patients with coronary heart disease (CHD) and primary hypertension (PH). However, little is known about the glucometabolic state of PH patients with normal fasting blood glucose (FBG). Methods Oral glucose tolerance test (OGTT) was performed for 445 in-hospital PH patients with normal FBG and re-performed for those patients with impaired glucose tolerance (IGT) during the follow-up period. Results Diabetes mellitus (DM), IGT, and AGM (including IGT and DM) accounted for 4.4, 24.5, and 28.9% of patients, respectively. Prevalence of AGM in patients with higher haemoglobin A1c (HbA1c) (,6.0%), risk factors (CHD, overweight, hyperlipidaemia, proteinuria) was significantly higher than that in patients without these factors. Regression analysis showed that age, overweight, proteinuria, HbA1c, and CRP were the independent risk factors of AGM. Follow-up data in 98 IGT patients showed that no improvement of glucometabolism was found, but contrarily, a significant increase of new onset of impaired fasting glucose (IFG) and DM was found after 9 months (P < 0.05), even if diet control and moderate exercise were adopted. Conclusions AGM is prevalent and underestimated in PH patients with normal FBG, and it will develop even if therapeutic life-style changes are adopted. Except for FBG, more attention should be paid to postprandial blood glucose. OGTT should be a routine procedure for PH patients, especially in-hospital PH patients, regardless of normal FBG, and active drug intervention for IGT patients with PH may be recommended. Copyright © 2009 John Wiley & Sons, Ltd. [source] New Annular Tissue Doppler Markers of Pulmonary HypertensionECHOCARDIOGRAPHY, Issue 8 2010Angel López-Candales M.D., F.A.C.C., F.A.S.E. Background: Tissue Doppler imaging (TDI) of mitral (MA) and tricuspid annulus (TA) events characterizes systolic and diastolic properties of each respective ventricle. However, the effect of chronic pulmonary hypertension (cPH) on these TDI annular events has not been well described. Methods: Measurements of right ventricular (RV) performance with TDI of the lateral mitral and tricuspid annuli, to measure isovolumic contraction (IVC) and systolic (S) signals were recorded from 50 individuals without PH and from 50 patients with cPH. To avoid confounding variables, all patients had normal left ventricular ejection fraction and were in normal sinus rhythm at the time of the examination. Results: As expected, markers of RV systolic performance were markedly reduced while LV systolic function remained largely unaffected in cPH patients when compared to patients without PH. TDI interrogation of the MA revealed lengthening of the time interval between IVC and systolic signal (70 ± 17 msec) when compared to individuals without PH (43 ± 8 msec; P < 0.0001). In contrast, cPH markedly shortened the time interval between IVC and the TA systolic signal (34 ± 12 msec) when compared to individuals without PH (65 ± 17 msec; P < 0.0001). Conclusions: cPH lengthens time interval between the IVC and the MA systolic signal while shortening this same interval when the TA is interrogated with TDI; reflecting the potential influence that cPH exerts in biventricular performance. Whether measuring these intervals be routinely used in the follow-up of cPH patients will require further study. (Echocardiography 2010;27:969-976) [source] Noninvasive Estimation of Pulmonary Vascular Resistance in Pulmonary HypertensionECHOCARDIOGRAPHY, Issue 5 2009Navin Rajagopalan M.D. Background: Determination of pulmonary vascular resistance (PVR) in patients with suspected or known pulmonary hypertension (PH) requires right heart catheterization. Our purpose was to use Doppler echocardiography to estimate PVR in patients with PH. Methods: Patient population consisted of 52 patients (53 ± 12 years; 35 females) who underwent Doppler echocardiography and right heart catheterization within 24 hours of each other. The ratio of peak tricuspid regurgitation velocity (TRV) and right ventricular outflow time-velocity integral (VTIRVOT) was measured via transthoracic echocardiography and correlated to invasively determined PVR. A linear regression equation was generated to determine PVR by echocardiography based upon the TRV/VTIRVOT ratio. PVR by echocardiography was compared to invasive PVR using Bland-Altman analysis. Results: Significant correlation was demonstrated between TRV/VTIRVOT and PVR by catheterization (r = 0.73; P < 0.001). However, Bland-Altman analysis showed that agreement between PVR determined by echocardiography and invasive PVR was poor (bias = 0; standard deviation = 4.3 Wood units). In a subset of patients with invasive PVR < 8 Wood units (26 patients), correlation between TRV/VTIRVOT and invasive PVR was strong (r = 0.94; P < 0.001). In these patients, agreement between PVR by echocardiography and invasive PVR was satisfactory (bias = 0; standard deviation = 0.5 Wood units). There was no correlation between TRV/VTIRVOT and invasive PVR in patients with PVR > 8 Wood units (n = 26; r = 0.17). Conclusion: While TRV/VTIRVOT correlates significantly with PVR, using it to estimate PVR in a PH patient population cannot be recommended. [source] Association of Coronary Sinus Diameter with Pulmonary HypertensionECHOCARDIOGRAPHY, Issue 9 2008Yilmaz Gunes M.D. Background: Impaired venous drainage secondary to increased right atrial pressure (RAP) may result in coronary sinus (CS) dilatation.,Methods: Two hundred fifteen patients referred for transthoracic echocardiography were included in the study. CS diameters were measured from apical four-chamber view with the transducer being slightly tilted posteriorly to the level of the dorsum of the heart. Pulmonary artery systolic pressure (PASP) is estimated by measurement of tricuspid regurgitation velocity (v) and estimate RAP based on size and collapsibility of inferior vena cava (VCI) with the formula PASP: 4v2+RAP. Patients with PASP >35 mmHg were considered to have pulmonary hypertension (PH).,Results: CS diameter was measured in 80.3% of the patients with normal PASP (8.1 ± 2.4 mm) and 93.1% of the patients having PH (12.3 ± 2.5 mm). PASP was significantly correlated with CS diameter (r = 0.647, P < 0.001), RA volume index (r = 0.631, P < 0.001), RV volume index (r = 0.475, P < 0.001), VCI diameter (r = 0.365, P < 0.001), and left ventricular ejection fraction (LVEF) (r =,0.270, P < 0.001). CS diameter was also correlated significantly with estimated RAP (r = 0.557, P < 0.001), RA volume index (r = 0.520, P < 0.001), RV volume index (r = 0.386, P < 0.001), LVEF (r =,0.327, P < 0.001), and VCI diameter (r = 0.313, P < 0.001). Multivariate analyses, testing for independent predictive information of CS size, VCI diameter, RA and RV volume indexes, and estimated RAP for the presence of PH revealed that estimated RAP (beta = 0.465, P < 0.001) and CS size (beta = 0.402, P = 0.003) were the significant predictors.,Conclusions: Coronary sinus is dilated in patients with pulmonary hypertension. Coronary sinus diameter significantly correlates with PASP, RAP, right heart chamber volumes, LVEF, and VCI diameter. [source] Cardiovascular Regulation through Hypothalamic GABAA Receptors in a Genetic Absence Epilepsy Model in RatEPILEPSIA, Issue 2 2002Rezzan Gülhan Aker Summary: ,Purpose: ,-Aminobutyric acid (GABA) plays a vital role in both central cardiovascular homeostasis and pathogenesis of epilepsy. Epilepsy affects autonomic nervous system functions. In this study, we aimed to clarify the role of GABAA receptors in hypothalamic cardiovascular regulation in a genetically determined animal model of absence epilepsy. Methods: Nonepileptic Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) were instrumented with a guide cannula for drug injection and extradural electrodes for EEG recording. After a recovery period, iliac arterial catheters were inserted for direct measurement of mean arterial pressure and heart rate. Bicuculline, a GABAA -receptor antagonist, was injected into the dorsomedial (DMH) or posterior (PH) hypothalamic nuclei of nonepileptic control rats or GAERS. Blood pressure, heart rate, and EEG recordings were performed in conscious unrestrained animals. Results: Bicuculline injections into the hypothalamus produced increases in blood pressure and heart rate of both control rats and GAERS. The DMH group of GAERS showed a twofold increase in the blood pressure and the heart rate compared with those of control rats. Pressor responses to bicuculline, when microinjected into the PH, were similar in the nonepileptic animals and GAERS. Conversely, the amplitude of tachycardic responses to the administration of bicuculline into the PH was significantly higher in GAERS compared with those of control rats. Conclusions: The bicuculline-induced increases in blood pressure and heart rate were more prominent when given in the DMH of GAERS. These results indicate an increased GABAA receptor,mediated cardiovascular response through the DMH in conscious rats with absence epilepsy. [source] Expression of PI(4,5)P2 -binding proteins lowers the PI(4,5)P2 level and inhibits Fc,RIIA-mediated cell spreading and phagocytosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Ewelina Szyma Abstract We found that Fc,RII-mediated cell spreading and phagocytosis were correlated with an increase of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] level in cells. During the spreading, a long-lasting elevation of PI(4,5)P2 and concomitant actin polymerization occurred. Filopodia and lamellae of spreading cells were enriched in phosphatidylinositol 4-phosphate 5-kinase I, (PIP5-kinase I,) that colocalized with PI(4,5)P2 and actin filaments. Both spreading and phagocytosis were inhibited by expression of the C374,440 fragment of PIP5-kinase I, or the pleckstrin homology domain of phospholipase C,1 (PLC,1 -PH), two probes binding PI(4,5)P2. These probes reduced the amount of PI(4,5)P2 in the cells, evoked reorganization of the actin cytoskeleton and abolished PI(4,5)P2 elevation during phagocytosis. Simultaneously, PLC,1 -PH-GFP reduced the amount of PIP5-kinase I, associated with the plasma membrane. In vitro studies demonstrated that PIP5-kinase I,-GST bound PI(4,5)P2, phosphatidylinositol 4-monophosphate, and less efficiently, phosphatidic acid. The data suggest that the PLC,1 -PH domain, and possibly also the C374,440 fragment, when expressed in cells, can compete with endogenous PIP5-kinase I, for PI(4,5)P2 binding in the plasma membrane leading eventually to PI(4,5)P2 depletion. [source] Empathy and Strategic Interaction in Crises: A Poliheuristic PerspectiveFOREIGN POLICY ANALYSIS, Issue 2 2009Jonathan W. Keller Empirical evidence supports the poliheuristic (PH) theory of decision making, which states that leaders typically employ a two-stage non-compensatory decision-making process. In stage one leaders reject options that do not meet some minimum criteria of acceptability on one or more dimensions, and in stage two they choose among the remaining options using a more rational utility-maximizing rule. While PH theory has primarily been applied at the monadic level, to explain the process and content of states' decisions, we contend it has important implications for strategic interaction and can help to explain outcomes in world politics. Specifically, we argue that a crucial variable shaping crisis outcomes is the degree to which leaders' non compensatory decision criteria in stage one include options' acceptability to the opponent. When leaders empathize with their opponent and screen out those options the opponent considers unacceptable, crises will be resolved more quickly and with a lower likelihood of escalation. Empathy introduced during the second, utility-maximizing stage, may also dampen conflict but is less effective than stage one empathy. We illustrate this dyadic non compensatory model by examining two cases involving the U.S.,China and U.S.,Iraq bilateral relationships. [source] Poliheuristic Theory, Bargaining, and Crisis Decision MakingFOREIGN POLICY ANALYSIS, Issue 4 2007Min Ye In the past decade, the application of the Poliheuristic (PH) theory to foreign policy decisions of various types, by numerous leaders, and in association with different research methods, has demonstrated its theoretical merit in integrating the divided rational choice and psychological/cognitive approaches. This article argues for a complementary relationship between PH and formal theory. On the one hand, PH can provide a framework in which abstract formal models can be connected with specific domestic as well as international circumstances. On the other hand, formal theory sharpens the rational analysis used in the second conceptual stage of PH. In this study, I formulate a revised Rubinstein bargaining model with war as an outside option and apply it to Chinese crisis decision making during the Second and Fourth Taiwan Strait Crisis. In sum, this study makes three contributions to the literature on international crises and foreign policy analysis. First, it gives formal explanations on how PH can contribute to the game-theoretic approach in foreign policy analysis. Second, it presents what Bueno de Mesquita and Lalman (1992) called a "domestic politics version" of the canonical Rubinstein bargaining game, connecting international interactions with individual participants' domestic politics. Finally, it provides a way to test abstract game-theoretic models in particular domestic and international contexts of foreign policy making. [source] Chinese Choices: A Poliheuristic Analysis of Foreign Policy Crises, 1950,1996FOREIGN POLICY ANALYSIS, Issue 1 2005Patrick James This paper uses the Poliheuristic Theory (PH), developed by Mintz, which incorporates both psychological and rational choice components in a synthesis of these previously isolated approaches, to explain decision making in Chinese foreign policy crises. China is an interesting initial case for this project for two reasons. One is its importance as a permanent member of the UN Security Council and rising superpower. The other is China's reputation as a nearly unique "black box",an especially challenging case,with regard to decision making in foreign policy crises. Taken from the authoritative compilation of the International Crisis Behavior (ICB) Project, the nine cases (with available data) in which China is a crisis actor span the period from 1950 to 1996. A comparative analysis of Chinese decision making in times of crisis is used to test hypotheses derived from the PH. The hypotheses focus on how decisions are anticipated to occur over two stages. Principal expectations are that the non compensatory rule, which places priority on political considerations, will determine viable alternatives at the first stage, while choices more in line with expected value maximization or lexicographic ordering will characterize the second stage. [source] Effects of longitudinal variations in stream habitat structure on fish abundance: an analysis based on subunit-scale habitat classificationFRESHWATER BIOLOGY, Issue 9 2002Mikio Inoue SUMMARY 1.,Stream reaches contain assortments of various habitat types that can be defined at different spatial scales, such as channel unit (e.g. pools, riffles) and subunit (patches within channel units). We described longitudinal (upstream,downstream) patterns of stream habitat structure by considering subunits as structural elements, and examined their effects on the abundance of masu salmon (Oncorhynchus masou) and rosyface dace (Leuciscus ezoe) in a third-order tributary of the Teshio River in northern Hokkaido, Japan. 2.,Nine subunit types were determined on the basis of water depth, current velocity and substrate, using 0.5 × 0.5 m grids. Although both masu salmon and rosyface dace used pools as a major habitat, the former preferred a subunit type occurring at pool heads (PH subunit) while the latter preferred a slow-current edge type (SE-2 subunit). 3.,Along the course of the stream, slow-edge subunits (SE-1, 2 and 3) increased in frequency downstream while fast-edge subunits (FE-1 and 2) decreased, suggesting a downstream development of slow-current edges. Regression analyses indicated that longitudinal variation in masu salmon abundance was explained by the area of PH, rather than pools. Masu salmon density increased with the area of PH. Rosyface dace abundance was explained by a combination of water depth and the area of SE-2, both effects being positive. 4.,Longitudinal variations in the abundance of both species were related to the abundance of their preferred habitat at the subunit scale, rather than channel-unit scale. The results emphasise the importance of fine-scale patchiness when examining stream fish habitats. [source] Intraseasonal climate and habitat-specific variability controls the flowering phenology of high alpine plant speciesFUNCTIONAL ECOLOGY, Issue 2 2010Karl Hülber Summary 1. ,High alpine plants endure a cold climate with short growing seasons entailing severe consequences of an improper timing of development. Hence, their flowering phenology is expected to be rigorously controlled by climatic factors. 2. ,We studied ten alpine plant species from habitats with early and late melting snow cover for 2 years and compared the synchronizing effect of temperature sums (TS), time of snowmelt (SM) and photoperiod (PH) on their flowering phenology. Intraseasonal and habitat-specific variation in the impact of these factors was analysed by comparing predictions of time-to-event models using linear mixed-effects models. 3. ,Temperature was the overwhelming trigger of flowering phenology for all species. Its synchronizing effect was strongest at or shortly after flowering indicating the particular importance of phenological control of pollination. To some extent, this pattern masks the common trend of decreasing phenological responses to climatic changes from the beginning to the end of the growing season for lowland species. No carry-over effects were detected. 4. ,As expected, the impact of photoperiod was weaker for snowbed species than for species inhabiting sites with early melting snow cover, while for temperature the reverse pattern was observed. 5. ,Our findings provide strong evidence that alpine plants will respond quickly and directly to increasing temperature without considerable compensation due to photoperiodic control of phenology. [source] Metalloproteinase-9 in circulating monocytes in pulmonary hypertensionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2006Caroline Cantini-Salignac Abstract The role of matrix metalloproteinases (MMPs) in pulmonary hypertension (PH) is complex as MMPs are involved in both the vascular and cardiac remodelling associated with PH. To gain insight into this problem, monocytes were isolated from pulmonary arterial blood in patients suffering from PH, related to chronic obstructive pulmonary disease (n = 6), chronic pulmonary thromboembolism (n = 3) or pulmonary arterial hypertension (n = 8). The severity of PH was associated with decreases in cardiac index (CI) and mixed venous blood oxygen saturation (SO2), and an increase in right atrial pressure (). Monocyte pro-MMP-9 content (zymography) was positively correlated with SO2 (r = 0.73, P < 0.05) and CI (r = 0.66, P < 0.05), and negatively with (r = 0.54, P < 0.05); there was no significant correlation with pulmonary vascular resistance. In conclusion, the pro-MMP-9 content of circulating monocytes was lower in the more severe forms of PH which showed heart failure suggesting that such MMP enzymatic activity reflects heart failure following pulmonary vascular and myocardial remodelling in PH. [source] The phosphatidylinositol-3 kinase (PI3K)-Akt pathway suppresses neurite branch formation in NGF-treated PC12 cellsGENES TO CELLS, Issue 8 2003Maiko Higuchi Background:, Previous studies have shown that phosphatidylinositol-3 kinase (PI3K) plays an important role in NGF (nerve growth factor)-induced neurite elongation. However, the roles of the PI3K pathway in neurite branch formation were not fully understood. Also, it was not clear where the PI3K pathway is activated during branch formation. Results:, We found that the treatment of PC12 cells with the PI3K inhibitor LY294002 resulted in a marked increase in the number of neurite branch points, suggesting a suppressive role of PI3K in neurite branch formation. Expression of a constitutively active form of Akt, a downstream effector of PI3K, decreased the number of branch points, whereas that of a dominant-negative form of Akt increased it. In contrast, inhibition of neither Rac, mTOR nor GSK3, other effectors of PI3K, promoted branch formation. Importantly, the phosphorylated form of endogenous Akt was localized at the tips of growth cones, but devoid of small branches in NGF-treated PC12 cells. A GFP-fusion protein of the plekstrin-homology (PH) domain of Akt was also localized at the tips of growth cones. Conclusions:, The PI3K-Akt pathway thus plays a key role in suppression of neurite branch formation in NGF-treated PC12 cells. Summary figure, Figure Summary figure,. working model for the regulation of neuritogenesis in PC12 cells. PI3K may mediate NGF regulation of neuritogenesis via two pathways. Rac induces neurite elongation and branch formation. Akt induces neurite elongation, but prevents branch formation. [source] Cytosolic calcium regulates liver regeneration in the rat,HEPATOLOGY, Issue 2 2010Laura Lagoudakis Liver regeneration is regulated by growth factors, cytokines, and other endocrine and metabolic factors. Calcium is important for cell division, but its role in liver regeneration is not known. The purpose of this study was to understand the effects of cytosolic calcium signals in liver growth after partial hepatectomy (PH). The gene encoding the calcium-binding protein parvalbumin (PV) targeted to the cytosol using a nuclear export sequence (NES), and using a discosoma red fluorescent protein (DsR) marker, was transfected into rat livers by injecting it, in recombinant adenovirus (Ad), into the portal vein. We performed two-thirds PH 4 days after Ad-PV-NES-DsR or Ad-DsR injection, and liver regeneration was analyzed. Calcium signals were analyzed with fura-2-acetoxymethyl ester in hepatocytes isolated from Ad-infected rats and in Ad-infected Hela cells. Also, isolated hepatocytes were infected with Ad-DsR or Ad-PV-NES-DsR and assayed for bromodeoxyuridine incorporation. Ad-PV-NES-DsR injection resulted in PV expression in the hepatocyte cytosol. Agonist-induced cytosolic calcium oscillations were attenuated in both PV-NES,expressing Hela cells and hepatocytes, as compared to DsR-expressing cells. Bromodeoxyuridine incorporation (S phase), phosphorylated histone 3 immunostaining (mitosis), and liver mass restoration after PH were all significantly delayed in PV-NES rats. Reduced cyclin expression and retinoblastoma protein phosphorylation confirmed this observation. PV-NES rats exhibited reduced c-fos induction and delayed extracellular signal-regulated kinase 1/2 phosphorylation after PH. Finally, primary PV-NES,expressing hepatocytes exhibited less proliferation and agonist-induced cyclic adenosine monophosphate responsive element binding and extracellular signal-regulated kinase 1/2 phosphorylation, as compared with control cells. Conclusion: Cytosolic calcium signals promote liver regeneration by enhancing progression of hepatocytes through the cell cycle. (HEPATOLOGY 2010;) [source] MicroRNAs control hepatocyte proliferation during liver regeneration,HEPATOLOGY, Issue 5 2010Guisheng Song MicroRNAs (miRNAs) constitute a new class of regulators of gene expression. Among other actions, miRNAs have been shown to control cell proliferation in development and cancer. However, whether miRNAs regulate hepatocyte proliferation during liver regeneration is unknown. We addressed this question by performing 2/3 partial hepatectomy (2/3 PH) on mice with hepatocyte-specific inactivation of DiGeorge syndrome critical region gene 8 (DGCR8), an essential component of the miRNA processing pathway. Hepatocytes of these mice were miRNA-deficient and exhibited a delay in cell cycle progression involving the G1 to S phase transition. Examination of livers of wildtype mice after 2/3 PH revealed differential expression of a subset of miRNAs, notably an induction of miR-21 and repression of miR-378. We further discovered that miR-21 directly inhibits Btg2, a cell cycle inhibitor that prevents activation of forkhead box M1 (FoxM1), which is essential for DNA synthesis in hepatocytes after 2/3 PH. In addition, we found that miR-378 directly inhibits ornithine decarboxylase (Odc1), which is known to promote DNA synthesis in hepatocytes after 2/3 PH. Conclusion: Our results show that miRNAs are critical regulators of hepatocyte proliferation during liver regeneration. Because these miRNAs and target gene interactions are conserved, our findings may also be relevant to human liver regeneration. (HEPATOLOGY 2010) [source] Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn,HEPATOLOGY, Issue 3 2008Chun-Ping Cui Hepatic stimulating substance (HSS) was first isolated from weanling rat liver in 1975 and found to stimulate hepatic DNA synthesis both in vitro and in vivo. Since then, mammalian and human HSS have been investigated for their potential to treat hepatic diseases. However, the essential nature in composition and structure of HSS remain puzzling because HSS has not been completely purified. Heating, ethanol precipitation, and ion-exchange chromatographies had been carried out to isolate the protein with specific stimulating activity from newborn calf liver, and [3H]thymidine deoxyribose (TdR)/bromodeoxyuridine (BrdU) incorporation and carboxyfluorescein diacetate succinimidyl ester (CFSE)-based proliferation assay to determine the bioactivity in vitro and in vivo. We report the purification of a novel 30-kDa protein from a crude extract of calf liver HSS. This protein is a member of the leucine-rich acidic nuclear protein family (LANP) and has been named hepatopoietin Cn (HPPCn). Studies of partially hepatectomized (PH) mice show that levels of HPPCn messenger RNA (mRNA) increase after liver injury. Furthermore, the recombinant human protein (rhHPPCn) was shown to stimulate hepatic DNA synthesis and activate signaling pathways involved in hepatocyte proliferation in vitro and in vivo. Conclusion: HPPCn is a novel hepatic growth factor that plays a role in liver regeneration. (HEPATOLOGY 2008;47:986,995.) [source] Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOPHEPATOLOGY, Issue 4 2004Giovanna M. Ledda-Columbano It has been shown that the magnitude of DNA synthesis and the time at which maximal DNA synthesis occurs after two-thirds partial hepatectomy (PH) is greatly reduced in the liver of aged rodents compared to young animals. This reduction could represent an intrinsic defect in proliferation or a more specialized change in the response to PH. We therefore evaluated the proliferative capacity of hepatocytes in aged animals, following treatment with primary liver mitogens. We show that treatment of 12-month-old CD-1 mice with the hepatomitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) caused an increase in hepatocyte proliferation similar to that seen in young (8-week-old) mice. The labeling index was 82% in the livers of aged mice versus 76% in young animals. Histological observation demonstrated that the number of hepatocytes entering mitoses was similar in both groups; the mitotic indices were 2.5 per thousand and 2.7 per thousand, respectively. Additional experiments showed that the timing of DNA synthesis and M phase were nearly identical in both aged and young mice. Stimulation of hepatocyte DNA synthesis was associated with increased expression of several cell cycle-associated proteins (cyclin D1, cyclin A, cyclin B1, E2F, pRb, and p107); all were comparable in aged mice and young mice. TCPOBOP treatment also increased expression of the Forkhead Box transcription factor m1b (Foxm 1b) to a similar degree in both groups. In conclusion, hepatocytes retain their proliferative capacity in old age despite impaired liver regeneration. These findings suggest that therapeutic use of mitogens would alleviate the reduction in hepatocyte proliferation observed in the elderly. (Hepatology 2000;40:981,988). [source] A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liverHEPATOLOGY, Issue 3 2001Barbara Akhurst Several reliable and reproducible methods are available to induce oval cells in rat liver. Effective methods often involve inhibiting proliferation in hepatocytes using an alkylating agent, then subjecting the rat to partial hepatectomy (PH). The surgery is difficult to perform reproducibly in mice. Approaches that do not include partial hepatectomy, such as administration of D -galactosamine, are ineffective in mice. We found that a choline-deficient, ethionine-supplemented (CDE) diet, which is very effective in rats, leads to high morbidity and mortality when administered to mice. This article outlines an alternative protocol by which a CDE diet can be administered to mice. This diet is shown to be highly effective for oval cell induction, without causing high mortality. It takes less time and is at least as effective as other commonly used protocols for inducing oval cells in mice. (HEPATOLOGY 2001;34:519-522.) [source] Earlier expression of the transcription factor HFH-11B diminishes induction of p21CIP1/WAF1 levels and accelerates mouse hepatocyte entry into S-phase following carbon tetrachloride liver injuryHEPATOLOGY, Issue 6 2001Xinhe Wang Partial hepatectomy (PH) or toxic liver injury induces the proliferation of terminally differentiated hepatic cells to regenerate the original size of the adult liver. Previous PH liver regeneration studies showed that premature transgenic expression of the Forkhead Box M1b (FoxM1b, HFH-11B) transcription factor accelerated hepatocyte entry into DNA replication (S-phase). In this study, we used carbon tetrachloride (CCl4) liver injury to induce a different type of mouse liver regeneration and show that premature hepatic HFH-11B levels also accelerate the onset of hepatocyte S-phase in this injury model. Unlike PH liver regeneration, earlier hepatocyte proliferation after CCl4 liver injury is correlated with diminished transgenic hepatic levels of p21CIP1/WAF1 at the G1/S transition of the cell cycle. Differential hybridization of cDNA arrays and RNase protection studies determined that CCl4 regenerating liver of transgenic mice displayed early stimulated expression of the S-phase promoting cyclin D1 and cyclin E and sustained levels of Cdc25a phosphatase genes. Compared with previous PH liver regeneration studies, our data suggest that premature expression of HFH-11B activates distinct S-phase promotion pathways in the CCl4 liver injury model. Although proliferating transgenic hepatocytes induced by either PH or CCl4 liver injury displayed early expression of identical M-phase cyclin genes (cyclin B1, B2, A2, and F), only CCl4 regenerating transgenic liver exhibited earlier expression of the M-phase promoting Cdc25b. These studies suggest that CCl4 injury of transgenic liver not only uses the same mechanisms as PH to mediate accelerated hepatocyte entry into mitosis, but also promotes M-phase entry by stimulating Cdc25b expression. [source] Hetero-,-systems from 2 + 2 cycloreversion, part 2.1Ab initio thermochemical study of heterocyclobutanes 2 + 2 cycloreversion to form heteroethenes H2C=X (X=NH, O, SiH2, PH, S),HETEROATOM CHEMISTRY, Issue 7 2007Leonid E. Gusel'nikov Ab initio and DFT thermochemical study of diradical mechanism of 2 + 2 cycloreversion of parent heterocyclobutanes and 1,3-diheterocyclobutanes, cyclo -(CH2CH2CH2X), and cyclo -(CH2XCH2X), where X = NH, O, SiH2, PH, S, was undertaken by calculating closed-shell singlet molecules at three levels of theory: MP4/6-311G(d)//MP2/6-31G(d)+ZPE, MP4/6-311G(d,p)//MP2/6-31G (d,p)+ZPE, and B3LYP/6-311+G(d,p)+ZPE. The enthalpies of 2 + 2 cycloreversion decrease on going from group 14 to group 16 elements, being substantially higher for the second row elements. Normally endothermic 2 + 2 cycloreversion is predicted to be exothermic for 1,3-diazetidine and 1,3-dioxtane. Strain energies of the four-membered rings were calculated via the appropriate homodesmic reactions. The enthalpies of ring opening via the every possible one-bond homolysis that results in the formation of the corresponding 1,4-diradical were found by subtracting the strain energies from the central bond dissociation energies of the heterobutanes CH3CH2,CH2XH, CH3CH2,XCH3, and HXCH2,XCH3. The latter energies were determined via the enthalpies of the appropriate dehydrocondensation reactions, using C,H and X,H bond energies in CH3XH calculated at G2 level of theory. Except 1,3-disiletane, in which ring-opening enthalpy attains 69.7 kcal/mol, the enthalpies of the most economical ring openings do not exceed 60.7 kcal/mol. The 1,4-diradical decomposition enthalpies found as differences between 2 + 2 cycloreversion and ring-opening enthalpies were negative, the least exothermicity was calculated for , CH2SiH2CH2CH2. The only exception was 1,3-disiletane, which being diradical, CH2SiH2CH2SiH2, decomposed endothermically. Since decomposition of the diradical containing two silicon atoms required extra energy, raising the enthalpy of the overall reaction to 78.9 kcal/mol, 1,3-disiletane was predicted to be highly resisting to 2 + 2 cycloreversion. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:704,720, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20377 [source] Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the anesthetized ratHIPPOCAMPUS, Issue 1 2006Jesse Jackson Abstract Independent and combined electrical stimulation pairings of the medial septum (MS), posterior hypothalamus (PH), and reticular pontine oralis (RPO) of the brainstem were performed in the acute urethane anesthetized rat, while recording field activity from electrodes in either the stratum oriens or stratum moleculare of the hippocampal formation. Theta frequency and power were measured during independent stimulation of each nuclei and during combined stimulation using three pairings: (1) MS,PH (2) MS,RPO and (3) PH,RPO. Each pairing consisted of parameters known to elicit theta of a high frequency for one nucleus, and parameters known to elicit a low frequency for the second nucleus. This methodology allowed us to observe whether one nucleus preferentially modulated theta activity in the hippocampus in terms of frequency and power. The MS was observed to reset theta frequency in both the upward and downward direction when stimulated in combination with either the PH (Experiment 1) or the RPO (Experiment 2). In Experiment 3 (PH,RPO), the structure receiving the higher intensity stimulation had the predominate effect on theta frequency. With MS stimulation combinations, the power of the elicited theta activity was found to increase over the independent stimulation in some cases during Experiment 1. Likewise, in Experiment 2, the combined stimulation produced a power that in most cases was significantly greater than that measured during the independent stimulations. This effect was not observed with PH and RPO stimulation combinations. The combined stimulation of the PH and RPO yielded a power similar to the independent PH stimulations. The findings support the following conclusions: (1) the major theta generating activity of the ascending brainstem synchronizing pathways involves projections from the RPO to the PH, relayed through the MS, to the hippocampal formation; and (2) that the MS directly controls theta amplitude and secondarily translates the level of ascending brainstem activity into the appropriate frequency of hippocampal theta. © 2005 Wiley-Liss, Inc. [source] Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the freely moving ratHIPPOCAMPUS, Issue 1 2006Brian H. Bland Abstract Rats implanted with hippocampal recording electrodes were tested in a wheel-running apparatus under three conditions: (1) independent electrical stimulation of the medial septal nucleus (MS); (2) independent electrical stimulation of the posterior hypothalamic nucleus (PH); and (3) combined electrical stimulation of the MS and PH using pairings of two stimulation conditions, 7 or10 Hz stimulation of the MS, and a low- or high-intensity PH stimulation. Quantitative measures of running speed were taken, and hippocampal recordings were subjected to fast-Fourier transform analysis. Electrical stimulation of the PH induced wheel-running behavior; running speed and the accompanying hippocampus (HPC) theta frequency increased with increase in stimulation intensity. Electrical stimulation of the MS failed to induce wheel-running behavior despite the fact that HPC theta was induced at the frequency of the applied stimulation (7 and 10 Hz). Electrical stimulation of the MS reset the frequency of HPC theta induced by PH stimulation in both the upward and downward directions and increased theta power, while wheel-running speed was modulated in a downward direction only. © 2005 Wiley-Liss, Inc. [source] Representation of place by monkey hippocampal neurons in real and virtual translocationHIPPOCAMPUS, Issue 2 2003Etsuro Hori Abstract The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place-selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place-selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place-selective responses, into geometric relationships in a two-dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map. Hippocampus 2003;13:190,196. © 2003 Wiley-Liss, Inc. [source] |