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Sample records for vnmwt hypothalamic-pituitary-adrenocortical hpa

  1. Neuropeptides and the hypothalamic-pituitary-adrenocortical (HPA) system: review of recent research strategies in depression.

    Science.gov (United States)

    Hatzinger, M

    2000-04-01

    Depressed patients show a variety of alterations in hypothalamic-pituitary-adrenocortical (HPA) system regulation which is reflected by increased pituitary-adrenocortical hormone secretion at baseline and a number of aberrant neuroendocrine function tests. The latter include the combined dexamethasone (DEX) suppression/corticotropin-releasing hormone (CRH) challenge test, in which CRH was able to override DEX induced suppression of ACTH and cortisol secretion. Whereas the abnormal HPA activation in these patients improved in parallel with clinical remission, persistent HPA dysregulation was associated with an increased risk of relapse. Moreover, healthy subjects at high genetic risk for depression also showed this phenomenon as a trait marker. In consequence, it has been concluded that HPA alteration and development as well as course of depression may be causally related. As evidenced from clinical and preclinical studies, underlying mechanisms of these abnormalities involve impairment of central corticosteroid receptor function which leads to enhanced activity of hypothalamic neurons synthesising and releasing vasopressin and CRH. These neuropeptides mediate not only neuroendocrine but also behavioural effects. Recent research provided evidence that CRH can induce depression-like symptoms in animals and that these signs are mediated through the CRH1 receptor subtype. Hence, therapeutical application of new compounds acting more specifically on the HPA system such as CRH1 receptor antagonists appear to be a promising approach for future treatment options of depression. In conclusion, research in neuroendocrinology provided new insights into the underlying pathophysiology of depression and, in consequence, may lead to the development of new therapeutic tools.

  2. Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

    Science.gov (United States)

    Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

    2016-01-01

    Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

  3. Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

    2014-08-01

    The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

  4. Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development.

    Science.gov (United States)

    Hostinar, Camelia E; Sullivan, Regina M; Gunnar, Megan R

    2014-01-01

    Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.

  5. Sex-specific associations between sleep problems and hypothalamic-pituitary-adrenocortical axis activity in children.

    Science.gov (United States)

    Pesonen, Anu-Katriina; Kajantie, Eero; Heinonen, Kati; Pyhälä, Riikka; Lahti, Jari; Jones, Alexander; Matthews, Karen A; Eriksson, Johan G; Strandberg, Timo; Räikkönen, Katri

    2012-02-01

    Sleep problems are associated with reduced physical and mental health. Altered function of the hypothalamic-pituitary-adrenocortical axis (HPAA) may be one underlying mechanism. We studied the associations between sleep problems and HPAA activity in children. A cross-sectional epidemiological cohort study. Salivary cortisol was sampled throughout one day at home and during the Trier Social Stress Test for Children (TSST-C) in clinic. Sleep disorders were measured with a parent-rated Sleep Disturbance Scale for Children, and sleep duration measured by actigraphy for one week. 284 (51% girls) 8-year-old children. Boys with sleep problems (≥ 85 th percentile in any of the sleep-wake transition, arousal, excessive daytime somnolence or sleep hyperhydrosis subscales) had lower diurnal salivary cortisol levels and salivary cortisol responses to TSST-C stress in comparison to boys without sleep problems. Girls with sleep problems (≥ 85 th percentile in disorders of initiating and maintaining sleep) displayed a higher overall level of salivary cortisol during the TSST-C. Salivary cortisol responses to stress were lower in boys and higher in girls with more than one sleep problem. Sleep problems in children are associated with altered HPAA function, after controlling for actual sleep quantity measured by actigraphy. Boys with sleep problems had lower HPAA activity and girls with sleep problems had higher HPAA activity, compared to children without sleep problems. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Maternal prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis function in children.

    Science.gov (United States)

    Räikkönen, Katri; Seckl, Jonathan R; Heinonen, Kati; Pyhälä, Riikka; Feldt, Kimmo; Jones, Alexander; Pesonen, Anu-Katriina; Phillips, David I W; Lahti, Jari; Järvenpää, Anna-Liisa; Eriksson, Johan G; Matthews, Karen A; Strandberg, Timo E; Kajantie, Eero

    2010-11-01

    Overexposure to glucocorticoids has been proposed as a mechanism by which prenatal adversity 'programs' the function of the hypothalamic-pituitary-adrenocortical axis (HPAA), thereby increasing the risk of adult diseases. Glycyrrhizin, a natural constituent of licorice, potently inhibits 11β-hydroxysteroid dehydrogenase type 2, the feto-placental barrier to the higher maternal cortisol levels. We studied if maternal consumption of glycyrrhizin in licorice associates with HPAA function in children. Diurnal salivary cortisol and salivary cortisol during the Trier Social Stress Test for Children (TSST-C) were measured in children (n=321, mean age=8.1, SD=0.3 years) whose mothers consumed varying levels of glycyrrhizin in licorice during pregnancy; exposure-level groups were labeled high (≥500 mg/week), moderate (250-499 mg/week) and zero-low (0-249 mg/week). In comparison to the zero-low exposure group, children in the high exposure group had 19.2% higher salivary cortisol awakening peak, 33.1% higher salivary cortisol awakening slope, 15.4% higher salivary cortisol awakening area under the curve (AUC), 30.8% higher baseline TSST-C salivary cortisol levels, and their salivary cortisol levels remained high throughout the TSST-C protocol (P-values HPAA function by overexposure to glucocorticoids. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Higher levels of physical activity are associated with lower hypothalamic-pituitary-adrenocortical axis reactivity to psychosocial stress in children.

    Science.gov (United States)

    Martikainen, Silja; Pesonen, Anu-Katriina; Lahti, Jari; Heinonen, Kati; Feldt, Kimmo; Pyhälä, Riikka; Tammelin, Tuija; Kajantie, Eero; Eriksson, Johan G; Strandberg, Timo E; Räikkönen, Katri

    2013-04-01

    Children who undertake more physical activity (PA) not only have more optimal physical health but also enjoy better mental health. However, the pathways by which PA affects well-being remain unclear. To address this question, we examined whether objectively measured daytime PA was associated with diurnal hypothalamic-pituitary-adrenocortical axis (HPAA) activity and HPAA responses to psychosocial stress. We conducted a cross-sectional study in a birth cohort in Helsinki, Finland. We studied 258 8-year-old children. PA was assessed with wrist-worn accelerometers. Overall PA and percentage of time spent in vigorous PA (VPA) were categorized by sex into thirds. Salivary cortisol was measured diurnally and in response to the Trier Social Stress Test for Children. The children in different PA groups did not show differences in diurnal salivary cortisol (P > .10 for overall PA and VPA). Children with the highest levels of overall PA or VPA showed no, or only small, increases over time in salivary cortisol after stress (P = .10 and P =.03 for time in analyses of PA and VPA, respectively), whereas children belonging to the lowest and intermediate thirds showed significant increases over time in salivary cortisol after stress (P ≤ .002 for time in the analyses of overall PA and VPA). These results suggest that children with lower levels of daytime PA have higher HPAA activity in response to stress. These findings may offer insight into the pathways of PA on physical and mental well-being.

  8. Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA-Axis Reactivity during a Psychosocial Stressor

    Science.gov (United States)

    Fisher, Philip A.; Kim, Hyoun K.; Bruce, Jacqueline; Pears, Katherine C.

    2012-01-01

    Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without…

  9. Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA-Axis Reactivity during a Psychosocial Stressor

    Science.gov (United States)

    Fisher, Philip A.; Kim, Hyoun K.; Bruce, Jacqueline; Pears, Katherine C.

    2012-01-01

    Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without…

  10. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D. (Eastern Virginia Medical School, Norfolk (USA))

    1990-12-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of (3H)F/(14C)E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production.

  11. Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic-pituitary-adrenocortical axis responsiveness to stress.

    Science.gov (United States)

    Wulsin, Aynara C; Herman, James P; Solomon, Matia B

    2010-08-01

    Glucocorticoid dyshomeostasis is observed in a proportion of depressed individuals. As a result, glucocorticoid receptor (GR) antagonists are currently being tested as potential anti-depressants. The current study was designed to test the efficacy of mifepristone, a GR antagonist, in mitigating behavioral, neuroendocrine and central nervous system (CNS) responses to an acute stressor. Adult male rats were treated for 5 days with mifepristone (10 mg/kg) and then exposed to the forced swim test (FST). Treatment with mifepristone decreased immobility and increased swimming (but not climbing) behavior in the FST, consistent with anti-depressant action. In addition, mifepristone dampened the ACTH response to FST exposure. In the CNS, mifepristone increased c-Fos expression in all subdivisions of the medial prefrontal cortex (mPFC) and decreased neuronal activity in some subdivisions of the hippocampus including the CA2, CA3, and hilus region of the dentate gyrus in animals exposed to FST. In contrast, mifepristone increased neuronal activity in the ventral subiculum (output region of the hippocampus) and decreased c-Fos expression in the central amygdala (CeA) in animals exposed to FST. These data suggest that anti-depressant efficacy and perhaps HPA dampening properties of RU486 are related to alterations in key limbic circuits mediating CNS stress responses, resulting in enhanced stress inhibition (via the mPFC and ventral subiculum) as well as decreased stress excitation (central amygdala). Overall the data suggest that drugs targeting the glucocorticoid receptor may ameliorate stress dysfunction associated with depressive illness.

  12. Effect of a high-fat--high-fructose diet, stress and cinnamon on central expression of genes related to immune system, hypothalamic-pituitary-adrenocortical axis function and cerebral plasticity in rats.

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    Marissal-Arvy, Nathalie; Batandier, Cécile; Dallennes, Julien; Canini, Frédéric; Poulet, Laurent; Couturier, Karine; Hininger-Favier, Isabelle; Moisan, Marie-Pierre; Roussel, Anne-Marie; Mormède, Pierre

    2014-04-14

    The intake of a high-fat/high-fructose (HF/HFr) diet is described to be deleterious to cognitive performances, possibly via the induction of inflammatory factors. An excess of glucocorticoids is also known to exert negative effects on cerebral plasticity. In the present study, we assessed the effects of an unbalanced diet on circulating and central markers of inflammation and glucocorticoid activity, as well as their reversal by dietary cinnamon (CN) supplementation. A group of male Wistar rats were subjected to an immune challenge with acute lipopolysaccharide under a HF/HFr or a standard diet. Another group of Wistar rats were fed either a HF/HFr or a control diet for 12 weeks, with or without CN supplementation, and with or without restraint stress (Str) application before being killed. We evaluated the effects of such regimens on inflammation parameters in the periphery and brain and on the expression of actors of brain plasticity. To assess hypothalamic-pituitary-adrenocortical axis activity, we measured the plasma concentrations of corticosterone and the expression of central corticotrophin-releasing hormone, mineralocorticoid receptor, glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase. We found that the HF/HFr diet induced the expression of cytokines in the brain, but only after an immune challenge. Furthermore, we observed the negative effects of Str on the plasma concentrations of corticosterone and neuroplasticity markers in rats fed the control diet but not in those fed the HF/HFr diet. Additionally, we found that CN supplementation exerted beneficial effects under the control diet, but that its effects were blunted or even reversed under the HF/HFr diet. CN supplementation could be beneficial under a standard diet. [corrected].

  13. 白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响%Influences of Extract of Peony Radix Alba on Behavior and Hypothalamic-pituitary-adrenocortical Axis in Depressive Rats Model with Damaged Olfactory Bulb

    Institute of Scientific and Technical Information of China (English)

    王景霞; 张建军; 苗春平; 刘妍; 林清; 陈振振

    2011-01-01

    Objective: To investigate the influences of extract from Peony Radix Alba on the behavioral and hypothalamic-pituitary-adrenocortical (HPA) axis changes in rats with damaged olfactory bulb (DOB). Method: The tests of open-field and step-down passive avoidance were used to observe the behaviors of rats.Radioimmunoassay (RIA) was used to analyze the level of corticotropin releasing hormone (CRH) in hypothalamus, adrenocorticotropic hormone (ACTH) in pituitary gland and cortisol (CORT) in serum of rats with DOB. Result: The rats had a characteristic hyperactivity in the test of "open-field" and learning deficits in stepdown passive avoidance ( P < 0. 05 ), and their levels of CRH, ACTH and CORT increased significantly ( P < 0. 05). The extract of Peony Radix Alba at the dose of 70,35 mg·kg-1 corrected the behavioral changes (P < 0. 05 ) and decreased the levels of CRH, ACTH and CORT ( P < 0. 05). Conclusion: The extract of Peony Radix Alba can correct behavioral changes in rats with DOB, and its regulating effect on HPA axis is one of the mechanisms for treating depression.%目的:研究白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑一垂体.肾上腺(HPA)轴的影响.方法:将嗅球损毁大鼠随机分为对照组、模型组、阳性药氟西汀2.5 mg·kg-1组以及白芍提取物70,35,17.5 mg·kg-1组,采用敞箱法、跳台法观察嗅球损毁大鼠的行为变化,间时用放免法分析白芍提取物对嗅球损毁大鼠下丘脑促肾上腺皮质激素释放素(CRH)、垂体促肾上腺皮质激素(ACTH)和血清皮质酮(CORT)含量的影响.结果:大鼠嗅球损毁后敞箱行为出现明显变化,水平运动和垂直运动显著增加,白芍提取物中、高剂量组可显著降低大鼠水平运动和垂直运动的得分;跳台试验中,造模后大鼠训练期和测试期的错误次数显著增加,自芍提取物中、高剂量组能显著降低嗅球损毁大鼠训练期和测试期的触电次数;嗅球损毁大

  14. 芍药内酯苷对嗅球切除抑郁模型大鼠行为学以及下丘脑-垂体-肾上腺轴功能的影响%Effect of albiflorin on behavior and hypothalamic-pituitary-adrenocortical axis in olfactory bulbectomized rats

    Institute of Scientific and Technical Information of China (English)

    陈岚; 龚正华; 薛瑞; 张亭亭; 李云峰; 洪浩; 张有志

    2014-01-01

    目的:探讨芍药内酯苷(Alb)的抗抑郁作用及其对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法采用切除大鼠嗅球制备抑郁模型,恢复14 d后每天2次给予盐酸丙咪嗪(IMI)5.0 mg·kg -1,Alb 2.5,5.0和10.0 mg·kg -1,连续给药14 d。开场实验检测大鼠的酶联免疫法检测血清中皮质酮(CO RT)及促肾上腺皮质激素(ACTH)含量;Western蛋白质印迹法检测海马糖皮质激素受体(GR)表达水平。结果与假手术组相比,嗅球切除模型组大鼠运动距离、运动时间和运动速度均显著增加(P<0.01);给药7 d 后,Alb 10.0 mg·kg -1显著降低嗅球切除大鼠运动时间、速度和距离(P<0.05);给药14 d 后,Alb 5.0和10.0 mg·kg -1均可以显著降低嗅球切除大鼠运动时间、速度和距离(P<0.05)。嗅球切除模型组大鼠血清CORT和ACTH 水平显著升高(P<0.01),海马 GR 表达下降(P<0.01),给予 Alb 2.5,5.0和10.0 mg·kg -1可显著降低嗅球切除大鼠血清CORT和ACTH水平(P<0.05);Western蛋白质印迹法结果表明,Alb 5.0和10.0 mg·kg -1可增加海马GR的表达(P<0.05)。结论芍药内酯苷对嗅球切除模型大鼠具有明确的抗抑郁行为效应,其抗抑郁作用机制可能与抑制H PA功能亢进有关。%OBJECTIVE Toexploretheantidepressanteffectsofalbiflorinandtheinvolvementof hypothalamic-pituitary-adrenocortical (HPA) axis function in its antidepressant potency.METHODS Two weeks after the olfactory bulbectomized (OB)surgery,albiflorin (2.5 ,5.0 ,10.0 mg·kg -1 ,ig) and imipramine 5.0 mg·kg -1 (ig)were given to rats twice a day for 14 d.The open-field test was con-ducted to evaluate the move ment distance,move ment ti me and velocity of olfactory bulbecto mized rats and sham-operated rats.The serum levels of corticosterone(CORT)and adrenocorticotropic hormone (ACTH)in rats were measured by the

  15. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

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    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  16. Neuroendorine and epigentic mechanisms subserving autonomic imbalance and HPA dysfunction in the metabolic syndrome

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    Erwin eLemche

    2016-04-01

    Full Text Available Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA and hypothalamic-pituitary adrenocortical (HPA axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signalling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS and diet-induced obesity (DIO programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression, melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications.

  17. Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome.

    Science.gov (United States)

    Lemche, Erwin; Chaban, Oleg S; Lemche, Alexandra V

    2016-01-01

    Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications.

  18. Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress.

    Science.gov (United States)

    Ryan, Karen K; Mul, Joram D; Clemmensen, Christoffer; Egan, Ann E; Begg, Denovan P; Halcomb, Kristen; Seeley, Randy J; Herman, James P; Ulrich-Lai, Yvonne M

    2014-04-01

    The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were placed into 3 groups (n=15/group) according to genotype [wild-type (WT); heterozygous mutant (HET); and homozygous mutant (HOM)]. Basal (pre-stress) plasma adrenocorticotropic hormone (ACTH) and corticosterone were measured in the AM and PM, and the HPA axis response to restraint was assessed in the AM. Rats were perfused at 2h after restraint to assess the effect of loss of MC4R on stress-induced c-Fos immunolabeling in stress-regulatory brain regions. We find that basal (non-stress) AM and PM plasma ACTH and corticosterone showed a normal diurnal rhythm that was not altered according to genotype. Consistent with this, adrenal and thymus weights were unaffected by genotype. However, the plasma ACTH and corticosterone responses to restraint were significantly reduced by loss of MC4R function. Likewise, stress-induced c-Fos immunolabeling in both PVH and MeA was significantly reduced by loss of Mc4r function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic and stress systems.

  19. The damage of hippocampus and the dysregulation of the HPA axis in T2DM%2型糖尿病海马损伤与HPA轴功能紊乱

    Institute of Scientific and Technical Information of China (English)

    蔡懿婷; 刘伟

    2009-01-01

    2型糖尿病患者出现下丘脑-垂体-肾上腺轴(HPA轴)功能紊乱,可能和海马损伤有关.一方面HPA轴功能紊乱可能通过引起海马胰岛素抵抗,突触可塑性改变,以及糖皮质激素受体紊乱影响海马功能及负反馈调节.另一方面,慢性应激所引起的海马损伤也可以导致HPA轴功能紊乱,从而形成恶性循环.本文就2型糖尿病患者HPA轴与海马损伤的关系作简要概述.%There is some evidence of hypothalamic-pituitary-adrenocortical(HPA)axis dysfunction in type 2 diabetes mellitus(T2DM).It may be associated with the damage of hippocampus.In one side,dysregulation of the HPA axis may induce insulin resistance in the hippocampus.changes in hippocampal synaptic plasticity and disarrangement of glucocorticoid receptor.In the other side,the hippocampal damage which induced by chronic stress may result in dysregulation of the HPA axis,thus creating a vicious cycle.This article will discuss the relationship between the HPA axis and the damage of hippocampus in T2DM.

  20. Relations among Posttraumatic Stress Disorder, Comorbid Major Depression, and HPA Function: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Morris, Matthew C.; Compas, Bruce E.; Garber, Judy

    2012-01-01

    Exposure to traumatic stress is associated with increased risk for posttraumatic stress disorder (PTSD) and alterations of hypothalamic-pituitary-adrenocortical (HPA) function. Research linking traumatic stress with HPA function in PTSD has been inconsistent, however, in part due to (a) the inclusion of trauma-exposed individuals without PTSD (TE) in control groups and (b) a failure to consider comorbid major depressive disorder (MDD) and moderating variables. This meta-analysis of 47 studies (123 effect sizes, N=6,008 individuals) revealed that daily cortisol output was lower for PTSD (d=−.36, SE=.15, p=.008) and PTSD+MDD (d=−.65, SE=.25, p=.008) groups relative to no trauma controls (NTC); TE and NTC groups did not differ significantly from each other. Afternoon/evening cortisol was lower in TE (d=−.25, SE=.09, p=.007) and PTSD (d=−.27, SE=.12, p=.021) groups and higher in PTSD+MDD groups (d=.49, SE=.24, p=.041) relative to NTC. Post-DST cortisol levels were lower in PTSD (d=−.40, SE=.12, p<.001), PTSD+MDD (d=−.65, SE=.14, p<.001), and TE groups (d=−.53, SE=.14, p<.001) relative to NTC. HPA effect sizes were moderated by age, sex, time since index event, and developmental timing of trauma exposure. These findings suggest that enhanced HPA feedback function may be a marker of trauma-exposure rather than a specific mechanism of vulnerability for PTSD, whereas lower daily cortisol output may be associated with PTSD in particular. PMID:22459791

  1. Structural Stigma and Hypothalamic-Pituitary-Adrenocortical Axis Reactivity in Lesbian, Gay, and Bisexual Young Adults

    Science.gov (United States)

    Hatzenbuehler, Mark L.; McLaughlin, Katie A.

    2013-01-01

    Background Youth exposed to extreme adverse life conditions have blunted cortisol responses to stress. Purpose To examine whether growing up in highly stigmatizing environments similarly shapes stigmatized individuals’ physiological responses to identity-related stress. Methods We recruited 74 lesbian, gay, and bisexual young adults (mean age=23.68) from 24 states with varying levels of structural stigma surrounding homosexuality. State-level structural stigma was coded based on several dimensions, including policies that exclude sexual minorities from social institutions (e.g., same-sex marriage). Participants were exposed to a laboratory stressor, the Trier Social Stress Test (TSST), and neuroendocrine measures were collected. Results LGB young adults who were raised in highly stigmatizing environments as adolescents evidenced a blunted cortisol response following the TSST compared to those from low-stigma environments. Conclusions The stress of growing up in environments that target gays and lesbians for social exclusion may exert biological effects that are similar to traumatic life experiences. PMID:24154988

  2. Gender Differences in Sensitivity of the Hypothalamic Pituitary Adrenocortical Axis to Stress Like Stimulation

    Science.gov (United States)

    1991-12-05

    with significant hypercortisolism, including major depression and anorexia nervosa , are significantly more common in women than in men (Gold et al...major depression and anorexia nervosa , are much more common in women than men. I t should be noted however, that Rabin et a l . 1991. have shown that...CRH in normal women is interesting, given the fact that several states associated 14 with hypercortisolism, depression, anorexia nervosa and

  3. Structural stigma and hypothalamic-pituitary-adrenocortical axis reactivity in lesbian, gay, and bisexual young adults.

    Science.gov (United States)

    Hatzenbuehler, Mark L; McLaughlin, Katie A

    2014-02-01

    Youth exposed to extreme adverse life conditions have blunted cortisol responses to stress. This study aims to examine whether growing up in highly stigmatizing environments similarly shapes stigmatized individuals' physiological responses to identity-related stress. We recruited 74 lesbian, gay, and bisexual young adults (mean age = 23.68) from 24 states with varying levels of structural stigma surrounding homosexuality. State-level structural stigma was coded based on several dimensions, including policies that exclude sexual minorities from social institutions (e.g., same-sex marriage). Participants were exposed to a laboratory stressor, the Trier Social Stress Test (TSST), and neuroendocrine measures were collected. Lesbian, gay, and bisexual young adults who were raised in highly stigmatizing environments as adolescents evidenced a blunted cortisol response following the TSST compared to those from low-stigma environments. The stress of growing up in environments that target gays and lesbians for social exclusion may exert biological effects that are similar to traumatic life experiences.

  4. Dopamine D2-like receptors modulate freezing response, but not the activation of HPA axis, during the expression of conditioned fear.

    Science.gov (United States)

    de Oliveira, Amanda R; Reimer, Adriano E; Reis, Fernando M C V; Brandão, Marcus L

    2017-02-01

    Considering the complexity of aversive information processing and defensive response expression, a combined action of stress modulators may be required for an optimal performance during threatening situations. Dopamine is now recognized as one of the most active modulators underlying states of fear and anxiety. On the other hand, activation of hypothalamic-pituitary-adrenocortical (HPA) axis, which leads to the release of corticosterone in rodents, has been considered a key part of the stress response. The current study is an extension of prior work investigating modulatory effects of dopamine and corticosterone on conditioned fear expression. We have showed that corticosterone, acting through mineralocorticoid receptors in the ventral tegmental area (VTA), upregulates dopaminergic system in the basolateral amygdala (BLA), enabling the expression of conditioned freezing response. The novel question addressed here is whether VTA-BLA dopaminergic signaling is necessary for increases in corticosterone during conditioned fear expression. Using site-specific treatment with D2-like agonist quinpirole (VTA) and D2-like antagonist sulpiride (BLA), we evaluated freezing and plasma corticosterone in rats exposed to a light used as aversive conditioned stimulus (CS). Intra-VTA quinpirole and intra-BLA sulpiride significantly decreased freezing expression in the conditioned fear test, but this anxiolytic-like effect of the dopaminergic drugs was not associated with changes in plasma corticosterone concentrations. Altogether, data suggest that interferences with the ability of the CS to activate the dopaminergic VTA-BLA pathway reduce the expression of freezing, but activation of the HPA axis seems to occur upstream of the recruitment of dopaminergic mechanisms in conditioned fear states.

  5. 创伤后应激障碍患者的HPA轴功能变化的时间序列特征%Temporal characteristics of change in HPA activity among PTSD patients

    Institute of Scientific and Technical Information of China (English)

    张权; 陈崝; 王玮文; 邓慧华

    2016-01-01

    Posttraumatic stress disorder (PTSD) is associated with abnormal functioning of the hypothalamic- pituitary-adrenocortical (HPA) axis, as shown by alterations of cortisol levels. However, results on the link of cortisol level with PTSD are inconsistent. Recent studies imply that PTSD patients show temporal characteristics of the change in cortisol level with the elevation at early stage and thereafter the decrease relative to the normal basal cortisol level after traumatic exposure. The temporal characteristics might be disturbed or masked by some factors, such as characteristics of biomarker, course of PTSD, type and intensity of stressor and comorbid disease. The present review suggested that future research needs to further profile temporal characteristics of change in cortisol level among PTSD patients by controlling the influencing factors and utilizing long-term follow-up design in combination with acute-stress and chronic- stress biomarkers and investigate whether it can be used to predict and intervene PTSD through cortisol treatment. Considering that cortisol level is regulated by metabolism and antagonism procedures, the use of multi-biomarkers will facilitate the reliable evaluation of the HPA axis activity among PTSD patients.%已知创伤后应激障碍(posttraumatic stress disorder, PTSD)患者表现出HPA轴(hypothalamic-pituitary- adrenocortical axis)功能异常,而皮质醇是反映PTSD患者HPA轴功能的重要生物标记。近期的研究结果提示, PTSD患者的皮质醇水平变化可能有明显的时间序列特征,即应激事件发生后先升高,后下降至正常水平之下。这一特征受到生物标记的时间特性,患者病程,应激源类型和强度,伴生疾病等因素的干扰和掩蔽。未来研究应进一步采用长期追踪设计,控制干扰因素的影响,结合急性应激和慢性应激生物标记来综合验证PTSD患者皮质醇水平变化的时间序列特征;并利用该特征预

  6. Blunted hypothalamic-pituitary-adrenocortical axis responsivity to stress in persons with a family history of alcoholism.

    Science.gov (United States)

    Sorocco, Kristen H; Lovallo, William R; Vincent, Andrea S; Collins, Frank L

    2006-03-01

    Abstinent alcoholics show a blunted stress cortisol response that may be a consequence of drinking or a preexisting risk marker. We tested cortisol responses to psychological stress in 186 18-30 year-old, healthy social drinkers having no personal history of alcohol or drug dependence, 91 of whom had one or two alcoholic parents (FH+) and 95 having no family alcoholism for two generations (FH-). We predicted that, similar to alcoholic patients, the FH+ would have reduced stress cortisol responses that would be partially determined by their temperament characteristics, specifically antisocial tendencies as measured by the California Psychological Inventory. On a stress day, subjects performed continuous simulated public speaking and mental arithmetic tasks for 45 min, and on a control day they sat and rested for the same time period. The FH+ who were low in sociability had smaller cortisol responses than FH-, high-sociability persons (t=2.27, p=.02). These two groups were not different in diurnal cortisol secretion patterns or affective responses to the stressors. Persons with a familial risk for alcoholism who have more antisocial tendencies may have altered central nervous system responses to emotionally relevant social challenges. Disrupted cortisol stress responses may serve as a risk marker for the development of substance use disorders.

  7. [THE INFLUENCE OF MELANIN ON THE GASTRIC MUCOSA AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS UNDER ACUTE STRESS CONDITIONS].

    Science.gov (United States)

    Golyshkin, D V; Falalyeyeva, T M; Neporada, K S; Beregova, T V

    2015-01-01

    We studied the influence of melanin from yeast-like fungi Nadsoniella nigra strain X1 on the changes of the levels of adrenocorticotropic hormone (ACTH) and cortisol in blood serum of rats, adrenal glands weight ratio and lesions of the gastric mucosa (GM) caused by neuromuscular tension by Selye. Melanin administration restored functioning of the hypothalamic-pituitary-adrenal axis that was evident by an increase of ACTH concentration by 42% and a decrease of cortisol concentration by 19% compared to the rats injected with water (group 2). In rats treated with melanin, the adrenal glands weight ratio, didn't differ from intact control group of the rats. Melanin decreased ulcers area by 64% and reduced the content of free hydroxyproline by 29%, the free fucose by 16% and the free hexuronic acids by 24% in the GM compared to the group 2 of the rats. It is established that the mechanism of melanin stress-protective properties are based on its regulation of the glucocorticoids secretion and prevention of GM collagen and extracellular matrix substances depolymerization. Melanin possesses gastroprotective properties and is a perspective agent for preventing and treatment of consequences of the stress influence on the organism.

  8. Relationship between Depression and HPA Axis and Intervention by Traditional Chinese Medicine%抑郁症与HPA轴关系及中药干预的研究进展

    Institute of Scientific and Technical Information of China (English)

    柴丽; 赵博

    2011-01-01

    It is very important that hyperactivity of hypothalamic-pituitary-adrenocortical (HPA) axis is one of the pathophysiological mechanism of depression. Previous studies have festimated that plasma level of corticotropin-releasinghormone ( CRH ) , adrenocorticotropichormone ( ACTH ), glucocorticoid ( GC ) have increased significantly,meanwhile the sustained increasing level of GC has reduced the number of the hippocampus in the glucocorticoid receptor (GR), and mineralocorticoid receptor (MR)/GR ratio became imbalance, therefore destroying the hippocampal neurons. The hippocampus itself could mediate the activities of HPA axis, the destruction of hippocampal neurons has become so weaker to mediate the HPA axis; while the increasing level of GC, so that the number and function of GR have reduced, GC negative feedback inhibition to HPA axis has decreased to make it function more hyperactivity.%介绍了抑郁症与肾上腺轴的关系以及中药干预相关机制的最新研究资料.查阅CNKI数据库相关文献39篇.研究表明抑郁症患者血浆中促肾上腺皮质激素释放激素、促肾上腺皮质激素、糖皮质激素浓度升高,一方面糖皮质激素的持续升高使海马中糖皮质激素受体数量减少、盐皮质激素受体/糖皮质激素受体比例失衡,进而破坏海马神经元;另一方面,海马本身能抑制下丘脑-垂体-肾上腺轴的活性,海马神经元的破坏使抑制下丘脑-垂体-肾上腺轴的作用减弱;同时糖皮质激素的升高,使糖皮质激素受体的数量和功能降低,造成糖皮质激素对下丘脑-垂体-肾上腺轴负反馈抑制作用减弱,使其功能更为亢进,形成恶性循环.认为中医药具有多靶点、多层面、多轴点的作用特征,通过对HPA轴来干预抑郁症具有一定的现实意义.

  9. The Presence of a Best Friend Buffers the Effects of Negative Experiences

    Science.gov (United States)

    Adams, Ryan E.; Santo, Jonathan Bruce; Bukowski, William M.

    2011-01-01

    The goal of the current study was to examine how the presence of a best friend might serve as protection against the effect of negative experiences on global self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A total of 103 English-speaking male (n = 55) and female (n = 48) participants from Grade 5 (M = 10.27 years) and…

  10. Inhibition and Exuberance in Preschool Classrooms: Associations with Peer Social Experiences and Changes in Cortisol across the Preschool Year

    Science.gov (United States)

    Tarullo, Amanda R.; Mliner, Shanna; Gunnar, Megan R.

    2011-01-01

    Associations between behavioral inhibition and activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a stress-sensitive neuroendocrine system indexed by salivary cortisol, have varied widely across studies. In the current study, we examined the role of peer social experiences in moderating patterns of association between…

  11. The Presence of a Best Friend Buffers the Effects of Negative Experiences

    Science.gov (United States)

    Adams, Ryan E.; Santo, Jonathan Bruce; Bukowski, William M.

    2011-01-01

    The goal of the current study was to examine how the presence of a best friend might serve as protection against the effect of negative experiences on global self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A total of 103 English-speaking male (n = 55) and female (n = 48) participants from Grade 5 (M = 10.27 years) and…

  12. Inhibition and Exuberance in Preschool Classrooms: Associations with Peer Social Experiences and Changes in Cortisol across the Preschool Year

    Science.gov (United States)

    Tarullo, Amanda R.; Mliner, Shanna; Gunnar, Megan R.

    2011-01-01

    Associations between behavioral inhibition and activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a stress-sensitive neuroendocrine system indexed by salivary cortisol, have varied widely across studies. In the current study, we examined the role of peer social experiences in moderating patterns of association between…

  13. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  14. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  15. 严重创伤后应激反应的调控机理%Molecular biological responses to severe posttraumatic stress

    Institute of Scientific and Technical Information of China (English)

    刘都户; 粟永萍; 程天民

    2001-01-01

    Traumatic stress in the normal individual results in activationof the sympatho-adrenal system causing a rise in noradrenaline and adrenaline, acute phase response in liver ,and activation of the hypothalamic-pituitary-adrenocortical(HPA)system resulting in elevated levels of cortisol. Studies in animals and in humans with posttraumatic stress disorder indicate that successful adaptation to stress is a prerequisite for the survival of all organisms living in an enviroment in which noxious stimuli are constantly present.

  16. HPA-projektet

    DEFF Research Database (Denmark)

    Jensen, Bente; Langager, Søren; Haahr-Pedersen, Jakob

    Et kvalificeringsmateriale som er udviklet i forbindelse med HPA-intervention og undersægele af dens effekter i daginstitutioner og døgninstuitutioner......Et kvalificeringsmateriale som er udviklet i forbindelse med HPA-intervention og undersægele af dens effekter i daginstitutioner og døgninstuitutioner...

  17. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  18. Fetal and Neonatal HPA Axis.

    Science.gov (United States)

    Wood, Charles E; Walker, Claire-Dominique

    2015-12-15

    Stress is an integral part of life. Activation of the hypothalamus-pituitary-adrenal (HPA) axis in the adult can be viewed as mostly adaptive to restore homeostasis in the short term. When stress occurs during development, and specifically during periods of vulnerability in maturing systems, it can significantly reprogram function, leading to pathologies in the adult. Thus, it is critical to understand how the HPA axis is regulated during developmental periods and what are the factors contributing to shape its activity and reactivity to environmental stressors. The HPA axis is not a passive system. It can actively participate in critical physiological regulation, inducing parturition in the sheep for instance or being a center stage actor in the preparation of the fetus to aerobic life (lung maturation). It is also a major player in orchestrating mental function, metabolic, and cardiovascular function often reprogrammed by stressors even prior to conception through epigenetic modifications of gametes. In this review, we review the ontogeny of the HPA axis with an emphasis on two species that have been widely studied-sheep and rodents-because they each share many similar regulatory mechanism applicable to our understanding of the human HPA axis. The studies discussed in this review should ultimately inform us about windows of susceptibility in the developing brain and the crucial importance of early preconception, prenatal, and postnatal interventions designed to improve parental competence and offspring outcome. Only through informed studies will our public health system be able to curb the expansion of many stress-related or stress-induced pathologies and forge a better future for upcoming generations.

  19. Sex differences in the HPA axis.

    Science.gov (United States)

    Goel, Nirupa; Workman, Joanna L; Lee, Tiffany T; Innala, Leyla; Viau, Victor

    2014-07-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a major component of the systems that respond to stress, by coordinating the neuroendocrine and autonomic responses. Tightly controlled regulation of HPA responses is critical for maintaining mental and physical health, as hyper- and hypo-activity have been linked to disease states. A long history of research has revealed sex differences in numerous components of the HPA stress system and its responses, which may partially form the basis for sex disparities in disease development. Despite this, many studies use male subjects exclusively, while fewer reports involve females or provide direct sex comparisons. The purpose of this article is to present sex comparisons in the functional and molecular aspects of the HPA axis, through various phases of activity, including basal, acute stress, and chronic stress conditions. The HPA axis in females initiates more rapidly and produces a greater output of stress hormones. This review focuses on the interactions between the gonadal hormone system and the HPA axis as the key mediators of these sex differences, whereby androgens increase and estrogens decrease HPA activity in adulthood. In addition to the effects of gonadal hormones on the adult response, morphological impacts of hormone exposure during development are also involved in mediating sex differences. Additional systems impinging on the HPA axis that contribute to sex differences include the monoamine neurotransmitters norepinephrine and serotonin. Diverse signals originating from the brain and periphery are integrated to determine the level of HPA axis activity, and these signals are, in many cases, sex-specific.

  20. Long-term effects of early life stress exposure: Role of epigenetic mechanisms.

    Science.gov (United States)

    Silberman, Dafne M; Acosta, Gabriela B; Zorrilla Zubilete, María A

    2016-07-01

    Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders.

  1. Learning about stress: neural, endocrine and behavioral adaptations.

    Science.gov (United States)

    McCarty, Richard

    2016-09-01

    In this review, nonassociative learning is advanced as an organizing principle to draw together findings from both sympathetic-adrenal medullary and hypothalamic-pituitary-adrenocortical (HPA) axis responses to chronic intermittent exposure to a variety of stressors. Studies of habituation, facilitation and sensitization of stress effector systems are reviewed and linked to an animal's prior experience with a given stressor, the intensity of the stressor and the appraisal by the animal of its ability to mobilize physiological systems to adapt to the stressor. Brain pathways that regulate physiological and behavioral responses to stress are discussed, especially in light of their regulation of nonassociative processes in chronic intermittent stress. These findings may have special relevance to various psychiatric diseases, including depression and post-traumatic stress disorder (PTSD).

  2. Broadband S-band class E HPA

    NARCIS (Netherlands)

    Wanum, van M.; Dijk, van R.; Hek, de A.P.; Vliet, van F.E.

    2009-01-01

    A broadband class E High Power Amplifier (HPA) is presented. This HPA is designed to operate at S-band (2.75 to 3.75 GHz). A power added efficiency of 50% is obtained for the two stage amplifier with an output power of 35.5 dBm on a chip area of 5.25 times 2.8 mm2.

  3. Broadband S-band Class E HPA

    NARCIS (Netherlands)

    Wanum, M. van; Dijk, R. van; Hek, A.P. de; Vliet, F.E. van

    2009-01-01

    A broadband class E High Power Amplifier (HPA) is presented. This HPA is designed to operate at S-band (2.75 to 3.75 GHz). A power added efficiency of 50% is obtained for the two stage amplifier with an output power of 35.5 dBm on a chip area of 5.25 × 2.8 mm2.

  4. Trimeresurus venom inhibition of anti-HPA-1a and anti-HPA-1b antibody binding to human platelets.

    Science.gov (United States)

    Wlodar, S J; Stone, D L; Sinor, L T

    1995-01-01

    A solid-phase red cell adherence assay was used to demonstrate the specific inhibitory effect of seven species of Trimeresurus snake venom on the binding of HPA-1a- and HPA-1b-specific platelet antibodies. Trimeresurus venom did not inhibit the binding of HLA-, HPA-3a-, HPA-3b-, HPA-4a-, HPA-5a-, and HPA-5b-specific platelet antibodies. Venom from other genera of snakes, including representatives from Agkistrodon, Ancistrodon, Bitis, Bothrops, Bungarus, Causus, Crotalus, Dendroaspis, Ecis, Micrurus, Naja, Notechis, Ophiophagus, Pseudechis, Sepedon (Hemachatus), and Vipera, all failed to specifically inhibit anti-HPA-1a and HPA-1b binding. These results may indicate that the component in Trimeresurus snake venom previously reported to bind to the platelet GPIIb-IIIa complex, inhibiting fibrinogen binding, binds close to the HPA-1a and HPA-1b epitopes.

  5. A users guide to HPA axis research.

    Science.gov (United States)

    Spencer, Robert L; Deak, Terrence

    2016-11-18

    Glucocorticoid hormones (cortisol and corticosterone - CORT) are the effector hormones of the hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system. CORT is a systemic intercellular signal whose level predictably varies with time of day and dynamically increases with environmental and psychological stressors. This hormonal signal is utilized by virtually every cell and physiological system of the body to optimize performance according to circadian, environmental and physiological demands. Disturbances in normal HPA axis activity profiles are associated with a wide variety of physiological and mental health disorders. Despite numerous studies to date that have identified molecular, cellular and systems-level glucocorticoid actions, new glucocorticoid actions and clinical status associations continue to be revealed at a brisk pace in the scientific literature. However, the breadth of investigators working in this area poses distinct challenges in ensuring common practices across investigators, and a full appreciation for the complexity of a system that is often reduced to a single dependent measure. This Users Guide is intended to provide a fundamental overview of conceptual, technical and practical knowledge that will assist individuals who engage in and evaluate HPA axis research. We begin with examination of the anatomical and hormonal components of the HPA axis and their physiological range of operation. We then examine strategies and best practices for systematic manipulation and accurate measurement of HPA axis activity. We feature use of experimental methods that will assist with better understanding of CORT's physiological actions, especially as those actions impact subsequent brain function. This research approach is instrumental for determining the mechanisms by which alterations of HPA axis function may contribute to pathophysiology.

  6. Differentiation of Keratinocytes Modulates Skin HPA Analog.

    Science.gov (United States)

    Wierzbicka, Justyna M; Żmijewski, Michał A; Antoniewicz, Jakub; Sobjanek, Michal; Slominski, Andrzej T

    2017-01-01

    It is well established, that epidermal keratinocytes express functional equivalent of hypothalamus-pituitary-adrenal axis (HPA) in order to respond to changing environment and maintain internal homeostasis. We are presenting data indicating that differentiation of primary neonatal human keratinocytes (HPEKp), induced by prolonged incubation or calcium is accompanied by significant changes in the expression of the elements of skin analog of HPA (sHPA). Expression of CRF, UCN1-3, POMC, ACTH, CRFR1, CRFR2, MC1R, MC2R, and GR (coded by NR3C1 gene) were observed on gene/protein levels along differentiation of keratinocytes in culture with similar pattern seen by immunohistochemistry on full thickness skin biopsies. Expression of CRF was more pronounced in less differentiated keratinocytes, which corresponded to the detection of CRF immunoreactivity preferentially in the stratum basale. POMC expression was enhanced in more differentiated keratinocytes, which corresponded to detection of ACTH immunoreactivity, predominantly in the stratum spinosum and stratum granulosum. Expression of urocortins was also affected by induction of HPEKp differentiation. Immunohistochemical studies showed high prevalence of CRFR1 in well differentiated keratinocytes, while smaller keratinocytes showed predominantly CRFR2 immunoreactivity. MC2R mRNA levels were elevated from days 4 to 8 of in vitro incubation, while MC2R immunoreactivity was the highest in the upper layers of epidermis. Similar changes in mRNA/protein levels of sHPA elements were observed in HPEKp keratinocytes treated with calcium. Summarizing, preferential expression of CRF and POMC (ACTH) by populations of keratinocytes on different stage of differentiation resembles organization of central HPA axis suggesting their distinct role in physiology and pathology of the epidermis. J. Cell. Physiol. 232: 154-166, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Cloning and Expression of Helicobacter pylori HpaA Gene

    Directory of Open Access Journals (Sweden)

    Moein Farshchian

    2009-01-01

    Full Text Available Objective: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomaand gastric mucosa-associated lymphoid tissue (MALT lymphoma. Antibiotictherapies do not protect from potential re-infection and have a risk for development of drugresistance. Therefore, prophylactic vaccine mediated protection against H. pylori is an attractiveclinical interest. H. pylori adhesin A (HpaA is a conserved surface lipoprotein and playsimportant roles in the pathogenesis of infection. In this study the recombinant protein (rHpaAwas over-expressed in E.coli.Materials and Methods: The hpaA gene was amplified by PCR. Prokaryote expression vectorpET28a-hpaA was constructed, and used to transform E.coli BL21DE3. The expressionof recombinant protein induced by IPTG was examined by SDS-PAGE. Western blot wereused to determine immunoreactivity of rHpaA by a rabbit polyclonal antibodies against wholecell of H. pylori.Results: The hpaA gene nucleotide sequence in the recombinant plasmid vector of pET-28-a-hpaA was consistent with that of H.pylori hpaA as published in the GenBank. SDS-PAGEdemonstrated that the constructed prokaryotic expression efficiently produced rHpaA at the1.5 mmol/L of IPTG. HpaA fusion protein was able to react with the rabbit polyclonal antibodyagainst whole cells of H. pylori.Conclusion: A prokaryotic expression system pET-28a-hpaA-BL21 with high efficiency of H.pylori hpaA gene was successfully established and the HpaA fusion protein showed satisfactoryimmunoreactivity. These results indicate that production of a specific recombinant proteinis an alternative and potentially more expeditious strategy for development of H. pylori vaccine.

  8. Childhood stressful events, HPA axis and anxiety disorders.

    Science.gov (United States)

    Faravelli, Carlo; Lo Sauro, Carolina; Godini, Lucia; Lelli, Lorenzo; Benni, Laura; Pietrini, Francesco; Lazzeretti, Lisa; Talamba, Gabriela Alina; Fioravanti, Giulia; Ricca, Valdo

    2012-02-22

    Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

  9. Polymorphism of the human platelet alloantigens HPA-3 and HPA-9w in the Chinese Han population%汉族人群血小板同种抗原HPA-3、HPA-9w多态性分布

    Institute of Scientific and Technical Information of China (English)

    黄慧; 冯明亮; 沈彤; 沈伟; 印彪; 刘达庄

    2007-01-01

    目的 研究我国不同汉族人群血小板同地区种抗原HPA-3、HPA-9w多态性.方法 采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific primers,PCR-SSP)技术对1000名来自不同省份汉族无关献血者进行HPA-3、HPA-9w抗原基因分型.结果 在调查的1000名汉族人群中HPA-3a、HPA-3b基因频率分别为0.5935和0.4065,HPA-9全为a/a纯合子.经x2检测,符合Hardy-Weinberg平衡.不同地区汉族人群之间比较,广东省与陕西、黑龙江、浙江、云南、江苏5省的HPA-3多态性分布差异有统计学意义,其余省份之间多态性分布差异无统计学意义.中国汉族人群与越南人、澳大利亚人HPA-3的多态性分布差异有统计学意义.结论 在随机输血中供受者HPA-3抗原不配合比例达0.3661,这为研究同种免疫血小板减少症、开展血小板同型输注提供了理论基础.

  10. The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

    Science.gov (United States)

    Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

    2014-09-17

    We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

  11. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models?

    Science.gov (United States)

    Veenema, Alexa H

    2009-10-01

    Early life stress (child and adolescent abuse, neglect and trauma) induces robust alterations in emotional and social functioning resulting in enhanced risk for the development of psychopathologies such as mood and aggressive disorders. Here, an overview is given on recent findings in primate and rodent models of early life stress, demonstrating that chronic deprivation of early maternal care as well as chronic deprivation of early physical interactions with peers are profound risk factors for the development of inappropriate aggressive behaviors. Alterations in the hypothalamic-pituitary-adrenocortical (HPA), vasopressin and serotonin systems and their relevance for the regulation of aggression are discussed. Data suggest that social deprivation-induced inappropriate forms of aggression are associated with high or low HPA axis (re)activity and a generally lower functioning of the serotonin system in adulthood. Moreover, genetic and epigenetic modifications in HPA and serotonin systems influence the outcome of early life stress and may even moderate adverse effects of early social deprivation on aggression. A more comprehensive study of aggression, neuroendocrine, neurobiological and (epi)genetic correlates of early life stress using animal models is necessary to provide a better understanding of the invasive aggressive deficits observed in humans exposed to child maltreatment.

  12. Cannabinoids and glucocorticoids modulate emotional memory after stress.

    Science.gov (United States)

    Akirav, Irit

    2013-12-01

    Bidirectional and functional relationships between glucocorticoids and the endocannabinoid system have been demonstrated. Here, I review the interaction between the endocannabinoid and glucocorticoid/stress systems. Specifically, stress is known to produce rapid changes in endocannabinoid signaling in stress-responsive brain regions. In turn, the endocannabinoid system plays an important role in the downregulation and habituation of hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also recruit the endocannabinoid system to exert rapid negative feedback control of the HPA axis during stress. It became increasingly clear, however, that cannabinoid CB1 receptors are also abundantly expressed in the basolateral amygdala (BLA) and other limbic regions where they modulate emotional arousal effects on memory. Enhancing cannabinoids signaling using exogenous CB1 receptor agonists prevent the effects of acute stress on emotional memory. I propose a model suggesting that the ameliorating effects of exogenously administered cannabinoids on emotional learning after acute stress are mediated by the decrease in the activity of the HPA axis via GABAergic mechanisms in the amygdala. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Directory of Open Access Journals (Sweden)

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  14. Cloning and expression of the HpaI restriction-modification genes.

    OpenAIRE

    Ito, H; Shimato, H; Sadaoka, A; Kotani, H; Kimizuka, F; Kato, I

    1992-01-01

    The genes from Haemophilus parainfluenzae encoding the HpaI restriction-modification system were cloned and expressed in Escherichia coli. From the DNA sequence, we predicted the HpaI endonuclease (R.HpaI) to have 254 amino acid residues (Mr 29,630) and the HpaI methyltransferase (M.HpaI) to have 314 amino acid residues (37,390). The R.HpaI and M.HpaI genes overlapped by 16 base pairs on the chromosomal DNA. The genes had the same orientation. The clone, named E. coli HB101-HPA2, overproduced...

  15. Recombinant HpaA purified from Escherichia coli has biological properties similar to those of native Helicobacter pylori HpaA.

    Science.gov (United States)

    Lundstrom, Anneli M; Bolin, Ingrid; Bystrom, Mona; Nystrom, Susanne

    2003-03-01

    The aim of this study was to recombinantly produce and purify Helicobacter pylori adhesin A (HpaA) from Escherichia coli and compare it to purified native H. pylori HpaA, for potential use as a vaccine antigen. The hpaA gene was cloned from H. pylori, transferred to two different expression vectors, and transformed into E. coli. Expression of rHpaA was analysed by immunoblot, inhibition ELISA, and semi-quantitative dot-blot. Using affinity chromatography, rHpaA was purified from E. coli and native HpaA from H. pylori. The binding of both purified proteins to sialic acid was analysed and antibody titres to native and rHpaA were compared after intraperitoneal immunisation of C57/Bl mice. The rHpaA protein was highly expressed in E. coli from both vectors. Purified recombinant and native HpaA bound similarly to fetuin but also to the non-sialylated asialofetuin. Both native HpaA and rHpaA induced comparable amounts of specific antibodies in serum after immunisation and they were identical in double immunodiffusion. In conclusion, rHpaA was successfully produced in E. coli. Purified rHpaA showed biological properties similar to those of native HpaA isolated from H. pylori and may therefore be further used as an antigen in the development of a vaccine against H. pylori infection.

  16. Latent inhibition is disrupted by acute and repeated administration of corticosterone.

    Science.gov (United States)

    Shalev, U.; Feldon, J.; Weiner, I.

    1998-12-01

    Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

  17. The response of circulating brain natriuretic peptide to academic stress in college students.

    Science.gov (United States)

    Amir, Offer; Sagiv, Moran; Eynon, Nir; Yamin, Chen; Rogowski, Ori; Gerzy, Yishay; Amir, Ruthie E

    2010-01-01

    Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.

  18. Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency.

    Science.gov (United States)

    Cohan, Pejman

    2016-01-01

    Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS).

  19. Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function.

    Science.gov (United States)

    Dinces, Sarah M; Romeo, Russell D; McEwen, Bruce S; Tang, Akaysha C

    2014-01-01

    In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the

  20. Modified dexamethasone suppression-corticotropin-releasing hormone stimulation test: A pilot study of young healthy volunteers and implications for alcoholism research in adolescents and young adults.

    Science.gov (United States)

    Sher, Leo; Cooper, Thomas B; Mann, J John; Oquendo, Maria A

    2006-01-01

    The key neuroendocrine component of a response to stress is the hypothalamic-pituitary-adrenocortical (HPA) system. Abnormalities in the HPA system have been implicated in the pathophysiology of psychiatric disorders such as depression, post-traumatic stress disorder, alcoholism and suicide. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA-system function in psychiatric disorders. This neuroendocrine test consists of the administration of a low dose of dexamethasone at 11 pm and the measurement of cortisol levels at one or more time points on the following day. After corticotropin-releasing hormone (CRH) became available for clinical studies, the DST was combined with CRH administration. In this test, patients are pretreated with a single dose of dexamethasone at 11 pm and receive human CRH intravenously at 3 pm the following day. The resulting DST-CRH test proved to be much more sensitive in detecting HPA system alterations than the DST. We have modified the DST-CRH test and used ovine CRH instead of human CRH in a pilot study of a group of young healthy volunteers. Results indicated that it produces results similar to the results obtained with human CRH. This suggests that ovine CRH can be used in psychiatric research. Alcoholism is associated with abnormalities in HPA function. Nonalcoholic subjects with a family history of alcoholism exhibit lower plasma ACTH and beta-endorphin as well as lower ACTH, cortisol, and beta-endorphin responses to psychological stress and CRH stimulation. This suggests that in children of alcoholics, alterations in the mechanisms that regulate HPA axis activity predate the development of alcohol dependence and may be considered inherited traits. Therefore, studies of the HPA system in persons at risk for alcoholism may help understand the neurobiological mechanisms of predisposition to alcoholism.

  1. Optimal beamforming in MIMO systems with HPA nonlinearity

    KAUST Repository

    Qi, Jian

    2010-09-01

    In this paper, multiple-input multiple-output (MIMO) transmit beamforming (TB) systems under the consideration of nonlinear high-power amplifiers (HPAs) are investigated. The optimal beamforming scheme, with the optimal beamforming weight vector and combining vector, is proposed for MIMO systems with HPA nonlinearity. The performance of the proposed MIMO beamforming scheme in the presence of HPA nonlinearity is evaluated in terms of average symbol error probability (SEP), outage probability and system capacity, considering transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, namely, parameters of nonlinear HPA, numbers of transmit and receive antennas, and modulation order of phase-shift keying (PSK), on performance. ©2010 IEEE.

  2. Cellular and molecular mechanisms of antiretroviral effects of HPA23.

    Science.gov (United States)

    Dormont, D; Yeramian, P; Lambert, P; Spire, B; Daveloose, D; Barre-Sinoussi, F C; Chermann, J C

    1988-01-01

    HPA23 is an antimonio-tungstate that exhibits numerous antiviral activities both in vivo and in vitro. It has been described as a competitive inhibitor of human immunodeficiency virus (HIV) reverse transcriptase (RT). Patients treated with daily injections of HPA23 show an inhibition of HIV RT activity in cell culture in 60% of the cases. Using biophysical (electronic spin resonance [ESR]), ultrastructural (microspectroscopic analysis), chemical (spectroscopy), and biological (cell culture) assays, HPA23 cellular and molecular mechanisms may be summarized as follows: 1) competitive inhibition of HIV-RT, 2) no or slight effect on cells infected with HIV in culture, 3) interactions with the cell membranes when long incubations are performed, and 4) antiviral activity possibly mediated by immune modulator effect of the drug.

  3. Human platelet antigen (HPA)-1a peptides do not reliably suppress anti-HPA-1a responses using a humanized severe combined immunodeficiency (SCID) mouse model.

    Science.gov (United States)

    Jackson, D J; Eastlake, J L; Kumpel, B M

    2014-04-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs most frequently when human platelet antigen (HPA)-1a-positive fetal platelets are destroyed by maternal HPA-1a immunoglobulin (Ig)G antibodies. Pregnancies at risk are treated by administration of high-dose intravenous Ig (IVIG) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating some allergic and autoimmune diseases. The HPA-1a/1b polymorphism is Leu/Pro33 on β3 integrin (CD61), and the anti-HPA-1a response is restricted to HPA-1b1b and HLA-DRB3*0101-positive pregnant women with an HPA-1a-positive fetus. We investigated whether or not HPA-1a antigen-specific peptides that formed the T cell epitope could reduce IgG anti-HPA-1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells (PBMC) in blood donations from HPA-1a-immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient (SCID) mice with peptides and HPA-1a-positive platelets. Human anti-HPA-1a in murine plasma was quantitated at intervals up to 15 weeks. HPA-1a-specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA-1a peptides in vitro, stimulation of anti-HPA-1a responses by these peptides occurred in vivo. However, with a second donation from one of these women which, uniquely, had high HPA-1a-specific T cell proliferation in vitro, marked suppression of the anti-HPA-1a response by HPA-1a peptides occurred in vivo. HPA-1a peptide immunotherapy in this model depended upon reactivation of HPA-1a T cell responses in the donor. For FNAIT, we suggest that administration of antigen-specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies.

  4. Human platelet antigen (HPA)-1a peptides do not reliably suppress anti-HPA-1a responses using a humanized severe combined immunodeficiency (SCID) mouse model

    Science.gov (United States)

    Jackson, D J; Eastlake, J L; Kumpel, B M

    2014-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs most frequently when human platelet antigen (HPA)-1a-positive fetal platelets are destroyed by maternal HPA-1a immunoglobulin (Ig)G antibodies. Pregnancies at risk are treated by administration of high-dose intravenous Ig (IVIG) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating some allergic and autoimmune diseases. The HPA-1a/1b polymorphism is Leu/Pro33 on β3 integrin (CD61), and the anti-HPA-1a response is restricted to HPA-1b1b and HLA-DRB3*0101-positive pregnant women with an HPA-1a-positive fetus. We investigated whether or not HPA-1a antigen-specific peptides that formed the T cell epitope could reduce IgG anti-HPA-1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells (PBMC) in blood donations from HPA-1a-immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient (SCID) mice with peptides and HPA-1a-positive platelets. Human anti-HPA-1a in murine plasma was quantitated at intervals up to 15 weeks. HPA-1a-specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA-1a peptides in vitro, stimulation of anti-HPA-1a responses by these peptides occurred in vivo. However, with a second donation from one of these women which, uniquely, had high HPA-1a-specific T cell proliferation in vitro, marked suppression of the anti-HPA-1a response by HPA-1a peptides occurred in vivo. HPA-1a peptide immunotherapy in this model depended upon reactivation of HPA-1a T cell responses in the donor. For FNAIT, we suggest that administration of antigen-specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies. PMID:24261689

  5. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet.

    Science.gov (United States)

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts.

  6. Social crowding stress diminishes the pituitary-adrenocortical and hypothalamic histamine response to adrenergic stimulation.

    Science.gov (United States)

    Bugajski, J; Gadek-Michalska, A; Borycz, J

    1993-12-01

    Social stress of crowding almost totally reduced the rise in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a beta-adrenergic receptor agonist, after 3 and 7 day of crowding and substantially diminished that response after 14 and 21 days. Crowding stress totally abolished the increase in hypothalamic histamine induced by isoprenaline in control rats. Crowding also significantly diminished the increase in serum corticosterone evoked by clonidine, an alpha 2-adrenergic agonist, and abolished the clonidine-induced elevation in hypothalamic histamine levels. The stimulatory effect of phenylephrine, an alpha 1-adrenergic agonist, on corticosterone secretion was only moderately diminished in crowded rats. Neither phenylephrine nor crowding stress changed significantly the hypothalamic histamine levels. These results indicate that social stress of crowding considerably impairs the hypothalamic-pituitary-adrenocortical responsiveness to central beta- and alpha 2-adrenergic receptor stimulation. Crowding also abolishes the rise in hypothalamic histamine induced by beta- and alpha 2-adrenergic agonist, suggesting a role of hypothalamic histamine in the HPA adaptation to the social stress of crowding.

  7. Cytokines as biomarkers in depressive disorder: current standing and prospects.

    Science.gov (United States)

    Lichtblau, Nicole; Schmidt, Frank M; Schumann, Robert; Kirkby, Kenneth C; Himmerich, Hubertus

    2013-10-01

    The frequently observed co-occurrence of depressive disorders and inflammatory diseases suggests a close connection between the nervous and the immune systems. Increased pro-inflammatory and type 1 cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ, appear to be an important link. Cytokines are synthesized by immune cells in the blood and peripheral tissues and by glial cells in the central nervous system (CNS). Evidence suggests that the blood-brain barrier (BBB) is permeable to cytokines and immune cells, and that afferent nerves, e.g. the vagus nerve, mediate the communication between peripheral inflammatory processes and CNS. Cytokines such as IL-1ß, TNF-α and IFN-γ seem to contribute to the pathophysiology of depression by activating monoamine reuptake, stimulating the hypothalamic-pituitary-adrenocortical (HPA) axis and decreasing production of serotonin due to increased activity of indolamine-2,3-dioxygenase (IDO). However, critical appraisal of these hypotheses is required, because cytokine elevation is not specific to depression. Moreover, several effective antidepressants such as amitriptyline and mirtazapine have been shown to increase cytokine production. When applying immunomodulatory therapies, these drugs may increase the risk of specific side effects such as infections or interact with antidepressant drugs on important functions of the body such as the coagulation system.

  8. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    Science.gov (United States)

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  9. The presence of a best friend buffers the effects of negative experiences.

    Science.gov (United States)

    Adams, Ryan E; Santo, Jonathan Bruce; Bukowski, William M

    2011-11-01

    The goal of the current study was to examine how the presence of a best friend might serve as protection against the effect of negative experiences on global self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A total of 103 English-speaking male (n = 55) and female (n = 48) participants from Grade 5 (M = 10.27 years) and Grade 6 (M = 11.30 years) completed booklets about their experiences that occurred 20 min previously and how they felt about themselves at the moment, and they provided saliva multiple times per day over the course of 4 consecutive days. Having a best friend present during an experience significantly buffered the effect of the negativity of the experience on cortisol and global self-worth. When a best friend was not present, there was a significant increase in cortisol and a significant decrease in global self-worth as the negativity of the experience increased. When a best friend was present, there was less change in cortisol and global self-worth due to the negativity of the experience.

  10. 长春地区无偿献血者HPA1-6,15基因分型%Genetic frequency distribution of HPA1-6,15 in ChangChun in China

    Institute of Scientific and Technical Information of China (English)

    于江虹; 杨帆; 焦立新; 刘铁梅

    2011-01-01

    Objective This study is devised to discover the frequencies and principle of HPA genes in Han ethinity in North East of China and to build a donor group with HPA-1a,-2a,-4a,-5a,-6a negative or known HPA antigen types.Methods We randomly collected 172 blood samples from regular paletlet donors ,distracted DNA using TIANGEN kit, measured DNA concentration and purity ,tested using PCR-SSP then did the statistic analysis.Results The frequency of each HPA phenotype is HPA-1aa 0.988 ,HPA-1ab 0.012, HPA- 2aa 0.833 ,HPA- 2ab 0.159, HPA- 2bb 0.008 ,HPA-3aa 0.355, HPA-3ab 0.482, HPA-3bb 0.163, HPA-4aa 0.988,HPA-4ab 0.012, HPA-5aa 0.971 ,HPA-5ab 0.029, HPA-6aa 0.977 ,HPA-6ab 0.023, HPA-15aa 0.286, HPA-15ab 0.498, HPA-15bb 0.216, respectively.We didn ,t find HPA-1bb、-4bb、-5bb、-6bb.The frequency of each HPA genotype is HPA-1a 0.994,HPA-2a 0.913, HPA-3a 0.596, HPA-4a 0.994, HPA-5a 0.985, HPA-6a 0.988, HPA-15a 0.535, respectively.Among them,the frequency of HPA-1a、-4a is above 99%.The mismatch rate of each genotype is HPA-1a 0.011, HPA-2a 0.147, HPA-3a 0.366 ,HPA-4a 0.011, HPA-5a 0.028, HPA-6a 0.023, HPA-15a 0.374 ,respectively.Conclusion This study helps to build a donor group with known HPA antigen types.It will help to promote the detection rate of platelet antibody and to supply the patients with HPA-matched platelets.%目的 调查北方汉族人群人类血小板抗原(HPA)的基因频率及分布规律.建立一支HPA-1a,-2a,-4a,-5a,-6a阴性及已知HPA抗原的献血者队伍.方法 随机抽取172名长春地区固定无偿血小板捐献者静脉血3ml,枸橼酸钠抗凝;采用TIANGEN试剂盒提取DNA.基因定量仪测定DNA的浓度和纯度.采用PCR-SSP方法进行试验.最后进行统计学分析.结果 各表现型的频率分别是:HPA-1aa 0.988,HPA-1ab 0.012,HPA-2aa 0.833,HPA-2ab 0.159,HPA-2bb 0.008,HPA-3aa 0.355,HPA-3ab 0.482,HPA-3bb 0.163,HPA-4aa 0.988,HPA-4ab 0.012,HPA-5aa 0.971,HPA-5ab 0.029,HPA-6aa 0.977,HPA-6ab 0.023,HPA-15aa 0.286,HPA-15ab 0

  11. Frequência dos antígenos plaquetários humanos (HPA) em pacientes trombocitopênicos e predisposição à incompatibilidade transfusional

    OpenAIRE

    Juliana Vieira dos Santos Bianchi; Maria Regina Andrade de Azevedo; Eduardo Jens; Youko Nukui; Dalton Alencar Ficher Chamone

    2012-01-01

    OBJECTIVE: The objective of this study was to evaluate the frequencies of human platelet antigens in oncohematological patients with thrombocytopenia and to analyze the probability of their incompatibility with platelet transfusions. METHODS: Platelet antigen genotyping was performed by sequence-specific primer polymerase chain reaction (SSP-PCR) for the HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b; HPA-15a, HPA-15b alleles in 150 patients of the Hematology S...

  12. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

  13. 吉林地区人群HPA-1~6,15系统基因多态性分析%HPA-1~6,15 system gene polymorphism analysis in jilin

    Institute of Scientific and Technical Information of China (English)

    杨帆; 韩瑜; 焦立新; 鲁威; 金成日; 陈琳; 牛潼; 李俊玮

    2016-01-01

    目的:调查吉林地区人群人类血小板抗原(HPA)基因多态性。方法采用 PCR-SSP 方法对419名血小板捐献志愿者进行血小板抗原 HPA-1~6,15系统基因分型,通过统计方法对分型结果进行基因多态性分析。结果血小板抗原 HPA-1~6,15系统基因频率分别为 HPA-1aa 0.984,HPA-1ab 0.016,HPA-2aa 0.872,HPA-2ab 0.123, HPA-2bb 0.004,HPA-3aa 0.350,HPA-3ab 0.483,HPA-3bb 0.166,HPA-4aa 0.992,HPA-4ab 0.008,HPA-5aa 0.996,HPA-5ab 0.004,HPA-6aa 0.984,HPA-6ab 0.016,HPA-15aa 0.318,HPA-15ab 0.492,HPA-15bb 0.190。结论吉林地区人群 HPA-1~6和 HPA-15系统基因多态性具有本地区特点,HPA-3和 HPA-15系统不配合率最高, HPA-2系统次之。%Objective Survey the crowd in jilin area human platelet antigen (HPA)gene polymorphism.Methods The PCR-SSP method in 419 platelet donors for genotyping antigen HPA_1-6,15 system,the statistical method to clas-sification results for gene polymorphism analysis.Results The frequency of HPA pherotype is HPA-1aa 0.984,HPA-1ab 0.016,HPA-2aa 0.872,HPA-2ab 0.123,HPA-2bb 0.004,HPA-3aa 0.350,HPA-3ab 0.483,HPA-3bb 0.166, HPA-4aa 0.992,HPA-4ab 0.008,HPA-5aa 0.996,HPA-5ab 0.004,HPA-6aa 0.984,HPA-6ab 0.016,HPA-15aa 0.318,HPA-15ab 0.492,HPA-15bb 0.190.Conclusion HPA-1~6,15 system are polymorphic gene frequency distri-bution,the HPA-3 and 15 system,high heterozygosity,it is worth noting that the HPA-2 gene.

  14. Polymorphism of HPA1-7,15 antigens in Chongqing Han population%重庆汉族人群 HPA 1-7、15多态性分布

    Institute of Scientific and Technical Information of China (English)

    毛伟; 王芳; 王跃华; 黄霞; 宋正利; 张蕾; 程磊

    2009-01-01

    目的 了解重庆地区汉族人群人类血小板抗原(HPA)1-7、15抗原分布的多态性.方法 采用PCR-SSO技术对重庆地区无血缘关系的血小板无偿捐献者进行HPA1-7、15 HPA基因分型.结果 HPA各等位基因的频率分别为HPA-1a:0.995 3、HPA-1b:0.004 7;HPA-2a:0.936 2、HPA-2b:0.063 8;HPA-3a:0.575 0、HPA-3b:0.425 0;HPA-4a:0.996 2、HPA-4b:0.003 8;HPA-5a:0.941 8、HPA-5b:0.058 2;HPA-6a:0.985 9、HPA-6b:0.014 1;HPA-7a:1.000 0、HPA-7b:0.000 0;HPA-15a:0.541 3、HPA-15b:0.458 7.结论 重庆地区HPA基因频率呈现其自身的特点.应建立本地区的血小板供者分型数据库.

  15. Cumulative Stress and Cortisol Disruption among Black and Hispanic Pregnant Women in an Urban Cohort

    Science.gov (United States)

    Suglia, Shakira Franco; Staudenmayer, John; Cohen, Sheldon; Enlow, Michelle Bosquet; Rich-Edwards, Janet W.; Wright, Rosalind J.

    2010-01-01

    While adult hypothalamic-pituitary-adrenocortical (HPA) axis functioning is thought to be altered by traumatic experiences, little data exist on the effects of cumulative stress on HPA functioning among pregnant women or among specific racial and ethnic groups. Individuals may be increasingly vulnerable to physiological alterations when experiencing cumulative effects of multiple stressors. These effects may be particularly relevant in urban poor communities where exposure to multiple stressors is more prevalent. The goal of this study was to explore the effects of multiple social stressors on HPA axis functioning in a sample of urban Black (n = 68) and Hispanic (n = 132) pregnant women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS). Pregnant women were administered the Revised Conflict Tactics Scale (R-CTS) survey to assess interpersonal violence, the Experiences of Discrimination (EOD) survey, the Crisis in Family Systems-Revised (CRISYS-R) negative life events survey, and the My Exposure to Violence (ETV) survey, which ascertains exposure to community violence. A cumulative stress measure was derived from these instruments. Salivary cortisol samples were collected five times per day over three days to assess area under the curve (AUC), morning change, and basal awakening response in order to characterize diurnal salivary cortisol patterns. Repeated measures mixed models, stratified by race/ethnicity, were performed adjusting for education level, age, smoking status, body mass index and weeks pregnant at time of cortisol sampling. The majority of Hispanic participants (57%) had low cumulative stress exposure, while the majority of Black participants had intermediate (35%) or high (41%) cumulative stress exposure. Results showed that among Black but not Hispanic women, cumulative stress was associated with lower morning cortisol levels, including a flatter waking to bedtime rhythm. These analyses suggest that the combined

  16. Cumulative Stress and Cortisol Disruption among Black and Hispanic Pregnant Women in an Urban Cohort.

    Science.gov (United States)

    Suglia, Shakira Franco; Staudenmayer, John; Cohen, Sheldon; Enlow, Michelle Bosquet; Rich-Edwards, Janet W; Wright, Rosalind J

    2010-12-01

    While adult hypothalamic-pituitary-adrenocortical (HPA) axis functioning is thought to be altered by traumatic experiences, little data exist on the effects of cumulative stress on HPA functioning among pregnant women or among specific racial and ethnic groups. Individuals may be increasingly vulnerable to physiological alterations when experiencing cumulative effects of multiple stressors. These effects may be particularly relevant in urban poor communities where exposure to multiple stressors is more prevalent. The goal of this study was to explore the effects of multiple social stressors on HPA axis functioning in a sample of urban Black (n = 68) and Hispanic (n = 132) pregnant women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS). Pregnant women were administered the Revised Conflict Tactics Scale (R-CTS) survey to assess interpersonal violence, the Experiences of Discrimination (EOD) survey, the Crisis in Family Systems-Revised (CRISYS-R) negative life events survey, and the My Exposure to Violence (ETV) survey, which ascertains exposure to community violence. A cumulative stress measure was derived from these instruments. Salivary cortisol samples were collected five times per day over three days to assess area under the curve (AUC), morning change, and basal awakening response in order to characterize diurnal salivary cortisol patterns. Repeated measures mixed models, stratified by race/ethnicity, were performed adjusting for education level, age, smoking status, body mass index and weeks pregnant at time of cortisol sampling. The majority of Hispanic participants (57%) had low cumulative stress exposure, while the majority of Black participants had intermediate (35%) or high (41%) cumulative stress exposure. Results showed that among Black but not Hispanic women, cumulative stress was associated with lower morning cortisol levels, including a flatter waking to bedtime rhythm. These analyses suggest that the combined

  17. HpaA from Xanthomonas is a regulator of type III secretion.

    Science.gov (United States)

    Lorenz, Christian; Kirchner, Oliver; Egler, Monique; Stuttmann, Johannes; Bonas, Ulla; Büttner, Daniela

    2008-07-01

    The Gram-negative plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria employs a type III secretion (T3S) system to inject effector proteins into the host cell cytoplasm. Efficient secretion of several effector proteins depends on the cytoplasmic global T3S chaperone HpaB. In this study, we show that HpaB interacts with the virulence factor HpaA, which is secreted by the T3S system and translocated into the plant cell. HpaA promotes secretion of pilus, translocon and effector proteins and therefore appears to be an important control protein of the T3S system. Protein-protein interaction studies and the analysis of HpaA deletion derivatives revealed that the C-terminal protein region, which contains a HpaB binding site, is crucial for the contribution of HpaA to T3S. Secretion of pilus and translocon proteins is not affected when HpaA is expressed as an N-terminal deletion derivative that lacks the secretion and translocation signal. Our data suggest that binding of HpaA to HpaB within the bacterial cell favours secretion of extracellular components of the secretion apparatus. Secretion of HpaA presumably liberates HpaB and thus promotes effector protein secretion after assembly of the T3S apparatus.

  18. Effortful Control and Parenting: Associations with HPA Axis Reactivity in Early Childhood

    Science.gov (United States)

    Kryski, Katie R.; Dougherty, Lea R.; Dyson, Margaret W.; Olino, Thomas M.; Laptook, Rebecca S.; Klein, Daniel N.; Hayden, Elizabeth P.

    2013-01-01

    While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however,…

  19. Cloning and Expression of Helicobacter pylori HpaA Gene

    OpenAIRE

    Moein Farshchian; Saman Hoseinkhani; Javad Atoofi; Shahin Najar Peerayeh

    2009-01-01

    Objective: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomaand gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Antibiotictherapies do not protect from potential re-infection and have a risk for development of drugresistance. Therefore, prophylactic vaccine mediated protection against H. pylori is an attractiveclinical interest. H. pylori adhesin A (HpaA) is a conserved surface lipoprotein and playsimportant roles in the pathogenesis of...

  20. Early calibration of the HPA axis by maternal psychopathology.

    Science.gov (United States)

    Laurent, Heidemarie

    2017-02-01

    Given the central role of stress-responsive neurophysiology in mental and physical health, it is important to understand how particular patterns of stress responsivity may become entrained by the early caregiving environment. In this study we investigated links between maternal depression and anxiety symptom profiles and within-infant development of hypothalamic-pituitary-adrenal (HPA) axis responses from 6 to 18 months of life. Associations with infant cognitive and social-emotional development were also tested to gauge the adjustment implications of HPA response trajectories. Mothers from a low-income community sample reported their symptoms at 3, 6, 12, and 18 months postnatal, and infants engaged in interpersonal stress tasks at 6, 12, and 18 months. Four saliva samples were taken at each time to assess cortisol responses, and a developmental screener at 18 months provided an index of infant adjustment. Multilevel modeling results revealed an association between maternal symptoms and infant HPA axis sensitization-i.e., a higher cortisol reactivity slope that increased over time. In particular, early (3-month) depression symptoms among mothers who had crossed a diagnostic threshold for major depressive disorder predicted this pattern of response, which in turn related to poorer infant developmental outcomes. Results are considered in terms of adaptive calibration of stress response systems, which may come at a cost to individual psychosocial functioning.

  1. Simultaneous genotyping of HPA-17w to -21w by PCR-SSP in Chinese Cantonese.

    Science.gov (United States)

    Zhou, Haojie; Ding, Haoqiang; Chen, Yangkai; Li, Xiaofan; Ye, Xin; Nie, Yongmei

    2015-01-01

    Studies have reported the polymorphism of human platelet antigen (HPA)-17w, -18w, -19w, -20w, and -21w. However, the distribution of these five antigens in Chinese Cantonese is still unknown. In this study, we designed new sequence-specific primers for HPA-19w to -21w and used published primers for HPA-17w and -18w to develop a polymerase chain reaction with the sequence-specific primers (PCR-SSP) method for simultaneously genotyping HPA-17w to -21w. A total of 820 unrelated Cantonese apheresis platelet donors in Guangzhou were involved in this study. Among the five HPAs, complete a/a homozygosity was observed for HPA-17w to -20w with an allele frequency of 1.0000. For HPA-21w, nine individuals (9/820, 1.10%) were found to be HPA-21a/bw heterozygous and the allele frequencies of HPA-21a and HPA-21bw were 0.9945 (1631/1640) and 0.0055 (9/1640), respectively. The reliability of the PCR-SSP method was determined by comparing with the genotyping results by DNA sequencing, and no inconsistencies were observed between the two methods. This study provides a reliable PCR-SSP method for simultaneously genotyping HPA-17w to -21w and could improve HPA-matched platelet transfusion in Chinese Cantonese.

  2. Stress-related development of obesity and cortisol in women.

    Science.gov (United States)

    Vicennati, Valentina; Pasqui, Francesca; Cavazza, Carla; Pagotto, Uberto; Pasquali, Renato

    2009-09-01

    Chronic exposure to environmental stress may play a role in the development of obesity, through hyperactivation of the hypothalamic-pituitary-adrenocortical (HPA) axis. This study investigated the dynamics of weight gain and the activity of the HPA axis in women who developed weight gain after a stressful event. This is a case-control retrospective study. Two groups of age-matched premenopausal women were selected. One (n = 14) included women characterized by a rapid weight gain following a stressful event, defined as the "stress-related obesity " (SRO) group, and the other (n = 21) women with nonstress-related development of obesity, defined as the "nonstress-related obesity " (NSRO) group. Twenty-one healthy premenopausal women served as normal-weight controls. Baseline hormonal and metabolic parameters, and 24-h urinary free cortisol (UFC/24 h) excretion rate (as a measure of HPA-axis activity) were measured in all women. Anthropometry, diet, and physical activity were similar in both obese groups. Both obese groups showed similar metabolic and hormonal profiles, but the SRO group had UFC/24 h values (41.1 +/- 14.3 microg) significantly higher (P < 0.001) with respect to the NSRO (26.6 +/- 17.6 microg) or the normal-weight control groups (21.1 +/- 9.8 microg). Moreover, time (years) to achieve maximum Deltaweight gain (kg) and the Deltaweight gain/time ratio were significantly shorter (P < 0.001) and higher (P < 0.001) in the SRO group with respect to the NSRO group, respectively. In the SRO group, there was a tendency to a significant correlation between UFC/24 h and the Deltaweight gain/time ratio. These findings support the concept that SRO has distinct pathophysiological mechanisms, including hyperactivity of the HPA axis.

  3. Genetic polymorphism of HPA-1 to -5, HPA-15 alloantigensystem in Qingdao Han population%青岛地区汉族人群HPA-1-5,15多态性分布研究

    Institute of Scientific and Technical Information of China (English)

    焦淑贤; 刘晓华; 迟晓云; 孙旭敏; 李长缨; 胡彬; 杨志夏; 丛培芳

    2008-01-01

    目的 研究青岛地区汉族人群人类血小板抗原(HPA)1-5,15抗原分布多态性.方法 采用 PCR-SSP方法 对青岛地区918名无血缘关系固定血小板无偿捐献者进行HPA1-5及HPA-15系统的基因分型.结果 各被检系统等位基因频率分别是1a= 0.9940,1b= 0.0060, 2a=0.9319,2b=0.0681,3a=0.5822,3b=0.4178,4a=0.9897,4b=0.0104,5a=0.9804,5b=0.0196,15a=0.4913,15b=0.5087;HPA基因频率分布与国内资料比较, HPA-1与北方人群(河南),HPA-2 与南方人群(四川)差异有统计学意义;与台湾人群HPA-2,-4,与日本人群HPA-2,-3,-5,与美国黑人HPA-1,-2,-5,与白人HPA-1,-4,-5,-15分别有统计学显著性差异.结论 青岛地区汉族人群HPA分布具有本地人群特点.本组HPA数据分布符合Hardy-Weinberg平衡定律,可以作为北方汉族人群HPA基因分布频率数据库和青岛本地化血小板供者HPA资料库.

  4. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

    Science.gov (United States)

    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  5. Construction of a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA.

    Science.gov (United States)

    Xu, Can; Li, Zhao-Shen; Du, Yi-Qi; Tu, Zhen-Xing; Gong, Yan-Fang; Jin, Jing; Wu, Hong-Yu; Xu, Guo-Ming

    2005-01-07

    To construct a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA gene and to detect its immunogenicity. Genomic DNA of the standard H pylori strain 17 874 was isolated as the template, hpaA gene fragment was amplified by polymerase chain reaction (PCR) and cloned into pUCmT vector. DNA sequence of the amplified hpaA gene was assayed, then cloned into the eukaryotic expression vector pIRES through enzyme digestion and ligation reactions. The recombinant plasmid was used to transform competent Escherichia coli DH5alpha, and the positive clones were screened by PCR and restriction enzyme digestion. Then, the recombinant pIRES-hpaA was used to transform LB5000 and the recombinant plasmid isolated from LB5000 was finally used to transform SL7207. After that, the recombinant strain was grown in vitro repeatedly. In order to identify the immunogenicity of the vaccine in vitro, the recombinant pIRES-hpaA was transfected to COS-7 cells using Lipofectamine2000, the immunogenicity of expressed HpaA protein was detected with SDS-PAGE and Western blot. The 750-base pair hpaA gene fragment was amplified from the genomic DNA and was consistent with the sequence of H pylori hpaA by sequence analysis. It was confirmed by PCR and restriction enzyme digestion that H pylori hpaA gene was inserted into the eukaryotic expression vector pIRES and a stable recombinant live attenuated Salmonella typhimurium DNA vaccine carrying H pylori hpaA gene was successfully constructed and the specific strip of HpaA expressed by pIRES-hpaA was detected through Western blot. The recombinant attenuated Salmonella typhimurium DNA vaccine strain expressing HpaA protein with immunogenicity can be constructed and it may be helpful for further investigating the immune action of DNA vaccine in vivo.

  6. Construction of a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA

    Institute of Scientific and Technical Information of China (English)

    Can Xu; Zhao-Shen Li; Yi-Qi Du; Zhen-Xing Tu; Yan-Fang Gong; Jing Jin; Hong-Yu Wu; Guo-Ming Xu

    2005-01-01

    AIM: To construct a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA gene and to detect its immunogenicity.METHODS: Genomic DNA of the standard H pylori strain 17 874 was isolated as the template, hpaA gene fragment was amplified by polymerase chain reaction (PCR) and cloned into pUCmT vector. DNA sequence of the amplified hpaA gene was assayed, then cloned into the eukaryotic expression vector pIRES through enzyme digestion and ligation reactions. The recombinant plasmid was used to transform competent Escherichia coliDH5α, and the positive clones were screened by PCR and restriction enzyme digestion. Then, the recombinant pIRES-hpaA was used to transform LB5000 and the recombinant plasmid isolated from LB5000 was finally used to transform SL7207. After that, the recombinant strain was grown in vitrorepeatedly. In order to iclentify the immunogenicity of the vaccinein vitro, the recombinant pIRES-hpaA was transfected to COS-7 cells using LipofectamineTM2000, the immunogenicity of expressed HpaA protein was detected with SDS-PAGE and Western blot.RESULTS: The 750-base pair hpaA gene fragment was amplified from the genomic DNA and was consistent with the sequence of H pylori hpaA by sequence analysis. It was confirmed by PCR and restriction enzyme digestion that H pylori hpaA gene was inserted into the eukaryotic expression vector pIRES and a stable recombinant live attenuated Salmonella typhimurium DNA vaccine carrying H pylori hpaA gene was successfully constructed and the specific strip of HpaA expressed by pIRES-hpaA was detected through Western blot.CONCLUSION: The recombinant attenuated Salmonella typhimurium DNA vaccine strain expressing HpaA protein with immunogenicity can be constructed and it may be helpful for further investigating the immune action of DNA vaccine in vivo.

  7. HPA axis dysregulation in men with hypersexual disorder.

    Science.gov (United States)

    Chatzittofis, Andreas; Arver, Stefan; Öberg, Katarina; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

    2016-01-01

    Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels ≥ 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Åsberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.

  8. [Mode and size of HPA-typed platelet apheresis donor bank in Chinese Han population].

    Science.gov (United States)

    Dai, Yu-Dong

    2010-08-01

    This study was purposed to determine the mode and size of human platelet antigens (HPA) typed platelet apheresis donor bank. The published data of HPA distribution collected from Chinese Han population of 16 provinces were analyzed. The combined data were tested with the Hardy-Weinberg equilibrium. The results showed that the bb homozygote was not detected in HPA-1, -4, -6, -10, and b gene was not found in HPA-7-9, 11-14, -16. There were 648 combined HPA 1-16 genotypes in Chinese Han population, and the cumulative frequency of 42 combinations higher than 0.001 were 0.9763. The highest frequency (0.2012) in combination was HPA-(7-8-9-11-12-13-14-16) aa - (1-4-5-6-10) aa-2aa-3ab-15ab. The probability of HPA dual antigen mismatch in HPA-15, -3 and -2 was higher than the 0.1, and the probability in the HPA-1, -5, and -6 was between 0.01 - 0.1. The probability of full-match in HPA1-16 antigens was 0.3195 in Chinese Han population after the random blood transfusion. According to the curve drawn by donor number (N) versus frequency (F), the regression equation LogN = -0.4394 x Ln (F) +0.4324 was derived at P = 95%. If the derived frequency (product of HPA frequency and ABO frequency) is 0.005, then the N should be 576.07 at least in Chinese Han population. It is concluded that the mode of regional, multi-center database of HPA-typed platelet apheresis donor bank may be acceptable in Chinese Han population, and the suitable number of HPA-typed platelet donor in one bank may be 600. Therefore, the bank can be used to treat the platelet transfusion refractoriness (PTR) caused by HPA-15, 3 and 2 mismatch mainly, and can be expanded effectively in similar genetic background to deal with the low-frequency HPA antigens mismatch. The number of HPA-typed platelet apheresis donor influences not only on the frequency of HPA, but also on the frequency of ABO group.

  9. Anti-HPA-1b Mediated Posttransfusion Purpura: A Case Report

    Directory of Open Access Journals (Sweden)

    O. P. Arewa

    2013-01-01

    Full Text Available Posttransfusion purpura (PTP is an uncommon, but potentially fatal, transfusion reaction characterized by profound thrombocytopenia and bleeding. PTP is caused by alloimmunization to human platelet specific antigens following blood component transfusion. Although there is evidence of a wide serological spectrum of culprit antibodies implicated, Anti-human-platelet-antigen- (HPA- 1a is the most common antibody in cases reported. We report a case of posttransfusion purpura in an African American. The patient was negative for HPA-1a antibodies, but anti-HPA-1b was identified with a platelet phenotype of HPA-1a/HPA-1a. Although less common, HPA-1b antibody may be an important consideration in posttransfusion purpura diagnosed in patients of African descent.

  10. Prevalence of the HPA-18w to -21w alleles in the Chinese Han population.

    Science.gov (United States)

    Liu, Y; Hong, X; Xu, X; Ying, Y; He, J; Zhu, F; Lv, H; Yan, L

    2013-04-01

    Recently, four new platelet alloantigen (HPA) systems HPA-18w to-21w were identified. However, genotyping for HPA-18w to -21w alleles was rarely reported. Here, we established a polymerase chain reaction sequence-based typing (PCR-SBT) method and investigated the distribution of HPA-18w to -21w alleles in the Chinese Han population. The specific primers of HPA-18w, -19w, -20w and -21w were designed, and the PCR products were bidirectionally sequenced. 855 randomly selected platelet donors were genotyped for HPA-18w to -21w with the PCR-SBT method. The results showed that all individuals were monomorphic for HPA-18w to HPA-20w with a/a homozygous frequency of 1.0 and absence of HPA-18bw to -20bw alleles. The frequencies of the HPA-21a/21a and HPA-21a/21b genotypes were 0.981(839/855) and 0.019(16/855), respectively. Seven mutations were confirmed on sequenced region separate from HPA polymorphisms, including ITGA2 (IVS17+48G>A and IVS17+72G>A), ITGA2B (IVS19-26C>G) and ITGB3 (IVS4+234C>T, IVS11-19 T>C, IVS11-104T>C and GT repeats from IVS11-131 to IVS11-109). These data will provide useful information for diagnosis, prevention and treatment of alloimmune thrombocytopaenia.

  11. Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice.

    Science.gov (United States)

    Albu, Stefana; Romanowski, Christoph P N; Letizia Curzi, M; Jakubcakova, Vladimira; Flachskamm, Cornelia; Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Schmidt, Ulrike; Rein, Theo; Holsboer, Florian; Hausch, Felix; Paez-Pereda, Marcelo; Kimura, Mayumi

    2014-04-01

    FK506-binding protein 51 (FKBP51) is a co-chaperone of the glucocorticoid receptor, functionally linked to its activity via an ultra-short negative feedback loop. Thus, FKBP51 plays an important regulatory role in the hypothalamic-pituitary-adrenocortical (HPA) axis necessary for stress adaptation and recovery. Previous investigations illustrated that HPA functionality is influenced by polymorphisms in the gene encoding FKBP51, which are associated with both increased protein levels and depressive episodes. Because FKBP51 is a key molecule in stress responses, we hypothesized that its deletion impacts sleep. To study FKBP51-involved changes in sleep, polysomnograms of FKBP51 knockout (KO) mice and wild-type (WT) littermates were compared at baseline and in the recovery phase after 6-h sleep deprivation (SD) and 1-h restraint stress (RS). Using another set of animals, the 24-h profiles of hippocampal free corticosterone levels were also determined. The most dominant effect of FKBP51 deletion appeared as increased nocturnal wake, where the bout length was significantly extended while non-rapid eye movement sleep (NREMS) and rapid eye movement sleep were rather suppressed. After both SD and RS, FKBP51KO mice exhibited less recovery or rebound sleep than WTs, although slow-wave activity during NREMS was higher in KOs, particularly after SD. Sleep compositions of KOs were nearly opposite to sleep profiles observed in human depression. This might result from lower levels of free corticosterone in FKBP51KO mice, confirming reduced HPA reactivity. The results indicate that an FKBP51 deletion yields a pro-resilience sleep phenotype. FKBP51 could therefore be a therapeutic target for stress-induced mood and sleep disorders.

  12. Adaptation of the hypothalamic-pituitary hormones during intensive endurance training.

    Science.gov (United States)

    Bobbert, T; Brechtel, L; Mai, K; Otto, B; Maser-Gluth, C; Pfeiffer, A F H; Spranger, J; Diederich, S

    2005-11-01

    Physical activity leads to changes in the hypothalamic-pituitary hormonal system. However, acute and long-term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic-pituitary-adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11beta-hydroxysteroid-dehydrogenase system (11beta-HSD). Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24-h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon. Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11beta-HSD-1 was up-regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic-pituitary-hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training. The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11beta-HSD system. Changes in the other hypothalamic-pituitary hormonal axes were the result of long-term differences in training levels and were not altered by the marathon.

  13. Honeywell HPA200精密气压计测量异常现象分析%Abnormal measure analysis of the Honeywell HPA200 precision barometer

    Institute of Scientific and Technical Information of China (English)

    张栋

    2011-01-01

    In order to solve the transnormal error which measured by the Honeywell HPA200 precision barometer,factors that related to the phenomenon are compared. The EMI characters of the HPA200 barometer have been found that the basic factor is the 400 MHz wireless interphone. Then,the hardware of the LC band reject filter is designed to lower the measure error value by the HPA200 precision barometer. The measure error is obviously reduced by the HPA200 barometer with the LC band reject filter in practice,and the ability of the anti-EMI is improved. Finally,the measure accuracy of the system demand is met by the HPA200 barometer with the LC band reject filter.%为了解决Honeywell HPA200精密气压计出现的严重超标的测量异常现象,通过分析对比相关的因素,查找验证HPA200精密气压计受到400 MHz无线对讲机的电磁干扰,依此设计硬件LC带阻滤波器,来滤除400 MHz左右的确定性干扰信号.最终通过实际测试和验证,LC带阻滤波器可以增强HPA200精密气压计抗干扰能力,降低气压计测量误差,并达到HPA200精密气压计的测量指标要求.

  14. Hpa1 harpin needs nitroxyl terminus to promote vegetative growth and leaf photosynthesis in Arabidopsis

    Indian Academy of Sciences (India)

    Xiaojie Li; Liping Han; Yanying Zhao; Zhenzhen You; Chunling Zhang; Zhenzhen You; Hansong Dong; Chunling Zhang

    2014-03-01

    Hpa1 is a harpin protein produced by Xanthomonas oryzae, an important bacterial pathogen of rice, and has the growth-promoting activity in plants. To understand the molecular basis for the function of Hpa1, we generated an inactive variant protein, Hpa1NT, by deleting the nitroxyl-terminal region of the Hpa1 sequence and compared Hpa1NT with the full-length protein in terms of the effects on vegetative growth and related physiological responses in Arabidopsis. When Hpa1 was applied to plants, it acted to enhance the vegetative growth but did not affect the floral development. Enhanced plant growth was accompanied by induced expression of growth-promoting genes in plant leaves. The growth-promoting activity of Hpa1 was further correlated with a physiological consequence shown as promoted leaf photosynthesis as a result of facilitated CO2 conduction through leaf stomata and mesophyll cells. On the contrary, plant growth, growth-promoting gene expression, and the physiological consequence changed little in response to the Hpa1NT treatment. These analyses suggest that Hpa1 requires the nitroxyl-terminus to facilitate CO2 transport inside leaf cells and promote leaf photosynthesis and vegetative growth of the plant.

  15. HpaA Is Essential for Helicobacter pylori Colonization in Mice

    OpenAIRE

    Carlsohn, Elisabet; Nyström, Johanna; Bölin, Ingrid; Nilsson, Carol L.; Svennerholm, Ann-Mari

    2006-01-01

    Infection with the human gastric pathogen Helicobacter pylori can give rise to chronic gastritis, peptic ulcer, and gastric cancer. All H. pylori strains express the surface-localized protein HpaA, a promising candidate for a vaccine against H. pylori infection. To study the physiological importance of HpaA, a mutation of the hpaA gene was introduced into a mouse-adapted H. pylori strain. To justify that the interruption of the hpaA gene did not cause any polar effects of downstream genes or ...

  16. 使用Taqman PCR技术建立人类血小板抗原-1~5、15分型体系%Establishment of HPA-1-to-5 and HPA-15 genotyping systems by Taqman PCR

    Institute of Scientific and Technical Information of China (English)

    沈彤; 赵玉林; 刘熔增; 刘达庄

    2011-01-01

    Objective To investigate gene frequencies of HPA-l-to-5 and HPA-15 from apheresis platelet donors in Shanghai,and evaluate a new genotyping technique. Methods A total of 500 platelet aphresis donors were genotyped for HPA-\\-to-5 and HPA-15 antigen systems by means of Taqman PCR,and 100 samples were selected randomly for comparison by PCR-SSP. Results The gene frequencies of HPA-la, HPA-1 b, HPA-2a, HPA-2b, HPA-3a, HPA-U, HPAAa, HPAAb, HPA-5a,HPA-5b,HPA-15a and HPA-I5b identified using Taqman PCR were 0.999,0.001,0. 953,0.047,0.582,0.418, 0.999,0.001,0.988,0. 012,0. 524 and 0. 476,respectively. In one case for typing HPA-5 allele.the result obtained by Taqman PCR was different compared with PCR-SSP. Conclusion The allele gene frequencies of EPA systems are not significantly different between Shanghai area and other regions in China,meanwhile,the results are comparable to the frequency distribution of HPA in Chinese Hans and fit Hardy-Weinberg equilibrium. Difference observed in the distribution of HPA-5 may be the result of nonspecific amplification of PCR-SSP according to sequencing confirmation. Taqman PCR technique with high specificity and timesaving advantages has good application prospect in typing for HPA systems,which is available as a significant complement to existing methods.%目的 了解上海地区单采血小板献血人群HPA-1~5、15多态性分布,分析评估新的分型技术.方法 利用TaqMan PCR技术对500份上海地区单采血小板供者标本进行HPA-1~5、15抗原系统等位基因分型,并随机抽取100份标本使用PCR-SSP技术进行比对.结果 HPA各等位基因频率分别为HPA-1a:0.999,HPA-1b:0.001,HPA-2a:0.953,HPA-2b:0.047,HPA-3a:0.582,HPA-3b:0.418,HPA-4a:0.999,HPA-4b:0.001,HPA-5a:0.988,HPA-5b:0.012,HPA-15a:0.524,HPA-15b:0.476;有1份标本HPA-5等位基因与SSP检测结果产生差异.结论 上海地区HPA各等位基因频率与国内各地区人群分布无明显差异,与中国汉族人群HPA分布情况基

  17. HPA-axis activity as a predictor of future disruptive behaviors in young adolescents

    NARCIS (Netherlands)

    Sondeijker, Frouke E. P. L.; Ferdinand, Robert F.; Oldehinkel, Albertine J.; Tiemeier, Henning; Ormel, Johan; Verhulst, Frank C.

    2008-01-01

    Low HPA-axis activity has been proposed as a risk factor for disruptive behaviors. However longitudinal data on this topic are practically lacking. In the present study we investigated if low HPA-axis activity predicted future disruptive behaviors. We included 1,399 boys and girls from the Dutch gen

  18. Bouncing back - trauma and the HPA-axis in healthy adults

    Directory of Open Access Journals (Sweden)

    Ellen Renée Klaassens

    2010-12-01

    Full Text Available Dysregulation of the hypothalamic–pituitary–adrenal (HPA-axis is thought to underlie stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD. Some studies have reported HPA-axis dysregulation in trauma-exposed (TE adults in the absence of psychiatric morbidity. In this dissertation we set out to unravel part of the mechanism that underlies the complex relations between trauma exposure, stress regulation, and psychopathology. Mentally healthy TE subjects were compared with non-trauma-exposed (NE healthy controls. To distinguish between the potential effects of childhood trauma and adulthood trauma, we included women exposed to childhood trauma as well as men who were exposed to trauma during adulthood. Basal HPA-axis functioning was assessed with salivary cortisol samples. HPA-axis reactivity was assessed with the dexamethasone/corticotropin-releasing hormone (Dex/CRH test. The results show that childhood trauma exposure is associated with an attenuated cortisol response after the Dex/CRH challenge test in women. In contrast, trauma exposure during adulthood was not associated with alterations in HPA-axis regulation after the Dex/CRH test. Neither childhood trauma nor adulthood trauma were associated with basal HPA-axis functioning. Childhood trauma rather than adulthood trauma may chronically affect HPA-axis functioning. Since the association between adulthood trauma and resilience to psychopathology cannot be explained by HPA-axis functioning alone, other factors must play a role.

  19. Co-occurring manic symptomatology influences HPA axis alterations in depression

    NARCIS (Netherlands)

    Jabben, Nienke; Nolen, Willem A.; Smit, Johannes H.; Vreeburg, Sophie A.; Beekman, Aartjan T. F.; Penninx, Brenda

    2011-01-01

    Although dysfunctioning of the HPA axis is considered to be a core pathophysiological process in mood disorders, the evidence with regard to depression remains conflicting. This could partly be due to the large heterogeneity within mood disorders, since HPA axis abnormalities may also be associated

  20. 广州地区汉族人群HPA-14多态性调查

    Institute of Scientific and Technical Information of China (English)

    黎美娜; 汪传喜; 滕青; 聂咏梅

    2010-01-01

    目的 调查广州地区汉族人群HPA-14多态性.方法 用PCR-SSP法对200例广州地区汉族无偿血小板献血者进行HPA-14基因分型.结果 HPA-14a和14b的基因频率分别为1.0000和0.0000;与其他国家和地区基因频率数据相符;在随机输血中HPA-14抗原不配伍的机会为0.结论 获得广州地区汉族人群HPA-14基因频率,可为建立广州地区血小板供者库和开展血小板同型输注提供实验数据.

  1. Associations between anthropometrical measurements, body composition, single-nucleotide polymorphisms of the hypothalamus/pituitary/adrenal (HPA) axis and HPA axis functioning.

    Science.gov (United States)

    Rutters, Femke; Nieuwenhuizen, Arie G; Lemmens, Sofie G T; Bouwman, Freek; Mariman, Edwin; Westerterp-Plantenga, Margriet S

    2011-06-01

    The relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and (visceral) obesity may be explained by single-nucleotide polymorphisms (SNPs) of the HPA axis. Objective  To investigate the relationship between the HPA axis SNP's 'BclI' in the glucocorticoid receptor gene and C8246T in the POMC gene and anthropometric measurements, body composition, 5-h cortisol concentrations, HPA axis feedback sensitivity, as well as HPA axis feedback sensitivity under stress in men and women. DESIGN/SUBJECTS/MEASUREMENTS: We assessed in 92 men and 102 women (18-55 years, BMI 19-41 kg/m(2) ) anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test and HPA axis functioning under a challenged condition consisting of a standardized high intensity test with ingestion of 4 mg dexamethasone. In female participants, the 8246C allele carriers compared to the 8246T allele carries were associated with a higher 5-h cortisol exposure (1·52 × 10(5) ± 0·8 vs 1·18 × 10(5) ± 0·6 nm·min, P < 0·05) and higher baseline postdexamethasone cortisol concentrations (54·5 ± 35·6 vs 37·4 ± 18·5 nm, P < 0·05). In male participants regarding the C8246T allele carriers and in both male and female participants regarding the BclI genotypes, no significant differences in anthropometric measurements, body composition and HPA axis functioning were observed. Multiple regression analysis showed that only increased 5-h cortisol exposure significantly related to changes in anthropometric measurements and body composition; the BclI and C8246T genotypes were not associated. Our preliminary data show that in both men and women (18-55 years, BMI 19-41 kg/m(2) ), the SNP's BclI and C8246T of the HPA axis were primarily related to altered HPA axis functioning, rather than to altered anthropometric measurements and body

  2. [Cloning, expression and identification of hpaA gene from a clinical isolate of Helicobacter pylori].

    Science.gov (United States)

    Mao, Ya-Fei; Yan, Jie; Li, Li-Wei

    2003-02-01

    To clone Helicobacter pylori adhesin (hpaA) gene,to construct the expression vector of the gene and to identify immunogenicity of the fusion protein. The hpaA gene from a clinical isolate Y06 of H.pylori was amplified by high fidelity PCR. The nucleotide sequence of the target DNA amplification fragment was sequenced after T-A cloning. The expression vector pET32a with inserted hpaA gene was constructed. hpaA fusion protein was expressed in E.coli strain BL21DE3 induced by IPTG at different dosages. Western blot using antibody against whole cell of H.pylori as well as immunodiffusion assay using antiserum of rabbit against the fusion protein was applied to determine immunogenicity of the fusion protein. In comparison with the reported corresponding sequences, the homology of nucleotide sequence of the cloned hpaA gene was from 94.25% approximate, equals 97.32%, while the homology of its putative amino acid sequence was as high as 95.38% approximate, equals 98.46%. The expression output of HpaA fusion protein in pET32a-hpaA-BL21DE3 system was approximately 40% of the total bacterial proteins. HpaA fusion protein was able to combine with antibody against whole cell of H.pylori and induce rabbit to preduce high titer antibody after the animal was immunized with the protein. An expression system with high efficiency of H.pylori hpaA gene has been established successfully. The expressed HpaA fusion protein with satisfactory immunogenicity and immunoreactivity can be used as antigen in H.pylori vaccine.

  3. Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Shuhong Shi; Hui Zhang

    2014-01-01

    Objective:Our study aimed to investigate the relationships between the clinico-pathologic features and the hepa-ranase (Hpa) and CD222 expressions in bladder carcinoma. Methods:The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues (controls) were assessed using the immunohistochemical stain-ing method. Results:The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42%and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens (P<0.01). Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma (P<0.01). A positive correlation was observed between the expressions of Hpa and CD222 (P<0.05). The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging (P<0.05). The 5-year survival rate was significantly higher in negative expression of the Hpa group than that in the positive expression group (P<0.05). Compared with the non-co-positive expression group, the 5-year survival rate in the co-positive expression of Hpa and CD222 group was significantly lower (P<0.05). Conclusion:High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Our results provide helpful information for the further diagnosis and therapy of bladder carcinoma.

  4. Lower immunglobulin A levels but not lower cortisol or α-amylase activity in children with chronic tension-type headache.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Fernández-Mayoralas, Daniel M; Arroyo-Morales, Manuel; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; Díaz-Rodríguez, Lourdes; Pareja, Juan A

    2011-03-01

    The study was designed to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), immunoglobulin A (IgA) (immune system) concentrations and α-amylase (sympathetic nervous system [SNS]) activity between children with chronic tension-type headache (CTTH) and healthy children. Thirty-six children, 10 boys and 26 girls (age: 9 ± 2 years) with CTTH and 36 age- and sex-matched healthy children were recruited. Salivary cortisol, α-amylase activity, salivary flow rate, IgA concentration and IgA rate were collected from non-stimulated saliva. A headache diary was used for collecting data on intensity, frequency and duration of headache for four weeks. Children with CTTH showed lower IgA concentration (p = .008) and IgA rate (p = .039), but not lower cortisol concentration (p = .447), salivary flow rate (p = .289) or α-amylase activity (p = .559), as compared to healthy children. Neither age (p > .582) nor gender (p > .227) influenced salivary markers. A significant association between the number of years with headache and IgA concentration (r(s) = - 0.385; p = .023) was found: the greater the number of years with headache, the lower the IgA concentration. These results suggest that children with CTTH present with deficits in the immune system, but not dysfunction in the HPA axis or SNS. Future studies are needed to elucidate the direction of these relationships.

  5. Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction.

    Science.gov (United States)

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction.

  6. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome.

    Science.gov (United States)

    Kim, Hee Kyung; Yoon, Jee Hee; Jeong, Yun Ah; Kang, Ho Cheol

    2016-12-01

    In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown. Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test. Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001). The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  7. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Hee Kyung Kim

    2016-12-01

    Full Text Available BackgroundIn subclinical Cushing syndrome (SC, it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA axis after adrenalectomy between patients with overt Cushing syndrome (OC and SC remain unknown.MethodsThirty-six patients (10 with OC and 26 with SC with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH stimulation test.ResultsLevels of basal 24-hour urine free cortisol (UFC, serum cortisol after an overnight dexamethasone suppression test (DST, and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001, with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001.ConclusionThe HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  8. The polymorphism of HPA-1 ~ 6,15 in Tibetan blood donors from Lhasa%拉萨藏族献血人群HPA-1~6、15基因多态性

    Institute of Scientific and Technical Information of China (English)

    李梦丹; 王珏; 宋宁; 辛友盼; 李晓娟; 扎西顿珠; 刘忠; 陈强

    2013-01-01

    Objective To investigate the allele distribution of HPA-1 ~ 6,15 in Titetan blood donors from Lhasa.Methods The genotyping of HPA-1 ~ 6,15 were performed by the PCR with sequence-specific primers (PCR-SSP).A total of 405 healthy volunteer unrelated Tibetan blood donors were included.Results The allele frequencies of HPAs for 405Tibetan individuals were HPA-1a:0.9383,HPA-1b:0.061 7;HPA-2a:0.971 6,HPA-2b:0.028 4;HPA-3a:0.617 3,HPA-3b:0.382 7 ;HPA-4a:0.992 6,HPA-4b:0.007 4 ;HPA-5a:0.949 4,HPA-5b:0.050 6;HPA-6a:0.991 4,HPA-6b:0.008 6;HPA-15a:0.603.7,HPA-15b:0.396 3,respectively.The comparison with data of other ethnic groups showed that the allele frequencies of HPA-1,HPA-2,HPA-3,HPA-4,HPA-5 and HPA-15 were all significantly different between Tibetan and South Chinese Han (n =1 554).While compared with Xinjiang Khalkhas (n =105),such a significant difference was only found in HPA-2 system.The HPA-1b allele frequency in the Tibetan was significantly lower than that found in Caucasian from Germany (n =119),but significantly higher than the other compared Mongolian race except for Xinjiang Khalkhas.Conclusion Our study demonstrates that the distribution of HPA-1 ~6,15 in Tibetan exhibit unique characteristics.%目的 了解血小板特异性抗原(HPA)-1~6、15基因多态性在拉萨藏族献血人群中的分布特征.方法 采用聚合酶链式反应-序列特异性引物(PCR-SSP)技术对405名藏族无关献血者作HPA-1~6、15基因分型.结果 405名无关献血者HPA各等位基因的频率分别为:HPA-1a:0.9383,HPA-1b:0.061 7;HPA-2a:0.971 6,HPA-2b:0.028 4;HPA-3a:0.617 3,HPA-3b:0.382 7;HPA-4a:0.992 6,HPA-4b:0.007 4; HPA-5a:0.949 4,HPA-5b:0.050 6; HPA-6a:0.991 4,HPA-6b:0.008 6;HPA-15a:0.603 7,HPA-15b:0.396 3.人群资料比对结果显示,与南方汉族人群(n=1 554)相比,拉萨藏族献血人群HPA-1、HPA-2、HPA-3、HPA-4、HPA-5、HPA-15系统基因频率具有明显差异;与新疆柯尔克孜族人群(n =105)相比,仅HPA-2系统基因频率

  9. The polymorphism of HPA-1 ~6、15 in Chinese Han population%2458名中国汉族人类HPA-1~6、15基因多态性的研究

    Institute of Scientific and Technical Information of China (English)

    周丹; 张印则; 庄乃保; 孔令魁

    2012-01-01

    Objective To analyze human platelet antigens (HPA)1-6,15 polymorphism,and study the allele frequencies in the North Chinese Han and South Chinese Han. Methods The genotypes of HPA1 -6,15 systems were performed by FLOW-SSO for 2 458 samples. Results The gene frequencies were 0.991 7,0.008 3,0.955 2,0.044 8,0.558 6,0.441 4,0.998 0,0.0020,0.986 2,0.013 8,0.985 6,0.0144,0.545 2,0.454 8 for HPA-la,HPA-lb,HPA-2a,HPA-2b,HPA-3a,HPA-3b,HPA-4a,HFA-4b,HPA-5a,HPA-5b,HPA-6a,HPA-6b,HPA-15a,HPA-15b,respectively.The phenotype frequencies of HPAl-6,15 in the South Chinese Han was compared to the frequencies in the north Chinese Han. There is significant deviation from Hardy-Weinbery equilibrium within HPA-l ,3 in the south Chinese Han and north Chinese Han(χ2 = 15. 032 0、5.418 8 ,P <0.05). There was a good fit to Hardy-Weinbery equilibrium within each group. Conclusion The highest heterozygotes are HPA-3 and HPA-15,which indicate that the original difference of HPA-l and HPA-3 in South and North of China. In order to provide HPA-matched platelet transfusion in alloimmune thromboeytopenic patients,the building of China HPA-typed plateletpheresis donor registry is very useful%目的 分析中国汉族人群HPA-1~6、15系统的基因多态性,研究中国南、北方汉族人群HPA-1~6、15的基因分布.方法 采用Luminex结合序列特异性寡核苷酸探针(flow-sequence specific oligonucleotide probes,FLOW-SSO)方法对2458名深圳市机采血小板无偿捐献者(其中南方人群1 554人,北方人群904人)进行HPA-1~6,15系统基因分型.采用聚合酶链反应-序列特异性引物(PCR-sequence specific primer,PCR-SSP)方法对有疑问的标本及罕见抗原(如HPA-1b/1b、2b/2b、5b/5b等)做进一步确认.结果 中国汉族人群中HPA-1 ~6、15基因频率分别为,HPA-1a0.991 7,HPA-1b 0.008 3,HPA-2a 0.955 2,HPA-2b 0.044 8,HPA-3a0.558 6,HPA-3b 0.441 4,HPA-4a0.9980,HPA-4b0.0020,HPA-5a0.986 2,HPA-5b0.013 8,HPA-6a0.985 6,HPA-6b0.0144,HPA-15a0.545 2,HPA

  10. The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

    Science.gov (United States)

    Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

    2012-01-01

    Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

  11. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  12. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Science.gov (United States)

    Zhu, Li-Juan; Liu, Meng-Ying; Li, Huan; Liu, Xiao; Chen, Chen; Han, Zhou; Wu, Hai-Yin; Jing, Xing; Zhou, Hai-Hui; Suh, Hoonkyo; Zhu, Dong-Ya; Zhou, Qi-Gang

    2014-01-01

    Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  13. 广州汉族人群HPA-9多态性调查

    Institute of Scientific and Technical Information of China (English)

    陈扬凯; 夏文杰; 叶欣; 罗广平; 付涌水; 徐秀章; 丁浩强; 邓晶

    2008-01-01

    目的 调查广州地区汉族人群血小板抗原HPA-9多态性分布情况.方法 用PCR-SSP技术对144例广州地区固定机采血小板供者进行HPA-9基因分型.结果 检出HPA-9a 144例,未检出HPA-9bw.研究人群HPA-9的基因型分布与H-W法则吻合.与不同国家和地区HPA-9基因频率比较无显著性差异(P>0.900).结论 填补了广州地区人群HPA-9多态性分布数据的空白,可以作为本地区血小板供者HPA资料库.

  14. From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants.

    Science.gov (United States)

    Pecoraro, Norman; Dallman, Mary F; Warne, James P; Ginsberg, Abigail B; Laugero, Kevin D; la Fleur, Susanne E; Houshyar, Hani; Gomez, Francisca; Bhargava, Aditi; Akana, Susan F

    2006-08-01

    The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly flexible operating characterisitics. Major drivers include two circadian drivers, two extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up (systemic) threats, and two intra-hypothalamic networks coordinating behavioral, autonomic, and neuroendocrine outflows. These various networks jointly and flexibly control HPA axis output of periodic (oscillatory) functions and a range of adventitious systemic or psychological threats, including predictable daily cycles of energy flow, actual metabolic deficits over many time scales, predicted metabolic deficits, and the state-dependent management of post-prandial responses to feeding. Evidence is provided that reparation of metabolic derangement by either food or glucocorticoids results in a metabolic signal that inhibits HPA activity. In short, the HPA axis is intimately involved in managing and remodeling peripheral energy fluxes, which appear to provide an unidentified metabolic inhibitory feedback signal to the HPA axis via glucocorticoids. In a complementary and perhaps a less appreciated role, adrenocortical hormones also act on brain to provide not only feedback, but feedforward control over the HPA axis itself and its various drivers, as well as coordinating behavioral and autonomic outflows, and mounting central incentive and memorial networks that are adaptive in both appetitive and aversive motivational modes. By centrally remodeling the phenotype, the HPA axis provides ballistic and predictive control over motor outflows relevant to the type of stressor. Evidence is examined concerning the global hypothesis that the HPA axis comprehensively induces integrative phenotypic plasticity, thus

  15. Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

    Science.gov (United States)

    Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

    2015-05-01

    Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity.

  16. Revised stereochemistry of ceramide-trafficking inhibitor HPA-12 by X-ray crystallography analysis.

    Science.gov (United States)

    Ueno, Masaharu; Huang, Yi-Yong; Yamano, Akihito; Kobayashi, Shū

    2013-06-07

    In response to Berkeš's report revising the stereochemistry of HPA-12, an important ceramide-trafficking inhibitor that was discovered and synthesized and its stereochemistry determined in 2001, the synthesis and the stereochemistry were reinvestigated. A large-scale synthetic method for HPA-12 based on a Zn-catalyzed asymmetric Mannich-type reaction in water was developed. Single crystals of HPA-12 for X-ray crystallographic analysis were obtained from ethyl propionate/n-hexane, and the stereochemistry was definitely determined to be 1R,3S, consistent with Berkeš's revised structure.

  17. [Analysis of gene polymorphism of HPA and HLA-I in Chinese Xi'an voluntary platelet donors].

    Science.gov (United States)

    Wang, Xiao-Fang; Liu, Meng-Li; Zhou, Dang-Xia; Qi, Jun; Liu, Sheng; Wang, Tian-Ju

    2011-12-01

    To study the allele frequencies and their polymorphism characteristics of human platelet antigen (HPA) and human leucocyte antigen-I (HLA-I) in Chinese xi'an population, the types of HPA and HLA-I in 375 Chinese xi'an voluntary platelet donors were detected by PCR-SSP and PCR-SSO as well as flow cytometry with magnetic beads, and were analyzed. The results showed that there was no polymorphism in HPA-7-HPA-14, HPA-16 and HPA-17 which only expressed-aa type, the -bb type was only detected in HPA-3 and HPA-15, 9 out of 16 samples for the HPA-5ab phenotype simultaneously expressed HPA-15ab, the other 7 samples expressed HPA-15bb, no HPA-15aa phenotype was observed. Phenotypes detected in this study were HPA-1aa-17aa, HPA-1ab, -2ab, -3ab, -3bb, -4ab, -5ab, -6ab, -15ab and -15bb. Among 375 cases, HLA-A specificity of 16 species was observed, which accounted for 76% (16/21) of detectable phenotype specificity in this locus, moreover, 11 species showed frequency > 1%; HLA-B specificity of 36 species was observed which accounted for 84% (36/43) of detectable phenotype specificity in this locus, moreover 23 species showed frequency > 1%, these species were covered by common specific HLA-I in northern China, 264 species haplotype HLA-A-B were found in 375 cases, the frequency of 30 species was > 1%. It is concluded that the gene frequency distribution of HPA and HLA-I in Chinese Xi'an population is in accordance with population of northern China on the whole, but it has its own characteristics.

  18. A truncated form of HpaA is a promising antigen for use in a vaccine against Helicobacter pylori.

    Science.gov (United States)

    Flach, Carl-Fredrik; Svensson, Natascha; Blomquist, Margareta; Ekman, Annelie; Raghavan, Sukanya; Holmgren, Jan

    2011-02-01

    HpaA is a Helicobacter pylori-specific lipoprotein that has been shown to be an effective protective antigen for mucosal vaccination against H. pylori infection in mice. However, detergents are needed for the purification of full-length HpaA (HpaA(full)), which might confer toxicity, thus making HpaA(full) unsuitable for use in a human vaccine. We here describe a recombinantly produced truncated version of HpaA (HpaA(trunc)), which is easily purified without the use of detergents. Evaluation in the murine H. pylori infection model showed that sublingual immunization with HpaA(trunc) was equally immunogenic and protective as immunization with HpaA(full). Immunization with a combination of HpaA(trunc) and recombinant UreB protein induced strong immune responses to both antigens and importantly had a strong synergistic effect on protection, associated with synergistically increased expression of IL-17 in the stomach. Notably, sublingual immunization with HpaA(trunc) and UreB was superior to corresponding intragastric immunization with regard to the level of protection induced. In conclusion, HpaA(trunc) is a promising, readily produced, non-toxic recombinant antigen for inclusion in a mucosal vaccine against H. pylori infection, which may preferably be given sublingually together with UreB. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

    Directory of Open Access Journals (Sweden)

    Mello Andrea de Abreu Feijó de

    2003-01-01

    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  20. Family environment is associated with HPA-axis activity in adolescents : The TRAILS study

    NARCIS (Netherlands)

    Marsman, R.; Nederhof, E.; Rosmalen, J.G.; Oldehinkel, A.J.; Ormel, J.; Buitelaar, J.K.

    2012-01-01

    The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection

  1. Performance analysis of AF cooperative systems with HPA nonlinearity in semi-blind relays

    KAUST Repository

    Qi, Jian

    2012-12-01

    In this paper, dual-hop amplify-and-forward (AF) cooperative systems in the presence of high-power amplifier (HPA) nonlinearity at semi-blind relays, are investigated. Based on the modified AF cooperative system model taking into account the HPA nonlinearity, the expression for the output signal-to-noise ratio (SNR) at the destination node is derived, where the interference due to both the AF relaying mechanism and the HPA nonlinearity is characterized. The performance of the AF cooperative system under study is evaluated in terms of average symbol error probability (SEP), which is derived using the moment-generating function (MGF) approach, considering transmissions over Nakagami-m fading channels. Numerical results are provided and show the effects of some system parameters, such as the HPA parameters, numbers of relays, quadrature amplitude modulation (QAM) order, Nakagami parameters, on performance. © 2012 IEEE.

  2. HpaA is essential for Helicobacter pylori colonization in mice.

    Science.gov (United States)

    Carlsohn, Elisabet; Nyström, Johanna; Bölin, Ingrid; Nilsson, Carol L; Svennerholm, Ann-Mari

    2006-02-01

    Infection with the human gastric pathogen Helicobacter pylori can give rise to chronic gastritis, peptic ulcer, and gastric cancer. All H. pylori strains express the surface-localized protein HpaA, a promising candidate for a vaccine against H. pylori infection. To study the physiological importance of HpaA, a mutation of the hpaA gene was introduced into a mouse-adapted H. pylori strain. To justify that the interruption of the hpaA gene did not cause any polar effects of downstream genes or was associated with a second site mutation, the protein expression patterns of the mutant and wild-type strains were characterized by two different proteomic approaches. Two-dimensional differential in-gel electrophoresis analysis of whole-cell extracts and subcellular fractionation combined with nano-liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry for outer membrane protein profiling revealed only minor differences in the protein profile between the mutant and the wild-type strains. Therefore, the mutant strain was tested for its colonizing ability in a well-established mouse model. While inoculation with the wild-type strain resulted in heavily H. pylori-infected mice, the HpaA mutant strain was not able to establish colonization. Thus, by combining proteomic analysis and in vivo studies, we conclude that HpaA is essential for the colonization of H. pylori in mice.

  3. [Construction of hpaA gene-engineered attenuated Salmonella typhimurium vaccine strain].

    Science.gov (United States)

    Zhu, Senlin; Chen, Minhu; Chen, Jie; Hu, Pinjin; Li, Guoqing

    2002-02-01

    To express Helicobacter pylori hpaA gene in attenuated Salmonella typhimurium vaccine vehicle, and elucidate the potential value of attenuated Salmonella typhimurium as a vector expressing Helicobacter pylori antigens, by means of molecular biology, 783 bp hpaA gene was cloned into NcoI-SalI site of a procaryotic expression plasmid pTrc99A, and the recombinant plasmid was then used to transform an attenuated Salmonella typhimurium vaccine strain SL3261, and the positive clones were screened by PCR and restriction enzyme digestion. HpaA expression was analyzed by SDS-PAGE and Western blot. Two and 10 days after recombinant strain intragastric immunization, the C57BL/6 mice was sacrificed, and the spleen and terminal ileum was cultured for recombinant strain. The results showed that a recombinant procaryotic expression plasmid pTrc99A-hpaA was constructed, and the recombinant plasmid was then introduced into an attenuated Salmonella typhimurium vaccine strain SL3261 successfully. HpaA was expressed in the recombinant strains as a 30 kD protein, and also its immunogenicity was confirmed by Western blot. Recombinant strain was found in both spleen and terminal ileum of each mouse two and ten days after intragastric immunization. We concluded that a recombinant live attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori hpaA gene was constructed and identified, and this work will help to develop oral recombinant live vaccine strains against Helicobacter pylori infection.

  4. Restriction fragment length polymorphism in the adhesin gene hpaA of Helicobacter pylori.

    Science.gov (United States)

    Evans, D G; Evans, D J; Lampert, H C; Graham, D Y

    1995-08-01

    To assess the degree of restriction fragment length polymorphism (RFLP) in the Helicobacter pylori adhesin gene hpaA and to determine the molecular basis of RFLP in this gene. A 375-bp, polymerase chain reaction-amplified internal sequence of hpaA, obtained from 50 different H. pylori isolates, was restricted with Sau3A and HinfI, individually. Polymerase chain reaction products representing different RFLP types were sequenced. Seven different polymorphic types were found in hpaA. Base substitutions at only four positions, two in Sau3A and two in HinfI sites, account for all of the RFLP types, including the size of the restriction fragments determined by gel electrophoresis. Most, 90%, of the base substitutions are very conservative, i.e., either do not change the encoded amino acid or substitute a homologous amino acid, and cause no detectable antigenic or functional effect on hpaA. The region of hpaA encoding the receptor-binding motif was particularly well conserved. RFLP typing of hpaA using Sau3A and HinfI provides an additional tool for comparing the genetic relatedness of H. pylori isolates collected during epidemiological and/or treatment studies.

  5. Age of Trauma Onset and HPA Axis Dysregulation Among Trauma-Exposed Youth.

    Science.gov (United States)

    Kuhlman, Kate Ryan; Vargas, Ivan; Geiss, Elisa G; Lopez-Duran, Nestor L

    2015-12-01

    The hypothalamic-pituitary-adrenal axis (HPA axis) is a pathway through which childhood trauma may increase risk for negative health outcomes. The HPA axis is sensitive to stress throughout development; however, few studies have examined whether timing of exposure to childhood trauma is related to differences in later HPA axis functioning. Therefore, we examined the association between age of first trauma and HPA axis functioning among adolescents, and whether these associations varied by sex. Parents of 97 youth (aged 9-16 years) completed the Early Trauma Inventory (ETI), and youth completed the Socially-Evaluated Cold-Pressor Task (SECPT). We measured salivary cortisol response to the SECPT, the cortisol awakening response, and diurnal regulation at home across 2 consecutive weekdays. Exposure to trauma during infancy related to delayed cortisol recovery from peak responses to acute stress, d = 0.23 to 0.42. Timing of trauma exposure related to diverging patterns of diurnal cortisol regulation for males, d = 0.55, and females, d = 0.57. Therefore, the HPA axis may be susceptible to developing acute stress dysregulation when exposed to trauma during infancy, whereas the consequences within circadian cortisol regulation may occur in the context of later trauma exposure and vary by sex. Further investigations are warranted to characterize HPA axis sensitivity to exposure to childhood trauma across child development.

  6. Potassium Influence NRA、HPA and PODA on Leaves of Fiber Flax

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The effecf of potassium fertilizer on Nitrate Reductase Activity (NRA), Hydrogen Peroxide Activity (HPA) ,Peroxidase Activity (PODA) in the fiber flax was studied on campus of NEAU in 1995 and 1996. The result showed that the changing of NRA,HPA and PODA was same in the period from the quick growth to blossom period in the different treamets. NAR and HPA was the highest in the quick growth period then cut down gradually,and PODA was just right contrary. The other side,it was obviously different to NRA, HPA and PODA in the different Potassium levels. NRA and HPA presented the highest enzyme activity in the trea ment of K2O 22.5kg · ha-1. PODA in creased gradually with the increase of Potassium. PODA was the high est in the treament of K2O 67.5kg · ha-1. But all of the Potassium treatments was higher than CK whatever NRA,HPA and PODA. Potassium may enhanced the primary stem yield and fiber percentage and lead to fiber yield rising.

  7. Seizure-induced disinhibition of the HPA axis increases seizure susceptibility.

    Science.gov (United States)

    O'Toole, Kate K; Hooper, Andrew; Wakefield, Seth; Maguire, Jamie

    2014-01-01

    Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.

  8. Stressing diabetes? The hidden links between insulinotropic peptides and the HPA axis.

    Science.gov (United States)

    Diz-Chaves, Yolanda; Gil-Lozano, Manuel; Toba, Laura; Fandiño, Juan; Ogando, Hugo; González-Matías, Lucas C; Mallo, Federico

    2016-08-01

    Diabetes mellitus exerts metabolic stress on cells and it provokes a chronic increase in the long-term activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, perhaps thereby contributing to insulin resistance. GLP-1 receptor (GLP-1R) agonists are pleiotropic hormones that not only affect glycaemic and metabolic control, but they also produce many other effects including activation of the HPA axis. In fact, several of the most relevant effects of GLP-1 might involve, at least in part, the modulation of the HPA axis. Thus, the anorectic activity of GLP-1 could be mediated by increasing CRF at the hypothalamic level, while its lipolytic effects could imply a local increase in glucocorticoids and glucocorticoid receptor (GC-R) expression in adipose tissue. Indeed, the potent activation of the HPA axis by GLP-1R agonists occurs within the range of therapeutic doses and with a short latency. Interestingly, the interactions of GLP-1 with the HPA axis may underlie most of the effects of GLP-1 on food intake control, glycaemic metabolism, adipose tissue biology and the responses to stress. Moreover, such activity has been observed in animal models (mice and rats), as well as in normal humans and in type I or type II diabetic patients. Accordingly, better understanding of how GLP-1R agonists modulate the activity of the HPA axis in diabetic subjects, especially obese individuals, will be crucial to design new and more efficient therapies for these patients.

  9. Role of Paraventricular Nucleus Glutamate Signaling in Regulation of HPA Axis Stress Responses.

    Science.gov (United States)

    Evanson, Nathan K; Herman, James P

    The hypothalamus-pituitary-adrenal (HPA) axis is the main neuroendocrine arm of the stress response, activation of which leads to the production of glucocorticoid hormones. Glucocorticoids are steroid hormones that are secreted from the adrenal cortex, and have a variety of effects on the body, including modulation of the immune system, suppression of reproductive hormones maintenance of blood glucose levels, and maintenance of blood pressure. Glutamate plays an important role in coordination of HPA axis output. There is strong evidence that glutamate drives HPA axis stress responses through excitatory signaling via ionotropic glutamate receptor signaling. However, glutamate signaling via kainate receptors and group I metabotropic receptors inhibit HPA drive, probably via presynaptic inhibitory mechanisms. Notably, kainate receptors are also localized in the median eminence, and appear to play an excitatory role in control of CRH release at the nerve terminals. Finally, glutamate innervation of the PVN undergoes neuroplastic changes under conditions of chronic stress, and may be involved in sensitization of HPA axis responses. Altogether, the data suggest that glutamate plays a complex role in excitation of CRH neurons, acting at multiple levels to both drive HPA axis responses and limit over-activation.

  10. PCR-SSP法检测HPA-15基因频率的可靠性分析%Analysis on reliability of PCR-SSP method in detecting gene frequencies of HPA-15

    Institute of Scientific and Technical Information of China (English)

    朱春燕; 聂咏梅; 周豪杰

    2015-01-01

    目的 探讨聚合酶链反应-序列特异性引物(PCR-SSP)法检测人类血小板抗原(HPA)-15基因的可靠性.方法 设计序列特异性引物,采用PCR-SSP法对惠州地区100例无偿血小板献血者进行HPA-15基因分型,同时采用DNA测序法检测HPA-15基因频率,与PCR-SSP方法检测结果进行比对.结果 PCR-SSP法检测HPA-15a和HPA-15b的基因频率分别为0.535 0和0.465 0,DNA测序法检测HPA-15a和HPA-15b的基因频率分别为0.530 0和0.470 0,两种方法检测HPA-15基因频率差异无统计学意义(P>0.05).结论 PCR-SSP方法可作为一种快速、便捷、可靠的筛查HPA-15基因频率技术,可为临床病人提供HPA-15相合的血小板.

  11. Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood.

    Science.gov (United States)

    Davis, Elysia Poggi; Head, Kevin; Buss, Claudia; Sandman, Curt A

    2017-01-01

    Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6-9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6-9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain. Copyright © 2016. Published by Elsevier Ltd.

  12. Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

    Science.gov (United States)

    Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

    2017-10-01

    Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T3) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

  13. Effects of a poverty-alleviation intervention on salivary cortisol in very low-income children

    Science.gov (United States)

    Fernald, Lia; Gunnar, Megan R

    2009-01-01

    Correlational studies have shown associations between social class and salivary cortisol suggestive of a causal link between childhood poverty and activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a quasi-experimental design, we evaluated the association between a family’s participation in a large-scale, conditional cash transfer program in Mexico (Oportunidades, formerly Progresa) during the child’s early years of life and children’s salivary cortisol (baseline and responsivity). We also examined whether maternal depressive symptoms moderated the impact of program participation. Low-income households (income Oportunidades program, three saliva samples were obtained from children age 2-6 years old from intervention and comparison households (n=1197). Maternal depressive symptoms were obtained using the Center for Epidemiologic Studies-Depression Scale (CES-D). Children who had been in the Oportunidades program had lower salivary cortisol levels when compared with those who had not participated in the program, while controlling for a wide range of individual-, household- and community-level variables. Reactivity patterns did not differ between intervention and comparison children. Maternal depression moderated the association between Oportunidades program participation and baseline salivary cortisol in children. Specifically, there was a large and significant Oportunidades program effect of lowering cortisol in children of mothers with high depressive symptoms but not in children of mothers with low depressive symptomatology. These findings provide the strongest evidence to date that the economic circumstances of the family impact the child’s developing stress system and provide a mechanism through which poverty early in life could impact life-course risk for physical and mental health disorders. PMID:19406546

  14. Poverty-alleviation program participation and salivary cortisol in very low-income children.

    Science.gov (United States)

    Fernald, Lia C H; Gunnar, Megan R

    2009-06-01

    Correlational studies have shown associations between social class and salivary cortisol suggestive of a causal link between childhood poverty and activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a quasi-experimental design, we evaluated the associations between a family's participation in a large-scale, conditional cash transfer program in Mexico (Oportunidades, formerly Progresa) during the child's early years of life and children's salivary cortisol (baseline and responsivity). We also examined whether maternal depressive symptoms moderated the effect of program participation. Low-income households (income Oportunidades program, three saliva samples were obtained from children aged 2-6 years from intervention and comparison households (n=1197). Maternal depressive symptoms were obtained using the Center for Epidemiologic Studies-Depression Scale (CES-D). Results were that children who had been in the Oportunidades program had lower salivary cortisol levels when compared with those who had not participated in the program, while controlling for a wide range of individual-, household- and community-level variables. Reactivity patterns of salivary cortisol did not differ between intervention and comparison children. Maternal depression moderated the association between Oportunidades program participation and baseline salivary cortisol in children. Specifically, there was a large and significant Oportunidades program effect of lowering cortisol in children of mothers with high depressive symptoms but not in children of mothers with low depressive symptomatology. These findings provide the strongest evidence to date that the economic circumstances of a family can influence a child's developing stress system and provide a mechanism through which poverty early in life could alter life-course risk for physical and mental health disorders.

  15. HPA Axis in Major Depression: Cortisol, Clinical Symptomatology, and Genetic Variation Predict Cognition

    Science.gov (United States)

    Keller, Jennifer; Gomez, Rowena; Williams, Gordon; Lembke, Anna; Lazzeroni, Laura; Murphy, Greer M.; Schatzberg, Alan F.

    2016-01-01

    The Hypothalamic Pituitary Adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance, and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology, and HPA genetic variation play in cognitive performance. Patients with major depression with psychosis (PMD) and without psychosis (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol, and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms, and variation in genes, NR3C1 (glucocorticoid receptor - GR) and NR3C2 (minercorticoid receptor – MR) that encode for glucocorticoid and mineralcorticoid receptors, predicted cognitive performance. Beyond the effects of cortisol, demographics, and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and healthy controls. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory. PMID:27528460

  16. Antigenic properties of HpaA and Omp18, two outer membrane proteins of Helicobacter pylori.

    Science.gov (United States)

    Voland, Petra; Hafsi, Nadia; Zeitner, Marco; Laforsch, Stephanie; Wagner, Hermann; Prinz, Christian

    2003-07-01

    Outer membrane proteins (OMPs) are incorporated into the outer plasma membrane of Helicobacter pylori and are important for, e.g., ion transport, adherence, structural and osmotic stability, and bacterial virulence but may also be antigenic due to their surface exposure. Previous proteome-based approaches with H. pylori lysates determined a strong serological reaction towards two H. pylori OMPs, HpaA (TIGR HP0797) and Omp18 (TIGR HP1125). PCR was used to detect DNA encoding the two proteins, and a positive signal was found in all H. pylori strains tested. Proteins were cloned and expressed in the human kidney cell line HK293 with the QiaExpressionist system with a C-terminal His tag. Only sera from infected persons showed a positive reaction with the recombinant proteins. Recombinant HpaA (rHpaA) and rOmp18 were incubated with human peripheral blood mononuclear cells and induced secretion of interleukin-12 (IL-12) and IL-10 from these cells. To determine the effect on antigen-presenting cells, human blood monocytic and dendritic cells (DCs) were isolated by magnetic cell separation. rOmp18 and rHpaA strongly stimulated major histocompatibility class II and CD83 expression 7- to 10-fold on isolated DCs. rHpaA and rOmp18 failed to stimulate IL-8 secretion from monocytes but increased secretion of IL-12 and IL-10 from DCs significantly. In summary, HpaA and Omp18 are recognized by human dendritic cells and induce their maturation as well as antigen presentation. HpaA and Omp18 of H. pylori thereby appear to have a specific antigenic potential in humans.

  17. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition.

    Science.gov (United States)

    Keller, J; Gomez, R; Williams, G; Lembke, A; Lazzeroni, L; Murphy, G M; Schatzberg, A F

    2016-08-16

    The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.Molecular Psychiatry advance online publication, 16 August 2016; doi

  18. What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

    Directory of Open Access Journals (Sweden)

    Andressa Bortoluzzi

    2015-12-01

    Full Text Available Introduction: Anxiety disorders (AD share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. Objective: To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Methods: Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD. We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530 with real time polymerase chain reaction (PCR. The instruments used to diagnose and assess the severity of AD were the Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL and the Screen for Child and Anxiety related Emotional Disorders (SCARED. Results: We failed to detect any associations between AD and genetic polymorphisms in HPA-linked genes (p > 0.05. Conclusion: To our knowledge, this is the first study evaluating these specific polymorphisms in relation to AD in adolescents, which encourages us to design further research on the subject.

  19. Human platelet specical antigen-17bw (HPA-17bw) genotyping and genetic frequency study%血小板特异性抗原HPA-17bw基因分型及基因频率调查

    Institute of Scientific and Technical Information of China (English)

    刘衍春; 薛敏; 吴敏慧; 许剑锋; 唐荣才

    2009-01-01

    目的 对HPA-17bw基因分型并调查其在部分汉族人群中的分布.方法 采用PCR-SSP方法 对无亲缘关系的健康无偿献血者HPA-17bw进行基因分型,采用基因计数法进行基因频率、基因型频率的计算.结果 259名正常人的HPA-17bw基因频率为0.000; HPA-17 bw/bw的基因型频率为0.000.结论 HPA-17bw为低频抗原,259份汉族样本中尚检测不出HPA-17bw.

  20. Construction of hpaA gene from a clinical isolate of Helicobacter pylori and identification of fusion protein.

    Science.gov (United States)

    Mao, Ya-Fei; Yan, Jie; Li, Li-Wei; Li, Shu-Ping

    2003-07-01

    To clone hpaA gene from a clinical strain of Helicobacter pylori and to construct the expression vector of the gene and to identify immunity of the fusion protein. The hpaA gene from a clinical isolate Y06 of H.pylori was amplified by high fidelity PCR. The nucleotide sequence of the target DNA amplification fragment was sequenced after T-A cloning. The recombinant expression vector inserted with hpaA gene was constructed. The expression of HpaA fusion protein in E.coli BL21DE3 induced by IPTG at different dosages was examined by SDS-PAGE. Western blot with commercial antibody against whole cell of H.pylori as well as immunodiffusion assay with self-prepared rabbit antiserum against HpaA fusion protein were applied to determine immunity of the fusion protein. ELISA was used to detect the antibody against HpaA in sera of 125 patients infected with H.pylori and to examine HpaA expression of 109 clinical isolates of H.pylori. In comparison with the reported corresponding sequences, the homologies of nucleotide and putative amino acid sequences of the cloned hpaA gene were from 94.25-97.32 % and 95.38-98.46 %, respectively. The output of HpaA fusion protein in its expression system of pET32a-hpaA-BL21DE3 was approximately 40 % of the total bacterial proteins. HpaA fusion protein was able to combine with the commercial antibody against whole cell of H.pylori and to induce rabbit producing specific antiserum with 1:4 immunodiffusion titer after the animal was immunized with the fusion protein. 81.6 % of the serum samples from 125 patients infected with H.pylori (102/125) were positive for HpaA antibody and all of the tested isolates of H.pylori (109/109) were detectable for HpaA. A prokaryotic expression system with high efficiency of H.pylori hpaA gene was successfully established. The HpaA expressing fusion protein showed satisfactory immunoreactivity and antigenicity. High frequencies of HpaA expression in different H.pylori clinical strains and specific antibody

  1. Seventy-two-hour preservation, resuscitation, and transplantation of an isolated rat heart with high partial pressure carbon monoxide gas (PCO = 400 hPa) and high partial pressure carbon dioxide (PCO(2) = 100 hPa).

    Science.gov (United States)

    Hatayama, Naoyuki; Yoshida, Yu; Seki, Kunihiro

    2010-01-01

    The cardiac cavity of an isolated rat heart was filled with a Krebs-Henseleit (KH) solution, and the heart was hung in a high-pressure chamber. After the high-pressure chamber had been filled with a mixed gas (PCO = 400 hPa, PCO(2) = 100 hPa, PO(2) = 900 hPa, PHe = 5600 hPa) and preserved for 72 h, we performed a cervical ectopic heart transplantation on a recipient rat and resuscitated the preserved heart. This is the first incidence in the world of a mammalian organ having been successfully preserved and resuscitated after 72 h via a desiccation method.

  2. Polymorphism of HPA-21 in Han blood donors in Guangzhou,China%广州地区汉族献血人群HPA-21多态性调查

    Institute of Scientific and Technical Information of China (English)

    周豪杰; 汪传喜; 聂咏梅

    2013-01-01

    目的 了解广州汉族献血人群人类血小板抗原(HPA)-21多态性.方法 设计HPA-21的序列特异性引物(SSP),采用SSP法对200名广州汉族无偿血小板献血者作HPA-21基因分型,并采用DNA测序验证.结果 200名献血者中,198例为HPA-21a/-21a纯合子,2例为HPA-21a/-21b杂合子,并经DNA测序证实.广州汉族献血人群HPA-21a和HPA-21b的等位基因频率分别为99.50%和0.50%,与Hardy-Weinberg平衡吻合;在随机输血中HPA-21抗原不配合的机会为0.99%.结论 所获得的广州汉族献血人群HPA-21基因频率数据,有助于建立本地血小板供者库和开展血小板同型输注.

  3. Two cases report of rare platelet antigen HPA-21bw allele%两例罕见的血小板抗原HPA-21bw等位基因报告

    Institute of Scientific and Technical Information of China (English)

    周豪杰; 聂咏梅; 李晓帆; 汪传喜

    2013-01-01

    目的:调查中国人群人类血小板抗原HPA-21w多态性.方法:采用聚合酶链反应-序列特异性引物法(PCR-SSP)基因分型技术,对广州汉族血小板献血者进行HPA-21w基因分型,并使用PCR扩增HPA-21w基因片段,进行DNA测序验证.结果:在200例受检者中发现2例HPA-21 a/b杂合子个体,DNA测序表明GPIIIa编码基因1960位G→A,导致GPIIIa膜糖蛋白第628位谷氨酸被赖氨酸所取代,产生HPA-21 bw抗原特异性.中国人群HPA-21 bw的等位基因频率为0.50%.结论:在中国人群首次检出HPA-21 bw等位基因,提示在血小板同种免疫症的诊断和血小板输注治疗中,该抗原具有免疫学意义.%Objective:To study the polymorphism of human platelet antigen HPA-21 w in the Chinese population.Methods:A total of 200 Han voluntary platelet donors in Guangzhou were genotyped for HPA-21w by using a polymerase chain reaction-sequence specific primers (PCR-SSP) method.In order to confirm the genotyping result,a fragment of HPA-21w gene was amplified and then sequenced directly.Results:Two individuals with a rare HPA-21a/b genotype were found by using PCR-SSP method.DNA-sequencing showed that a single G to A substitution at nucleotide 1960 occurred,resulting in the replacement of a glutamic acid with a lysine acid at position 628 of GPIIIa protein.This substitution generated antigenic specificity HPA-21bw.The allele frequency of HPA-21bw was 0.50% in the Chinese population.Conclusion:This is the first study reported the rare HPA-21bw allele in the Chinese population.The detection of two rare HPA-21 bw alleles suggests that HPA-21 bw should be considered in platelet alloimmunization syndromes and platelet transfusion therapy.

  4. A case of neonatal alloimmune thrombocytopenia in the presence of both anti-HPA-4b and anti-HPA-5b antibody: clinical and serological analysis of the subsequent pregnancy.

    Science.gov (United States)

    Kiyokawa, Tomoko; Koh, Yangsook; Mimura, Kazuya; Nakayama, Kotarosumitomo; Hosokawa, Mika; Sakuragi, Mikiko; Morikawa, Tamayo; Nakao, Mayumi; Aochi, Hiroshi; Fukumori, Yasuo; Kanagawa, Takeshi; Nagamine, Keisuke; Kimura, Tadashi; Tomiyama, Yoshiaki

    2014-10-01

    Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected. In such cases it is very difficult to determine which antibody is the dominant antibody in NAIT. In this case report, we describe a NAIT case (first sibling) with severe thrombocytopenia and cephalhematoma in the presence of both anti-HPA-4b and anti-HPA-5b antibodies in the maternal serum. We carefully examined titers of anti-HPA antibodies during the subsequent pregnancy with HPA-4b-positive and HPA-5b-negative fetus determined by amniocentesis at gestational week 16. We administered IVIG (1 g/kg/w) to the mother from gestational week 32 to 35. The mother subsequently delivered a second sibling with normal platelet count by cesarean section. Although we could not completely rule out the involvement of anti-HPA-4b, our findings suggested that anti-HPA-5b was implicated in the NAIT in the first sibling.

  5. Relationships between psychological distress, coping styles, and HPA axis reactivity in healthy adults.

    Science.gov (United States)

    Hori, Hiroaki; Ozeki, Yuji; Teraishi, Toshiya; Matsuo, Junko; Kawamoto, Yumiko; Kinoshita, Yukiko; Suto, Shiho; Terada, Sumio; Higuchi, Teruhiko; Kunugi, Hiroshi

    2010-10-01

    Psychological distress and coping styles have been suggested to relate to altered function in the hypothalamic-pituitary-adrenal (HPA) axis, although there remains much to be understood about their relationships. High and low cortisol levels (or reactivity) both represent HPA axis dysfunction, with accumulated evidence suggesting that they are linked to different types of psychopathology. The dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test has been extensively used to identify HPA axis abnormalities in various psychiatric conditions including mood disorders; however, the possible associations of psychological distress and coping styles with HPA axis function have not been well documented using this test. Here, we examined the relationships of HPA axis reactivity as measured by the DEX/CRH test with subjectively perceived psychological distress and coping styles, both of which were assessed with self-report questionnaires, in 121 healthy volunteers. Subjects were divided into three groups by the cortisol suppression pattern, namely the incomplete-suppressors (DST-Cortisol ≥ 5 μg/dL or DEX/CRH-Cortisol ≥ 5 μg/dL), moderate-suppressors (DST-Cortisol psychological distress. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Post-stress rumination predicts HPA axis responses to repeated acute stress.

    Science.gov (United States)

    Gianferante, Danielle; Thoma, Myriam V; Hanlin, Luke; Chen, Xuejie; Breines, Juliana G; Zoccola, Peggy M; Rohleder, Nicolas

    2014-11-01

    Failure of the hypothalamus-pituitary-adrenal (HPA) axis to habituate to repeated stress exposure is related with adverse health outcomes, but our knowledge of predictors of non-habituation is limited. Rumination, defined as repetitive and unwanted past-centered negative thinking, is related with exaggerated HPA axis stress responses and poor health outcomes. The aim of this study was to test whether post-stress rumination was related with non-habituation of cortisol to repeated stress exposure. Twenty-seven participants (n=13 females) were exposed to the Trier Social Stress Test (TSST) twice on consecutive afternoons. Post-stress rumination was measured after the first TSST, and HPA axis responses were assessed by measuring salivary cortisol 1 min before, and 1, 10, 20, 60, and 120 min after both TSSTs. Stress exposure induced HPA axis activation on both days, and this activation showed habituation indicated by lower responses to the second TSST (F=3.7, p=0.015). Post-stress rumination after the first TSST was associated with greater cortisol reactivity after the initial stress test (r=0.45, pHPA axis responses. This finding implicates rumination as one possible mechanism mediating maladaptive stress response patterns, and it might also offer a pathway through which rumination might lead to negative health outcomes.

  7. Overnight suppression of HPA axis after mineraolocorticoid receptor stimulation: A sleep endocrine study.

    Science.gov (United States)

    Demiralay, Cüneyt; Agorastos, Agorastos; Jahn, Holger; Kellner, Michael; Yassouridis, Alexander; Wiedemann, Klaus

    2015-05-30

    Nocturnal hyperactivity of hypothalamic-pituitary-adrenal axis (HPA) indicates decreased feedback inhibition with stress-related conditions such as major depression and sleep disorders. To characterize the role of mineralocorticoid (MR) in regulation of HPA axis activity during nocturnal sleep and involvement in sleep architecture, we investigated sleep endocrine effects of the MR agonist fludrocortisone in healthy men after pretreatment with metyrapone to minimize the impact of endogenous cortisol. Subjects (n=8) were treated on three occasions in a single-blinded design in random order with a) metyrapone, b) fludrocortisone after metyrapone, and c) placebo. Polysomnography was recorded and blood samples were drawn for determination of adrenocorticotropic hormone (ACTH) and cortisol during the entire night. After metyrapone administration ACTH was significantly enhanced, while overall nocturnal cortisol secretion remained largely unchanged. Whereas administration of fludrocortisone induced a significant inhibitory effect on basal ACTH and cortisol secretion, no considerable effects on sleep pattern were detectable. While the involvement of MR in sleep regulation needs further study, endocrine findings underline the role of MR in tonic regulation of HPA axis during nocturnal sleep and demonstrate the ability of fludrocortisone to further suppress HPA axis activity overnight. Additional studies would be required to evaluate endocrine and clinical fludrocortisone effects in depressive patients showing HPA hyperactivity.

  8. Alcohol and pregnancy: Effects on maternal care, HPA axis function, and hippocampal neurogenesis in adult females.

    Science.gov (United States)

    Workman, Joanna L; Raineki, Charlis; Weinberg, Joanne; Galea, Liisa A M

    2015-07-01

    Chronic alcohol consumption negatively affects health, and has additional consequences if consumption occurs during pregnancy as prenatal alcohol exposure adversely affects offspring development. While much is known on the effects of prenatal alcohol exposure in offspring less is known about effects of alcohol in dams. Here, we examine whether chronic alcohol consumption during gestation alters maternal behavior, hippocampal neurogenesis and HPA axis activity in late postpartum female rats compared with nulliparous rats. Rats were assigned to alcohol, pair-fed or ad libitum control treatment groups for 21 days (for pregnant rats, this occurred gestation days 1-21). Maternal behavior was assessed throughout the postpartum period. Twenty-one days after alcohol exposure, we assessed doublecortin (DCX) (an endogenous protein expressed in immature neurons) expression in the dorsal and ventral hippocampus and HPA axis activity. Alcohol consumption during pregnancy reduced nursing and increased self-directed and negative behaviors, but spared licking and grooming behavior. Alcohol consumption increased corticosterone and adrenal mass only in nulliparous females. Surprisingly, alcohol consumption did not alter DCX-expressing cell density. However, postpartum females had fewer DCX-expressing cells (and of these cells more immature proliferating cells but fewer postmitotic cells) than nulliparous females. Collectively, these data suggest that alcohol consumption during pregnancy disrupts maternal care without affecting HPA function or neurogenesis in dams. Conversely, alcohol altered HPA function in nulliparous females only, suggesting that reproductive experience buffers the long-term effects of alcohol on the HPA axis.

  9. Metabotropic glutamate receptor-mediated signaling dampens the HPA axis response to restraint stress.

    Science.gov (United States)

    Evanson, Nathan K; Herman, James P

    2015-10-15

    Glutamate is an important neurotransmitter in the regulation of the neural portion of hypothalamus-pituitary-adrenal (HPA) axis activity, and signals through ionotropic and metabotropic receptors. In the current studies we investigated the role of hypothalamic paraventricular group I metabotropic glutamate receptors in the regulation of the HPA axis response to restraint stress in rats. Direct injection of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG) into the PVN prior to restraint leads to blunting of the HPA axis response in awake animals. Consistent with this result, infusion of the group I receptor antagonist hexyl-homoibotenic acid (HIBO) potentiates the HPA axis response to restraint. The excitatory effect of blocking paraventricular group I metabotropic glutamate signaling is blocked by co-administration of dexamethasone into the PVN. However, the inhibitory effect of DHPG is not affected by co-administration of the cannabinoid CB1 receptor antagonist AM-251 into the PVN. Together, these results suggest that paraventricular group I metabotropic glutamate receptor signaling acts to dampen HPA axis reactivity. This effect appears to be similar to the rapid inhibitory effect of glucocorticoids at the PVN, but is not mediated by endocannabinoid signaling.

  10. Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling.

    Science.gov (United States)

    Malek, Hamed; Ebadzadeh, Mohammad Mehdi; Safabakhsh, Reza; Razavi, Alireza; Zaringhalam, Jalal

    2015-12-01

    In the work presented here, a novel mathematical model was developed to explore the bi-directional communication between the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory cytokines in acute inflammation. The dynamic model consists of five delay differential equations 5D for two main pro-inflammatory cytokines (TNF-α and IL-6) and two hormones of the HPA axis (ACTH and cortisol) and LPS endotoxin. The model is an attempt to increase the understanding of the role of primary hormones and cytokines in this complex relationship by demonstrating the influence of different organs and hormones in the regulation of the inflammatory response. The model captures the main qualitative features of cytokine and hormone dynamics when a toxic challenge is introduced. Moreover, in this work a new simple delayed model of the HPA axis is introduced which supports the understanding of the ultradian rhythm of HPA hormones both in normal and infection conditions. Through simulations using the model, the role of key inflammatory cytokines and cortisol in transition from acute to persistent inflammation through stability analysis is investigated. Also, by employing a Markov chain Monte Carlo (MCMC) method, parameter uncertainty and the effects of parameter variations on each other are analyzed. This model confirms the important role of the HPA axis in acute and prolonged inflammation and can be a useful tool in further investigation of the role of stress on the immune response to infectious diseases.

  11. Time-of-day-dependent adaptation of the HPA axis to predictable social defeat stress.

    Science.gov (United States)

    Koch, C E; Bartlang, M S; Kiehn, J T; Lucke, L; Naujokat, N; Helfrich-Förster, C; Reber, S O; Oster, H

    2016-12-01

    In modern societies, the risk of developing a whole array of affective and somatic disorders is associated with the prevalence of frequent psychosocial stress. Therefore, a better understanding of adaptive stress responses and their underlying molecular mechanisms is of high clinical interest. In response to an acute stressor, each organism can either show passive freezing or active fight-or-flight behaviour, with activation of sympathetic nervous system and the hypothalamus-pituitary-adrenal (HPA) axis providing the necessary energy for the latter by releasing catecholamines and glucocorticoids (GC). Recent data suggest that stress responses are also regulated by the endogenous circadian clock. In consequence, the timing of stress may critically affect adaptive responses to and/or pathological effects of repetitive stressor exposure. In this article, we characterize the impact of predictable social defeat stress during daytime versus nighttime on bodyweight development and HPA axis activity in mice. While 19 days of social daytime stress led to a transient reduction in bodyweight without altering HPA axis activity at the predicted time of stressor exposure, more detrimental effects were seen in anticipation of nighttime stress. Repeated nighttime stressor exposure led to alterations in food metabolization and reduced HPA axis activity with lower circulating adrenocorticotropic hormone (ACTH) and GC concentrations at the time of predicted stressor exposure. Our data reveal a circadian gating of stress adaptation to predictable social defeat stress at the level of the HPA axis with impact on metabolic homeostasis underpinning the importance of timing for the body's adaptability to repetitive stress.

  12. The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations.

    Science.gov (United States)

    Čupić, Željko; Stanojević, Ana; Marković, Vladimir M; Kolar-Anić, Ljiljana; Terenius, Lars; Vukojević, Vladana

    2016-05-18

    Stress and alcohol use are interrelated-stress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic-pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complex-low/moderate acute ethanol challenge (8 mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol.

  13. Semiautomation of platelet HPA-1a phenotyping by SPRCA and ELISA.

    Science.gov (United States)

    Mohabir, L A; Porter, L

    1997-01-01

    An enzyme-linked immunosorbent assay (ELISA) and solid phase red cell adherence assay (SPRCA) were assessed for platelet HP-1a typing in U well microplates. Both methods were partially automated by the use of the Tecan RSP 8051ID robotic sampler and the SLT 400 ATC plate reader with Soft2000 software. Pretreatment of the adherent platelets with chloroquine diphosphate or citric acid enabled anti-HPA-1a, even when contaminated with HLA class 1 antibodies, to be used for typing. Of 675 antenatal samples, 13 were identified as HPA-1a negative. A further 36 known donor HPA-1a negative samples were correctly typed by both methods. Concordant results were obtained for the ELISA and SPRCA. All presumed HPA-1a negatives were confirmed by either polymerase chain reaction using sequence-specific primers (PCR-SSP) or by monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The two semiautomated systems provide simple, accurate, reproducible, and secure ways for large scale HPA-1a phenotyping. The SPRCA can also be performed as a manual technique for small batches of samples.

  14. [HPA distribution characteristics of platelet donor population in Mudanjiang area of China and establishment of its database].

    Science.gov (United States)

    Liu, Bing-Xian; Gao, Guang-Ping; Wang, Dan; Zhang, Yan; Yu, Xiu-Qing; Xia, Dong-Mei; Zhou, Rui-Hua; Zhang, Hua; Ma, Qiang; Liu, Jie

    2012-06-01

    This study was aimed to explore the distribution characteristics of the human platelet antigen (HPA) gene of human platelet donors and its polymorphism in Mudanjiang area of Heilongjiang Province in China, to determine platelet antigen system with clinical significance by judging the rate of incompatibility of HPA, as well as to establish a database of donors' HPA. The genotyping of 154 unrelated platelet donors was performed by means of PCR-SSP. The frequencies of gene and genotype were calculated and compared with that in other areas. The results showed that the genes 1a-17a of HPA-a were all expressed in the 154 healthy and unrelated platelet donors. Only genes 1b, 2b, 3b, 5b, 6b and 15b of HPA-b were expressed while genes 4b, 7b-14b, 16b were not expressed. Among the genotypes, aa homozygosity was predominant and HPA15 had the greatest heterozygosity, while HPA3 had lower heterozygosity. There were 23 combined types of HPA, 5 of them had a rate higher than 10%, and the frequencies of the other 18 were lower than 8%. HPA genotype frequencies showed a good consistency to Hardy-Weinberg equilibrium. It is concluded that the distribution of the allele polymorphism of HPA1-HPA17 in Mudanjiang area has its own characteristics, compared with other areas and some countries, the local HPA genotype database of platelet donors is established in Mudanjiang area, which can provide the matching donors for clinical use with immunological significance.

  15. Systematic identification of immunodominant CD4+ T cell responses to HpaA in Helicobacter pylori infected individuals.

    Science.gov (United States)

    Hu, Jian; Chen, Li; Yang, Wuchen; Li, Bin; Sun, Heqiang; Wei, Shanshan; He, Yafei; Zhao, Zhuo; Yang, Shiming; Zou, Quanming; Chen, Weisan; Guo, Hong; Wu, Chao

    2016-08-23

    In mice, antigen-specific CD4+ T cell response is indispensible for the protective immunity against Helicobacter pylori (H. pylori). It has been demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization protected mice from H. pylori infection in a CD4+ T cell dependent manner. However, much remains unclear concerning the human CD4+ T cell responses to HpaA. We conducted a systematic study here to explore the immunodominant, HpaA-specific CD4+ T cell responses in H. pylori infected individuals. We found that HpaA-specific CD4+ T cell responses varied remarkably in their magnitude and had broad epitope-specificity. Importantly, the main responses focused on two regions: HpaA76-105 and HpaA130-159. The HLA-DRB1*0901 restricted HpaA142-159 specific CD4+ T cell response was the most immunodominant response at a population level. The immunodominant epitope HpaA142-159 was naturally presented and highly conserved. We also demonstrated that it was not the broad peptide specificity, but the strength of HpaA specific CD4+ T cell responses associated with gastric diseases potentially caused by H. pylori infection. Such investigation will aid development of novel vaccines against H. pylori infection.

  16. Effectiveness of vaccination with recombinant HpaA from Helicobacter pylori is influenced by host genetic background.

    Science.gov (United States)

    Sutton, Philip; Doidge, Christopher; Pinczower, Gideon; Wilson, John; Harbour, Stacey; Swierczak, Agnieszka; Lee, Adrian

    2007-07-01

    Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine.

  17. 大连地区汉族人群HPA-15基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    周世航; 刘铭; 于卫健; 宫本兰

    2009-01-01

    目的 分析大连地区汉族人群血小板特异性抗原HPA-15基因多态性,探讨其在血小板输注中的临床意义.方法 采用PCR-SSP法对大连地区100名汉族无血缘关系血小板捐献者的HPA-15系统进行基因分型.结果 大连地区汉族人群HPA-15aa、HPA-15ab、HPA-15bb基因型频率分别为0.360 0、0.440 0、0.200 0.HPA-15a、HPA-15b的基因频率分别为0.580 0、0.420 0.与我国其他地区汉族人群比较,分布差异无统计学意义.在随机输血中,HPA-15抗原不配合概率为0.368 5.结论 在随机输血中,HPA-15抗原不配合概率高,在血小板输注中应加以重视.

  18. Provision of HPA-1a (PlA1)-negative platelets for neonatal alloimmune thrombocytopenia: screening, testing, and transfusion protocol.

    Science.gov (United States)

    Munizza, M; Nance, S; Keashen-Schnell, M A; Sherwood, W; Murphy, S

    1999-01-01

    HPA-1a-negative platelet products are not routinely available for newborns with alloimmune thrombocytopenia. In this article we describe a program established to identify normal pheresis donors who are HPA-1a-negative and to organize their future donations so that our regional blood center would always have an HPA-1a-negative platelet product available. The solid phase red cell adherence assay was used for initial screening of platelet pheresis products. HPA-1a-negative donors were confirmed with the platelet suspension immunofluorescence test using three anti-HPA-1a sera. Screening of 2600 plateletpheresis donor samples identified 40 HPA-1a-negative donors. Of these, 36 are active and are coded for recognition on the daily pheresis inventory sheet. Theoretically, assuming four donations per year and donors' cooperation with scheduling, these 36 donors would enable us to have at least one HPA-1a-negative product available every day. In addition, a decision tree for patient management using platelet serology and availability of HPA-1a-negative products was developed. The GTI-PAK trade mark 12 is the major technique used for serologic screening of mothers of patients thought to have neonatal alloimmune thrombocytopenia. By screening pheresis donors and developing a clinical decision tree, HPA-1a-negative products, a rare resource, can be fully utilized.

  19. Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis.

    Science.gov (United States)

    Marković, Vladimir M; Čupić, Željko; Maćešić, Stevan; Stanojević, Ana; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.

  20. The CERT antagonist HPA-12: first practical synthesis and individual binding evaluation of the four stereoisomers.

    Science.gov (United States)

    Santos, Cécile; Fleury, Laurence; Rodriguez, Frédéric; Markus, Jozef; Berkeš, Dušan; Daïch, Adam; Ausseil, Frédéric; Baudoin-Dehoux, Cécile; Ballereau, Stéphanie; Génisson, Yves

    2015-05-01

    The first unified synthetic route to the four enantiopure HPA-12 stereoisomers in multi-gram scale is reported based on Crystallization-Induced Asymmetric Transformation (CIAT) technology. This preparative stereoselective synthesis allowed the unprecedented comparative evaluation of HPA-12 stereoisomers regarding their interaction with the CERT START domain. In vitro binding assay coupled to in silico docking approach indicate a possible interaction for the four derivatives. The first TR-FRET homogeneous-phase assay was developed to quantify their binding to the START domain, allowing complete determination of HPA-12 EC₅₀. Results indicate that not only the (1R,3S) lead to the strongest binding, but that both 1R and 3S stereocenters similarly contribute to extent of recognition This automated homogenous assay further opens up promising prospect for the identification of novel potential CERT antagonist by means of high throughput screening.

  1. Inter-relation between autonomic and HPA axis activity in children and adolescents.

    Science.gov (United States)

    Rotenberg, Sivan; McGrath, Jennifer J

    2016-05-01

    Stress research in youth typically considers either the autonomic nervous system or HPA axis. However, these systems are highly coordinated and physically interconnected. We examined whether the inter-relation between cardio-autonomic and HPA axis measures was better associated with perceived stress than their singular associations. Children and adolescents (N=201) collected saliva samples to measure cortisol (AUCAG, AUCI, maximum), wore an electrocardiogram monitor for 24h to derive heart rate variability (HRV; LF, HF, LF/HF ratio), and completed the Perceived Stress Scale. The interaction between sympathovagal modulation (LF, LF/HF ratio) and cortisol awakening response (AUCAG, AUCI, maximum) explained significantly greater variance in perceived stress than either stress system alone. Higher sympathovagal modulation combined with higher cortisol awakening response was associated with greater perceived stress. Findings suggest that the inter-relation between cardio-autonomic and HPA axis activity may advance our understanding of how stress impacts health.

  2. Two-way CSI-assisted AF relaying with HPA nonlinearity

    KAUST Repository

    Qi, Jian

    2015-09-11

    In this paper, we investigate half-duplex two-way dual-hop channel state information (CSI)-assisted amplify-andforward (AF) relaying in the presence of high-power amplifier (HPA) nonlinearity at relays. The expression for the end-toend signal-to-noise ratio (SNR) is derived as per the modified system model by taking into account the interference caused by relaying scheme and HPA nonlinearity. The system performance of the considered relaying network is evaluated in terms of average symbol error probability (SEP) in Nakagami-m fading channels, by making use of the moment-generating function (MGF) approach. Numerical results are provided and show the effects of several parameters, such as quadrature amplitude modulation (QAM) order, number of relays, HPA parameters, and Nakagami parameter, on performance. © 2015 IEEE.

  3. Compensation for HPA nonlinearity and I/Q imbalance in MIMO beamforming systems

    KAUST Repository

    Qi, Jian

    2010-10-01

    In this paper, we investigate the effects of high-power amplifier (HPA) nonlinearity and in-phase and quadrature-phase (I/Q) imbalance on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems. Specifically, we propose a compensation method for HPA nonlinearity and I/Q imbalance together in MIMO TB systems. The performance of the MIMO TB system under study is evaluated in terms of the average symbol error probability (SEP) and system capacity, considering transmission over uncorrelated frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, such as the HPA parameters, image-leakage ratio, numbers of transmit and receive antennas, length of pilot symbols, and modulation order of phase-shift keying (PSK), on performance. © 2010 IEEE.

  4. Mathematical modeling of the hypothalamic–pituitary–adrenal gland (HPA) axis, including hippocampal mechanisms

    DEFF Research Database (Denmark)

    Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

    2013-01-01

    non-negative and bounded, which can be interpreted as a mathematical formulation of homeostasis. No oscillating solutions are present when using physiologically reasonable parameter values. This indicates that the ultradian rhythm originate from different mechanisms.Using physiologically reasonable......This paper presents a mathematical model of the HPA axis. The HPA axis consists of the hypothalamus, the pituitary and the adrenal glands in which the three hormones CRH, ACTH and cortisol interact through receptor dynamics. Furthermore, it has been suggested that receptors in the hippocampus have...

  5. Construction of hpaA gene from a clinical isolate of Helicobacter pyloriand identification of fusion protein

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Mao; Jie Yan; Li-Wei Li; Shu-Ping Li

    2003-01-01

    AIM: To clone hpaA gene from a clinical strain of Helicobacter pylori and to construct the expression vector of the gene and to identify immunity of the fusion protein.METHODS: The hpaA gene from a clinical isolate Y06 of H.pylori was amplified by high fidelity PCR. The nucleotide sequence of the target DNA amplification fragment was sequenced after T-A cloning. The recombinant expression vector inserted with hpaA gene was constructed. The expression of HpaA fusion protein in E. coli BL21DE3 induced by IPTG at different dosages was examined by SDS-PAGE.Western blot with commercial antibody against whole cell of H. pylorias well as immunodiffusion assay with selfprepared rabbit antiserum against HpaA fusion protein were applied to determine immunity of the fusion protein. ELISA was used to detect the antibody against HpaA in sera of 125 patients infected with H. pylori and to examine HpaA expression of 109 clinical isolates of H. pylori.RESULTS: In comparison with the reported corresponding sequences, the homologies of nucleotide and putative amino acid sequences of the cloned hpaA gene were from 94.25-97.32 % and 95.38-98.46 %, respectively. The output of HpaA fusion protein in its expression system of pET32ahpaA-BL21DE3 was approximately 40 % of the total bacterial proteins. HpaA fusion protein was able to combine with the commercial antibody against whole cell of H. pyloriand to induce rabbit producing specific antiserum with 1:4immunodiffusion titer after the animal was immunized with the fusion protein. 81.6 % of the serum samples from 125patients infected with H.pylori(102/125) were positive for HpaA antibody and all of the tested isolates of H.pylori(109/109) were detectable for HpaA.CONCLUSION: A prokaryotic expression system with high efficiency of H.pylorihpaA gene was successfully established.The HpaA expressing fusion protein showed satisfactory immunoreactivity and antigenicity. High frequencies of HpaA expression in different H. pyloriclinicalstrains

  6. Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation.

    Science.gov (United States)

    Lucas, Geoff; Culliford, Steven; Green, Frances; Sidra, Gamal; Calvert, Anthony; Green, Ann; Harrison, Penny; Harvey, John; Allen, Dave; Smillie, David; Masurekar, Ashish; Marks, David; Russell, Nigel; Massey, Edwin

    2010-02-01

    Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA-selected PLTs. This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA-A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient-derived HPA-1a antibodies. In two patients, anti-HPA-1a was detected post-BMT and in the third patient, anti-HPA-1a was detected during pre-BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9-10 months posttransplant. The patients remained PLT-transfusion dependent and failed to achieve satisfactory increments following random donor or HLA-matched PLT transfusions. After the identification of HPA-1a antibodies, the patients were supported by HPA-1a(-) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA-1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient-derived HLA antibodies. The prolonged persistence of recipient-derived PLT-specific antibodies following BMT has to our knowledge not been described previously. HPA-1a antibodies were associated with protracted PLT-transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA-specific antibodies followed by transfusion support with HPA-selected PLTs provided the cornerstone of the hemostatic management in these cases.

  7. Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model

    Science.gov (United States)

    2011-09-01

    AD_________________ Award Number: W81XWH-08-1-0661 TITLE: Medial Prefrontal Cortex and HPA Axis...August 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Medial Prefrontal Cortex and HPA Axis Roles In Generation of PTSD-Like Symptoms In SPS Model...emotional regulation (specific aim #3). 15. SUBJECT TERMS PTSD, SPS, anxiety, fear, conditioning, prefrontal cortex , hippocampus, amygdala 16

  8. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    Science.gov (United States)

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  9. Transgenic Expression of a Functional Fragment of Harpin Protein Hpa1 in Wheat Represses English Grain Aphid Infestation

    Institute of Scientific and Technical Information of China (English)

    XU Man-yu; ZHOU Ting; ZHAO Yan-ying; LI Jia-bao; XU Heng; DONG Han-song; ZHANG Chun-ling

    2014-01-01

    The harpin protein Hpa1 produced by the rice bacterial blight pathogen promotes plant growth and induces plant resistance to pathogens and insect pests. The region of 10-42 residues (Hpa110-42) in the Hpa1 sequence is critical as the isolated Hpa110-42 fragment is 1.3-7.5-fold more effective than the full length in inducing plant growth and resistance. Here we report that transgenic expression of Hpa110-42 in wheat induces resistance to English grain aphid, a dominant species of wheat aphids. Hpa110-42-induced resistance is effective to inhibit the aphid behavior in plant preference at the initial colonization stage and repress aphid performances in the reproduction, nymph growth, and instar development on transgenic plants. The resistance characters are correlated with enhanced expression of defense-regulatory genes (EIN2, PP2-A, and GSL10) and consistent with induced expression of defense response genes (Hel, PDF1.2, PR-1b, and PR-2b). As a result, aphid infestations are alleviated in transgenic plants. The level of Hpa110-42-induced resistance in regard to repression of aphid infestations is equivalent to the effect of chemical control provided by an insecticide. These results suggested that the defensive role of Hpa110-42 can be integrated into breeding germplasm of the agriculturally signiifcant crop with a great potential of the agricultural application.

  10. Climate Prediction Center (CPC)Equatorial Zonally-Averaged 50-hPa Zonal Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 50-hPa zonal wind anomalies averaged over the Equator. The anomalies are departures from the...

  11. A case of neonatal HPA-1b allo-immune thrombocytopenia

    NARCIS (Netherlands)

    van der Vlugt, AH; Hepkema, BG; Tamminga, RYJ

    1999-01-01

    We present a case of a newborn with neonatal alloimmune thrombocytopenia (NAIT) due to fete-maternal incompatibility for the thrombocyte allo-antigen HPA-1b. We discuss the policy of platelet transfusions and suggest to treat NAIT early on with thrombocytes transfusions from selected compatible

  12. Climate Prediction Center (CPC)Area-averaged 850-hPa Western Pacific Trade Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 135oE-180o (western equatorial...

  13. Climate Prediction Center (CPC)Area-averaged 850-hPa Eastern Pacific Trade Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 135oW-120oW (eastern...

  14. Efficacy of HPA Lanolin® in treatment of lip alterations related to chemotherapy

    Directory of Open Access Journals (Sweden)

    Paulo Sergio da Silva Santos

    2013-04-01

    Full Text Available The side effects of chemotherapy on the lips may cause esthetic and functional impact and increase the risk of infection. HPA Lanolin® is an option for supportive therapy because it has anti-inflammatory, antimicrobial and moisturizing properties. Objective: To evaluate the efficacy of this product in the prevention of lip alterations in a population of patients undergoing chemotherapy. Material and Methods: Patients undergoing chemotherapy (n = 57 were examined and distributed into two groups: study (used HPA Lanolin® and control (without supportive therapy on the lips. We evaluated the patients two weeks after chemotherapy, registering oral alterations, symptoms of pain, discomfort, limitation of mouth opening and dehydration, classified according to a visual analogue scale. Results: Patients who used HPA Lanolin® had lower dehydration and experienced improvement of lip dryness (p<0.001. The main symptoms were dehydration, discomfort, limitation of mouth opening, pain. The main clinical signs were dry lips, mucositis, cheilitis, hematoma, swelling and cracking. We found no difference concerning the variables of pain, discomfort, and limitation of mouth opening between the study and control group. Conclusions: We suggest that HPA Lanolin® is effective in reducing the symptoms of dehydration and the signs of lip dryness resulting from toxicity of chemotherapy, proving to be an interesting alternative supportive therapy for cancer patients.

  15. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  16. Climate Prediction Center (CPC)Area-averaged 850-hPa Central Pacific Trade Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 175oW-140oW (central...

  17. Investigations of HPA Function and the Enduring Consequences of Stressors in Adolescence in Animal Models

    Science.gov (United States)

    McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, Catherine; Waters, Patti

    2010-01-01

    Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system.…

  18. Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study.

    Science.gov (United States)

    van der Knaap, Lisette J; Oldehinkel, Albertine J; Verhulst, Frank C; van Oort, Floor V A; Riese, Harriëtte

    2015-08-01

    Early life adversity and psychopathology are thought to be linked through HPA-axis deregulation. Changes in methylation levels of stress reactivity genes such as the glucocorticoid receptor gene (NR3C1) can be induced by adversity. Higher NR3C1 methylation levels have been associated with a reduced NR3C1 expression, possibly leading to impaired negative feedback regulation of the HPA-axis. In this study we tested whether methylation levels of NR3C1 were associated with HPA-axis regulation, operationalized as cortisol responses. In 361 adolescents (mean age 16.1, SD=0.6), salivary cortisol samples were collected before, during, and after a social stress task, from which response measures (cortisol activation and recovery) were calculated. Higher NR3C1 methylation levels were associated with a flattened cortisol recovery slope, indicating a delayed recovery time. Cortisol response activation was not associated with NR3C1 methylation. These results suggest that methylation of NR3C1 may impair negative feedback of the HPA-axis in adolescents.

  19. HPA-Axis Activation as a Key Moderator of Childhood Trauma Exposure and Adolescent Mental Health.

    Science.gov (United States)

    Kuhlman, Kate R; Geiss, Elisa G; Vargas, Ivan; Lopez-Duran, Nestor

    2017-02-18

    Individual differences in a child's sensitivity to stress may influence whether youth exposed to trauma develop symptoms of psychopathology. We examined the interaction between HPA-axis reactivity to an acute stressor and exposure to different types of childhood trauma as predictors of mental health symptoms in a sample of youth. Youth (n = 121, ages 9-16; 47% female) completed a standardized stress task, including 5 post-stress salivary cortisol samples. Parents also completed the Child Behavior Checklist as a measure of child internalizing and externalizing symptoms in the past month, and completed the Early Trauma Inventory (ETI) as a measure of their child's trauma exposure. More emotional abuse and non-intentional trauma were associated with greater internalizing symptoms. Youth exposed to physical abuse who demonstrated slower HPA-axis reactivity had elevated internalizing and externalizing symptoms. Youth exposed to emotional abuse or non-intentional traumatic events who demonstrated faster HPA-axis reactivity had elevated internalizing and externalizing symptoms. Profiles of exaggerated or attenuated HPA-axis reactivity to acute stress may be risk factors for psychopathology in children facing different stressful social environments.

  20. In Search of HPA Axis Dysregulation in Child and Adolescent Depression

    Science.gov (United States)

    Guerry, John D.; Hastings, Paul D.

    2011-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

  1. HPA-axis hormone modulation of stress response circuitry activity in women with remitted major depression.

    Science.gov (United States)

    Holsen, L M; Lancaster, K; Klibanski, A; Whitfield-Gabrieli, S; Cherkerzian, S; Buka, S; Goldstein, J M

    2013-10-10

    Decades of clinical and basic research indicate significant links between altered hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. Fifteen women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for the measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, pHPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission.

  2. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  3. Climate Prediction Center (CPC) Area-average 200-hPa Zonal Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 200-hPa zonal wind anomalies averaged over the area 5oN ? 5oS, 165oW-110oW. The anomalies are...

  4. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  5. GaN C-band HPA for phased-array applications

    NARCIS (Netherlands)

    Wanum, M. van; Hek, A.P. de; Vliet, F.E. van

    2013-01-01

    In the UMS GH25-10 GaN MMIC technology a Cband high power amplifier (HPA) has been realized. The current design is primarily intended for use in a space-based SAR system with a center frequency of 5.4 GHz and a sweep bandwidth of 100 MHz. To enable reuse of the amplifier in other radar systems such

  6. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  7. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  8. Long-term effects of early parental loss due to divorce on the HPA axis.

    Science.gov (United States)

    Bloch, Miki; Peleg, Ido; Koren, Danny; Aner, Hamotal; Klein, Ehud

    2007-04-01

    We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (peffect reached a trend level (peffect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.

  9. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  10. Climate Prediction Center (CPC)Equatorial Zonally-averaged 30-hPa Zonal Wind Anomalies

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 30-hPa zonal wind anomalies averaged over the Equator. The anomalies are departures from the...

  11. Early-life stress and HPA axis trigger recurrent adulthood depression.

    Science.gov (United States)

    Juruena, Mario F

    2014-09-01

    It is now broadly accepted that psychological stress may change the internal homeostatic state of an individual. During acute stress, adaptive physiological responses occur, which include hyperactivity of the HPA axis. Whenever there is an acute interruption of this balance, illness may result. The social and physical environments have an enormous impact on our physiology and behavior, and they influence the process of adaptation or 'allostasis'. It is correct to state that at the same time that our experiences change our brain and thoughts, namely, changing our mind, we are changing our neurobiology. Increased adrenocortical secretion of hormones, primarily cortisol in major depression, is one of the most consistent findings in neuropsychiatry. A significant percentage of patients with major depression have been shown to exhibit increased concentrations of cortisol, an exaggerated cortisol response to adrenocorticotropic hormone, and an enlargement of both the pituitary and adrenal glands. The maintenance of the internal homeostatic state of an individual is proposed to be based on the ability of circulating glucocorticoids to exert negative feedback on the secretion of hypothalamic-pituitary-adrenal (HPA) hormones through binding to mineralocorticoid (MR) and glucocorticoid (GR) receptors limiting the vulnerability to diseases related to psychological stress in genetically predisposed individuals. The HPA axis response to stress can be thought of as a mirror of the organism's response to stress: acute responses are generally adaptive, but excessive or prolonged responses can lead to deleterious effects. Evidence indicates that early-life stress can induce persistent changes in the ability of the HPA axis to respond to stress in adulthood. These abnormalities appear to be related to changes in the ability of hormones to bind to GR and MR receptors. First episodes may begin with an environmental stressor, but if the cycles continue or occur unchecked, the brain

  12. Weight loss by calorie restriction versus bariatric surgery differentially regulates the HPA axis in male rats

    Science.gov (United States)

    Grayson, Bernadette E.; Hakala-Finch, Andrew P.; Kekulawala, Melani; Laub, Holly; Egan, Ann E.; Ressler, Ilana B.; Woods, Stephen C.; Herman, James P.; Seeley, Randy J.; Benoit, Stephen C.; Ulrich-Lai, Yvonne M.

    2015-01-01

    Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in 5 groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n=7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n=11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n=11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n=11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n=12). Compared to Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentrations and increased hypothalamic corticotropin releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results suggest that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches. PMID:25238021

  13. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    Science.gov (United States)

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.

  14. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon

    2015-12-01

    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  15. Frequency of human platelet antigens in oncohematological patients with thrombocytopenia and the probability of incompatibility to platelet transfusions Frequência dos antígenos plaquetários humanos (HPA) em pacientes trombocitopênicos e predisposição à incompatibilidade transfusional

    OpenAIRE

    Juliana Vieira dos Santos Bianchi; Maria Regina Andrade de Azevedo; Eduardo Jens; Youko Nukui; Dalton Alencar Ficher Chamone

    2012-01-01

    OBJECTIVE: The objective of this study was to evaluate the frequencies of human platelet antigens in oncohematological patients with thrombocytopenia and to analyze the probability of their incompatibility with platelet transfusions. METHODS: Platelet antigen genotyping was performed by sequence-specific primer polymerase chain reaction (SSP-PCR) for the HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b; HPA-15a, HPA-15b alleles in 150 patients of the Hematology S...

  16. A case report: HPA-21bw allele found in a neonatal thrombocytopenia patient%1例新生儿血小板减少症患儿发现HPA-21bw等位基因报告

    Institute of Scientific and Technical Information of China (English)

    周豪杰; 邓晶; 丁浩强; 聂咏梅

    2013-01-01

    目的 调查新生儿血小板减少症患儿是否携带人类血小板抗原HPA-21w等位基因.方法 对20例新生儿血小板减少症患儿及其母亲采用DNA测序方法进行HPA-21bw基因分型.结果 DNA测序表明1例新生儿血小板减少症患儿GPⅢa编码基因1 960位G→A,为HPA-21 a/b杂合子;而其母亲为HPA-21 a/a纯合子,与患儿HPA-21bw不配合.结论 在新生儿血小板减少症患儿中首次检出HPA-21 bw等位基因,提示HPA-21 bw抗原是中国人群引起新生儿同种免疫性血小板减少症的潜在抗原位点.

  17. Genotyping of platelet antigens HPA-2 with melting curve analysis%血小板抗原HPA-2基因分型熔解曲线法分析

    Institute of Scientific and Technical Information of China (English)

    陈渝宁; 王延伟

    2013-01-01

    目的 建立熔解曲线分析法进行HPA-2基因分型,并检测大连地区汉族人群HPA-2等位基因频率.方法 实时荧光PCR后用熔解曲线分析法进行HPA-2基因分型,与常规PCR-SSP方法进行比较,用熔解曲线分析法对辽宁地区155名汉族血小板捐献者的HPA-2系统进行基因分型,获得HPA-2等位基因分布数据,并与国内部分地区的人群进行比较.结果 基因型为HPA-2aa的样本,熔解曲线呈现单一的峰型,Tm值在(85±1)℃;基因型为HPA-2ab的样本熔解曲线呈现双峰型,Tm值在(80±1)℃和(85±1)℃;基因型为HPA-2bb的样本熔解曲线呈现单一的峰型,Tm值在(80±1)℃.熔解曲线分析法基因分型结果与PCR-SSP法完全一致.大连地区汉族人群HPA-2 a、HPA-2b等位基因频率分别为0.9161,0.0838.与南京、上海、新疆地区汉族人群以及新疆地区维吾尔族人群均很相似(P>0.05),但与海南黎族人群相比差异有统计学意义(P<0.05).结论 应用熔解曲线分析法进行HPA-2基因分型具有简单、快速、准确等优点,优于常规的PCR-SSP方法;HPA-2等位基因频率分布在国内存在种族差异.

  18. Hypothalamic-pituitary-adrenal (HPA) axis functioning in relation to body fat distribution.

    Science.gov (United States)

    Rutters, Femke; Nieuwenhuizen, Arie G; Lemmens, Sofie G T; Born, Jurriaan M; Westerterp-Plantenga, Margriet S

    2010-06-01

    To relate hypothalamic-pituitary-adrenal (HPA) axis functioning and HPA feedback functioning to body fat distribution in normal weight to obese subjects. 91 men and 103 women [age 18-45 years, BMI 19-35 kg/m(2), waist-to-hip ratio (WHR) 0.6-1.1]. Anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test, and HPA axis functioning under a challenged condition consisting of a standardized high-intensity test with ingestion of 4 mg dexamethasone. In men, an inverse relationship was observed between 5-h cortisol exposure (nmol/ml) and fat mass index (FMI) (kg/m(2)) (r = -0.55, P < 0.001). In women, relationships were observed between 5-h cortisol exposure (nmol/ml.min) and WHR (r = -0.49, P < 0.001), maximal workload (r = 0.32, P < 0.001) as well as oral contraceptive use (r = 0.38, P < 0.001). Similarly, in men, an inverse relationship was observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and FMI (r = -0.53, P < 0.001). In women, relationships were observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and WHR (r = -0.43, P < 0.001), maximal workload (r = 0.30, P < 0.001) as well as oral contraceptive use (r = 0.43, P < 0.001) in women. Moreover, an inverse relationship was observed between HPA axis functioning in a challenged condition expressed as percentage increase of cortisol concentrations after standardized high-intensity test with ingestion of 4 mg dexamethasone (%) and waist circumference (r = -0.21, P < 0.10) in men and WHR (r = -0.21, P < 0.05) in women. In men, strong positive relationships were observed between FMI and waist circumference (r = 0.85, P < 0.001), as well as waist-to-hip ratio (r = 0.70, P < 0.001). Disturbance of HPA axis

  19. The rOmp22-HpaA fusion protein confers protective immunity against helicobacter pylori in mice.

    Science.gov (United States)

    Huang, Xueyong; Xu, Bianli; Duan, Guangcai; Song, Chunhua

    2013-10-01

    Helicobacter pylori (H. pylori) plays an essential role in the development of various gastroduodenal diseases; however, no vaccines preventing H. pylori infection have been available now. This study was to evaluate the protective effect of rOmp22-HpaA fusion protein against H. pylori infection in mouse model and to screen the candidate to be used in the development of an oral vaccine against H. pylori. rOmp22, rHpaA, rOmp22+rHpaA, and rOmp22-HpaA groups were used to immunize mice with mLT63 as adjuvant by intragastric route, respectively, four times at 1-week intervals. Two weeks after last immunization, all of the animals were orally challenged with H. pylori NCTC11637 and then were killed after another 2 weeks. The mice gastric tissue of all groups was separated to detect the presence of infection by urease tests, to culture H. pylori, and to observe the histological characteristics. The protective effect against H. pylori challenge in mice immunized with rOmp22-HpaA fusion protein and mLT63 adjuvant was significantly higher than PBS and mLT63 control groups (P HpaA groups (P > 0.05). rOmp22-HpaA fusion protein retained immunogenicity and could be used as an antigen candidate in the development of an oral vaccine against H. pylori infection.

  20. HpaA shows variable surface localization but the gene expression is similar in different Helicobacter pylori strains.

    Science.gov (United States)

    Lundström, A M; Blom, K; Sundaeus, V; Bölin, I

    2001-11-01

    Due to earlier contradictory results regarding the localization of the putative Helicobacter pylori adhesin A (HpaA), we aimed to compare the gene and protein expression and surface localization of HpaA in different H. pylori strains. Five H. pylori strains were cultivated for 11 days and analysed by Northern blot analysis, flow cytometry (FCM), semi-quantitative dot blot, colony blot, immuno-electron microscopy (IEM), and phase-contrast microscopy. The highest transcriptional activity of the hapA gene as observed after 3-4 days of cultivation and two mRNA transcripts of 1600 and 3100 nucleotides, respectively, were detected in all five strains with the hpaA probe. We also showed by reverse transcription-polymerase chain reaction (RT-PCR) that the hpaA gene is co-transcribed with the downstream omp18 gene. The highest total HpaA protein production in bacteria occurred between day 3 and 7, as determined by semi-quantitative dot blot, and was similar in the different strains. The maximal proportion of cells with HpaA on the bacterial surface, detected by FCM, was for strain SS1, 90%; Hel 344, 60%; CCUG 17875, 61%; CCUG 17874, 86% and for strain AH 244 only 35%. By IEM HpaA was detected in all strains both on the bacterial surface and on the flagellar sheath. Copyright 2001 Academic Press.

  1. Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress.

    Science.gov (United States)

    Girotti, Milena; Donegan, Jennifer J; Morilak, David A

    2013-07-01

    Abnormal basal activity and stress-evoked reactivity of the hypothalamic-pituitary-adrenal (HPA) axis are often seen in depression, implicating HPA axis dysfunction as a potentially causative or exacerbating factor. Chronic stress is also a factor in depression, but it is not known what may underlie the shift from adaptive to maladaptive HPA activity over the course of chronic stress. Interleukin 6 (IL-6), a stress-inducible cytokine that signals through gp130 and IL-6Rα receptors to activate the JAK/STAT3 signaling cascade, is elevated in some subtypes of depression, and may have a modulatory effect on HPA activation, raising the possibility that IL-6 contributes to depression through effects on the HPA axis. In this study, we examined the effects of three different stress modalities, acute footshock, chronic intermittent cold (CIC) stress and chronic unpredictable stress (CUS) on IL-6 signaling in the hypothalamus. We also investigated whether IL-6 modulates the HPA response to chronic stress, by blocking IL-6 signaling in the brain during CIC stress using either a neutralizing antibody or an inhibitor of STAT3 phosphorylation. We show that IL-6 and STAT3 in the hypothalamus are activated in response to footshock and CUS. We also found that basal IL-6 signaling through the JAK/STAT3 pathway is required for the sustained CORT response to chronic, but not acute, cold stress and therefore is a potential determinant of plasticity in the HPA axis specifically during chronic stress exposure.

  2. Skin under the (Spot)-Light: Cross-Talk with the Central Hypothalamic-Pituitary-Adrenal (HPA) Axis.

    Science.gov (United States)

    Jozic, Ivan; Stojadinovic, Olivera; Kirsner, Robert S F; Tomic-Canic, Marjana

    2015-06-01

    UV radiation is among the most prevalent stressors in humans and diurnal rodents, exerting direct and indirect DNA damage, free-radical production, and interaction with specific chromophores that affects numerous biological processes. In addition to its panoply of effects, UVB (290-320 nm) radiation can specifically affect various local neuroendocrine activities by stimulating the expression of corticotropin-releasing hormone (CRH), urocortin, proopiomelanocortin (POMC), and POMC-derived peptides. Although very little is known about the interplay between the central hypothalamic-pituitary-adrenal (HPA) axis and the skin HPA axis analog, in the current issue Skobowiat and Slominski propose a novel mechanism by which exposure to UVB activates a local HPA axis in skin, which in turn activates the central HPA axis, with the requirement of a functional pituitary gland. This is the first evidence of the local HPA axis in skin contributing to the central neuroendocrine response. This raises intriguing possibilities regarding how local production of cortisol and other HPA axis molecules in skin influence overall systemic levels of cortisol and help regulate local and central HPA axes in the context of homeostasis, skin injury, and inflammatory skin disorders.

  3. Habitual physical activity (HPA) as a factor in sustained executive function in Alzheimer-type dementia: a cohort study.

    Science.gov (United States)

    Farina, Nicolas; Tabet, Naji; Rusted, Jennifer

    2014-01-01

    Evidence from studies on healthy older adults and mild cognitive impairment (MCI) populations suggests that physical activity interventions have a positive effect on executive function. In this study, we consider whether HPA is positively associated with executive function in Alzheimer's disease (AD). Eighty-two participants with a diagnosis of mild to moderate AD completed six measures of executive function. Objective measures of physical status were taken. In addition, informants completed questionnaires on the participants' HPA and other lifestyle factors. A composite measure of executive function was the primary outcome. A multistage multiple regression was used to determine how much variance HPA accounted for. The final model comprised disease severity, cognitive reserve, cognitive activities, neuropsychiatric status and HPA status. The final model accounted for a total of 57% of the variance of executive performance, of which HPA itself accounted for 8% of the variance. HPA status is associated executive performance in an AD population even after controlling for key covariates. The findings encourage clinicians to recommend HPA and its cognitive benefits to AD patients and their carers.

  4. Hydroxytyrosol from tyrosol using hydroxyphenylacetic acid-induced bacterial cultures and evidence of the role of 4-HPA 3-hydroxylase.

    Science.gov (United States)

    Liebgott, Pierre-Pol; Amouric, Agnès; Comte, Alexia; Tholozan, Jean-Luc; Lorquin, Jean

    2009-12-01

    Hydroxytyrosol (HTyr) is a potent natural antioxidant found in olive mill wastewaters. Bacterial conversion of 4-tyrosol (2-(4-hydroxyphenyl)-ethanol) to HTyr was reported in a limited number of bacterial species including Pseudomonas aeruginosa. In this work, we studied this conversion, taking as a model the newly isolated Halomonas sp. strain HTB24. It was first hypothesized that the enzyme responsible for 4-tyrosol hydroxylation in HTyr was a 4-hydroxyphenylacetic acid 3-hydroxylase (HPAH, EC 1.14.13.3), previously known to convert 4-hydroxyphenylacetic acid (4-HPA) into 3,4-dihydroxyphenylacetic acid (3,4-DHPA) in P. aeruginosa. Cloning and expression of hpaB (oxygenase component) and hpaC (reductase component) genes from P. aeruginosa confirmed this hypothesis. Furthermore, using cultures of HTB24 containing 4-tyrosol, it was shown that 4-HPA accumulation preceded 4-tyrosol hydroxylation. We further demonstrated that the synthesis of HPAH activity was induced by 4-HPA, with the latter compound being formed from 4-tyrosol oxidation by aryl-dehydrogenases. Interestingly, similar results were obtained with other 4-HPA-induced bacteria, including P. aeruginosa, Serratia marcescens, Escherichia coli, Micrococcus luteus and other Halomonas, thus demonstrating general hydroxylating activity of 4-tyrosol by the HPAH enzyme. E. coli W did not have aryl-dehydrogenase activity and hence were unable to oxidize 4-tyrosol to 4-HPA and HTyr to 3,4-DHPA, making this bacterium a good candidate for achieving better HTyr production.

  5. 幽门螺杆菌重组Bb-hpaA-vacA疫苗的构建%Construction of recombinant Bb-hpaA-vacA vaccine of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    王国富; 高峰; 吴利先

    2012-01-01

    To construct the recombinant Bb hpaA vacA vaccine of Helicobacter pylori, hpaA and vacA antigen genes were amplified by PCR and the fusion gene hpaA vacA was obtained with gene SOEing. Then the fusion gene was cloned into Escherichia coli Bifidobacteria shuttle plasmid pGEX lλT to construct pGEX hpaA vacA. The recombinant plasmid was elec troporated into Bifidobacteria bifidum (Bb) to construct rBb hpaA vacA vaccine. The recombinant protein was analyzed by SDS PAGE. Its immunogenicity was identified by Western blotting. A 1500bp fusion gene of hpaA vacA was successfully am plified by PCR and cloned into pGEX 1λT by restriction analysis, and the rBb hpaA vacA vaccine was successfully constructed by PCR and restriction analysis. The recombinant protein could be expressed in B. Bifidium and it has immunogenicity. In this way, the rBb hpaA vacA vaccine of Helicobacter pylori is successfully constructed, which lays the experimental foundation of exploitation and utilization of this vaccine.%目的 构建幽门螵杆菌(Hp)重组双歧杆菌(Bb)Bb-hpaA-vacA疫苗.方法 通过PCR分别扩增hpaA和va-cA抗原编码基因,然后采用基因拼接法(gene SOEing)剪接hpaA和vacA,得到hpaA-vacA融合基因;将该融合基因定向克隆到大肠埃希菌-双歧杆菌穿梭表达载体pGEX-1λT,构建重组质粒pGEX-hpaA-vacA,电穿孔法将该质粒导入Bb,构建幽门螺杆菌重组hpaA-vacA疫苗,然后用SDS-PAGE和Western blotting鉴定表达的重组蛋白.结果 PCR成功扩增出分子量约为1500 bp的hpaA-vacA融合基因,双酶切证实hpaA-vacA融合基因成功插入pGEX-1λT中,并成功转化入双歧杆菌,而且重组蛋白能在双岐杆菌中得到正确表达,Western blotting显示重组蛋白具有免疫原性.结论成功构建螺杆菌rBb-hpaA-vacA疫苗,为该疫苗的进一步研究奠定了基础.

  6. The putative neuraminyllactose-binding hemagglutinin HpaA of Helicobacter pylori CCUG 17874 is a lipoprotein.

    Science.gov (United States)

    O'Toole, P W; Janzon, L; Doig, P; Huang, J; Kostrzynska, M; Trust, T J

    1995-11-01

    The ability of certain strains of Helicobacter pylori to cause sialic acid-sensitive agglutination of erythrocytes has been attributed to the HpaA protein (D.G. Evans, T.K. Karjalainen, D. J. Evans, Jr., D. Y. Graham, and C.H. Lee, J. Bacteriol. 175:674-683, 1993), the gene for which has been cloned and sequenced. On the basis of the hydropathy plot of HpaA and the presence of a potential lipoprotein signal sequence and modification site, and because of the similarities of these features with those of the cell envelope lipoprotein Lpp20 of H. pylori, we examined the possibility that HpaA was also a lipoprotein. Posttranslational processing of the HpaA protein expressed by the cloned gene was sensitive to globomycin, an inhibitor of the lipoprotein-specific signal peptidase II. Antibodies raised to the putative sialic acid-binding region of HpaA failed to bind to the surface of H. pylori cells in immunoelectron microscopy but instead were observed to have labeled the cytoplasm when thin sections were examined. This antibody recognized a 29,000-M(r) protein in Western blots (immunoblots) of cell extracts of H. pylori and Escherichia coli cells expressing the cloned hpaA gene. Determination of the sequence of hpaA from strain CCUG 17874 indicated significant differences from that determined by Evans and coworkers in the above-mentioned study, including extension of the gene into the open reading frame 3 downstream of hpaA to produce a protein with an M(r) of 26,414. Localization of HpaA indicated that it was predominantly located in the cytoplasmic fraction of the cell in both E. coli and H. pylori. HpaA was not observed in the sarkosyl-insoluble outer membrane fraction. An isogenic mutant generated by insertional inactivation of hpaA was unaffected in its ability to bind four different human cell lines as well as fixed sections of gastric tissue and had hemagglutination properties identical to those of the wild type. The data collectively suggest that HpaA is a

  7. Systematic identification of immunodominant CD4+ T cell responses to HpaA in Helicobacter pylori infected individuals

    OpenAIRE

    Hu, Jian; Chen, Li; Yang, Wuchen; Li, Bin; Sun, Heqiang; Wei, Shanshan; He, Yafei; Zhao, Zhuo; Yang, Shiming; Zou, Quanming; Chen, Weisan; Guo, Hong; Wu, Chao

    2016-01-01

    In mice, antigen-specific CD4+ T cell response is indispensible for the protective immunity against Helicobacter pylori (H. pylori). It has been demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization protected mice from H. pylori infection in a CD4+ T cell dependent manner. However, much remains unclear concerning the human CD4+ T cell responses to HpaA. We conducted a systematic study here to explore the immunodominant, HpaA-specific CD4+ T cell responses in H. pylori ...

  8. Sensitivity analysis of FBMC-based multi-cellular networks to synchronization errors and HPA nonlinearities

    Science.gov (United States)

    Elmaroud, Brahim; Faqihi, Ahmed; Aboutajdine, Driss

    2017-01-01

    In this paper, we study the performance of asynchronous and nonlinear FBMC-based multi-cellular networks. The considered system includes a reference mobile perfectly synchronized with its reference base station (BS) and K interfering BSs. Both synchronization errors and high-power amplifier (HPA) distortions will be considered and a theoretical analysis of the interference signal will be conducted. On the basis of this analysis, we will derive an accurate expression of signal-to-noise-plus-interference ratio (SINR) and bit error rate (BER) in the presence of a frequency-selective channel. In order to reduce the computational complexity of the BER expression, we applied an interesting lemma based on the moment generating function of the interference power. Finally, the proposed model is evaluated through computer simulations which show a high sensitivity of the asynchronous FBMC-based multi-cellular network to HPA nonlinear distortions.

  9. Performance of MC-MC CDMA Systems with Nonlinear Models of HPA

    CERN Document Server

    Gergis, Labib Francis

    2011-01-01

    A new wireless communication system denoted as Multi-Code Multi-Carrier CDMA (MC-MC CDMA), which is the combination of Multi-Code CDMA and Multi-Carrier CDMA, is analyzed in this paper. This system can satisfy multi-rate services using multi-code schemes and muti-carrier services used for high rate transmission. The system is evaluated using Traveling Wave Tube Amplifier (TWTA). This type of amplifiers continue to offer the best microwave high power amplifiers (HPA) performance in terms of power efficiency, size and cost, but lag behind Solid State Power Amplifiers (SSPA's) in linearity. This paper presents a technique for improving TWTA linearity. The use of predistorter (PD) linearization technique is described to provide TWTA performance comparable or superior to conventional SSPA's. The characteristics of the PD scheme is derived based on the extension of Saleh's model for HPA.

  10. Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep.

    Science.gov (United States)

    Chiang, Jessica J; Tsai, Kim M; Park, Heejung; Bower, Julienne E; Almeida, David M; Dahl, Ronald E; Irwin, Michael R; Seeman, Teresa E; Fuligni, Andrew J

    2016-09-01

    The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n=316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency.

  11. Hair Cortisol Analysis: A Promising Biomarker of HPA Activation in Older Adults.

    Science.gov (United States)

    Wright, Kathy D; Hickman, Ronald; Laudenslager, Mark L

    2015-06-01

    Prolonged stress is a potentially harmful and often undetected risk factor for chronic illness in older adults. Cortisol, one indicator of the body's hormonal responses to stress, is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and is commonly measured in saliva, urine, or blood samples. Cortisol possesses a diurnal pattern and thus collection timing is critical. Hair cortisol is a proxy measure to the total retrospective activity of the HPA axis over the preceding months, much like hemoglobin A1c is a proxy measure of glucose control over the past 3 months. The aim of this review is to examine a novel biomarker, hair cortisol, as a practical measure of long-term retrospective cortisol activity associated with chronic stress in older adults. Hair cortisol analysis advances the science of aging by better characterizing chronic stress as a risk factor for chronic illness progression and as a biomarker of the effectiveness of stress reduction interventions.

  12. Characterization of 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of Escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase.

    Science.gov (United States)

    Xun, L; Sandvik, E R

    2000-02-01

    4-Hydroxyphenylacetate 3-hydroxylase (HpaB and HpaC) of Escherichia coli W has been reported as a two-component flavin adenine dinucleotide (FAD)-dependent monooxygenase that attacks a broad spectrum of phenolic compounds. However, the function of each component in catalysis is unclear. The large component (HpaB) was demonstrated here to be a reduced FAD (FADH(2))-utilizing monooxygenase. When an E. coli flavin reductase (Fre) having no apparent homology with HpaC was used to generate FADH(2) in vitro, HpaB was able to use FADH(2) and O(2) for the oxidation of 4-hydroxyphenylacetate. HpaB also used chemically produced FADH(2) for 4-hydroxyphenylacetate oxidation, further demonstrating that HpaB is an FADH(2)-utilizing monooxygenase. FADH(2) generated by Fre was rapidly oxidized by O(2) to form H(2)O(2) in the absence of HpaB. When HpaB was included in the reaction mixture without 4-hydroxyphenylacetate, HpaB bound FADH(2) and transitorily protected it from rapid autoxidation by O(2). When 4-hydroxyphenylacetate was also present, HpaB effectively competed with O(2) for FADH(2) utilization, leading to 4-hydroxyphenylacetate oxidation. With sufficient amounts of HpaB in the reaction mixture, FADH(2) produced by Fre was mainly used by HpaB for the oxidation of 4-hydroxyphenylacetate. At low HpaB concentrations, most FADH(2) was autoxidized by O(2), causing uncoupling. However, the coupling of the two enzymes' activities was increased by lowering FAD concentrations in the reaction mixture. A database search revealed that HpaB had sequence similarities to several proteins and gene products involved in biosynthesis and biodegradation in both bacteria and archaea. This is the first report of an FADH(2)-utilizing monooxygenase that uses FADH(2) as a substrate rather than as a cofactor.

  13. Diurnal cortisol rhythms in Tsimane' Amazonian foragers: new insights into ecological HPA axis research.

    Science.gov (United States)

    Nyberg, Colleen H

    2012-02-01

    Although a growing body of research has documented important pathways by which the HPA axis mediates the interface between the psychosocial world and individual health, there is a paucity of data from nonwestern populations, particularly from those populations with distinct nutritional and infectious disease ecologies. The specific objectives of this study are: (1) to document variation in diurnal cortisol rhythms among the Tsimane', a remote population in the Bolivian Amazon, (2) to explore this variation by age and by gender, and (3) to compare diurnal rhythms from this study to other population based studies of cortisol conducted in industrialized nations. Salivary cortisol samples were collected twice daily, immediately upon waking and before bed, for three consecutive days from 303 participants (age 1.6-82 years, 1564 samples) in conjunction with the Tsimane' Amazonian Panel Study (TAPS). Cortisol rhythms showed strong age effects across the developmental span, with basal levels and slopes increasing into adulthood, although individuals older than 60 years demonstrated a precipitous flattening of the diurnal slope. Cortisol profiles were elevated in adult females compared to their age-matched male counterparts, and diurnal slopes, as well as mean cortisol concentrations among the Tsimane' were the lowest reported in any population based study of HPA axis function. Although the within-population variation in cortisol profiles was consistent with the established correlates of time of day, age, and sex, the between-population comparisons revealed dramatically lower levels of HPA activity among the Tsimane'. This study provides a benchmark against which to reference cortisol levels from industrialized populations, and expands the range of documented variation in HPA axis function in a nonwestern context.

  14. Hyper- and hypocortisolism in bipolar disorder - A beneficial influence of lithium on the HPA-axis?

    Science.gov (United States)

    Maripuu, Martin; Wikgren, Mikael; Karling, Pontus; Adolfsson, Rolf; Norrback, Karl-Fredrik

    2017-04-15

    A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naïve to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Cross sectional study design. There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reunion behavior after social separation is associated with enhanced HPA recovery in young marmoset monkeys.

    Science.gov (United States)

    Taylor, Jack H; Mustoe, Aaryn C; Hochfelder, Benjamin; French, Jeffrey A

    2015-07-01

    The relationships that offspring develop with caregivers can exert a powerful influence on behavior and physiology, including the hypothalamic-pituitary-adrenal (HPA) axis. In many mammalian species, offspring-caregiver relationships are largely limited to interactions with mother. Marmoset monkeys receive care in early life from multiple classes of caregivers in addition to the mother, including fathers and siblings. We evaluated whether affiliative social interactions with family members in marmosets were associated with differences in cortisol reactivity to a short-term social separation stressor, and whether these variations in affiliative interactions upon reunion predicted how well marmosets subsequently regulated HPA axis function after cessation of the stressor. Marmosets were separated from the family for 8h at three developmental time points (6-, 12-, and 18-months of age), and interactions of the separated marmoset with the family group were recorded during reunion. Urinary cortisol was measured prior to social separation, every 2h during the separation, and on the morning after separation. Heightened cortisol reactivity during social separation did not predict affiliative social behavior upon reunion but higher rates of grooming and play behavior predicted enhanced HPA regulation. Marmosets with higher rates of grooming and play with family members upon reunion had post-stress cortisol levels closer to preseparation baseline than marmosets with lower rates of affiliative reunion behavior. Combined with previous research showing the early programming effects of social interactions with caregivers, as well as the buffering effect of a close social partner during stress, the current study highlights the high degree of behavioral and HPA adaptability to social stressors across development in marmoset monkeys.

  16. Antigenic Properties of HpaA and Omp18, Two Outer Membrane Proteins of Helicobacter pylori

    OpenAIRE

    Voland, Petra; Hafsi, Nadia; Zeitner, Marco; Laforsch, Stephanie; Wagner, Hermann; Prinz, Christian

    2003-01-01

    Outer membrane proteins (OMPs) are incorporated into the outer plasma membrane of Helicobacter pylori and are important for, e.g., ion transport, adherence, structural and osmotic stability, and bacterial virulence but may also be antigenic due to their surface exposure. Previous proteome-based approaches with H. pylori lysates determined a strong serological reaction towards two H. pylori OMPs, HpaA (TIGR HP0797) and Omp18 (TIGR HP1125). PCR was used to detect DNA encoding the two proteins, ...

  17. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys.

    Science.gov (United States)

    Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L; Kaburu, Stefano S K; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2017-02-01

    Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = -0.07, t(89) = -2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r(s) = -0.627, p = 0.039) and adult HCCs (r(s) = -0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

  18. Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology.

    Science.gov (United States)

    Klaassens, Ellen R; van Noorden, Martijn S; Giltay, Erik J; van Pelt, Johannes; van Veen, Tineke; Zitman, Frans G

    2009-08-01

    Exposure to childhood trauma may induce persistent changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning. We included 10 women exposed to significant childhood trauma and 12 non-exposed women. All women were between 29 and 64 years old,mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as 1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) challenge test. Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to dex/CRH administration were found in the trauma exposed compared to the non-exposed women (F(1,20)=5.08, p=0.04 and F(1,20)=5.23, p=0.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status,somewhat weakened the associations for cortisol as well as ACTH (F(1,16)=3.30, p=0.09) and F(1,16)=2.17, p=0.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected.Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.

  19. 野油菜黄单胞菌hpa2基因的突变和功能分析%Mutagenesis and functional characterization of hpa2 gene in Xanthomonas campestris pv.campestris

    Institute of Scientific and Technical Information of China (English)

    姜伯乐; 蒋国凤; 黄佩芳; 杭小红; 荆龙; 杨艳; 何勇强; 唐纪良

    2008-01-01

    利用自杀质粒pK18mob诱变野油菜黄单胞菌Xcc 8004的hpa2基因,获得整合突变体PK3001.致病性和过敏反应检测发现,hpa2突变体PK3001过敏反应完全丧失,但致病性无明显变化.利用gus报告基因和RT-PCR检测hpa2基因的表达调控,结果表明,hpa2基因在基本培养基上高表达,且受hrpG、hrpX正向调控.

  20. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    Directory of Open Access Journals (Sweden)

    Wieke de Vente

    2015-01-01

    Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

  1. Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a antibodies.

    Science.gov (United States)

    Liu, Zhi-Jian; Bussel, James B; Lakkaraja, Madhavi; Ferrer-Marin, Francisca; Ghevaert, Cedric; Feldman, Henry A; McFarland, Janice G; Chavda, Chaitanya; Sola-Visner, Martha

    2015-09-01

    Incompatibility of the human platelet antigen-1 (HPA-1) system is the most common cause of fetal/neonatal alloimmune thrombocytopenia (F/NAIT) and is thought to be mediated by accelerated clearance of antibody-opsonized fetal platelets. We evaluated the effect of maternal sera containing anti-HPA-1a antibodies (F/NAIT sera) on in vitro megakaryopoiesis. Compared with control maternal sera, 14 out of 17 F/NAIT sera significantly reduced megakaryocyte (MK) number. This finding was associated with increased apoptosis and cell death of early MKs/MK progenitors, but normal maturation and differentiation of surviving MKs. An analysis of platelet counts in infants born to mothers following antenatal intravenous immunoglobulin (IVIG) ± prednisone therapy demonstrated a significant and moderately strong correlation between the MK growth in cultures and the infants' platelet counts at birth. These findings suggest that maternal anti-HPA-1a antibodies can suppress fetal megakaryopoiesis by inducing early cell death and that this influences the neonatal platelet count. Thus, the ability of maternal antibodies to suppress MK growth is a potential predictive factor for the fetal response to maternal IVIG therapy.

  2. GABAergic regulation of the HPA and HPG axes and the impact of stress on reproductive function.

    Science.gov (United States)

    Camille Melón, Laverne; Maguire, Jamie

    2016-06-01

    The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes are regulated by GABAergic signaling at the level of corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH) neurons, respectively. Under basal conditions, activity of CRH and GnRH neurons are controlled in part by both phasic and tonic GABAergic inhibition, mediated by synaptic and extrasynaptic GABAA receptors (GABAARs), respectively. For CRH neurons, this tonic GABAergic inhibition is mediated by extrasynaptic, δ subunit-containing GABAARs. Similarly, a THIP-sensitive tonic GABAergic current has been shown to regulate GnRH neurons, suggesting a role for δ subunit-containing GABAARs; however, this remains to be explicitly demonstrated. GABAARs incorporating the δ subunit confer neurosteroid sensitivity, suggesting a potential role for neurosteroid modulation in the regulation of the HPA and HPG axes. Thus, stress-derived neurosteroids may contribute to the impact of stress on reproductive function. Interestingly, excitatory actions of GABA have been demonstrated in both CRH neurons at the apex of control of the HPA axis and in GnRH neurons which mediate the HPG axis, adding to the complexity for the role of GABAergic signaling in the regulation of these systems. Here we review the effects that stress has on GnRH neurons and HPG axis function alongside evidence supporting GABAARs as a major interface between the stress and reproductive axes.

  3. Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti-HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia.

    Science.gov (United States)

    Bakchoul, Tamam; Greinacher, Andreas; Sachs, Ulrich J; Krautwurst, Annika; Renz, Harald; Harb, Habi; Bein, Gregor; Newman, Peter J; Santoso, Sentot

    2013-07-18

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is often caused by maternal alloantibodies against the human platelet antigen (HPA)-1a, which opsonizes fetal platelets (PLTs). Subsequent PLT destruction is mediated via the Fc part of the alloantibodies. The monoclonal antibody (mAb) SZ21 binds to the HPA-1a epitope and inhibits the binding of maternal alloantibodies. However, it also promotes complement activation and phagocytosis. Deglycosylation of antibodies abrogates the Fc-related effector functions. We modified the N-glycan of SZ21 by endoglycosidase F. The in vivo transplacental transport of N-glycan-modified (NGM)-SZ21 was not impaired. When injected into pregnant mice, both native-SZ21 and NGM-SZ21 were transported equally into fetal circulation (8.9% vs 8.7%, respectively, P = .58). Neither the binding properties of NGM-SZ21 to HPA-1a in surface plasmon resonance, nor the inhibition of anti-HPA-1a-induced PLT phagocytosis, were affected by N-glycan modification. NGM-SZ21 prevented PLT destruction induced by maternal anti-HPA-1a antibodies in vivo in a mouse model (PLT clearance after 5 hours; 18% vs 62%, in the presence or absence of NGM-SZ21, respectively, P = .013). Deglycosylation of SZ21 abrogates Fc-effector functions without interfering with placental transport or the ability to block anti-HPA-1a binding. Humanized, deglycosylated anti-HPA-1a mAbs may represent a novel treatment strategy to prevent anti-HPA-1a-mediated PLT destruction in FNAIT.

  4. aph(3')-IIb, a gene encoding an aminoglycoside-modifying enzyme, is under the positive control of surrogate regulator HpaA.

    Science.gov (United States)

    Zeng, Lin; Jin, Shouguang

    2003-12-01

    Pseudomonas aeruginosa harbors a chromosomal aminoglycoside phosphotransferase gene, aph(3')-IIb, which confers P. aeruginosa resistance to several important aminoglycoside antibiotics, including kanamycin A and B, neomycin B and C, butirosin, and seldomycin F5. The aph(3')-IIb gene has been found to be regulated by an AraC-type transcriptional regulator (HpaA) encoded by a gene located upstream of the aph(3')-IIb gene. In the presence of 4-hydroxyphenylacetic acid (4-HPA), HpaA activates the expression of aph(3')-IIb as well as that of the hpa regulon which encodes metabolic enzymes for the utilization of 4-HPA. hpaA and aph(3')-IIb form an operon, and in response to the presence of 4-HPA, the wild-type P. aeruginosa strain PAK (but not its hpaA mutant strain) displays increased resistance to neomycin. A survey of 39 clinical and 19 environmental isolates of P. aeruginosa demonstrated in all of them the presence of an hpaA-aph gene cluster, while 56 out of the 58 isolates are able to utilize the 4-HPA as a sole carbon source, suggesting a feature common to P. aeruginosa strains. Interestingly, a larger portion of clinical isolates than environmental isolates showed 4-HPA-induced resistance to neomycin. The aph(3')-IIb gene product is likely to function as a metabolic enzyme which has a cross-reactivity with aminoglycosides. These findings provide new insight into the possible mechanism of P. aeruginosa antibiotic resistance.

  5. The hypothalamo-pituitary-adrenal (HPA) axis in sheep is attenuated during lactation in response to psychosocial and predator stress.

    Science.gov (United States)

    Ralph, C R; Tilbrook, A J

    2016-04-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis by psychosocial stress is attenuated during lactation. We tested the hypothesis that lactating ewes will have attenuated HPA axis responses to isolation and restraint but will have greater responses to predator stress in the form of barking dogs. We imposed two 4 h stressors: psychosocial stress (isolation and restraint of ewes) and predator stress (barking dogs). Blood was collected intravenous every 10 min from nonlactating ewes (n = 6), lactating ewes with lambs present but not able to be suckled (n = 6), and lactating ewes with lambs present and able to be suckled (n = 6). Plasma cortisol and oxytocin were measured. For nonlactating ewes, cortisol increased (P HPA axis response to a stressor that may be perceived to threaten the welfare of themselves and/or their offspring. The role of oxytocin in attenuation of the HPA axis to stress in sheep is unclear from the current research and requires further investigation.

  6. The psychology of HPA axis activation: Examining subjective emotional distress and control in a phobic fear exposure model.

    Science.gov (United States)

    Mayer, Stefanie E; Snodgrass, Michael; Liberzon, Israel; Briggs, Hedieh; Curtis, George C; Abelson, James L

    2017-02-09

    The HPA axis plays a key role in mediating the effects of "stress" on health, but clarifying mechanisms requires an understanding of psycho-biological linkages. There has long been an implicit assumption that subjective emotional distress (e.g., fear) should activate the HPA axis. Although this assumption was challenged 25 years ago (Curtis, 1976), laboratory studies in humans are limited. In this study we sought to replicate Curtis' findings and extend it by investigating if presence or absence of stressor control shapes HPA axis reactivity in a phobic fear exposure model. We recruited 19-45-year-old specific phobia participants (n=32 spider/snake phobia; n=14 claustrophobia) and gradually exposed them to their feared object or situation while measuring hormonal (ACTH and cortisol) and subjective (emotional distress, perceived control) responses. Utilizing a dyadic yoked design, we compared HPA reactivity when the pace of exposure was controlled by participants to identical exposure given to matched participants in the absence of control. Results showed that phobic fear exposure generated intense emotional distress without a corresponding increase in HPA axis activity. Although our actual manipulation of control failed to impact HPA responses, perceived control during exposure was associated with lower cortisol, an effect that was moderated by actual availability of stressor control. Our findings replicate Curtis' findings and challenge the still common but unsupported assumption that HPA axis activity reflects subjective distress. These results also highlight the importance of both perceived and actual aspects of stressor control in understanding what is truly "stressful" to the HPA axis system.

  7. 遗传性面孔失认症(HPA)的三例报告%Three Case Reports of Hereditary Prosopagnosia (HPA)

    Institute of Scientific and Technical Information of China (English)

    王晖

    2009-01-01

    遗传性面孔失认症(HPA)是没有脑损伤情况下存在的一种先天性的面部认知障碍,是面孔识别领域的新发现.本研究通过筛查问卷和诊断访谈对来自长春高校的548名大学生进行测查,首次在中国长春地区发现了三例HPA症人;确认了HPA在黄种人中存在的事实;同时发现HPA症人具有辨别方向困难和内部表象缺失等认知特征.

  8. Evidence for a Role of Adolescent Endocannabinoid Signaling in Regulating HPA Axis Stress Responsivity and Emotional Behavior Development.

    Science.gov (United States)

    Lee, Tiffany T-Y; Gorzalka, Boris B

    2015-01-01

    Adolescence is a period characterized by many distinct physical, behavioral, and neural changes during the transition from child- to adulthood. In particular, adolescent neural changes often confer greater plasticity and flexibility, yet with this comes the potential for heightened vulnerability to external perturbations such as stress exposure or recreational drug use. There is substantial evidence to suggest that factors such as adolescent stress exposure have longer lasting and sometimes more deleterious effects on an organism than stress exposure during adulthood. Moreover, the adolescent neuroendocrine response to stress exposure is different from that of adults, suggesting that further maturation of the adolescent hypothalamic-pituitary-adrenal (HPA) axis is required. The endocannabinoid (eCB) system is a potential candidate underlying these age-dependent differences given that it is an important regulator of the adult HPA axis and neuronal development. Therefore, this review will focus on (1) the functionality of the adolescent HPA axis, (2) eCB regulation of the adult HPA axis, (3) dynamic changes in eCB signaling during the adolescent period, (4) the effects of adolescent stress exposure on the eCB system, and (5) modulation of HPA axis activity and emotional behavior by adolescent cannabinoid treatment. Collectively, the emerging picture suggests that the eCB system mediates interactions between HPA axis stress responsivity, emotionality, and maturational stage. These findings may be particularly relevant to our understanding of the development of affective disorders and the risks of adolescent cannabis consumption on emotional health and stress responsivity.

  9. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    Science.gov (United States)

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.

  10. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.

    Science.gov (United States)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J; Coleman, Jonathan R I; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E; Herren, Chantal; Hogendoorn, Sanne M; Hudson, Jennifer L; Krause, Karen; Lyneham, Heidi J; Morris, Talia; Nauta, Maaike; Rapee, Ronald M; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C; Silverman, Wendy K; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C; Wong, Chloe C Y

    2015-12-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  11. Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

    Science.gov (United States)

    Melhem, Nadine M; Keilp, John G; Porta, Giovanna; Oquendo, Maria A; Burke, Ainsley; Stanley, Barbara; Cooper, Thomas B; Mann, J John; Brent, David A

    2016-05-01

    Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output (β=-0.47, 95% CI (-0.83, -0.11), p=0.01) compared with offspring with suicide-related behavior (SRB) but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socio-economic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol before the TSST (β=-0.45, 95% CI (-0.74, -0.17), p=0.002). However, there were no significant differences between the groups on cortisol reactivity to stress (β=4.5, 95% CI (-12.9, 22), p=0.61). Although subjects with suicide attempt and SRB have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high risk for suicidal behavior for targeted prevention and intervention efforts.

  12. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity.

    Science.gov (United States)

    Kozachik, Sharon L; Page, Gayle G

    2016-05-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic-pituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up-down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.

  13. Childhood trauma and HPA axis functionality in offspring of bipolar parents.

    Science.gov (United States)

    Schreuder, Merel M; Vinkers, Christiaan H; Mesman, Esther; Claes, Stephan; Nolen, Willem A; Hillegers, Manon H J

    2016-12-01

    Children of a parent with bipolar disorder (bipolar offspring) have an increased risk for mood disorders. While genetic factors play a significant role in this population, susceptibility to environmental stress may also significantly contribute to this vulnerability for mood disorders. Childhood trauma has consistently been found to increase the risk for mood disorders, with persisting consequences for hypothalamic-pituitary-adrenal (HPA) axis functionality. However, it is currently unknown whether childhood trauma specifically affects HPA axis activity in individuals with a familial risk for bipolar disorder. Therefore, we investigated the effects of childhood trauma on daytime and evening cortisol levels and dexamethasone suppression in bipolar offspring (N=70) and healthy controls (N=44). In our study we found no significant differences in daytime and evening cortisol levels as well as dexamethasone suppression between bipolar offspring and healthy controls (all p-values>0.43). In contrast, childhood trauma differentially affected daytime cortisol levels in the bipolar offspring compared to healthy controls (childhood trauma X bipolar offspring interaction, β=-7.310, p=0.0414) with an effect of childhood trauma on daytime cortisol in bipolar offspring at trend level (p=0.058). In the bipolar offspring group, lifetime or current psychiatric diagnoses, and stressful life events separately did not affect cortisol levels or dexamethasone suppression (all p-values>p=0.50). These findings were independent of current or lifetime psychiatric diagnosis. In conclusion, trauma-related changes in daytime HPA axis activity appear to be a specific trait in bipolar offspring who have increased risk for mood disorders compared to healthy individuals.

  14. Effects of stress on pain in horses and incorporating pain scales for equine practice.

    Science.gov (United States)

    Wagner, Ann E

    2010-12-01

    The stress response represents an animal's attempt to reestablish the body's homeostasis after injury, intense physical activity, or psychological strain. Two different neuroendocrine pathways may be activated in stressful situations: the hypothalamic-pituitary-adrenocortical axis, leading to increased cortisol levels, and the sympathoadrenomedullar system, leading to increased catecholamine levels. By applying some of the evaluation methods described in this article in the appropriate clinical situations, equine veterinarians can almost certainly improve their ability to recognize and manage pain in horses.

  15. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients. A case-control study

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed......, a positive association between post-DST cortisol and Rey's Complex figure test (1.3; 95% CI 0.3-3.6; P =¿0.02) was found. We found no significant associations between other memory functions and cortisol measures. Conclusions: Contrary to our hypothesis, we found a positive association between cortisol levels...

  16. Effect of reproductive status on hypothalamic-pituitary-adrenal (HPA) activity and reactivity in male California mice (Peromyscus californicus).

    Science.gov (United States)

    Harris, Breanna N; Saltzman, Wendy

    2013-03-15

    Previous studies indicate that reproductive condition can alter stress response and glucocorticoid release. Although the functional significance of hypothalamic-pituitary-adrenal (HPA) axis modulation by breeding condition is not fully understood, one possible explanation is the behavior hypothesis, which states that an animal's need to express parental behavior may be driving modulation of the HPA axis. This possibility is consistent with findings of blunted activity and reactivity of the HPA axis in lactating female mammals; however, effects of reproductive status on HPA function have not been well characterized in male mammals that express parental behavior. Therefore, we tested this hypothesis in the monogamous and biparental California mouse. Several aspects of HPA activity were compared in males from three reproductive conditions: virgin males (housed with another male), non-breeding males (housed with a tubally ligated female), and first-time fathers (housed with a female and their first litter of pups). In light of the behavior hypothesis we predicted that new fathers would differ from virgin and non-breeding males in several aspects of HPA function and corticosterone (CORT) output: decreased amplitude of the diurnal rhythm in CORT, a blunted CORT increase following predator-odor stress, increased sensitivity to glucocorticoid negative feedback, and/or a blunted CORT response to pharmacological stimulation. In addition, we predicted that first-time fathers would be more resistant to CORT-induced suppression of testosterone secretion, as testosterone is important for paternal behavior in this species. We found that virgin males, non-breeding males and first-time fathers did not display any CORT differences in diurnal rhythm, response to a predator-odor stressor, or response to pharmacological suppression or stimulation. Additionally, there were no differences in circulating testosterone concentrations. Adrenal mass was, however, significantly lower in new

  17. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers.

    Science.gov (United States)

    Ghevaert, Cedric; Herbert, Nina; Hawkins, Louise; Grehan, Nicola; Cookson, Philip; Garner, Steve F; Crisp-Hihn, Abigail; Lloyd-Evans, Paul; Evans, Amanda; Balan, Kottekkattu; Ouwehand, Willem H; Armour, Kathryn L; Clark, Mike R; Williamson, Lorna M

    2013-07-18

    Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcγ receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Δnab blocks monocyte chemiluminescence by >75%. In this first-in-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Δnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Δnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Δnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers.

  18. EURAMET.M.P-S9: comparison in the negative gauge pressure range -950 to 0 hPa

    Science.gov (United States)

    Saxholm, S.; Otal, P.; AltintaS, A.; Bermanec, L. G.; Durgut, Y.; Hanrahan, R.; Kocas, I.; Lefkopoulos, A.; Pražák, D.; Sandu, I.; Åetina, J.; Spohr, I.; Steindl, D.; Tammik, K.; Testa, N.

    2016-01-01

    A comparison in the negative gauge pressure range was arranged in the period 2011 - 2012. A total of 14 laboratories participated in this comparison: BEV (Austria), CMI (Czech Republic), DANIAmet-FORCE (Denmark), EIM (Greece), HMI/FSB-LPM (Croatia), INM (Romania), IPQ (Portugal), LNE (France), MCCAA (Malta), METROSERT (Estonia), MIKES (Finland), MIRS/IMT/LMT (Slovenia), NSAI (Ireland) and UME (Turkey). The project was divided into two loops: Loop1, piloted by MIKES, and Loop2, piloted by LNE. The results of the two loops are reported separately: Loop1 results are presented in this paper. The transfer standard was Beamex MC5 no. 25516865 with internal pressure module INT1C, resolution 0.01 hPa. The nominal pressure range of the INT1C is -1000 hPa to +1000 hPa. The nominal pressure points for the comparison were 0 hPa, -200 hPa, -400 hPa, -600 hPa, -800 hPa and -950 hPa. The reference values and their uncertainties as well as the difference uncertainty between the laboratory results and the reference values were determined from the measurement data by Monte Carlo simulations. Stability uncertainty of the transfer standard was included in the final difference uncertainty. Degrees of equivalences and mutual equivalences between the laboratories were calculated. Each laboratory reported results for all twelve measurement points, which means that there were 168 reported values in total. Some 163 of the 168 values (97 %) agree with the reference values within the expanded uncertainties, with a coverage factor k = 2. Among the laboratories, four different methods were used to determine negative gauge pressure. It is concluded that special attention must be paid to the measurements and methods when measuring negative gauge pressures. There might be a need for a technical guide or a workshop that provides information about details and practices related to the measurements of negative gauge pressure, as well as differences between the different methods. The comparison is

  19. 南京地区汉族人群血小板特异性HPA-7c等位基因频率的调查

    Institute of Scientific and Technical Information of China (English)

    薛敏; 刘衍春; 马玲

    2012-01-01

    目的 调查南京地区汉族献血者人群中HPA-7c的等位基因频率.方法 采用PCR-SSP方法检测HPA -7a、b、c的3个等位基因.结果 在被调查的1 065人中,未检出HPA-7c等位基因.HPA-7a的等位基因频率为1.000,HPA-7b和-7c的等位基因频率都为0.结论 南京地区汉族献血者人群中尚未发现HPA-7c等位基因的存在.

  20. Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

    Directory of Open Access Journals (Sweden)

    W.M. Quinteiro-Filho

    2009-10-01

    Full Text Available Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days isogenic BALB/c mice in each experiment. Cyhalothrin i increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05, concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05, and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05; ii increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05, and iii decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05 and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05 in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

  1. Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression

    Directory of Open Access Journals (Sweden)

    Landgraf Rainer

    2011-03-01

    Full Text Available Abstract Background Neuronal mechanisms underlying affective disorders such as major depression (MD are still poorly understood. By selectively breeding mice for high (HR, intermediate (IR, or low (LR reactivity of the hypothalamic-pituitary-adrenocortical (HPA axis, we recently established a new genetic animal model of extremes in stress reactivity (SR. Studies characterizing this SR mouse model on the behavioral, endocrine, and neurobiological levels revealed several similarities with key endophenotypes observed in MD patients. HR mice were shown to have changes in rhythmicity and sleep measures such as rapid eye movement sleep (REMS and non-REM sleep (NREMS as well as in slow wave activity, indicative of reduced sleep efficacy and increased REMS. In the present study we were interested in how far a detailed spectral analysis of several electroencephalogram (EEG parameters, including relevant frequency bands, could reveal further alterations of sleep architecture in this animal model. Eight adult males of each of the three breeding lines were equipped with epidural EEG and intramuscular electromyogram (EMG electrodes. After recovery, EEG and EMG recordings were performed for two days. Results Differences in the amount of REMS and wakefulness and in the number of transitions between vigilance states were found in HR mice, when compared with IR and LR animals. Increased frequencies of transitions from NREMS to REMS and from REMS to wakefulness in HR animals were robust across the light-dark cycle. Detailed statistical analyses of spectral EEG parameters showed that especially during NREMS the power of the theta (6-9 Hz, alpha (10-15 Hz and eta (16-22.75 Hz bands was significantly different between the three breeding lines. Well defined distributions of significant power differences could be assigned to different times during the light and the dark phase. Especially during NREMS, group differences were robust and could be continuously monitored

  2. Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.

    Science.gov (United States)

    Gastón, M S; Cid, M P; Salvatierra, N A

    2017-03-01

    Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABAA receptor competitive antagonist) but not by diazepam (a GABAA receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABAA receptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABAA receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABAA receptor.

  3. Prenatal treatment with glucocorticoids sensitizes the hpa axis response to stress among full-term infants.

    Science.gov (United States)

    Davis, Elysia Poggi; Waffarn, Feizal; Sandman, Curt A

    2011-03-01

    The objective of this study was to determine the consequences for HPA axis functioning among healthy full-term newborns of prenatal treatment with the synthetic glucocorticoid (GC), betamethasone, which is the routine treatment for threatened preterm delivery. Ninety full-term infants were recruited into two study groups (30 betamethasone treated; 60 comparison group matched for GA at birth and sex). The cortisol and behavioral response to the painful stress of a heel-stick blood draw was assessed 24 hr after birth. Full-term infants exposed to prenatal betamethasone displayed a larger cortisol response to the heel-stick procedure, despite no differences in baseline levels. Further, within the recommended window of betamethasone administration (24-34 gestational weeks), infants exposed to betamethasone earlier in gestation displayed the largest cortisol response to the heel-stick. These data add to accumulating evidence that prenatal exposure to elevated GCs programs the development of the HPA axis. Copyright © 2010 Wiley Periodicals, Inc.

  4. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  5. Mitigating HPA Axis Dysregulation Associated With Placement Changes in Foster Care

    Science.gov (United States)

    Fisher, Philip A.; Van Ryzin, Mark J.; Gunnar, Megan R.

    2012-01-01

    Summary Maltreated foster children often exhibit alterations in diurnal hypothalamic-pituitary-adrenal (HPA) axis activity that are characterized by lower cortisol levels upon waking and smaller declines in morning-to-evening cortisol levels. Previous research has shown that this dysregulated pattern is associated with high caregiver stress levels over the course of foster care placements. In contrast, therapeutic interventions that emphasize consistent and responsive caregiving have been associated with more regulated cortisol rhythms. In this paper, two related issues were explored: whether placement changes (i.e., moving between foster homes or from a foster home to a permanent placement) were associated with more blunted daily cortisol rhythms and whether a caregiver-based intervention exerted a protective effect in this context. Because the intervention program has components specifically designed to prepare foster children for placement changes and to maintain consistent parenting techniques despite them, a prevention effect on HPA axis dysregulation during placement changes was hypothesized. The results of linear mixed modeling analyses showed that placement changes predicted dysregulation in cortisol rhythms in the regular foster care group but not in the intervention foster care group. These findings are discussed in terms of implications for child welfare policy and practice. PMID:20888698

  6. Aging and the HPA axis: Stress and resilience in older adults.

    Science.gov (United States)

    Gaffey, Allison E; Bergeman, C S; Clark, Lee Anna; Wirth, Michelle M

    2016-09-01

    Hypothalamic-pituitary-adrenal (HPA) axis function may change over the course of aging, and altered diurnal or stress-induced secretion of the hormone cortisol could predispose older adults to negative health outcomes. We propose that psychological resilience may interact with diurnal cortisol to affect health outcomes later in life. Emotion regulation and social support are two constructs that contribute to resilience and exhibit age-specific patterns in older adults. Determining how the use of resilience resources interacts with age-related diurnal cortisol will improve our understanding of the pathways between stress, resilience, and well-being. In this review, we assess published studies evaluating diurnal cortisol in older adults to better understand differences in their HPA axis functioning. Evidence thus far suggests that diurnal cortisol may increase with age, although cross-sectional studies limit the conclusions that can be drawn. We also review extant evidence connecting age-specific signatures of emotion regulation and social support with diurnal cortisol. Conclusions are used to propose a preliminary model demonstrating how resilience resources may modulate the effects of cortisol on health in aging.

  7. Climatology of the 500-hPa mediterranean storms associated with Saudi Arabia wet season precipitation

    Science.gov (United States)

    Almazroui, Mansour; Kamil, S.; Ammar, K.; Keay, Kevin; Alamoudi, A. O.

    2016-11-01

    The relationship between the Mediterranean 500-hPa storm tracks and wet season (November-April) rainfall over Saudi Arabia is investigated. The analysis is based on the application of an objective tracking scheme to the 6-hourly 500-hPa geopotential height ERA-Interim dataset (0.75° × 0.75°) for the period 1979-2012. The resulting tracks are then associated with the ERA-Interim rainfall events over Saudi Arabia. The association procedure showed that 34 % of the tracks are related to about 70 % of the rainfall. These associated tracks are used to construct climatology. A climatology of these storm tracks revealed that the eastern Mediterranean region is the preferred location for cyclogenesis with a maximum in the southwest parts of the Black Sea. The study also examined the mean radius, average intensity and average depth of the storms. The number of tracks in winter (December-February) is about 60 % of the total number which confirms the major contribution of the Mediterranean storms to rainfall over Saudi Arabia. A significant negative trend was found for storm cyclogenesis over the central Mediterranean, and the Black sea. A significant trend decrease in track density is observed over most of the northern parts of Saudi Arabia. The peaks of storm activities are observed in December and January in 1996, 1997 and 2009. Storm activity generally declines after 2000, especially in the second half of the wet season months (February-April).

  8. Assessing behavioural effects of chronic HPA axis activation using conditional CRH-overexpressing mice.

    Science.gov (United States)

    Dedic, Nina; Touma, Chadi; Romanowski, Cristoph P; Schieven, Marcel; Kühne, Claudia; Ableitner, Martin; Lu, Ailing; Holsboer, Florian; Wurst, Wolfgang; Kimura, Mayumi; Deussing, Jan M

    2012-07-01

    The corticotropin-releasing hormone (CRH) and its cognate receptors have been implicated in the pathophysiology of stress-related disorders. Hypersecretion of central CRH and elevated glucocorticoid levels, as a consequence of impaired feedback control, have been shown to accompany mood and anxiety disorders. However, a clear discrimination of direct effects of centrally hypersecreted CRH from those resulting from HPA axis activation has been difficult. Applying a conditional strategy, we have generated two conditional CRH-overexpressing mouse lines: CRH-COE ( Del ) mice overexpress CRH throughout the body, while CRH-COE ( APit ) mice selectively overexpress CRH in the anterior and intermediate lobe of the pituitary. Both mouse lines show increased basal plasma corticosterone levels and consequently develop signs of Cushing's syndrome. However, while mice ubiquitously overexpressing CRH exhibited increased anxiety-related behaviour, overexpression of CRH in the pituitary did not produce alterations in emotional behaviour. These results suggest that chronic hypercorticosteroidism alone is not sufficient to alter anxiety-related behaviour but rather that central CRH hyperdrive on its own or in combination with elevated glucocorticoids is responsible for the increase in anxiety-related behaviour. In conclusion, the generated mouse lines represent valuable animal models to study the consequences of chronic CRH overproduction and HPA axis activation.

  9. Gene × environment vulnerability factors for PTSD: the HPA-axis.

    Science.gov (United States)

    Mehta, Divya; Binder, Elisabeth B

    2012-02-01

    Post-traumatic stress disorder (PTSD) is a severely debilitating psychiatric condition. Although a lifetime trauma incidence of 40-90% has been reported in the general population, the overall lifetime prevalence for PTSD ranges between 7-12%, suggesting individual-specific differences towards the susceptibility to PTSD. While studies investigating main genetic effects associated with PTSD have yielded inconsistent findings, there is growing evidence supporting the role of gene-environment (G × E) interactions in PTSD. The hypothalamus pituitary adrenal (HPA) axis is one of the main systems activated after exposure to a trauma and perturbations in this system are one of the more consistent neurobiological abnormalities observed in PTSD. Genes regulating the HPA-axis are therefore interesting candidates for G × E studies in PTSD. This article will review the concept and initial results of G × E interactions with polymorphisms in these genes for PTSD. In addition, the use of alternate phenotypes and more complex interaction models such as G × G × E or G × E × E will be explored. Finally, putative molecular mechanisms for these interactions will be presented. The research presented in this article indicates that a combined analysis of environmental, genetic, endophenotype and epigenetic data will be necessary to better understand pathomechanisms in PTSD. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Screening of peptides binding to HpaA of Helicobacter pylori from a random phage library%与幽门螺杆菌HpaA定植相关的功能性亲和肽的筛选

    Institute of Scientific and Technical Information of China (English)

    朱俊谕; 向一郎; 李琳; 杨厅; 潘剑珍; 王庆林; 吴翔

    2013-01-01

    目的 HpaA是幽门螺杆菌(Helicobacter pylori)的主要粘附因子,参与幽门螺杆菌在人胃黏膜上的定植过程.特异性阻断HpaA与人胃上皮细胞的粘附,可能成为阻断Hp感染的新方法,从而弥补常规治疗中出现的毒副作用大、耐药性等问题.方法 以人工合成的HpaA主要结构域KRTIQKKRTIQK多肽为靶标,应用噬菌体随机十二肽库进行筛选,经过3轮淘选,提取阳性噬菌体克隆ssDNA,测序并进行序列分析.通过相应的分析软件对亲和肽进行分析比对.结果 通过多次筛选与富集,获得了与HpaA相互作用的功能分子ASPH、EGR2.运用软件模拟发现ASPH、EGR2均能与HpaA分子高度吻合.结论 通过噬菌体肽库技术筛选出与幽门螺杆菌主要粘附分子HpaA相互作用的2个功能分子,可能参与幽门螺杆菌的定植与致病过程,为进一步研究幽门螺杆菌在人胃内致病的机制和多肽治疗方法提供了依据.%Objective Helicobacter pylori adhesin A (HpaA) is the main adhesion factor of H.pylori and is involved in the bacterial colonization of human gastric mucosa.Specifically inhibiting the adhesion of H.pylori to human epithelial cells may be a possible way to inhibit H.pylori infection.This treatment could also deal with other issues such as adverse reactions to conventional treatment and drug resistance.Methods Short synthetic peptides of HpaA's major domain KRTIQK were used as a target to screen for compatible short peptides from a phage display library.Positive phage clones were obtained by 3 rounds of biopanning,followed by single-stranded DNA extraction and sequencing.Results Repeated screening and enrichment yielded the functional molecules ASPH and EGR2,both of which interact with HpaA.A software simulation indicated that ASPH and EGR2 closely bind to HpaA molecules.Conclusion Two functional candidates that interact with HpaA were identified from a phage display library.This lays the theoretic foundation for

  11. Development of a single-antigen magnetic bead assay (SAMBA) for the sensitive detection of HPA-1a alloantibodies using tag-engineered recombinant soluble β3 integrin.

    Science.gov (United States)

    Skaik, Younis; Battermann, Anja; Hiller, Oliver; Meyer, Oliver; Figueiredo, Constanca; Salama, Abdulgabar; Blasczyk, Rainer

    2013-05-31

    Timely and accurate testing for human platelet antigen 1a (HPA-1a) alloantibodies is vital for clinical diagnosis of neonatal alloimmune thrombocytopenia (NAIT). Current antigen-specific assays used for the detection of HPA-1 alloantibodies are technically very complex and cumbersome for most diagnostic laboratories. Hence, we designed and applied recombinant soluble (rs) β3 integrins displaying HPA-1a or HPA-1b epitopes for the development of a single-antigen magnetic bead assay (SAMBA). Soluble HPA-1a and HPA-1b were produced recombinantly in human embryonic kidney 293 (HEK293) cells and differentially tagged. The recombinant soluble proteins were then immobilized onto paramagnetic beads and used for analysis of HPA-1 alloantibodies by enzyme-linked immunosorbent assay (ELISA). HPA-1a serum samples (n=7) from NAIT patients, inert sera and sera containing non-HPA-1a antibodies were used to evaluate the sensitivity and specificity of the SAMBA. Fusion of V5-His or GS-SBP-His tags to the rsβ3 integrins resulted in high-yield expression. SAMBA was able to detect all HPA-1a and -1b alloantibodies recognized by monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). No cross-reactions between the sera were observed. Two out of seven of the HPA-1a alloantibody-containing sera demonstrated weak to moderate reactivity in MAIPA but strong signals in SAMBA. SAMBA provides a very reliable method for the detection of HPA-1 antibodies with high specificity and sensitivity. This simple and rapid assay can be adapted for use in any routine laboratory and can be potentially adapted for use on automated systems.

  12. T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a-specific, HLA-DRB3*0101-restricted CD4+ T cells.

    Science.gov (United States)

    Ahlen, Maria Therese; Husebekk, Anne; Killie, Mette Kjaer; Skogen, Bjørn; Stuge, Tor B

    2009-04-16

    T-cell responses have been implicated in the development of HPA-1a-induced neonatal alloimmune thrombocytopenia (NAIT). However, HPA-1a-specific T cells have neither been isolated nor characterized. Here, we aimed to determine whether HPA-1a-specific T cells could be isolated from HPA-1a-immunized women. In the present study, peripheral blood mononuclear cells (PBMCs) from an HPA-1a-alloimmunized woman were cultured for weeks in the presence of HPA-1a peptide, labeled with CFSE, and assayed for antigen-specific proliferation. Individual proliferating cells were isolated by fluorescence-activated cell sorting and expanded in culture. Antigen specificity and HLA restriction were determined by cytokine secretion (enzyme-linked immunospot [ELISPOT]) and proliferation assays. Several CD3(+)CD4(+) T-cell clones were isolated that proliferated and secreted cytokines in response to HPA-1a peptide. Two of these clones have been established in long-term culture in our laboratory. Both of these recognize synthetic as well as naturally processed HPA-1a antigen, and the recognition is restricted by the MHC molecule HLA-DRB3*0101 that is strongly associated with NAIT. These HPA-1a-specific T-cell clones represent unambiguous evidence for the association of T-cell responses with NAIT, and they will serve as unique tools to elucidate the cellular immune response that may result in NAIT.

  13. Correlation between polymorphism of platelet alloantigen genes HPA-1-5 and type 2 diabetes complication by carotid atherosclerosis in a Chinese population.

    Science.gov (United States)

    Zhang, Y H; Xu, S F; Zheng, J; Hong, H S; Fan, L M

    2015-05-04

    We investigated the association between the polymorphism of human platelet alloantigen genes HPA-1-HPA-5 and the complication of type 2 diabetes mellitus (T2DM) by carotid atherosclerosis (CA) among Han people in Guiyang District, China. Ninety-nine T2DM patients were selected from the Affiliated Hospital of Guiyang Medical College and divided into a CA(+) group and a CA(-) group. A control group comprised 100 healthy people from the medical examination center of the same hospital. Genomic DNA from all the subjects was isolated by phenol-chloroform extraction and target genes were amplified using sequence-specific primer-polymerase chain reaction, followed by gene type detection of HPA. There were significant differences in allele and genotype frequencies of HPA-1, -2, -3, and -5 among the three groups [CA(+), CA(-), and the control group] (P HPA-1, -2, and -3 between groups CA(+) and CA(-) and the control group (P HPA-5 between the CA(+) and CA(-) groups (P HPA-5. There may be a correlation between T2DM and polymorphism of HPA-1-3. Polymorphism of HPA- 5 is probably a risk factor for CA complicating T2DM.

  14. Characterization of 4-Hydroxyphenylacetate 3-Hydroxylase (HpaB) of Escherichia coli as a Reduced Flavin Adenine Dinucleotide-Utilizing Monooxygenase

    OpenAIRE

    2000-01-01

    4-Hydroxyphenylacetate 3-hydroxylase (HpaB and HpaC) of Escherichia coli W has been reported as a two-component flavin adenine dinucleotide (FAD)-dependent monooxygenase that attacks a broad spectrum of phenolic compounds. However, the function of each component in catalysis is unclear. The large component (HpaB) was demonstrated here to be a reduced FAD (FADH2)-utilizing monooxygenase. When an E. coli flavin reductase (Fre) having no apparent homology with HpaC was used to generate FADH2 in ...

  15. Preservation by desiccation of isolated rat hearts for 48 hours using carbon monoxide (PCO = 4,000 hPa) and oxygen (PO(2) = 3,000 hPa).

    Science.gov (United States)

    Hatayama, Naoyuki; Naito, Munekazu; Hirai, Shuichi; Yoshida, Yu; Kojima, Tomohiro; Seki, Kunihiro; Li, Xiao-Kang; Itoh, Masahiro

    2012-01-01

    It is currently said that CO has anti-inflammatory and antiapoptosis effects and it has attracted attention as a medical gas. We used CO for rat hearts and conducted a preservation experiment. We isolated rat hearts, placed them into a specially made chamber, filled the chamber with a gas mixture of PCO (4,000 hPa) and PO(2) (3,000 hPa), and preserved the hearts in a refrigerator at 4°C for 48 h. We then performed a heterotrophic transplantation on the neck of each recipient rat and resuscitated the preserved hearts. We herein report our findings.

  16. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

    Science.gov (United States)

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders.

    Science.gov (United States)

    Dalvie, Shareefa; Fabbri, Chiara; Ramesar, Raj; Serretti, Alessandro; Stein, Dan J

    2016-02-01

    Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD-AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD-SUD comorbidity, PRKCI deserves further investigation in BD-AUD.

  18. Alloantibodies to human platelet glycoprotein antigens (HPA) and HLA class 1 in a cross section of Nigerian antenatal women.

    Science.gov (United States)

    Jeremiah, Zaccheaus Awortu; Atiegoba, Anne Ifeanyi; Mgbere, Osaro

    2011-01-01

    The prevalence of antibodies to human platelet antigens (HPA) and human leukocyte antigens (HLA) class 1 antigens among Nigerian pregnant women has not been reported in our country. This study was therefore aimed at screening the obstetric population for evidence of alloimmunization due to human platelet and HLA class 1 antigens. One hundred and forty four (144) pregnant women attending the obstetric clinic of Military Hospital, Port Harcourt, participated in the study. Their sera were tested for antibodies to HPA and HLA class 1 antigens using GTI PakPlus solid phase ELISA Kit. The total prevalence rate of antibody production was 60.5% (87 out of 144). Among the positive samples, 60 had platelet glycoprotein specific antibodies (41.7%) and 27 had HLA class 1 antibodies (18.8%). In 39.6% of the pregnant women, both platelet specific antibodies and HLA class 1 antibodies appeared. The prevalence of platelet specific glycoprotein antibodies were obtained as follows: GP 11b/111a 12 (8.3%), GP 1a/11a 35 (20.8%), GP Ib/IX 18 (12.5%) and GP IV 9 (6.3%). The prevalence of each platelet antibody subgroup was obtained as follows: anti-HPA-1a,-3a,-4a (4.2%), anti-HPA-1b,-3b,-4a (4.2%), anti-HPA-30 5a and anti-GP Ib/IX (12.5% each), anti-HPA-5b (8.3%) and anti-GP IV (6.3%). A high prevalence rate of human platelet arid cytotoxic antibodies has been observed in our obstetric population. There is need to establish platelet serology laboratory for the proper antenatal and postnatal management of pregnant mothers in this region.

  19. The putative neuraminyllactose-binding hemagglutinin HpaA of Helicobacter pylori CCUG 17874 is a lipoprotein.

    OpenAIRE

    O'Toole, P W; Janzon, L; Doig, P; Huang, J.; Kostrzynska, M; Trust, T. J.

    1995-01-01

    The ability of certain strains of Helicobacter pylori to cause sialic acid-sensitive agglutination of erythrocytes has been attributed to the HpaA protein (D.G. Evans, T.K. Karjalainen, D. J. Evans, Jr., D. Y. Graham, and C.H. Lee, J. Bacteriol. 175:674-683, 1993), the gene for which has been cloned and sequenced. On the basis of the hydropathy plot of HpaA and the presence of a potential lipoprotein signal sequence and modification site, and because of the similarities of these features with...

  20. Relationships between 700 hPa height anomalies and 1 April snowpack accumulations in the western USA

    Science.gov (United States)

    McCabe, G.J.; Legates, D.R.

    1995-01-01

    Relationships between atmospheric circulation and the temporal and spatial distribution of snowpack accumulations in the western USA are examined. In general, above-average snowpack accumulations are associated with negative 700 hPa height anomalies over the eastern North Pacific Ocean and the western USA. These anomalies are indicative of anomalous cyclonic circulation, which produces an anomalous westerly flow of moist air from the eastern North Pacific Ocean into the western USA and increases winter precipitation and snowpack accumulations. Below-average snowpack accumulations at most of the snowcourse stations are associated with positive 700 hPa anomalies over the western USA. -from Authors

  1. Methylation of HPA axis related genes in men with hypersexual disorder.

    Science.gov (United States)

    Jokinen, Jussi; Boström, Adrian E; Chatzittofis, Andreas; Ciuculete, Diana M; Öberg, Katarina Görts; Flanagan, John N; Arver, Stefan; Schiöth, Helgi B

    2017-03-10

    Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy

  2. The signal peptide-like segment of hpaXm is required for its association to the cell wall in transgenic tobacco plants

    Science.gov (United States)

    Li, Le; Miao, Weiguo; Liu, Wenbo; Zhang, Shujian

    2017-01-01

    Harpins, encoded by hrp (hypersensitive response and pathogenicity) genes of Gram-negative plant pathogens, are elicitors of hypersensitive response (HR). HpaXm is a novel harpin-like protein described from cotton leaf blight bacteria, Xanthomonas citri subsp. malvacearum—a synonym of X. campestris pv. malvacearum (Smith 1901–1978). A putative signal peptide (1-MNSLNTQIGANSSFL-15) of hpaXm was predicted in the nitroxyl-terminal (N-terminal)by SignalP (SignalP 3.0 server). Here, we explored the function of the N-terminal leader peptide like segment of hpaXm using transgenic tobacco (Nicotiana tabacum cv. Xanthi nc.). Transgenic tobacco lines expressing the full-length hpaXm and the signal peptide-like segment-deleted mutant hpaXmΔLP were developed using transformation mediated by Agrobacterium tumefaciens. The target genes were confirmed integrated into the tobacco genomes and expressed normally. Using immune colloidal-gold detection technique, hpaXm protein was found to be transferred to the cytoplasm, the cell membrane, and organelles such as chloroplasts, mitochondria, and nucleus, as well as the cell wall. However, the deletion mutant hpaXmΔLP expressed in transgenic tobacco was found unable to cross the membrane to reach the cell wall. Additionally, soluble proteins extracted from plants transformed with hpaXm and hpaXmΔLP were bio-active. Defensive micro-HR induced by the transgene expression of hpaXm and hpaXmΔLP were observed on transgenic tobacco leaves. Disease resistance bioassays to tobacco mosaic virus (TMV) showed that tobacco plants transformed with hpaXm and with hpaXmΔLP exhibited enhanced resistance to TMV. In summary, the N-terminal signal peptide-like segment (1–45 bp) in hpaXm sequence is not necessary for transgene expression, bioactivity of hpaXm and resistance to TMV in transgenic tobacco, but is required for the protein to be translocated to the cell wall. PMID:28141855

  3. Surface expression of Helicobacter pylori HpaA adhesion antigen on Vibrio cholerae, enhanced by co-expressed enterotoxigenic Escherichia coli fimbrial antigens.

    Science.gov (United States)

    Tobias, Joshua; Lebens, Michael; Wai, Sun Nyunt; Holmgren, Jan; Svennerholm, Ann-Mari

    2017-04-01

    Helicobacter pylori infection can cause peptic ulceration and is associated with gastric adenocarcinoma. This study aimed to construct and characterize a non-virulent Vibrio cholerae O1 strain, which grows more rapidly than H. pylori, as vector for H. pylori antigens for possible use as a vaccine strain against H. pylori. This was done by recombinant expression of the H. pylori adhesion antigen HpaA alone or, as a proof of principle, together with different colonization factor (CF) antigens of enterotoxigenic Escherichia coli (ETEC) which may enhance immune responses against HpaA. A recombinant V. cholerae strain co-expressing HpaA and a fimbrial CF antigens CFA/I or CS5, but not the non-fimbrial CF protein CS6, was shown to express larger amounts of HpaA on the surface when compared with the same V. cholerae strain expressing HpaA alone. Mutations in the CFA/I operon showed that the chaperon, possibly together with the usher, was involved in enhancing the surface expression of HpaA. Oral immunization of mice with formaldehyde-inactivated recombinant V. cholerae expressing HpaA alone or together with CFA/I induced significantly higher serum antibody responses against HpaA than mice similarly immunized with inactivated HpaA-expressing H. pylori bacteria. Our results demonstrate that a non-virulent V. cholerae strain can be engineered to allow strong surface expression of HpaA, and that the expression can be further increased by co-expressing it with ETEC fimbrial antigens. Such recombinant V. cholerae strains expressing HpaA, and possibly also other H. pylori antigens, may have the potential as oral inactivated vaccine candidates against H. pylori. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. aph(3′)-IIb, a Gene Encoding an Aminoglycoside-Modifying Enzyme, Is under the Positive Control of Surrogate Regulator HpaA

    Science.gov (United States)

    Zeng, Lin; Jin, Shouguang

    2003-01-01

    Pseudomonas aeruginosa harbors a chromosomal aminoglycoside phosphotransferase gene, aph(3′)-IIb, which confers P. aeruginosa resistance to several important aminoglycoside antibiotics, including kanamycin A and B, neomycin B and C, butirosin, and seldomycin F5. The aph(3′)-IIb gene has been found to be regulated by an AraC-type transcriptional regulator (HpaA) encoded by a gene located upstream of the aph(3′)-IIb gene. In the presence of 4-hydroxyphenylacetic acid (4-HPA), HpaA activates the expression of aph(3′)-IIb as well as that of the hpa regulon which encodes metabolic enzymes for the utilization of 4-HPA. hpaA and aph(3′)-IIb form an operon, and in response to the presence of 4-HPA, the wild-type P. aeruginosa strain PAK (but not its hpaA mutant strain) displays increased resistance to neomycin. A survey of 39 clinical and 19 environmental isolates of P. aeruginosa demonstrated in all of them the presence of an hpaA-aph gene cluster, while 56 out of the 58 isolates are able to utilize the 4-HPA as a sole carbon source, suggesting a feature common to P. aeruginosa strains. Interestingly, a larger portion of clinical isolates than environmental isolates showed 4-HPA-induced resistance to neomycin. The aph(3′)-IIb gene product is likely to function as a metabolic enzyme which has a cross-reactivity with aminoglycosides. These findings provide new insight into the possible mechanism of P. aeruginosa antibiotic resistance. PMID:14638496

  5. Postnatal masculinization alters the HPA axis phenotype in the adult female rat.

    Science.gov (United States)

    Seale, J V; Wood, S A; Atkinson, H C; Harbuz, M S; Lightman, S L

    2005-02-15

    The ability of postnatal testosterone propionate (TP) to masculinize both behaviour and gonadal cyclicity in the female rat is well documented. We have investigated whether postnatal androgen also has an organizational effect on another sexually dimorphic neuroendocrine system--the hypothalamo-pituitary-adrenal (HPA) axis. Female rats were exposed to a single injection of testosterone propionate (TP) or oil within 24 h of birth. As adults, rats were either ovariectomized and given 17beta-oestradiol replacement (OVXE2) or sham ovariectomized with cholesterol implants (SHOVX). An automated sampling system collected blood from unanaesthetized adult female rats every 10 min over a 24-h period, during a mild psychological stress (noise) and following an immunological lipopolysaccharide stress (LPS). Neonatal TP-treated SHOVX rats had a significant reduction in the number, height, frequency and amplitude of corticosterone pulses over the basal 24-h period, compared to both the neonatal oil-treated and TP-treated OVXE2 animals. The corticosterone response to both noise and LPS was also significantly decreased for the TP-treated SHOVX females. Three hours post-LPS administration, TP females had significantly lower values of paraventricular nucleus (PVN) corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and anterior pituitary proopiomelanocortin (POMC) mRNAs and greater PVN glucocorticoid receptor (GR) mRNA expression compared to the oil-treated controls. E2 replacement in adult TP rats normalized all the mRNA levels, except for PVN GR mRNA which did fall towards the levels of the oil-control animals. A single injection of TP within 24 h of birth disrupts the development of the characteristic female pattern of corticosterone secretion and the normal female HPA response to stress, resulting in a pattern similar to that seen in males. These effects can be reversed by E2 treatment in the adult TP female rat.

  6. Behavioral sexual dimorphism in models of anxiety and depression due to changes in HPA axis activity.

    Science.gov (United States)

    Kokras, Nikolaos; Dalla, Christina; Sideris, Antonios C; Dendi, Artemis; Mikail, Hudu G; Antoniou, Katerina; Papadopoulou-Daifoti, Zeta

    2012-01-01

    Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticosterone, the main HPA axis stress hormone, in male and female adrenalectomized rats with oral (25 μg/ml) corticosterone replacement (ADXR). Subsequently we investigated the behavioral performance of ADXR rats in the open field, light/dark and forced swim test (FST). Male ADXR rats showed less anxiety-like behavior when compared to sham-operated controls, despite adequate corticosterone replacement. They further showed increased swimming and reduced climbing behavior in the FST, while immobility duration did not differ from sham-operated males. On the contrary, adrenalectomy and corticosterone replacement did not have significant effects on the female behavioral response. Females were generally more active and presented less anxiety-like behavior than males, while they exhibited higher depressive-like symptomatology in the FST. ADXR affected behavioral responses predominantly in males, which in turn modified sex differences in the behavioral profile. Females in proestrous and estrous did not differ from females in diestrous and methestrous in any measured behavioral response. Present results suggest that the male and not the female behavioral responses in models of anxiety and depression were mainly affected by ADXR. These findings may play a significant role in explaining the differential coping strategy of the two sexes in response to stressful experiences. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  7. Frequency of anti-glycoprotein Ia/IIa (anti-HPA-5b,-5a and anti-glycoprotein IIb/IIIa (anti-HPA-1a,-3a,-4a alloantibodies in multiparous women of African descent

    Directory of Open Access Journals (Sweden)

    Zaccheaus A Jeremiah

    2010-05-01

    Full Text Available Zaccheaus A Jeremiah1, Justina E Oburu2, Osaro Erhabor1, Fiekumo I Buseri1, Teddy C Adias31Haematology and Blood Transfusion Science Unit, Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Nigeria; 2Department of Haematology and Blood Transfusion, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria; 3Rivers State University of Science and Technology, Port Harcourt, NigeriaBackground: Human platelet antibodies are often implicated in some disease conditions, such as neonatal alloimmune thrombocytopenia (NAIT, idiopathic thrombocytopenic purpura (ITP and platelet refractoriness. The frequencies of these alloantibodies have not been reported in Nigeria and West Africa.Methods: Screening for allontibodies to human platelet antigens (HPA was undertaken using the GTI PakPlus® qualitative solid phase ELISA reagent. Platelet count was done using the ICSH approved procedure using 1% ammonium oxalate reagent.Study design: A cross-section of apparently healthy adult Nigerian multiparous non-pregnant women, who were staff of a tertiary health facility in the Niger Delta, Nigeria, were screened for alloantibodies to human platelet antigens.Results: Of the one hundred (100 women screened, the prevalence of anti-glycoprotein IIb/IIIa (anti-HPA-Ia,-3a,-4a was zero percent (0%, anti-glycoprotein Ia/IIa (anti-HPA-5b accounted for 30% of results, while anti-glycoprotein Ia/IIa (anti-HPA-5a was 18%. Parity was found to exert significant influence on the development to HPA antibodies (Fisher’s Exact Test = 11.683, P < 0.05; 13.577, P < 0.01. The platelet count of the women did not appear to exert any influence on the development of the antibodies (P > 0.05.Conclusion: This study has observed a high prevalence of anti-HPA-5b in our sample population. The prevalence of alloantibodies to HPA antigens was found to associate strongly with parity. These results indicate that there is a

  8. 武汉地区人群血小板特异性基因(HPA-1~17)的多态性分析%Analysis of gene polymorphism of HPA-1 to-17 alloantigen system in Wuhan population

    Institute of Scientific and Technical Information of China (English)

    陈涵薇; 任明; 张浩; 谢松丽; 沈钢; 陈国安

    2014-01-01

    目的:研究武汉地区人群HPA-1~17基因的多态性及其表达频率,建立HPA基因型资料库.方法:采用序列特异性引物-聚合酶链反应(SSP-PCR)对284名健康的已加入中华骨髓库的血小板捐献者HPA基因进行分型,计算基因型频率、基因频率.结果:武汉地区健康血小板捐献者中检测出HPA-a基因中的1a~17a基因;各基因独立的分布频率中,HPA-1a(98.77%)、2a(97.01%)、3a(59.68%)、4a(99.82%)、5a(99.82%)、6a(98.42%)、15a(49.47%),HPA-7a~14a、16a和17a均为100%.仅检测出HPA-b基因中HPA-1b(1.23%)、2b(2.99%)、3b(40.32%)、4b(0.18%)、5b(0.18%)、6b(1.58%)、15b(50.53%),未检测出HPA-7b~14b、16b和17b.文中调查和分析了HPA基因组合型及其频率,发现武汉地区HPA基因有28种组合型,其中仅有3种基因组合型频率>10%(44%),另外25种基因组合型的频率均<9%(56%).在与国内外不同地区人群HPA基因多态性分布的比较分析中发现,武汉地区人群中HPA基因频率与上海、成都地区人群没有差异性,与美国、英国、欧洲人群有较有明显差异,而与日本人群的差异较小.结论:HPA-3、15系统具有多态性,在随机血小板输注中,供受者HPA-3、HPA-15系统不配合的机会分别为36.54%、37.50%,是HPA配合性输注关注重点.HPA基因多态性研究数据有利于指导地区性血小板供者库库容的设计,配合临床开展选择适合性血小板输注具有重要意义.

  9. Modeling and molecular dynamics simulations of the V33 variant of the integrin subunit β3: Structural comparison with the L33 (HPA-1a) and P33 (HPA-1b) variants.

    Science.gov (United States)

    Jallu, Vincent; Poulain, Pierre; Fuchs, Patrick F J; Kaplan, Cecile; de Brevern, Alexandre G

    2014-10-01

    The human platelet alloantigen (HPA)-1 system, the first cause of alloimmune thrombocytopenia in Caucasians, results from leucine-to-proline substitution (alleles 1a and 1b) of residue 33 in β3 subunit of the integrin αIIbβ3. A third variant with a valine (V33) has been described. Although leucine and valine share similar physicochemical properties, sera containing alloantibodies to the HPA-1a antigen variably reacted with V33-β3, suggesting structural alterations of β3. To analyze the effect of the L33V transition, molecular dynamics simulations were performed on a 3D structural model of the V33 form of the whole β3 extracellular domain (690 residues). Dynamics of the PSI (carrying residue 33), I-EGF-1, and I-EGF-2 domains of β3 were compared to previously obtained dynamics of HPA-1a structure and HPA-1b structural model using classical and innovative developments (a structural alphabet). Clustering approach and local structure analysis showed that L33-β3 and V33-β3 mostly share common structures co-existing in different dynamic equilibria. The L33V substitution mainly displaces the equilibrium between common structures. These observations can explain the variable reactivity of anti-HPA-1a alloantibodies suggesting that molecular dynamic plays a key role in the binding of these alloantibodies. Unlike the L33P substitution, the L33V transition would not affect the structure flexibility of the β3 knee, and consequently the functions of αIIbβ3.

  10. Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

    NARCIS (Netherlands)

    van der Werf-Eldering, MJ; Riemersma-van der Lek, RF; Burger, H.; Holthausen, E.A.E.; Aleman, A.; Nolen, W.A.

    2012-01-01

    Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Method

  11. Taking Stress Response out of the Box: Stability, Discontinuity, and Temperament Effects on HPA and SNS across Social Stressors in Mother-Infant Dyads

    Science.gov (United States)

    Laurent, Heidemarie K.; Ablow, Jennifer C.; Measelle, Jeffrey

    2012-01-01

    This study investigated continuity and stability of hypothalamic-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) response measures in mother-infant dyads across 2 different types of social stress sessions. Synchrony of response trajectories across systems (SNS-HPA coordination) and partners (mother-infant attunement) was addressed, as…

  12. The effect of chronic selective serotonin reuptake inhibitor treatment on serotonin(1B) receptor sensitivity and HPA axis activity

    NARCIS (Netherlands)

    Jongsma, M.E.; Bosker, F.J; Cremers, T.I.F.H.; Westerink, B.H.C.; Den Boer, J.A.

    2005-01-01

    The authors have investigated 5-HT1B receptor function in prefrontal cortex and dorsal hippocampus as well as the HPA axis response after subchronic (24 h) and chronic (15 days) treatment with the SSRI citalopram. All experiments were carried out in presence of citalopram to prevent rapid resensitiz

  13. The Moderating Role of Sensory Overresponsivity in HPA Activity: A Pilot Study with Children Diagnosed with ADHD

    Science.gov (United States)

    Reynolds, Stacey; Lane, Shelly J.; Gennings, Chris

    2010-01-01

    Objective: To determine if sensory overresponsivity (SOR) is a moderating condition impacting the activity of the Hypothalamic Pituitary Adrenal (HPA) Axis in children with ADHD. Method: Participants were children with (n = 24) and without ADHD (n = 24). Children in the ADHD group were divided into SOR (ADHDs) and non-SOR (ADHDt) groups using the…

  14. Effects of atrazine (ATR), deisopropylatrazine (DIA), Diaminochlorotriazine (DACT) on the hypothalamic-pituitary-adrenal (HPA) axis in female rats

    Science.gov (United States)

    We previously reported that a single dose of the herbicide ATR stimulated the HPA axis in the male rat while equimolar doses of its primary metabolite, DACT, had a minimal effect. In this study, we evaluated the effects of one or four daily doses of ATR, DACT, and an intermediat...

  15. Coupling of the HPA and HPG axes in the context of early life adversity in incarcerated male adolescents.

    Science.gov (United States)

    Dismukes, Andrew R; Johnson, Megan M; Vitacco, Michael J; Iturri, Florencia; Shirtcliff, Elizabeth A

    2015-09-01

    The effects of early life adversity can be observed across the lifespan, and the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes could be mechanistic intermediaries underlying this phenomenon. The current study examined 50 adolescent males aged 12-18 in a maximum-security correctional and treatment setting. Saliva samples were collected five times a day for 2 days and assayed for cortisol, testosterone, and DHEA. Youth completed semi-structured life stress interviews and self-reports of child maltreatment to index adversity. When youth had higher testosterone levels, they had higher cortisol and DHEA levels, indicating positive "coupling" of the HPA-HPG axes. In addition, children experiencing greater life adversity had tighter coupling of the HPA-HPG axes. Additional analyses hint that coupling may be driven largely by HPG axis functioning. Results indicate that positive coupling of the HPA-HPG axis is observed within incarcerated adolescents, especially for those with the greatest life stress.

  16. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    Science.gov (United States)

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  17. Effects of Prenatal and Postnatal Parent Depressive Symptoms on Adopted Child HPA Regulation: Independent and Moderated Influences

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Harold, Gordon T.; Reiss, David

    2013-01-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck…

  18. EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS

    Science.gov (United States)

    Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotrop...

  19. Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?

    Science.gov (United States)

    Du, Xin; Pang, Terence Y

    2015-01-01

    There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA)-axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioral deficits and/or mood disorders. Dysregulation of the HPA-axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, antidepressant drugs, such as the selective serotonin reuptake inhibitors have been shown to alter HPA-axis activity. In this review, we will summarize the current state of knowledge regarding HPA-axis pathology in Alzheimer's, PD and HD, differentiating between prodromal and later stages of disease progression when evidence is available. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the preclinical evidence to better inform prospective, intervention studies.

  20. Does HPA-Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?

    Science.gov (United States)

    Lengua, Liliana J.; Zalewski, Maureen; Fisher, Phil; Moran, Lyndsey

    2013-01-01

    The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic-pituitary-adrenal (HPA)-axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool-age children (N?=?306, 36-39?months) and their mothers, recruited to over-represent low-income…

  1. Frequency of human platelet antigens in oncohematological patients with thrombocytopenia and the probability of incompatibility to platelet transfusions Frequência dos antígenos plaquetários humanos (HPA em pacientes trombocitopênicos e predisposição à incompatibilidade transfusional

    Directory of Open Access Journals (Sweden)

    Juliana Vieira dos Santos Bianchi

    2012-01-01

    Full Text Available OBJECTIVE: The objective of this study was to evaluate the frequencies of human platelet antigens in oncohematological patients with thrombocytopenia and to analyze the probability of their incompatibility with platelet transfusions. METHODS: Platelet antigen genotyping was performed by sequence-specific primer polymerase chain reaction (SSP-PCR for the HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b; HPA-15a, HPA-15b alleles in 150 patients of the Hematology Service of the Hospital das Clínicas (FMUSP. RESULTS: The allele frequencies found were: HPA-1a: 0.837; HPA-1b: 0.163; HPA-2a: 0.830; HPA-2b: 0.170; HPA-3a: 0.700; HPA-3b: 0.300; HPA-4a: 1; HPA-4b: 0; HPA-5a: 0.887; HPA-5b: 0.113; HPA-15a: 0.457 and HPA-15b: 0.543. CONCLUSIONS: Data from the present study showed that the A allele is more common in the population than the B allele, except for HPA-15. This suggests that patients homozygous for the B allele are more predisposed to present alloimmunization and refractoriness to platelet transfusions by immune causes. Platelet genotyping could be of great value in the diagnosis of alloimmune thrombocytopenia and to provide compatible platelet concentrates for these patients.OBJETIVO: Esse estudo tem o objetivo de avaliar a frequência dos HPAs em pacientes onco-hematológicos trombocitopênicos e analisar a probabilidade de incompatibilidade associada à transfusão de plaquetas. MÉTODOS: A genotipagem plaquetária foi realizada para os alelos HPA-1a, HPA-1b; HPA-2a, HPA-2b; HPA-3a, HPA-3b; HPA-4a, HPA-4b; HPA-5a, HPA-5b; HPA-15a, HPA-15b por PCR-SSP em 150 pacientes atendidos pelo Serviço de Hematologia do Hospital das Clínicas da FMUSP. RESULTADOS: As frequências alélicas encontradas foram: HPA-1a: 0,837; HPA-1b: 0,163; HPA-2a: 0,830; HPA-2b: 0,170; HPA-3a: 0,700; HPA-3b: 0,300; HPA-4a: 1; HPA-4b: 0; HPA-5a: 0,887; HPA-5b: 0,113; HPA-15a: 0,457; HPA-15b: 0,543. CONCLUSÃO: A análise dos HPAs neste estudo

  2. HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

    Science.gov (United States)

    Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

    2017-03-01

    It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125, p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

  3. A review of Atypical depression in relation to the course of depression and changes in HPA axis organization.

    Science.gov (United States)

    O'Keane, Veronica; Frodl, Thomas; Dinan, Timothy G

    2012-10-01

    Depression is a clinically heterogenous condition defined by sub-types that can have diametrically opposed features, such as sleep and appetite. Within the same individual these features may change over time, and different symptom clusters may respond selectively to different treatments. It has been hypothesized that different pathophysiological processes may be operating in the different sub-types of depression and specifically that Melancholic depression may be associated with relative overactivity, and Atypical depression with relative hypoactivity, of the hypothalamic drive of the HPA axis. A consistent finding that emerges from the literature is that the experience of depression alters over the course of the illness with the features of Atypical depression dominating a more chronic clinical picture. This suggests that different stress states characterize the different profiles of depression as the illness becomes more chronic. There is evidence that the corticotropin-releasing hormone (CRH) control of HPA axis output is reduced in Atypical, compared to Melancholic, sub-types, but there is no convincing evidence that overall HPA activity, i.e., cortisol output, reduces. We suggest that there is a "switch" in the regulation of the HPA system from CRH to arginine vasopressin (AVP) control as stress becomes more sustained or repeated; resulting in an altered homeostasis within the HPA system. Cortisol, and the neuropeptides CRH and AVP, have different neurobiological, behavioural and experiental effects. The "switch" process should result in different neuropeptide/cortisol combinations and ratios and may explain the changing profile of depression over time. The heuristic merit in making a distinction between the different clinical states of depression will be discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Sexual orientation and diurnal cortisol patterns in a cohort of U.S. young adults.

    Science.gov (United States)

    Austin, S Bryn; Rosario, Margaret; McLaughlin, Katie A; Roberts, Andrea L; Gordon, Allegra R; Sarda, Vishnudas; Missmer, Stacey; Anatale-Tardiff, Laura; Scherer, Emily A

    2016-07-01

    Sexual minorities in the United States are at elevated risk of bullying, discrimination, and violence victimization, all stressors that have been linked to psychological and behavioral stress responses including depressive and anxious symptoms and substance use. Acute and chronic stressors may also elicit physiologic stress responses, including changes in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Few studies, however, have examined the relationship between minority sexual orientation and diurnal cortisol patterns. The present study included 1670 young adults ages 18-32 years (69% female, 31% male) from the Growing Up Today Study, a prospective cohort of U.S. youth. Participants provided five saliva samples over one day to estimate diurnal cortisol patterns. Sexual orientation groups included: completely heterosexual with no same-sex partners (referent), completely heterosexual with same-sex partners/mostly heterosexual, and gay/lesbian/bisexual. Covariates included perceived stress and stressful life events in the past month. Sex-stratified multilevel models of log-transformed cortisol values were used to model diurnal cortisol patterns, and generalized estimating equations were used to model area under the curve (AUC), both with respect to ground (AUCg) and increase (AUCi). Among females, sexual minorities reported significantly more stressful life events in the past month than their heterosexual counterparts. In adjusted multilevel models, sexual orientation was not significantly associated with diurnal cortisol patterns or with AUCg or AUCi in either females or males. There were no significant interactions between sexual orientation and stressful life events. Time-varying negative mood was significantly associated with higher cortisol levels across the day for both female and male participants, after adjusting for all covariates. This study from a large cohort of U.S. young adults did not detect a relationship between sexual

  5. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

  6. Histochemical Study of N-acetylgalactosamine Containing Glycoconjugate in Intraductal Carcinoma of the Breast by HPA Lectin

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Arab

    2006-01-01

    Full Text Available Introduction: Glycoconjugates are a class of glycoproteins or glycolipids, their terminal sugars are responsible for cell-cell and/or cell-extracellular matrix interactions. Aberrant glycosylation of these compounds are one of the most important aspects of cellular transformation, metastasis and escape of tumoral cells from immune system and resistance to antineoplastic drugs. Recent studies showed that patients with HPA (helix pomatia agglutinin positive intraductal carcinoma cells have worse prognosis compared to patients with HPA negative cells. The aim of the present study was to define the presence of GalNac terminal sugar in glycoconjugate of different grades of intraductal breast carcinoma and to compare the degree and the pattern of reactivity of tumoral cells to HPA lectin. Materials and Methods: The paraffin blocks belonging to 20 patients of intraductal carcinoma was chosen from pathology archive of Khatam-Al-Anbia hospital in Zahedan and 5-7 micrometer sections were prepared. Two expert pathologists determined histopathological grading independently. The lectin histochemistry was performed using HPA. The same observers determined histochemical grading. Data were analyzed by NPAR (non-parametric test of Mann Whitney. Results: Results of this study revealed that the pattern and the degree of histochemical reactivity of neoplastic cells differ in all grades of intraductal carcinoma. Histochemical staining showed significant difference between grades of intraductal carcinoma of the breast (p<0.003. The lowest reactivity was seen in grade I and the highest in grade III. Furthermore, the reaction of tumoral cells was primarily confined to apical surfaces of cells in grade I, to the Golgi zone in grade II, and to a diffuse cytoplasmic distribution in grade III. Conclusion: Our data suggest that the HPA reactivity of tumoral cells were different in all grades of intraductal carcinoma. The tumor cells showed aberrant glycosylation, which

  7. Study on the degradation of dye wastewater by catalytic Ag+/HPA/TiO2%Ag+/HPA/TiO2复合膜制备及光催化降解染料废水的研究

    Institute of Scientific and Technical Information of China (English)

    刘辉; 邹继颖; 武双双; 戎贵文

    2016-01-01

    选择杂多酸(HPA)和磷钨酸(H3PW12O40)作为无机前驱体,四异丙氧基钛(TTIP)作为钛源,采用溶胶-凝胶和旋涂技术,制备掺杂Ag+/HPA/TiO2复合膜.Ag+掺杂量分别为0.5%(wt,质量分数,下同)、1%、2%、3%和5%,探究对罗丹明B溶液的降解率变化.实验结果表明:Ag+掺杂量为0.5%、降解罗丹明B溶液为6.25mg/L时,降解率最大,达到87.12%.

  8. Psychological and environmental correlates of HPA axis functioning in parentally bereaved children: preliminary findings.

    Science.gov (United States)

    Kaplow, Julie B; Shapiro, Danielle N; Wardecker, Britney M; Howell, Kathryn H; Abelson, James L; Worthman, Carol M; Prossin, Alan R

    2013-04-01

    This study examined bereaved children's HPA-axis functioning (cortisol awakening response; CAR) in relation to psychological distress, coping, and surviving parents' grief reactions. Participants included 38 children (20 girls) with recent parental loss (previous 6 months) and 28 of their surviving caregivers (23 women) who were assessed using self-report instruments and in-person, semistructured interviews. Interviews involved discussions about the child's thoughts and feelings related to the loss. Participants provided 3 saliva samples at home (awakening, 30 minutes later, and evening) over 3 successive days, beginning on the day following the interview. Results show a significant relation between dampening of the child's Day 1 CAR and more symptoms of anxiety (r = -.45), depression (r = -.40), posttraumatic stress (r = -.45), and maladaptive grief (r = -.43), as well as higher levels of avoidant coping (r = -.53). Higher levels of parental maladaptive grief were also associated (r = -.47) with a dampening of the child's Day 1 CAR. Our results raise the possibility that blunted CAR may be a result of accumulating allostatic load and/or a result of emotionally challenging events (discussions regarding the deceased) and their subsequent processing (or lack thereof) within the family, which may be particularly stressful for those bereaved children experiencing high levels of psychological distress, avoidant coping, and parental maladaptive grief.

  9. Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion

    Directory of Open Access Journals (Sweden)

    Michelle eWirth

    2011-08-01

    Full Text Available Stress and social isolation are well-known risk factors for psychopathology. However, more research is needed as to the physiological mechanisms by which social support buffers the impacts of stress. Research in animal models suggests important roles for progesterone (P and its product, the neuroactive steroid allopregnanolone (ALLO, in stress and psychopathology. These hormones are produced in brain and periphery during stress in rodents, and down-regulate anxiety behavior and HPA axis activity. Human clinical populations, including depressed patients, have alterations in ALLO levels, but it is unclear whether these basal hormone level differences have clinical import. To begin to address this question, this review examines the role of P and ALLO in stress physiology, and the impact of these hormones on mood, in healthy humans. Evidence largely supports that P and ALLO increase during stress in humans. However, P/ALLO administration appears to cause only mild effects on mood and subjective anxiety, while exerting effects consistent with GABA receptor modulation. Additionally, P is linked to motivation for affiliation / social contact; P (and ALLO release may be especially responsive to social rejection. These observations lead to the novel hypothesis that stress-related P/ALLO production functions not only to down-regulate stress and anxiety, but also to promote social contact as a long-term coping strategy. Malfunctioning of the P/ALLO system could therefore underlie depression partly by decreasing propensity to affiliate with others.

  10. Analysis of power efficiencies of polar transmitter and HPA in OFDM communication system

    Science.gov (United States)

    Ryu, Heung-Gyoon

    2014-02-01

    Polar transmitter is known as good candidates for high data rate systems such as OFDM (orthogonal frequency division multiplexing) because they can obtain high-efficiency switched-mode radio frequency (RF) power amplifiers. But it is important to consider the nonlinear effects and power efficiency of the amplifier in the OFDM communication systems. High PAPR (peak-to-average power ratio) causes performance degradation by non-linear distortion in OFDM communication system. So to avoid non-linear distortion, back-off is needed. In addition, output of amplifier is lower and the power efficiency is reduced because of back-off. In this article, we compare PAE (power added efficiency) of polar transmitter in OFDM system and PAE of HPA (high power amplifier) in OFDM system. Also, we analyse PAE according to back-off in DFT-spread OFDM (discrete Fourier transform-spread OFDM), which is PAPR reduction method and we compare with PAE of polar transmitter in OFDM system. And we analyse output spectrum of OFDM and DFT-spread OFDM system. Through spectrum analysis, we analyse PAE of OFDM and DFT-spread OFDM, which is satisfied with output spectrum mask of 3rd generation long term evolution (3G LTE) and also compare with PAE polar transmitter of OFDM system, which is satisfied with spectrum mask. Finally, we analyse PAE according to modulation method and analyse PAE of OFDM and DFT-spread OFDM at same bit error rate.

  11. An Efficient Measure for Nonlinear Distortion Severity due to HPA in Downlink DS-CDMA Signals

    Directory of Open Access Journals (Sweden)

    Helaly TarekK

    2010-01-01

    Full Text Available This paper deals with the nonlinear distortion (NLD effects of high power amplifiers (HPAs on direct sequence-code division multiple access systems. Such a distortion drastically degrades the system performance in terms of bit error rate (BER degradation and spectral regrowth. Much effort has been conducted to minimize NLD. A key requirement to do so is to define a certain measure for the HPA nonlinearity, which when reduced often allows NLD to also be reduced. Several measures were proposed such as peak-to-average power ratio, instantaneous power variance, and cubic metric. In this paper, we show that such measures are not closely related to NLD and their reduction does not always lead to optimum performance. Hence, we introduce an efficient measure, namely, nonlinearity severity (NLS, to characterize NLD effects, as an alternative to the existing measures. The NLS is characterized by having direct link to the system performance as it is formulated based on the signal characteristics contributing to BER performance and spectral regrowth. Additionally, a major advantage of the NLS measure is that it is linked to the IBO level allowing the possibility of improving performance at all IBO levels of interest.

  12. Relationship of Arctic sea ice and Northern Hemispheric 500 hPa Polar vortices

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Using the NCEP/NCAR reanalysis monthly 500 hPa height data on a 2.5 latitude-longitude grid and 1°×1° sea ice data, the polar vortex area, intensity index and arctic sea ice area index are calculated respectively, and the meridional distribution, period variation and the abrupts in the long range trend are analyzed to study their relationship. The results show that the meridional distribution of sea ice and polar vortex h-ave distinctive difference, the relative positions of them are different in the eastern and western hemispheres, and exept they have periods of 4 months, quasi half year, quasi year, 4-5 years and 10 years commonly, and each of them has its own respective variation as well. The sea ice area is decreasing apparently since 1980's, so is the polar vortex area, but their abrupt changge time are different totally. The area of sea ice and polar vortex has prominent positive correlation, but the relationship of sea ice intensity, polar vortex intensity, polar vortex area is complicated.

  13. aph(3′)-IIb, a Gene Encoding an Aminoglycoside-Modifying Enzyme, Is under the Positive Control of Surrogate Regulator HpaA

    OpenAIRE

    Zeng, Lin; Jin, Shouguang

    2003-01-01

    Pseudomonas aeruginosa harbors a chromosomal aminoglycoside phosphotransferase gene, aph(3′)-IIb, which confers P. aeruginosa resistance to several important aminoglycoside antibiotics, including kanamycin A and B, neomycin B and C, butirosin, and seldomycin F5. The aph(3′)-IIb gene has been found to be regulated by an AraC-type transcriptional regulator (HpaA) encoded by a gene located upstream of the aph(3′)-IIb gene. In the presence of 4-hydroxyphenylacetic acid (4-HPA), HpaA activates the...

  14. Analysis and compensation for the joint effects of HPA nonlinearity, I/Q imbalance and crosstalk in MIMO beamforming systems

    KAUST Repository

    Qi, Jian

    2011-03-01

    In this paper, we investigate the joint effects of high-power amplifier (HPA) nonlinearity, in-phase/quadrature-phase (I/Q) imbalance and crosstalk, on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems, and propose a compensation method for the three impairments together. The performance of the MIMO TB system equipped with the proposed compensation scheme is evaluated in terms of average symbol error probability and capacity when transmissions are performed over uncorrelated Rayleigh fading channels. Numerical results are provided and show the effects on performance of several system parameters, namely, the HPA parameters, image-leakage ratio, crosstalk, numbers of antennas, length of pilot symbols and phase-shift keying modulation order. © 2011 IEEE.

  15. Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations

    DEFF Research Database (Denmark)

    Gudmand-Høyer, Johanne; Ottesen, Stine Timmermann; Ottesen, Johnny T.

    2014-01-01

    In the Western world approximately 10% of the population experience severe depression at least once in their lifetime and many more experience a mild form of depression. Depression has been associated with malfunctions in the hypothalamus–pituitary–adrenal (HPA) axis. We suggest a novel mechanistic...... non-linear model capable of showing both circadian as well as ultradian oscillations of the hormone concentrations related to the HPA-axis. The fast ultradian rhythm is assumed to originate from the hippocampus whereas the slower circadian rhythm is assumed to be caused by the circadian clock....... The model is able to describe the oscillatory patterns in hormone concentration data from 29 patients and healthy controls. Using non-linear mixed effects modeling with statistical hypothesis testing, three of the model parameters are identified to be related to depression. These parameters represent...

  16. Effects of parental depressive symptoms on child adjustment moderated by HPA: Within- and between-family risk

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

    2012-01-01

    Child hypothalamic-pituitary-adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ( n =210 families). Adoptive parents’ depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA activity measured through salivary cortisol at 54 months. Children’s daily cortisol levels and day-to-day variability were tested as moderators of longitudinal associations between parent and child symptoms at within- and between-family levels. Mothers’ symptoms related directly to child internalizing, but child evening cortisol moderated effects of fathers’ symptoms on internalizing, and of both parents’ symptoms on externalizing. Different paths of within-family risk dynamics vs. between-family risk synergy were found for internalizing vs. externalizing outcomes. PMID:23013523

  17. 血小板特异性抗原HPA-2基因分型的研究

    Institute of Scientific and Technical Information of China (English)

    王砚冰

    2012-01-01

    @@ 血小板表面具有复杂的血型抗原,通常将其分为两类:一类是血小板相关抗原,主要由红细胞的ABO血型系统和HLA决定;另一类是血小板特异性抗原(Human platelet antigen,HPA ),由血小板特有的抗原决定簇组成,表现血小板独特的遗传多态性.HPA 位于血小板膜糖蛋白上,是血小板本身固有的抗原.同种血小板抗体一般由输血、妊娠或造血干细胞移植等免疫刺激而产生[1].

  18. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2015-03-01

    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  19. Does HPA-Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?

    OpenAIRE

    Lengua, Liliana J.; Zalewski, Maureen; Fisher, Phil; Moran, Lyndsey

    2013-01-01

    The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic–pituitary–adrenal (HPA)-axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool-age children (N = 306, 36–39 months) and their mothers, recruited to over-represent low-income families, we explored the associations among diurnal cortisol levels and effortful control, and we tested a model in which diurnal cortisol and effortful ...

  20. Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?

    Science.gov (United States)

    Du, Xin; Pang, Terence Y.

    2015-01-01

    There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic–pituitary–adrenal (HPA)-axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioral deficits and/or mood disorders. Dysregulation of the HPA-axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, antidepressant drugs, such as the selective serotonin reuptake inhibitors have been shown to alter HPA-axis activity. In this review, we will summarize the current state of knowledge regarding HPA-axis pathology in Alzheimer’s, PD and HD, differentiating between prodromal and later stages of disease progression when evidence is available. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the preclinical evidence to better inform prospective, intervention studies. PMID:25806005

  1. Studies on the Performance of Water Stabilizer HPA%水质稳定剂HPA的性能研究

    Institute of Scientific and Technical Information of China (English)

    汪朝阳; 李景宁; 刘利林; 田道远

    2001-01-01

    测定了系列不同浓度的HPA及HPA/Zn2+/BTA复配液的缓蚀和阻垢的数据,结果表明HPA具有良好的缓蚀性能,适宜于腐蚀型水质使用,为进一步开发性能优异的水处理剂提供了基本的参考.

  2. Activation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression.

    Science.gov (United States)

    Torres, Rafael Carvalho; Magalhães, Nathalia Santos; E Silva, Patrícia M R; Martins, Marco A; Carvalho, Vinicius F

    2016-10-01

    Increased hypothalamus-pituitary-adrenal axis (HPA) activity in diabetes is strongly associated with several morbidities noted in patients with the disease. We previously demonstrated that hyperactivity of HPA axis under diabetic conditions is associated with up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal and down-regulation of glucocorticoid receptors (GR and MR) in pituitary. This study investigates the role of peroxisome proliferator-activated receptor (PPAR)-γ in HPA axis hyperactivity in diabetic rats. Diabetes was induced by intravenous injection of alloxan into fasted rats. The PPAR-γ agonist rosiglitazone and/or PI3K inhibitor wortmannin were administered daily for 18 consecutive days, starting 3days after diabetes induction. Plasma ACTH and corticosterone were evaluated by radioimmunoassay, while intensities of MC2R, proopiomelanocortin (POMC), GR, MR, PI3K p110α and PPAR-γ were assessed using immunohistochemistry. Rosiglitazone treatment inhibited adrenal hypertrophy and hypercorticoidism observed in diabetic rats. Rosiglitazone also significantly reversed the diabetes-induced increase in the MC2R expression in adrenal cortex. We noted that rosiglitazone reduced the number of corticotroph cells and inhibited both anterior pituitary POMC expression and plasma ACTH levels. Furthermore, rosiglitazone treatment was unable to restore the reduced expression of GR and MR in the anterior pituitary of diabetic rats. Rosiglitazone increased the number of PPAR-γ(+) cells and expression of PI3K p110α in both anterior pituitary and adrenal cortex of diabetic rats. In addition, wortmannin blocked the ability of rosiglitazone to restore corticotroph cell numbers, adrenal hypertrophy and plasma corticosterone levels in diabetic rats. In conclusion, our findings revealed that rosiglitazone down-regulates HPA axis hyperactivity in diabetic rats via a mechanism dependent on PI3K activation in pituitary and adrenal glands.

  3. Crossover of the hypothalamic pituitary-adrenal/interrenal (HPA, -thyroid (HPT, and -gonadal (HPG axes in testicular development

    Directory of Open Access Journals (Sweden)

    Diana C. Castañeda Cortés

    2014-08-01

    Full Text Available Besides the well-known function of thyroid hormones (THs for regulating metabolism, it has recently been discovered that THs are also involved in testicular development in mammalian and non-mammalian species. THs, in combination with follicle stimulating hormone (FSH, lead to androgen synthesis in Denio rerio, which results in the onset of spermatogenesis in the testis, potentially relating the hypothalamic-pituitary-thyroid gland (HPT to the hypothalamic-pituitary-gonadal (HPG axes. Furthermore, studies in non-mammalian species have suggested that by stimulating the thyroid-stimulating hormone (TSH, THs can be induced by corticotropin-releasing hormone (CRH. This suggests that the hypothalamic-pituitary-adrenal/interrenal gland (HPA axis might influence the HPT axis. Additionally, it was shown that hormones pertaining to both HPT and HPA could also influence the HPG endocrine axis. For example, high levels of androgens were observed in the testis in Odonthestes bonariensis during a period of stress-induced sex determination, which suggests that stress hormones influence the gonadal fate towards masculinization. Thus, this review highlights the hormonal interactions observed between the HPT, HPA and HPG axes using a comparative approach in order to better understand how these endocrine systems could interact with each other to influence the development of testes.

  4. Mathematical modeling of light-mediated HPA axis activity and downstream implications on the entrainment of peripheral clock genes.

    Science.gov (United States)

    Mavroudis, Panteleimon D; Corbett, Siobhan A; Calvano, Steven E; Androulakis, Ioannis P

    2014-10-15

    In this work we propose a semimechanistic model that describes the photic signal transduction to the hypothalamic-pituitary-adrenal (HPA) axis that ultimately regulates the synchronization of peripheral clock genes (PCGs). Our HPA axis model predicts that photic stimulation induces a type-1 phase response curve to cortisol's profile with increased cortisol sensitivity to light exposure in its rising phase, as well as the shortening of cortisol's period as constant light increases (Aschoff's first rule). Furthermore, our model provides insight into cortisol's phase and amplitude dependence on photoperiods and reveals that cortisol maintains highest amplitude variability when it is entrained by a balanced schedule of light and dark periods. Importantly, by incorporating the links between HPA axis and PCGs we were able to investigate how cortisol secretion impacts the entrainment of a population of peripheral cells and show that disrupted light schedules, leading to blunted cortisol secretion, fail to synchronize a population of PCGs which further signifies the loss of circadian rhythmicity in the periphery of the body.

  5. Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders.

    Science.gov (United States)

    Leszczyńska-Rodziewicz, Anna; Szczepankiewicz, Aleksandra; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2013-01-01

    Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  6. Association, Haplotype, and Gene-Gene Interactions of the HPA Axis Genes with Suicidal Behaviour in Affective Disorders

    Directory of Open Access Journals (Sweden)

    Anna Leszczyńska-Rodziewicz

    2013-01-01

    Full Text Available Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA. Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1. The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  7. The Effect of Nicotine on HPA Axis Activity in Females is Modulated by the FKBP5 Genotype.

    Science.gov (United States)

    Koopmann, Anne; Bez, Jennifer; Lemenager, Tagrid; Hermann, Derik; Dinter, Christina; Reinhard, Iris; Schuster, Rilana; Wiedemann, Klaus; Winterer, Georg; Kiefer, Falk

    2016-05-01

    Tobacco smoking modulates activity in the hypothalamic-pituitary-adrenal (HPA) axis and is used to cope with stress, especially by females. The single nucleotide polymorphism (SNP) rs1360780, linked to FK506-binding protein 51 (FKBP5), has been shown to affect HPA axis functioning, and has thus been suggested as a promising candidate for indicating vulnerability to stress-related disorders. The aim of this study was to investigate the interaction between nicotine consumption and rs1360780 on cortisol plasma levels in females. A total of 296 female smokers (assessed by the Fagerström Test for Nicotine Dependence; FTND) were genotyped for the SNP rs1360780. We measured participants' cortisol plasma concentration in blood plasma collected 3 h after standardized tobacco smoking exposure. In the 36 TT-homozygotes, we found a significant negative correlation between the FTND sum score and cortisol plasma concentrations. Using linear regression analysis, we found that the FTND sum score accounted for 12.4% of the variance of cortisol plasma levels. This association was not detected in C-allele carriers. Our results suggest that nicotine is an important confounder in the modulation of HPA axis activity by FKBP5. In light of these findings, future studies on FKBP5 should seek to include data on nicotine consumption as a covariate.

  8. H{sub 3}PW{sub 12}O{sub 40} (HPA), an efficient and reusable catalyst for biodiesel production related reactions. Esterification of oleic acid and etherification of glycerol

    Energy Technology Data Exchange (ETDEWEB)

    Sepulveda, Jorge H.; Vera, Carlos R.; Yori, Juan C.; Badano, Juan M., E-mail: jsepulve@fiq.unl.edu.a [Instituto de Investigaciones en Catalisis y Petroquimica, Santiago del Estero Santa Fe (Argentina); Santarosa, Daniel; Mandelli, Dalmo [Pontificia Universidade Catolica de Campinas, SP (Brazil). Faculdade Quimica

    2011-07-01

    In esterification of oleic acid with methanol at 25 deg C HPA displayed the highest activity. Moreover the HPA could be reused after being transformed into its cesium salt. In the reaction of etherification of glycerol HPA and Amberlyst 35W showed similar initial activity levels. The results of acid properties demonstrate that HPA is a strong protonic acid and that both surface and bulk protons contribute to the acidity. Because of its strong affinity for polar compounds, HPA is also seemingly dissolved in both oleic acid and methanol. The reaction in this case proceeds with the catalyst in the homogenous phase. (author)

  9. New insights into the role of perinatal HPA-axis dysregulation in postpartum depression.

    Science.gov (United States)

    Glynn, Laura M; Davis, Elysia Poggi; Sandman, Curt A

    2013-12-01

    Postpartum depression affects 10-20% of women following birth and exerts persisting adverse consequences on both mother and child. An incomplete understanding of its etiology constitutes a barrier to early identification and treatment. It is likely that prenatal hormone trajectories represent both markers of risk and also causal factors in the development of postpartum depression. During pregnancy the maternal hypothalamic-pituitary-adrenal axis undergoes dramatic alterations, due in large part, to the introduction of the placenta, a transient endocrine organ of fetal origin. We suggest that prenatal placental and hypothalamic-pituitary-adrenal axis dysregulation is predictive of risk for postpartum depression. In this model the positive feedback loop involving the systems regulating the products of the HPA axis results in higher prenatal levels of cortisol and placental corticotropin-releasing hormone. Greater elevations in placental corticotropin-releasing hormone are related to a disturbance in the sensitivity of the anterior pituitary to cortisol and also perhaps to decreased central corticotropin-releasing hormone secretion. Secondary or tertiary adrenal insufficiencies of a more extreme nature, which emerge during the prenatal period, may be predictive of an extended or more pronounced postpartum hypothalamic-pituitary-adrenal refractory period, which in turn represents a risk factor for development of postpartum depression. In addition to reviewing the relevant existing literature, new data are presented in support of this model which link elevated placental corticotropin-releasing hormone with low levels of ACTH at 3-months postpartum. Future research will further elucidate the role of hypothalamic-pituitary-adrenal axis dysregulation in postpartum depression and also whether prenatal placental and hypothalamic-pituitary-adrenal profiles might prove useful in the early identification of mothers at risk for postpartum mood dysregulation. Copyright © 2013

  10. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.

    Science.gov (United States)

    Zschucke, Elisabeth; Renneberg, Babette; Dimeo, Fernando; Wüstenberg, Torsten; Ströhle, Andreas

    2015-01-01

    According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly trained (HT) and sedentary (SED) young men was randomized to either exercise on a treadmill at moderate intensity (60-70% VO2max; AER) for 30 min, or to perform 30 min of "placebo" exercise (PLAC). 90 min later, an fMRI experiment was conducted using an adapted version of the Montreal Imaging Stress Task (MIST). The subjective and psychoneuroendocrine (cortisol and α-amylase) changes induced by the exercise intervention and the MIST were assessed, as well as neural activations during the MIST. Finally, associations between the different stress responses were analysed. Participants of the AER group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced α-amylase and cortisol fluctuations. With regard to the sustained BOLD signal, we found higher bilateral hippocampus (Hipp) activity and lower prefrontal cortex (PFC) activity in the AER group. Participants with a higher aerobic fitness showed lower cortisol responses to the MIST. As the Hipp and PFC are brain structures prominently involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, these findings indicate that the acute stress-buffering effect of exercise relies on negative feedback mechanisms. Positive affective changes after exercise appear as important moderators largely accounting for the effects related to physical fitness.

  11. Memory consolidation during sleep: interactive effects of sleep stages and HPA regulation.

    Science.gov (United States)

    Wagner, Ullrich; Born, Jan

    2008-01-01

    Sleep is critically involved in the consolidation of previously acquired memory traces. However, nocturnal sleep is not uniform but is subject to distinct changes in electrophysiological and neuroendocrine activity. Specifically, the first half of the night is dominated by slow wave sleep (SWS), whereas rapid eye movement (REM) sleep prevails in the second half. Concomitantly, hypothalamo-pituitary-adrenal (HPA) activity as indicated by cortisol release is suppressed to a minimum during early sleep, while drastically increasing during late sleep. We have shown that the different sleep stages and the concomitant glucocorticoid release are interactively involved in the consolidation of different types of memories. SWS-rich early sleep has been demonstrated to benefit mainly the consolidation of hippocampus-dependent declarative memories (i.e. facts and episodes). In contrast, REM sleep-rich late sleep was shown to improve in particular emotional memories involving amygdalar function, as well as procedural memories (for skills) not depending on hippocampal or amygdalar function. Enhancing plasma glucocorticoid concentrations during SWS-rich early sleep counteracted hippocampus-dependent declarative memory consolidation, but did not affect hippocampus-independent procedural memory. Preventing the increase in cortisol during late REM sleep-rich sleep by administration of metyrapone impaired hippocampus-dependent declarative memory but enhanced amygdala-dependent emotional aspects of memory. The data underscore the importance of pituitary-adrenal inhibition during early SWS-rich sleep for efficient consolidation of declarative memory. The increase in cortisol release during late REM sleep-rich sleep may counteract an overshooting consolidation of emotional memories.

  12. Documenting stress in caregivers of transplantation patients: initial evidence of HPA dysregulation.

    Science.gov (United States)

    Bevans, Margaret F; Ross, Alyson; Wehrlen, Leslie; Klagholz, Stephen D; Yang, Li; Childs, Richard; Flynn, Sharon L; Remaley, Alan T; Krumlauf, Michael; Reger, Robert N; Wallen, Gwenyth R; Shamburek, Robert; Pacak, Karel

    2016-01-01

    There is growing evidence linking caregiver stress with an increased risk for morbidity and mortality. While the emotional and practical burden experienced by caregivers is well established, the physiological changes that may affect the caregiver's health are less understood. This study sought to compare self-reported stress, anxiety and depression along with neuroendocrine and immune markers of stress among adult caregivers of allogeneic hematopoietic stem cell transplantation patients during the acute transplant recovery period to matched non-caregivers controls. Biomarkers and self-reported data were collected at three points during the patient's HSCT: (1) before transplant, (2) after initial transplantation discharge (±7 days) and (3) 6 weeks after initial transplantation discharge. Mixed linear modeling was used to examine differences by group and time. Twenty-one caregivers and 20 controls completed all study procedures. The majority of caregivers were female (57% or 57.1%) and married (95.2%), with a mean age of 52 ± 11.4 years. Caregiver perceived stress, anxiety and depression scores were significantly higher than controls (p  0.05) for either group. Caregivers had significantly lower serum cortisol levels than controls at both discharge (p = 0.013; ES = 0.81) and 6 weeks after discharge (p = 0.028; ES = 0.72) but exhibited no significant relationship between self-reported stress and serum cortisol. In addition, caregivers showed a significant inverse relationship between stress and epinephrine levels (r(s)=-0.654, p = 0.021). These findings support the evidence of the caregiving experience being stressful. The counter-intuitive relationship between cortisol and epinephrine might suggest dysregulation of the HPA axis and central nervous system but additional research on the physiological impact of caregiving is warranted.

  13. Study on the preservation with CO (PCO = 200-2,000 hPa), resuscitation, and heterotopic transplantation of an isolated rat heart.

    Science.gov (United States)

    Yoshida, Yu; Hatayama, Naoyuki; Seki, Kunihiro

    2009-01-01

    In this experiment, CO was used as a gas mixture in a reversible relationship with O(2). CO was added in a gas form mixed with O(2). An isolated donor rat heart was obtained, exposed to a gas mixture such as PO(2) = 1,800 hPa and PCO = 200 hPa, and PO(2) = 1,000 hPa and PCO = 1,000 hPa in a 2 ATA high-pressure chamber and preserved in a refrigerator at 4 degrees C. This report demonstrates that significant reproducibility has been verified. The heart was removed from the refrigerator 24 h later and heterotopic heart transplantation was performed in the right neck of a recipient rat and the pulsating of the transplanted heart was detected by an electrocardiogram.

  14. Oral immunization with HpaA affords therapeutic protective immunity against H. pylori that is reflected by specific mucosal immune responses.

    Science.gov (United States)

    Nyström, Johanna; Svennerholm, Ann-Mari

    2007-03-30

    In the present study, we evaluated the capacity of Helicobacter pylori adhesin A (HpaA), a H. pylori specific colonization factor, to induce therapeutic protection against H. pylori infection in mice. We found that oral immunization of H. pylori infected mice with HpaA induced protection, i.e. significant reduction in bacterial load in the stomach. This was even more pronounced when a combination of HpaA and urease was used. The protection was strongly related to specific mucosal CD4+ T cell responses with a Th1 profile as well as to mucosal IgA responses locally in the stomach. These findings suggest that HpaA is a promising vaccine candidate antigen for use in a therapeutic vaccine against H. pylori.

  15. Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

    Directory of Open Access Journals (Sweden)

    Marieke J van der Werf-Eldering

    Full Text Available BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

  16. Identification of anti-HPA-1a allo-antibodies using IgG platelet antibody detection and crossmatch system assay with Galileo Echo.

    Science.gov (United States)

    Di Cristofaro, Julie; Frassati, Coralie; Montagnie, Rolande; Basire, Agnes; Merieux, Yves; Picard, Christophe

    2015-01-01

    Fetal/neonatal allo-immune thrombocytopenia is the most frequent and the most dangerous clinical condition involving anti-human platelet antigens (HPA)-1a allo-antibodies. Anti-HPA-1a allo-immunization requires rapid and accurate diagnosis to determine appropriate treatment. The Capture-P Ready-Screen assay (C-PRS) is a new qualitative immunoassay to detect IgG anti-human leukocyte antigen (HLA) and anti-HPA allo-antibodies. The aim of this study is to assess the identification of anti-HPA-1a allo-antibodies using the C-PRS assay, associated with HLA class I stripping reagents, on the automated benchtop analyzer Galileo Echo. Forty-nine sera were analyzed: without anti-HLA class I or anti-HPA allo-antibodies, with anti-HLA class I allo-antibodies, with anti-HPA-1a allo-antibodies, among which with anti-HLA class I allo-antibodies. None of the samples without allo-antibodies were reactive. Only anti-HLA antibodies, detected by cytotoxicity-dependent complement and not by Luminex, remained positive before and after stripping reagents. Of the 13 samples, anti-HPA-1a allo-antibodies that were correctly identified before and after incubation with HLA assassin reagent were 70% and 85%, respectively. Anti-glycoprotein auto-antibodies and anti-HLA allo-antibodies do not interfere with the detection of anti-HPA-1a antibodies. This preliminary study indicates that further improvement of the test will be helpful in developing a clinically useful assay in the future.

  17. Restriction fragment length polymorphism of adhesin gene hpaA from different Helicobacter pylori strains of Chongqing, China

    Institute of Scientific and Technical Information of China (English)

    Yu Hong; Xu-Hu Mao; Wei-Kun Zeng; Li-Ming Ma; Shen-Rong Jing; Quan-Ming Zou

    2005-01-01

    AIM: To assess the variability of adhesin gene hpaA between different Helicobacter pylori ( H pylori) strains with PCR-restriction fragment length polymorphism (RFLP). METHODS: Twelve different H pylori strains were chosento amplify the 710-bp segments of gene hpaA. These strains were NCTC11637, SS1; Chongqing clinical isolates CCS9801, CCS9802, CCS9803, CCS9806, CCS9809,CCS9810, CCS9813, which were gained from patients of gastritis; Mongolia gerbil adapted H pylori strains (abbreviation MG), which were gained from the following steps: gastric mucosal specimens of Mongolia gerbils infected by clinical isolate CCS9803 were cultured and detected, the positive H pylori strains were named as the first generation of Mongolia gerbil adapted H pylori strains(abbreviation MG1) and then were subcultured with healthy Mongolia gerbil to generate MG2, in turn to gain the ninth generation (abbreviation MG9). All hpaA segments, obtained from 12 different H pylori strains,were digested by HhaⅠ and HaeⅢ individually and analyzed by agarose gel electrophoresis. RESULTS: In all 12 strains, the 710-bp PCR products were successfully amplified and products were cloned to pMD18T vector respectively, then the recombinant plasmids were digested simultaneously with NcoⅠ and XhoⅠ to recover the small fragments. The objective fragments from 12 different H pylori strains digested with Hae Ⅲ could be seen as 4 types of bands and 5 types with Hha Ⅰ. According to the hpaA RFLP patterns, the 12 H pylori strains could be divided into 5 groups: group Ⅰ, NCTC11637 and SS1; group Ⅱ, CCS9809, which RFLP type digested with HaeⅢ wasthe same as strains of group Ⅰ, but HhaⅠ RFLP showeddifference compared with the other groups; group Ⅲ,CCS9810; group Ⅳ, CCS9803; group Ⅴ: CCS9801,CCS9802, CCS9806, CCS9813, MG1, MG3 and MG9. The sequence data of 12 hpaA segments were analyzed by DNAsis software and it was observed that: (1) The homologies of base pair and amino acid sequence

  18. Restriction fragment length polymorphism of adhesin gene hpaA from different Helicobacter pylori strains of Chongqing, China.

    Science.gov (United States)

    Hong, Yu; Mao, Xu-Hu; Zeng, Wei-Kun; Ma, Li-Ming; Jing, Shen-Rong; Zou, Quan-Ming

    2005-05-07

    To assess the variability of adhesin gene hpaA between different Helicobacter pylori (H pylori) strains with PCR-restriction fragment length polymorphism (RFLP). Twelve different H pylori strains were chosen to amplify the 710-bp segments of gene hpaA. These strains were NCTC11637, SS1; Chongqing clinical isolates CCS9801, CCS9802, CCS9803, CCS9806, CCS9809, CCS9810, CCS9813, which were gained from patients of gastritis; Mongolia gerbil adapted H pylori strains (abbreviation MG), which were gained from the following steps: gastric mucosal specimens of Mongolia gerbils infected by clinical isolate CCS9803 were cultured and detected, the positive H pylori strains were named as the first generation of Mongolia gerbil adapted H pylori strains (abbreviation MG1) and then were subcultured with healthy Mongolia gerbil to generate MG2, in turn to gain the ninth generation (abbreviation MG9). All hpaA segments, obtained from 12 different H pylori strains, were digested by HhaI and HaeIII individually and analyzed by agarose gel electrophoresis. In all 12 strains, the 710-bp PCR products were successfully amplified and products were cloned to pMD18-T vector respectively, then the recombinant plasmids were digested simultaneously with NcoI and XhoI to recover the small fragments. The objective fragments from 12 different H pylori strains digested with Hae III could be seen as 4 types of bands and 5 types with Hha I. According to the hpaA RFLP patterns, the 12 H pylori strains could be divided into 5 groups: group I, NCTC11637 and SS1; group II, CCS9809, which RFLP type digested with HaeIII was the same as strains of group I, but HhaI RFLP showed difference compared with the other groups; group III, CCS9810; group IV, CCS9803; group V: CCS9801, CCS9802, CCS9806, CCS9813, MG1, MG3 and MG9. The sequence data of 12 hpaA segments were analyzed by DNAsis software and it was observed that: (1) The homologies of base pair and amino acid sequence between strains NCTC11637, SS1, CCS

  19. Construction and identification of a recombinant attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori hpaA gene%表达幽门螺杆菌hpaA重组减毒鼠伤寒沙门氏菌的构建和鉴定

    Institute of Scientific and Technical Information of China (English)

    朱森林; 陈旻湖; 廖文俊; 陈洁; 胡品津

    2001-01-01

    Objective: To construct a recombinant live attenuated Salmonellaty phimurium vaccine strain expressing Helicobacter pylori hpaA gene.Methods: By g enetic engineering methods,hpaA gene was cloned into a procaryotic expression pl asmid pTrc99A,and the identified recombinant plasmid was then used to transform an attenuated Salmonella typhimurium vaccine strain SL3261,and the positive clon es were screened by PCR and restriction enzyme digestion. HpaA expression was an alyzed by SDS-PAGE and Western blot.Results:Confirmed by PCR and restriction en zyme digestion ,a recombinant procaryotic expression plasmid pTrc99A-hpaA was c o nstructed,and then introduced into an attenuated Sa lmonella typhimurium vaccine strain SL3261 successfully. HpaA was expressed in t he recombinant strains in the form of a dimer,and also its immunogenicity was co nfirmed by Western blot. Conclusion: A recombinant live attenuated Salmonella ty phimurium vaccine strain expressing Helicobacter pylori hpaA gene was constructe d and identified,and this work will help to develop an oral recombinant live vac cine against Helicobacter pylori.%目的:构建表达幽门螺杆菌(H.pylori)hpaA的重组减毒鼠伤寒沙门氏疫苗菌。方法:用基因工程的方法将hpaA基因克隆入原核表达质粒pTrc99A,并进行了基因测序。重组质粒经鉴定后再导入减毒鼠伤寒沙门氏菌SL3261,提取重组疫苗菌质粒,PCR和酶切鉴定,筛选阳性克隆。用SDS-PAGE电泳和Westernblot进行HpaA表达和鉴定。结果:经PCR和酶切证实,构建了含hpaA的重组原核表达质粒pTrc99A-hpaA,并将后者成功转化了减毒鼠伤寒沙门氏菌。HpaA能在疫苗菌中以二聚体形式表达,HpaA量约占全菌体蛋白量的17%,Westernblot证实其有免疫原性。结论:构建了表达H.pylorihpaA的重组减毒鼠伤寒沙门氏疫苗菌,为探索制备H.pylori口服活疫苗奠定了基础。

  20. [Immunoprotective effects of Helicobacter pylori UreB and HpaA bivalence recombinant vaccine with inner adjuvant on experimental infection in mice].

    Science.gov (United States)

    Mao, Ya-fei; Yan, Jie; Xu, Yang

    2005-09-01

    To determine the immunoprotective effects of rUreB and rHpaA bivalence genetic engineering vaccine with inner adjuvant of rLTB on BALB/c mice against H.pylori strain SS1 infection. rUreB, rHpaA, rLTB-rUreB-rHpaA, rLTKA63, rLTB and rLTB were collected by NTA-Ni affinity chromatography. Western blot was applied to demonstrate the immunoreactivity of the recombinant protein antigens. Adjuvant activities of rLTB, rCTB and rLTB-rUreB-rHpaA were determined by GM1-ELISA. H.pylori strain SS1-infected BALB/c mouse modal was established to measure immunoprotective effects of different compositions of antigens and adjuvants. H.pylori in gastric biopsy specimens was examined by routine isolation method and silver staining method. Two ELISAs were established to detect specific S-IgA in gastric juices and specific IgA in sera of the immunized mice. rUreB, rHpaA and rLTB-rUreB-rHpaA were recognized by commercial antibody against whole cell of H.pylori and were able to combine to the bovine GM1. The protective rate in the mice immunized with single rUreB or rHpaA was lower than 70%. When using rUreB or rHpaA plus rLTB or rCTB, the positive rates increased to 75.0%-83.3%. With different combination of antigens and adjuvants, the immunoprotective rate of rLTB-jrUreB-rHpaA was as high as 100%, and then was 91.7% for rUreB+rHpaA+rCTB+rLTKA63 and was 90.9% for rUreB+rHpaA+rLTB. Both the rLTB and rCTB showed remarkable effects to induce specific IgA in sera and specific S-IgA in gastric juices of the immunized mice, and the former showed stronger S-IgA-inducing ability than the latter. The positive rates of specific IgA were basically identical to the corresponding mouse immunoprotective rates. S-IgA positive rates specific to rUreB and rHpaA in rLTB-rUreB-rHpaA immunized mice were 100% and 91.7%, respectively. The rUreB and rHpaA possess qualified immunoreactivity and antigenicity. The rLTB and rCTB can show adjuvant activity of mucosal immunization. The high immunoprotective rate of

  1. Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor.

    Science.gov (United States)

    Kern, Simone; Oakes, Terrence R; Stone, Charles K; McAuliff, Emelia M; Kirschbaum, Clemens; Davidson, Richard J

    2008-05-01

    The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.

  2. 中国西安地区血小板捐献者HPA及HLA-I分型的研究%Analysis of Gene Polymorphism of HPA and HLA- I in Chinese Xi'an Voluntary Platelet Donors

    Institute of Scientific and Technical Information of China (English)

    王小芳; 刘孟黎; 周党侠; 齐珺; 刘晟; 王天菊

    2011-01-01

    为了研究中国西安地区人群HPA和HLA-I分型的分布及多态性,采用PCR-SSP和PCR-SSO流式微磁珠技术检测西安地区375位血小板无偿捐献者HPA和HLA-I分型并进行统计分析.结果发现,在HPA-1 - HPA-17中,HPA-7 - HPA-14、HPA-16和HPA-17只有-aa型,不具多态性;仅在HPA-3、HPA-15中检出-bb型.在16个表现型为HPA-5ab中有9个样本同时表达HPA-15ab,另7个样本表达-15bb,未见-15aa表型.此次检出的表型有HPA-1aa-17aa、HPA-1 ab、-2ab、-3ab、-3bb、-4ab、-5ab、-6ab、-15ab和-15bb.在375人中可观察到16种HLA-A特异性,占该座位可检出表型特异性的76%( 16/21),其中大于1%的有11种;观察到36种HLA-B特异性,占该座位可检出表型特异性的84% (36/43),其中大于1%的有23种,均涵盖在中国北方地区HLA -I特异性常见型里.在375人中观察到HLA-A-B单体型264种,频率大于1%的有30种.结论:西安地区人群HPA和HLA-I基因多态性基本符合中国北方地区分布情况,但具有西安地区特点.%To study the allele frequencies and their polymorphism characteristics of human platelet antigen (HP A) and human leucocyte antigen- I (HLA- I ) in Chinese xi'an population, the types of HP A and HLA- I in 375 Chinese xian voluntary platelet donors were detected by PCR-SSP and PCR-SSO as well as flow cytometry with magnetic beads, and were analyzed. The results showed that there was no polymorphism in HPA-7 - HPA-14 , HPA-16 and HPA-17 which only expressed-aa type, the -bb type was only detected in HPA-3 and HPA-15, 9 out of 16 samples for the HPA-5ab phenotype simultaneously expressed HPA-15ab, the other 7 samples expressed HPA-15bb, no HPA-15aa phe-notype was observed. Phenotypes detected in this study were HPA-laa-17aa, HPA-lab,-2ab,-3ab, -3bb, -4ab, -5ab, -6ab, -15ab and -15bb. Among 375 cases, HLA-A specificity of 16 species was observed, which accounted for 76% (16/21) of detectable phenotype specificity in this locus, moreover, 11 species

  3. Metoclopramide as pharmacological tool to assess vasopressinergic co-activation of the hypothalamus-pituitary-adrenal (HPA) axis: a study in healthy volunteers.

    Science.gov (United States)

    Jacobs, G E; Hulskotte, E G J; de Kam, M L; Zha, G; Jiang, J; Hu, P; Zhao, Q; van Pelt, J; Goekoop, J G; Zitman, F G; van Gerven, J M A

    2010-12-01

    The synthetic vasopressin (AVP) analogue desmopressin (dDAVP) has been used as pharmacological function test to quantify vasopressinergic co-activation of the hypothalamus-pituitary-adrenal (HPA) axis in the past. Such exogenous vasopressinergic stimulation may induce confounding cardiovascular, pro-coagulatory and anti-diuretic effects and low endogenous corticotrophin-releasing-hormone (CRH) levels may limit its potential to reliably assess co-activation. Alternatively, the dopamine-2-(D2)-antagonist metoclopramide is believed to induce co-activation indirectly by releasing endogenous AVP. We investigated this indirect co-activation with metoclopramide under conditions of low and enhanced endogenous CRH release in healthy volunteers. A randomized, double-blind, placebo-controlled, four-way crossover study was performed in 12 healthy males. CRH release was induced by administering an oral 5-hydroxytryptophan (5-HTP) 200 mg function test. Co-activation was investigated by administering metoclopramide 10mg intravenously around the expected maximal effect of 5-HTP. The neuroendocrine effects were compared to those of metoclopramide alone, the 5-HTP test alone and matching placebo. Metoclopramide safely induced HPA-axis activation by itself, and potently synergized 5-HTP-induced corticotrophinergic activation of the HPA axis. These findings are indicative of vasopressinergic co-activation and suggest a role for metoclopramide as a practical function test for co-activation of the HPA axis. However, its application will be hampered pending clarification of the exact pharmacological mechanism by which metoclopramide induces co-activation of the HPA axis.

  4. Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

    Science.gov (United States)

    Juul, Sarah H; Hendrix, Cassandra; Robinson, Brittany; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A; Johnson, Katrina C

    2016-02-01

    A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

  5. An Improved RSP Method to Detect HpaI Polymorphism in the Apolipoprotein C-1 Gene Promoter

    Directory of Open Access Journals (Sweden)

    Lavoie Tera

    2002-11-01

    Full Text Available Abstract Background An apolipoprotein C1 gene promoter polymorphism (CGTT insertion at position -317 is associated with familial dysbetalipoprotemia, cardiovascular diseases, and Alzheimer's disease. Restriction site polymorphism (RSP assays were previously established to detect this polymorphism. In this study, we introduce an improved RSP assay to detect this polymorphism. Methods This method included newly designed primers and only one round of PCR amplification which yields one short and specific APOC1 fragment followed by HpaI digestion. Briefly, It consists of three steps: 1 one round of PCR amplification of DNA sample, 2 HpaI enzyme digestion of PCR products, and 3 electrophoresis on an agarose gel to visualize the genotypes. This improved RSP method was applied to genotype 92 human samples collected from The Johns Hopkins Hospital. Results The observed allele frequencies for H1 and H2 from 92 genotyped human subjects were 0.707 and 0.293 respectively. The H2 allele frequency in the black subjects (0.350 was significantly (p = 0.024 higher than that in the white subjects (0.177. This method was more economical and convenient than the methods previously reported to detect this mutation in the APOC1 gene. Conclusions This assay will be readily applied to screen large sample sizes for population studies in a simple and cost effective way.

  6. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

    Science.gov (United States)

    Virgolini, Miriam B; Chen, Kevin; Weston, Doug D; Bauter, Mark R; Cory-Slechta, Deborah A

    2005-10-01

    Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

  7. Maternal depression across the first years of life compromises child psychosocial adjustment; relations to child HPA-axis functioning.

    Science.gov (United States)

    Apter-Levi, Yael; Pratt, Maayan; Vakart, Adam; Feldman, Michal; Zagoory-Sharon, Orna; Feldman, Ruth

    2016-02-01

    Maternal depression across the first years of life negatively impacts children's development. One pathway of vulnerability may involve functioning of the hypothalamic-pituitary-adrenal (HPA) axis. We utilize a community cohort of 1983 women with no comorbid risk repeatedly assessed for depression from birth to six years to form two groups; chronically depressed (N=40) and non-depressed (N=91) women. At six years, mother and child underwent psychiatric diagnosis, child salivary cortisol (CT) was assessed three times during a home-visit, mother-child interaction was videotaped, and child empathy was coded from behavioral paradigms. Latent Growth curve Model using Structural Equation Modeling (SEM) estimated the links between maternal depression and mother's negative parenting and three child outcomes; psychopathology, social withdrawal, and empathy as related to child CT baseline and variability. Depressed mothers displayed more negative parenting and their children showed more Axis-I psychopathology and social withdrawal. SEM analysis revealed that maternal depression was associated with reduced CT variability, which predicted higher child psychopathology and social withdrawal. Whereas all children exhibited similar initial levels of CT, children of controls reduced CT levels over time while children of depressed mothers maintained high, non-flexible levels. Mother negativity was related to lower initial CT levels, which predicted decreased empathy. Findings suggest that chronic maternal depression may compromise children's social-emotional adjustment by diminishing HPA-system flexibility as well as limiting the mother's capacity to provide attuned and predictable caregiving.

  8. Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity.

    Science.gov (United States)

    Lindqvist, D; Fernström, J; Grudet, C; Ljunggren, L; Träskman-Bendz, L; Ohlsson, L; Westrin, Å

    2016-12-06

    Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-valuesSuicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.

  9. Analysis of HPA gene Polymorphisms in Children with Acute or Chronic ITP%儿童急、慢性特发性血小板减少性紫癜HPA基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    唐利娟; 周晓姮; 宾琼; 黄小花; 罗建明

    2016-01-01

    目的:探讨广西地区儿童急、慢性特发性血小板减少性紫癜(ITP)的HPA-2和HPA-15等位基因频率分布情况及HPA-2和HPA-15基因多态性与儿童ITP发病的潜在联系.方法:收集2010年1月至2014年12月确诊为急性和慢性ITP的各46例患儿的临床资料,运用聚合酶链反应技术(PCR)结合直接测序方法,对急、慢性ITP两组各46例患儿及对照组48例健康儿童进行HPA-2和HPA-15基因分型.结果:3组之间HPA-2和HPA-15等位基因频率比较均有显著性差异(P<0.05),每2组比较分析显示,HPA-2和HPA-15等位基因频率在慢性ITP组与对照组间差异显著,有统计学意义(P<0.05),而急性ITP组与对照组及慢性ITP组与急性ITP组相比较差异均无统计学意义(P>0.05).结论:HPA-2与HPA-15基因多态性与儿童慢性ITP发病有关,与儿童急性ITP发病无关.

  10. 急性白血病患者HPA-1~6,15基因多态性与血小板输注疗效的相关性研究%Correlation between polymorphism of HPA-1~6,15 and the effect of platelet transfusion in patients with acute leukemia

    Institute of Scientific and Technical Information of China (English)

    苗菁; 曾小菁

    2014-01-01

    目的 通过检测人类血小板抗原1~6,15系统(Human platelet alloantigen,HPA-1~6,15),探讨HPA多态性与血小板输注疗效的相关性.方法 (1)收集30例输注2次以上血小板的急性白血病患者外周血标本,根据血小板回收率(Percentage platelet recovery,PPR)判定输注效果;(2)采用酚/氯仿方法提取DNA;(3)采用聚合酶链反应-序列特异性引物(Polymerase chain reaction-sequence specific primers,PCR-SSP)方法在相同条件下对血小板抗原IPA-1~6,15进行基因分型,分析HPA抗原与血小板输注疗效的关系.结果 (1)HPA-1~3、HPA-5~6、HPA-15系统等位基因呈多态性分布;HPA-4呈aa纯合子单态性分布,HPA-1、5、6基因以an纯合子为主,仅HPA-3、15见bb纯合子,b等位基因频率以HPA-2最高(0.65),其次依次为HPA-15 (0.349),HPA-3 (0.3).(2) 30例急性白血病患者中有21例血小板输注无效,无效率为70%,多集中于输注3次及以上组.结论 (1)抗-HPA引起血小板输注无效概率较小,主要发生在HPA-2、3、15系统,对需作HPA配型的患者只要针对此3个系统进行检测,就可提高输注效果.(2)临床应注重血小板输注治疗的个体化,减少输注次数,提高输注疗效.

  11. 福建汉族人群人类血小板抗原HPA-15多态性分析(附113例报告)%Human platelet antigen-15 polymorphism in Fujian Han populations

    Institute of Scientific and Technical Information of China (English)

    叶先仁; 刘燕玉; 陈玉娟

    2007-01-01

    目的 分析福建汉族人群人类血小板抗原(HPA)-15基因多态性,为临床血小板输注提供依据.方法 采用聚合酶链反应-序列特异引物法(PCR-SSP)技术对113名福建汉族健康个体进行HPA-15基因分型.结果 HPA-15aa、HPA-15ab及HPA-15bb的分布频率分别为0.274、0.522和10.204,与我国其他省份汉族人群比较,差异无统计学意义.HPA-15a、HPA-15b抗原不配合率分别为0.116和10.133.结论 HPA-15基因多态性区域差异不明显.HPA-15a/b抗原不配合率较HPA其他系统高,可能导致产生同种免疫性血小板抗体的概率增加,在临床血小板输注中的作用值得重视.

  12. 长沙地区汉族人血小板抗原(HPA1-17)基因多态性调查%Polymorphism of human platelet antigens 1-17 in Changsha Han population

    Institute of Scientific and Technical Information of China (English)

    张刚; 曹丽群; 谢毓滨; 钟待鸣

    2013-01-01

    Objective To investigate the genetic polymorphism of HPA1-17 antigens in Changsha Han population. Methods A total of 618 samples from unrelated platelet donors of Changsha were genotyped by Polymcrasc Chain Reaction with Sequence-Specific Primers(PCR-SSP). Results The allele frequencies of HPA-la, 2a, 3a, 4a, 5a, 6a, 15a were 0. 993,0. 968,0. 587,0. 994,0. 989,0. 989,0. 536, HPA-7a-17a( exclude 15a) were 1. 000, HPA-bw alleles were not detected. Conclusion The genotype of HPA can improve the safety and curative effect of the platelet transfusion. Gcnotyping can be used in HPA crossmatch and the diagnosis of alloimmune platelet disease.%目的 研究长沙地区汉族人群人类血小板特异性抗原HPA1-17基因多态性.方法采用PCR-SSP方法对长沙市血液中心 618名汉族无偿献血者进行HPA1-17系统基因分型.结果长沙地区 618名汉族无偿献血者HPA1a基因频率为99.3%,HPA2a基因频率为96.8%,HPA3a基因频率为58.7%,HPA4a基因频率为99.4%,HPA5a基因频率为98.9%,HPA6a基因频率为98.9%,HPA15a基因频率为53.6%.结论 长沙地区汉族人群HPA1-17的基因检测填补了地方空白,为建立血小板库奠定了基础,也为临床提供同型血小板输注提供可能.

  13. 中国南京地区汉族人群血小板HPA-1-18遗传多态性研究%Genetic Polymorphism of Human Platelet Antigens 1 -18 in Chinese Nanjing Han Population

    Institute of Scientific and Technical Information of China (English)

    薛敏; 刘衍春; 魏鹏

    2012-01-01

    The purpose of this study was to investigate the allele frequencies of the human platelet alloantigens 1-18 system (HPA-1 -18) in Chinese Nanjing unrelated and healthy Han population, so as to provide the credible basis to screen compatible platelets for transfusing patients. The genotypes of 18 HP A systems were determined by polymerase chain reaction using sequence-specific primer (PCR-SSP) for 300 samples. The results showed that the gene frequencies obtained from 300 Nanjing unrelated population were 0.9183 and 0.0817 for HPA-2a and -2b, 0. 6100 and 0. 3900 for HPA-3a and -3b, 0. 9733 and 0.0267 for HPASa and -5b, 0. 9883 and 0.0117 for HPA-6a and -6b, 0. 5250 and 0. 4750 for HPA-15a and -15b. All the tested individuals were homozygotes for HPA-1 a,-4a,-7a - 14a and HPA -16a - 18a. There was a good fit to Hardy-Weinberg equilibrium in each group. It is concluded that this study has confirmed the ethnic and regional difference of HPA, and HPA in Nanjing Han population has its own characteristics. The highest heterozygotes are HPA-3 and HPA -15, thus more atlention to HPA effects on clinical platelet matched transfusion should be paid.%本研究旨在调查南京地区无关健康人群人类血小板抗原1 -18(HPA-1 - 18)等位基因频率,为输血患者寻找相容性血小板提供可靠依据.使用PCR-SSP方法对300例南京地区非血缘健康志愿者血液样品进行人血小板抗原1 -18(HPA-1 - 18)等位基因分型.结果表明,南京地区300例非血缘人群HPA等位基因频率分别为:HPA-2a0.9183和-2b 0.0817;HPA-3a 0.6100和-3b 0.3900;HPA-5a 0.9733和-5b 0.0267;HPA-6a0.9883和-6b0.0117;HPA-15a 0.5250和-15b 0.4750.HPA-1a,-4a,-7a - 14a和HPA-16a -18a均是纯合子.结论:HPA抗原等位基因频率存在种族和地域差异.南京地区HPA抗原等位基因频率显示具有自身特点.HPA-3和HPA-15是最常见的杂合子,因此必须关注HPA在血小板临床输血中的作用.

  14. Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation

    Directory of Open Access Journals (Sweden)

    Roberta Giordano

    2006-01-01

    Full Text Available The hypothalamus-pituitary-adrenal (HPA axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP, a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR and mineralocorticoid (MR receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP, ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.

  15. The Defecation Index as a Measure of Emotionality: Questions Raised by HPA Axis and Prolactin Response to Stress in the Maudsley Model.

    Science.gov (United States)

    Blizard, David A; Eldridge, J Charles; Jones, Byron C

    2015-05-01

    The Maudsley Reactive and Maudsley Non-Reactive strains have been selectively bred for differences in open-field defecation (OFD), a putative index of stress. We investigated whether variations in the hypothalamic-pituitary-adrenal (HPA) axis are correlated with strain differences in OFD in the Maudsley model. Exposure to the open-field test did not result in increases in ACTH in male rats of either strain and there were no strain differences in the large increases in ACTH and corticosteroid that occurred in response to intermittent footshock. Parallel studies of prolactin showed that Maudsley Reactive rats had greater response to the open-field and to footshock than Maudsley Non-Reactive rats. The lack of correlation between strain differences in OFD and reactivity of the HPA axis is consistent with the idea that HPA response to stress and OFD reflect the output of different neural systems and that individual differences in emotionality, as indexed by OFD do not influence other measures of stress-reactivity in a simple manner, if at all. The reactivity of the prolactin system to the open-field test and lack of response of ACTH to the same situation is consistent with the idea that the prolactin system is sensitive to lower levels of stress than the HPA axis, a finding at variance with the presumed extreme sensitivity of the latter system. Earlier comparisons of the HPA axis in these strains implicate local factors such as neuropeptide-Y peptide in the adrenal in attenuating the response of the adrenal cortex to ACTH and hints at the complexity of regulation of the HPA axis.

  16. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-02-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.

  17. 十字花科黑腐病菌中转录调控因子HpaR1调控一个纤维素酶基因的表达%The Transcriptional Regulator HpaR1 of Xanthomonas campestris pv.campe-stris (Xcc) 8004 Regulates the Expression of a Extracellular Cellulase Gene

    Institute of Scientific and Technical Information of China (English)

    薛番艳; 苏辉昭; 刘兴艳; 梁伟; 李磊; 李瑞芳; 陆光涛

    2012-01-01

    十字花科黑腐病菌(Xcc8004)中的一个转录调控因子XC_2736 (HpaR1)在致病过程中具有重要的作用.前期研究发现该转录调控因子可能调控胞外纤维素酶的合成.为了解HpaR1对纤维素酶的转录调控机理,本研究对HpaR1进行原核表达纯化,并与488 bp的包含XC_0639的启动子区DNA片段进行凝胶电泳迁移率试验,发现HpaR1与XC_0639启动子可以发生结合.将488 bp的XC_0639的启动子DNA片段与报告基因gus融合,构建XC_0639的报告质粒pGUS0639r,分别导入野生型8004菌株和缺失突变体DM2736中,分析发现在突变体背景下GUS的表达水平比野生型背景明显降低.表明HpaR1正调控XC_0639的表达.构建XC_0639的极性整合突变体PK0639,检测发现PK0639几乎丧失胞外纤维素酶的活力;通过功能反式互补构建的互补菌株CPK0639可以恢复纤维素酶活性.研究结果表明HpaR1通过调控纤维素酶基因XC_0639的表达来调控细胞的纤维素酶活性.本研究为更深入地了解HpaR1如何调控细菌生理生化功能奠定了基础.%The transcriptional regulator XC-2736 {HpaRl) of X. campestris pv. campestris (Xcc) 8004 plays important roles in regulating bacterial diverse biological processes. Previous work showed that this transcriptional regulator might play role on extracellular cellulase. To illustrate the regulatory mechanism, HpaRl was over expressed, and electrophoretic mobility shift assays (EMSA) were performed using HpaRl protein and the promoter fragment end XCA-p of XC_0639. Results showed that HpaRl could specifically bind to the promoter fragment of XC_0639. The reporter plasmid pGUS0639r was constructed by fusing the promoter of XC_0639 with gus gene, and them been introduced into wild type strain 8004 and the HpaRl mutant DM2736, respectively. The expression level of GUS decreased significantly in the mutant, compared to the wild type background, suggesting HpaRl positively regulates the expression of XC_0639

  18. Investigation of the polymorphism of HPA-1 ~ 5 gene and the platelet transfusion refractoriness Dong ethnic group in Guizhou province, China%贵州省黔东南州侗族献血人群HPA-1~5多态性分析及随机输血不配合率研究

    Institute of Scientific and Technical Information of China (English)

    杨芳; 黄吉娥; 曾小菁; 杨普渝; 丛硕

    2013-01-01

    目的 调查贵州省侗族健康随机献血人群人类血小板抗原(human platelet antigen,HPA)1~5系统基因多态性分布特点.方法 采用聚合酶链-序列特异性引物技术(PCR-SSP)对贵州省无血缘关系侗族随机献血人154例血样进行HPA-1~5系统基因分型.结果 贵州省黔东南州侗族HPA-1a、2a、3a、4a、5a、基因频率分别是0.942、0.741、0.926、0.954、0.773,HPA-1b、2b、3b、4b、5b、基因频率分别是0.058、0.286、0.084、0.045、0.227;经,检验,结果符合Hardy-Weinberg遗传平衡定律.随机输血HPA不配合的发生率依次为:HPA-4:49.11%,HPA-2:32.%,HPA-5:28.94%,HPA-3:14.35%,HPA-1:10.33%.与其他研究比较:贵州省侗族人群HPA-1~5系统基因频率与不同人群相比较:HPA-1与中国汉族、海南黎族、新疆维吾尔族相比较差异有统计学意义(P<0.05);HPA-2与贵州省黔东南州苗族、中国汉族、新疆柯尔克孜族、海南黎族、西藏藏族、浙江畲族、美国白人相比较均差异有统计学意义(P<0.05);HPA-3、4与贵州省黔东南州苗族、中国汉族、新疆维吾尔族、新疆柯尔克孜族、海南黎族、西藏藏族、浙江畲族、广西瑶族、美国黑人、美国白人相比较差异有统计学意义(P <0.05);HPA-5与贵州省黔东南州苗族、中国汉族、新疆柯尔克孜族、海南黎族、淅江畲族、广西瑶族、美国白人相比较均差异有统计学意义(P<0.05).结论 贵州省侗族献血人群HPA-1~5系统基因具有独特的分布频率和群体结构特点,且不配合率较高,应建立本地区的血小板献血者基因分型数据库.

  19. Study on multi-PCR-SSP technique for HPA-1 ~ 17bw genotyping and the distribution of HPAs polymorphism in Chinese Zhuang population%多重PCR-SSP技术应用于HPA-1~17bw基因分型研究和广西壮族人群HPA多态性的分布

    Institute of Scientific and Technical Information of China (English)

    申卫东; 李丽兰; 廖燕; 赵桐茂; 吴国光

    2014-01-01

    目的 建立应用于HPA-1~ 17bw基因分型的多重聚合酶链反应-序列特异性引物(PCR-SSP)技术,对广西壮族人群HPA多态性分布进行调查.方法 设计多种HPA序列特异性引物的组合,在1个PCR反应体系中同时扩增多个HPA基因,根据扩增片断的有无和大小,指定相应的HPA基因型,并以17例国际合作研究项目提供的HPA参比DNA配组标本,以及100例已知HPA型的血小板供者的DNA标本作验证.使用验证后的技术对2659名无血缘关系的广西壮族人群展开PA-1~17bw的基因分型和抗原多态性研究.结果 建立了由16种PCR引物混合液,其中有6种多重PCR引物混合液组成的PCR-SSP反应体系,可用于HPA-1~17bw等位基因的检测.以HPA参比DNA配组标本,以及已知HPA型的供者的DNA标本的检测作验证,HPA分型结果完全一致;在2 659名广西壮族人群中各HPA等位基因频率分布为:HPA-1a和-1b为0.991 5和0.008 5,HPA-2a和-2b为0.956 9和0.043 1,HPA-3a和-3b为0.512 2和0.487 8,HPA-5a和-5b为0.985 0和0.015 0,HPA-6a和-6b为0.985 1和0.014 9,HPA-15a和-15b为0.5256和0.474 4;HPA-4、HPA-7~14bw、HPA-16~ 17bw只有a/a的纯合子;HPA-2~3、HPA-6bw以及HPA-15均存在a/a和b/b纯合子基因型个体.结论 多重PCR-SSP技术应用于HPA基因分型减少了PCR扩增反应数量,节省了人力、物力,HPA分型系统性强,可用于大量标本的HPA-1~ 17bw基因分型等研究和筛查工作;应用该方法研究证明广西壮族人群HPA多态性分布具有民族特征,有助于对壮族人群血小板免疫学特点的了解.

  20. Study on genetic frequency of HPA-2 of Zhuang nationality in Guangxi Zhuang Autonomous Region%广西壮族自治区壮族居民血小板抗原HPA-2基因分布频率研究

    Institute of Scientific and Technical Information of China (English)

    廖燕; 申卫东; 李丽兰; 周先果; 何保仁; 刘学军; 刘金莲; 黄惠妮

    2014-01-01

    目的:探讨广西壮族自治区壮族居民HAP-2基因分布频率,指导相关血小板输注的治疗决策。方法采用聚合酶链式单核苷酸多态性方法对2659名广西壮族自治区壮族健康成年人的血液样本进行HPA-2基因分型检测,用直接测序法解决HPA-2分型差异。结果 HPA-2a/2a、HPA-2a/2b和HPA-2b/2b的等位基因频率分别为0.9157、0.0824和0.0019;测得基因多态性位点与数据库收录信息全部吻合,未发现新的单核苷酸多肽性(SNP)位点。广西壮族自治区壮族居民HPA-2a/2b基因的杂合程度与大多数亚洲国家的研究结果相似,与非洲人相比存在显著差异。结论该研究有助于确定该地区居民HPA-2多态性分布及其潜在临床意义,能更好地理解和治疗壮族免疫性介导的血小板疾病。%Objective To determine the gene distribution frequency of human platelet antigen (HPA)-2 of Guangxi Zhuang Autonomous Region,so as to guide treatment decisions concerning platelet(PLT) transfusion. Methods The polymerase chain single nucleotide polymorphism was adopted to determine the genetic typing of HPA-2 among 2 659 health adults in Guangxi Zhuang Autonomous Region,and the direct sequencing was employed to resolve the genetic difference of HPA-2. Results Allele frequencies of HPA-2a/2a,HPA-2a/2b and HPA-2b/2b were 0.915 7,0.082 4 and 0.001 9,respectively. The detected gene poly-morphism site was completely identical to the information in database ,and no new single nucleotide polymorphism (SNP) site was discov ered. The degree of heterozygosis of HPA-2a/2b of Zhuang nationality was similar to the research results of most Asian counties,but compared with the African,the difference was significant. Conclusion This study contributes to determine the polymorphism distribution of HPA-2 in Guangxi and its potential clinical significance ,and it is beneficial to understand and treat immune-mediated PLA disease of Zhuang nationality.

  1. Productivity and biochemical properties of green tea in response to full-length and functional fragments of HpaGXooc, a harpin protein from the bacterial rice leaf streak pathogen Xanthomonas oryzae pv. oryzicola

    Indian Academy of Sciences (India)

    Xiaojing Wu; Tingquan Wu; Juying Long; Qian Yin; Yong Zhang; Lei Chen; Ruoxue Liu; Tongchun Gao; Hansong Dong

    2007-09-01

    Harpin proteins from plant pathogenic bacteria can stimulate hypersensitive cell death (HCD), drought tolerance, defence responses against pathogens and insects in plants, as well as enhance plant growth. Recently, we identified nine functional fragments of HpaGXooc, a harpin protein from Xanthomonas oryzae pv. oryzicola, the pathogen that causes bacterial leaf streak in rice. Fragments HpaG1–94, HpaG10–42, and HpaG62–138, which contain the HpaGXooc regions of the amino acid sequence as indicated by the number spans, exceed the parent protein in promoting growth, pathogen defence and HCD in plants. Here we report improved productivity and biochemical properties of green tea (Camellia sinensis) in response to the fragments tested in comparison with HpaGXooc and an inactive protein control. Field tests suggested that the four proteins markedly increased the growth and yield of green tea, and increased the leaf content of tea catechols, a group of compounds that have relevance in the prevention and treatment of human diseases. In particular, HpaG1–94 was more active than HpaGXooc in expediting the growth of juvenile buds and leaves used as green tea material and increased the catechol content of processed teas. When tea shrubs were treated with HpaHXooc and HpaG1–94 compared with a control, green tea yields were over 55% and 39% greater, and leaf catechols were increased by more than 64% and 72%, respectively. The expression of three homologues of the expansin genes, which regulate plant cell growth, and the CsCHS gene encoding a tea chalcone synthase, which critically regulates the biosynthesis of catechols, were induced in germinal leaves of tea plants following treatment with HpaG1–94 or HpaGXooc. Higher levels of gene expression were induced by the application of HpaG1–94 than HpaGXooc. Our results suggest that the harpin protein, especially the functional fragment HpaG1–94, can be used to effectively increase the yield and improve the biochemical

  2. 湖北汉族人群人血小板同种抗原系统基因分型研究%Genotyping of HPA Blood Group by PCR-SSP in Hubei Han Population of Chinese

    Institute of Scientific and Technical Information of China (English)

    罗成伟; 胡丽华; 王琳; 饶神宗

    2003-01-01

    目的研究湖北汉族人群人血小板同种抗原系统(HPA)基因型及其多态性分布特征,并与其他种族相比较.方法用DNA提取试剂盒提取外周血标本中的DNA,用聚合酶链式反应-序列特异性引物(PCR-SSP)扩增HPA等位基因.结果 100名健康、无血缘关系的湖北汉族人群HPA基因频率为HPA-la:0.97、HPA-1b:0.03;HPA-2a:0.98、HPA 2b:0.02;HPA-3a:0.82、HPA-3b:0.18;HPA-4a:0.99、HPA-4b:0.01;HPA 5a:0.91、HPA-5b:0.09(P>0.05,u=1,符合Hardy-Weinberg公式).结论 HPA血型系统多态性具有人群特征,在不同的国家和地区HPA基因频率均不相同.与其他种族相比,中国人群HPA血型系统中a基因频率较高,b基因频率较低,理论杂合率与实际杂合率均低于其他种族,说明在中国人群中由b基因不合所引起的同种免疫病理反应要低于其他种族人群.

  3. Measurement of Balmer and Lyman X-rays in antiprotonic hydrogen isotopes at pressures below 300 hPa

    Energy Technology Data Exchange (ETDEWEB)

    Bacher, R.; Bluem, P.; Gotta, D.; Heitlinger, K.; Rohmann, D.; Schneider, M.; Egger, J.; Simons, L.M.; Elsener, K.

    1989-09-01

    X-rays of Balmer and Lyman transitions in antiprotonic hydrogen and of Balmer transitions in antiprotonic deuterium were observed at pressures below 300 hPa using Si(Li) semiconductor detectors. The measurement was performed at the LEAR-facility at a beam momentum of 202 MeV/c. In order to stop antiprotons in a low pressure gaseous target with high efficiency, a novel technique, the cyclotron trap has been used. Absolute yields were determined and compared with cascade calculations. A distinct difference in the cascade of antiprotonic hydrogen and deuterium is found. The parameters of strong interaction in antiprotonic hydrogen are determined to be /epsilon//sub 1s/=-(620+-100) eV, /Gamma//sub 1s/=(1130+-170) eV and /Gamma//sub 2p/=(32+-10) meV. (orig.).

  4. Suicidal intent and the HPA-axis characteristics of suicide attempters with major depressive disorder and adjustment disorders.

    Science.gov (United States)

    Lindqvist, Daniel; Träskman-Bendz, Lil; Vang, Fredrik

    2008-01-01

    The main purpose of the study was to investigate Hypothalamic-Pituitary-Adrenal (HPA) axis characteristics in relation to suicidal intent among suicide attempters with Major Depressive Disorder (MDD) and Adjustment Disorders (AD). The relationship between suicidal intent, assessed by means of the Suicidal Intent Scale (SIS), and serum cortisol after a Dexamethasone Suppression Test (DST) was investigated in 78 suicide attempters, divided into diagnostic subgroups. There was a significant negative correlation between suicidal intent and post DST cortisol in patients with MDD. Our findings may be attributed to pathophysiological processes, where a high suicidal intent is revealed during a potential chronic course of MDD, which in turn results in a seemingly normal stress system.

  5. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  6. Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

    Science.gov (United States)

    Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

    2015-02-01

    There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Decreased daytime illumination leads to anxiety-like behaviors and HPA axis dysregulation in the diurnal grass rat (Arvicanthis niloticus)

    Science.gov (United States)

    Ikeno, Tomoko; Deats, Sean P.; Soler, Joel; Lonstein, Joseph S.; Yan, Lily

    2016-01-01

    The impact of ambient light on mood and anxiety is best exemplified in seasonal affective disorder, in which patients experience depression and anxiety in winter when there is less light in the environment. However, the brain mechanisms underlying light-dependent changes in affective state remain unclear. Our previous work revealed increased depression-like behaviors in the diurnal Nile grass rat (Arvicanthis niloticus) housed in a dim light-dark (dim-LD) cycle as compared to the controls housed in a bright light-dark (bright-LD) condition. As depression is often comorbid with anxiety and is associated with dysregulation of the body's stress response system, the present study examined the anxiety-like behaviors as well as indicators of the hypothalamic-pituitary-adrenal (HPA) axis functioning in the grass rats. Animals housed in dim-LD showed increased anxiety-like behaviors compared to bright-LD controls, as revealed by fewer entries and less time spent at the center in the open field test and more marbles buried during the marble-burying test. Following the marble-burying test, dim-LD animals showed higher plasma corticosterone (CORT) levels and hippocampal Fos expression. Although the daily CORT rhythm was comparable between bright-LD and dim-LD groups, the day/night variation of corticotropin-releasing hormone mRNA expression in the paraventricular nucleus was diminished in dim-LD animals. In addition, glucocorticoid receptor and mineralocorticoid receptor mRNA expression were higher in the hippocampus of dim-LD animals. The results suggest that in diurnal species, reduced daytime illumination can lead to increased anxiety-like behaviors and altered HPA axis functioning, providing insights into the link between decreased environmental illumination and negative emotion. PMID:26684510

  8. New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice.

    Science.gov (United States)

    Chen, Chieh V; Brummet, Jennifer L; Lonstein, Joseph S; Jordan, Cynthia L; Breedlove, S Marc

    2014-03-01

    Men are less likely than women to suffer from anxiety disorders. Because gonadal hormones play a crucial role in many behavioral sex differences, they may underlie sex differences in human anxiety. In rodents, testosterone (T) exerts anxiolytic effects via the androgen receptor (AR): we found that male mice with a naturally-occurring mutation rendering the AR dysfunctional, referred to as spontaneous testicular feminization mutation (sTfm), showed more anxiety-like behaviors than wildtype (WT) males. Here, we used Cre-lox recombination technology to create another dysfunctional allele for AR. These induced Tfm (iTfm) animals also displayed more anxiety-like behaviors than WTs. We further found that AR-modulation of these behaviors interacts with circadian phase. When tested in the resting phase, iTfms appeared more anxious than WTs in the open field, novel object and elevated plus maze tests, but not the light/dark box. However, when tested during the active phase (lights off), iTfms showed more anxiety-related behavior than WTs in all four tests. Finally, we confirmed a role of T acting via AR in regulating HPA axis activity, as WT males with T showed a lower baseline and overall corticosterone response, and a faster return to baseline following mild stress than did WT males without T or iTfms. These findings demonstrate that this recombined AR allele is a valuable model for studying androgenic modulation of anxiety, that the anxiolytic effects of AR in mice are more prominent in the active phase, and that HPA axis modulation by T is AR dependent.

  9. HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

    Science.gov (United States)

    Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

    2016-07-01

    Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

  10. Decreased daytime illumination leads to anxiety-like behaviors and HPA axis dysregulation in the diurnal grass rat (Arvicanthis niloticus).

    Science.gov (United States)

    Ikeno, Tomoko; Deats, Sean P; Soler, Joel; Lonstein, Joseph S; Yan, Lily

    2016-03-01

    The impact of ambient light on mood and anxiety is best exemplified in seasonal affective disorder, in which patients experience depression and anxiety in winter when there is less light in the environment. However, the brain mechanisms underlying light-dependent changes in affective state remain unclear. Our previous work revealed increased depression-like behaviors in the diurnal Nile grass rat (Arvicanthis niloticus) housed in a dim light-dark (dim-LD) cycle as compared to the controls housed in a bright light-dark (bright-LD) condition. As depression is often comorbid with anxiety and is associated with dysregulation of the body's stress response system, the present study examined the anxiety-like behaviors as well as indicators of the hypothalamic-pituitary-adrenal (HPA) axis functioning in the grass rats. Animals housed in dim-LD showed increased anxiety-like behaviors compared to bright-LD controls, as revealed by fewer entries and less time spent at the center in the open field test and more marbles buried during the marble-burying test. Following the marble-burying test, dim-LD animals showed higher plasma corticosterone (CORT) levels and hippocampal Fos expression. Although the daily CORT rhythm was comparable between bright-LD and dim-LD groups, the day/night variation of corticotropin-releasing hormone mRNA expression in the paraventricular nucleus was diminished in dim-LD animals. In addition, glucocorticoid receptor and mineralocorticoid receptor mRNA expression were higher in the hippocampus of dim-LD animals. The results suggest that in diurnal species, reduced daytime illumination can lead to increased anxiety-like behaviors and altered HPA axis functioning, providing insights into the link between decreased environmental illumination and negative emotion.

  11. The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes

    Directory of Open Access Journals (Sweden)

    Maria Therese Ahlen

    2012-01-01

    Full Text Available Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT. In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75. Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.

  12. Suitability of GaN and LDMOS for 70–82% efficiency 120–200W HPA addressing spaceborne P-band radar applications

    DEFF Research Database (Denmark)

    Le Gallou, N.; Vidkjær, Jens; Poivey, C.

    2012-01-01

    This paper addresses the development of P-band (435 MHz) HPA based on different technologies (GaN HEMT, LDMOS FET) for future use in pace radar applications in the context of the Biomass project. In particular best in class PAE of 70%–82% is targeted and achieved for power levels of 120W. In order...

  13. HPA-axis activity and externalizing behavior problems in early adolescents from the general population : the role of comorbidity and gender The TRAILS study

    NARCIS (Netherlands)

    Marsman, Rianne; Swinkels, Sophie H. N.; Rosmalen, Judith G. M.; Oldehinkel, Albertine J.; Ormel, Johan; Buitelaar, Jan K.

    2008-01-01

    Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used

  14. Construction of a recombinant Lactococcus lactis strain expressing a fusion protein of Omp22 and HpaA from Helicobacter pylori for oral vaccine development.

    Science.gov (United States)

    Zhang, Rongguang; Duan, Guangcai; Shi, Qingfeng; Chen, Shuaiyin; Fan, Qingtang; Sun, Nan; Xi, Yuanlin

    2016-11-01

    To develop orally administrated anti-Helicobacter pylori vaccination, a Lactococcus lactis strain was genetically constructed for fusion expression of H. pylori protective antigens HpaA and Omp22. The fusion gene of omp22 and hpaA with an adapter encoding three glycines was cloned from a plasmid pMAL-c2x-omp22-hpaA into Escherichia coli MC1061 and L. lactis NZ3900 successively using a shutter vector pNZ8110. Expression of the fusion gene in L. lactis was induced with nisin resulting in production of proteins with molecular weights of 50 and 28 kDa. Both of them were immunoreactive with mouse anti-H. pylori sera as determined via western blotting. Oral vaccination of BALB/c mice using the L. lactis strain carrying pNZ8110-omp22-hpaA elicited significant systematic humoral immune response (P < 0.05). This is the first report showing that a fusion protein of two H. pylori antigens was efficiently expressed in L. lactis with immunogenicity. This is a considerable step towards H. pylori vaccines.

  15. hpaA mutants of Xanthomonas campestris pv. vesicatoria are affected in pathogenicity but retain the ability to induce host-specific hypersensitive reaction.

    Science.gov (United States)

    Huguet, E; Hahn, K; Wengelnik, K; Bonas, U

    1998-09-01

    Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot disease on pepper and tomato plants. We reported previously that the main hrp (hypersensitive reaction and pathogenicity) gene cluster in X. c. pv. vesicatoria contains six transcription units, designated hrpA to hrpF. We present here the sequence of the hrpD operon and an analysis of non-polar mutants in each of the six genes. Three genes, hrcQ, hrcR and hrcS, are predicted to encode conserved components of type III protein secretion systems in plant and mammalian pathogenic bacteria. For hrpD5 and hrpD6, homologues have only been found in Ralstonia solanacearum. Interestingly, the hrpD operon contains one gene, hpaA (for hrp-associated), which is specifically required for disease development. hpaA mutants are affected in pathogenicity, but retain in part the ability to induce avirulence gene-mediated, host-specific hypersensitive reaction (HR). In addition, HpaA was found to contain two functional nuclear localization signals, which are important for the interaction with the plant. We propose that HpaA is an effector protein that may be translocated into the host cell via the Hrp secretion pathway.

  16. The Role of Wet Wrap Therapy in Skin Disorders - A literature Review

    DEFF Research Database (Denmark)

    Andersen, Rosa Marie; Thyssen, Jacob P; Maibach, Howard I

    2015-01-01

    with wet wrap bandages compared to emollients only. While temporary suppression of hypothalamic-pituitary-adrenocortical-axis was seen due to systemic bioactivity of corticosteroids, no long-term observation studies on putative adverse-effects were identified. One hypothesis suggests that wet wrap therapy......, evaluates current knowledge about wet wrap therapy. Wet wrap therapy superimposed topical corticosteroids appears more efficient than emollients only, at least for short-time treatments. Despite higher efficacy, there is a tendency towards more frequent infections when topical corticosteroids are covered...

  17. Study on the allele polymorphism of HPA in hans from shandong province%山东汉族人群血小板特异性抗原基因的多态性研究

    Institute of Scientific and Technical Information of China (English)

    朱传福; 王淑荣; 王玫; 刘艳; 张萍; 宋永红; 聂向民; 焦波

    2006-01-01

    目的研究山东汉族人群血小板特异性抗原(HPA)1~5和15系统基因多态性分布特点.方法采用PCR-序列特异性引物(PCR-SSP)技术对234例无血缘关系,汉族,血小板志愿捐献者进行HPA-1~5和HPA-15系统基因分型,计算等位基因频率、基因型频率并与其他种族、地区人群相关资料比较.结果等位基因频率由高到低依次为HPA-4a、-1a、-5a、-2a、-3a、-15a、-15b、-3b、-2b、-5b、-1b,未检到HPA-4b.基因型频率由高到低依次为HPA-4a4a、-1a1a、-5a5a、-2a2a、-15a15b、-3a3b、-3a3a、-15a15a、-3b3b、-15b15b、-2a2b、-5a5b、-1a1b,未检到HPA-1b1b、-5b5b和HPA-2b2b.与报道的东方人群比较,有显著性差异的系统有HPA-2、-3、-5(P<0.005);与西方人群比较,HPA-1、-2、-3、-5系统有显著性差异(P<0.005),HPA-4无种族间显著性差异.HPA-15系统的基因分布与越南、德国、奥地利人近似,而与印地安人有较大差异(P<0.005).结论 HPA存在明显的种族和地域性差异.山东汉族人发生HPA同种免疫的可能风险抗原基因主要有HPA-3a,-3b,-2b,-5b,-1b,其次为HPA-15a、-15b.

  18. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress.

    Science.gov (United States)

    Uban, Kristina A; Comeau, Wendy L; Ellis, Linda A; Galea, Liisa A M; Weinberg, Joanne

    2013-10-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  19. Hpa和bFGF在口腔鳞癌中的表达及其意义%The expressions and significance of Hpa and bFGF in oral squamous-cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhong Chen; Xiaodong Zheng; Hongchao Feng

    2009-01-01

    Objective: To investigate the expressions of heparanase (Hpa) and basic fibroblast growth factor (bFGF) in oral squamous-cell carcinoma (OSCC), and to evaluate the relationship between the expressions and tumor angiogenesis and progression. Methods: The expressions of Hpa mRNA and bFGF mRNA of OSCC were examined using in situ hybridization. The microvascular density (MVD) was assessed through immunohistochemistry staining. Results: The expressions of Hpa mRNA and bFGF mRNAwere associated with tumor MVD and lymph node metastasis. Concomitant expression of Hpa mRNA and bFGF mRNA was associated with higher tumor MVD as compared with expression of either factor alone. Conclusion: Hpa and bFGF might contribute to the angiogenesis and lymph node metastasis in OSCC and they cooperate in promoting vascularization.

  20. 贵州黔东南州苗族人群HPA-1~5、15多态性调查

    Institute of Scientific and Technical Information of China (English)

    杨芳; 黄吉娥; 丛硕; 曾小菁; 涂贵兰; 李天才

    2012-01-01

    目的 调查贵州省黔东南州苗族健康随机献血人群人类血小板抗原(human platelet antigen,HPA) 1-5、15系统基因多态性分布特点.方法 采用聚合酶链-序列特异性引物技术(PCR-SSP)对贵州省黔东南州无血缘关系苗族随机献血人群100例血样进行HPA-1~5、15系统基因分型.结果 贵州省黔东南州苗族HPA-1a、2a、3a、4a、5a、15a基因频率分别是0.950、0.900、0.830、0.985、0.975、0.585,HPA-1b、2b、3b、4b、5b、15b基因频率分别是0.050、0.100、0.170、0.015、0.025、0.4150;与其他研究比较:HPA-1与新疆维吾尔族、海南黎族、中国汉族相比较差异有统计学意义(P<0.05);HPA-2与新疆维吾尔族、海南黎族、菲律宾、泰国相比较差异有统计学意义(P<0.05);HPA-3与我国其它研究相比较差异均有统计学意义(P<0.05);HPA-4与其它研究相比较差异无统计学意义(P>0.05);HPA-5与国内新疆维吾尔族相比较差异有统计学意义(P<0.05);HPA-15与新疆维吾尔族、海南黎族族、印度尼西亚相比较差异有统计学意义(P<0.05).结论 贵州省黔东南州苗族人群HPA分布具有本地人群特点.本组HPA数据分布符合Hardy-Weinberg平衡定律,可以作为贵州省黔东南州苗族HPA基因分布频率数据库和血小板供者HPA资料库.

  1. Research on the clinical value between gene polymorphism of HPA 1-6,9,15 and platelet transfusion refractoriness%患者HPA 1-6,9,15基因多态性对血小板输注无效的临床意义

    Institute of Scientific and Technical Information of China (English)

    李园; 曾惠; 吴海兵; 赵晓燕; 颜敏超; 郭晓

    2016-01-01

    目的:观察人类血小板特异性抗原(human platelet alloantigens, HPA)1-6,9,15系统及其基因多态性与血小板输注无效( platelet transfusion refractoriness, PTR)的研究。方法选取40例血小板输注无效患者的外周血标本和供者标本,对其进行血小板特异性糖蛋白抗体检测,根据血小板回收率评判血小板输注效果,采用聚合酶链式反应( PCR)结合直接测序方法,对供、患者进行HPA1-6,9,15抗原系统基因进行分型,动态观察患者同型血小板输注后血小板恢复百分率(percent platelet recovery,PPR),探讨HPA基因多态性和血小板输注无效的关系。结果患者和供者HPA-1、4、9均未检测出HPA-b基因,呈呈aa纯合子单态性分布;HPA-5、6则主要以aa纯合子为多,较少看到bb纯合子。而HPA-2、3、15呈明显多态性分布,HPA-2、3、5、6、15等位基因频率均呈多态性分布。结论对反复多次发生血小板输注无效的患者,除需考虑HLA基因相关外,还与HPA基因多态性相关。在做HPA配型时,多数人只需检测供者与患者HPA2、3、15基因就可以显著减少血小板输注无效的发生。%Objective To research the clinical value between gene polymorphism of human platelet alloantigens (HPA) 1-6, 9, 15 and platelet transfusion refractoriness ( PTR) .Methods Totally 40 patients with platelet transfusion refractoriness( PTR) were randomly selected, and patients and donors’ peripheral blood specimens were collected and tested these samples with platelet GP specific antibodies, and judged the results of platelet transfusion, and with the help of the combination of PCR and direct sequencing for classification of HPA 1-6,9,15 antigens and observe the percent platelet recovery ( PPR ) after the same type of platelet transfusion, and explore the relationship between HPA gene polymorphism and PTR. Results There was no HPA-b gene was found

  2. 甘肃人群人类血小板抗原HPA-15多态性调查%Investigation on gene frequency of human platelet antigen-15 system in Gansu

    Institute of Scientific and Technical Information of China (English)

    唐朝晖; 李国英; 刘圆圆; 薛双林; 王明禄; 李元荣

    2013-01-01

    Objective:To study the polymorphism of human platelet antigen HPA-15 system in Gansu population,and evaluate its role in matching platelet transfusion.Methods:The blood samples were collected from 201 healthy unrelated platelet donors in Gansu blood center for HPA-15 system genotyping using PCR-SSP assay.Results:Gene frequencies of HPA-15a and 15b were 0.6194 and 0.3806.In comparison to other 9 ethnic groups,there were 7 ethnic groups showing significant differences in HPA-15 distribution.The incompatibility ratios in random platelet transfusion were 0.1239 and 0.2365 for HPA-15a and-15b antigens,total of 0.3604.Conclusion:The distribution of HPA-15 system in Gansu population were investigated for the first time.The present data indicate that the ratio of HPA-15 antigen incompatibility in random platelet transfusion is up to 36.04%,providing a basis for further study on matched platelet transfusion.%目的:研究甘肃人群人类血小板抗原HPA-15系统多态性,评估其在血小板配型输注中的作用.方法:采用PCR-SSP技术对201名健康无血缘关系的血小板捐献者进行HPA-15系统基因分型.结果:HPA-15a和15b基因频率分别为0.6194和0.3806;同国内其它9个地区人群的HPA-15分布相比较,与7个地区人群有显著性差异.在随机输血中HPA-15a和15b抗原不配合的机会分别为0.1239和0.2365,a、b抗原不配合率合计为0.3604.结论:本调查数据表明,随机输血中供受者HPA-15抗原不配合比例在甘肃人群中高达36.04%,这对研究血小板同种免疫性疾病和开展相合血小板输注具有指导意义.

  3. The investigation of gene frequency of human platelet antigen-3 system in Gansu%甘肃人群人类血小板抗原HPA-3多态性调查

    Institute of Scientific and Technical Information of China (English)

    李国英; 刘圆圆; 薛双林; 王明禄; 李元荣; 张海红; 方丽华; 唐朝晖

    2013-01-01

    目的:研究甘肃人群人类血小板抗原HPA-3系统多态性,评估其在血小板配型输注中的作用.方法:采用PCR-SSP技术对201名健康无血缘关系的血小板捐献者进行HPA-3系统基因分型.结果:HPA-3a和3b基因频率分别为0.6368和0.3632;同国内其它9个地区人群的HPA-3分布相比较,与5个地区人群有显著性差异.在随机输血中HPA-3a和3b抗原不配合的机会分别为0.1145和0.2411,a、b抗原不配合率合计为0.3556.结论:调查数据表明,随机输血中供受者HPA-3抗原不配合比例在甘肃人群中高达35.56%,这对研究血小板同种免疫性疾病和开展相合血小板输注具有指导意义.%Objective:To study the polymorphism of the human platelet antigen (HPA - 3) system in Gansu population, and evaluate its role in matched platelet transfusion. Methods: Two hundred and one blood samples selected from 201 unrelated platelet donors of Gansu blood center were genotyped for HPA - 3 system using PCR - SSP assay. Results; The distribution of the HPA - 3 alleles were genetic polymorphisms. Gene frequency of 3a and 3b were 0.6368 and 0. 3632. In comparison to other 9 ethnic groups, significant differences were observed in the distribution of HPA - 3 in 5 groups. The chances of incompatibility in random platelet transfusion were 0.1145 and 0.2411 for HPA -3a and -3b antigens, total 3a and 3b was 0. 3556. Conclusion; The distribution of HPA - 3 systems in Gansu population were investigated for the first time. The present data indicate that the chance of HPA -3 antigen incompatibility in random platelet transfusion is up to 35. 56%. This study provides a basis for further stud-y on matched transfusion of platelet.

  4. AIRS observations of seasonal variability in meridional temperature gradient over Indian region at 100 hPa

    Indian Academy of Sciences (India)

    A Gupta; S K Dhaka; V Panwar; R Bhatnagar; V Kumar; Savita M Datta; S K Dash

    2013-02-01

    To investigate the temperature changes at 100 hPa over Indian region from Arabian Sea (AS) to Bay of Bengal (BOB), analysis is performed using Atmospheric Infra Red Sounder (AIRS) temperature and outgoing long-wave radiation (OLR) data of 9 years (2003–2011). Fine-scale temperature variations have been studied and shown for summer (March–April–May, MAM), summer monsoon (June–July–August–September, JJAS) and winter (November–December–January–February, NDJF) months. Similarities and differences in the latitudinal and longitudinal variation of temperature and the possible causes have been examined. During MAM and NDJF, the temperature increases latitudinally by ∼2–3 K and ∼4–5 K from 3.5° to 20.5°N, respectively. However, the temperature decreases by ∼2.0–2.5 K during JJAS. A similar contrasting behaviour is observed in latitudinal temperature gradient. For MAM and NDJF, the gradient decreases from ∼0.18 to ∼0.14 K/deg and ∼0.25 to ∼0.18 K/deg, respectively, as we move longitudinally from 60° to 90°E; however, for JJAS, it increases from ∼0.10 to ∼0.14 K/deg over the same longitudes. It is found that latitudinal temperature gradient for NDJF is larger by about a factor of 1.5. Analysis suggests latitudinal change in temperature occurs due to low OLR (proxy of convection) and its northward progression during summer monsoon. Correlation coefficient (xy) between OLR and temperature is computed latitudinally (3.5° to 20.5°N) at different longitudes and during JJAS (monsoon months), xy is negative (∼−0.73) over 60° and 70°E longitudes, but it turns positive (∼0.92) over 80° and 90°E longitudes (which is convectively active region), suggesting a close association between low temperature and low OLR. Land–sea contrast is also observed in temperature at 100 hPa with a slight increase (∼0.5 K) from sea to land.

  5. 幽门螺杆菌融合基因vacA-hpaA的克隆及在大肠杆菌和双歧杆菌中的表达%Cloning and expression of hpaA-vacA fusion gene of Helicobacter pylori in E.coli and B.bifidium

    Institute of Scientific and Technical Information of China (English)

    王国富; 高峰; 薛士鹏; 吴利先

    2011-01-01

    目的 构建幽门螺杆菌融合基因vacA-hpaA的大肠杆菌-双歧杆菌穿梭表达质粒,并观察其在大肠杆菌(E.coli)和双歧杆菌(B.bifidium)中的表达情况.方法 通过PCR得到hpaA-vacA融合基因,将该融合基因定向克隆到大肠埃希菌-双歧杆菌穿梭表达载体pGEX-1λT,构建重组质粒pGEX-hpaA-vacA,电穿孔转化入大肠杆菌BL21和双歧杆菌.转化菌经IPTG诱导,然后用SDS-PAGE和Western blotting方法鉴定表达的重组蛋白.结果 构建了重组质粒pGEX-vacA-hpaA,vacA-hpaA融合基因的分子量约为1548bp;经SDS-PAGE分析,在大肠杆菌中表达出85kD的融合蛋白,表达的蛋白约占细菌总蛋白的20.5%;在双岐杆菌中也能得到正确表达,但表达量较大肠杆菌低,占细菌总蛋白约8.5%.Western blotting结果确认了该条带为hpaA-vacA融合基因的产物.结论 构建的重组质粒pGEX-hpaA-vacA能够在大肠杆菌及双歧杆菌中获得表达.

  6. Proton transfer mass spectrometry at 11 hPa with a circular glow discharge: Sensitivities and applications

    Science.gov (United States)

    Hanson, D. R.; Koppes, M.; Stoffers, A.; Harsdorf, R.; Edelen, K.

    2009-04-01

    The design and testing of a circular glow discharge ion source on a custom built proton transfer mass spectrometer are described. Also, issues important for quantitative measurements of volatile organic compounds using this instrument were investigated. Detailed calibration procedures based on gravimetry are presented, and representative outdoor air data are shown. Calibrations yield a good sensitivity, up to a few Hz/pptv for some compounds, and the detection limit (S/N = 3) is ~100 pptv or better for methanol, acetaldehyde and acetone (5 s sampling time with a 5 s zero). Detection limits are much lower for most other compounds due to high sensitivity and low background. For ions with m/z > ~90 the background signals are very low and species that appear efficiently at these m/z can be detected at the 10 pptv level in a few seconds. Ion breakup processes for alcohols show that a major product ion of mono-functional alcohols is at 57 u, presumably C4H9+. Oxalic acid is an interesting case in that a major product ion appears on an even mass, 46 u, presumably CO2H2+. The circular glow discharge source is easy to construct and deploy in proton transfer mass spectrometry studies at ~11 hPa. Continuous use of the system over time periods of many days and stable operation over time periods of months to years between disassembly and cleaning demonstrates its robustness.

  7. Effects of HPA-nonlinearity on a 4-DPSK/OFDM-signal for a digital sound broadcasting signal

    Science.gov (United States)

    Rapp, Christoph

    1991-10-01

    Orthogonal Frequency Division Multiplexing (OFDM) in conjunction with a 4 Differential Phase Shift Keying (DPSK) modulation format has been proposed for the future Digital Audio Broadcasting system (DAB), that should provide compact disk sound quality in portable, vehicular and fixed receivers. With properly chosen parameters, this system should be appropriate for both terrestrial and satellite transmission. The influence of the nonlinear distorsions introduced by the High Power Amplifier (HPA) of the transmitter is examined. In particular, the degradations in power efficiency due to intermodulation effects and backoff operating, as well as spectral degradations are investigated. It is shown for three different kinds of limiting amplifier models, that even with an output backoff in the region of 5 to 6 dB, the degradation of, for example a 512 carrier 4 DPSK/OFDM system relative to the linear case is below 1.7 dB (Pb = 0.0001), while the regenerated sidelobes of the transmitted spectrum are kept below -20 dB.

  8. Type III-Dependent Translocation of HrpB2 by a Nonpathogenic hpaABC Mutant of the Plant-Pathogenic Bacterium Xanthomonas campestris pv. vesicatoria

    Science.gov (United States)

    Scheibner, Felix; Schulz, Steve; Hausner, Jens; Marillonnet, Sylvestre

    2016-01-01

    ABSTRACT The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria employs a type III secretion (T3S) system to translocate effector proteins into plant cells. The T3S apparatus spans both bacterial membranes and is associated with an extracellular pilus and a channel-like translocon in the host plasma membrane. T3S is controlled by the switch protein HpaC, which suppresses secretion and translocation of the predicted inner rod protein HrpB2 and promotes secretion of translocon and effector proteins. We previously reported that HrpB2 interacts with HpaC and the cytoplasmic domain of the inner membrane protein HrcU (C. Lorenz, S. Schulz, T. Wolsch, O. Rossier, U. Bonas, and D. Büttner, PLoS Pathog 4:e1000094, 2008, http://dx.doi.org/10.1371/journal.ppat.1000094). However, the molecular mechanisms underlying the control of HrpB2 secretion are not yet understood. Here, we located a T3S and translocation signal in the N-terminal 40 amino acids of HrpB2. The results of complementation experiments with HrpB2 deletion derivatives revealed that the T3S signal of HrpB2 is essential for protein function. Furthermore, interaction studies showed that the N-terminal region of HrpB2 interacts with the cytoplasmic domain of HrcU, suggesting that the T3S signal of HrpB2 contributes to substrate docking. Translocation of HrpB2 is suppressed not only by HpaC but also by the T3S chaperone HpaB and its secreted regulator, HpaA. Deletion of hpaA, hpaB, and hpaC leads to a loss of pathogenicity but allows the translocation of fusion proteins between the HrpB2 T3S signal and effector proteins into leaves of host and non-host plants. IMPORTANCE The T3S system of the plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria is essential for pathogenicity and delivers effector proteins into plant cells. T3S depends on HrpB2, which is a component of the predicted periplasmic inner rod structure of the secretion apparatus. HrpB2 is secreted during the early stages of the

  9. The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress response in rat offspring exposed prenatally to polyriboinosinic-polyribocytidylic-acid (PIC).

    Science.gov (United States)

    Maayan, Rachel; Ram, Edward; Biton, Doron; Cohen, Hagit; Baharav, Ehud; Strous, Rael D; Weizman, Abraham

    2012-07-11

    Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic-polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions.

  10. Immediate effects of maternal deprivation on the (reactivity of the HPA axis differ in CD1 and C57Bl/6J mouse pups

    Directory of Open Access Journals (Sweden)

    Nikolaos P Daskalakis

    2014-11-01

    Full Text Available The postnatal development of the mouse is characterised by a period of hypo-responsiveness of the hypothalamic-pituitary-adrenal (HPA axis to mild stressors. Maternal deprivation (MD during this period can disrupt the quiescence of the HPA-axis. The present study examined the influence of strain (outbred CD1 versus inbred C57BL/6J mice on some central and peripheral components of the HPA-axis in neonatal mice (5 day-old in the presence of their mother or after 24 h MD (on postnatal day 4 under basal or mild stressful conditions. In the presence of the dam, adrenal corticosterone (CORT secretion was low in both mouse strains. Compared to CD1 mice, C57BL/6J had lower CORT levels associated with higher ACTH levels and ACTH/CORT ratio (i.e., lower adrenal sensitivity to ACTH, and higher glucocorticoid receptor (GR mRNA expression in the paraventricular nucleus. Although MD disinhibited the HPA-axis in both strains as reflected by increased basal CORT and ACTH, we found a strain-dependent pattern. MD increased CORT more in C57BL/6J, compared to CD1 mice, together with a lower ACTH/CORT ratio (i.e., higher adrenal sensitivity to ACTH, while GR mRNA was no longer different in the two strains. However, this increased adrenal sensitivity in maternally deprived C57BL/6J mice was not reflected in their CORT response to a subsequent novelty stressor, possibly due to a MD-induced ceiling effect in their steroidogenic capacity.In conclusion, the immediate outcome of MD depends on the genetic background of the mother-infant dyad, suggesting that maybe also the outcome in later-life cannot be generalized. genetic background of the mother-infant dyad, predicting that the outcome in later-life cannot be generalized.

  11. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    Science.gov (United States)

    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  12. The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis.

    Science.gov (United States)

    Navarria, Andrea; Tamburella, Alessandra; Iannotti, Fabio A; Micale, Vincenzo; Camillieri, Giovanni; Gozzo, Lucia; Verde, Roberta; Imperatore, Roberta; Leggio, Gian Marco; Drago, Filippo; Di Marzo, Vincenzo

    2014-09-01

    In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.

  13. In search of the HPA axis activity in unipolar depression patients with childhood trauma: Combined cortisol awakening response and dexamethasone suppression test.

    Science.gov (United States)

    Lu, Shaojia; Gao, Weijia; Huang, Manli; Li, Lingjiang; Xu, Yi

    2016-07-01

    The aim of the present study was to examine the impact of childhood trauma on HPA axis activity both in depression patients and healthy controls in order to determine the role of HPA axis abnormalities in depression and to find the differences in HPA axis functioning that may lead certain individuals more susceptible to the depressogenic effects of childhood trauma. Eighty subjects aged 18-45 years were recruited into four study groups (n = 18, depression patients with childhood trauma exposures, CTE/MDD; n = 17, depression patients without childhood adversity, non-CTE/MDD; n = 23, healthy persons with childhood trauma, CTE/non-MDD; and n = 22, healthy persons without childhood adversity, non-CTE/non-MDD). Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of CAR and underwent a 1 mg-dexamethasone suppression test (DST). Regardless of depression, subjects with CTE exhibited an enhanced CAR and the CAR areas under the curve to ground (AUCg) were associated with their childhood trauma questionnaire (CTQ) physical neglect scores and CTQ total scores. In addition, the CTE/MDD group also showed a highest post-DST cortisol concentration and a decreased glucocorticoid feedback inhibition among four groups of subjects. The present findings suggested that childhood trauma was associated with hyperactivity of HPA axis as measured with CAR, potentially reflecting the vulnerability for developing depression after early life stress exposures. Moreover, dysfunction of the GR-mediated negative feedback control might contribute to the development of depression after CTE.

  14. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    Science.gov (United States)

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  15. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    OpenAIRE

    Hall, Jessica M. F.; desAnges Cruser; Alan Podawiltz; Mummert, Diana I.; Harlan Jones; Mummert, Mark E.

    2012-01-01

    Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental i...

  16. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  17. Taking stress response out of the box: stability, discontinuity, and temperament effects on HPA and SNS across social stressors in mother-infant dyads.

    Science.gov (United States)

    Laurent, Heidemarie K; Ablow, Jennifer C; Measelle, Jeffrey

    2012-01-01

    This study investigated continuity and stability of hypothalamic-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) response measures in mother-infant dyads across 2 different types of social stress sessions. Synchrony of response trajectories across systems (SNS-HPA coordination) and partners (mother-infant attunement) was addressed, as were associations with infant temperament. Primiparous mothers and their 18-month-old infants (n = 86 dyads) completed an attachment stressor--Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978)--at Session 1 and challenge stressors--cleanup task and emotion task battery--at Session 2. Mother and infant saliva samples collected to index pre-stress, stress, and post-stress response during each session were assayed for cortisol (HPA marker) and salivary alpha-amylase (sAA; SNS marker). Multilevel modeling of cortisol/sAA trajectories across sessions revealed rank-order stability in mother/infant stress measures but discontinuity in absolute levels; cortisol trajectories were higher during attachment stress, and sAA trajectories were higher during challenge stress. Varying degrees of mother-infant attunement were found across sessions/systems. Infant surgency predicted higher stress measures, and negative affect and effortful control predicted lower stress measures, though associations depended on session/system. Findings are discussed in terms of advancing a multisystemic, contextual definition of developing stress responsiveness.

  18. Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder.

    Science.gov (United States)

    Masdrakis, Vasilios G; Markianos, Manolis; Oulis, Panagiotis

    2015-09-30

    A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic-pituitary-adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic.

  19. A flagellar sheath protein of Helicobacter pylori is identical to HpaA, a putative N-acetylneuraminyllactose-binding hemagglutinin, but is not an adhesin for AGS cells.

    Science.gov (United States)

    Jones, A C; Logan, R P; Foynes, S; Cockayne, A; Wren, B W; Penn, C W

    1997-09-01

    The gene encoding a 29-kDa flagellar sheath protein was cloned and found to be similar to hpaA, reported to encode an N-acetylneuraminyllactose-binding fibrillar hemagglutinin (D. G. Evans, T. K. Karjalainen, D. J. Evans, Jr., D. Y. Graham, and C. H. Lee, J. Bacteriol. 175:674-683, 1993). The transcriptional start was mapped by primer extension from Helicobacter pylori mRNA, indicating an active consensus promoter at a location different from that suggested by Evans et al. Immunogold labelling of the flagellar sheath with a monoclonal antibody to HpaA was demonstrated in four strains, contrary to previous reports of a surface (D. G. Evans, T. K. Karjalainen, D. J. Evans, Jr., D. Y. Graham, and C. H. Lee, J. Bacteriol. 175:674-683, 1993) or a cytoplasmic (P. W. O'Toole, L. Janzon, P. Doig, J. Huang, M. Kostrzynska, and T. J. Trust, J. Bacteriol. 177:6049-6057, 1995) locale. Agglutination of erythrocytes and adherence to AGS cells by a delta hpaA mutant were no different from those of the parent strain, confirming a recent finding of O'Toole et al.

  20. 人类血小板抗原1-16基因与血小板输注无效风险研究%Human Platelet Antigen HPA-1-16 gene and platelet transfusion refractoriness

    Institute of Scientific and Technical Information of China (English)

    李志强; 乐嘉宜; 刘建军; 王恒石; 陆君; 瞿益华; 徐文皓

    2009-01-01

    目的 探讨HPA-1-16基因多态性分布与血小板输注无效相关性.方法 应用PCR-SSP法对上海地区268名汉族人群行HPA-1-16基因检测;应用ELISA法对49名反复输血的恶性血液病患者行血小板抗-HLA-Ⅰ与抗-HPA筛查试验.结果 上海地区汉族人群HPA-1-16系统中,HPA-1-6,15系统等位基因频率1a=0.988 9,1b=0.011 1,2a=0.888 1,2b=0.111 9,3a=0.598 9,3b=0.401 1,4a=0.996 3,4b=0.003 7,5a=0.990 7,5b=0.009 3,6a=0.983 2,6b=0.016 8,15a=0.641 8,15b=0.358 2,均呈多态性分布;其余HPA-7-14,16系统等位基因均呈单线性分布.HPA-1,2,4-6,15系统主要以aa纯合子基因型频率分别为0.977 6,0.779 9,0.992 5,0.981 3,0.966 4,0.432 8.在HPA-2、3、15系统中出现bb纯合子基因型,其频率均为0.003 7,0.153 0,0.149 2外,其余系统均未出现bb纯合子基因型.另外,在HPA-1-6,15系统中出现ab杂合子基因型,其频率分别为0.022 4,0.216 4,0.496 3,0.007 5,0.018 7,0.033 6,0.418 0,以HPA-3杂合度最高,其次次序为HPA-15、HPA-2.在随机输血中,HPA不合发生率以HPA-3为最高(0.365 0),其次分别为HPA-15(0.354 1)、HPA-2(0.179 0).49名反复输血的恶性血液病患者中,有61.22%(30名)输血后相继出现抗-HLA-Ⅰ,而始终未检出抗-HPA.结论 上海地区汉族人群血小板输注无效的主要原因是抗-HLA-Ⅰ所致;只需检测供者与受(患)者的HPA-2、-3、-15基因相合,就可基本达到血小板匹配性输注.

  1. Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats

    Directory of Open Access Journals (Sweden)

    Jiang Jun-Xia

    2010-04-01

    Full Text Available Abstract Background Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA axis is the neuroendocrine-immnue pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4 between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats. Methods Ovalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor was given via intracerebroventricular injection (i.c.v 30 min before challenge. Lung resistance (RL and dynamic lung compliance (Cdyn were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH and corticosterone (CORT were measured using the ELISA kits. Results Antigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng, but not by BLT2 antagonist LY255283. Conclusions LTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through

  2. Genetic transformation of cotton with a harpin-encoding gene hpaXoo confers an enhanced defense response against different pathogens through a priming mechanism

    Directory of Open Access Journals (Sweden)

    Song Congfeng

    2010-04-01

    Full Text Available Abstract Background The soil-borne fungal pathogen Verticillium dahliae Kleb causes Verticillium wilt in a wide range of crops including cotton (Gossypium hirsutum. To date, most upland cotton varieties are susceptible to V. dahliae and the breeding for cotton varieties with the resistance to Verticillium wilt has not been successful. Results Hpa1Xoo is a harpin protein from Xanthomonas oryzae pv. oryzae which induces the hypersensitive cell death in plants. When hpa1Xoo was transformed into the susceptible cotton line Z35 through Agrobacterium-mediated transformation, the transgenic cotton line (T-34 with an improved resistance to Verticillium dahliae was obtained. Cells of the transgenic T-34, when mixed with the conidia suspension of V. dahliae, had a higher tolerance to V. dahliae compared to cells of untransformed Z35. Cells of T-34 were more viable 12 h after mixing with V. dahliae conidia suspension. Immunocytological analysis showed that Hpa1Xoo, expressed in T-34, accumulated as clustered particles along the cell walls of T-34. In response to the infection caused by V. dahliae, the microscopic cell death and the generation of reactive oxygen intermediates were observed in leaves of T-34 and these responses were absent in leaves of Z35 inoculated with V. dahliae. Quantitative RT-PCR analysis indicated that five defense-related genes, ghAOX1, hin1, npr1, ghdhg-OMT, and hsr203J, were up-regulated in T-34 inoculated with V. dahliae. The up-regulations of these defense-relate genes were not observed or in a less extent in leaves of Z-35 after the inoculation. Conclusions Hpa1Xoo accumulates along the cell walls of the transgenic T-34, where it triggers the generation of H2O2 as an endogenous elicitor. T-34 is thus in a primed state, ready to protect the host from the pathogen. The results of this study suggest that the transformation of cotton with hpa1Xoo could be an effective approach for the development of cotton varieties with the

  3. Establishment of genotyping method for human platelet antigens of HPA-15 system by PCR-SBT%人类血小板抗原-15系统PCR-SBT分型技术的建立

    Institute of Scientific and Technical Information of China (English)

    丁浩强; 叶欣; 姬艳丽; 陈扬凯

    2011-01-01

    Objective To establish a reliable genotyping method for human platelet antigen HPA-15 system by PCR-SBT and to use this method in the further HPA genotyping of volunteer platelet donors. Methods A total of 200 volunteer platelet donors in Guangzhou were genotyped by both our method and the G&T American kit at HPA-15system. For quality control, ten coded samples distributed by the 14th Platelet Genotyping and Serology Workshop of the International Society of Blood Transfusion(ISBT) and 4 control samples of Inno-train were genotyped by our method simultaneously. Results A concordance rate of 100% was observed between the results obtained by our established PCR-SBT method and the results provided by ISBT report and Inno-train. The HPA gene frequencies in the 200 random platelet donors were 0. 430 and 0. 570 for HPA-15a and HPA-15b respectively. Conclusion PCR-SBT assay established in our study provides a high resolution,high throughput and accurate method for HPA-15 system genotyping. The assay can directly discover new allelie genes and shows a broad prospect in its further applications.%目的 建立人类血小板抗原(HPA)-15系统的分型方法,并应用于血小板供者库的HPA基因定型法采用本研究合成的引物及G & T公司的商品化试剂盒,应用PCR-SBT技术对200名随机的汉族血小板捐献者进行HPA-15系统基因分型,采用第14届ISBT血小板协作组提供的10份质控标本以及德国Inno-train公司提供白质控样品作为平行对照,进行验证.结果 200名汉族血小板志愿捐献者HPA基因频率为HPA-15a0.430,HPA1560.570;基因分型结果与ISBT公布的结果及Inno-train公司提供的质控样品的结果完全一致.结论 所建立6HPA基因PCR-SBT分型技术具有高分辨率、高通量、高精确度、能直接发现新的等位基因等特点,具有广泛的应用前景.

  4. Research development of interfered drugs for the dysregulation of HPA axis%HPA轴功能紊乱干预药物的研究进展

    Institute of Scientific and Technical Information of China (English)

    王晓丽; 贾正平; 张汝学

    2013-01-01

    目的对近年来基于下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal ,HPA)轴功能调节治疗2型糖尿病和其他代谢疾病的药物做以综述,为H PA轴功能紊乱引起的相关疾病的治疗提供理论参考。方法查阅国内外文献,分析、总结 H PA轴功能紊乱干预药物的研究现状和研究前景。结果 HPA轴功能紊乱,尤其是 HPA轴功能亢进在2型糖尿病、抑郁症等疾病的发病过程中发挥重要作用;目前有以下几类通过作用于HPA轴不同靶点调节HPA轴功能的药物,即11β-HSD1抑制剂、糖皮质激素受体拮抗剂、多巴胺受体拮抗剂和选择性5-H T再摄取抑制剂等,具体机制还有待进一步阐明。结论通过调节H PA轴活性有可能达到预防和治疗2型糖尿病及其他相关疾病的目的。%Objective To review the recent researches of drugs based on the regulation of hypothalamic-pituitary-adrenal (HPA) ax-is for treating type 2 diabetes mellitus and other metabolic diseases ,and to provide a theoretical reference for curing diseases which resulted in the dysregulation of HPA axis .Method The recent literatures were scanned ,and the current study situation and pros-pect of interfered drugs for the dysregulation of HPA axis were analyzed and summarized .Results The dysregulation of HPA ax-is ,especially the hyperactivity of HPA axis ,takes an important part in the pathogenesy of type 2 diabetes mellitus ,depression , and other diseases .Currently ,there are some drugs which may be used to regulate the action of HPA axis ,such as 11β-HSD1 in-hibitors ,glucocorticoid receptor antagonists ,dopamine receptor antagonists ,selective 5-HT reuptake inhibitors and so on .but the mechanism needs further to clarify .Conclusion It is possible that type 2 diabetes and other related diseases may be prevented and treated through modulating the activity of HPA axis .

  5. Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101-positive antigen-presenting cells.

    Science.gov (United States)

    Anani Sarab, Gholamreza; Moss, Michael; Barker, Robert N; Urbaniak, Stanislaw J

    2009-08-27

    In neonatal alloimmune thrombocytopenia, almost all human platelet antigen (HPA)-1b1b mothers who produce anti-HPA-1a antibody through carrying an HPA-1a fetus are human histocompatibility leukocyte antigen (HLA)-DRB3*0101 positive. It is predicted that the HPA-1a Leu(33) polymorphism forms part of an HLA-DRB3*0101-restricted T-helper epitope, and acts as an anchor residue for binding this class II molecule. However, it is not known whether any corresponding peptides are naturally processed and presented from platelet glycoprotein. In this study, peptides displayed by a homozygous HLA-DRB3*0101 antigen-presenting cell line were identified after pulsing with recombinant HPA-1a (Leu(33) plexin-semaphorin-integrin domain). The peptides were eluted from HLA-DR molecules, fractionated by high performance liquid chromatography, and analyzed by tandem mass spectrometry. A "nested set" of naturally presented HPA-1a-derived peptides, each containing the Trp(25)-Leu(33) core epitope, was identified, with the most abundant member being the 16-mer Met(22)-Arg(37). These peptides may provide the basis for novel treatments to tolerize the corresponding T-helper response in women at risk of neonatal alloimmune thrombocytopenia.

  6. Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone, -corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

    DEFF Research Database (Denmark)

    Knorr, Ulla; Vinberg, Maj; Klose, Marianne

    2009-01-01

    BACKGROUND: Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothes......BACKGROUND: Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We...... hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test...... from baseline to the end of intervention. METHODS: The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day...

  7. Correlation of human platelet alloantigens-1 to-6 and-15 polymorphisms with acute myocardial infarction%HPA1~6、15基因多态性与急性心肌梗死相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈赟; 曾小菁

    2012-01-01

    目的 研究贵州地区人类血小板抗原(HPA1 ~6、15)基因多态性与急性心肌梗死(acute myocardial infarction,AMI)的相关性.方法 选择AMI患者86例(61.05 ± 10.27岁),符合1979年WHO诊断标准,并行冠脉造影证实;对照组85例(60.74±6.88岁),排除心脑血管疾病及血栓性疾病.采用序列特异性引物-聚合酶链反应(SSP-PCR)技术扩增目的基因,进行HPA基因分型,回归分析其在AMI中的危险因素.结果 ①与对照组比较,AMI组HPA2基因多态性差异有统计学意义(P <0.01,OR=34.169,95% CI 14.553 ~80.221),而HPA1、3~6、15基因多态性差异无统计学意义(P>0.05);②影响AMI发病的多因素回归分析显示:与对照组比较,AMI组中HPA1 ab基因型差异无统计学意义(P>0.05),但其在AMI发病的危险度比HPA1 aa纯合子增加了4.256倍;HPA2aa基因型和HPA2b等位基因差异有统计学意义(P <0.01,OR =0.148,95% CI 0.071 ~0.307;P <0.01,OR =6.221,95%CI3.201 ~ 12.091).结论 ①HPA1ab杂合子患AMI的危险度较HPA1aa纯合子增加;②HPA2aa纯合子可能是AMI发病的保护因子,而HPA2b等位基因可能是AMI 发病的独立遗传性危险因素.%Objective To investigate the correlation between gene polymorphism of human platelet antigens (HPA1-6, 15) in Cuizhou Province and acute myocardial infarction (AMI). Methods A total of86 newly diagnosed AMI patients with a mean age of 61. 05 ± 10. 27 years, who were in line with 1979 WHO diagnostic criteria, identified with coronary angiography and hospitalized in our affiliated hospital form April 2010 to October 2010 were enrolled in this study. Another 85 health individuals with a mean age of 60. 74 ±6. 88 and without any cardiovascular disease and thrombosis served as control. Sequence-specific primer-polymerase chain reaction (SSP-PCR) was employed to amplify the target gene, and genotype HPA gene. Regression analysis was used to analyze whether its polymorphism was the risk

  8. Plant aquaporins: structure meets function as associating with sensing of Xanthomonas oryzae Hpa1 and subsequent signal transduction%植物水通道蛋白结构与功能及其识别与转导水稻黄单胞菌Hpa1信号的机制

    Institute of Scientific and Technical Information of China (English)

    尤真真; 高蓉; 田珊; 董汉松

    2013-01-01

    Plant aquaporin proteins basically mediate water transport through cell membranes,and also affect plant-microbe interactions and plant defense responses.Molecular mechanisms that underlie the dual function are unclear.Recently,the rice and Arabidopsis aquaporins OsPIP1; 2 and AtPIP1 ; 4 interact with Hpa1,a protein secreted by type Ⅲ pathway in Xanthomonas oryzae pathovars oryzae and oryzicola,which cause bacterial blight disaese and bacterial leaf streak disease of rice,respectively have been determined.When applied to plants or produced in transgenic plants,Hpa1 localizes to the apoplast and induces hydrogen peroxide generation in the same cellular location.The generation of hydrogen peroxide is dependent on the NADPH oxidase located at the plasma membrane.In response to Hpa1,moreover,the apoplastic hydrogen peroxide translocates to the cytoplasm with subcequent effects of enhancing plant defense responses to bacterial pathogens.According to established models in regard to the topological structure of aquaporins,the performance of bacterial type Ⅲ secretion,and subcellular trafficking of hydrogen peroxide in plants,it is necessary to identify the functional domain for OsPIP1 ; 2 interacting with Hpa1,and elucidate molecular features and structural basis of the OsPIP1 ; 2-Hpa1 interaction.Signal transduction triggered by the molecular interaction may be linked with the role of OsPIP1 ; 2 Hpa1 interaction in modulating translocation of apoplastic hydrogen peroxide to the cytoplasm,thus connecting the signal translocation with defense responses in rice.The OsPIP1 ; 2-Hpa1 interaction may also play a role in facilitating the translocation of X.oryzae type Ⅲ effector proteins from the bacterial cell to the plant cell because Hpa1 has been suggested as a candidate of tyep-Ⅲ effector translocators.With this hypothesis,studies are to further reveal regulatory mechanisms of plant-pathogen interactions,offerring a significant extension of aquaporins' functions over

  9. Analysis of association between genetic polymorphism of human platelet antigens HPA-1-5 and type 2 diabetes combined with carotid atherosclerosis of Han people in Guiyang%贵阳地区汉族人群 HPA-1~5基因多态性与2型糖尿病合并颈动脉粥样硬化的关系

    Institute of Scientific and Technical Information of China (English)

    郑婧; 徐时方; 张亚华; 洪欢山; 范良敏

    2014-01-01

    Objective To study the association between genetic polymorphism of human platelet antigens HPA -1-5 and type 2 diabetes combined with carotid atherosclerosis ( CA) of Han people in Guiyang .Methods 99 patients with type 2 diabetes (diabetes group) and 100 healthy controls (normal group) were enrolled in this case-control study.The di-abetes group was devided into two groups , which was CA( +) (combined with CA) and CA( -) (non-CA).Phenol-chloroform method was used to extract the genomic DNA and sequence-specific primers-polymerase chain reaction ( SSP-PCR) technique was applied for amplification of the target gene and genotyping .Results The allele frequency and geno-type of HPA-1, 2, 3, 5 showed significant differences among the normal group , CA(+) group and CA(-) group (all P<0.05).The allele frequency and genotype of HPA-1, 2, 3 showed significant differences between the normal group and the diabetes group (all P<0.05).The allele frequency and genotype of HPA-5 showed significant differences between CA (+) and CA(-) (P<0.05).Logistic regression analysis showed that age , duration of diabetes, hypertension, smok-ing, overweight, dyslipidemia, genetic polymorphism of HPA-5 were risk factors of CA in patients with type 2 diabetes. Conclusions There is a possible correlation between genetic polymorphism of human platelet antigens HPA -1, 2, 3 and occurrence of type 2 diabetes.Genetic polymorphism of HPA-5 may be the risk factor of type 2 diabetes with CA.%目的:研究贵阳地区汉族人群中人类血小板抗原(HPA)1~5基因多态性与2型糖尿病合并颈动脉粥样硬化的相关性。方法2型糖尿病患者99例(糖尿病组),按有无颈动脉粥样硬化分为CA (+)组( n=56)和CA (-)组( n=43)两个亚组,同期健康体检者100例作为正常组,采用酚-氯仿法提取基因组DNA,序列特异性引物-多聚酶链反应(SSP-PCR)技术扩增目的基因,进行HPA基因分型。结果正

  10. Anomalías de circulación atmosférica en 500 y 1000 hpa asociada a la sequía producida en la Argentina durante enero de 2003 a marzo de 2004 Anomalies of the atmospheric circulation at 500 and 1000 hpa associated with the dry period in Argentina from january 2003 to march 2004

    Directory of Open Access Journals (Sweden)

    Adelia Perla Alessandro

    2008-03-01

    Full Text Available Neste trabalho se analisa e descreve a situação sinótica associada à precipitação e temperatura do território argentino durante o ano de 2003 e o primeiro trimestre de 2004. A escolha deste período obedece à falta de precipitações em pelo menos dez províncias argentinas, o que ocasionou grandes prejuízos econômicos no setor agropecuário. Com o intuito de determinar as causas deste déficit de precipitações foram analisados os campos médios de altura geopotencial nos níveis de 500 e 1000 hPa e suas anomalias. Em 2003, o déficit de precipitação se associa principalmente às anomalias de geopotencial no nível de 500 hPa, que mostram um fluxo dominante de SO que atravessa o país diagonalmente entre 45°S e 30°S. Em 1000 hPa o anticiclone subtropical do Atlântico se encontra enfraquecido, deslocado para o norte e afastado do continente, enquanto que o anticiclone subrtopical do Pacífico está mais intenso e deslocado para leste respeito da sua posição normal. No primeiro trimestre de 2004 a seca se deve principalmente à presença de uma crista no nível de 500 hPa posicionada no centro do país. As anomalias médias de temperatura do período considerado resultam positivas sobre toda a Argentina. Em 2003, essas anomalias se devem à contribuição do fluxo do N-NE desde o norte do país, à subsidência ocasionada pelo anticiclone do Pacífico mais deslocado para o interior do continente e a orografia. No primeiro trimestre de 2004 as anomalias se originam devido ao fluxo do norte e à freqüente circulação anticiclônica no Atlântico ao sul de 35°S.This paper analyzes and describes the synoptic situation associated with precipitation and temperature in Argentina during 2003 and the first quarter of 2004. The period was selected as during that time drought affected at least ten Argentine provinces, causing great agricultural and ranching losses. In order to find the causes of such rainfall deficit the mean and

  11. 慢性应激对大鼠糖代谢的影响及初步机制%Effects and preliminary mechanism of chronic stress on glycometabolism in rats

    Institute of Scientific and Technical Information of China (English)

    张汝学; 马海港; 周珺; 李茂星; 贾正平

    2013-01-01

    目的:探讨慢性应激对大鼠糖代谢的影响及初步机制.方法:采用纱布束缚、PVC束缚筒束缚、大鼠固定架制动和悬尾四种应激方式,四种方式随机交替进行,应激时间为5周,每天记录动物的饮食量和饮水量,每周检测体质量和空腹血糖、第3周进行胰岛素耐量实验,第1、5周进行腹腔注射糖耐量实验,实验结束后处死所有大鼠,测定相关指标.结果:长期慢性应激可以造成大鼠空腹血糖的轻微升高、胰岛素耐量异常和糖耐量异常,另外,脾脏、胸腺指数降低,肾脏和肾上腺指数升高,血清总胆固醇升高,肝糖原和肌糖原显著降低,血清FFA水平升高,胰岛素、瘦素水平降低,皮质酮水平升高.结论:慢性非损伤性应激可能通过激活HPA轴影响大鼠的神经-内分泌-免疫调节网络,促进大鼠胰岛素抵抗和糖尿病的发生.%Objective:To investigate the effects of chronic stress on glycometabolism in rats and its mechanism.Methods:Rats were exposed to four stressors which restrainted the experimental animals with absorbent gauze,PVC tube,frisket and hanging tail for five weeks respectively.The food-intake and drinking were recorded everyday.The body weight and fasting plasma glucose were measured every week.The insulin tolerance test was performed at the third week,while the glucose tolerance test was performed at the first and fifth week respectively.Results:Chronic stress caused the increase of the fasting plasma glucose and the damaged insulin tolerance and glucose tolerance.The organ indexes of thymus and spleen were decreased,while they were increased for the kidney and adrenal.The levels of insulin,leptin and glycogen were down-regulated,and the levels of total cholesterol FFA and corticosterone were increased simultaneously.Conclusion:Chronic stress causes diabetes mellitus and insulin resistance by affecting the nerves-endocrine-immunological network through activation of hypothalamic-pituitary-adrenocortical

  12. 血小板膜糖蛋白Ibα基因HPA-2、Kozak序列多态性与脑梗死的相关性研究%Relationship between the HPA-2 and Kozak sequence polymorphism of platelet membrane glycoprotein and cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    郑敏; 郝跃伟; 刘雪平; 赵婷婷

    2008-01-01

    目的 探讨血小板膜糖蛋白(platelet membrane glyCO2protein,GP)Ibα基因HPA-2、Kozak序列多态性与脑梗死的相关性.方法 选取316例经CT/MRI证实的脑梗死患者做病例组,209例与病例组年龄、性别相匹配的无脑血管病人群做对照组.采用聚合酶链反应-限制性片断长度多态性(polymerase chain reactionrestriction fragment lengthpolymorphism,PcR-RFLP)技术检测人类血小板抗原-2(human platelet antigen-2,HPA-2)及Kozak序列多态性在两组中的分布频率.结果 病例组GPIbα基因HPA-2等位基因频率、基因型与对照组相比差异无统计学意义(P>0.05).病例组Kozak序列C等位基因频率为25.95%,对照组C等位基因频率为18.18%,两组间差异具有统计学意义(x=8.132 3,P<0.01).结论 GPIbα基因HPA-2序列多态性与脑梗死无相关性;Kozak序列多态性可能是脑梗死的遗传易感因素.

  13. 汉族人血小板GPⅡb HPA-3基因多态性与冠心病的相关性研究%Association between platelet membrane glycoprotein IIb polymorphism and coronary heart disease in Han people

    Institute of Scientific and Technical Information of China (English)

    薛梅; 陈可冀; 殷惠军

    2009-01-01

    目的: 观察血小板膜糖蛋白(GP)Ⅱb人类血小板抗原-3(HPA-3)基因多态性,在北京河北地区汉族人中各基因型的分布频率,分析该多态性与冠心病易感性的相关性.方法: 本研究采用病例对照设计,筛选符合冠心病、健康人入选标准的212例冠心病患者及106例健康对照人群为研究对象,记录冠脉造影病变支数,采用TaqMan探针技术检测HPA-3基因多态性.结果: 大于45岁的人群中,至少含有1个HPA-3b等位基因者较HPA-3a/3a原生型纯合子,冠心病人(72.4%/27.6%)多于健康人(57.1%/42.9%),不同基因型在冠心病组和健康对照组两组间的分布具有显著差异(P<0.05);冠心病患者不同病变支数基因型构成无显著差异(P>0.05).以是否患冠心病为因变量的二分类Binary Logistic回归分析,校正年龄、性别、体重指数对冠心病的影响后,结果显示HPA-3多态位点基因型与冠心病发病密切相关,含有至少1个HPA-3b等位基因者较HPA-3a/HPA-3a纯合型发生冠心病的危险性是2.105倍.结论: GPⅡb的HPA-3多态位点是汉族人冠心病发病的独立危险因素,尤其在年龄>45岁的人群中表现明显.

  14. Investigation on polymorphism of human platelet antigen-6 in Han population in Guangzhou by SSP and sequencing method%SSP法和测序法对广州汉族人群HPA-6多态性调查

    Institute of Scientific and Technical Information of China (English)

    黎美娜; 汪传喜; 滕青; 聂咏梅

    2010-01-01

    目的:调查广州汉族人群HPA-6多态性.方法:采用SSP法和测序法对200例广州汉族无偿血小板献血员进行HPA-6基因分型.结果:HPA-6a和-6b的基因频率分别为0.977 5和0.022 5,符合Hardy-Weinberg平衡.与中国其他地区人群及亚洲其他地区人群比较差异无显著性,但和其他洲人群分布存在统计学差异:在随机输血中HPA-6抗原不配合的机会为0.043 0.结论:获得广州汉族人群HPA-6频率数据.对建立本地血小板供者库和开展血小板同型输注具有指导意义.

  15. HPA-axis function and grey matter volume reductions: imaging the diathesis-stress model in individuals at ultra-high risk of psychosis.

    Science.gov (United States)

    Valli, I; Crossley, N A; Day, F; Stone, J; Tognin, S; Mondelli, V; Howes, O; Valmaggia, L; Pariante, C; McGuire, P

    2016-05-03

    The onset of psychosis is thought to involve interactions between environmental stressors and the brain, with cortisol as a putative mediator. We examined the relationship between the cortisol stress response and brain structure in subjects at ultra-high risk (UHR) for psychosis. Waking salivary cortisol was measured in 22 individuals at UHR for psychosis and 17 healthy controls. Grey matter volume was assessed using magnetic resonance imaging at 3 T. The relationship between the stress response and grey matter volume was investigated using voxel-based analyses. Our predictions of the topography of cortisol action as a structural brain modulator were informed by measures of brain glucocorticoid and mineralcorticoid receptor distribution obtained from the multimodal neuroanatomical and genetic Allen Brain Atlas. Across all subjects, reduced responsivity of the hypothalamus-pituitary-adrenal (HPA) axis was correlated with smaller grey matter volumes in the frontal, parietal and temporal cortex and in the hippocampus. This relationship was particularly marked in the UHR subjects in the right prefrontal, left parahippocampal/fusiform and parietal cortices. The subgroup that subsequently developed psychosis showed a significant blunting of HPA stress response, observed at trend level also in the whole UHR sample. Altered responses to stress in people at high risk of psychosis are related to reductions in grey matter volume in areas implicated in the vulnerability to psychotic disorders. These areas may represent the neural components of a stress vulnerability model.

  16. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function.

    Science.gov (United States)

    Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Valadas, Jorge S; Gomes, Rui; Temido-Ferreira, Mariana; Shmidt, Tatiana; Baqi, Younis; Buée, Luc; Müller, Christa E; Hamdane, Malika; Outeiro, Tiago F; Bader, Michael; Meijsing, Sebastiaan H; Sadri-Vakili, Ghazaleh; Blum, David; Lopes, Luísa V

    2016-08-11

    Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.

  17. Investigation of the differences between deepening and intensification for 500-hpa cyclones in central and East Mediterranean region during warm season of the year

    Directory of Open Access Journals (Sweden)

    S. Spanos

    2006-01-01

    Full Text Available The maximum deepening rate per cyclone track is determined by the maximum height drop at the center of the cyclone (500-hPa low on the basis of all the 6-h successive steps in its life cycle. The geopotential height gradient is calculated over the entire low area and the calculation continued with the variation of the gradient in the successive steps. The maximum intensification rate per cyclone is then determined as the maximum increase of the gradient in the life cycle. Maximum deepening rate for the 500-hPa cyclones in the area does not exceed, on average, 12 gpm/6 h. Maximum intensification which is 1.4 gpm/100 Km*6 h on average, occurs in the early stages of the cyclone's life cycle. This on the average happens approximately 9 h after the first time the low is detected. At the gulf of Genoa and the Adriatic Sea, cyclones usually show the maximum intensification after the maximum deepening. At Turkey's cyclogenesis area, however, this order is reversed. The spatial distributions of maximum intensification in the three sub-periods, indicate that it mainly occurs over Seas during late warm periods and over land during early and middle warm periods. Such a behavior underlines the role of low-level instability in cyclone development.

  18. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    Jessica M. F. Hall

    2012-01-01

    Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  19. EURAMET.M.P-S9 / EURAMET 1170, LOOP2. Comparison in the negative gauge pressure range -950 to 0 hPa

    Science.gov (United States)

    Otal, P.; Boineau, F.; Medina, N.; Pražák, D.; Wüthrich, C.; Saxholm, S.; Sabuga, W.; Kocas, I.; Durgut, Y.

    2017-01-01

    This report gives the results of a comparison of pressure standards of seven European National Metrology institutes in the range of negative gauge pressure from -950 hPa to 0 hPa. This comparison was piloted by LNE and was carried out from January 2011 to March 2012. This work is a part of the EURAMET project 1170 and is registered as a supplementary comparison EURAMET.M.P-S9. The transfer standard used was a pressure monitor RPM4 A160Ks manufactured by DH Instruments Inc., with a resolution of 0.1 Pa. The reference values have been determined from the weighted mean of the deviations reported by the participants for each specified pressure. Seventy-three of the seventy-seven values (96%) reported by the laboratories agree with the reference values within the expanded uncertainties with a coverage factor k = 2. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Asymmetric Synthesis and Binding Study of New Long-Chain HPA-12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT.

    Science.gov (United States)

    Ďuriš, Andrej; Daïch, Adam; Santos, Cécile; Fleury, Laurence; Ausseil, Frédéric; Rodriguez, Frédéric; Ballereau, Stéphanie; Génisson, Yves; Berkeš, Dušan

    2016-05-01

    A series of 12 analogues of the Cer transfer protein (CERT) antagonist HPA-12 with long aliphatic chains were prepared as their (1R,3S)-syn and (1R,3R)-anti stereoisomers from pivotal chiral oxoamino acids. The enantioselective access to these intermediates as well as their ensuing transformation relied on a practical crystallization-induced asymmetric transformation (CIAT) process. Sonogashira coupling followed by triple bond reduction and thiophene ring hydrodesulfurization (HDS) into the corresponding alkane moieties was then implemented to complete the synthetic routes delivering the targeted HPA-12 analogues in concise 4- to 6-step reaction sequences. Ten compounds were evaluated regarding their ability to bind to the CERT START domain by using the recently developed time-resolved FRET-based homogeneous (HTR-FRET) binding assay. The introduction of a lipophilic appendage on the phenyl moiety led to an overall 10- to 1000-fold enhancement of the protein binding, with the highest effect being observed for a n-hexyl residue in the meta position. The importance of the phenyl ring for the activity was indicated by the reduced potency of the 3-deoxyphytoceramide aliphatic analogues. The 1,3-syn stereoisomers were systematically more potent than their 1,3-anti analogues. In silico studies were used to rationalized these trends, leading to a model of protein recognition coherent with the stronger binding of (1R,3S)-syn HPAs.

  1. Two-year stability of individual differences in (para)sympathetic and HPA-axis responses to public speaking in childhood and adolescence.

    Science.gov (United States)

    van den Bos, Esther; Westenberg, P Michiel

    2015-03-01

    Long-term stability of individual differences in stress responses has repeatedly been demonstrated in adults, but few studies have investigated the development of stability in adolescence. The present study was the first to investigate the stability of individual differences in heart rate, parasympathetic (RMSSD, pNN50, HF), sympathetic (LF/HF, SC), and HPA-axis (salivary cortisol) responses in a youth sample (8-19 years). Responses to public speaking were measured twice over 2 years. Stability was moderate for absolute responses and task delta responses of HR, RMSSD, pNN50, and HF. Stability was lower for SC and task delta responses of LF/HF and cortisol. Anticipation delta responses showed low stability for HR and cortisol. The latter was moderated by age or puberty, so that individual differences were more stable in more mature individuals. The results support the suggestion that stress responses may be reset during adolescence, but only for the HPA axis. © 2014 Society for Psychophysiological Research.

  2. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.

    Science.gov (United States)

    Hall, Jessica M F; Cruser, Desanges; Podawiltz, Alan; Mummert, Diana I; Jones, Harlan; Mummert, Mark E

    2012-01-01

    Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  3. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function

    Science.gov (United States)

    Batalha, Vânia L.; Ferreira, Diana G.; Coelho, Joana E.; Valadas, Jorge S.; Gomes, Rui; Temido-Ferreira, Mariana; Shmidt, Tatiana; Baqi, Younis; Buée, Luc; Müller, Christa E.; Hamdane, Malika; Outeiro, Tiago F.; Bader, Michael; Meijsing, Sebastiaan H.; Sadri-Vakili, Ghazaleh; Blum, David; Lopes, Luísa V.

    2016-01-01

    Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer’s disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer’s and age-related cognitive impairments may rely on its ability to modulate GR actions. PMID:27510168

  4. Genotyping of human platelet antigen 15 by melting curve analysis%熔解曲线分析法用于HPA-15基因分型的研究

    Institute of Scientific and Technical Information of China (English)

    周世航; 刘铭; 于卫建; 宫本兰

    2011-01-01

    目的 探讨熔解曲线分析法用于HPA-15基因分型,了解大连地区汉族人群HPA-15基因多态性.方法 设计合成HPA-15等位基因特异性引物和1条公共引物,其中在2条等位基因特异性引物的5末端分别加入具有不同长度并富含GC碱基的序列.使用这3条引物,进行实时PCR反应.在PCR反应后,进行熔解曲线分析,依据PCR产物熔解温度的差异,进行基因分型.应用熔解曲线分析法和常规PCR-SSP法对100名大连地区汉族人群的血液标本进行HPA-15基因分型.此外对熔解曲线分析法的重复性进行评价.结果 100个血液标本的熔解曲线分析法和常规PCR-SSP法的基因分型结果是完全一致的.10个血标本的2次熔解曲线分析结果是一致的.大连地区汉族人群HPA- 15a、-15b基因频率分别为0.58和0.42.大连地区汉族人群与国内部分地区汉族人群相比,HPA-15等位基因频率的差异无统计学意义(P>0.05).与新疆维吾尔族人群相比,HPA-15等位基因频率差异有统计学意义(P<0.05).结论 HPA的熔解曲线基因分型方法具有快速、简单、准确、通量高、重复性好等优点,要优于常规的PCR-SSP法.在国内HPA-15等位基因分布存在着种族差异.%Objective To investigate genotyping of human platelet antigen 15 ( HPA-15) by using melting curve analysis, and study the polymorphism of human platelet antigen 15 in Dalian Han population. Methods Two HPA-15 allele-spe-cific primer and a common primer were designed and synthesized. Two GC-rich tails of different lengths were attached to 5' end of HPA-15 allele-specific PCR primers. Real-time PCR was carried out with the three primers. After real-time PCR, melting curve analysis was performed. By differences of the melting temperatures of the PCR products,HPA-15 can be geno-typed. One hundred blood samples were genotyped for HPA-15 by the melting curve analysis and conventional PCR-SSP. Moreover,the reproducibility of melting curve

  5. The Platte River - High Plains Aquifer (PR-HPA) Long Term Agroecosystem Research (LTAR) Network - Data and Technological Resources to Address Current and Emerging Issues in Agroecosystems.

    Science.gov (United States)

    Okalebo, J. A.; Wienhold, B.; Suyker, A.; Erickson, G.; Hayes, M. J.; Awada, T.

    2015-12-01

    The Platte River - High Plains Aquifer (PR-HPA) is one of 18 established Long Term Agroecosystem Research (LTAR) networks across the US. PR-HPA is a partnership between the Institute of Agriculture and Natural Resources at the University of Nebraska-Lincoln (UNL), the USDA-ARS Agroecosystem Management Research Unit (AMRU) in Lincoln, and the USDA-ARS Environmental Management Research Unit (EMRU) in Clay Center, NE. The PR-HPA network encompasses 27,750 ha of research sites with data going back to the early 1900s. A partial list of on-going research projects include those encompassing long-term manuring and continuous corn (Est. 1912), dryland tillage plots (Est. 1970), soil nutrients and tillage (Est. 1983), biofuel feedstock studies (Est. 2001), and carbon sequestration study (Est. 2000). Affiliated partners include the National Drought Mitigation Center (NDMC) that develops measures to improve preparedness and adaptation to climate variability and drought; the High Plains Regional Climate Center (HPRCC) that coordinates data acquisition from over 170 automated weather stations and around 50 automated soil moisture network across NE and beyond; the AMERIFLUX and NEBFLUX networks that coordinate the water vapor and carbon dioxide flux measurements across NE with emphasis on rainfed and irrigated crop lands; the ARS Greenhouse gas Reduction through Agricultural Carbon Enhancement network (GRACEnet) and the Resilient Economic Agricultural Practices (REAP) project; and the Center for Advanced Land Management Information Technologies (CALMIT) that assists with the use of geospatial technologies for agriculture and natural resource applications. Current emphases are on addressing present-day and emerging issues related to profitability and sustainability of agroecosystems. The poster will highlight some of the ongoing and planned efforts in research pertaining to climate variability and change, water sustainability, and ecological and agronomic challenges associated

  6. Analysis of gene polymorphism of human platelet antigen 1-17 system in platelet donors of Kunming%昆明地区单采血小板献血者HPA1-17系统基因多态性的分析

    Institute of Scientific and Technical Information of China (English)

    朱祥明; 姚杰; 李开红; 杨通汉; 姚富柱; 汤戎; 赵杨; 苏品璨; 罗臻; 涂源泉; 郭萍

    2011-01-01

    目的 研究昆明地区单采血小板献血者HPAl-17基因多态性,建立已知型血小板献血者基因数据资料库.方法 分别PCR-SSP方法对1000名昆明地区无血缘关系的单采血小板献血者做HPA-1-17系统基因分型,计算基因型频率、基因频率,并与其他人群进行比较.结果 在昆明地区人群中均检测到HPA-1a,2a,4a-14a,16a,17a基因;HPA-4a,7a-14a,16a,17a呈现单态性,未检测出相应的等位基因HPA-b;对于HPA-1、-2、-5、-6主要以a/a纯合子为多,a/a基因型频率分别是0.989、0.96、0.99、0.98,没有b/b纯合子出现.在HPA1-17中,具有最高杂合度的是HPA-15,基因型HPA15a/15a,HPA15a/15b,HPA 15b/15b频率分别是0.392、036、0.248;HPA-3在其次,基因型HPA3a/3a,HPA3a/3b,HPA3b/3b频率分别是0.339、0.467、0.194.经x 2检验,结果符合Hardy-Weinberg遗传平衡定律.结论 昆明地区单采血小板献血者HPA1-17基因频率与中国南方汉族接近,也呈现其自身的特点,应建立本地区的单采血小板献血者基因分型数据库.

  7. Analysis of Genotype of HLA/HPA and Antibody Specificity in Platelet Transfusion Refractoriness Patients%血小板输注无效患者HLA和HPA基因型及其抗体特异性的分析

    Institute of Scientific and Technical Information of China (English)

    邓晶; 徐秀章; 叶欣; 王嘉励; 夏文杰; 邵媛; 陈扬凯; 丁浩强

    2014-01-01

    目的 探讨人类白细胞抗原(HLA)和人类血小板抗原(HPA)复合抗体诱发的血小板输注无效(PTR)患者的HPA/HLA基因型及抗体特异性.方法 选择2010年1月至2012年6月,于广州血液中心行血小板(PLT)配型的PTR患者中,6例同时具有HLA-Ⅰ类抗体和HPA抗体的患者作为研究对象(本研究遵循的程序符合广州血液中心人体试验委员会制定的伦理学标准,得到该委员会批准,并征得受试对象的知情同意).采用酶联免疫吸附试验方法检测患者HLA抗体及PLT特异性糖蛋白(GP)抗体,应用序列特异性引物-聚合酶链反应(PCR-SSP)方法对患者HLA及HPA 1~17进行基因分型,根据HLA/HPA基因型和单克隆抗体特异性俘获血小板抗原实验(MAIPA)的抗体检测结果确认抗体特异性.结果 6例PTR患者的抗HLA-Ⅰ类抗体中,以抗HLA-A*2、-A* 11及-B* 40最为常见;PLT特异性GP抗体以GPⅡb/Ⅲa抗体阳性为主,占83.3%(5/6);经MAIPA PLT抗体特异性分析,3例(50.0%,3/6)患者存在抗HPA-3a抗体,2例(33.3%,2/6)患者HPA-3b抗体呈阳性,仅1例(16.7%,1/6)患者的HPA-5b抗体呈阳性.结论 临床上,对存在复合抗体的疑难PTR患者进行HLA/HPA基因型及其抗体特异性分析,能避免患者HLA/HPA抗体相应的PLT抗原输注,寻找与患者HLA/HPA基因型相匹配的献血者,可提高患者的PLT输注疗效,避免血液资源的浪费.%Objective To analyze the genotype of human leukocyte antigen (HLA)/human platelet antigen (HPA) and the antibody specificity in platelet transfusion refractoriness (PTR) patients caused by HLA antibodies combined with HPA antibodies.Methods From January 2010 to June 2012,a total of 6 patients who had HLA class Ⅰ antibodies and HPA antibodies were selected as research subjects from PTR patients who accepted platelet (PLT) crossmatch in Guangzhou Blood Center.HLA antibodies and antibody of membrane glycoprotein (GP) were measured by enzyme-linked immunosorbent assay (ELISA

  8. Analysis of Genetic Polymorphism in DongGuan Randomized Donors' HPA 1-6 Antigens%现居东莞人群人类血小板1-6抗原系统基因分型研究

    Institute of Scientific and Technical Information of China (English)

    师玲玲; 王德文; 刘赴平

    2009-01-01

    目的 研究现居东莞人群人类血小板抗原(human Platelet antigen,HAP)1-6系统基因分型及其多态性分布特征.方法 用DNA提取试剂盒提取外周血标本中的DNA,用聚合酶链式反应-序列特异性引物(PCR-SSP)扩增HPA等位基因.结果 80名健康、无血缘关系的现居东莞人群每个样本均检测到HPA-1a、2a、4a、5a、6a基因;HPA-4a、5a呈现纯合子单态性,未检测出相应的等位基因HPA-b;对于HPA-1、-2、-6主要以a/a纯合子为多,a/a基因型频率分别是0.975、0.725、0.9625,没有b/b纯合子出现.结论 HPA血型系统多态性具有人群特征.与其他种族相比,现居东莞人群HPA血型系统中a基因频率较高,b基因频率较低,提示在现居东莞人群中由b基因不合所引起的同种免疫病理反应要低于其他种族人群.现居东莞人群HPA-1、-2、-3、-6系统具有多态性,HPA-2、-3抗原杂和率比较高,提示在临床输血实践中可能具有重要的免疫学意义.同时,在此次研究数据的基础上建立了现居东莞人群血小板基因频率数据库和血小板基因型已知供者库.%Objective To characterize the allele frequencies and its polymorphisms of human platelet 1-6 antigen (HPA) in DongGuan population. Methods The genomic DNA of 80 healthy and unrelated individuals from blood donors was extracted from the peripheral blood samples with DNA extraction kit reagent and genotyped for by polymerase chain reaction with sequence specific primers (PCR-SSP). Results HPA-1a, 2a, 4a, 5a ,6a alleles were found in each of the samples. HPA-4a, 5a all showed homozygous genotype with no responsive HPA-b alleles were found. HPA-1, -2, -6 mainly showed a/a homozygous, the frequencies of homozygous HPA-1a/a, 2a/a, 6a/a were 0.975, 0.725, 0.9625 respectively, and homozygous (b/b) were not detected. Conclusion Polymorphism of HPA has differential population characteristic. Compared with other populations, population in DongGuan displayed higher

  9. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

    Science.gov (United States)

    Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

    2017-03-06

    There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Differences among Helicobacter pylori strains isolated from three different populations and demonstrated by restriction enzyme analysis of an internal fragment of the conserved gene hpaA.

    Science.gov (United States)

    Evans, D G; Queiroz, D M; Mendes, E N; Svennerholm, A M; Evans, D J

    1999-06-01

    Our goal was to test the idea that Helicobacter pylori genotypes vary from one population to another. Analysis of Sau3A and HinfI restriction fragment-length polymorphism (RFLP) in a 375-bp polymerase chain reaction amplicon of hpaA was used to compare 31 H. pylori isolates from a relatively small and genetically homogeneous population (Goteborg, Sweden) with those of large, genetically heterogeneous populations located in two different countries (50 isolates from Houston, TX, and 69 isolates from Minas Gerais, a state in the southeastern region of Brazil). Five different Sau3A and three different HinfI restriction patterns were found; different combinations of these comprise 10 different RFLP types, I through X. The RFLP types found in the United States and Brazil collections were very similar, except for two Brazil isolates belonging to type VIII and five Brazil isolates belonging to type X, neither type found in the United States. The overall profile of H. pylori isolates from Sweden was remarkably different, with 18 of 31 (58%) having a new Sau3A restriction pattern, termed gS; 10 of these 18 isolates had HinfI restriction pattern E (RFLP type VIII), and 8 had HinfI restriction pattern F (RFLP type IX). No isolates from Sweden belonged to RFLP type III or type X. RFLP typing of a 375-bp polymerase chain reaction-amplified DNA fragment of H. pylori hpaA revealed that H. pylori genotypes can and do vary from one population to another. We conclude that the unique RFLP profile shown by the group of H. pylori isolates from Goteborg is the result of a cohort effect in this relatively small, stable, genetically homogeneous population. Also, the overall similarity between RFLP profiles of the H. pylori isolates from Texas and Minas Gerais coincides with the fact that although geographically distanced, these populations are similar in being large, dynamic, and genetically heterogeneous.

  11. 河南汉族人群血小板抗原HPA1-16bw基因多态性研究%Study on genetic polymorphism of human platelet antigens 1 to 16bw in Han population of Henan province

    Institute of Scientific and Technical Information of China (English)

    滑世轩; 王书勤; 岑东; 燕备战

    2011-01-01

    Objective To investigate the allele frequencies of human platelet alloantigens (HP A) in Han population of Henan prov ince, and establish the gene bank of platelet antigens for local population in order to provide experimental evidence for compatible platelet transfusion. Methods The HPA\\ to I6610 of 160 unrelated and healthy Henan subjects were genotyped by polymerase chain reaction with sequence-specific primer ( PCR-SSP). Results The frequencies of HPA-l to 6 and HPA-15 were as follows ;0.987 5 and 0.012 5 for HPA-la and 16, 0. 946 9 and 0. 053 1 for HPA-2a and 26, 0. 590 6 and 0. 409 4 for HPA-3a and 36, 0. 996 9 and 0.003 1 for HPAAa and 46, 0.990 6 and 0. 009 4 for HPA-5a and 5b, 0. 981 2 and 0. 018 8 for HPASa and 6b, 0. 540 6 and 0.459 4 for HPA-15a and 156. Only a/a homozygosity of HPA7-14bw and HPA-I6bw were detectable and both the gene frequencies was 1.000 0. The detected HPA gene frequencies corresponded to Hardy-Weinberg equilibrium. The distribution of HPA gene showed ethnic and regional diversity. Conclusion The heterozygous rate of HPA-15 and HPA-3 were the highest in Han population of Henaa province. HPA genotyping could conduce to reduce the incidence of immune thrombocytopenia during transfusion of platelet.%目的 研究河南地区汉族人群血小板抗原基因分布频率,建立地区性血小板抗原基因库,为血小板配合输注提供实验依据.方法 用序列特异性引物聚合酶链反应(PCR-SSP)对160例无血缘关系的河南汉族体检健康者进行HPA1-16bw系统基因分型.结果 HPA1-6和HPA-15基因频率分别为1a 0.987 5,1b 0.012 5;2a 0.946 9,2b 0.053 1;3a 0.590 6,3b0.409 4; 4a0.996 9,4b0.003 1;5a0.990 6,5b0.009 4;6a0.981 2,6b0.018 8;15a0.540 6,15b 0.459 4.HPA7-14bw,16bw仅检测到a/a等位基因,基因频率均为1.000 0.经x2检验各系统HPA符合Hardy-Weinberg平衡法则.HPA基因分布存在种族和地区差异.结论 河南汉族人HPA-15和HPA-3基因型杂合率最高.HPA基因分型有助于输

  12. Analysis of human platelet antigen 1 -17 and Caba gene polymorphism in Yancheng Hans population%盐城地区汉族人血小板抗原HPA-1~17,Caba基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    蒋钰瑶; 黄宏亮

    2014-01-01

    Objective To investigate the distribution of human platelet antigen (HPA) 1-17 and Caba gene in Yancheng Han population ,and to build a fixed HPA database of apheresis platelet donor in the local area .Methods A total of 200 blood samples ,collected from platelet donors of Han population in Yancheng ,were genotyped by poly‐merase chain reaction with sequence specific primers(PCR‐SSP) .Theχ2 test was used to compare the expected value and observed value of genotype distribution in HPA blood group system .The genotype distribution whether matching Hardy‐Weinberg genetic equilibrium was verified ,and data were compared with those in other areas .Results The gene frequencies of HPA‐1a ,2a ,3a ,4a ,5a ,6a and 15a were 0 .995 0 ,0 .937 5 ,0 .572 5 ,0 .992 5 ,0 .985 0 ,0 .987 5 , 0 .542 5 respectively in 200 platelet donors of Han population in Yancheng ,and presented polymorphism distribution . HPA 7-14 ,16-17 and Caba presented a single linear distribution .The incidence of platelet transfusion refractorines in HPA 2-3 ,15 was higher than 10% .Conclusion This study could verify the characteristics of the distribution of HPA gene in Han population of Yancheng .To establish the local HPA genotype database of platelet donors in Yancheng could provide probability for HPA‐matched platelets infusion .%目的:研究盐城地区汉族人群血小板特异性抗原人类血小板同种抗原1~17(HPA1~17),Caba的基因分布,建立本地区固定机采血小板供者 HPA数据库。方法应用序列特异性引物聚合酶链式反应(PCR‐SSP)技术,对盐城市中心血站200名汉族固定血小板献血者的血液进行HPA1~17,Caba基因分型。用χ2检验统计分析各 HPA血型系统基因分布的期望值与观察值,验证其是否符合 Hardy‐Weinberg平衡定律,并与国内外人群相比较。结果盐城地区200名汉族血小板献血者的HPA‐1a、2a、3a、4a、5a、6a、15a的基因频率分别为0.9950、0

  13. Genetic evidence for host specificity in the adhesin-encoding genes hxaA of Helicobacter acinonyx, hnaA of H. nemestrinae and hpaA of H. pylori.

    Science.gov (United States)

    Evans, D G; Lampert, H C; Nakano, H; Eaton, K A; Burnens, A P; Bronsdon, M A; Evans, D J

    1995-09-22

    Gastric and non-gastric species of Helicobacter were examined for the presence of the adhesin-encoding gene, hpaA, from the human-associated gastric Helicobacter H. pylori (Hp), and for adhesin subunit protein HpaA. Amplification of a 375-bp internal DNA fragment of hpaA by PCR demonstrated the presence of the gene in Hp and in two closely related gastric Helicobacters, H. nemestrinae (Hn) and H. acinonyx (Hx), but not in the more distantly related H. felis (Hf) and H. mustelae (Hm). The non-gastric Helicobacters, H. canis (Hc), H. muridarum (Hr), H. fennelliae (He) and H. cinaedi (Hi), were all negative for hpaA. An immunoblot assay of water extracts with adhesin-specific antibody confirmed these results. The deduced amino acid (aa) sequences of Hp HpaA and Hn adhesin A (hereafter termed HnaA) are very similar, having identical receptor-binding motifs (rbm); also, the hemagglutination (HA) properties of Hn and Hp cells were indistinguishable. In contrast, the rbm of Hx adhesin A (hereafter termed HxaA), compared to that of Hp, contained a non-conservative aa substitution (Ile to Thr); also, there was variance in five consecutive aa from 10 to 14 residues upstream from the rbm. We conclude that these aa substitutions in HxaA are probably responsible for the difference in receptor recognition of this adhesin, as evidenced by the resistance of Hx HA to inhibition with N-acetylneuraminyl-alpha(2,3)-lactose. These results are consistent with the biological similarity between the natural host(s) of Hp and Hn; i.e., human and non-human primates, and the dissimilarity between these hosts and the feline host, the cheetah.

  14. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    Science.gov (United States)

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  15. The roles of puberty and age in explaining the diminished effectiveness of parental buffering of HPA reactivity and recovery in adolescence.

    Science.gov (United States)

    Doom, Jenalee R; Hostinar, Camelia E; VanZomeren-Dohm, Adrienne A; Gunnar, Megan R

    2015-09-01

    Parental support is a powerful regulator of stress and fear responses for infants and children, but recent evidence suggests it may be an ineffective stress buffer for adolescents. The mechanisms underlying this developmental shift are not well-understood. The goal of the present study was to examine the independent and joint contributions of pubertal status and chronological age in explaining this shift. A sample of 75 typically developing youth (M age=12.95 years, SD=0.70, range=11.7-14.6 years; 37 females) was recruited to complete a modified Trier Social Stress Test (TSST-M) in the laboratory. Participants were recruited in such a way as to disentangle pubertal stage and chronological age by phone screening for markers of pubertal stage and then recruiting roughly equal numbers of younger and older, pre/early and mid/late pubertal youth who were then randomly assigned within groups to condition. The TSST-M was used as the stressor and youth prepared either with their parent or stranger (parent condition: N=39). Pubertal stage was confirmed by the Petersen Pubertal Development Scale at the time of testing and treated, along with chronological age, as a continuous variable in the analyses. The results revealed an interaction of pubertal stage and support condition for cortisol reactivity to the TSST-M such that preparing for the speech with the parent became a less potent buffer of the HPA axis as pubertal stage increased. Age did not interact with condition in predicting cortisol reactivity. In contrast, the parent's presence during speech preparation decreased in its effectiveness to hasten recovery of the HPA axis as children got older, but pubertal stage was not predictive of recovery rate. These patterns were specific to cortisol and were not observed with salivary alpha-amylase levels or subjective stress ratings for the task. These analyses suggest that the switch away from using parents as social buffers may be the result of neurobiological mechanisms

  16. 中国汉族人群HPA分型单采血小板供者库的建立模式与库容%Mode and Size of HPA-Typed Plalelet Apheresis Donor Bank in Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    戴宇东

    2010-01-01

    本研究探讨建立中国汉族人群HPA分型单采血小板供者库的模式和合适的库容水平.研究方法为合并分析公开发表的中国16个省份的汉族血小板献血者人群人类血小板抗原(human platelet antigen,HPA)分布多态性群体调查数据.对HPA多态性群体调查数据进行Hardy-Weinberg平衡检验.结果表明,HPA-1、-4、-6、-10未检出bb纯合子,HPA-7-9,11-14、-16未检出b基因.HPA 1-16系统相互独立存在于血小板表面.中国汉族人群中发现了648种HPA组合,其中42种频率高于0.001的组合的累积频率迭0.9763,频率最高(0.2012)的组合为:HPA-(7-8-9-11-12-13-14-16)aa-(1-4-5-6-10)aa-2aa-3ab-15ab.HPA对偶抗原不配合概率高于0.1的系统有HPA-15、-3和-2,对偶抗原不配合概率介于0.01-0.1的系统有HPA-1、-5和-6.中国汉族人群供受者间随机输血HPA1-16系统对偶抗原全匹配概率为0.3195.根据库容(N)随频率(F)变化的曲线,推导得到在P=95%时的回归方程LogN=-0.4394×Ln(F)+0.4324.使用该公式推测综合频率(HPA和ABO的频率乘积)为0.005的库容至少需要为576.07人.结论:中国汉族人群HPA分型单采血小板供者库应采用单库容600名供者的区域多中心联合建库模式,它既能解决当地主要的HPA-15、3和2系统不配合造成的血小板输注无效(platelet transfusion refractoriness,PTR),还可以在遗传背景相近的区域有效地扩大建库规模以解决HPA低频抗原的不配合问题.在评估HPA分型血小板供者库容时不仅要考虑HPA的频率还同时要考虑ABO血型分布频率对库容的影响.

  17. A Comparative Characterization of the HPA-MCM-48 Type Catalysts Produced by the Direct Hydrothermal and Room Temperature Synthesis Methods

    Directory of Open Access Journals (Sweden)

    Y. Gucbilmez

    2012-01-01

    Full Text Available MCM-48 type support materials synthesized by the direct hydrothermal synthesis (HTS and room temperature synthesis (RTS methods were incorporated with tungstophosphoric acid (TPA in the range of 10–40 wt% by using a wet impregnation technique in methanol solutions. Resulting HPA-MCM-48 catalysts were characterized by the XRD, Nitrogen Physisorption, SEM, TEM, EDS, and FT-IR methods in order to determine the effects of different initial synthesis conditions on the catalyst properties. RTS samples were found to have better crystalline structures, higher BET surface areas, and higher BJH pore volumes than HTS samples. They also had slightly higher TPA incorporation, except for the 40 wt% samples, as evidenced by the EDS results. Keggin ion structure was preserved, for both methods, even at the highest acid loading of 40 wt%. It was concluded that the simpler and more economical RTS method was more successful than the HTS method for heteropoly acid incorporation into MCM-48 type materials.

  18. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Allen, R.C.; Zoghbi, H.Y.; Moseley, A.B.; Rosenblatt, H.M.; Belmont, J.W. (Baylor College of Medicine, Houston (United States))

    1992-12-01

    The human androgen-receptor gene (HUMARA; GenBank) contains a highly polymorphic trinucleotide repeat in the first exon. The authors have found that the methylation of HpaII and HhaI sites less than 100 pb away from this polymorphic short tandem repeat (STR) correlates with X inactivation. The close proximity of the restriction-enzyme sites to the STR allows the development of a PCR assay that distinguishes between the maternal and paternal alleles and identifies their methylation status. The accuracy of this assay was tested on (a) DNA from hamster/human hybrid cell lines containing either an active or inactive human X chromosome; (b) DNA from normal males and females; and (c) DNA from females showing nonrandom patterns of X inactivation. Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27[beta] probes, which detect X inactivation patterns by Southern blot analysis. In order to demonstrate one application of this assay, the authors examined X inactivation patterns in the B lymphocytes of potential and obligate carriers of X-linked agammaglobulinemia. 42 refs., 5 figs., 1 tab.

  19. Recurrent climate winter regimes in reconstructed and modelled 500 hPa geopotential height fields over the North Atlantic/European sector 1659-1990

    Energy Technology Data Exchange (ETDEWEB)

    Casty, C.; Xoplaki, E.; Luterbacher, J.; Wanner, H. [University of Bern, Institute of Geography, Bern (Switzerland); University of Bern, NCCR Climate (Switzerland); Handorf, D.; Dethloff, K. [Alfred Wegener Institute for Polar and Marine Research, Potsdam (Germany); Raible, C.C. [University of Bern, Climate and Environmental Physics (Switzerland); Gonzalez-Rouco, J.F. [University of Madrid, Department of Astrophysics and Atmospheric Sciences (Spain); Weisheimer, A. [Free University of Berlin, Institute of Meteorology (Germany)

    2005-06-01

    Recurrent climate winter regimes are examined from statistically reconstructed and modelled 500 hPa geopotential height fields over the North Atlantic/European sector for the period 1659-1990. We investigate the probability density function of the state space spanned by the first two empirical orthogonal functions of combined winter data. Regimes are detected as patterns that correspond to areas of the state space with an unexpected high recurrence probability using a Monte Carlo approach. The reconstruction and the model reveal four recurrent climate regimes. They correspond to the two phases of the North Atlantic Oscillation and two opposite blocking patterns. Complemented by the investigation of the temporal evolution of the climate regimes this leads to the conclusion that the reconstructed and the modelled data for this geographic sector reproduce low-frequency atmospheric variability in the form of regime-like behaviour. The overall evidence for recurrent climate regimes is higher for the model than for the reconstruction. However, comparisons with independent data sources for the period 1659-1990 revealed a more realistic temporal evolution of the regimes for the reconstructed data. (orig.)

  20. Effects of air-sea interaction on extended-range prediction of geopotential height at 500 hPa over the northern extratropical region

    Science.gov (United States)

    Wang, Xujia; Zheng, Zhihai; Feng, Guolin

    2017-02-01

    The contribution of air-sea interaction on the extended-range prediction of geopotential height at 500 hPa in the northern extratropical region has been analyzed with a coupled model form Beijing Climate Center and its atmospheric components. Under the assumption of the perfect model, the extended-range prediction skill was evaluated by anomaly correlation coefficient (ACC), root mean square error (RMSE), and signal-to-noise ratio (SNR). The coupled model has a better prediction skill than its atmospheric model, especially, the air-sea interaction in July made a greater contribution for the improvement of prediction skill than other months. The prediction skill of the extratropical region in the coupled model reaches 16-18 days in all months, while the atmospheric model reaches 10-11 days in January, April, and July and only 7-8 days in October, indicating that the air-sea interaction can extend the prediction skill of the atmospheric model by about 1 week. The errors of both the coupled model and the atmospheric model reach saturation in about 20 days, suggesting that the predictable range is less than 3 weeks.

  1. Anomalías de circulación atmosférica en 500 y 1000 hpa asociada a la sequía producida en la Argentina durante enero de 2003 a marzo de 2004 Anomalies of the atmospheric circulation at 500 and 1000 hpa associated with the dry period in Argentina from january 2003 to march 2004

    OpenAIRE

    Adelia Perla Alessandro

    2008-01-01

    Neste trabalho se analisa e descreve a situação sinótica associada à precipitação e temperatura do território argentino durante o ano de 2003 e o primeiro trimestre de 2004. A escolha deste período obedece à falta de precipitações em pelo menos dez províncias argentinas, o que ocasionou grandes prejuízos econômicos no setor agropecuário. Com o intuito de determinar as causas deste déficit de precipitações foram analisados os campos médios de altura geopotencial nos níveis de 500 e 1000 hPa e ...

  2. Expression and clinical significance of Hpa and uPA in thyroid carcinoma%Hpa、uPA 在分化型甲状腺癌组织中表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    李建业; 鲁凯; 姚壮凯; 耿强; 张哲雄; 孙志超

    2015-01-01

    Objective To study the relationship between heparanase( Hpa) , urokinase type plasminogen activator( uPA) expression and lymph node metastasis in thyroid carcinoma.Methods Immunohistochemieal SP method was used to analyze the expression of Hpa and uPA in 113 cases of thyroid carcinoma and 134 cases of be-nign thyroid nodules.The expression of Hpa and uPA in thyroid carcinoma and its clinical significance were ana-lyzed.Results The positive expression rate of Hpa and uPA in thyroid carcinoma and benign nodular thyroid tis-sue were 82.30%,16.42%and 89.38%, 11.19%.The positive expression rate of Hpa and uPA in carcinoma tissues with lymph metastasis and without metastasis were 93.94%,100% and 65.96%,74.47%.Expression of Hpa and uPA in thyroid carcinoma group was significantly higher than that of benign thyroid nodules group( P<0.001) .The rate of positive expression in lymph metastatic tissues were significantly higher than those in tissue without metastasis( P<0.001) .Hpa and uPA expression in thyroid carcinoma tissues was positively correlated( r=0.437, P=0.021).Conclusion The expression of Hpa and uPA is closely related with the occurrence and metastasis of thyroid carcinoma.%目的:研究乙酰肝素酶( heparanase,Hpa)、尿激酶纤溶酶原激活剂( urokinase type plasmino-gen activator,uPA)在甲状腺癌组织中的表达与淋巴结转移的关系。方法采用免疫组化SP法检测113例甲状腺癌及134例良性甲状腺结节组织中Hpa、uPA蛋白的表达情况,分析Hpa、uPA蛋白在甲状腺癌中表达及其临床意义。结果 Hpa、uPA在甲状腺癌及良性甲状腺结节组织中表达阳性率分别为82.30%、89.38%和16.42%、11.19%,甲状腺癌组织中Hpa、uPA的表达高于良性甲状腺结节(P<0.001)。在甲状腺癌有、无淋巴结转移组Hpa、uPA蛋白表达阳性率分别93.94%、100%和65.96%、74.47%,甲状腺癌组织中有周围淋巴结转移组Hpa、uPA的表达高于

  3. O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

    Directory of Open Access Journals (Sweden)

    Mario F Juruena

    2004-09-01

    abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.OBJECTIVES: Changes in the hypothalamic-pituitary-adrenocortical (HPA system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR, several studies have examined the number and/or function of GRs in depressed patients. METHODS: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRF in various brain regions postulated to be involved in the causality of depression. RESULTS: This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signalling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Although the effects of antidepressants on glucocorticoid hormones and their receptors are relevant for the therapeutic action of these drugs, the molecular mechanisms underlying these effects are unclear. We propose that antidepressants in humans could inhibit steroid transporters localised on the blood-brain barrier and in neurones, like the multidrug resistance p-glycoprotein, and thus increase the access of cortisol to the brain and the glucocorticoid-mediated negative feedback on the HPA axis. CONCLUSION: Enhanced cortisol action

  4. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    Science.gov (United States)

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant.

  5. HPA-1 polymorphism of αIIbβ3 modulates platelet adhesion onto immobilized fibrinogen in an in-vitro flow system

    Directory of Open Access Journals (Sweden)

    Mihalj Mario

    2007-02-01

    Full Text Available Abstract Background Platelet adhesion and subsequent thrombus formation on a subendothelial matrix at the site of vascular damage play a crucial role in the arrest of posttraumatic bleeding but also in different pathological thrombotic events, such as acute coronary syndrome and stroke. Recently published studies have clearly demonstrated that platelet integri αIIbβ3 is intimately involved in the occlusive thrombus formation at the site of endothelial damage. Therefore, any genetic variation in the expression of this receptor may lead to an excessive bleeding or excessive thrombus formation. In this study, we evaluated the influence of HPA-1 polymorphism of integrin αIIbβ3 on platelet adhesion onto immobilized fibrinogen using an in vitro system simulating blood flow. Methods Platelets in anticoagulated whole blood [49 healthy previously genotyped blood donors were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 50 s-1, 500 s-1 and 1500 s-1. A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 sec, 1 and 5 minutes after start of perfusion. Results During perfusion, the platelet adhesion linearly increased with regard to exposition time and shear rate. Perfusion of blood preincubated with Abciximab over fibrinogen-coated cover-slips showed reduced platelet adherence (absolute fluorescence: 168 ± 35 U vs. 53000 ± 19000 at control experiments, p Conclusion Our data support the contention that genetically determined variants of platelet integrins αIIbβ3 could play a role in arterial thrombogenesis and thus confirm the hypothesis derived from epidemiological studies.

  6. Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

    Science.gov (United States)

    Jiang, Sunny Zhihong; Eiden, Lee E

    2016-07-01

    We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

  7. Analysis of Genetic Polymorphism in Randomized Donor's HPA 1-16 Antigens and Establishment of Typed Platelet Donor Data Bank%献血者血小板1-16抗原基因遗传多态性分析及已知HPA型供者数据库的建立

    Institute of Scientific and Technical Information of China (English)

    孙国栋; 段现民; 张彦平; 尹志柱; 牛小利; 李艳凤; 牛海江; 赵有良

    2005-01-01

    本研究的目的是分析人类血小板抗原(human platelet antigen,HPA)基因多态性,根据分布频率来判断HPA抗原不配合比率以及抗体产生的机会,确定有临床意义的血小板抗原系统,并建立邯郸地区血小板基因频率数据库和供者库.采用SSP-PCR方法对邯郸地区148名随机献血者进行HPA1-16抗原32个等位基因的检测分析,并与不同人群的分布频率进行比较.结果表明:每个样本均检测到HPA-1a、2a、4a-14a、16a基因;HPA-4a、7a-14a、16a呈现单态性,未检测出相应的等位基因HPA-b;对于HPA-1、-2、-5、-6主要以a/a纯合子为多,a/a基因型频率分别是0.9595、0.8108、0.9865、0.9797,没有b/b纯合子出现.在HPA1-16中,具有最高杂合度的是HPA-15,基因型HPA15a/15a、HPA15a/15b、HPA15b/15b频率分别是0.2230、0.5270、0.2500;HPA-3在其次,基因型HPA3a/3a、HPA3a/3b、HPA3b/3b频率分别是0.3851、0.5135、0.1014.经x2检验,结果符合Hardy-Weinberg遗传平衡定律.邯郸地区随机献血者HPA1-5系统基因频率与石家庄地区相似(P>0.05);与我国台湾人群进行HPA1-13、HPA-15的比较,HPA-1、-2、-6具有明显的不同(P<0.05),其它相似(P>0.05);与韩国人群进行HPA1-8的比较,除HPA-3具有明显不同外(P<0.05),其余均相似(P>0.05);与美国黑人进行HPA1-5的比较,HPA-1、-2、-5具有明显的差异(P<0.05);与英国人进行HPA1-11的比较,HPA-1、-5具有明显的不同(P<0.05).结论:北方地区中国人群HPA-2、-3、5、-15系统具有多态性,且HPA抗原分布不配合比率较高,这必然造成免疫暴露的机会增加,提示在临床上可能具有重要的免疫学意义.同时,在此次研究数据的基础上建立了邯郸地区血小板基因频率数据库和血小板已知型供者库.

  8. NF-κB和HPA在口腔鳞状细胞癌中的表达及意义%Expression and significance of NF-κB and HPA in oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴祥冰; 王荣艳; 田涛; 徐佳; 朱声荣

    2011-01-01

    目的:应用组织微阵列技术,检测口腔鳞癌中核转录因子KB(NF-κB)和乙酰肝素酶(HPA)的表达,探讨两者之间的关系及其临床意义.方法:应用组织微阵列技术和免疫组化方法,检测146例口腔鳞癌、48例正常口腔黏膜中NF-KB和HPA的表达.应用SPSS13.0软件包对数据进行χ2检验和Spearman相关分析.结果:NF-KB和HPA在口腔鳞癌中的阳性表达率分别为69.2%和63.7%,显著高于正常口腔黏膜组(P<0.05).NF-κB和HPA在口腔鳞癌中的表达与肿瘤的分化程度、临床分期和有无区域淋巴结或远处转移相关(P<0.05),而与患者性别、年龄、肿瘤发生部位无关(P>0.05).NF-κB的表达与HPA的表达呈正相关(r=0.7301,P<0.05).结论:NF-κB与HPA协同作用.促进口腔鳞癌的发生、发展.%PURPOSE: To detect the expression of NF-κB and HPA in oral squamous cell carcinoma (OSCC) by tissue microarray assay and investigate their clinical significance. METHODS: Tissue microarray assay and immunohistochemistry were applied to detect the expression of NF-κB and HPA in 146 cases of OSCC and 48 cases of normal control. Chisquare test and Spearman rank correlation were performed using SPSS 13.0 software package for statistics. RESULTS:The positive rates of NF-κB and HPA were 69.2% and 63.7% ,respectively.There was significant difference compared with normal oral mucosa (P<0.05). The expression of NF-κB and HPA in OSCC was significantly correlated with histological differentiation, clinical stage and lymph node or distant metastasis (P<O.05), but not with sex and age of the patients or site of the tumor (P>0.05).The expression of NF-κB had a significant positive correlation with the expression of HPA in OSCC (r=0.7301,P<0.05). CONCLUSION: The expression of NF-κB and HPA may have synergistic effect on the carcinogenesis and progression of OSCC.

  9. PCR直接测序法检测人类血小板抗原HPA-1~-17bW基因型的探讨%Study on human platelet antigen -1~-17bw genotyping by PCR sequencing based typing methods

    Institute of Scientific and Technical Information of China (English)

    申卫东; 廖燕; 何保仁; 李丽兰; 赵桐茂; 吴国光

    2010-01-01

    目的:建立人类血小板抗原(Human platelet antigen,HPA)基因系统PCR扩增产物直接测序的方法并对序列进行分析.方法:PCR扩增HPA-1~-17bw基因片段,将PCR扩增产物纯化后直接进行DNA序列测定.结果:聚合酶链式反应-序列特异性引物(PCR-SSP)和直接测序法(SBT)对HPA已知型的血小板供者常见和罕见的HPA-1bb、HPA-2bb和HPA-6bb纯合子等供者的分型结果是一致的.结论:成功建立人类血小板抗原HPA1-17bw基因系统的PCR直接测序方法,能够准确可靠地鉴定HPA多态性,并能进一步应用于血小板免疫学和人类遗传学研究.

  10. 中国牡丹江地区献血人群HPA基因分布特征的研究及数据库的建立%HPA Distribution Characteristics of Platelet Donor Population in Mudanjiang Area of China and Establishment of Its Database

    Institute of Scientific and Technical Information of China (English)

    刘丙现; 刘杰; 高广平; 王丹; 张彦; 于秀清; 夏冬梅; 周锐华; 郑华; 马嫱

    2012-01-01

    This study was aimed to explore the distribution characteristics of the human platelet antigen (HPA) gene of human platelet donors and its polymorphism in Mudanjiang area of Heilongjiang Province in China, to determine platelet antigen system with clinical significance by judging the rate of incompatibility of HPA, as well as to establish a database of donors'HPA. The genotyping of 154 unrelated platelet donors was performed by means of PCR-SSP. The frequencies of gene and genotype were calculated and compared with that in other areas. The results showed that the genes la - 17a of HPA-a were all expressed in the 154 healthy and unrelated platelet donors. Only genes 1b, 2b,3b,5b, 6b and 15b of HPA-b were expressed while genes 4b, 7b - 14b, 16b were not expressed. Among the genotypes, aa homozygosity was predominant and HPAI5 had the greatest heterozygosity, while HPA3 had lower heterozygosity. There were 23 combined types of HPA, 5 of them had a rate higher than 10% , and the frequencies of the other 18 were lower than 8%. HPA genotype frequencies showed a good consistence to Hardy-Weinberg equilibrium. It is concluded that the distribution of the allele polymorphism of HPAI ~HPA17 in Mudanjiang area has its own characteristics, compared with other areas and some countries, the local HPA genotype database of platelet donors is established in Mudanjiang area, which can provide the matching donors for clinical use with immunological significance.%本研究旨在探讨中国牡丹江地区献血人群HPA基因及其多态性分布特征,判断HPA抗原不配合比率,确定有临床意义的抗原系统,建立已知HPA基因型血小板献血者数据库.采用PCR- SSP方法对154名无血缘关系的献血者做HPA基因分型,计算基因频率与基因型频率,并与国内外不同人群进行比较.结果表明,154名健康、无血缘关系的献血者均表达出HPA-a基因中的1a -17a基因;仅表达HPA-b基因中的1b、2b、3b、5b、6b和15b,未表达HPA4

  11. Expression of HPA in human astrocytoma and its effects on invasiveness of tumor cells%脑星形细胞瘤中HPA的表达及其对肿瘤细胞侵袭力的影响

    Institute of Scientific and Technical Information of China (English)

    刘宏雷; 易力; 翟晓莉

    2016-01-01

    Objective To investigate the expression of heparanase ( HPA) in human astrocytoma and its effects on invasiveness of tumor cells .Methods The expression levels of HPA were detected by immunohistochemical assay and Real time-PCR in 75 cases of human astrocytoma tissues and 40 cases of normal brain tissues .The small interfering RNA (siRNA) knockdown technique was used to silence the expressions of PHA protein and mRNA in astrocytoma U 87 cells.The expression levels of HPA,vascular endothelium growth factor (VEGF), matrix metalloproteinases-9 (MMP) as well as the changes of invasiveness of tumor cells were detected by Real time-PCR, Western Blot and Transwell assay .Results The expressions of PHA were not observed in normal brain tissues .The positive expression rate of HPA protein was 78.67%(59/75) in astrocytoma tissues, which was significantly higher than that [0(0/40)] in normal brain tissues ( P <0.05), moreover, the positive expression rate of HPA mRNA was significantly higher than that in normal brain tissues ( P <0.05). The positive expression rate of HPA at gradeⅡ~Ⅳof astrocytoma was gradually increased ,and the positive rate was 60.00%(15/25), 79.31% (23/29), 90.48% (19/21),respectively,and there was a significant difference among them ( P <0.05).Furthermore the positive expression rate of HPA in tumor metastasis group was significantly higher than that in non-metastasis group ( P <0.05).The siRNA could effectively inhibit the expressions of HPA in U 87 cells and could down-regulate the expressions of VEGF , MMP-9, at the same time, which could obviously decrease the cell counts of permeating cell membrane ( P <0.05).Conclusion The high-expressions of HPA exist in astrocytoma tissues ,moreover, which are gradually increased with the malignant degree of tumor .The invasiveness of tumor cells is obviously decreased afterHPA is silenced by siRNA ,thus,PHA may become a potential target point in treatment of astrocytoma .%目

  12. HPA axis gene expression and DNA methylation profiles in rats exposed to early life stress, adult voluntary ethanol drinking and single housing

    Directory of Open Access Journals (Sweden)

    Aniruddha eTodkar

    2016-01-01

    Full Text Available The neurobiological basis of early life stress (ELS impact on vulnerability to alcohol use disorder is not fully understood. The effect of ELS, adult ethanol consumption and single housing, on expression of stress and DNA methylation regulatory genes as well as blood corticosterone levels was investigated in the hypothalamus and pituitary of adult out-bred Wistar rats subjected to different rearing conditions. A prolonged maternal separation of 360 min (MS360 was used to study the effect of ELS, and a short maternal separation of 15 min (MS15 was used as a control. Voluntary ethanol drinking was assessed using a two-bottle free choice paradigm to simulate human episodic drinking. The effects of single housing and ethanol were assessed in conventional animal facility rearing (AFR conditions.Single housing in adulthood was associated with lower Crhr1 and higher Pomc expression in the pituitary, whereas ethanol drinking was associated with higher expression of Crh in the hypothalamus and Crhr1 in the pituitary, accompanied by lower corticosterone levels. As compared to controls with similar early life handling, rats exposed to ELS displayed lower expression of Pomc in the hypothalamus, and higher Dnmt1 expression in the pituitary. Voluntary ethanol drinking resulted in lower Fkbp5 expression in the pituitary and higher Crh expression in the hypothalamus, independently of rearing conditions. In rats exposed to ELS, water and ethanol drinking was associated with higher and lower corticosterone levels, respectively,. The use of conventionally reared rats as control group yielded more significant results than the use of rats exposed to short maternal separation.Positive correlations, restricted to the hypothalamus and ELS group, were observed between the expression of the HPA receptor and the methylation-related genes. Promoter DNA methylation and expression of respective genes did not correlate suggesting that other loci are involved in

  13. 血小板膜糖蛋白Ⅱb HPA-3基因多态性与中国汉族人缺血性卒中的相关性%Correlation between platelet membrane glycoprotein Ⅱb HPA-3 polymorphism and ischemic stroke in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    王栋梁; 孙岩; 李新; 韩瑞发; 王林; 王纪佐

    2013-01-01

    Objective To investigate the distribution of glycoprotein (GP) Ⅱ b HPA-3 polymorphism in Chinese Han population in Tianjin and its correlation with ischemic stroke.Methods The patients in this study were divided into either a ischemic stroke group (n =150) or a control group (n =135).Genotyping was conducted by using polymerase chain reaction-restriction fragment length polymorphism and was verified by sampling sequencing Each genotype and allele frequency distribution and its correlation with ischemic stroke were compared.Results The ab genotype,bb genotype and b allele frequency in the patient group were significantly higher than those in the control group (P =0.000),while aa genotype and a allele frequency were significantly lower than those in the control group (P =0.000).There were no significant differences in the frequencies of GPⅡ b genotype and b allele between the different gender and the age groups in the patient group.Although there were no significant differences in genotype frequencies between all etiologic subtypes,b allele frequency in the large artery atherosclerotic stroke subgroup was significantly higher than that in the small vascular occlusive stroke subgroup and that in the cardioembolism subgroup (61.8% vs.46.7% vs.47.5% ;x2 =6.573,P =0.037).Multivariate logistic regression analysis showed that hypertension (odds ratio [OR] 7.475,95% confidence interval [CI]3.700-15.003; P =0.000) and b allele (OR 3.678,95% CI 1.245-10.863; P =0.018) were the independent risk factors for ischemic stroke.Conclusions GP Ⅱ b HPA-3 polymorphism may be associated with the risk of ischemic stroke onset.Carrying b allele may be an independent risk factor for ischemic stroke,especially large artery atherosclerotic stroke.%目的 探讨天津市汉族人群血小板膜糖蛋白(glycoprotein,GP)Ⅱb HPA-3基因多态性的分布情况及其与缺血性卒中的关系.方法 缺血性卒中组150例,对照组135例,应用聚合酶链反应-限制性内

  14. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis.

    Science.gov (United States)

    Liu, Hua; Wang, Yi; Zheng, Jian; Li, Guangming; Chen, Tao; Lei, Jianguo; Mao, Yiting; Wang, Jun; Liu, Wei; Zhao, Ge; Tacey, Mark; Yan, Bernard

    2017-01-01

    Background/aims Platelet glycoproteins play a crucial role in the initial stage of thrombus formation and may contribute to the pathophysiology of atherosclerosis. Polymorphisms in glycoprotein genes alter the function of the protein, possibly leading to increased risk of ischemic stroke. However, previous genetic association studies that examined the relationship between glycoprotein genes polymorphisms and ischemic stroke have yielded inconsistent results. This study aimed to evaluate the association between glycoprotein genes and ischemic stroke by the application of meta-analysis. Methods Relevant studies were identified by an extensive search through databases. The quality of included studies was assessed independently using the Newcastle-Ottawa Scale. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and a meta-regression model was used to explore the study-level variables and to describe the heterogeneity in included studies. Egger's test and funnel plot were used to assess publication bias. Results A total of 60 studies (9 polymorphisms) were included and identified in the current meta-analysis. The Newcastle-Ottawa Scale scores ranged from 7 to 9 except for two studies with Newcastle-Ottawa Scale scores of 6. The T allele or TT genotype of the glycoprotein Ia C807T polymorphism were associated with an increased susceptibility to ischemic stroke in combined population (807T allele: OR, 95%CI: 1.24, 1.03-1.50, p = 0.02) or Asian populations (807T allele: OR, 95%CI: 1.31, 1.10-1.54, p = 0.002 and 807TT genotype: OR, 95%CI: 1.53, 1.13-2.08, p = 0.006, respectively), and the Ser allele of HPA-3 was associated with increased risk of ischemic stroke in combined population or in Asians (OR, 95%CI: 1.21, 1.04-1.40, p = 0.01 or 1.54, 1.18-2.01, p = 0.001). Of

  15. Effects of lactose as an inducer on expression of Helicobacter pylori rUreB and rHpaA,and Escherichia colirLTKA63 and rLTB

    Institute of Scientific and Technical Information of China (English)

    Jie Yan; Shou-Feng Zhao; Ya-Fei Mao; Yi-Hui Luo

    2004-01-01

    AIM: To demonstrate the effect of lactose as an inducer on expression of the recombinant proteins encoded by Helicobacter pylori ureB and hpaA, and Escherichia coli LTB and LTKA63 genes and to determine the optimal expression parameters.METHODS: By using SDS-PAGE and BIO-RAD gel image analysis system, the outputs of the target recombinant proteins expressed by pET32a-ureB-E. coliBL21, pET32ahpaA-E. coliBL21, pET32a-L TKA63-E. coliBL21 and pET32aLTB-E.coliBL21 were measured when using lactose as inducer at different dosages, original bacterial concentrations,various inducing temperatures and times. The results of the target protein expression induced by lactose were compared to those by isopropyl-β-D-thiogalactoside (IPTG).The proteins were expressed in E.coli.RESULTS: Lactose showed higher efficiency of inducing the expression of rHpaA, rUreB, rLTB and rLTKA63 than IPTG. The expression outputs of the target recombinant proteins induced at 37 ℃ were remarkably higher than those at 28 ℃. Other optimal expression parameters for the original bacterial concentrations, dosages of lactose and inducing time were 0.8, 50 g/L and 4 h for rHpaA; 0.8, 100 g/L and 4 h for rLTKA63; 1.2, 100 g/Land 5 h for both rUreB and rLTB, respectively.CONCLUSION: Lactose, a sugar with non-toxicity and low cost, is able to induce the recombinant genes to express the target proteins with higher efficiency than IPTG. The results in this study establish a beneficial foundation for industrial production of H pylori genetic engineering vaccine.

  16. Prediction of glycolipid-binding domains from the amino acid sequence of lipid raft-associated proteins: application to HpaA, a protein involved in the adhesion of Helicobacter pylori to gastrointestinal cells.

    Science.gov (United States)

    Fantini, Jacques; Garmy, Nicolas; Yahi, Nouara

    2006-09-12

    Protein-glycolipid interactions mediate the attachment of various pathogens to the host cell surface as well as the association of numerous cellular proteins with lipid rafts. Thus, it is of primary importance to identify the protein domains involved in glycolipid recognition. Using structure similarity searches, we could identify a common glycolipid-binding domain in the three-dimensional structure of several proteins known to interact with lipid rafts. Yet the three-dimensional structure of most raft-targeted proteins is still unknown. In the present study, we have identified a glycolipid-binding domain in the amino acid sequence of a bacterial adhesin (Helicobacter pylori adhesin A, HpaA). The prediction was based on the major properties of the glycolipid-binding domains previously characterized by structural searches. A short (15-mer) synthetic peptide corresponding to this putative glycolipid-binding domain was synthesized, and we studied its interaction with glycolipid monolayers at the air-water interface. The synthetic HpaA peptide recognized LacCer but not Gb3. This glycolipid specificity was in line with that of the whole bacterium. Molecular modeling studies gave some insights into this high selectivity of interaction. It also suggested that Phe147 in HpaA played a key role in LacCer recognition, through sugar-aromatic CH-pi stacking interactions with the hydrophobic side of the galactose ring of LacCer. Correspondingly, the replacement of Phe147 with Ala strongly affected LacCer recognition, whereas substitution with Trp did not. Our method could be used to identify glycolipid-binding domains in microbial and cellular proteins interacting with lipid shells, rafts, and other specialized membrane microdomains.

  17. The evaluation of the 500 hPa geopotential height′s main modes in East Asia as done by the CMIP5 models%CMIP5模式对东亚500 hPa 高度场主要模态时空结构模拟能力的评估

    Institute of Scientific and Technical Information of China (English)

    黄海玲; 江志红; 王志福; 陈威霖

    2015-01-01

    Based on the 1961-2005 monthly 500 hPa geopotential height data from the Nation Center for Environmental Pre-diction (NCEP),this paper evaluates the winter′s and summer′s 500 hPa geopotential height in East Asia (EA)as are simula-ted by the 39 climate models in the the Phase 5 of the Coupled Model Intercomparison Project (CMIP5)historical simulation experiment.The Empirical Orthogonal Function (EOF),Taylor figures,Probability Density Functions (PDFs)and two as-sessment indicators have been used to find the models which are better in simulating the winter and summer circulation modes in EA.The results show that:(1)The models considered are able to simulate reasonably the main modes in both winter and sum-mer,especially winter.(2)IPSL-CM5B-LR,MPI-ESM-P,CMCC-CMS,FGOALS-g2 and HadGEM2-ES are the models bet-ter at reproducing the winter′s spatial structures,while ECEARTH,CanESM2,CMCC-CM,GFDL-ESM2G and IPSL-CM5A-MR are better at reproducing the summer′s spatial structures.It′s found that all the models considered are able to simulate rea-sonably these main modes with Western Pacific (WP)being the mode which is best spatially simulated and,the third mode be-ing worst in the winter,but the first mode being the mode which is best spatially simulated with WP being worst in the sum-mer.(3)From a temporal point of view,it is found that of all the modes for the winter the second mode simulations are best, then is WP,while for the summer the second mode also is simulated best,then are EAP and WP.CESM1-FASTCHEM,HadGEM2-ES,INM-CM4,GISS-E2-H and BCC-CSM1-1 are better at reproducing winter′s PDF and CCSM4,HadGEM2-CC,GFDL-CM3, MRI-CGCM3,NorESM1-M are better at reproducing summer′s.And,(4)considering of spatial and temporal structures,HadGEM2-ES,IPSL-CM5B-LR,CESM1-FASTCHEM,INM-CM4 and BCC-CSM1-1 are better than the other 34 models for the winter,and ECEARTH,CMCC-CM,CCSM4,CANESM2 and MIROC5 are better for the summer.%利用第5次耦合模式比较计划(CMIP5

  18. Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.

    Science.gov (United States)

    Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

    2017-01-01

    Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27-53, UreA183-203, HpaA132-141, and HSP60189-203), and also the epitope-rich regions of urease B subunit (UreB158-251 and UreB321-385) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158-172, UreB181-195, UreB211-225, UreB349-363, HpaA132-141, and HSP60189-203). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4(+) T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori. These results indic ate that a multivalent epitope

  19. Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    Le Guo

    2017-08-01

    Full Text Available Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP, heat shock protein 60 (HSP60 and H. pylori adhesin A (HpaA was constructed based on mucosal adjuvant cholera toxin B subunit (CTB, Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203, and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385 predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203. In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell response, IgG, and secretory IgA (sIgA antibodies to H. pylori. These results indic

  20. Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

    Science.gov (United States)

    Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

    2017-08-29

    Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4(+) T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

  1. Inhibitive Effect of Polypeptide Extract from Scorpion Venom (PESV) on the Expression of HPA and VEGF in SKOV3 Cell Lines*%蝎毒多肽提取物对卵巢癌SKOV3细胞HPA与VEGF抑制作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    李晓辉; 张维东; 王兆朋; 张月英; 贾青; 王朝霞

    2012-01-01

    Objective: To investigate the effect of polypeptide extract ftom scorpion venom(PESV) on the expression of HPA and VEGF in SKOV3 cell lines, and to explore the antiangiogenic mechanisms. Methods: SKOV3 cells were divided into control group and PESV group. Immohistochemistry was performed to determine the expression of HPA and VEGF in each group .Western-blot was used to detect the protein expression of HPA. Results: Compared with that in the control group, the expression of HPA and VEGF was significantly downregulated in PESVgroup, and the amount of HPA on protein level reduced significantly. Conclusions: PESV can inhibit the growth of SKOV3 cells, and the mechanism is probably related with the inhibition of the expression of HPA and VEGF.%目的:研究蝎毒多肽提取物(polypeptide extract from scorpion venom,PESV)对卵巢癌SKOV3细胞HPA与VEGF表达的影响,进一步探讨其抗血管生成的分子机制.方法:卵巢癌SKOV3细胞分为对照组、PESV组,免疫组织化学方法检测各组HPA、VEGF的表达,western-blot方法检测各组HPA在蛋白水平的表达.结果:与对照组相比,PESV组HPA、VEGF表达明显降低(P<0.05),进一步检测发现PESV组HPA在蛋白水平表达亦明显下调(P<0.05).结论:PESV能够抑制卵巢癌SKOV3细胞的生长,其机制可能与抑制HPA、VEGF的表达有关.

  2. Studies on HPA gene donor registry for platelet transfusion refractoriness in Xinxiang area%新乡地区HPA基因分型供者库在免疫性血小板输注无效中的应用研究

    Institute of Scientific and Technical Information of China (English)

    庞桂芝; 张趁利; 别立莉; 孙学兰; 娄白敏; 高吴双; 申家辉; 赵凤莲

    2015-01-01

    目的 建立新乡地区已知HPA-1-18基因型的无偿机采血小板供者库,为临床血小板输注无效(PRT)患者提供HPA相合的血小板,方法 建立PCR-SSP检测HPA-1-18基因型检测方法;采用固相凝集法对52名PRT患者,做血小板同种抗体筛查;应用HLA抗体特异性试剂盒检测患者血清群体反应性抗体;对血小板同种抗体筛查阳性患者,采用已知HPA基因型的标准谱血小板傲抗体鉴定,并对其进行HPA基因分型;采取HPA抗体无对应抗原的供者血小板进行输注.结果 成功检测出150名无偿血小板捐献者HPA-1-18基因型.在52例PRT病例中,检出血小板同种抗体23例(阳性率44%),其中5例鉴定为抗-HPA (21.7%),分别为HPA-3a 2例;HPA-15b 3例;其余HLA抗体阳性18例.结论 对PRT患者采用HPA基因型相合的方法进行输注取得临床效果.

  3. 新疆汉族人群血小板抗原1-5、15系统基因多态性分析%Analysis on the genetic polymorphism of Human Platelet Antigen (HPA) 1-5 and 15 systems in Xinjiang Hart Chinese

    Institute of Scientific and Technical Information of China (English)

    左宏莉; 纳斯尔阿吉·买买提艾力; 郭伟鹏; 卢申; 金琼华; 黄鑫淼; 张志欣; 吐尔洪·克雏尔

    2009-01-01

    目的 调查研究与血小板输注无效关系密切的人类血小板抗原(human platelet antigen,HPA)1-5及15系统基因在新疆汉族人群中的遗传多态性.方法 采用聚合酶链一序列特异性引物(PCR.SSP)法对101例无血缘关系的新疆汉族血样进行HPA基因分型.结果 新疆汉族HPA-1a、2a、3a、4a、5a、15a基因频率分别是0.985 1、0.920 8、0.544 6、1、0.950 5、0.465 3,HPA-1b、2b、3b、4b、5b、15b基因频率分别是0.014 9、0.079 2、0.455 4、0、0.0495、0.534 7,新疆汉族HPA基因频率与维吾尔族人群相比,HPA-1a、1b基因频率差异具有统计学意义(P<0.05).结论 HPA-1、2、3、5、15系统均具有多态性,HPA-3、15系统具有高度多态性.

  4. THE SECULAR TREND VARIATIONS AND ABRUPT CHANGE OF NORTHERN 500 hPa GEOPOTENTIAL HEIGHT%北半球500 hPa高度场趋势变化与突变

    Institute of Scientific and Technical Information of China (English)

    陈辉; 施能; 王永波

    2000-01-01

    The trends and abrupt variations of Northern hemisphere (NH) 500 hPa seasonal geopotential height are examined using the data for the period 195l~1998. Evidence suggests that low (high) latitude 500 hPa geopotential height displays a remarkably positive (negative) trend; the positive anomaly of the height is maintained over NW Africa, the western Mediterranean Sea and northern North Africa, mid-Pacific at lower latitudes, Lake Baikal and area to the east and NW North America; the height drops significantly over the Aleutians and North pacific, the area to the south of the Greenland and NE North America and the sector to the north of the Arabian sea. Further, analysis of abrupt change shows that the 500 hPa circulations experience noticeable sudden change twice, once around the early 1960s and again in 1976, during which, however, the height exhibits great difference between the Pacific and Atlantic. In the first case it drops (rises) over the mid Atlantic at lower latitudes (NW Africa) in contrast to the height rise (drop) over the mid-Pacific at lower latitudes and Lake Baikal (the North Pacific) in the second abruptness. Statistical test indicates that in the 1976 case the low-latitude positive abrupt change is even more noticeable compared to the negative of the North pacific, thus representing a large-scale jumping event of the northern 500 hPa height.%用1951~1998年的资料研究了北半球500 hPa四季高度场的长期趋势变化。结果表明。48年来低纬度500 hPa高度场多为正趋势而高纬度则多为负趋势。近48年低纬的西北非洲、地中海及以西的北非北部,低纬度的中太平洋、贝加尔湖及以东地区,西北北美的高度呈持续正趋势;而阿留申及北太平洋、格林兰以南及东北北美、阿拉伯海以北高度明显降低。突变分析表明,大约60年代初及1976年。500 hPa发生明显的环流突变。这两次变化在两大洋上的500 hPa有明显不同,第1次表现为

  5. Anomalías de circulación atmosférica en 500 y 1000 hpa asociada a la sequía producida en la Argentina durante enero de 2003 a marzo de 2004

    OpenAIRE

    Alessandro, Adelia Perla

    2008-01-01

    Neste trabalho se analisa e descreve a situação sinótica associada à precipitação e temperatura do território argentino durante o ano de 2003 e o primeiro trimestre de 2004. A escolha deste período obedece à falta de precipitações em pelo menos dez províncias argentinas, o que ocasionou grandes prejuízos econômicos no setor agropecuário. Com o intuito de determinar as causas deste déficit de precipitações foram analisados os campos médios de altura geopotencial nos níveis de 500 e 1000 hPa e ...

  6. Effect of Paroxetine on HPA Axis in Type 2 Diabetes Mellitus Patients with Depression%帕罗西汀对2型糖尿病并发抑郁患者HPA轴的影响

    Institute of Scientific and Technical Information of China (English)

    李杰

    2013-01-01

    [Objective]To explore the effect of paroxetine on hypothalamic-pituitary-adrenal(HPA) axis function in type 2 diabetic patients with depression.[Results] Totally 70 type 2 diabetic patients with depression were randomly divided into the observation group and the control group with 35 cases in each.The control group was given conventional therapy of diabetes mellitus,while the observation group was given paroxetine treatment on the basis of the treatment of control group.After 8 weeks of treatment,blood glucose control and depressive symptoms in two groups before and after treatment were observed.HPA axis of corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH) and cortisol(Cor) levels were detected.[Results]Compared before the treatment,fasting plasma glucose(FPG),2h postprandial glucose (2hPG) and Hamilton depression scale(HAMD) score in two groups obviously decreased(P <0.05 or P <0.01).The observation group was better than the control group(P <0.05).Compared with before the treatment,plasma levels of CRH,ACTH and Cor in observation group obviously decreased(P <0.05),but there was no significant difference between the observation group and control group(P <0.05).[Conclusion]Paroxetine can effectively improve blood sugar levels in type 2 diabetic patients with depression and relieve depression.Its mechanism of action may be related to the regulation of HPA axis.%[目的]探讨帕罗西汀对2型糖尿病(T2DM)并发抑郁患者下丘脑-垂体-肾上腺(HPA)轴功能的影响.[方法]将70例T2DM抑郁症患者随机分为观察组和对照组各35例.对照组给予糖尿病常规治疗,观察组在对照组基础上联用帕罗西汀治疗;用药8周后观察两组患者治疗前后血糖控制及抑郁症状改善情况,并检测HPA轴中促肾上腺皮质激素释放激素(CRH)、肾上腺皮质激素(ACTH)及皮质醇(Cor)水平变化.[结果]两组患者空腹血糖(FPG)、餐后2h血糖(2hPG)水平及汉密尔顿抑郁量

  7. Inhibitory effect of siRNA on HPA gene expression in SKOV3 cells%siRNA抑制卵巢癌细胞株SKOV3 HPA基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    辛晓燕; 毛敬; 刘玉; 于月成; 李萍

    2006-01-01

    目的: 研究siRNA对卵巢癌细胞株SKOV3中乙酰肝素酶(heparanase,HPA)基因表达的抑制作用.方法: 设计合成两对HPA编码基因的反向重复序列,中间间隔9个核苷酸序列,通过定向克隆至载体PGenesil-1,构建siRNA真核表达载体,经稳定转染SKOV3细胞后应用RT-PCR、real-time PCR及免疫组化技术检测卵巢癌细胞中HPA基因mRNA及蛋白表达水平的抑制情况.结果: 测序证实成功地构建了编码2条shRNA的siRNA真核表达载体.通过RT-PCR、real-time PCR及免疫组化技术检测转染siRNA的SKOV3细胞,与对照组相比,HPA mRNA表达水平和蛋白表达水平明显降低.结论:构建的PGenesil-1(+)-HPA重组质粒能有效的抑制HPA基因在卵巢癌细胞株SKOV3中的表达,为研究HPA基因在肿瘤细胞中的调节途径和肿瘤的基因治疗提供了新的方法.

  8. Study on the Polymorphism of HPA-15 in Hans From Shandong Province of China%中国山东地区汉族人群血小板特异性抗原-15基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    朱传福; 王玫; 刘艳; 张萍; 宋永红; 聂向民

    2006-01-01

    血小板表面具有复杂的血型抗原,一类为ABO血型抗原和HLA血型抗原;另一类为血小板特异性抗原(Human Platelet Antigen,HPA),表现血小板独特的遗传多态性。HPA-15是1990年Kelton等报道的一个新血小板抗原系统,它首先被发现于不相合的输血患者,随后又在新生儿同种免疫血小板减少症患者中发现,2003年命名为血小板特异性抗原-15。目前,仅有关于其他种族HPA-15基因分布的报道。本研究采用PCR-SSP基因分型方法,对108例无血缘关系汉族人HPA-15系统进行基因分型,调查中国山东地区汉族人HPA-15基因多态性,报告如下。

  9. Analysis on the genetic polymorphism of human platelet antigen (HPA)1~5 and 15 systems in Uighurs%维吾尔族血小板抗原1~5、15系统基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    吐尔洪·克维尔; 左宏莉; 方春富; 杨勇; 文国新

    2006-01-01

    目的:调查研究与血小板输注无效关系密切的人类血小板抗原(human platelet antigen,HPA)1~5及15系统基因在维吾尔族人群中的遗传多态性;分析民族差异,确定各系统临床意义,从而建立已知基因型血小板供者库.方法:采用聚合酶链-序列特异性引物技术(PCR-SSP)对153例无血缘关系的纯维吾尔族血样进行了HPA基因分型.结果:维吾尔族HPA-1a、2a、3a、4a、5a、15a基因频率分别是 0.911 8、0.888 9、0.545 8、0.993 5、0.921 6、0.441 2,维吾尔族HPA-1b、2b、3b、4b、5b、15b基因频率分别是0.088 2、0.111 1、0.454 2、0.006 5、0.078 4、0.558 8,维吾尔族HPA基因频率与汉族人群相比,HPA-1a、1b、3a、3b、5a、5b基因频率差异具有统计学意义(P<0.05);与西藏藏族人群相比,HPA- 3a、3b、5b基因频率差异具有统计学意义(P<0.05).结论:维吾尔族人群中HPA1~5、15系统12个等位基因都可以检测到.在不同的个体中它们以纯合子或杂合子状态表达,但未检测到纯合子1b或纯合子4b型个体.HPA- 1、2、3、4 、5、15系统均具有多态性,其中HPA-3、15系统具有高度多态性,这使免疫暴露的机会增加.维吾尔族人群与汉族人群的HPA-1a、1b、3a、3b、5a、5b基因频率存在明显差异,与藏族人群的HPA- 3a、3b、5b基因频率存在明显差异.

  10. 广西瑶族人群血小板膜糖蛋白ⅠbαHPA-2基因多态性及其临床意义%Genetic Polymorphism and Clinical Significance of Human Platelet Antigen-2 in Platelet Membrane Glycoprotein Ⅰ bα of Yao Minority Population in Guangxi Zhuang Autonomous Region

    Institute of Scientific and Technical Information of China (English)

    廖燕; 申卫东; 李丽兰; 周先果; 何保仁; 刘金莲; 黄惠妮

    2014-01-01

    目的 探讨广西瑶族人群血小板膜糖蛋白(GP)Ⅰ bα人类血小板抗原(HPA)-2基因多态性及其临床意义.方法 2009年3月至2010年5月,选择广西瑶族健康成年人883例为研究对象,采集其血液样本,采用聚合酶链反应-序列特异性引物(PCR-SSP)法对其HPA基因分型进行检测.采集样本前均经受试对象本人的知情同意,并与之签订临床研究知情同意书.结果 本组883份血液样本中,HPA-2a/2a,HPA-2a/2b及HPA-2b/2b的基因型频率分别为0.763 3,0.218 6和0.018 1.HPA-2a与HPA-2b的等位基因频率分别为0.872 6与0.127 4,与大部分欧洲国家研究的基因型频率相似,但与中国汉族和东南亚人相比,差异较大.本组883份血样中,发现1例罕见HPA-2b/2b 482T/T突变.结论 本研究明确了广西瑶族人群主要血小板GP Ⅰ ba多态性的特征,可为将来研究血小板GPⅠbα在个体易感血栓性疾病和抗血栓治疗提供重要参考依据,更好地应用于理解和治疗免疫介导的血小板疾病.%Objective To investigate the genetic polymorphism and clinical significance of human platelet antigen (HPA)-2 in platelet membrane glycoprotein (GP) Ⅰ bα in Yao minority population of Guangxi Zhuang Autonomous Region.Methods From March 2009 to May 2010,a total of 883 healthy adults from Yao minority in Guangxi Zhuang Autonomous Region were randomly selected into the study and their blood samples were collected.HPA