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Sample records for activation syndrome mas

  1. [Hepatic manifestation of a macrophage activation syndrome (MAS)].

    PubMed

    Nagel, Michael; Schwarting, Andreas; Straub, Beate K; Galle, Peter R; Zimmermann, Tim

    2017-04-04

    Background Elevated liver values are the most common pathological laboratory result in Germany. Frequent findings, especially in younger patients, are nutritive- or medicamentous- toxic reasons, viral or autoimmune hepatitis. A macrophage activation syndrome (MAS) may manifest like a viral infectious disease with fever, hepatosplenomegaly and pancytopenia and is associated with a high mortality. It is based on an enhanced activation of macrophages with increased cytokine release, leading to organ damage and multi-organ failure. In addition to genetic causes, MAS is commonly associated with infections and rheumatic diseases. We report the case of a 26-year-old female patient suffering from MAS as a rare cause of elevated liver enzymes. Methods Patient characteristics, laboratory values, liver histology, bone marrow and radiological imaging were documented and analyzed. Case Report After an ordinary upper airway infection with bronchitis, a rheumatic arthritis appeared and was treated with leflunomide und methotrexate. In the further course of the disease, the patient developed an acute hepatitis with fever, pancytopenia and massive hyperferritinemia. Immunohistochemistry of the liver biopsy revealed hemophagocytosis and activation of CD68-positive macrophages. In the radiological and histological diagnostics of the liver and bone marrow, an MAS was diagnosed as underlying disease of the acute hepatitis. Under therapy with prednisolone, the fever disappeared and transaminases and ferritin rapidly normalized. Conclusion Aside from the frequent causes of elevated liver values in younger patients, such as nutritive toxic, drug induced liver injury, viral or autoimmune hepatitis, especially in case of massive hyperferritinemia, a MAS should be considered as a rare cause of acute liver disease.

  2. [Effect of Astragali Radix in improving early renal damage in metabolic syndrome rats through ACE2/Mas pathway].

    PubMed

    Wang, Qiong-ying; Liang, Wei; Jiang, Cheng; Li, Ning-yin; Xu, Han; Yang, Mi-na; Lin, Xin; Yu, Heng; Chang, Peng; Yu, Jing

    2015-11-01

    To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.

  3. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    PubMed

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  4. Decomposition of adsorbed VX on activated carbons studied by 31P MAS NMR.

    PubMed

    Columbus, Ishay; Waysbort, Daniel; Shmueli, Liora; Nir, Ido; Kaplan, Doron

    2006-06-15

    The fate of the persistent OP nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) {(DES)2}. Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed.

  5. Angiotensin II and 1-7 during aging in Metabolic Syndrome rats. Expression of AT1, AT2 and Mas receptors in abdominal white adipose tissue.

    PubMed

    Rubio-Ruíz, M E; Del Valle-Mondragón, L; Castrejón-Tellez, V; Carreón-Torres, E; Díaz-Díaz, E; Guarner-Lans, V

    2014-07-01

    Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.

  6. Macrophage activation syndrome in the era of biologic therapy.

    PubMed

    Grom, Alexei A; Horne, AnnaCarin; De Benedetti, Fabrizio

    2016-05-01

    Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a 'cytokine storm'. Although increasingly recognized as a life-threatening complication of various rheumatic diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.

  7. Macrophage activation syndrome in the course of monogenic autoinflammatory disorders.

    PubMed

    Rigante, Donato; Emmi, Giacomo; Fastiggi, Michele; Silvestri, Elena; Cantarini, Luca

    2015-08-01

    An overwhelming activation of cytotoxic T cells and well-differentiated macrophages leading to systemic overload of inflammatory mediators characterizes the so-called macrophage activation syndrome (MAS); this potentially life-threatening clinical entity may derive from several genetic defects involved in granule-mediated cytotoxicity but has been largely observed in patients with juvenile idiopathic arthritis, many rheumatologic diseases, infections, and malignancies. The occurrence of MAS in the natural history or as the revealing clue of monogenic autoinflammatory disorders (AIDs), rare conditions caused by disrupted innate immunity pathways with overblown release of proinflammatory cytokines, has been only reported in few isolated patients with cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome since 2001. All these patients displayed various clinical, laboratory, and histopathologic features of MAS and have often required intensive care support. Only one patient has died due to MAS. Defective cytotoxic cell function was documented in a minority of patients. Corticosteroids were the first-line treatment, but anakinra was clinically effective in three refractory cases. Even if MAS and AIDs share multiple clinical features as well as heterogeneous pathogenetic scenes and a potential response to anti-interleukin-1 targeted therapies, MAS requires a prompt specific recognition in the course of AIDs due to its profound severity and high mortality rate.

  8. Immobilized MAS1 lipase showed high esterification activity in the production of triacylglycerols with n-3 polyunsaturated fatty acids.

    PubMed

    Wang, Xiumei; Li, Daoming; Qu, Man; Durrani, Rabia; Yang, Bo; Wang, Yonghua

    2017-02-01

    Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fatty acids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fatty acids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles.

  9. Macrophage activation syndrome: why and what should a gastroenterologist know.

    PubMed

    Jayakar, Bijal A; Hashkes, Philip J

    2011-03-01

    We recently treated a patient with adult-onset Still's disease who developed macrophage activation syndrome (MAS) secondary to disseminated histoplasmosis while being treated with adalimumab. The gastroenterology service was consulted early, before diagnosis, as the patient presented with elevated liver enzymes and disseminated intravascular coagulation. MAS is an exaggerated immune response that can develop as a primary condition or secondary to infections, drugs and various diseases, resulting in liver dysfunction, encephalopathy, pancytopenia and disseminated intravascular coagulation. The development of MAS has also been reported in patients with inflammatory bowel disease and post-liver transplantation and has been triggered by medications used by gastroenterologists, particularly sulfasalazine and anti-tumor necrosis factor biologic modifiers. Therefore, we present a review on etiology, pathogenesis, clinical and laboratory features, and treatment of MAS with a focus on gastrointestinal aspects and presentations. MAS is a life threatening condition with a high mortality rate if untreated. Therefore it is important to recognize this condition early. As these patients may occasionally present to gastroenterologists we hope this review will increase awareness of this rare, but serious syndrome.

  10. Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis.

    PubMed

    Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

    2013-01-01

    In this contribution the ability of (19)F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T(1)((1)H) and T(1ρ)((1)H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in (19)F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around (19)F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded (19)F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way (19)F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

  11. Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

    NASA Astrophysics Data System (ADS)

    Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

    In this contribution the ability of 19F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T1(1H) and T1ρ(1H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in 19F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around 19F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded 19F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way 19F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

  12. Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis

    PubMed Central

    Cao, Xi; Yang, Fangyuan; Shi, Tingting; Yuan, Mingxia; Xin, Zhong; Xie, Rongrong; Li, Sen; Li, Hongbing; Yang, Jin-Kui

    2016-01-01

    The classical axis of renin-angiotensin system (RAS), angiotensin (Ang)-converting enzyme (ACE)/Ang II/AT1, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas) in hepatic steatosis is still unclear. Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2−/y) mice. Meanwhile, oxidative stress and inflammation were also aggravated in ACE2−/y mice. On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation-related genes were up-regulated. In vitro, Ang-(1–7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what’s more, Akt inhibitors reduced ACE2-mediated lipid metabolism. Furthermore, ACE2-mediated Akt activation could be attenuated by blockade of ATP/P2 receptor/Calmodulin (CaM) pathway. These results indicated that Ang-(1–7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. Our findings support the potential role of ACE2/Ang-(1–7)/Mas axis in prevention and treatment of hepatic lipid metabolism. PMID:26883384

  13. Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis.

    PubMed

    Xiao, Hong-Li; Li, Chun-Sheng; Zhao, Lian-Xing; Yang, Jun; Tong, Nan; An, Le; Liu, Qi-Tong

    2016-11-01

    Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

  14. The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

    PubMed Central

    2013-01-01

    Background Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Discussion There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. Summary Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”. PMID:23968282

  15. Disruption of vascular endothelial homeostasis in systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: The dynamic roles of angiopoietin-1 and -2.

    PubMed

    Tasaki, Yuko; Shimizu, Masaki; Inoue, Natsumi; Mizuta, Mao; Nakagishi, Yasuo; Wada, Taizo; Yachie, Akihiro

    2016-04-01

    To assess the role of angiopoietin (Ang)-1 and Ang-2 and to investigate the clinical significance of serum levels of them in systemic juvenile idiopathic arthritis (s-JIA)-associated macrophage activation syndrome (MAS), we determined these levels in 51 patients with s-JIA, 11 patients with polyarticular JIA (poly-JIA), 12 patients with virus associated hemophagocytic syndrome (VAHS), 12 patients with Kawasaki disease (KD), and 15 age-matched healthy controls (HC). The results were compared with clinical features of MAS. During the MAS phase, serum Ang-1 levels were significantly decreased compared with those during the active and inactive phases. Serum Ang-2/1 ratio were significantly elevated during the MAS phase, compared with those during the active and inactive phases. There was a rapid increase in the Ang-2/1 ratio at the onset of MAS. Serum Ang-1 and the Ang-2/1 ratio significantly correlated with measures of disease activity, including AST and LDH. Ang-2/1 dysregulation was also observed in patients with VAHS, whereas not observed in most cases of KD. The homeostasis of vascular endothelial function by Ang-1 and Ang-2 is disrupted in MAS. Serum Ang-1 levels and the Ang-2/1 ratio might represent promising indicators of disease activity for MAS.

  16. Mas-Related Gene (Mrg) C Activation Attenuates Bone Cancer Pain via Modulating Gi and NR2B

    PubMed Central

    Lu, Cui’e; Lei, Yishan; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    Objective This study is to investigate the role of Mas-related gene (Mrg) C in the pathogenesis and treatment of bone cancer pain (BCP). Methods BCP mouse model was established by osteosarcoma cell inoculation. Pain-related behaviors were assessed with the spontaneous lifting behavior test and mechanical allodynia test. Expression levels of MrgC, Gi, and NR2B in the spinal cord were detected with Western blot analysis and immunohistochemistry. Results Pain-related behavior tests showed significantly increased spontaneous flinches (NSF) and decreased paw withdrawal mechanical threshold (PWMT) in mouse models of BCP. Western blot analysis showed that, compared with the control group and before modeling, all the expression levels of MrgC, Gi, and NR2B in the spinal cord of BCP mice were dramatically elevated, which were especially increased at day 7 after operation and thereafter, in a time-dependent manner. Moreover, the treatment of MrgC agonist BAM8-22 significantly up-regulated Gi and down-regulated NR2B expression levels, in the spinal cord of BCP mice, in a time-dependent manner. On the other hand, anti-MrgC significantly down-regulated Gi expression, while dramatically up-regulated NR2B expression, in the BCP mice. Similar results were obtained from the immunohistochemical detection. Importantly, BAM8-22 significantly attenuated the nociceptive behaviors in the BCP mice. Conclusion Our results indicated the MrgC-mediated Gi and NR2B expression alterations in the BCP mice, which might contribute to the pain hypersensitivity. These findings may provide a novel strategy for the treatment of BCP in clinic. PMID:27152740

  17. Angiotensin (1-7) induces MAS receptor internalization.

    PubMed

    Gironacci, Mariela M; Adamo, Hugo P; Corradi, Gerardo; Santos, Robson A; Ortiz, Pablo; Carretero, Oscar A

    2011-08-01

    Angiotensin (Ang) (1-7) is the endogenous ligand for the G protein-coupled receptor Mas, a receptor associated with cardiac, renal, and cerebral protective responses. Physiological evidence suggests that Mas receptor (MasR) undergoes agonist-dependent desensitization, but the underlying molecular mechanism regulating receptor activity is unknown. We investigated the hypothesis that MasR desensitizes and internalizes on stimulation with Ang-(1-7). For this purpose, we generated a chimera between the MasR and the yellow fluorescent protein (YFP; MasR-YFP). MasR-YFP-transfected HEK 293T cells were incubated with Ang-(1-7), and the relative cellular distribution of MasR-YFP was observed by confocal microscopy. In resting cells, MasR-YFP was mostly localized to the cell membrane. Ang-(1-7) induced a redistribution of MasR-YFP to intracellular vesicles of various sizes after 5 minutes. Following the time course of [(125)I]Ang-(1-7) endocytosis, we observed that half of MasR-YFP underwent endocytosis after 10 minutes, and this was blocked by a MasR antagonist. MasR-YFP colocalized with Rab5, the early endosome antigen 1, and the adaptor protein complex 2, indicating that the R is internalized through a clathrin-mediated pathway and targeted to early endosomes after Ang-(1-7) stimulation. A fraction of MasR-YFP also colocalized with caveolin 1, suggesting that at some point MasR-YFP traverses caveolin 1-positive compartments. In conclusion, MasR undergoes endocytosis on stimulation with Ang-(1-7), and this event may explain the desensitization of MasR responsiveness. In this way, MasR activity and density may be tightly controlled by the cell.

  18. High field 27Al MAS NMR and TPD studies of active sites in ethanol dehydration using thermally treated transitional aluminas as catalysts

    SciTech Connect

    Hu, Jian Zhi; Xu, Suochang; Kwak, Ja Hun; Hu, Mary Y.; Wan, Chuan; Zhao, Zhenchao; Szanyi, Janos; Bao, Xinhe; Han, Xiuwen; Wang, Yong; Peden, Charles H. F.

    2016-04-01

    High field quantitative 27Al MAS NMR and temperature programmed desorption (TPD) of ethanol are used to study the surface and phase transformation of gamma-Al2O3 during calcination in the temperature range of 500 to 1300 degrees C. Following ethanol adsorption, ethylene is generated during TPD with a desorption temperature > 200 degrees C. With increasing calcination temperature prior to TPD, the amount of ethylene produced decreases monotonically. Significantly, 27Al MAS NMR reveals that the amount of penta-coordinate Al3+ ions (Lewis acid sites) also decreases with increasing calcination temperature. In fact, a strong correlation between the amount of penta-coordinate Al3+ ions and the amount of strongly adsorbed ethanol molecules (i.e., the ones that convert to ethylene during TPD) is obtained. This result indicates that the penta-coordinate aluminum sites are the catalytic active sites on alumina surfaces during ethanol dehydration reaction across the entire course of gamma- to alpha-Al2O3 phase transformations.

  19. Angiotensin-(1-7) administration attenuates Alzheimer's disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation.

    PubMed

    Chen, Jin-Liang; Zhang, Dong-Ling; Sun, Yue; Zhao, Yu-Xing; Zhao, Ke-Xiang; Pu, Die; Xiao, Qian

    2017-03-27

    Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1-7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0±0.39 vs. 1.0±0.33, 39.39±1.11% vs. 25.62±3.07%, respectively, P<0.01). Ang-(1-7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-β oligomer and both soluble and insoluble β-amyloid peptide 1-42 (Aβ 1-42) and Aβ 1-40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.

  20. Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease Successfully Treated with Anakinra

    PubMed Central

    Kato, Hiroshi

    2016-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of Adult-Onset Still's disease (Still's disease). Whereas an increasing body of evidence supports interleukin-1 (IL-1) blockade as a promising treatment for Still's disease, whether it is therapeutic for MAS associated with Still's disease remains unclear. We report a 34-year-old Caucasian man with one-decade history of TNF-blockade-responsive seronegative arthritis who presented with abrupt onset of fever, serositis, bicytopenia, splenomegaly, hepatitis, and disseminated intravascular coagulation. Striking hyperferritinemia was noted without evidence of infection, malignancy, or hemophagocytosis on bone marrow biopsy. NK cells were undetectable in the peripheral blood, whereas soluble IL-2 receptor was elevated. His multiorgan disease resolved in association with methylprednisolone pulse therapy, Anakinra, and a tapering course of prednisone. This case reinforces the notion that Still's disease is inherently poised to manifest MAS as one of the clinical phenotypes by shedding light on the role of IL-1 underlying both Still's disease and related MAS. PMID:27818826

  1. [Macrophage activation syndrome in a patient with systemic juvenile idiopathic arthritis].

    PubMed

    Tavares, Anna Carolina Faria Moreira Gomes; Ferreira, Gilda Aparecida; Guimarães, Luciano Junqueira; Guimarães, Raquel Rosa; Santos, Flávia Patrícia Sena Teixeira

    2015-01-01

    Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein-Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemic-onset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.

  2. Investigation of the Structure and Active Sites of TiO2 Nanorod Supported VOx Catalysts by High-Field and Fast-Spinning 51V MAS NMR

    SciTech Connect

    Hu, Jian Z.; Xu, Suochang; Li, Weizhen; Hu, Mary Y.; Deng, Xuchu; Dixon, David A.; Vasiliu, Monica; Craciun, Raluca; Wang, Yong; Bao, Xinhe; Peden, Charles HF

    2015-07-02

    Supported VOx/TiO2-Rod catalysts were studied by 51V MAS NMR at high field using a sample spinning rate of 55 kHz. The superior spectral resolution allows for the observation of at least five vanadate species. The assignment of these vanadate species was carried out by quantum mechanical calculations of 51V NMR chemical shifts of model V-surface structures. Methanol oxidative dehydrogenation (ODH) was used to establish the correlation between the reaction rate and the various surface V-sites. It is found that monomeric V-species dominated the catalyst at low vanadium loadings with two peaks observed at about -502 and -529 ppm. V-dimers with two bridged oxygen appeare at about -555 ppm. Vanadate dimers and polyvanadates connected by one bridged oxygen atom between two adjacent V atoms resonate at about -630 ppm. A positive correlation is found between the V-dimers related to the -555 ppm peak and the ODH rate while a better correlation is obtained by including monomeric contributions. This result indicates that surface V-dimers related to the -555 ppm peak are the major active sites for ODH reaction despite mono-V species are more catalytic active but their relative ratios are decreased dramatically at high V-loadings. Furthermore, a portion of the V-species is found invisible. In particular, the level of such invisibility increases with decreased level of V-loading, suggesting the existence of paramagnetic V-species at the surface.

  3. Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?

    PubMed Central

    2012-01-01

    Introduction Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH. Methods We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival. Results Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 μg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002). Conclusions Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population. PMID:22715953

  4. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

    PubMed

    Ravelli, Angelo; Minoia, Francesca; Davì, Sergio; Horne, AnnaCarin; Bovis, Francesca; Pistorio, Angela; Aricò, Maurizio; Avcin, Tadej; Behrens, Edward M; De Benedetti, Fabrizio; Filipovic, Lisa; Grom, Alexei A; Henter, Jan-Inge; Ilowite, Norman T; Jordan, Michael B; Khubchandani, Raju; Kitoh, Toshiyuki; Lehmberg, Kai; Lovell, Daniel J; Miettunen, Paivi; Nichols, Kim E; Ozen, Seza; Pachlopnik Schmid, Jana; Ramanan, Athimalaipet V; Russo, Ricardo; Schneider, Rayfel; Sterba, Gary; Uziel, Yosef; Wallace, Carol; Wouters, Carine; Wulffraat, Nico; Demirkaya, Erkan; Brunner, Hermine I; Martini, Alberto; Ruperto, Nicolino; Cron, Randy Q

    2016-03-01

    To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

  5. Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

    PubMed Central

    Ravelli, Angelo; Minoia, Francesca; Davì, Sergio; Horne, AnnaCarin; Bovis, Francesca; Pistorio, Angela; Aricò, Maurizio; Avcin, Tadej; Behrens, Edward M; De Benedetti, Fabrizio; Filipovic, Alexandra; Grom, Alexei A; Henter, Jan-Inge; Ilowite, Norman T; Jordan, Michael B; Khubchandani, Raju; Kitoh, Toshiyuki; Lehmberg, Kai; Lovell, Daniel J; Miettunen, Paivi; Nichols, Kim E; Ozen, Seza; Pachlopnik Schmid, Jana; Ramanan, Athimalaipet V; Russo, Ricardo; Schneider, Rayfel; Sterba, Gary; Uziel, Yosef; Wallace, Carol; Wouters, Carine; Wulffraat, Nico; Demirkaya, Erkan; Brunner, Hermine I; Martini, Alberto; Ruperto, Nicolino; Cron, Randy Q

    2016-01-01

    Objective To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation. PMID:26848401

  6. High Systemic Levels of the Cytokine-Inducing HMGB1 Isoform Secreted in Severe Macrophage Activation Syndrome

    PubMed Central

    Palmblad, Karin; Schierbeck, Hanna; Sundberg, Erik; Horne, Anna-Carin; Harris, Helena Erlandsson; Henter, Jan-Inge; Antoine, Daniel J; Andersson, Ulf

    2014-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. High mobility group box 1 (HMGB1) is a nuclear protein extensively leaked extracellularly during necrotic cell death or actively secreted by natural killer (NK) cells, macrophages and additional cells during infection or sterile injury. Extracellular HMGB1 orchestrates key events in inflammation as a prototypic alarmin. The redox states of its three cysteines render the molecule mutually exclusive functions: fully reduced “all-thiol HMGB1” exerts chemotactic activity; “disulfide HMGB1” has cytokine-inducing, toll-like receptor 4 (TLR4)-mediated effects—while terminally oxidized “sulfonyl HMGB1” lacks inflammatory activity. This study examines the kinetic pattern of systemic HMGB1 isoform expression during therapy in four children with severe MAS. Three of the four patients with underlying systemic rheumatic diseases were treated with biologics and two suffered from triggering herpes virus infections at the onset of MAS. All patients required intensive care unit therapy due to life-threatening illness. Tandem mass-spectrometric analysis revealed dramatically increased systemic levels of the cytokine-inducing HMGB1 isoform during early MAS. Disease control coincided with supplementary etoposide therapy initiated to boost apoptotic cell death, when systemic HMGB1 levels drastically declined and the molecule emerged mainly in its oxidized, noninflammatory isoform. Systemic interferon (IFN)-γ and ferritin peaked concomitantly with HMGB1, whereas interleukin (IL)-18 and monocyte chemotactic protein (MCP)-1 levels developed differently. In conclusion, this work provides new insights in HMGB1 biology, suggesting that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of disulfide HMGB1 antagonists to improve outcome of MAS. PMID:25247290

  7. Genetics Home Reference: activated PI3K-delta syndrome

    MedlinePlus

    ... Health Conditions activated PI3K-delta syndrome activated PI3K-delta syndrome Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Activated PI3K-delta syndrome is a disorder that impairs the immune ...

  8. Intrapulmonary activation of the angiotensin-converting enzyme type 2/angiotensin 1-7/G-protein-coupled Mas receptor axis attenuates pulmonary hypertension in Ren-2 transgenic rats exposed to chronic hypoxia.

    PubMed

    Hampl, V; Herget, J; Bíbová, J; Baňasová, A; Husková, Z; Vaňourková, Z; Jíchová, Š; Kujal, P; Vernerová, Z; Sadowski, J; Červenka, L

    2015-01-01

    The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

  9. High field 27Al MAS NMR and TPD studies of active sites in ethanol dehydration using thermally treated transitional aluminas as catalysts

    SciTech Connect

    Hu, Jian Zhi; Xu, Suochang; Kwak, Ja Hun; Hu, Mary Y.; Wan, Chuan; Zhao, Zhenchao; Szanyi, Janos; Bao, Xinhe; Han, Xiuwen; Wang, Yong; Peden, Charles H. F.

    2016-04-01

    Gamma-, sigma- and theta-Al2O3 are well known metastable “transitional” alumina structural polymorphs. Upon heating, Al2O3 transitions to the so-called and Al2O3 polymorphs and finally forms the thermally stable Al2O3. The poorly developed crystallinity and co-existence of the , , and Al2O3 prior to forming all Al2O3, making it difficult to characterize the structures as well as to quantify the various phases of the transition alumina. As a result, there are significant controversies in the literatures. In this work, a detailed NMR analysis was carried out at high magnetic field on three special aluminum oxide samples where the, , , Al2O3 phases are made dominant, respectively, by controlling the synthesis conditions. The goal is to simplify, including making unambiguous, spectral assignments in 27Al MAS NMR spectra of transition alumina that have not yet been commonly agreed previously. Specifically, quantitative 1D 27Al MAS NMR was used to quantify the ratios of the different alumina structural units, 2D MQMAS 27Al MAS was used for obtaining the highest spectral resolution to guide the analysis of the 1D spectrum, and a saturation pulse sequence was integrated into the 1D NMR to select the amorphous structures, including obtain spectra where the penta-coordinate sites are observed with enhanced relative intensity. Collectively, this study uniquely assigns Al-peaks (both octahedral and tetrahedral) to the Al2O3 and the Al2O3 phases and offers a new way of understanding, including quantifying, the different structural units and sites in transition alumina samples.

  10. An application of active optics to x-ray imaging: X-mas (x-ray milli arc-second) Project

    NASA Astrophysics Data System (ADS)

    Tsujimoto, Masahiro; Kitamoto, Shunji; Ohkubo, Yohsuke; Sato, Jun'ichi; Watanabe, Takeshi; Sudoh, Keisuke; Sekiguchi, Akiko; Suga, Kazuharu; Sekiguchi, Hiroyuki

    2006-06-01

    We report the current status of the "X-mas" (X-ray milli-arcsecond) project. X-mas is an application of the AO technology to the X-ray optics, aiming to obtain high-resolution defraction-limited X-ray images. Our X-ray telescope employs the Newton optics with a paraboloid primary and a 31-element deformable secondary mirrors. The aperture of the primary mirror is 80 millimeters with the focal length of 2 meters. Multi-layer coating of the mirrors by silicon and molybdenum realizes a large reflectivity of ~60% for the primary and 30-50% for the secondary mirror at 13.5 nm, which enables us to construct a normal incidence optics at this wavelength. We use a laser guide source and a wave front sensor to optimize the form of the secondary deformable mirror for the purpose of offsetting the large-scale figure errors in the X-ray optics. A back-side illumination X-ray CCD detector manufactured by Hamamatsu Photonics is used for X-ray detections. We have assembled all these elements and started to accumulate data. Closed-loop AO is in operation for the laser guide source. Likely X-ray images are obtained through the telescope. The results in 2005-2006 are presented.

  11. An atypical presentation of adult-onset Still’s disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature

    PubMed Central

    Manson, Daniel K.; Horn, Evelyn M.; Haythe, Jennifer

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still’s disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting. PMID:27162622

  12. Serum lipolytic activity in Reye's syndrome.

    PubMed

    Kang, E S; Matsuo, N; Nagai, T; Greenhaw, J; Williams, P L

    1989-09-15

    High levels of the serum free fatty acids (FFA) are found in Reye's syndrome (RS). While this is attributed to enhanced adipose tissue lipolysis, the possibility that intravascular lipolysis could augment this process was investigated by measuring lipase activity in sera from RS and other subjects. Ordinarily, lipolytic activity is not detectable in serum from unheparinized subjects. Significant lipolytic activities ranging from 1-3 mumol/ml serum per hour were detected in sera from 5 of the 7 RS patients studied. Similar activities were also found in sera from two other subjects one of whom was a long-term survivor of RS and the other who had recurrent bouts of biliary obstruction and encephalopathy. Lipase activity was negligible in the serum from 2 other RS patients, 4 other long-term survivors of RS, 2 siblings, one RS parent and in 20 disease controls including patients with influenza, diabetic ketoacidosis and cerebral edema, meningitis and febrile infections with diarrhea and vomiting. None of these individuals had received heparin. An inverse relationship was found between LPL and hepatic lipase (HL) activities. Glucose levels tended to correlate directly with LPL and inversely with HL activity. The basis for the presence of LPL activity in RS sera is not known but the presence of serum lipase activity in unheparinized patients supports the notion that the TG in the circulating lipoprotein particles probably also serve as another source of FFA in the sera of RS patients.

  13. Chronic Fatigue Syndrome (CFS): Managing Activities and Exercise

    MedlinePlus

    ... Fatigue Syndrome (CFS) Share Compartir Managing Activities and Exercise On this Page Avoiding Extremes Developing an Activity ... recent manageable level of activity. Strength and Conditioning Exercises Strength and conditioning exercises are an important component ...

  14. Dysregulated microRNA Activity in Shwachman-Diamond Syndrome

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0124 TITLE: Dysregulated microRNA Activity in Shwachman- Diamond Syndrome PRINCIPAL INVESTIGATOR: Carl Novina...SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0124 Dysregulated microRNA Activity in Shwachman- Diamond Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Shwachman- Diamond Syndrome (SDS) is an inherited bone marrow failure primarily affecting myeloid

  15. Disturbance of vasodilation via protease-activated receptor 2 in SHRSP.Z-Lepr fa/IzmDmcr rats with metabolic syndrome.

    PubMed

    Kagota, Satomi; Maruyama, Kana; Wakuda, Hirokazu; McGuire, John J; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2014-10-01

    Protease-activated receptor-2 (PAR2) activation causes vascular inflammation and vasodilation, but its role in metabolic syndrome (MetS) remains uncertain. Therefore, we examined whether the PAR2-induced vasodilation of SHRSP.Z-Lepr(fa)/IzmDmcr rats (SHRSP.ZF) is impaired and if so, whether administering telmisartan is protective. PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly), relaxed the isolated superior and first-order branches of mesenteric arteries (MAs) from Wistar-Kyoto rats (WKY) and SHRSP.ZF. Superior-MA relaxation by 2fly was less in SHRSP.ZF than in WKY. Relaxation of first-order MAs by 2fly was the same in SHRSP.ZF and WKY. NO synthase inhibitor partially reduced 2fly-induced relaxation of superior and first-order MAs in SHRSP.ZF and WKY; inhibition of relaxation was proportionately larger in SHRSP.ZF. In SHRSP.ZF, nitroprusside-induced relaxation and the expression of soluble guanylyl cyclase decreased. In SHRSP.ZF, telmisartan reversed these abnormalities, and decreased blood pressure and serum levels of thiobarbituric acid reactive substances, an index of oxidative stress. Vasodilation via PAR2 activation was preserved in small-caliber MAs, in contrast to large-caliber MAs, even when MetS reduced NO-dependent relaxation mechanisms. NO and non-NO relaxing factor(s) contributed to PAR2-mediated relaxation in MAs, and the balance between factors may be altered to preserve vasodilation in MetS. Telmisartan prevented vascular dysfunction in MetS by protecting arteries against oxidative stress.

  16. Intragenic suppression of a constitutively active allele of Gsα associated with McCune-Albright syndrome.

    PubMed

    Tobar-Rubin, Raquel; Sultan, Dahlia; Janevska, Daniela; Turcic, Kyle; Carroll, Julie; Ooms, Laura; Pals-Rylaarsdam, Robin

    2013-04-01

    McCune-Albright syndrome (MAS) is a human genetic disorder caused by a mutation that constitutively activates the G(s)α subunit by abolishing GTP hydrolysis. MAS patients suffer from a range of endocrinopathies as well as polyostotic fibrous dysplasia of bone. We previously identified an intragenic suppressor of the MAS mutation in a yeast system, which substituted two residues in the GTP-binding site of Gpa1: L318P and D319V to suppress the constitutive activity of an R297H mutation, corresponding to the human F222P, D223V, and R201H mutations respectively. To extend these studies, the human GNAS gene was subjected to site-directed mutagenesis. Constructs expressing the MAS mutation (R201H), the MAS mutation plus the mutations homologous to the yeast suppressors (R201H, F222P/D223V), or the yeast suppressor mutation alone (F222P/D223V) were transfected into HEK293 cells, and basal and receptor-stimulated cAMP levels were measured. Expression of R201H increased the basal cAMP levels and decreased the EC(50) for hormone-stimulated cAMP production. These effects were dependent on the amount of R201H protein expressed. R201H, F222P/D223V abolished the constitutive activity of the MAS mutation and caused responses to hormone that were not different from those measured in cells expressing WT G(s)α. Interestingly, F222P/D223V behaved similar to R201H in causing increases in basal cAMP production, thus demonstrating constitutive activity. Substitution of another acidic (E) or polar (N, T, and G) amino acid at position 223 caused no suppression of R201H activity, while substitution of a second nonpolar amino acid (A) at this position partially suppressed, and the larger polar I residue completely suppressed the effects of R201H.

  17. Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis

    PubMed Central

    Park, Joon Hyeong; Seo, Yu Mi; Han, Seung Beom; Kim, Ki Hwan; Rhim, Jung Woo; Chung, Nack Gyun; Kim, Myung Shin; Kang, Jin Han

    2016-01-01

    Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded. PMID:27826329

  18. Physical Activity Patterns of Youth with Down Syndrome

    ERIC Educational Resources Information Center

    Esposito, Phil E.; MacDonald, Megan; Hornyak, Joseph E.; Ulrich, Dale A.

    2012-01-01

    The purpose of this study was to examine the physical activity patterns of children with Down syndrome. A cross-sectional approach and accelerometry were used to measure the time children with Down syndrome (N = 104) spent in sedentary, light, and moderate-to-vigorous physical activity. Results indicated that adolescents from ages 14 to 15 years…

  19. Hymenoptera Allergy and Mast Cell Activation Syndromes.

    PubMed

    Bonadonna, Patrizia; Bonifacio, Massimiliano; Lombardo, Carla; Zanotti, Roberta

    2016-01-01

    Mast cell activation syndrome (MCAS) can be diagnosed in patients with recurrent, severe symptoms from mast cell (MC)-derived mediators, which are transiently increased in serum and are attenuated by mediator-targeting drugs. When KIT-mutated, clonal MC are detected in these patients, a diagnosis of primary MCAS can be made. Severe systemic reactions to hymenoptera venom (HV) represent the most common form of anaphylaxis in patients with mastocytosis. Patients with primary MCAS and HV anaphylaxis are predominantly males and do not have skin lesions in the majority of cases, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase (≤11.4 ng/ml) in these patients does not exclude a diagnosis of mastocytosis. Patients with primary MCAS and HV anaphylaxis have to undergo lifelong venom immunotherapy, in order to prevent further potentially fatal severe reactions.

  20. Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis.

    PubMed

    Jain, Deepak; Aggarwal, Hari K; Rao, Avinash; Mittal, Anshul; Jain, Promil

    2016-01-01

    Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily ("quotidian") for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non-remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids.

  1. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  2. Physical activity and metabolic syndrome in liver transplant recipients.

    PubMed

    Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J

    2013-10-01

    There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver

  3. Physical Activity and Walking Onset in Infants with Down Syndrome

    ERIC Educational Resources Information Center

    Lloyd, Meghann; Burghardt, Amy; Ulrich, Dale A.; Angulo-Barroso, Rosa

    2010-01-01

    Infants with Down syndrome (DS) are described as being less active and they also experience significant delays in motor development. It is hypothesized that early infant physical activity may be influential for the acquisition of independent walking. Physical activity was monitored longitudinally in 30 infants with DS starting at an average age of…

  4. Hansen's disease with McCune-Albright syndrome.

    PubMed

    Kumar, Kvs Hari; Dhull, P; Bisht, Ys

    2012-10-01

    McCune-Albright syndrome (MAS) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen's disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen's disease along with underlying MAS and report the same in this report.

  5. MAS2-8 radar and digital control unit

    NASA Technical Reports Server (NTRS)

    Oberg, J. M.; Ulaby, F. T.

    1974-01-01

    The design of the MAS 2-8 (2 to 8 GHz microwave-active spectrometer), a ground-based sensor system, is presented. A major modification in 1974 to the MAS 2-8, that of a control subsystem to automate the data-taking operation, is the prime focus. The digital control unit automatically changes all system parameters except FM rate and records the return signal on paper tape. The overall system operation and a detailed discussion of the design and operation of the digital control unit are presented.

  6. Activity syndromes and metabolism in giant deep-sea isopods

    NASA Astrophysics Data System (ADS)

    Wilson, Alexander D. M.; Szekeres, Petra; Violich, Mackellar; Gutowsky, Lee F. G.; Eliason, Erika J.; Cooke, Steven J.

    2017-03-01

    Despite growing interest, the behavioural ecology of deep-sea organisms is largely unknown. Much of this scarcity in knowledge can be attributed to deepwater animals being secretive or comparatively 'rare', as well as technical difficulties associated with accessing such remote habitats. Here we tested whether two species of giant marine isopod (Bathynomus giganteus, Booralana tricarinata) captured from 653 to 875 m in the Caribbean Sea near Eleuthera, The Bahamas, exhibited an activity behavioural syndrome across two environmental contexts (presence/absence of food stimulus) and further whether this syndrome carried over consistently between sexes. We also measured routine metabolic rate and oxygen consumption in response to a food stimulus in B. giganteus to assess whether these variables are related to individual differences in personality. We found that both species show an activity syndrome across environmental contexts, but the underlying mechanistic basis of this syndrome, particularly in B. giganteus, is unclear. Contrary to our initial predictions, neither B. giganteus nor B. tricarinata showed any differences between mean expression of behavioural traits between sexes. Both sexes of B. tricarinata showed strong evidence of an activity syndrome underlying movement and foraging ecology, whereas only male B. giganteus showed evidence of an activity syndrome. Generally, individuals that were more active and bolder, in a standard open arena test were also more active when a food stimulus was present. Interestingly, individual differences in metabolism were not related to individual differences in behaviour based on present data. Our study provides the first measurements of behavioural syndromes and metabolism in giant deep-sea isopods.

  7. Physical Activity, Metabolic Syndrome, and Overweight in Rural Youth

    ERIC Educational Resources Information Center

    Moore, Justin B.; Davis, Catherine L.; Baxter, Suzanne Domel; Lewis, Richard D.; Yin, Zenong

    2008-01-01

    Background: Research suggests significant health differences between rural dwelling youth and their urban counterparts with relation to cardiovascular risk factors. This study was conducted to (1) determine relationships between physical activity and markers of metabolic syndrome, and (2) to explore factors relating to physical activity in a…

  8. Fluid flow dynamics in MAS systems.

    PubMed

    Wilhelm, Dirk; Purea, Armin; Engelke, Frank

    2015-08-01

    The turbine system and the radial bearing of a high performance magic angle spinning (MAS) probe with 1.3mm-rotor diameter has been analyzed for spinning rates up to 67kHz. We focused mainly on the fluid flow properties of the MAS system. Therefore, computational fluid dynamics (CFD) simulations and fluid measurements of the turbine and the radial bearings have been performed. CFD simulation and measurement results of the 1.3mm-MAS rotor system show relatively low efficiency (about 25%) compared to standard turbo machines outside the realm of MAS. However, in particular, MAS turbines are mainly optimized for speed and stability instead of efficiency. We have compared MAS systems for rotor diameter of 1.3-7mm converted to dimensionless values with classical turbomachinery systems showing that the operation parameters (rotor diameter, inlet mass flow, spinning rate) are in the favorable range. This dimensionless analysis also supports radial turbines for low speed MAS probes and diagonal turbines for high speed MAS probes. Consequently, a change from Pelton type MAS turbines to diagonal turbines might be worth considering for high speed applications. CFD simulations of the radial bearings have been compared with basic theoretical values proposing considerably smaller frictional loss values. The discrepancies might be due to the simple linear flow profile employed for the theoretical model. Frictional losses generated inside the radial bearings result in undesired heat-up of the rotor. The rotor surface temperature distribution computed by CFD simulations show a large temperature gradient over the rotor.

  9. Fluid flow dynamics in MAS systems

    NASA Astrophysics Data System (ADS)

    Wilhelm, Dirk; Purea, Armin; Engelke, Frank

    2015-08-01

    The turbine system and the radial bearing of a high performance magic angle spinning (MAS) probe with 1.3 mm-rotor diameter has been analyzed for spinning rates up to 67 kHz. We focused mainly on the fluid flow properties of the MAS system. Therefore, computational fluid dynamics (CFD) simulations and fluid measurements of the turbine and the radial bearings have been performed. CFD simulation and measurement results of the 1.3 mm-MAS rotor system show relatively low efficiency (about 25%) compared to standard turbo machines outside the realm of MAS. However, in particular, MAS turbines are mainly optimized for speed and stability instead of efficiency. We have compared MAS systems for rotor diameter of 1.3-7 mm converted to dimensionless values with classical turbomachinery systems showing that the operation parameters (rotor diameter, inlet mass flow, spinning rate) are in the favorable range. This dimensionless analysis also supports radial turbines for low speed MAS probes and diagonal turbines for high speed MAS probes. Consequently, a change from Pelton type MAS turbines to diagonal turbines might be worth considering for high speed applications. CFD simulations of the radial bearings have been compared with basic theoretical values proposing considerably smaller frictional loss values. The discrepancies might be due to the simple linear flow profile employed for the theoretical model. Frictional losses generated inside the radial bearings result in undesired heat-up of the rotor. The rotor surface temperature distribution computed by CFD simulations show a large temperature gradient over the rotor.

  10. MAS NMR of HIV-1 protein assemblies

    NASA Astrophysics Data System (ADS)

    Suiter, Christopher L.; Quinn, Caitlin M.; Lu, Manman; Hou, Guangjin; Zhang, Huilan; Polenova, Tatyana

    2015-04-01

    The negative global impact of the AIDS pandemic is well known. In this perspective article, the utility of magic angle spinning (MAS) NMR spectroscopy to answer pressing questions related to the structure and dynamics of HIV-1 protein assemblies is examined. In recent years, MAS NMR has undergone major technological developments enabling studies of large viral assemblies. We discuss some of these evolving methods and technologies and provide a perspective on the current state of MAS NMR as applied to the investigations into structure and dynamics of HIV-1 assemblies of CA capsid protein and of Gag maturation intermediates.

  11. Physical activity patterns of youth with Down syndrome.

    PubMed

    Esposito, Phil E; MacDonald, Megan; Hornyak, Joseph E; Ulrich, Dale A

    2012-04-01

    The purpose of this study was to examine the physical activity patterns of children with Down syndrome. A cross-sectional approach and accelerometry were used to measure the time children with Down syndrome (N = 104) spent in sedentary, light, and moderate-to-vigorous physical activity. Results indicated that adolescents from ages 14 to 15 years were the most sedentary and spent the least amount of time in light and moderate-to-vigorous physical activity. A general trend of decreasing physical activity as children increase in age was found. This trend is similar to that found among typically developing youth. Participants in this study were found to spend a majority of their day engaged in sedentary activities. Results indicate that most participants were not accumulating the recommended 60 minutes of moderate or vigorous physical activity.

  12. Activation of Mas oncogene-related gene (Mrg) C receptors enhances morphine-induced analgesia through modulation of coupling of μ-opioid receptor to Gi-protein in rat spinal dorsal horn.

    PubMed

    Wang, D; Chen, T; Zhou, X; Couture, R; Hong, Y

    2013-12-03

    Mas oncogene-related gene (Mrg) G protein-coupled receptors are exclusively expressed in small-sized neurons in trigeminal and dorsal root ganglia (DRG) in mammals. The present study investigated the effect of MrgC receptor activation on morphine analgesic potency and addressed its possible mechanisms. Intrathecal (i.t.) administration of the specific MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22, 3 nmol) increased morphine-induced analgesia and shifted the morphine dose-response curve to the left in rats. Acute morphine (5 μg) reduced the coupling of μ-opioid receptors (MORs) to Gi-, but not Gs-, protein in the spinal dorsal horn. The i.t. BAM8-22 (3 nmol) prevented this change of G-protein repertoire while the inactive MrgC receptor agonist BAM8-18 (3 nmol, i.t.) failed to do so. A double labeling study showed the co-localization of MrgC and MORs in DRG neurons. The i.t. BAM8-22 also increased the coupling of MORs to Gi-protein and recruited Gi-protein from cytoplasm to the cell membrane in the spinal dorsal horn. Application of BAM8-22 (10nM) in the cultured ganglion explants for 30 min increased Gi-protein mRNA, but not Gs-protein mRNA. The present study demonstrated that acute administration of morphine inhibited the repertoire of MOR/Gi-protein coupling in the spinal dorsal horn in vivo. The findings highlight a novel mechanism by which the activation of MrgC receptors can modulate the coupling of MORs with Gi-protein to enhance morphine-induced analgesia. Hence, adjunct treatment of MrgC agonist BAM8-22 may be of therapeutic value to relieve pain.

  13. Hyperferritinemic syndrome: Still's disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients.

    PubMed

    Betancur, Juan-Felipe; Navarro, Erika-Paola; Echeverry, Alex; Moncada, Pablo A; Cañas, Carlos A; Tobón, Gabriel J

    2015-11-01

    There are four medical conditions characterized by high levels of ferritin, the macrophage activation syndrome (MAS), adult onset Still' s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), and septic shock, that share similar clinical and laboratory features, suggesting a common pathogenic mechanism. This common syndrome entity is termed "the hyperferritinemic syndrome." Here, we describe two different cases of hyperferritinemic syndrome triggered by Chikungunya fever virus infection: a 21-year-old female with SLE and a 32-year-old male patient who developed AOSD after the coinfection of dengue and Chikungunya viruses.

  14. Clonal mast cell activation syndrome with anaphylaxis to sulfites.

    PubMed

    Cifuentes, Liliana; Ring, Johannes; Brockow, Knut

    2013-01-01

    Sulfites are rarely suspected as causative agents of immediate-type hypersensitivity. We report on a 49-year-old male patient who developed recurrent severe hypotension after food ingestion. A diagnosis of monoclonal mast cell activation syndrome was established. In the double-blind, placebo-controlled food challenge, the patient reacted to potassium metabisulfite with anaphylaxis.

  15. Physical activity in obesity and metabolic syndrome.

    PubMed

    Strasser, Barbara

    2013-04-01

    Biological aging is typically associated with a progressive increase in body fat mass and a loss of lean body mass. Owing to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Lifestyle modification, specifically changes in diet, physical activity, and exercise, is considered the cornerstone of obesity management. However, for most overweight people it is difficult to lose weight permanently through diet or exercise. Thus, prevention of weight gain is thought to be more effective than weight loss in reducing obesity rates. A key question is whether physical activity can extenuate age-related weight gain and promote metabolic health in adults. Current guidelines suggest that adults should accumulate about 60 minutes of moderate-intensity physical activity daily to prevent unhealthy weight gain. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to better metabolic control.

  16. Activation of spinal MrgC-Gi-NR2B-nNOS signaling pathway by Mas oncogene-related gene C receptor agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice

    PubMed Central

    Sun, Yu’e; Zhang, Juan; Lei, Yishan; Lu, Cui’e; Hou, Bailing; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    Objectives: In the present study, we investigate the effects of Mas oncogene-related gene (Mrg) C receptors (MrgC) on the expression and activation of spinal Gi protein, N-methyl-D-aspartate receptor subunit 2B (NR2B), and neuronal nitric oxide synthase (nNOS) in mouse model of bone cancer pain. Methods: The number of spontaneous foot lift (NSF) and paw withdrawal mechanical threshold (PWMT) were measured after inoculation of tumor cells and intrathecal injection of MrgC agonist bovine adrenal medulla 8-22 (BAM8-22) or MrgC antagonist anti-MrgC for 14 days after operation. Expression of spinal MrgC, Gi protein, NR2B and nNOS and their phosphorylated forms after inoculation was examined by immunohistochemistry and Western blotting. Double labeling was used to identify the co-localization of NR2B or nNOS with MrgC in spinal cord dorsal horn (SCDH) neurons. The effects of intrathecal injection of BAM8-22 or anti-MrgC on nociceptive behaviors and the corresponding expression of spinal MrgC, Gi protein, NR2B and nNOS were also investigated. Results: The expression of spinal MrgC, Gi protein, NR2B, and nNOS was higher in tumor-bearing mice in comparison to sham mice or normal mice. Intrathecal injection of MrgC agonist BAM8-22 significantly alleviated bone cancer pain, up-regulated MrgC and Gi protein expression, and down-regulated the expression of spinal p-NR2B, t-nNOS and p-nNOS in SCDH on day 14 after operation, whereas administration of anti-MrgC produced the opposite effect. Meanwhile, MrgC-like immunoreactivity (IR) co-localizes with NR2B-IR or nNOS-IR in SCDH neurons. Conclusions: The present study demonstrates that MrgC-activated spinal Gi-NR2B-nNOS signaling pathway plays important roles in the development of bone cancer pain. These findings may provide a novel strategy for the treatment of bone cancer pain. PMID:27158400

  17. Mas' Making and Pedagogy: Imagined Possibilities

    ERIC Educational Resources Information Center

    Fournillier, Janice B.

    2009-01-01

    In this article I draw on an ethnographic case study that examined mas' makers' perceptions of the learning/teaching practices at work in the production of costumes for Trinidad and Tobago's annual Carnival celebrations. During the 2005 Carnival season I spent four months in the field, my country of birth, and collected data through participant…

  18. Activation of the ACE2/Ang-(1-7)/Mas pathway reduces oxygen-glucose deprivation induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction

    PubMed Central

    Zheng, Jiaolin; Li, Guangze; Chen, Shuzhen; Chen, Ji; Buck, Joshua; Zhu, Yulan; Xia, Huijing; Lazartigues, Eric; Chen, Yanfang; Olson, James E.

    2014-01-01

    We previously demonstrated that mice which overexpress human renin and angiotensinogen (R+A+) show enhanced cerebral damage in both in vivo and in vitro experimental ischemia models. Angiotensin converting enzyme 2 (ACE2) counteracts the effects of angiotensin (Ang-II) by transforming it into Ang-(1-7), thus reducing the ligand for the AT1 receptor and increasing stimulation of the Mas receptor. Triple transgenic mice, SARA, which specifically overexpress ACE2 in neurons of R+A+ mice were used to study the role of ACE2 in ischemic stroke using oxygen and glucose deprivation (OGD) of brain slices as an in vitro model. We examined tissue swelling, the production of reactive oxygen species (ROS), and cell death in cerebral cortex (CX) and the hippocampal CA1 region during OGD. Expression levels of NADPH oxidase isoforms, Nox2 and Nox4 were measured using western blots. Results show that SARA mice and R+A+ mice treated with the Mas receptor agonist Ang-(1-7) had less swelling, cell death, and ROS production in CX and CA1 areas compared to those in R+A+ animals. Treatment of slices from SARA mice with the Mas antagonist A779 eliminated this protection. Finally, western blots revealed less Nox2 and Nox4 expression in SARA mice compared with R+A+ mice both before and after OGD. We suggest that reduced brain swelling and cell death observed in SARA animals exposed to OGD results from diminished ROS production coupled with lower expression of NADPH oxidases. Thus, the ACE2/Ang-(1-7)/Mas receptor pathway plays a protective role in brain ischemic damage by counteracting the detrimental effects of Ang-II-induced ROS production. PMID:24814023

  19. Physical activity and walking onset in infants with Down syndrome.

    PubMed

    Lloyd, Meghann; Burghardt, Amy; Ulrich, Dale A; Angulo-Barroso, Rosa

    2010-01-01

    Infants with Down syndrome (DS) are described as being less active and they also experience significant delays in motor development. It is hypothesized that early infant physical activity may be influential for the acquisition of independent walking. Physical activity was monitored longitudinally in 30 infants with DS starting at an average age of 10 months participating in a treadmill training intervention. Actiwatches were placed on infants' trunk and right ankle for a 24-hr period, every other month until walking onset. Data were analyzed to separate sedentary-to-light activity (low-act) and moderate-to-vigorous activity (high-act). Results showed that more leg high-act at an average age of 12 and 14 months is related to earlier onset of walking. It is recommended that early leg activity should be promoted in infants with DS.

  20. Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome.

    PubMed

    Nordstrøm, Marianne; Hansen, Bjørge Herman; Paus, Benedicte; Kolset, Svein Olav

    2013-12-01

    In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16-45 years with Down syndrome (DS), Williams syndrome (WS) and Prader-Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support. On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA. When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p=0.011, 95% CI: -10.9; -80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p<0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p<0.001, 95% CI: -14.2; -45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p=0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p=0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p<0.001 95% CI: -40.4; -85.8). When adjusted for BMI no differences in

  1. Ganser-like Syndrome After Loss of Psychic Self-activation Syndrome: Psychogenic or Organic?

    PubMed Central

    Kaphan, Elsa; Barbeau, Emmanuel; Royère, Marie L.; Guedj, Eric; Pelletier, Jean; Ali Chérif, André

    2014-01-01

    Very few data are available on the long-term changes in the cognitive abilities of patients with loss of psychic self-activation syndrome (LPSAS). Here, we present a 25-year follow-up study on a case of LPSAS resulting from bilateral pallidal lesions caused by carbon monoxide intoxication. Typical signs of LPSAS were observed, showing no changes in severity, but Ganser syndrome (GS) gradually developed and worsened during the follow-up period. GS is generally assumed to be a psychogenic syndrome, but an organic etiology has been suspected by the authors of several case reports. Here, atypical features of GS plead against the independence of GS and LPSAS. DaTSCAN and brain 18FDG-PET were performed. Since left hippocampal hypometabolism has been previously described in patients with functional amnesia, it is possible that long periods of mental inactivity may have psychological consequences, but the atypical features of GS also suggest that an organic mechanism may be involved. PMID:25280796

  2. Children with Down Syndrome in Mainstream Schools: Peer Interaction in Activities

    ERIC Educational Resources Information Center

    Dolva, Anne-Stine; Hemmingsson, Helena; Gustavsson, Anders; Borell, Lena

    2010-01-01

    The objective of this qualitative study was to explore peer interaction in the context of school activities in mainstream classes that included pupils with Down syndrome together with their peers without disabilities in order to identify enabling conditions. Six children with Down syndrome, each of whom was the only one with Down syndrome in a…

  3. The Marfan Syndrome. Fact Sheet [and] Physical Education and Activity Guidelines.

    ERIC Educational Resources Information Center

    National Marfan Foundation, Port Washington, NY.

    This document consists of two brochures, the first explaining the Marfan Syndrome and a second providing guidelines for physical education and activity for people who have this syndrome are provided. The brochure on factual information about Marfan syndrome outlines the associated medical problems involving the cardiovascular system, the skeleton,…

  4. Sealed rotors for in situ high temperature high pressure MAS NMR

    DOE PAGES

    Hu, Jian Z.; Hu, Mary Y.; Zhao, Zhenchao; ...

    2015-07-06

    Magic angle spinning (MAS) nuclear magnetic resonance (NMR) investigations on heterogeneous samples containing solids, semi-solids, liquid and gases or a mixture of them under non-conventional conditions of a combined high pressure and high temperature, or cold temperature suffer from the unavailability of a perfectly sealed rotor. Here, we report the design of reusable and perfectly-sealed all-zircornia MAS rotors. The rotors are easy to use and are suitable for operation temperatures from below 0 to 250 °C and pressures up to 100 bar. As an example of potential applications we performed in situ MAS NMR investigations of AlPO₄-5 molecular sieve crystallization,more » a kinetic study of the cyclohexanol dehydration reaction using 13C MAS NMR, and an investigation of the metabolomics of intact biological tissue at low temperature using 1H HR-MAS NMR spectroscopy. The in situ MAS NMR experiments performed using the reported rotors allowed reproduction of the results from traditional batch reactions, while offering more detailed quantitative information at the molecular level, as demonstrated for the molecular sieve synthesis and activation energy measurements for cyclohexanol dehydration. The perfectly sealed rotor also shows promising application for metabolomics studies using 1H HR-MAS NMR.« less

  5. Sealed rotors for in situ high temperature high pressure MAS NMR

    SciTech Connect

    Hu, Jian Z.; Hu, Mary Y.; Zhao, Zhenchao; Xu, Souchang; Vjunov, Aleksei; Shi, Hui; Camaioni, Donald M.; Peden, Charles H. F.; Lercher, Johannes A.

    2015-07-06

    Magic angle spinning (MAS) nuclear magnetic resonance (NMR) investigations on heterogeneous samples containing solids, semi-solids, liquid and gases or a mixture of them under non-conventional conditions of a combined high pressure and high temperature, or cold temperature suffer from the unavailability of a perfectly sealed rotor. Here, we report the design of reusable and perfectly-sealed all-zircornia MAS rotors. The rotors are easy to use and are suitable for operation temperatures from below 0 to 250 °C and pressures up to 100 bar. As an example of potential applications we performed in situ MAS NMR investigations of AlPO₄-5 molecular sieve crystallization, a kinetic study of the cyclohexanol dehydration reaction using 13C MAS NMR, and an investigation of the metabolomics of intact biological tissue at low temperature using 1H HR-MAS NMR spectroscopy. The in situ MAS NMR experiments performed using the reported rotors allowed reproduction of the results from traditional batch reactions, while offering more detailed quantitative information at the molecular level, as demonstrated for the molecular sieve synthesis and activation energy measurements for cyclohexanol dehydration. The perfectly sealed rotor also shows promising application for metabolomics studies using 1H HR-MAS NMR.

  6. The relationship between physical activity levels and metabolic syndrome in male white-collar workers

    PubMed Central

    Ko, Kwang-Jun; Kim, Eon-Ho; Baek, Un-Hyo; Gang, Zhao; Kang, Seol-Jung

    2016-01-01

    [Purpose] Physical activity is important for preventing and managing metabolic syndrome. White-collar workers can be inherently predisposed to chronic diseases, as their jobs are primarily sedentary. The purpose of this study was to examine the relationship between physical activity and metabolic syndrome in male white-collar workers. [Subjects and Methods] Physical activity and metabolic syndrome factors were measured in 331 male public office workers. Physical activity was classified as high (N=101), moderate (N=115), or low (N=111) using the International Physical Activity Questionnaire. To diagnose metabolic syndrome, the U.S. National Cholesterol Education Program’s standard was used. [Results] Waist circumference and triglyceride levels, factors of metabolic syndrome, were significantly higher in the low physical activity group than in the moderate or high activity group. High-density lipoprotein cholesterol was significantly lower in the low physical activity group than in the moderate or high activity group. Waist circumference and fasting glucose were negatively correlated with physical activity level, and HDL cholesterol showed a positive correlation with waist circumference. The odds ratios for metabolic syndrome were 2.03 times higher (95% confidence interval, 1.01–4.09) in the low physical activity group than in the high physical activity group. [Conclusion] Low physical activity was a risk factor for metabolic syndrome in white-collar workers. Therefore, increasing physical activity in daily life may prevent metabolic syndrome in white-collar workers. PMID:27942116

  7. The relationship between physical activity levels and metabolic syndrome in male white-collar workers.

    PubMed

    Ko, Kwang-Jun; Kim, Eon-Ho; Baek, Un-Hyo; Gang, Zhao; Kang, Seol-Jung

    2016-11-01

    [Purpose] Physical activity is important for preventing and managing metabolic syndrome. White-collar workers can be inherently predisposed to chronic diseases, as their jobs are primarily sedentary. The purpose of this study was to examine the relationship between physical activity and metabolic syndrome in male white-collar workers. [Subjects and Methods] Physical activity and metabolic syndrome factors were measured in 331 male public office workers. Physical activity was classified as high (N=101), moderate (N=115), or low (N=111) using the International Physical Activity Questionnaire. To diagnose metabolic syndrome, the U.S. National Cholesterol Education Program's standard was used. [Results] Waist circumference and triglyceride levels, factors of metabolic syndrome, were significantly higher in the low physical activity group than in the moderate or high activity group. High-density lipoprotein cholesterol was significantly lower in the low physical activity group than in the moderate or high activity group. Waist circumference and fasting glucose were negatively correlated with physical activity level, and HDL cholesterol showed a positive correlation with waist circumference. The odds ratios for metabolic syndrome were 2.03 times higher (95% confidence interval, 1.01-4.09) in the low physical activity group than in the high physical activity group. [Conclusion] Low physical activity was a risk factor for metabolic syndrome in white-collar workers. Therefore, increasing physical activity in daily life may prevent metabolic syndrome in white-collar workers.

  8. Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain.

    PubMed

    Forte, Brittany L; Slosky, Lauren M; Zhang, Hong; Arnold, Moriah R; Staatz, William D; Hay, Meredith; Largent-Milnes, Tally M; Vanderah, Todd W

    2016-12-01

    Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT2 antagonist had no effect; an AT1 antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain.

  9. Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

    PubMed Central

    Forte, Brittany L.; Slosky, Lauren M.; Zhang, Hong; Arnold, Moriah R.; Staatz, William D.; Hay, Meredith; Largent-Milnes, Tally M.; Vanderah, Todd W.

    2016-01-01

    Abstract Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT2 antagonist had no effect; an AT1 antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain. PMID:27541850

  10. Increased aortic intimal proliferation due to MasR deletion in vitro

    PubMed Central

    Alsaadon, Hiba; Kruzliak, Peter; Smardencas, Arthur; Hayes, Alan; Bader, Michael; Angus, Peter; Herath, Chandana; Zulli, Anthony

    2015-01-01

    A growing body of evidence suggests that the vascular actions of Ang-(1-7) appear to involve increased production of nitric oxide (NO), an important vasodilator, through the activation of MasR, thus indicating the involvement of the MasR in preventing endothelial dysfunction. However, it is unknown whether the MasR could be involved in the progression of the next step in atherosclerosis, neo-intimal formation. To determine whether the deletion of the MasR is involved in the development of intimal thickening in an in vitro model. Mice [three background controls (C57Bl/6) and 3 MasR (−/−)] were killed and the aortas excised and cleaned of connective tissue and cut into 3 mm rings. Rings were placed in an organ culture medium for 5 weeks, embedded in paraffin, cut at 5 μm and stained with haematoxylin and eosin and Masson’s trichrome. In addition, aortic reactivity was measured in organ baths. After 5 weeks of culture, the intima:media ratio increased in the aortas from MasR (−/−) mice compared to the control group by 4.5-fold (P < 0.01). However, no significant difference in nuclei area count (cell proliferation) between the MasR (−/−) mice and control group was observed (0.87 ± 0.29% vs. 0.94 ± 0.18%, respectively, P = ns). Functional studies showed only a minor vasoconstrictive and full vasodilative response. This study shows that the deletion of the MasR causes marked increase in the aortic intima:media ratio, which is not due to generalized cellular proliferation. These results provide a functional role for the MasR in atherogenesis. PMID:25676544

  11. Increased aortic intimal proliferation due to MasR deletion in vitro.

    PubMed

    Alsaadon, Hiba; Kruzliak, Peter; Smardencas, Arthur; Hayes, Alan; Bader, Michael; Angus, Peter; Herath, Chandana; Zulli, Anthony

    2015-06-01

    A growing body of evidence suggests that the vascular actions of Ang-(1-7) appear to involve increased production of nitric oxide (NO), an important vasodilator, through the activation of MasR, thus indicating the involvement of the MasR in preventing endothelial dysfunction. However, it is unknown whether the MasR could be involved in the progression of the next step in atherosclerosis, neo-intimal formation. To determine whether the deletion of the MasR is involved in the development of intimal thickening in an in vitro model. Mice [three background controls (C57Bl/6) and 3 MasR (-/-)] were killed and the aortas excised and cleaned of connective tissue and cut into 3 mm rings. Rings were placed in an organ culture medium for 5 weeks, embedded in paraffin, cut at 5 μm and stained with haematoxylin and eosin and Masson's trichrome. In addition, aortic reactivity was measured in organ baths. After 5 weeks of culture, the intima:media ratio increased in the aortas from MasR (-/-) mice compared to the control group by 4.5-fold (P < 0.01). However, no significant difference in nuclei area count (cell proliferation) between the MasR (-/-) mice and control group was observed (0.87 ± 0.29% vs. 0.94 ± 0.18%, respectively, P = ns). Functional studies showed only a minor vasoconstrictive and full vasodilative response. This study shows that the deletion of the MasR causes marked increase in the aortic intima:media ratio, which is not due to generalized cellular proliferation. These results provide a functional role for the MasR in atherogenesis.

  12. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome

    PubMed Central

    Seror, Raphaèle; Ravaud, Philippe; Bowman, Simon; Baron, Gabriel; Tzioufas, Athanasios; Theander, Elke; Gottenberg, Jacques-Eric; Bootsma, Hendrika; Mariette, Xavier; Vitali, Claudio

    2010-01-01

    Objective To develop a disease activity index for patients with primary Sjögren’s syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI). Methods Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific “domains” contributing to disease activity. For each domain, features of disease activity were classified in 3 or 4 levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0–10 physician global assessment (PhGA) scale, each expert scored the disease activity of 5 patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. Results All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.0001). Compared to 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. Conclusion The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardized evaluation of primary SS should facilitate clinical research and should be helpful as an outcome measure in clinical trials. PMID:19561361

  13. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of the macrophage activation syndrome: Re-analysis of a prior Phase III trial

    PubMed Central

    Shakoory, B.; Carcillo, J.A.; Chatham, W. W.; Amdur, R. L.; Zhao, H.; Dinarello, C.A.; Cron, R.Q.; Opal, S.M.

    2017-01-01

    Objective To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome (MAS). Despite equivocal results in sepsis trials, anakinra is effective in treating MAS, a similar entity with fever, disseminated intravascular coagulation (DIC), hepatobiliary dysfunction (HBD), cytopenias, and hyperferritinemia. Hence, sepsis patients with MAS features may benefit from IL-1 receptor blockade. Design Re-analysis of de-identified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis (Opal, et. al. Crit Care Med. 1997 Jul;25(7):1115–24). Setting Multi-center study recruiting through 91 centers from 11 countries in Europe and North America. Participants Sepsis patients with MODS and/or shock (original study) were re-grouped based on presence or absence of concurrent HBD and DIC as features of MAS (HBD/DIC group). The “non-HBD/DIC” group included patients with only HBD, only DIC or neither. Intervention Treatment with anakinra or placebo. Main Outcome(s) and Measure(s) 28-day mortality. Statistical analysis descriptive statistics, chi-square, ANOVA, logistic and Cox regression. Results Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent HBD/DIC was noted in 43 patients (5.6% of total, ages 18–75; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-HBD/DIC patients (71.4% vs. 70.8%, p=.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in HBD/DIC patients (65.4% anakinra vs. 35.3% placebo), with HR for death 0.28 (0.11–0.71, p = 0.0071) for the treatment group in Cox regression. Conclusions and Relevance In this subgroup analysis, IL-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent HBD/DIC. A

  14. BOREAS Level-1B MAS Imagery At-sensor Radiance, Relative X and Y Coordinates

    NASA Technical Reports Server (NTRS)

    Strub, Richard; Strub, Richard; Newcomer, Jeffrey A.; Ungar, Stephen

    2000-01-01

    For BOReal Ecosystem-Atmosphere Study (BOREAS), the MODIS Airborne Simulator (MAS) images, along with the other remotely sensed data, were collected to provide spatially extensive information over the primary study areas. This information includes detailed land cover and biophysical parameter maps such as fraction of Photosynthetically Active Radiation (fPAR) and Leaf Area Index (LAI). Collection of the MAS images occurred over the study areas during the 1994 field campaigns. The level-1b MAS data cover the dates of 21-Jul-1994, 24-Jul-1994, 04-Aug-1994, and 08-Aug-1994. The data are not geographically/geometrically corrected; however, files of relative X and Y coordinates for each image pixel were derived by using the C-130 INS data in a MAS scan model. The data are provided in binary image format files.

  15. Cassini's Maneuver Automation Software (MAS) Process: How to Successfully Command 200 Navigation Maneuvers

    NASA Technical Reports Server (NTRS)

    Yang, Genevie Velarde; Mohr, David; Kirby, Charles E.

    2008-01-01

    To keep Cassini on its complex trajectory, more than 200 orbit trim maneuvers (OTMs) have been planned from July 2004 to July 2010. With only a few days between many of these OTMs, the operations process of planning and executing the necessary commands had to be automated. The resulting Maneuver Automation Software (MAS) process minimizes the workforce required for, and maximizes the efficiency of, the maneuver design and uplink activities. The MAS process is a well-organized and logically constructed interface between Cassini's Navigation (NAV), Spacecraft Operations (SCO), and Ground Software teams. Upon delivery of an orbit determination (OD) from NAV, the MAS process can generate a maneuver design and all related uplink and verification products within 30 minutes. To date, all 112 OTMs executed by the Cassini spacecraft have been successful. MAS was even used to successfully design and execute a maneuver while the spacecraft was in safe mode.

  16. Serum prolidase activity in benign joint hypermobility syndrome

    PubMed Central

    2014-01-01

    Background Moderate joint laxity is widespread in many joints of the body, and this condition is considered to be caused by an abnormality in the collagen structure. This study was carried out to determine the serum prolidase activity in female patients with benign joint hypermobility syndrome (BJHS), and to evaluate its correlation with their clinical features. Methods A total of 45 patients with BJHS and 40 healthy controls were included in the study. All of the patients with BJHS met the Beighton diagnostic criteria. All the patients and the control group underwent a comprehensive examination of the locomotor system and took the New York Posture Rating Test. The examination and test results were recorded. Serum prolidase activity was measured in both the groups. Results Prolidase activity was significantly lower in patients with BJHS (479.52 ± 126.50) compared to the healthy controls (555.97 ± 128.77) (p = 0.007). We found no correlation between serum prolidase activity and Beighton scores or New York rating test scores. On the other hand, mean prolidase activity was significantly lower in patients with pes planus or hyperlordosis compared to those without (p = 0.05, p = 0.03, respectively). We did not find such a correlation with the other clinical features. Conclusions Significantly lower prolidase activity in patients with BJHS suggests that prolidase may affect the collagen metabolism and cause hyperlaxity. PMID:24612543

  17. A Case of Superior Mesenteric Artery Syndrome in a Healthy Active Duty Marine.

    PubMed

    Thota, Darshan; Portouw, Steven J; Bruner, David I

    2015-10-01

    Superior mesenteric artery (SMA) syndrome is an uncommon disorder that can lead to small bowel obstructions or perforations. Typical populations include young females with anorexia. However, there have been a few reports of healthy males with acute vomiting reported to have SMA syndrome. Our case report highlights an active duty Marine who developed SMA syndrome and the importance of recognizing this disease given the severity in delay of diagnosis in population of young healthy active duty members.

  18. Successful Targeted Treatment of Mast Cell Activation Syndrome with Tofacitinib.

    PubMed

    Afrin, Lawrence B; Fox, Roger W; Zito, Susan L; Choe, Leo; Glover, Sarah C

    2017-04-06

    Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile. For example, both activated KIT and numerous cytokine receptors activate the Janus kinases (JAKs). Thus, JAK-inhibiting therapies may be useful against the downstream inflammatory effects of MCAS. The oral JAK1/JAK3 inhibitor, tofacitinib, is currently approved for rheumatoid arthritis and is in clinical trials for other chronic inflammatory disorders. Herein, we report two MCAS patients who rapidly gained substantial symptomatic response to tofacitinib. Their improvement suggests need for further evaluation of this class of drugs in MCAS treatment. This article is protected by copyright. All rights reserved.

  19. Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation.

    PubMed

    Sobrino, Agua; Vallejo, Susana; Novella, Susana; Lázaro-Franco, Macarena; Mompeón, Ana; Bueno-Betí, Carlos; Walther, Thomas; Sánchez-Ferrer, Carlos; Peiró, Concepción; Hermenegildo, Carlos

    2017-04-01

    The Mas receptor is involved in the angiotensin (Ang)-(1-7) vasodilatory actions by increasing nitric oxide production (NO). We have previously demonstrated an increased production of Ang-(1-7) in human umbilical vein endothelial cells (HUVEC) exposed to estradiol (E2), suggesting a potential cross-talk between E2 and the Ang-(1-7)/Mas receptor axis. Here, we explored whether the vasoactive response and NO-related signalling exerted by E2 are influenced by Mas. HUVEC were exposed to 10nM E2 for 24h in the presence or absence of the selective Mas receptor antagonist A779, and the estrogen receptor (ER) antagonist ICI182780 (ICI). E2 increased Akt and endothelial nitric oxide synthase (eNOS) mRNA and protein expression, measured by RT-PCR and Western blot, respectively. Furthermore, E2 increased Akt activity (determined by the levels of phospho-Ser(473)) and eNOS activity (by the enhanced phosphorylation of Ser(1177), the activated form), resulting in increased NO production, which was measured by the fluorescence probe DAF-2-FM. These signalling events were dependent on ER and Mas receptor activation, since they were abolished in the presence of ICI or A779. In ex-vivo functional experiments performed with a small-vessel myograph in isolated mesenteric vessels from wild-type mice pre-contracted with noradrenaline, the relaxant response to physiological concentrations of E2 was blocked by ICI and A779, to the same extent to that obtained in the vessels isolated from Mas-deficient. In conclusion, E2 induces NO production and vasodilation through mechanisms that require Mas receptor activation.

  20. Physical Activity and Chronic Prostatitis/Chronic Pelvic Pain Syndrome

    PubMed Central

    Zhang, Ran; Chomistek, Andrea K.; Dimitrakoff, Jordan D.; Giovannucci, Edward L.; Willett, Walter C.; Rosner, Bernard A.; Wu, Kana

    2014-01-01

    Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relationship between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. Methods We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated based on the responses on the 2008 questionnaire. Participants with pain scores ≥ 8 were considered CP/CPPS cases (n=689). Results Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio (OR) comparing >35.0 to ≤3.5 MET-h/wk of physical activity was 0.72 (95% confidence interval (CI): 0.56, 0.92, p for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (p for trend 0.64). Conclusions Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-aged and older men. PMID:25116086

  1. Do Children with down Syndrome Perform Sufficient Physical Activity to Maintain Good Health? A Pilot Study

    ERIC Educational Resources Information Center

    Shields, Nora; Dodd, Karen J.; Abblitt, Casey

    2009-01-01

    Our pilot study investigated if children with Down syndrome engaged in the recommended 60 min of moderate to vigorous physical activity (MVPA) every day. Twenty-three children with Down syndrome (7 girls, 16 boys; mean age 11.7 years, SD = 3.1) wore a triaxial accelerometer for 7 consecutive days to measure their activity levels. The average…

  2. Identifying the Barriers and Facilitators to Participation in Physical Activity for Children with Down Syndrome

    ERIC Educational Resources Information Center

    Barr, M.; Shields, N.

    2011-01-01

    Background: Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Methods: Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged…

  3. AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection.

    PubMed

    da Costa Gonçalves, Andrey C; Fraga-Silva, Rodrigo A; Leite, Romulo; Santos, Robson A S

    2013-03-01

    The renin-angiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin-(1-7) appears to mediate penile erection by activation of the Mas receptor. Recently, we have shown that the erectile function of Mas gene-deleted mice was substantially reduced, which was associated with a marked increase in fibrous tissue in the corpus cavernosum. We have hypothesized that the synthetic non-peptide Mas agonist, AVE 0991, would potentiate penile erectile function. We showed that intracavernosal injection of AVE 0991 potentiated the erectile response of anaesthetized Wistar rats, measured as the ratio between corpus cavernosum pressure and mean arterial pressure, upon electrical stimulation of the major pelvic ganglion. The facilitatory effect of AVE 0991 on erectile function was dose dependent and completely blunted by the nitric oxide synthesis inhibitor, l-NAME. Importantly, concomitant intracavernosal infusion of the specific Mas receptor blocker, A-779, abolished the effect of AVE 0991. We demonstrated that AVE 0991 potentiates the penile erectile response through Mas in an NO-dependent manner. Importantly, these results suggest that Mas agonists, such as AVE 0991, might have significant therapeutic benefits for the treatment of erectile dysfunction.

  4. A novel α/β-hydrolase gene IbMas enhances salt tolerance in transgenic sweetpotato.

    PubMed

    Liu, Degao; Wang, Lianjun; Zhai, Hong; Song, Xuejin; He, Shaozhen; Liu, Qingchang

    2014-01-01

    Salt stress is one of the major environmental stresses in agriculture worldwide and affects crop productivity and quality. The development of crops with elevated levels of salt tolerance is therefore highly desirable. In the present study, a novel maspardin gene, named IbMas, was isolated from salt-tolerant sweetpotato (Ipomoea batatas (L.) Lam.) line ND98. IbMas contains maspardin domain and belongs to α/β-hydrolase superfamily. Expression of IbMas was up-regulated in sweetpotato under salt stress and ABA treatment. The IbMas-overexpressing sweetpotato (cv. Shangshu 19) plants exhibited significantly higher salt tolerance compared with the wild-type. Proline content was significantly increased, whereas malonaldehyde content was significantly decreased in the transgenic plants. The activities of superoxide dismutase (SOD) and photosynthesis were significantly enhanced in the transgenic plants. H2O2 was also found to be significantly less accumulated in the transgenic plants than in the wild-type. Overexpression of IbMas up-regulated the salt stress responsive genes, including pyrroline-5-carboxylate synthase, pyrroline-5-carboxylate reductase, SOD, psbA and phosphoribulokinase genes, under salt stress. These findings suggest that overexpression of IbMas enhances salt tolerance of the transgenic sweetpotato plants by regulating osmotic balance, protecting membrane integrity and photosynthesis and increasing reactive oxygen species scavenging capacity.

  5. A Novel α/β-Hydrolase Gene IbMas Enhances Salt Tolerance in Transgenic Sweetpotato

    PubMed Central

    Song, Xuejin; He, Shaozhen; Liu, Qingchang

    2014-01-01

    Salt stress is one of the major environmental stresses in agriculture worldwide and affects crop productivity and quality. The development of crops with elevated levels of salt tolerance is therefore highly desirable. In the present study, a novel maspardin gene, named IbMas, was isolated from salt-tolerant sweetpotato (Ipomoea batatas (L.) Lam.) line ND98. IbMas contains maspardin domain and belongs to α/β-hydrolase superfamily. Expression of IbMas was up-regulated in sweetpotato under salt stress and ABA treatment. The IbMas-overexpressing sweetpotato (cv. Shangshu 19) plants exhibited significantly higher salt tolerance compared with the wild-type. Proline content was significantly increased, whereas malonaldehyde content was significantly decreased in the transgenic plants. The activities of superoxide dismutase (SOD) and photosynthesis were significantly enhanced in the transgenic plants. H2O2 was also found to be significantly less accumulated in the transgenic plants than in the wild-type. Overexpression of IbMas up-regulated the salt stress responsive genes, including pyrroline-5-carboxylate synthase, pyrroline-5-carboxylate reductase, SOD, psbA and phosphoribulokinase genes, under salt stress. These findings suggest that overexpression of IbMas enhances salt tolerance of the transgenic sweetpotato plants by regulating osmotic balance, protecting membrane integrity and photosynthesis and increasing reactive oxygen species scavenging capacity. PMID:25501819

  6. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China

    PubMed Central

    Xiao, Jing; Shen, Chong; Chu, Min J.; Gao, Yue X.; Xu, Guang F.; Huang, Jian P.; Xu, Qiong Q.; Cai, Hui

    2016-01-01

    Background Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. Methods The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Results Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15–40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15–30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Conclusions Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also

  7. [Two cases of Lambert-Eaton syndrome with an increase of serum cholinesterase activity].

    PubMed

    Ciechanowski, K; Cebula, D

    1997-02-01

    Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with small cell lung cancer. An increase of serum cholinesterase activity was explained by induced release of biologically active proteins by neoplastic tissue.

  8. Cortical Activation During Levitation and Tentacular Movements of Corticobasal Syndrome

    PubMed Central

    Onofrj, Marco; Bonanni, Laura; Pizzi, Stefano Delli; Caulo, Massimo; Onofrj, Valeria; Thomas, Astrid; Tartaro, Armando; Franciotti, Raffaella

    2015-01-01

    Abstract Levitation and tentacular movements (LTM) are considered specific, yet rare (30%), features of Corticobasal Syndrome (CBS), and are erroneously classified as alien hand. Our study focuses on these typical involuntary movements and aims to highlight possible neural correlates. LTM were recognizable during functional magnetic resonance imaging (fMRI) in 4 of 19 CBS patients. FMRI activity was evaluated with an activation recognition program for movements, during LTM, consisting of levitaton and finger writhing, and compared with the absence of movement (rest) and voluntary movements (VM), similar to LTM, of affected and unaffected arm-hand. FMRI acquisition blocks were balanced in order to match LTM blocks with rest and VM conditions. In 1 of the 4 patients, fMRI was acquired only during LTM and with a different equipment. Despite variable intensity and range of involuntary movements, evidenced by videos, fMRI showed, during LTM, a significant (P<0.05–0.001) activation only of the contralateral primary motor cortex (M1). Voluntary movements of the affected and unaffected arm elicited the known network including frontal, supplementary, sensory-motor cortex, and cerebellum. Willed movements of the LTM-affected arm induced higher and wider activation of contralateral M1 compared with the unaffected arm. The isolated activation of M1 suggests that LTM is a cortical disinhibition symptom, not involving a network. Higher activation of M1 during VM confirms that M1 excitability changes occur in CBS. Our study calls, finally, attention to the necessity to separate LTM from other alien hand phenomena. PMID:26559277

  9. Cortical Activation During Levitation and Tentacular Movements of Corticobasal Syndrome.

    PubMed

    Onofrj, Marco; Bonanni, Laura; Delli Pizzi, Stefano; Caulo, Massimo; Onofrj, Valeria; Thomas, Astrid; Tartaro, Armando; Franciotti, Raffaella

    2015-11-01

    Levitation and tentacular movements (LTM) are considered specific, yet rare (30%), features of Corticobasal Syndrome (CBS), and are erroneously classified as alien hand. Our study focuses on these typical involuntary movements and aims to highlight possible neural correlates.LTM were recognizable during functional magnetic resonance imaging (fMRI) in 4 of 19 CBS patients. FMRI activity was evaluated with an activation recognition program for movements, during LTM, consisting of levitaton and finger writhing, and compared with the absence of movement (rest) and voluntary movements (VM), similar to LTM, of affected and unaffected arm-hand. FMRI acquisition blocks were balanced in order to match LTM blocks with rest and VM conditions. In 1 of the 4 patients, fMRI was acquired only during LTM and with a different equipment.Despite variable intensity and range of involuntary movements, evidenced by videos, fMRI showed, during LTM, a significant (P<0.05-0.001) activation only of the contralateral primary motor cortex (M1). Voluntary movements of the affected and unaffected arm elicited the known network including frontal, supplementary, sensory-motor cortex, and cerebellum. Willed movements of the LTM-affected arm induced higher and wider activation of contralateral M1 compared with the unaffected arm.The isolated activation of M1 suggests that LTM is a cortical disinhibition symptom, not involving a network. Higher activation of M1 during VM confirms that M1 excitability changes occur in CBS. Our study calls, finally, attention to the necessity to separate LTM from other alien hand phenomena.

  10. Dental perspectives in fibrous dysplasia and McCune-Albright syndrome.

    PubMed

    Akintoye, Sunday O; Boyce, Alison M; Collins, Michael T

    2013-09-01

    McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain, and compromised oral health. Maxillomandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There are limited data on the outcomes of dental treatments in maxillomandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillomandibular FD within the context of MAS.

  11. Dental Perspectives in Fibrous Dysplasia and McCune-Albright Syndrome

    PubMed Central

    Akintoye, Sunday O.; Boyce, Alison M.; Collins, Michael T.

    2013-01-01

    McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (PFD), endocrine disorders and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain and compromised oral health. Maxillo-mandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There is limited data on the outcomes of dental treatments in maxillo-mandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillo-mandibular FD within the context of MAS. PMID:23953425

  12. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  13. Immunomodulating activity of Pidotimod in children with Down syndrome.

    PubMed

    Zuccotti, G V; Mameli, C; Trabattoni, D; Beretta, S; Biasin, M; Guazzarotti, L; Clerici, M

    2013-01-01

    Acute respiratory tract infections (ARTIs) are the most frequent illnesses in pediatric age, frequently experienced in children with Down Syndrome (DS) due to the associated immune defects of both specific and non-specific immunity. Pidotimod, a synthetic immunostimulant, was shown to reduce the rates of ARTIs in children with DS, however the mechanisms associated with this effect is currently unknown. We analyzed immune parameters in DS children who received the seasonal 2011–2012 virosomal-adjuvanted influenza vaccine. Eighteen children aged 3-10 years (mean age 7.1+/-2.6 years) were randomly assigned (1:1 ratio) to receive Pidotimod 400 mg, administered orally once a day for 90 days or placebo. At the recruitment (T0) all children received a single dose of virosomal-adjuvanted influenza vaccine (Flu). Blood samples were collected at T0 and 3 months after the recruitment (T3) in order to evaluate innate and adaptative immune responses pathway. Flu-specific IgG1 and IgG3 levels in plasma samples were determined at pre-vaccination (T0), and 1 (T1) and 3 months (T3) post-vaccination. The use of Pidotimod was associated with the upregulation of a number of genes involved in the activation of innate immune responses and in antimicrobial activity. Interestingly the ratio of Flu-specific IgG1/IgG3 was skewed in pidotimod-treated individuals, suggesting a preferential activation of complement-dependent effector mechanisms. Although preliminary these data suggest that Pidotimod can potentiate the beneficial effect of immunization, possibly resulting in a stronger activity of both innate and adaptive immune responses.

  14. Physical Activity Engagement in Young People with Down Syndrome: Investigating Parental Beliefs

    ERIC Educational Resources Information Center

    Alesi, Marianna; Pepi, Annamaria

    2017-01-01

    Background: Despite the wide documentation of the physical/psychological benefits derived from regular physical activity (PA), high levels of inactivity are reported among people with Down syndrome. Method: Semi-structured interviews were conducted with 13 parents of young people with Down syndrome. Results Three facilitation themes were…

  15. Abnormal fMRI Activation Pattern during Story Listening in Individuals with Down Syndrome

    ERIC Educational Resources Information Center

    Reynolds Losin, Elizabeth A.; Rivera, Susan M.; O'Hare, Elizabeth D.; Sowell, Elizabeth R.; Pinter, Joseph D.

    2009-01-01

    Down syndrome is characterized by disproportionately severe impairments of speech and language, yet little is known about the neural underpinnings of these deficits. We compared fMRI activation patterns during passive story listening in 9 young adults with Down syndrome and 9 approximately age-matched, typically developing controls. The typically…

  16. Parents' Perceptions of Health and Physical Activity Needs of Children with Down Syndrome

    ERIC Educational Resources Information Center

    Menear, Kristi Sayers

    2007-01-01

    Individuals with Down syndrome typically have low fitness levels and obesity despite data that indicate physiological gains from physical activity and exercise interventions. Low fitness levels and obesity in individuals with Down syndrome may be related to sedentary lifestyles, social and recreational opportunities, or low motivation to be…

  17. Heteromerization Between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences.

    PubMed

    Cerrato, Bruno D; Carretero, Oscar A; Janic, Brana; Grecco, Hernán E; Gironacci, Mariela M

    2016-10-01

    Bradykinin B2 receptor (B2R) and angiotensin-(1-7) Mas receptor (MasR)-mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R-MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R-MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R-MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal-regulated kinase phosphorylation after angiotensin-(1-7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R-MasR but not in B2R-expressing cells. Angiotensin-(1-7) and bradykinin elicited antiproliferative effects only in cells expressing B2R-MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1-7) MasR-mediated effects. B2R-MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.

  18. Parents' perceptions of health and physical activity needs of children with Down syndrome.

    PubMed

    Sayers Menear, Kristi

    2007-07-01

    Individuals with Down syndrome typically have low fitness levels and obesity despite data that indicate physiological gains from physical activity and exercise interventions. Low fitness levels and obesity in individuals with Down syndrome may be related to sedentary lifestyles, social and recreational opportunities, or low motivation to be physically active. These causal influences on the overall health of individuals with Down syndrome may be related to parental or caregiver support. Through this study, parents of children with Down syndrome from preschool to adolescent ages were interviewed about their perceptions of the health and physical activity needs of their children. Data from four focus groups indicated the following most salient themes: (1) all parents believed participation in physical activity has immediate and long-term positive health impacts on their child with Down syndrome, and most of the parents thought their child would benefit from being more physically active, (2) most parents observed that their child participated in physical activities primarily for social reasons, most notably to be with their peers with or without Down syndrome or to be with their sibling(s), and that without such motivation their child would choose sedentary activities, (3) parents of teenagers identified a need for their child to learn an individual sport to have sporting opportunities that do not require ability-matched teammates and opponents, and (4) parents recognised their need for help from physical activity specialists through either parent education regarding home-based physical activity programmes or an increase in appropriate community-based physical activity programmes for their child with Down syndrome. The interview data suggest future research should evaluate the outcomes of long-term individualised home-based physical activity interventions for children with Down syndrome. Additionally, educators, recreation specialists, and therapists should assist

  19. Investigation of domain size in polymer membranes using double quantum filtered spin diffusion MAS NMR.

    SciTech Connect

    Fujimoto, Cy H.; Alam, Todd Michael; Cherry, Brian Ray; Cornelius, Christopher James

    2005-02-01

    Solid-state {sup 1}H magic angle spinning (MAS) NMR was used to investigate sulfonated Diels-Alder poly(phenlylene) polymer membranes. Under high spinning speed {sup 1}H MAS conditions, the proton environments of the sulfonic acid and phenylene polymer backbone are resolved. A double-quantum (DQ) filter using the rotor-synchronized back-to-back (BABA) NMR multiple-pulse sequence allowed the selective suppression of the sulfonic proton environment in the {sup 1}H MAS NMR spectra. This DQ filter in conjunction with a spin diffusion NMR experiment was then used to measure the domain size of the sulfonic acid component within the membrane. In addition, the temperature dependence of the sulfonic acid spin-spin relaxation time (T{sub 2}) was determined, providing an estimate of the activation energy for the proton dynamics of the dehydrated membrane.

  20. Hyponatremia, hypophosphatemia, and hypouricemia in a girl with macrophage activation syndrome.

    PubMed

    Yamazawa, Kazuki; Kodo, Kazuki; Maeda, Jun; Omori, Sayu; Hida, Mariko; Mori, Tetsuya; Awazu, Midori

    2006-12-01

    Macrophage activation syndrome, a life-threatening complication of rheumatic disorders, is accompanied by the overproduction of cytokines. We describe a girl with macrophage activation syndrome complicating systemic-onset juvenile arthritis who developed hyponatremia, hypophosphatemia, and hypouricemia associated with a high level of serum tumor necrosis factor alpha. Renal proximal tubule dysfunction was considered to be the cause, which may be attributable to tumor necrosis factor alpha.

  1. Oxidized LDL induces in vitro lymphocyte activation in antiphospholipid syndrome.

    PubMed

    Laczik, Renata; Szodoray, Peter; Veres, Katalin; Lakos, Gabriella; Sipka, Sandor; Szegedi, Gyula; Soltész, Pal

    2010-06-01

    Oxidized low-density lipoprotein (oxLDL) is a key feature of the atheromatosus plaque and plays a critical role in foam cell formation and perpetuation of inflammatory processes. In antiphospholipid syndrome (APS), oxLDL molecules form complexes with beta2GPI and become target antigens for autoantibodies, which are detectable in the sera of these patients. oxLDL takes part in the pathogenesis of APS and in the concomitant accelerated atherosclerosis, yet the exact associated immune mechanisms are not clear in details. The aim of this study was to assess the activation and proliferation response of peripheral blood mononuclear cells (PBMCs) derived from patients with APS in the presence of oxLDL. Thirteen patients with APS and nine healthy individuals were enrolled in the study. Separated PBMCs of these patients were cultured in the presence of immunogenic epitope of oxLDL. Lymphocyte proliferation and cytokine secretion (TNF-alpha, IL-2, IFN-gamma, IL-4, and IL-10) were assessed by ELISA. We found significant PBMC proliferation in APS compared to healthy controls (PI/proliferation index/APS: 1.76 vs. PI control: 0.56; p = 0.032). A significant IL-2 and IFN-gamma secretion were detected upon oxLDL stimulus in patients with APS compared to controls (IL-2 cytokine secretion index (CSI) APS: 278.5, IL-2 CSI controls: 65.1; p = 0.025; IFN-gamma CSI APS: 163.2, IFN-gamma CSI controls: 77.4; p = 0.025). Based on our findings, we assume that oxLDL via Th1-type cytokine production and lymphocyte proliferation may contribute to the perpetuation of immune processes in APS.

  2. [Multi-organ failure as first clinical sign of macrophage activation syndrome in childhood Still's disease].

    PubMed

    López-Sánchez, M; Rubio-López, I; Obeso-González, T; Teja-Barbero, J L; Santidrián-Miguel, J P; Peiro-Callizo, E

    2010-10-01

    Macrophage activation syndrome is a form of secondary haemophagocytic lymphohistiocytosis seen in the context of rheumatic diseases. It is seen most frequently in association with systemic onset juvenile arthritis or childhood Still's disease. Hemophagocytosis is part of a sepsis-like clinical syndrome caused by hypercytokinemia due to a highly stimulated but ineffective immune response. Coagulopathy and hemorrhages, decreased white cell count, elevated levels of aspartate aminotransferase, fever, rash, hepatosplenomegaly and central nervous system dysfunction are some of diagnostic criteria of macrophage activation syndrome, but it is very difficult to diagnose due to the lack of specific clinical signs. We report a 8-year-old child who was admitted to the ICU with lethargy, fever, acute respiratory failure, coagulopathy, metabolic acidosis and multiorgan failure. Septic shock was suspected, but he was diagnosed with macrophage activation syndrome and treated with corticosteroids and intravenous immunoglobulin and later discharged from the ICU.

  3. Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.

    PubMed

    Krey, Jocelyn F; Paşca, Sergiu P; Shcheglovitov, Aleksandr; Yazawa, Masayuki; Schwemberger, Rachel; Rasmusson, Randall; Dolmetsch, Ricardo E

    2013-02-01

    L-type voltage gated calcium channels have an important role in neuronal development by promoting dendritic growth and arborization. A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs). We report that channels with the Timothy syndrome alteration cause activity-dependent dendrite retraction in rat and mouse neurons and in induced pluripotent stem cell (iPSC)-derived neurons from individuals with Timothy syndrome. Dendrite retraction was independent of calcium permeation through the mutant channel, was associated with ectopic activation of RhoA and was inhibited by overexpression of the channel-associated GTPase Gem. These results suggest that Ca(V)1.2 can activate RhoA signaling independently of Ca(2+) and provide insights into the cellular basis of Timothy syndrome and other ASDs.

  4. Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

    PubMed

    Ng, Wan-Fai; Miller, Ariana; Bowman, Simon J; Price, Elizabeth J; Kitas, George D; Pease, Colin; Emery, Paul; Lanyon, Peter; Hunter, John; Gupta, Monica; Giles, Ian; Isenberg, David; McLaren, John; Regan, Marian; Cooper, Annie; Young-Min, Steven A; McHugh, Neil; Vadivelu, Saravanan; Moots, Robert J; Coady, David; MacKay, Kirsten; Dasgupta, Bhaskar; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; Griffiths, Bridget; Mitchell, Sheryl; Miyamoto, Samira Tatiyama; Trenell, Michael

    2017-04-01

    The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

  5. Effects of the mas-related gene (Mrg) C receptor agonist BAM6-22 on nociceptive reflex activity in naive, monoarthritic and mononeuropathic rats after intraplantar and intrathecal administration.

    PubMed

    Schröder, Wolfgang; Alique, Matilde; Herrero, Juan Fernando

    2016-01-05

    MrgC receptors are selectively expressed on peripheral and central terminals of small calibre nociceptive fibres. Peptide agonists of the MrgC receptor were reported to modulate nociceptive transmission exerting either pro- or antinociceptive effects depending on site of action and pain model used. Here, we investigated the effect of intraplantar and intrathecal administration of the selective MrgC receptor agonist BAM6-22 on mechanically and electrically evoked nociceptive reflex activity as a uniform readout measure in naïve, monoarthritic and mononeuropathic rats. In naïve rats, intraplantar BAM6-22 enhanced, whereas intrathecal BAM6-22 did not modulate mechanically-evoked nociceptive reflex activity. In monoarthritic rats, intraplantar BAM6-22 had no effect, whereas intrathecal BAM6-22 inhibited mechanically evoked nociceptive reflex activity. In mononeuropathic rats, BAM6-22 reduced mechanically evoked nociceptive reflex activity after both intraplantar and intrathecal administration. BAM6-22 did not modulate electrically evoked nociceptive reflex activity in any condition. Thus, the results of the present investigation confirm and add to previous studies demonstrating that site of action, (patho)-physiological state and stimulus modality determine the effect quality of MrgC receptor agonists. It still needs to be explored how concurrent activation of peripheral and spinal MrgC receptors modulates nociceptive processing under conditions of both acute and chronic pain to evaluate the therapeutic potential of putative small molecule MrgC receptor agonists as innovative analgesics.

  6. Physical Fitness and Physical Activity in Adolescents with Asperger Syndrome: A Comparative Study

    ERIC Educational Resources Information Center

    Borremans, Erwin; Rintala, Pauli; McCubbin, Jeffrey A.

    2010-01-01

    While physical activity is beneficial for youth with developmental disabilities, little is known about those individuals' fitness profile and levels of activity. Therefore the purpose of this study was to investigate the physical fitness profile and physical activity level of 30 adolescents with and without Asperger syndrome (AS). Evaluations were…

  7. The syndrome of `continuous muscle-fibre activity' cured: further studies

    PubMed Central

    Isaacs, Hyam; Heffron, J. J. A.

    1974-01-01

    Two cases suffering from the syndrome of `continuous muscle-fibre activity' have been followed-up for 14 years. These patients have gradually gone into remission and no longer require therapy. The results of recent histology, histochemistry, and electronmicroscopy, as well as sural nerve biopsy studies, are presented. The sarcoplasmic reticulum calcium binding activity and ATPase activity are normal. Images PMID:4281819

  8. Recreational Physical Activity and Premenstrual Syndrome in Young Adult Women: A Cross-Sectional Study

    PubMed Central

    Ronnenberg, Alayne G.; Zagarins, Sofija E.; Houghton, Serena C.; Takashima-Uebelhoer, Biki B.; Bertone-Johnson, Elizabeth R.

    2017-01-01

    Introduction It is estimated that up to 75% of premenopausal women experience at least one premenstrual symptom and 8–20% meet clinical criteria for premenstrual syndrome. Premenstrual syndrome substantially reduces quality of life for many women of reproductive age, with pharmaceutical treatments having limited efficacy and substantial side effects. Physical activity has been recommended as a method of reducing menstrual symptom severity. However, this recommendation is based on relatively little evidence, and the relationship between physical activity, premenstrual symptoms, and premenstrual syndrome remains unclear. Methods We evaluated the relationship between physical activity and premenstrual syndrome and premenstrual symptoms among 414 women aged 18–31. Usual premenstrual symptom experience was assessed with a modified version of the Calendar of Premenstrual Experiences. Total, physical, and affective premenstrual symptom scores were calculated for all participants. Eighty women met criteria for moderate-to-severe premenstrual syndrome, while 89 met control criteria. Physical activity, along with dietary and lifestyle factors, was assessed by self-report. Results Physical activity was not significantly associated with total, affective, or physical premenstrual symptom score. Compared to the women with the lowest activity, women in tertiles 2 and 3 of activity, classified as metabolic equivalent task hours, had prevalence odds ratios for premenstrual syndrome of 1.5 (95% CI: 0.6–3.7) and 0.9 (95% CI: 0.4–2.4), respectively (p-value for trend = 0.85). Conclusions We found no association between physical activity and either premenstrual symptom scores or the prevalence of premenstrual syndrome. PMID:28081191

  9. Allergic manifestations and cutaneous histamine responses in patients with McCune Albright syndrome

    PubMed Central

    2013-01-01

    Background McCune Albright syndrome (MAS) is a rare disorder characterized by precocious puberty, café-au-lait spots, and fibrous dysplasia. Its cause is an activating mutation in the GNAS gene, encoding a subunit of the stimulatory G protein, Gsalpha (Gsα). The action of any mediator that signals via Gsα and cyclic AMP can be up regulated in MAS. We had observed gastritis, gastroesophageal reflux, and anaphylaxis in McCune Albright patients. Objective As histamine is known to signal via histamine 1 (H1) and histamine 2 (H2) receptors, which couple with stimulatory G proteins, we attempted to mechanistically link histamine responsiveness to the activating GNAS mutation. We hypothesized that responsiveness to histamine skin testing would differ between MAS patients and healthy controls. Patients and methods After obtaining informed consent, we performed a systematic review of histamine responsiveness and allergic manifestations in 11 MAS patients and 11 sex-matched, Tanner-stage matched controls. We performed skin prick testing, quantifying the orthogonal diameters of wheals and erythema. We also quantitated G protein mRNA expression. Results The peak wheal and flare responses to histamine were significantly higher in MAS patients compared to controls. Conclusions This study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls. PMID:23663565

  10. Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats.

    PubMed

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of "metabolic syndrome rats", compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

  11. Object Recognition in Williams Syndrome: Uneven Ventral Stream Activation

    ERIC Educational Resources Information Center

    O'Hearn, Kirsten; Roth, Jennifer K.; Courtney, Susan M.; Luna, Beatriz; Street, Whitney; Terwillinger, Robert; Landau, Barbara

    2011-01-01

    Williams syndrome (WS) is a genetic disorder associated with severe visuospatial deficits, relatively strong language skills, heightened social interest, and increased attention to faces. On the basis of the visuospatial deficits, this disorder has been characterized primarily as a deficit of the dorsal stream, the occipitoparietal brain regions…

  12. Electrodermal Orienting Activity in Children with Down Syndrome.

    ERIC Educational Resources Information Center

    Martinez-Selva, Jose M.; And Others

    1995-01-01

    The elicitation and habituation of electrodermal orienting responses to auditory stimuli of 19 children with Down syndrome (DS) and a control group were compared. The DS children gave electrodermal orienting responses of a lower amplitude than did control subjects. No significant differences were found in either skin conductance levels or…

  13. Active surveillance for congenital rubella syndrome in Yangon, Myanmar.

    PubMed Central

    Thant, Kyaw-Zin; Oo, Win-Mar; Myint, Thein-Thein; Shwe, Than-Nu; Han, Aye-Maung; Aye, Khin-Mar; Aye, Kay-Thi; Moe, Kyaw; Thein, Soe; Robertson, Susan E.

    2006-01-01

    OBJECTIVE: Rubella vaccine is not included in the immunization schedule in Myanmar. Although surveillance for outbreaks of measles and rubella is conducted nationwide, there is no routine surveillance for congenital rubella syndrome (CRS). Therefore, we organized a study to assess the burden of CRS. METHODS: From 1 December 2000 to 31 December 2002 active surveillance for CRS was conducted among children aged 0-17 months at 13 hospitals and 2 private clinics in Yangon, the capital city. Children with suspected CRS had a standard examination and a blood sample was obtained. All serum samples were tested for rubella-specific IgM; selected samples were tested for rubella-specific IgG and for rubella RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). FINDINGS: A total of 81 children aged 0-17 months were suspected of having CRS. Of these, 18 children had laboratory-confirmed CRS (7 were IgM positive; 7 were RT-PCR positive; and 10 were IgG positive at > 6 months of age). One additional child who tested positive by RT-PCR and whose mother had had rubella during pregnancy but who had a normal clinical examination was classified as having congenital rubella infection. During 2001-02 no rubella outbreaks were detected in Yangon Division. In the 31 urban townships of Yangon Division, the annual incidence was 0.1 laboratory-confirmed cases of CRS per 1000 live births. CONCLUSION: This is the first population-based study of CRS incidence from a developing country during a rubella-endemic period; the incidence of CRS is similar to endemic rates found in industrialized countries during the pre-vaccine era. Rubella-specific IgG tests proved practical for diagnosing CRS in children aged > 6 months. This is one of the first studies to report on the use of rubella-specific RT-PCR directly on serum samples; further studies are warranted to confirm the utility of this method as an additional means of diagnosing CRS. PMID:16501710

  14. [Polyserositic syndromes and/or sectorial dysventilation with platelet activation induced by immunoallergic etiopathogenesis].

    PubMed

    De Luca, L

    1989-01-01

    The author from a study of 5 dysventilatorial syndromes (bronchiolitis-PNX, pneumomediastinal aerial cystis of lung) and 5 polysierositic syndromes pleuritis and peritonitis) evices that all these syndromes show in the anamnesis or in present a viral infection from influenzal virus or rubeola. In addition to that, the Authors shows the presence of a food allergy asserted by RAST and/or Skin Prick Tests or FBST (Food Bronchostimulation test) and the introduction of a food allergen during the viral infection, and a great platelet's activation. The Author, besides, shows the association normal VES and normal neutrophil cells in the dysventilatorial syndrome and high VES, and high neutrophil cells in the polysierositic syndromes; in all cases the negativity of culture exams. Starting from these points she worked out a new etiopathogenetic theory: the viral localization on the Peyer's plates cause the expression on the epithelial surface of the gut's cells of SELF HLA II type recognition. The food allergens' introduction causes a great reaction of II, III, IV, VI type which involves the bronchus, alveolus, and the serous epithelium by PAF activation, in all cases and in the polisierositic syndrome a neutrophil activation as well. The author advices to prize the importance of cortisone therapy and of exclusion of food allergen by diet, besides advices the antibiotic therapy for covering only.

  15. Identifying Facilitators and Barriers to Physical Activity for Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mahy, J.; Shields, N.; Taylor, N. F.; Dodd, K. J.

    2010-01-01

    Background: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. Method: Semi-structured interviews were conducted to elicit the views of adults with Down…

  16. Effect of a Selective Mas Receptor Agonist in Cerebral Ischemia In Vitro and In Vivo.

    PubMed

    Lee, Seyoung; Evans, Megan A; Chu, Hannah X; Kim, Hyun Ah; Widdop, Robert E; Drummond, Grant R; Sobey, Christopher G

    2015-01-01

    Functional modulation of the non-AT1R arm of the renin-angiotensin system, such as via AT2R activation, is known to improve stroke outcome. However, the relevance of the Mas receptor, which along with the AT2R forms the protective arm of the renin-angiotensin system, as a target in stroke is unclear. Here we tested the efficacy of a selective MasR agonist, AVE0991, in in vitro and in vivo models of ischemic stroke. Primary cortical neurons were cultured from E15-17 mouse embryos for 7-9 d, subjected to glucose deprivation for 24 h alone or with test drugs, and percentage cell death was determined using trypan blue exclusion assay. Additionally, adult male mice were subjected to 1 h middle cerebral artery occlusion and were administered either vehicle or AVE0991 (20 mg/kg i.p.) at the commencement of 23 h reperfusion. Some animals were also treated with the MasR antagonist, A779 (80 mg/kg i.p.) 1 h prior to surgery. Twenty-four h after MCAo, neurological deficits, locomotor activity and motor coordination were assessed in vivo, and infarct and edema volumes estimated from brain sections. Following glucose deprivation, application of AVE0991 (10-8 M to 10-6 M) reduced neuronal cell death by ~60% (P<0.05), an effect prevented by the MasR antagonist. By contrast, AVE0991 administration in vivo had no effect on functional or histological outcomes at 24 h following stroke. These findings indicate that the classical MasR agonist, AVE0991, can directly protect neurons from injury following glucose-deprivation. However, this effect does not translate into an improved outcome in vivo when administered systemically following stroke.

  17. Effect of a Selective Mas Receptor Agonist in Cerebral Ischemia In Vitro and In Vivo

    PubMed Central

    Lee, Seyoung; Evans, Megan A.; Chu, Hannah X.; Kim, Hyun Ah; Widdop, Robert E.; Drummond, Grant R.; Sobey, Christopher G.

    2015-01-01

    Functional modulation of the non-AT1R arm of the renin-angiotensin system, such as via AT2R activation, is known to improve stroke outcome. However, the relevance of the Mas receptor, which along with the AT2R forms the protective arm of the renin-angiotensin system, as a target in stroke is unclear. Here we tested the efficacy of a selective MasR agonist, AVE0991, in in vitro and in vivo models of ischemic stroke. Primary cortical neurons were cultured from E15-17 mouse embryos for 7–9 d, subjected to glucose deprivation for 24 h alone or with test drugs, and percentage cell death was determined using trypan blue exclusion assay. Additionally, adult male mice were subjected to 1 h middle cerebral artery occlusion and were administered either vehicle or AVE0991 (20 mg/kg i.p.) at the commencement of 23 h reperfusion. Some animals were also treated with the MasR antagonist, A779 (80 mg/kg i.p.) 1 h prior to surgery. Twenty-four h after MCAo, neurological deficits, locomotor activity and motor coordination were assessed in vivo, and infarct and edema volumes estimated from brain sections. Following glucose deprivation, application of AVE0991 (10−8 M to 10−6 M) reduced neuronal cell death by ~60% (P<0.05), an effect prevented by the MasR antagonist. By contrast, AVE0991 administration in vivo had no effect on functional or histological outcomes at 24 h following stroke. These findings indicate that the classical MasR agonist, AVE0991, can directly protect neurons from injury following glucose-deprivation. However, this effect does not translate into an improved outcome in vivo when administered systemically following stroke. PMID:26540167

  18. Do children with Down syndrome perform sufficient physical activity to maintain good health? A pilot study.

    PubMed

    Shields, Nora; Dodd, Karen J; Abblitt, Casey

    2009-10-01

    Our pilot study investigated if children with Down syndrome engaged in the recommended 60 min of moderate to vigorous physical activity (MVPA) every day. Twenty-three children with Down syndrome (7 girls, 16 boys; mean age 11.7 years, SD = 3.1) wore a triaxial accelerometer for 7 consecutive days to measure their activity levels. The average daily MVPA undertaken was 104.5 min ( SD = 35.3 min). Only 8 of 19 children (42.1%) completed at least 60 min of MVPA each day. Lower amounts of activity were associated with older children (r = -.67, p < .01). Parents, teachers, and health professionals need to encourage children with Down syndrome to take part in more frequent MVPA.

  19. Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart.

    PubMed

    Gava, Elisandra; de Castro, Carlos Henrique; Ferreira, Anderson J; Colleta, Heloísa; Melo, Marcos B; Alenina, Natalia; Bader, Michael; Oliveira, Laser A; Santos, Robson A S; Kitten, Gregory T

    2012-04-10

    In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT(2) on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and VI and fibronectin was performed using immunofluorescence-labeling and confocal microscopy. Picrosirius red staining was used for the histological assessment of the overall collagen distribution pattern. ECM proteins, metalloproteinases (MMP), ERK1/2 and p38 levels were quantified by western blot analysis. Gelatin zymography was used to evaluate the activity of MMP-2 and MMP-9. We observed that the relative levels of collagen types I and III and fibronectin are significantly higher in both the right ventricle and AV valves of neonatal Mas(-/-) mouse hearts (e.g., collagen type I: 85.28±6.66 vs 43.50±4.41 arbitrary units in the right ventricles of Mas(+/+) mice). Conversely, the level of collagen type VI was lower in the right ventricle and AV valves of Mas(-/-) mice. Adult Mas(-/-) mouse hearts presented similar patterns as observed in neonates. No significant differences in ECM protein level were detected in atria. Likewise, no changes in ECM levels were observed in AT(2) knockout mouse hearts. Although deletion of Mas induced a significant reduction in the level of the active form of MMP-2 in neonate hearts and a reduction of both MMP-2 and MMP-9 in adult Mas(-/-) mice, no significant differences were observed in MMP enzymatic activities when compared to controls. The levels of the active, phosphorylated forms of ERK1/2 and p38 were higher in hearts of both neonatal and adult Mas(-/-) mice. These observations suggest that Mas is involved in the selective expression of specific ECM proteins within both the ventricular myocardium and AV valves. The changes in the ECM profile may alter the connective tissue framework and contribute to

  20. Insulin resistance influences central opioid activity in polycystic ovary syndrome.

    PubMed

    Berent-Spillson, Alison; Love, Tiffany; Pop-Busui, Rodica; Sowers, MaryFran; Persad, Carol C; Pennington, Kathryn P; Eyvazaddeh, Aimee D; Padmanabhan, Vasantha; Zubieta, Jon-Kar; Smith, Yolanda R

    2011-06-30

    This pilot study describes a relationship between insulin resistance and μ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome (PCOS), suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that [1] patients with PCOS who are insulin-resistant (n = 7) had greater limbic μ-opioid receptor availability (nondisplaceable binding potential) than controls (n = 5); [2] receptor availability was correlated with severity of insulin resistance; and [3] receptor availability normalized after insulin-regulating treatment.

  1. ATPase activity of erythrocyte membrane in patients with trisomy 21 (Down's syndrome).

    PubMed

    Xue, Q M; Shen, D G; Dong, W

    1984-11-01

    ATPase activity of crythroyte membranes was determined in 25 cases of Down's syndrome verified by cytological and psychological examinations. The age range of the patients was 8-25 years; 16 males and 9 females. Thirty health male volunteers were selected as the control group. There was a marked reduction of total ATPase, Na+, K+-ATPase, Mg++ATPase activities and rate of ouabain inhibition in the patients with Down's syndrome. The authors suggest that there might exist transport defects in the red cell membranes in such patients.

  2. Ultra High Angular Resolution and sub-mas Astrometry with HST's FGS1r

    NASA Astrophysics Data System (ADS)

    Lallo, M.; Makidon, R. B.; Jong, D.; Nelan, E.

    2001-05-01

    The 3 Fine Guidance Sensors (FGS) - white-light shearing interferometers - are critical to the mission of the Hubble Space Telescope (HST) by providing highly accurate guiding for the observatory. Moreover, FGS1r in particular is a capable science instrument. Its two observing modes - Position Mode and Transfer Mode - support wide angle and narrow angle astrometry respectively. In Position Mode, a star's interferometric fringes are tracked to determine its angular position relative to other stars in the detector's field of view. Using this method, a star's parallax, proper motion, and reflex motion can be measured with a precision of about 1 mas per observation, while multi-epoch observing programs have yielded astrometry with accuracies approaching 0.2 mas for objects as bright as V=3 or as faint as V=16.5. Transfer Mode observations repeatedly scan an object's interferometric fringes to achieve sub-mas sampling of the fringe morphology with high signal-to-noise (conceptually analogous to imaging with a 1 mas pixel array). Post-observation analysis allows the measurement of angular separation, position angle and relative brightness of binary components, or a determination of the angular size of an extended object. Close binary systems with V < 12 can be detected down to 7 mas, while systems as faint as V=15 can be characterized to 12 mas, provided the magnitude difference between the components is less than about 2. (Wider systems with magnitude differences as large as 3.5 can be resolved.) Both FGS observing modes can be utilized to derive the total and fractional masses of binary systems, and thus the mass-luminosity relationship of the binary components. The FGS have also been used to observe and characterize non-point source objects, including Mira variables, asteroids, and active galactic nuclei, yielding information on the structure of these objects on scales as small as 8 mas. The FGS also function as 40 Hz photometers, offering milli-magnitude precision

  3. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation.

    PubMed

    Cui, S S; Bowen, R C; Gu, G B; Hannesson, D K; Yu, P H; Zhang, X

    2001-12-15

    Cannabis (i.e., marijuana and cannabinoids) is the most commonly used illicit drug in developed countries, and the lifetime prevalence of marijuana dependence is the highest of all illicit drugs in the United States. To provide clues for finding effective pharmacological treatment for cannabis-dependent patients, we examined the effects and possible mechanism of lithium administration on the cannabinoid withdrawal syndrome in rats. A systemic injection of the mood stabilizer lithium, at serum levels that were clinically relevant, prevented the cannabinoid withdrawal syndrome. The effects of lithium were accompanied by expression of the cellular activation marker Fos proteins within most oxytocin-immunoreactive neurons and a significant increase in oxytocin mRNA expression in the hypothalamic paraventricular and supraoptic nuclei. Lithium also produced a significant elevation of oxytocin levels in the peripheral blood. We suggest that the effects of lithium against the cannabinoid withdrawal syndrome are mediated by oxytocinergic neuronal activation and subsequent release and action of oxytocin within the CNS. In support of our hypothesis, we found that the effects of lithium against the cannabinoid withdrawal syndrome were antagonized by systemic preapplication of an oxytocin antagonist and mimicked by systemic or intracerebroventricular injection of oxytocin. These results demonstrate that oxytocinergic neuronal activation plays a critical role in the action of lithium against the cannabinoid withdrawal syndrome in rats, thus providing a potentially novel strategy for the treatment of cannabis dependence in humans.

  4. MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism.

    PubMed

    Prokop, Jeremy W; Rauscher, Frank J; Peng, Hongzhuang; Liu, Yuanjie; Araujo, Fabiano C; Watanabe, Ingrid; Reis, Fernando M; Milsted, Amy

    2014-05-01

    The ACE2 (angiotensin-converting enzyme 2)/Ang-(1-7) [angiotensin-(1-7)]/MAS axis of the RAS (renin-angiotensin system) has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind to and be activated by Ang-(1-7); however, the mechanisms of this activation are just starting to be understood. Although there are strong biochemical data regarding the regulation and activation of the AT1R (angiotensin II type 1 receptor) and the AT2R (angiotensin II type 2 receptor), with models of how AngII (angiotensin II) binds each receptor, fewer studies have characterized MAS. In the present study, we characterize the MAS promoter and provide a potential feedback mechanism that could compensate for MAS degradation following activation by Ang-(1-7). Analysis of ENCODE data for the MAS promoter revealed potential epigenetic control by KRAB (Krüppel-associated box)/KAP-1 (KRAB-associated protein-1). A proximal promoter construct for the MAS gene was repressed by the SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2, SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. The KRAB-KAP-1 complex can be tyrosine-nitrated, causing the dissociation of the KAP-1 protein and thus a potential loss of epigenetic control. Activation of MAS can lead to an increase in nitric oxide, suggesting a feedback mechanism for MAS on its own promoter. The results of the present study provide a more complete view of MAS regulation and, for the first time, suggest biochemical outcomes for nitration of the KRAB domain.

  5. Mas receptor deficiency is associated with worsening of lipid profile and severe hepatic steatosis in ApoE-knockout mice.

    PubMed

    Silva, Analina R; Aguilar, Edenil C; Alvarez-Leite, Jacqueline I; da Silva, Rafaela F; Arantes, Rosa M E; Bader, Michael; Alenina, Natalia; Pelli, Graziano; Lenglet, Sébastien; Galan, Katia; Montecucco, Fabrizio; Mach, François; Santos, Sérgio H S; Santos, Robson A S

    2013-12-01

    The classical renin-angiotensin system pathway has been recently updated with the identification of additional molecules [such as angiotensin converting enzyme 2, ANG-(1-7), and Mas receptor] that might improve some pathophysiological processes in chronic inflammatory diseases. In the present study, we focused on the potential protective role of Mas receptor activation on mouse lipid profile, liver steatosis, and atherogenesis. Mas/apolipoprotein E (ApoE)-double-knockout (DKO) mice (based on C57BL/6 strain of 20 wk of age) were fed under normal diet and compared with aged-matched Mas and ApoE-single-knockout (KO), as well as wild-type mice. Mas/ApoE double deficiency was associated with increased serum levels of atherogenic fractions of cholesterol, triglycerides, and fasting glucose compared with wild-type or single KO. Serum levels of HDL or leptin in DKO were lower than in other groups. Hepatic lipid content as well as alanine aminotransferase serum levels were increased in DKO compared with wild-type or single-KO animals. Accordingly, the hepatic protein content of mediators related to atherosclerotic inflammation, such as peroxisome proliferator-activated receptor-α and liver X receptor, was altered in an adverse way in DKO compared with ApoE-KO. On the other hand, DKO mice did not display increased atherogenesis and intraplaque inflammation compared with ApoE-KO group. In conclusion, Mas deletion in ApoE-KO mice was associated with development of severe liver steatosis and dyslipidemia without affecting concomitant atherosclerosis. Mas receptor activation might represent promising strategies for future treatments targeting both hepatic and metabolic alterations in chronic conditions clustering these disorders.

  6. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas

    PubMed Central

    Morales, María Gabriela; Abrigo, Johanna; Acuña, María José; Santos, Robson A.; Bader, Michael; Brandan, Enrique; Simon, Felipe; Olguin, Hugo; Cabrera, Daniel; Cabello-Verrugio, Claudio

    2016-01-01

    ABSTRACT Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophy in vivo using unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy. PMID:26851244

  7. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas.

    PubMed

    Morales, María Gabriela; Abrigo, Johanna; Acuña, María José; Santos, Robson A; Bader, Michael; Brandan, Enrique; Simon, Felipe; Olguin, Hugo; Cabrera, Daniel; Cabello-Verrugio, Claudio

    2016-04-01

    Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophyin vivousing unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy.

  8. Structural biology applications of solid state MAS DNP NMR.

    PubMed

    Akbey, Ümit; Oschkinat, Hartmut

    2016-08-01

    Dynamic Nuclear Polarization (DNP) has long been an aim for increasing sensitivity of nuclear magnetic resonance (NMR) spectroscopy, delivering spectra in shorter experiment times or of smaller sample amounts. In recent years, it has been applied in magic angle spinning (MAS) solid-state NMR to a large range of samples, including biological macromolecules and functional materials. New research directions in structural biology can be envisaged by DNP, facilitating investigations on very large complexes or very heterogeneous samples. Here we present a summary of state of the art DNP MAS NMR spectroscopy and its applications to structural biology, discussing the technical challenges and factors affecting DNP performance.

  9. Structural biology applications of solid state MAS DNP NMR

    NASA Astrophysics Data System (ADS)

    Akbey, Ümit; Oschkinat, Hartmut

    2016-08-01

    Dynamic Nuclear Polarization (DNP) has long been an aim for increasing sensitivity of nuclear magnetic resonance (NMR) spectroscopy, delivering spectra in shorter experiment times or of smaller sample amounts. In recent years, it has been applied in magic angle spinning (MAS) solid-state NMR to a large range of samples, including biological macromolecules and functional materials. New research directions in structural biology can be envisaged by DNP, facilitating investigations on very large complexes or very heterogeneous samples. Here we present a summary of state of the art DNP MAS NMR spectroscopy and its applications to structural biology, discussing the technical challenges and factors affecting DNP performance.

  10. Middle aortic syndrome in a teenager.

    PubMed

    Eyileten, Zeynep; Taşar, Mehmet; Yazıcıoğlu, Levent; Kaya, Bülent; Fitöz, Suat; Uysalel, Adnan

    2014-01-01

    Middle aortic syndrome (MAS) is a rare pathology that involves diffuse/segmental narrowing of the distal thoracic or abdominal aorta. The most common clinical manifestation is severe hypertension, which requires multiple antihypertensive medications and/or surgical repair. We report the surgical repair of MAS in a 14-year-old male.

  11. Magnetoencephalographic Analysis of Cortical Activity in Adults with and without Down Syndrome

    ERIC Educational Resources Information Center

    Virji-Babul, N.; Cheung, T.; Weeks, D.; Herdman, A. T.; Cheyne, D.

    2007-01-01

    Background: This preliminary study served as a pilot for an ongoing analysis of spectral power in adults with Down syndrome (DS) using a 151 channel whole head magnetoencephalography (MEG). The present study is the first step for examining and comparing cortical responses during spontaneous and task related activity in DS. Method: Cortical…

  12. Correlation between Glutathione Peroxidase Activity and Anthropometrical Parameters in Adolescents with Down Syndrome

    ERIC Educational Resources Information Center

    Ordonez, F. J.; Rosety-Rodriguez, M.

    2007-01-01

    Since we have recently found that regular exercise increased erythrocyte antioxidant enzyme activities such as glutathione peroxidase (GPX) in adolescents with Down syndrome, these programs may be recommended. This study was designed to assess the role of anthropometrical parameters as easy, economic and non-invasive biomarkers of GPX. Thirty-one…

  13. Primary Sjögren's syndrome--clinical and laboratory markers of disease activity.

    PubMed

    Oxholm, P

    1992-10-01

    Primary Sjögren's syndrome is a chronic autoimmune disorder of the lacrimal and salivary glands, reflecting general involvement of the exocrine tissues and leading to functional impairment. This polyglandular disease is often associated with systemic extraglandular manifestations, and laboratory tests usually indicate polyclonal B-lymphocyte hyperactivity. Clinical and laboratory markers monitoring the disease processes are needed for improved management of primary Sjögren's syndrome. However, incomplete knowledge of the long-term course of inflammation as well as of clinical manifestations makes precise and simple directions for monitoring disease activity in primary Sjögren's syndrome difficult. This review describes potential primary (eg, salivary gland histopathology, autoantibodies, soluble interleukin-2 receptors, and beta 2-microglobulin) and secondary disease activity markers (clinical and laboratory signs of glandular and extraglandular organ damage) and their known associations. The importance of genetic characteristics, patient age, and symptom duration for the disease activity markers is indicated. The systematic use of primary and secondary disease activity markers will improve our understanding of primary Sjögren's syndrome and help create better guidelines for monitoring the disease.

  14. The Marfan Syndrome: Physical Activity Guidelines for Physical Educators, Coaches and Physicians.

    ERIC Educational Resources Information Center

    Romeo, Thomas J.

    Intended for physical educators, this manual provides guidelines for providing safe and effective physical activity programs for children with Marfan syndrome, a congenital condition involving the connective tissues and the probable cause of sudden death by heart failure of some young competitive athletes in recent cases. The manual includes…

  15. Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex.

    PubMed

    Freund, M; Walther, T; von Bohlen Und Halbach, O

    2014-02-01

    Aside from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a G protein-coupled receptor being essential for angiotensin-(1-7) signaling. Mas is not only expressed in the periphery but also within the brain, e.g. in the dentate gyrus (DG) and the piriform cortex (PC). Since the DG is capable of adult neurogenesis, we examined the impact of a deletion of Mas upon adult neurogenesis. Deletion of Mas did not alter cell proliferation in the adult DG (as monitored with phosphohistone H3) and did not alter cell death (as monitored with activated Caspase 3). However, Mas deficiency resulted in an increase in the number of doublecortin (DCX) positive cells, indicating that lack of Mas increases the number of this cell population. Concerning the PC, it is discussed whether adult neurogenesis occurs under physiological conditions in this area. We could demonstrate that Mas deficiency has an impact on cell division and on the population of DCX-positive cells within the PC. Since Mas is not expressed before birth within the brain, our data may suggest that adult hippocampal neurogenesis and neurogenesis occurring during prenatal development share several common mechanisms, but are, at least in part, differentially regulated. Moreover, since deficiency for Mas increases the numbers of DCX-positive young neurons, blockage of Mas might be beneficial in stimulating neurogenesis in adults.

  16. Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas.

    PubMed

    Wood, Laura D; Noë, Michaël; Hackeng, Wenzel; Brosens, Lodewijk A A; Bhaijee, Feriyl; Debeljak, Marija; Yu, Jun; Suenaga, Masaya; Singhi, Aatur D; Zaheer, Atif; Boyce, Alison; Robinson, Cemre; Eshleman, James R; Goggins, Michael G; Hruban, Ralph H; Collins, Michael T; Lennon, Anne Marie; Montgomery, Elizabeth A

    2017-02-10

    McCune-Albright Syndrome (MAS) is a rare sporadic syndrome caused by post-zygotic mutations in the GNAS oncogene, leading to constitutional mosaicism for these alterations. Somatic activating GNAS mutations also commonly occur in several gastrointestinal and pancreatic neoplasms, but the spectrum of abnormalities in these organs in patients with MAS has yet to be systematically described. We report comprehensive characterization of the upper gastrointestinal tract in seven patients with MAS and identify several different types of polyps, including gastric heterotopia/metaplasia (7/7), gastric hyperplastic polyps (5/7), fundic gland polyps (2/7), and a hamartomatous polyp (1/7). In addition, one patient had an unusual adenomatous lesion at the gastroesophageal junction with high-grade dysplasia. In the pancreas, all patients had endoscopic ultrasound findings suggestive of intraductal papillary mucinous neoplasm (IPMN), but only two patients met the criteria for surgical intervention. Both of these patients had IPMNs at resection, one with low-grade dysplasia and one with high-grade dysplasia. GNAS mutations were identified in the majority of lesions analyzed, including both IPMNs and the adenomatous lesion from the gastroesophageal junction. These studies suggest that there is a broad spectrum of abnormalities in the gastrointestinal tract and pancreas in patients with MAS and that patients with MAS should be evaluated for gastrointestinal pathology, some of which may warrant clinical intervention due to advanced dysplasia.

  17. Resolution and polarization distribution in cryogenic DNP/MAS experiments

    PubMed Central

    Barnes, Alexander B.; Corzilius, Björn; Mak-Jurkauskas, Melody L.; Andreas, Loren B.; Bajaj, Vikram S.; Matsuki, Yoh; Belenky, Marina L.; Lugtenburg, Johan; Sirigiri, Jagadishwar R.; Temkin, Richard J.; Herzfeld, Judith; Griffin, Robert G.

    2014-01-01

    This contribution addresses four potential misconceptions associated with high-resolution dynamic nuclear polarization/magic angle spinning (DNP/MAS) experiments. First, spectral resolution is not generally compromised at the cryogenic temperatures at which DNP experiments are performed. As we demonstrate at a modest field of 9 T (380 MHz 1H), 1 ppm linewidths are observed in DNP/MAS spectra of a membrane protein in its native lipid bilayer, and <0.4 ppm linewidths are reported in a crystalline peptide at 85 K. Second, we address the concerns about paramagnetic broadening in DNP/MAS spectra of proteins by demonstrating that the exogenous radical polarizing agents utilized for DNP are distributed in the sample in such a manner as to avoid paramagnetic broadening and thus maintain full spectral resolution. Third, the enhanced polarization is not localized around the polarizing agent, but rather is effectively and uniformly dispersed throughout the sample, even in the case of membrane proteins. Fourth, the distribution of polarization from the electron spins mediated via spin diffusion between 1H–1H strongly dipolar coupled spins is so rapid that shorter magnetization recovery periods between signal averaging transients can be utilized in DNP/MAS experiments than in typical experiments performed at ambient temperature. PMID:20454732

  18. ADP-MAS: A Math and Science Curriculum.

    ERIC Educational Resources Information Center

    National Council of La Raza, Washington, DC.

    This curriculum, Academia del Pueblo-Math and Science (ADP-MAS), is an outgrowth of the National Council of La Raza's Project EXCEL, a supplemental educational enrichment model for at-risk Latino students to be operated by Latino community-based organizations or public institutions, including schools with substantial Latino populations. ADP-MAS…

  19. Sympathetic nervous activation in obesity and the metabolic syndrome--causes, consequences and therapeutic implications.

    PubMed

    Lambert, Gavin W; Straznicky, Nora E; Lambert, Elisabeth A; Dixon, John B; Schlaich, Markus P

    2010-05-01

    The world wide prevalence of obesity and the metabolic syndrome is escalating. Contrary to earlier experimental evidence, human obesity is characterised by sympathetic nervous activation, with the outflows to both the kidney and skeletal muscle being activated. While the mechanisms responsible for initiating the sympathetic activation remain to be unequivocally elucidated, hyperinsulinemia, obstructive sleep apnoea, increased circulating adipokines, stress and beta adrenergic receptor polymorphisms are implicated. The pattern of sympathetic activation may be the pathophysiological mechanism underpinning much obesity-related illnesses with the consequences including, amongst others, the development of hypertension, insulin resistance, diastolic dysfunction and renal impairment. While diet and exercise are the first line therapy for the treatment of obesity and the metabolic syndrome, pharmacological interventions targeting the sympathetic nervous system, either directly or indirectly are also likely to be of benefit. Importantly, the benefit may not necessarily be weight related but may be associated with a reduction in end organ damage.

  20. A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

    PubMed Central

    Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

    2011-01-01

    Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

  1. Controllability and hippocampal activation during pain expectation in fibromyalgia syndrome.

    PubMed

    González-Roldán, Ana María; Bomba, Isabelle C; Diesch, Eugen; Montoya, Pedro; Flor, Herta; Kamping, Sandra

    2016-12-01

    To examine the role of perceived control in pain perception, fibromyalgia patients and healthy controls participated in a reaction time experiment under different conditions of pain controllability. No significant differences between groups were found in pain intensity and unpleasantness ratings. However, during the expectation of uncontrollable pain, patients compared to controls showed higher hippocampal activation. In addition, hippocampal activity during the pain expectation period predicted activation of the posterior cingulate cortex (PCC), precuneus and hippocampus during pain stimulation in fibromyalgia patients. The increased activation of the hippocampus during pain expectation and subsequent activation of the PCC/precuneus during the lack of control phase points towards an influence of pain perception through heightening of alertness and anxiety responses to pain in fibromyalgia patients.

  2. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet.

    PubMed

    Pu, Peng; Gao, Dong-Mei; Mohamed, Salim; Chen, Jing; Zhang, Jing; Zhou, Xiao-Ya; Zhou, Nai-Jing; Xie, Jing; Jiang, Hong

    2012-02-01

    Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage.

  3. Detecting consciousness in a total locked-in syndrome: an active event-related paradigm.

    PubMed

    Schnakers, Caroline; Perrin, Fabien; Schabus, Manuel; Hustinx, Roland; Majerus, Steve; Moonen, Gustave; Boly, Melanie; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurelie; Laureys, Steven

    2009-08-01

    Total locked-in syndrome is characterized by tetraplegia, anarthria and paralysis of eye motility. In this study, consciousness was detected in a 21-year-old woman who presented a total locked-in syndrome after a basilar artery thrombosis (49 days post-injury) using an active event-related paradigm. The patient was presented sequences of names containing the patient's own name and other names. The patient was instructed to count her own name or to count another target name. Similar to 4 age- and gender-matched healthy controls, the P3 response recorded for the voluntarily counted own name was larger than while passively listening. This P3 response was observed 14 days before the first behavioral signs of consciousness. This study shows that our active event-related paradigm allowed to identify voluntary brain activity in a patient who would behaviorally be diagnosed as comatose.

  4. Life satisfaction and activity preferences in parents of Down's syndrome children.

    PubMed

    Bränholm, I B; Degerman, E A

    1992-03-01

    The impact of parenting a child with Down's syndrome on life satisfaction and non-work activities was investigated in 37 couples using mailed checklists. The results were compared with those found in all 89 parents from a randomly selected population. Only for 7 of the 41 non-work activities were there differences between the two groups of parents. The vast majority of both groups were satisfied or very satisfied with life as a whole and with partnership relations, sexual life and family life. The 8 domains of life satisfaction formed 3 factors. In congruence with previous findings in a non-selected sample these factors were significant classifiers for satisfaction with life as a whole, an expressive (emotion related) factor being the major classifier. The close similarities in non-work activities and life satisfaction are interpreted as a result of adequate adaptive resources within the majority of families of children with Down's syndrome.

  5. MAS/MILS Arc/Info point coverage for the western U.S. (excluding Hawaii)

    USGS Publications Warehouse

    Causey, J. Douglas

    1998-01-01

    The U.S. Geological Survey has two international and one regional digital database that contains information on mineral properties. This report describes the conversion of selected data from one of the international databases - MAS/MILS (Mineral Availability System/Mineral Industry Location System) - into a spatial data product. The MAS/MILS database, obtained from the U.S. Bureau of Mines (USBM) upon its closure, contains over 221,000 records of mineral properties and processing facilities throughout the world. However, the majority of the records in the database are of sites located in the western U.S. This is due to the extensive mineral activity that has occurred in the West, and the work done by mineral professionals in the Western, Alaska, and Intermountain Field Operations Centers of the USBM. The purpose of this project was to create a spatial coverage of the western U.S. containing mineral resource information. This coverage includes information for the states of Alaska, Arizona, California, Colorado, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming. For this report, locations from MAS/MILS were converted to a point coverage using a geographic information system (GIS). All work was done using Arc/Info v. 7.0.4. There are 128,441 points in the coverage.

  6. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis

    PubMed Central

    Simões e Silva, AC; Silveira, KD; Ferreira, AJ; Teixeira, MM

    2013-01-01

    Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases. PMID:23488800

  7. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

    PubMed

    Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

    2010-06-01

    Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The

  8. Spatially resolved solid-state MAS-NMR-spectroscopy.

    PubMed

    Scheler, U; Schauss, G; Blümich, B; Spiess, H W

    1996-07-01

    A comprehensive account of spatially resolved solid-state MAS NMR of 13C is given. A device generating field gradients rotating synchronously with the magic angle spinner is described. Spatial resolution and sensitivity are compared for phase and frequency encoding of spatial information. The suppression of spinning sidebands is demonstrated for both cases. Prior knowledge about the involved materials can be used for the reduction of data from spatially resolved spectra to map chemical structure. Indirect detection via 13C NMR gives access to the information about mobility from proton-wideline spectra. Two-dimensional solid-state spectroscopy with spatial resolution is demonstrated for a rotor synchronized MAS experiment which resolves molecular order as a function of space. By comparison of different experiments the factors affecting the spatial resolution are investigated.

  9. Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

    PubMed

    Campos, L M A; Omori, C H; Lotito, A P N; Jesus, A A; Porta, G; Silva, C A A

    2010-12-01

    Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients.

  10. 5'-adenosine monophosphate-activated protein kinase and the metabolic syndrome.

    PubMed

    Mor, Vijay; Unnikrishnan, M K

    2011-09-01

    Lifestyle changes such as physical inactivity combined with calorie-rich, low-fibre diets have triggered an explosive surge in metabolic syndrome, outlined as a cluster of heart attack risk factors such as insulin resistance, raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. By acting as a master-switch of energy homeostasis and associated pathophysiological phenomena, 5'-adenosine monophosphate-activated protein kinase (AMPK) appears to orchestrate the adaptive physiology of energy deficit, suggesting that the sedentary modern human could be suffering from chronic suboptimal AMPK activation. Addressing individual targets with potent ligands with high specificity may be inappropriate (it has not yielded any molecule superior to the sixty year old metformin) because this strategy cannot address a cluster of interrelated pathologies. However, spices, dietary supplements and nutraceuticals attenuate the multiple symptoms of metabolic syndrome in a collective and perhaps more holistic fashion with fewer adverse events. Natural selection could have favoured races that developed a taste for spices and dietary supplements, most of which are not only antioxidants but also activators of AMPK. The review will outline the various biochemical mechanisms and pathophysiological consequences of AMPK activation involving the cluster of symptoms that embrace metabolic syndrome and beyond. Recent advances that integrate energy homeostasis with a number of overarching metabolic pathways and physiological phenomena, including inflammatory conditions, cell growth and development, malignancy, life span, and even extending into environmental millieu, as in obesity mediated by gut microflora and others will also be outlined.

  11. Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke.

    PubMed

    van Rooy, Mia-Jeanne; Pretorius, Etheresia

    2015-03-01

    Stroke is the second most common cause of mortality in the world today, where transient ischemic attack (TIA) is a period of focal ischemia, the symptoms of which resemble a thromboembolic stroke. Contrary to stroke, TIA symptoms typically last less than one hour and necrosis is absent. Stroke is often preceded by TIA, making it an important predictor of future ischemic events. The causal role of atherosclerosis in the development of TIA is well established, however, research indicates that the atherosclerotic process begins years earlier with the development of metabolic syndrome, which affects approximately 45% of the adult population worldwide. Metabolic syndrome is present if three or more of the following is present: increased waist circumference, increased triglycerides, decreased HDL, increased fasting glucose and hypertension. This syndrome causes systemic inflammation that activates the coagulation system and may cause the formation of pathological thrombi. The role of platelets in stroke has been studied and platelet activation pathways identified. ADP and thromboxane A(2) are the most common activators of platelets in normal physiology. Several pharmacological treatments have been employed to prevent the activation of platelets, the most common of which include aspirin and P2Y(12)-inhibitors. Although treatment is administered strokes and subsequent TIAs are very common in individuals that suffered an initial event. This indicates that research needs to be done in order to elucidate new therapeutic targets, but also to better treat ischemic events to not only decrease the amount of recurring events but also decrease stroke mortality worldwide.

  12. Commercial facility site selection simulating based on MAS

    NASA Astrophysics Data System (ADS)

    Chao, Yi; Li, Qingquan; Zheng, Guizhou

    2008-10-01

    The location of commercial facility decides the benefit of the operator to a large degree. Existing location methods can express the static relationships between site selection result and location factors, but there still are some limites when express the dynamic and uncertain relationship between them. Hence, a dynamic, stochastic and forecastable location model should be built which can introduce the customer's behavior into the model and combine the macro pattern and micro spatial interaction. So the authors proposes Geosim-LM based on MAS. Geosim-LM has 3 kinds of agents, CustAgent, SiteAgent and GovAgent. They represent the customers, commercial fercilities and government. The land type, land price and traffic are the model environment. Then Geosim-LM is applied in the bank branches site evaluation and selection in Liwan district, Guangzhou. In existing bank branches site evaluation, there are 70% consistent in score grade between result of Geosim-LM after 200 round runing and actual rebust location. It proves the model is reliable and feasible. The conclusions can be get from the paper. MAS have advantages in location choice than existed methods. The result of Geosim-LM running can powerfully proves that building location model based on MAS is feasible.

  13. Systemic blood coagulation activation in acute coronary syndromes

    PubMed Central

    Undas, Anetta; Szułdrzyński, Konstanty; Brummel-Ziedins, Kathleen E.; Tracz, Wiesława; Zmudka, Krzysztof

    2009-01-01

    We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 non-anticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P < .001), thrombin B-chain formation (by 57.1%; P < .001), prothrombin consumption (by 27.9%; P = .012), fibrinogen consumption (by 27.0%; P = .02), factor (f) Va light chain generation (by 44.2%; P = .003), and accelerated fVa inactivation (by 76.1%; P < .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P < .001). FVa heavy chain availability was similar in both groups because of enhanced formation and activated protein C (APC)–mediated destruction. The velocity of coagulant reactions in AMI patients showed positive correlations with interleukin-6. Heparin treatment led to dampening of coagulant reactions with profiles similar to those for stable CAD. AMI-induced systemic activation of blood coagulation markedly modifies the pattern of coagulant reactions at the site of injury in peripheral vessels compared with that in stable CAD patients. PMID:18931343

  14. Inverse activity of masticatory muscles with and without trismus: a brainstem syndrome.

    PubMed

    Jelasic, F; Freitag, V

    1978-09-01

    Clinical and EMG findings in 10 cases of intrinsic brainstem lesions are reported with paradoxical activity of jaw closing muscles during jaw opening, with and without trismus. In five cases with trigeminal anaesthesia, the inverse activity of jaw closers is interpreted as a manifestation of disturbance in the central programming of mastication in the motor trigeminal area of the brainstem. Stretch reflex mechanisms and disinhibition of the trigeminal motor neurones play no part in the origin of inverse activity. The distinct brainstem syndrome can only be detected by EMG and the special clinical features.

  15. Speech-activated Myoclonus Mimicking Stuttering in a Patient with Myoclonus–Dystonia Syndrome

    PubMed Central

    Isaacs, David A.; Hedera, Peter

    2016-01-01

    Background Acquired neurogenic stuttering has been considered a fairly uncommon clinical occurrence; speech-activated myoclonus is a rare entity that can mimic stuttering and is caused by a wide array of etiologies. Case Report Here we report a patient with myoclonus–dystonia syndrome (MDS), due to an identified disease-causing mutation, who displayed speech-activated myoclonus mimicking stuttering. Discussion In MDS, myoclonus has only infrequently been reported to affect speech. This case further expands the spectrum of conditions causing the rare clinical phenomenon of speech-activated myoclonus. PMID:27441098

  16. [Plasmapheresis for macrophage activation syndrome and multiorgan failure as first presentation of juvenile dermatomyositis].

    PubMed

    Bustos B, R; Carrasco A, C; Toledo R, C

    2012-07-01

    The use of extracorporeal techniques for the treatment of paediatric diseases has expanded dramatically in the past decade. Plasmapheresis, a technique for exchanging plasma components with albumin or plasma, has been used in some rheumatologic conditions. We report the clinical course of a 7 years old boy with clinical and biological features of macrophage activation syndrome and multiorgan failure, at the time of presentation of severe juvenile dermatomyositis, and non responsive to corticosteroids, cyclosporine and immunoglobulin. After 4 days in the paediatric intensive care unit, plasmapheresis was used as rescue therapy. Repeated therapeutic plasmapheresis was effective for improving the multiorgan failure and laboratory abnormalities. The patient was discharged on the 21st hospital day with good functional condition. Plasmapheresis should be considered as rescue treatment in patients with life threatening macrophage activation syndrome and systemic onset of juvenile dermatomyositis.

  17. Metabolic syndrome: adenosine monophosphate-activated protein kinase and malonyl coenzyme A.

    PubMed

    Ruderman, Neil B; Saha, Asish K

    2006-02-01

    The metabolic syndrome can be defined as a state of metabolic dysregulation characterized by insulin resistance, central obesity, and a predisposition to type 2 diabetes, dyslipidemia, premature atherosclerosis, and other diseases. An increasing body of evidence has linked the metabolic syndrome to abnormalities in lipid metabolism that ultimately lead to cellular dysfunction. We review here the hypothesis that, in many instances, the cause of these lipid abnormalities could be a dysregulation of the adenosine monophosphate-activated protein kinase (AMPK)/malonyl coenzyme A (CoA) fuel-sensing and signaling mechanism. Such dysregulation could be reflected by isolated increases in malonyl CoA or by concurrent changes in malonyl CoA and AMPK, both of which would alter intracellular fatty acid partitioning. The possibility is also raised that pharmacological agents and other factors that activate AMPK and/or decrease malonyl CoA could be therapeutic targets.

  18. Relapsing macrophage activating syndrome in a 15-year-old girl with Still's disease: a case report

    PubMed Central

    2009-01-01

    Introduction Macrophage activating syndrome is a severe, potentially life-threatening condition that may accompany Still's disease. It is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenia, serious liver dysfunction, coagulopathy and neurologic involvement. The principal treatment for patients with this syndrome includes etoposide 150 mg/2 M twice a week for two weeks, dexamethasone 10 mg/2 M for two weeks and cyclosporine 3 mg/kg to 5 mg/kg for a longer period. Cases of relapse of macrophage activating syndrome are relatively rare. Case presentation We describe the case of a 15-year-old Iraqi girl with Still's disease who developed macrophage activating syndrome with acute respiratory distress syndrome that required resuscitation and mechanical ventilation. Following intensive treatment, including high dose steroids and cyclosporine, the patient improved significantly. Two weeks after cyclosporine was discontinued, however, she was readmitted with an acute relapse of macrophage activating syndrome manifested by spiking fever, arthralgias, maculopapular rash and leukocytosis. This time the patient recovered following the reintroduction of treatment with cyclosporine and the addition of mycophenolate mofetil (Cellcept). Conclusion We believe that cyclosporine is a cornerstone for the treatment of Still's disease. We recommend continuing this medication for several weeks following the patient's clinical recovery in order to prevent macrophage activating syndrome relapses. PMID:20062775

  19. Activity of LPO Processes in Women with Polycystic Ovarian Syndrome and Infertility.

    PubMed

    Kolesnikova, L I; Kolesnikov, S I; Darenskaya, M A; Grebenkina, L A; Nikitina, O A; Lazareva, L M; Suturina, L V; Danusevich, I N; Druzhinina, E B; Semendyaev, A A

    2017-01-01

    Specific features of LPO processes and antioxidant defense were studied in patients with polycystic ovarian syndrome (PCOS) and infertility. Changes in LPO processes in patients with PCOS were compensatory, which manifested in increased α-tocopherol and retinol concentrations and moderate decrease in superoxide dismutase activity. Intensification of prooxidant processes was found in the group of patients with infertility without PCOS. The observed changes necessitate differentiated approach to the treatment of these patients.

  20. Activity-Dependent Changes in MAPK Activation in the Angelman Syndrome Mouse Model

    ERIC Educational Resources Information Center

    Filonova, Irina; Trotter, Justin H.; Banko, Jessica L.; Weeber, Edwin J.

    2014-01-01

    Angelman Syndrome (AS) is a devastating neurological disorder caused by disruption of the maternal "UBE3A" gene. Ube3a protein is identified as an E3 ubiquitin ligase that shows neuron-specific imprinting. Despite extensive research evaluating the localization and basal expression profiles of Ube3a in mouse models, the molecular…

  1. Activity of daily living for Morquio A syndrome.

    PubMed

    Yasuda, Eriko; Suzuki, Yasuyuki; Shimada, Tsutomu; Sawamoto, Kazuki; Mackenzie, William G; Theroux, Mary C; Pizarro, Christian; Xie, Li; Miller, Freeman; Rahman, Tariq; Kecskemethy, Heidi H; Nagao, Kyoko; Morlet, Thierry; Shaffer, Thomas H; Chinen, Yasutsugu; Yabe, Hiromasa; Tanaka, Akemi; Shintaku, Haruo; Orii, Kenji E; Orii, Koji O; Mason, Robert W; Montaño, Adriana M; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

    2016-06-01

    The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of "Movement" and "Movement with cognition." Patients, who underwent HSCT and were followed up for over 10years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5years follow-up on average) were similar with the-age-matched controls below 10years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls.

  2. Activity of daily living for Morquio A syndrome

    PubMed Central

    Yasuda, Eriko; Suzuki, Yasuyuki; Shimada, Tsutomu; Sawamoto, Kazuki; Mackenzie, William G.; Theroux, Mary C.; Pizarro, Christian; Xie, Li; Miller, Freeman; Rahman, Tariq; Kecskemethy, Heidi H.; Nagao, Kyoko; Morlet, Thierry; Shaffer, Thomas H.; Chinen, Yasutsugu; Yabe, Hiromasa; Tanaka, Akemi; Shintaku, Haruo; Orii, Kenji E.; Orii, Koji O.; Mason, Robert W.; Montaño, Adriana M.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

    2016-01-01

    The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: “Movement,” “Movement with cognition,” and “Cognition.” Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10 years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of “Movement” and “Movement with cognition.” Patients, who underwent HSCT and were followed up for over 10 years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5 years follow-up on average) were similar with the-age-matched controls below 10 years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls. PMID:27161890

  3. Irregular 24-hour Activity Rhythms and the Metabolic Syndrome in Older Adults

    PubMed Central

    Sohail, Shahmir; Yu, Lei; Bennett, David A.; Buchman, Aron S.; Lim, Andrew S.P.

    2015-01-01

    Circadian rhythms – near 24-hour intrinsic biological rhythms – modulate many aspects of human physiology and hence disruption of circadian rhythms may have an important impact on human health. Experimental work supports a potential link between irregular circadian rhythms and several key risk factors for cardiovascular disease including hypertension, obesity, diabetes, and dyslipidemia, collectively termed the metabolic syndrome. While several epidemiological studies have demonstrated an association between shift-work and the components of the metabolic syndrome in working-age adults, there is a relative paucity of data concerning the impact of non-occupational circadian irregularity in older women and men. To address this question, we studied 7 days of actigraphic data from 1137 older woman and men participating in the Rush Memory and Aging Project, a community-based cohort study of the chronic conditions of aging. The regularity of activity rhythms was quantified using the nonparametric interdaily stability metric, and was related to the metabolic syndrome and its components obesity, hypertension, diabetes, and dyslipidemia. More regular activity rhythms were associated with a lower odds of having the metabolic syndrome (OR=0.69, 95%CI=0.60–0.80, p=5.8×10−7), being obese (OR=0.73, 95%CI=0.63–0.85, p=2.5×10−5), diabetic (OR=0.76, 95%CI=0.65–0.90, p=9.3×10−4), hypertensive (OR=0.78, 95%CI=0.66–0.91, p=2.0×10−3), or dyslipidemic (OR=0.82, 95%CI=0.72–0.92, p=1.2×10−3). These associations were independent of differences in objectively measured total daily physical activity or rest, and were not accounted for by prevalent coronary artery disease, stroke, or peripheral artery disease. Moreover, more regular activity rhythms were associated with lower odds of having cardiovascular disease (OR=0.83; 95%CI=0.73–0.95, p=5.7×10−3), an effect that was statistically mediated by the metabolic syndrome. We conclude that irregular activity

  4. The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome

    PubMed Central

    Spiropoulou, Christina F; Srikiatkhachorn, Anon

    2013-01-01

    The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity. PMID:23841977

  5. Force steadiness, muscle activity, and maximal muscle strength in subjects with subacromial impingement syndrome.

    PubMed

    Bandholm, Thomas; Rasmussen, Lars; Aagaard, Per; Jensen, Bente Rona; Diederichsen, Louise

    2006-11-01

    We investigated the effects of the subacromial impingement syndrome (SIS) on shoulder sensory-motor control and maximal shoulder muscle strength. It was hypothesized that both would be impaired due to chronic shoulder pain associated with the syndrome. Nine subjects with unilateral SIS who remained physically active in spite of shoulder pain and nine healthy matched controls were examined to determine isometric and isokinetic submaximal shoulder-abduction force steadiness at target forces corresponding to 20%, 27.5%, and 35% of the maximal shoulder abductor torque, and maximal shoulder muscle strength (MVC). Electromyographic (EMG) activity was assessed using surface and intramuscular recordings from eight shoulder muscles. Force steadiness was impaired in SIS subjects during concentric contractions at the highest target force level only, with muscle activity largely unaffected. No between-group differences in shoulder MVC were observed. The present data suggest that shoulder sensory-motor control is only mildly impaired in subjects with SIS who are able to continue with upper body physical activity in spite of shoulder pain. Thus, physical activity should be continued by patients with SIS, if possible, to avoid the loss in neural and muscle functions associated with inactivity.

  6. A General Protocol for Temperature Calibration of MAS NMR Probes at Arbitrary Spinning Speeds

    PubMed Central

    Guan, Xudong; Stark, Ruth E.

    2010-01-01

    A protocol using 207Pb NMR of solid lead nitrate was developed to determine the temperature of magic-angle spinning (MAS) NMR probes over a range of nominal set temperatures and spinning speeds. Using BioMAS and fastMAS probes with typical sample spinning rates of 8 and 35 kHz, respectively, empirical equations were devised to predict the respective sample temperatures. These procedures provide a straightforward recipe for temperature calibration of any MAS probe. PMID:21036557

  7. Valued Life Activities, Smoking Cessation, and Mood in Post-Acute Coronary Syndrome Patients

    PubMed Central

    Busch, Andrew M.; Srour, John Fani; Arrighi, James A.; Kahler, Christopher W.; Borrelli, Belinda

    2015-01-01

    Purpose Continued engagement in valued life activities is a protective factor for depression and has been linked to readiness to quit smoking in medical populations, but has never been examined among Acute Coronary Syndrome (ACS) patients. The purpose of this study is to investigate relationships among valued life activities, mood, and smoking post-ACS. Methods Participants were 54 post-ACS patients who were smoking before ACS hospitalization. Data on mood, smoking status, engagement in valued activities, restriction of valued activities, and satisfactory replacement of restricted activities was collected 1-12 months post-ACS. Results Depressive symptoms were associated with both less valued activity engagement and greater valued activity restriction. Positive affect was associated with greater valued activity engagement and negative affect was associated with greater valued activity restriction. Satisfactory replacement of restricted activities was associated with greater positive affect, fewer depressive symptoms, and quitting smoking post-ACS. The majority of these relationships remained significant after controlling for relevant covariates, including physical functioning. Conclusions Valued activity restriction and engagement may contribute to depressed mood and failure to quit smoking in ACS patients. Psychotherapies that target greater engagement in valued life activities deserve further investigation in ACS patients. PMID:25471466

  8. Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

    PubMed Central

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reininger, Belinda; McCormick, Joseph B.

    2016-01-01

    Purpose To measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans. Methods Participants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities. Results One thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity. Conclusions Meeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors. PMID:27054324

  9. Milli-Arcsecond (MAS) Imaging of the Solar Corona

    NASA Astrophysics Data System (ADS)

    Davila, Joseph M.; Oktem, Figen S.; Kamalabadi, Farzad; O'Neill, John; Novo-Gradac, Anne-Marie; Daw, Adrian N.; Rabin, Douglas M.

    2016-05-01

    Dissipation in the solar corona is believed to occur in extremely thin current sheets of order 1-100 km. Emission from these hot but thin current sheets should be visible in coronal EUV emission lines. However, this spatial scale is far below the resolution of existing imaging instruments, so these dissipation sites have never been observed individually. Conventional optics cannot be manufactured with sufficient surface figure accuracy to obtain the required spatial resolution in the extreme-ultraviolet where these hot plasmas radiate. A photon sieve, a diffractive imaging element similar to a Fresnel zone plate, can be manufactured to provide a few milli-arcsec (MAS) resolution, with much more readily achievable tolerances than with conventional imaging technology. Prototype photon sieve elements have been fabricated and tested in the laboratory. A full-scale ultra-high resolution instrument will require formation flying and computational image deconvolution. Significant progress has been made in overcoming these challenges, and some recent results in these areas are discussed. A simple design for a sounding rocket concept demonstration payload is presented that obtains 80 MAS (0.080 arcsec) imaging with a 100 mm diameter photon sieve to image Fe XIV 334 and Fe XVI 335. These images will show the structure of the corona at a resolution never before obtained, and they will also allow a study of the temperature structure in the dissipation region.

  10. Locomotor activity, object exploration and space preference in children with autism and Down syndrome.

    PubMed

    Kawa, Rafał; Pisula, Ewa

    2010-01-01

    There have been ambiguous accounts of exploration in children with intellectual disabilities with respect to the course of that exploration, and in particular the relationship between the features of explored objects and exploratory behaviour. It is unclear whether reduced exploratory activity seen with object exploration but not with locomotor activity is autism-specific or if it is also present in children with other disabilities. The purpose of the present study was to compare preschool children with autism with their peers with Down syndrome and typical development in terms of locomotor activity and object exploration and to determine whether the complexity of explored objects affects the course of exploration activity in children with autism. In total there were 27 children in the study. The experimental room was divided into three zones equipped with experimental objects providing visual stimulation of varying levels of complexity. Our results indicate that children with autism and Down syndrome differ from children with typical development in terms of some measures of object exploration (i.e. looking at objects) and time spent in the zone with the most visually complex objects.

  11. Dietary practices, physical activity, and body-mass index in a selected population of Down syndrome children and their siblings.

    PubMed

    Sharav, T; Bowman, T

    1992-06-01

    Thirty sibling pairs, each with one Down syndrome child between the ages of 2 and 14, were selected from families who had participated in an infant-stimulation program. The maternal and paternal educational levels were 14.9 and 16.9 years, respectively. The Down syndrome patients and their siblings were compared in terms of body-mass index, that is, weight/stature2 (w/s2); activity as measured on a questionnaire; and weekly caloric intake. There were no significant differences between the Down syndrome children and their siblings in terms of w/s2. The Down syndrome patients were less active than their siblings and spent significantly more time indoors, showing a preference for indoor activities. Caloric intake calculated as percentage of recommended allowance for height was somewhat less in the Down syndrome children--88.7%, compared with 95% in the siblings--but not significantly so. It is postulated that even though Down syndrome patients have been shown to be at risk for obesity, familial and other environmental factors, such as dietary control and involvement in physical activity, have an influence.

  12. The Relationship Between Physical Activity and the Metabolic Syndrome Score in Children

    PubMed Central

    McKune, Andrew J.; Brophy, Patricia; Geyer, Gabriel; Hickner, Robert C.

    2015-01-01

    The relationship between physical activity levels and the metabolic syndrome (MetSyn) score was examined in 72 boys and girls (9.5 ± 1.2 years). A fasting blood draw was obtained; waist circumference and blood pressure measured, and an accelerometer was worn for 5 days. Established cut points were used to estimate time spent in moderate, vigorous, moderate-to-vigorous (MVPA), and total physical activity. A continuous MetSyn score was created from blood pressure, waist circumference, high-density-lipoprotein, triglyceride, and glucose values. Regression analysis was used to examine the relationship between physical activity levels, the MetSyn score, and its related components. Logistic regression was used to examine the association between meeting physical activity recommendations, the MetSyn score, and its related components. All analyses were controlled for body mass index group, age, sex, and race. Time spent in different physical activity levels or meeting physical activity recommendations (OR: 0.87, 95%CI: 0.69-1.09) was not related with the MetSyn score after controlling for potential confounders (p>0.05). Moderate physical activity, MVPA, and meeting physical activity recommendations were related to a lower diastolic blood pressure (p<0.05). No other relationships were observed (p>0.05). While physical activity participation was not related with the MetSyn, lower diastolic blood pressure values were related to higher physical activity levels. PMID:25902555

  13. Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1.

    PubMed

    Morris, Rachael; Spencer, Shauna-Kay; Kyle, Patrick B; Williams, Jan Michael; Harris, Al'shondra; Owens, Michelle Y; Wallace, Kedra

    2016-01-01

    Women with hypertensive forms of pregnancy such as hemolysis-elevated liver enzymes-low platelet syndrome have increased circulating endothelin 1; however, the relationship between hypertension and endothelin 1 has not been studied. Using an animal model, we sought to determine whether there was an increased activation/dysfunction of endothelin 1, the effect of endothelin 1 receptor-A blockade on hypertension and other manifestations of hemolysis, elevated liver enzymes, and low platelets syndrome. On gestational day 12, timed-pregnant rats were infused with soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEndoglin; 4.7 and 7 µg/kg) via mini-osmotic pumps for 8 days. A subset of rats were treated with receptor-A antagonist (ABT-627, 5mg/kg) for 8 days. Rats with hemolysis-elevated liver enzymes-low platelet syndrome had significantly increased hypertension (P = .0001), circulating endothelin 1 (P = .03), and a significant 3.3- and 7.2-fold increase in preproendothelin messenger RNA (mRNA) expression in the placenta and liver (P = .01 and .04). Urinary protein:creatinine ratio was significantly increased in these animals (P = .0007), and circulating factors from these rats stimulated a significant increase in endothelial cell secretion of endothelin 1 (P = .001) in an in vitro assay. Blockade of the endothelin 1 receptor A significantly decreased hypertension (P = .001), circulating endothelin 1, and interleukin 17 (P = .004 and .003), placental preproendothelin mRNA expression (P = .016), and urinary protein:creatinine ratio (P = .007) in rats with hemolysis-elevated liver enzymes-low platelet syndrome. Blockade of the endothelin 1 receptor A significantly decreased hemolysis (P = .009), liver enzymes (P = .011), and significantly increased platelet levels (P = .03) and decreased circulating CD4+ and CD8+ T lymphocytes (P = .0004 and .0001) in rats infused with sFlt-1 and sEndoglin. These data support the hypothesis that endothelin 1 activation

  14. Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

    PubMed Central

    2016-01-01

    Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

  15. Radioiodine treatment in McCune-Albright syndrome with hyperthyroidism.

    PubMed

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Kashyap, Raghava; Manohar, Kuruva; Bhattacharya, Anish; Bhansali, Anil

    2012-07-01

    McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, "café-au-lait" spots and hyperfunctional endocrinopathies. Pathophysiological basis is activating mutation of the gene that encodes the alpha subunit of Gs membrane protein that stimulates the intracellular production of cAMP, conferring autonomous secretion of the gland in particular. One of the uncommon endocrine manifestations is hyperthyroidism. We present a patient who had café-au-lait spots, polyostotic fibrous dysplasia and hyperthyroidism. She was treated with radioactive iodine for the symptoms of hyperthyroidism and subsequently relieved from hyperthyroid features.

  16. Paraoxonase Activity and Lipid Profile in Paediatric Nephrotic Syndrome: A Cross-sectional Study

    PubMed Central

    Patil, Anuradha B.; Patil, Vidya S.; Ingleshwar, Deepti G.

    2016-01-01

    Introduction Dyslipidaemia of Nephrotic Syndrome (NS) is known to be linked to oxidative reactions and atherosclerosis. Paraoxonase (PON1) has been implicated in the prevention of Low Density Lipoprotein (LDL) lipid peroxidation and also degrades biologically active oxidised lipids in lipoprotein. Aim The present study was taken up to assess PON1 levels in paediatric nephrotic syndrome and also to see if any correlation exists between lipid parameters and PON1. Materials and Methods This study consists of Group 1 with 40 cases of NS in the age group of 2-14 years and Group 2 with 40 age and sex matched healthy controls. Lipid profile and paraoxonase activity was measured in serum samples of both the groups. Results Statistical analysis by student’s t-test showed that the mean levels of Total Cholesterol, Trigylycerides, LDL, and VLDL were significantly increased in Group 1 when compared to Group 2 (p <0.001). The mean levels of HDL were similar in both groups. The levels of PON1 were significantly lowered in Group 1 when compared to Group 2. Correlation studies showed no significant correlation between lipid profile and PON1. Conclusion Cases have atherosclerotic dyslipidaemia and significantly decreased PON1 activity. Decreased PON1 may lead to increased oxidation of LDL accelerating the process of atherosclerosis. PMID:27134858

  17. Macrophage activation syndrome as the initial manifestation of severe juvenile onset systemic lupus erythematosus. Favorable response to cyclophosphamide.

    PubMed

    Torres Jiménez, Alfonso; Solís Vallejo, Eunice; Zeferino Cruz, Maritza; Céspedes Cruz, Adriana; Sánchez Jara, Berenice

    2014-01-01

    The macrophage activation syndrome is a rare but potentially fatal complication of patients with autoimmune rheumatic diseases. This is a clinicopathological entity characterized by activation of histiocytes with prominent hemophagocytosis in the bone marrow and other reticuloendothelial systems. In patients with lupus it may mimic an exacerbation of the disease or infection. We report the case of a 7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage activation syndrome was simultaneously made with response to the use of cyclophosphamide.

  18. MAS C-Terminal Tail Interacting Proteins Identified by Mass Spectrometry- Based Proteomic Approach

    PubMed Central

    Tirupula, Kalyan C.; Zhang, Dongmei; Osbourne, Appledene; Chatterjee, Arunachal; Desnoyer, Russ; Willard, Belinda; Karnik, Sadashiva S.

    2015-01-01

    Propagation of signals from G protein-coupled receptors (GPCRs) in cells is primarily mediated by protein-protein interactions. MAS is a GPCR that was initially discovered as an oncogene and is now known to play an important role in cardiovascular physiology. Current literature suggests that MAS interacts with common heterotrimeric G-proteins, but MAS interaction with proteins which might mediate G protein-independent or atypical signaling is unknown. In this study we hypothesized that MAS C-terminal tail (Ct) is a major determinant of receptor-scaffold protein interactions mediating MAS signaling. Mass-spectrometry based proteomic analysis was used to comprehensively identify the proteins that interact with MAS Ct comprising the PDZ-binding motif (PDZ-BM). We identified both PDZ and non-PDZ proteins from human embryonic kidney cell line, mouse atrial cardiomyocyte cell line and human heart tissue to interact specifically with MAS Ct. For the first time our study provides a panel of PDZ and other proteins that potentially interact with MAS with high significance. A ‘cardiac-specific finger print’ of MAS interacting PDZ proteins was identified which includes DLG1, MAGI1 and SNTA. Cell based experiments with wild-type and mutant MAS lacking the PDZ-BM validated MAS interaction with PDZ proteins DLG1 and TJP2. Bioinformatics analysis suggested well-known multi-protein scaffold complexes involved in nitric oxide signaling (NOS), cell-cell signaling of neuromuscular junctions, synapses and epithelial cells. Majority of these protein hits were predicted to be part of disease categories comprising cancers and malignant tumors. We propose a ‘MAS-signalosome’ model to stimulate further research in understanding the molecular mechanism of MAS function. Identifying hierarchy of interactions of ‘signalosome’ components with MAS will be a necessary step in future to fully understand the physiological and pathological functions of this enigmatic receptor. PMID

  19. MODIS Airborne simulator (MAS) Final Report for CLASIC

    SciTech Connect

    Thomas Arnold; Steven Platnick

    2010-11-24

    The MAS was flown aboard the NASA ER-2 for the CLASIC field experiment, and for all data collected, provided calibrated and geolocated (Level-1B) radiance data for it’s 50 spectral bands (ranging in wavelength for 0.47 to 14.3 µm). From the Level-1B data, as directed in the Statement of Work, higher order (Level-2) data products were derived. The Level-2 products include: a) cloud optical thickness, b) cloud effective radius, c) cloud top height (temperature), d) cloud fraction, e) cloud phase products. Preliminary Level-1B and Level-2 products were provided during the field experiment (typically within one or two days of data collection). Final version data products were made available in December 2008 following considerable calibration analysis. Data collection, data processing (to Level-2), and discussion of the calibration work are summarized below.

  20. A hyper-ferritinemia syndrome evolving in recurrent macrophage activation syndrome, as an onset of amyopathic juvenile dermatomyositis: a challenging clinical case in light of the current diagnostic criteria.

    PubMed

    Poddighe, Dimitri; Cavagna, Lorenzo; Brazzelli, Valeria; Bruni, Paola; Marseglia, Gian Luigi

    2014-11-01

    Juvenile dermatomyositis is an immune-mediated inflammatory multi-system disease involving mainly striated muscles and skin. Typical dermatological features are fundamental to establish the diagnosis, especially whenever the myopathy is very mild or absent, as it occurs in the form called as amyopathic juvenile dermatomyositis. Sometimes, systemic rheumatic diseases can develop a hyperferritinemia syndrome characterized by hemophagocytosis, namely macrophage activation syndrome, which represents a severe and life-threatening complication. Here, we describe a complex clinical history characterized by a hyper-ferritinemia syndrome after infectious mononucleosis, leading to recurrent episodes of macrophage activation syndrome. Finally, the late onset of several skin changes brought to a diagnosis of amyopathic juvenile dermatomyositis.

  1. Food Waste Composting Study from Makanan Ringan Mas

    NASA Astrophysics Data System (ADS)

    Kadir, A. A.; Ismail, S. N. M.; Jamaludin, S. N.

    2016-07-01

    The poor management of municipal solid waste in Malaysia has worsened over the years especially on food waste. Food waste represents almost 60% of the total municipal solid waste disposed in the landfill. Composting is one of low cost alternative method to dispose the food waste. This study is conducted to compost the food waste generation in Makanan Ringan Mas, which is a medium scale industry in Parit Kuari Darat due to the lack knowledge and exposure of food waste recycling practice. The aim of this study is to identify the physical and chemical parameters of composting food waste from Makanan Ringan Mas. The physical parameters were tested for temperature and pH value and the chemical parameter are Nitrogen, Phosphorus and Potassium. In this study, backyard composting was conducted with 6 reactors. Tapioca peel was used as fermentation liquid and soil and coconut grated were used as the fermentation bed. Backyard composting was conducted with six reactors. The overall results from the study showed that the temperature of the reactors were within the range which are from 30° to 50°C. The result of this study revealed that all the reactors which contain processed food waste tend to produce pH value within the range of 5 to 6 which can be categorized as slightly acidic. Meanwhile, the reactors which contained raw food waste tend to produce pH value within the range of 7 to 8 which can be categorized as neutral. The highest NPK obtained is from Reactor B that process only raw food waste. The average value of Nitrogen is 48540 mg/L, Phosphorus is 410 mg/L and Potassium is 1550 mg/L. From the comparison with common chemical fertilizer, it shows that NPK value from the composting are much lower than NPK of the common chemical fertilizer. However, comparison with NPK of organic fertilizer shown only slightly difference value in NPK.

  2. Two examples of 'cuboid syndrome' with active bone pathology: why did manual therapy help?

    PubMed

    Matthews, Mark Lewis Gordon; Claus, Andrew Philip

    2014-10-01

    Cuboid syndrome describes lateral midfoot pain localised to the cuboid bone. Previously reported case studies promoted joint mobilisation or manipulation interventions. The assumed mechanism was correction of a subtle disruption to the calcaneocuboid joint position. There is an absence of evidence for correction of joint position, but there is evidence of neurophysiological mechanisms for pain modulation. This case study reports on a patient who suffered two occurrences of cuboid syndrome on opposite feet, three years apart. With both occurrences, joint mobilisation achieved rapid and lasting resolution of severe pain and functional limitations. This occurred despite the presence of an active bone pathology at the symptomatic cuboid (demonstrated with nuclear imaging), which could represent a stress reaction, transient osteoporosis, ischaemic necrosis, infection or neoplasm. This case contributes three considerations for clinical reasoning and manual therapy research. 1. Active local bone pathology could exist in other patients with pain at the cuboid, and other conditions where symptoms resolve with joint mobilisation. 2. Rapid and lasting symptom resolution fits with a hypothesis that joint mobilisation acted to reverse neurological sensitisation. 3. Lasting symptom resolution may be clinically associated with manual therapy, but mechanisms extending beyond temporary analgesia are yet to be identified.

  3. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    PubMed Central

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-01-01

    Background Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. Objective To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. Methods A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. Results The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Conclusion Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases. PMID:24652053

  4. Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette Syndrome

    PubMed Central

    Nagai, Yoko

    2015-01-01

    This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in epilepsy (small) and tics in Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g., syncope), or in relation to Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in epilepsy and TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behavior influence central thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated to gain a strong position within the next generation of treatment for epilepsy, as a non-invasive technique with minimal side effects. This approach also takes advantage of the current practical opportunity to utilize growing digital health technology. PMID:26441491

  5. Mental health and physical activity in women with polycystic ovary syndrome: a brief review.

    PubMed

    Conte, Francesca; Banting, Lauren; Teede, Helena J; Stepto, Nigel K

    2015-04-01

    This review was designed to consider the available literature concerning mental health and physical activity in women with polycystic ovary syndrome (PCOS). A systematic approach was taken and two electronic databases (PubMed and EBSCO Research articles published between 1970 and 2013) were searched in 2013 to inform a narrative review. Inclusion criteria encompassed requirements for the research to involve a physical activity intervention and assessment of mental health outcomes in women with PCOS. Seven articles considered mental health outcomes and physical activity interventions for women with PCOS. The results demonstrated positive outcomes following physical activity intervention for health-related quality of life, depression, and anxiety. Only one paper reported the independent effects of physical activity on mental health. All other interventions included multi-factor lifestyle interventions or did not establish a control group. Physical activity is likely to be beneficial to the mental health of women with PCOS; however, more research is required to establish the nature of the relationship between physical activity and mental health outcomes.

  6. Protective effects of Cornus mas fruit extract on carbon tetrachloride induced nephrotoxicity in rats.

    PubMed

    Es Haghi, M; Dehghan, G; Banihabib, N; Zare, S; Mikaili, P; Panahi, F

    2014-09-01

    Oxidative damage is implicated in the pathogenesis of kidney injury. Cornus mas is used for in renal aliments traditionally in Iran. The present study was aimed to investigate the antioxidant activity of C. mas fruit extract (CMFE) on carbon tetrachloride (CCl4) treated oxidative stress in Wistar albino rats. Forty two male albino rats were divided into seven groups. Group I served as a sham; Group II served as a normal control; Group III served as a toxic control, with CCl4 (1 ml/kg body weight; 80% in olive oil); Groups IV and V received CMFE at doses of 300 and 700 mg/kg before CCl4 injection; Groups VI and VII received extract at same doses orally at 2, 6, 12, 24 and 48 h after CCl4 intoxication. CCl4 injection produced a significant rise in serum markers of oxidative stress and lipid peroxidation product malondialdehyde along with the reduction of antioxidant enzymes such as superoxide dismuta, catalase and glutathion peroxidase. Serum creatinine, urea and uric acid concentrations were increased whereas level of protein and albumin were reduced. Treatment of rats with different doses of fruit extract (300 and 700 mg/kg) significantly (P < 0.05) ameliorated the alterations induced with CCl4 in lipid peroxidation, antioxidant defenses, biochemical and renal lesions. Based on these results, we conclude that CMFE protects kidney from oxidative stress induced by CCl4.

  7. Protective effects of Cornus mas fruit extract on carbon tetrachloride induced nephrotoxicity in rats

    PubMed Central

    Es.Haghi, M.; Dehghan, G.; Banihabib, N.; Zare, S.; Mikaili, P.; Panahi, F.

    2014-01-01

    Oxidative damage is implicated in the pathogenesis of kidney injury. Cornus mas is used for in renal aliments traditionally in Iran. The present study was aimed to investigate the antioxidant activity of C. mas fruit extract (CMFE) on carbon tetrachloride (CCl4) treated oxidative stress in Wistar albino rats. Forty two male albino rats were divided into seven groups. Group I served as a sham; Group II served as a normal control; Group III served as a toxic control, with CCl4 (1 ml/kg body weight; 80% in olive oil); Groups IV and V received CMFE at doses of 300 and 700 mg/kg before CCl4 injection; Groups VI and VII received extract at same doses orally at 2, 6, 12, 24 and 48 h after CCl4 intoxication. CCl4 injection produced a significant rise in serum markers of oxidative stress and lipid peroxidation product malondialdehyde along with the reduction of antioxidant enzymes such as superoxide dismuta, catalase and glutathion peroxidase. Serum creatinine, urea and uric acid concentrations were increased whereas level of protein and albumin were reduced. Treatment of rats with different doses of fruit extract (300 and 700 mg/kg) significantly (P < 0.05) ameliorated the alterations induced with CCl4 in lipid peroxidation, antioxidant defenses, biochemical and renal lesions. Based on these results, we conclude that CMFE protects kidney from oxidative stress induced by CCl4. PMID:25249718

  8. Acute Inhibition of MEK Suppresses Congenital Melanocytic Nevus Syndrome in a Murine Model Driven by Activated NRAS and Wnt Signaling.

    PubMed

    Pawlikowski, Jeffrey S; Brock, Claire; Chen, Sheau-Chiann; Al-Olabi, Lara; Nixon, Colin; McGregor, Fiona; Paine, Simon; Chanudet, Estelle; Lambie, Wendy; Holmes, William M; Mullin, James M; Richmond, Ann; Wu, Hong; Blyth, Karen; King, Ayala; Kinsler, Veronica A; Adams, Peter D

    2015-08-01

    Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRAS(Q61K) and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition.

  9. Meconium aspiration syndrome treatment - new approaches using old drugs.

    PubMed

    Ivanov, Vadim A

    2006-01-01

    Presently, modern medicine does not offer any disease-modifying treatment for meconium aspiration syndrome (MAS). Several medications with already established safety profiles when employed for similar or other conditions could be useful for MAS treatment. N-Acetylcysteine and DNAse have the capability to reduce viscosity and thickness of meconium by breaking disulfide bonds and slicing DNA, respectively. N-Acetylcysteine, antiprotease drugs, or low pH buffer solutions may have the capability to neutralize meconium's digestive enzymes responsible for lung damage in patients with MAS. All these compounds have great potential to reduce meconium's pathogenic properties which in turn could alleviate MAS severity.

  10. Electroencephalographical study of the Rett syndrome with special reference to the monorhythmic theta activities in adult patients.

    PubMed

    Ishizaki, A

    1992-05-01

    The long-term course of the EEG in the Rett syndrome is documented with reference to past studies. The monorhythmic theta activities in the waking state which were characteristically seen in adults with the Rett syndrome were investigated in patients aged between 27 and 28, using auto power spectra. They were often suppressed when the patients were excited or strained. Then the suppression was thought to elevate their conscious levels. The theta activities were often suppressed by calling, but not easily suppressed by other stimuli, especially the somatosensory stimuli of pain and touch. There were also abnormal findings in the ABR and blink reflexes. In the Rett syndrome we, therefore, suspect there are disturbances in the brain stem functions especially in the ascending reticular activating system which is related to elevation of the conscious level.

  11. Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

    PubMed

    Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto

    2016-01-01

    Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD).

  12. Tissue plasminogen activator is required for the development of fetal alcohol syndrome in mice.

    PubMed

    Noel, Melissa; Norris, Erin H; Strickland, Sidney

    2011-03-22

    Ethanol exposure during developmental synaptogenesis can lead to brain defects referred to as fetal alcohol syndrome (FAS), which can include mental health problems such as cognitive deficits and mental retardation. In FAS, widespread neuronal death and brain mass loss precedes behavioral and cognitive impairments in adulthood. Because tissue plasminogen activator (tPA) has been implicated in neurodegeneration, we examined whether it mediates FAS. Neonatal WT and tPA-/- mice were injected with ethanol to mimic FAS in humans. In WT mice, ethanol elicited caspase-3 activation, significant forebrain neurodegeneration, and decreased contextual fear conditioning in adults. However, tPA-deficient mice were protected from these neurotoxicities, and this protection could be abrogated by exogenous tPA. Selective pharmacological modulators of NMDA and GABAA receptor pathways revealed that the effects of tPA were mediated by the NR2B subunit of the NMDA receptor. This study identifies tPA as a critical signaling component in FAS.

  13. [Wolf-Parkinson-White syndrome. Intensive physical activity: the value of fulguration].

    PubMed

    Warin, J F; Haissaguerre, M; Le Métayer, P; Montserrat, P

    1989-08-01

    In subjects with Wolff-Parkinson-White syndrome an intense physical activity or the practice of sports may not only trigger off cardiac arrhythmias but also worsen their consequences and become life-threatening. A full electrophysiological study, including measurement of the anterograde refractory period of the accessory pathway, induction of atrial fibrillation and study of the effects of isoprenaline, seems to be indispensable to detect those patients who are most at risk. When the risk of potentially serious arrhythmia appears to be confirmed, catheter ablation of the accessory pathway may be the ideal solution, as it may cure the disease without the sequelae inherent in surgery. The results obtained in 19 athletes or subjects with intense physical activity (19) successes without preventive anti-arrhythmic treatment and at the cost of a single case of asymptomatic atrioventricular block) suggest that the catheter ablation technique will greatly benefit such patients.

  14. Fatal human anaplasmosis associated with macrophage activation syndrome in Greece and the Public Health response.

    PubMed

    Tsiodras, Sotirios; Spanakis, Nikos; Spanakos, Gregory; Pervanidou, Danai; Georgakopoulou, Theano; Campos, Elsa; Petra, Theofania; Kanellopoulos, Petros; Georgiadis, George; Antalis, Emmanouil; Kontos, Vassileios; Giannopoulos, Lambros A; Tselentis, Yiannis; Papa, Anna; Tsakris, Athanassios; Saroglou, George

    2017-02-08

    Human granulocytic anaplasmosis (HGA) is a tick-borne disease caused by Anaplasma phagocytophilum that has the potential to spread in new geographical areas. The first fatal case of HGA in Greece is presented. Fever of unknown origin, renal and respiratory insufficiency and development of macrophage activation syndrome characterized the clinical presentation. Amplification and sequencing of a fragment of the groEL gene revealed the presence of A. phagocytophilum. The epidemiological and clinical features were collected during an epidemiological investigation. Public health measures were instituted by the Hellenic Centre for Disease Control and Prevention. The Public Health intervention required the collaboration of epidemiologists, veterinarians and microbiologists. Emphasis was given to communication activities and misconceptions concerning canines and their role in the disease. The emergence of human anaplasmosis in a new geographical area highlights the importance of disease awareness and of the need for continued support for tick and tick-borne disease surveillance networks.

  15. Physical activity disparities by socioeconomic status among metabolic syndrome patients: The Fifth Korea National Health and Nutrition Examination Survey.

    PubMed

    Lee, Hyo; Kim, Byung-Hoon

    2016-02-01

    Physical activity plays an important role in preventing further progression of metabolic syndrome conditions to cardiovascular disease and type-2 diabetes. This study investigated physical activity disparities by socioeconomic status among metabolic syndrome patients. The fifth Korea National Health and Nutrition Examination Survey (2010-2012) data were analyzed (n=19,831). A revised definition of the US National Cholesterol Education Program Adult Treatment Panel III was used for screening metabolic syndrome patients. Using International Physical Activity Questionnaire, physical activity adherence was defined as participating in 150+ minutes of moderate-intensity physical activity, 75+ minutes of vigorous-intensity physical activity, or an equivalent combination of moderate-to vigorous-intensity physical activity per week. Socioeconomic status was measured by level of education and house-hold income. Among metabolic syndrome patients, physical activity adherence rate of first (lowest), second, third, and fourth quartile house-hold income group were 28.31% (95% confidence interval [CI], 26.14-30.28%), 34.68% (95% CI, 32.71-36.70), 37.44% (95% CI, 35.66-39.25), and 43.79% (95% CI, 41.85-45.75). Physical activity adherence rate of groups with elementary or lower, middle-school, high-school, and college or higher education degree were 25.17% (95% CI, 22.95-27.54), 38.2% (95% CI, 35.13-41.00), 39.60% (95% CI, 38.24-41.77), and 36.89% (95% CI, 35.77-38.03), respectively. This study found that physical activity adherence rate was lower in socioeconomically disadvantaged metabolic syndrome patients, which may aggravate health inequity status of Korean society.

  16. Meconium aspiration syndrome: possible pathophysiological mechanisms and future potential therapies.

    PubMed

    Lindenskov, Paal Helge Haakonsen; Castellheim, Albert; Saugstad, Ola Didrik; Mollnes, Tom Eirik

    2015-01-01

    Does meconium cause meconium aspiration syndrome (MAS) or is meconium discharge only a marker of fetal hypoxia? This dispute has lasted for centuries, but since the 1960s, detrimental effects of meconium itself on the lungs have been demonstrated in animal experiments. In clinical MAS, persistent pulmonary hypertension of the newborn is the leading cause of death in MAS. Regarding the complex chemical composition of meconium, it is difficult to identify a single agent responsible for the pathophysiology. However, considering that meconium is stored in the intestines, partly unexposed to the immune system, aspirated meconium could be recognized as ‘danger', representing damaged self. The common denominator in the pathophysiology could therefore be activation of innate immunity. Thus, a bulk of evidence implies that meconium is a potent activator of inflammatory mediators, including cytokines, complement, prostaglandins and reactive oxygen species. We hypothesize that the two main recognition systems of innate immunity, the Toll-like receptors and the complement system, recognize meconium as ‘danger', which leads not only to lung dysfunction but also to a systemic inflammatory response. This might have therapeutic implications in the future.

  17. Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives.

    PubMed

    Robinson, Cemre; Collins, Michael T; Boyce, Alison M

    2016-10-01

    Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript α-subunit, Gsα. Constitutive Gs signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton, this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and café-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions.

  18. Hyperphosphorylation of RyRs Underlies Triggered Activity in Transgenic Rabbit Model of LQT2 Syndrome

    PubMed Central

    Terentyev, Dmitry; Rees, Colin M.; Li, Weiyan; Cooper, Leroy L.; Jindal, Hitesh K.; Peng, Xuwen; Lu, Yichun; Terentyeva, Radmila; Odening, Katja E.; Daley, Jean; Bist, Kamana; Choi, Bum-Rak; Karma, Alain; Koren, Gideon

    2015-01-01

    Rationale Loss-of function mutations in HERG potassium channels underlie long QT syndrome (LQTS) type 2 (LQT2), and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasmamembrane-related pathways involved in arrhythmogenesis in LQTS, while pro-arrhythmic changes in intracellular Ca2+ handling remained unexplored. Objective We investigated the remodeling of Ca2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 in order to determine whether these changes contribute to triggered activity in the form of early afterdepolarizations (EADs). Methods and Results Confocal Ca2+ imaging revealed decrease in amplitude of Ca2+ transients and SR Ca2+ content in LQT2 myocytes. Experiments using SR-entrapped Ca2+ indicator demonstrated enhanced RyR-mediated SR Ca2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR in LQT2 myocytes vs. controls. Co-immunoprecipitation experiments demonstrated loss of protein phosphatases type 1 and type 2 from the RyR complex. Stimulation of LQT2 cells with β-adrenergic agonist isoproterenol resulted in prolongation of the plateau of action potentials accompanied by aberrant Ca2+ releases and EADs, which were abolished by inhibition of CaMKII. Computer simulations showed that late aberrant Ca2+ releases caused by RyR hyperactivity promote EADs and underlie the enhanced triggered activity through increased forward mode of NCX1. Conclusions Hyperactive, hyperphosphorylated RyRs due to reduced local phosphatase activity enhance triggered activity in LQT2 syndrome. EADs are promoted by aberrant RyR-mediated Ca2+ releases that are present despite a reduction of sarcoplasmic reticulum (SR) content. Those releases increase forward mode NCX1, thereby slowing repolarization and enabling L-type Ca2+ current reactivation. PMID:25249569

  19. Prevalence and Impact of Active and Passive Cigarette Smoking in Acute Respiratory Distress Syndrome

    PubMed Central

    Hsieh, S. Jean; Zhuo, Hanjing; Benowitz, Neal L.; Thompson, B. Taylor; Liu, Kathleen D.; Matthay, Michael A.; Calfee, Carolyn S.

    2014-01-01

    Objective Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome (ARDS). We sought to determine 1) the prevalence of cigarette smoke exposure in a diverse multi-center sample of ARDS patients, and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in ARDS. Design Analysis of the Albuterol for the Treatment of ALI (ALTA) and Omega ARDS Network studies. Setting Acute Respiratory Distress Syndrome Network hospitals. Patients Three hundred eighty one patients with ARDS. Interventions None. Measurements NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two NHLBI ARDS Network randomized controlled trials. Main Results Urine NNAL levels were consistent with active smoking in 36% of ARDS patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with NNAL levels in the active smoking range were younger and had a higher prevalence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared to patients with undetectable NNAL levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness. Conclusions In this first multicenter study of biomarker-determined cigarette smoke exposure in ARDS patients, we found that active cigarette smoke exposure was significantly more prevalent among ARDS patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by NNAL had similar severity of lung injury as patients with

  20. Crosstalk between circulating peroxisome proliferator-activated receptor gamma, adipokines and metabolic syndrome in obese subjects

    PubMed Central

    2013-01-01

    Background Peroxisome proliferator-activated receptor gamma (PPARγ) has direct and indirect function in adipokines production process. We aimed to assess the possible influence of circulating PPARγ on relative risk of metabolic syndrome and also examine the association between circulating PPARγ and adipokines levels among obese subjects. Methods A total of 96 obese subjects (body mass index (BMI) ≥30) were included in the current cross-sectional study. We assessed the body composition with the use of Body Composition Analyzer BC-418MA - Tanita. The MetS (metabolic syndrome) was defined based on the National Cholesterol Education Program Adult Treatment Panel III. All baseline blood samples were obtained following an overnight fasting. Serum concentrations of adipokines including Retinol binding protein 4 (RBP4), omentin-1, vaspin, progranulin, nesfatin-1 and circulating PPARγ was measured with the use of an enzyme-linked immunosorbent assay method. Statistical analyses were performed using software package used for statistical analysis (SPSS). Results We found main association between circulating PPARγ and body composition in obese population. The risk of metabolic syndrome in subjects with higher concentration of PPARγ was 1.9 fold in compared with lower concentration of PPARγ after adjustment for age, sex and BMI. There was significant association between PPARγ and adipokines, specially nesfatin-1 and progranulin. Defined adipokines pattern among participants demonstrated the markedly higher concentration of vaspin, RBP4 and nesfatin-1 in participants with MetS compared to non-MetS subjects. Conclusions It appears all of studied adipokines might have association with PPARγ level and might simultaneously be involve in some common pathway to make susceptible obese subjects for MetS. PMID:24330836

  1. Idiopathic Pulmonary Hemosiderosis in a Child with Recurrent Macrophage Activation Syndrome Secondary to Systemic Juvenile Idiopathic Arthritis

    PubMed Central

    Barut, Kenan; Sahin, Sezgin; Adrovic, Amra

    2017-01-01

    Macrophage activation syndrome, a severe complication of systemic juvenile idiopathic arthritis and other inflammatory diseases, represents one of the most important rheumatological emergencies. Delayed diagnosis could lead to life-threatening complications. Pulmonary hemosiderosis has been classically characterized by a triad of anemia, hemoptysis, and lung infiltrates on chest radiogram. Although the majority of patients of pulmonary hemosiderosis are considered idiopathic, secondary hemosiderosis associated with known diseases could be seen. In this case report, we aimed to present gradually increased pulmonary manifestations due to pulmonary hemosiderosis with recurrent macrophage activation syndrome attacks in a child with systemic juvenile idiopathic arthritis. PMID:28251009

  2. The Antithrombotic Effect of Angiotensin-(1–7) Involves Mas-Mediated NO Release from Platelets

    PubMed Central

    Fraga-Silva, Rodrigo Araújo; Pinheiro, Sergio Veloso Brant; Gonçalves, Andrey Christian Costa; Alenina, Nathalia; Bader, Michael; Santos, Robson Augusto Souza

    2008-01-01

    The antithrombotic effect of angiotensin(Ang)-(1–7) has been reported, but the mechanism of this effect is not known. We investigated the participation of platelets and receptor Mas-related mechanisms in this action. We used Western blotting to test for the presence of Mas protein in rat platelets and used fluorescent-labeled FAM-Ang-(1–7) to determine the specific binding for Ang-(1–7) and its displacement by the receptor Mas antagonist A-779 in rat platelets and in Mas−/ − and Mas+/+ mice platelets. To test whether Ang-(1–7) induces NO release from platelets, we used the NO indicator DAF-FM. In addition we examined the role of Mas in the Ang-(1–7) antithrombotic effect on induced thrombi in the vena cava of male Mas−/ − and Mas+/+ mice. The functional relevance of Mas in hemostasis was evaluated by determining bleeding time in Mas+/+ and Mas−/ − mice. We observed the presence of Mas protein in platelets, as indicated by Western Blot, and displacement of the binding of fluorescent Ang-(1–7) to rat platelets by A-779. Furthermore, in Mas+/+ mouse platelets we found specific binding for Ang-(1–7), which was absent in Mas−/ − mouse platelets. Ang-(1–7) released NO from rat and Mas+/+ mouse platelets, and A-779 blocked this effect. The NO release stimulated by Ang-(1–7) was abolished in Mas−/ − mouse platelets. Ang-(1–7) inhibited thrombus formation in Mas+/+ mice. Strikingly, this effect was abolished in Mas−/ −mice. Moreover, Mas deficiency resulted in a significant decrease in bleeding time (8.50 ± 1.47 vs. 4.28 ± 0.66 min). This study is the first to show the presence of Mas protein and specific binding for Ang-(1–7) in rat and mouse platelets. Our data also suggest that the Ang-(1–7) antithrombotic effect involves Mas-mediated NO release from platelets. More importantly, we showed that the antithrombotic effect of Ang-(1–7) in vivo is Mas dependent and that Mas is functionally important in hemostasis. PMID

  3. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters in Malaysian subjects.

    PubMed

    Al-Hamodi, Zaid H; Saif-Ali, Riyadh; Ismail, Ikram S; Ahmed, Khaled A; Muniandy, Sekaran

    2012-05-01

    The plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat insertion/deletion polymorphisms might be genetic determinations of increased or decreased of their plasma activities. The aim of this study was to investigate the association of plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat I/D polymorphisms with metabolic syndrome parameters in normal Malaysian subjects and to assess the impact of these polymorphisms on their plasma activities and antigens. The genetic polymorphisms were genotyped in 130 normal subjects. In addition, the plasma activities and antigens of plasminogen activator inhibitor-1 and tissue plasminogen activator as well as levels of insulin, glucose, and lipid profile at fasting state were investigated. The subjects with homozygous 4G/4G showed association with an increased triglyceride (p = 0.007), body mass index (p = 0.01) and diastolic blood pressure (p = 0.03). In addition, the plasminogen activator inhibitor-1 4G/5G polymorphism modulates plasma plasminogen activator inhibitor-1 activity and antigen and tissue plasminogen activator activity (p = 0.002, 0.014, 0.003) respectively. These results showed that, the plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters, plasminogen activator inhibitor-1 and tissue plasminogen activator activities in Malaysian subjects, and may serve to increase the risk of type 2 diabetes and cardiovascular disease in Malaysian subjects.

  4. [McCune-Albright syndrome associated with diabetes mellitus].

    PubMed

    Chihaoui, M; Hamza, N; Lamine, F; Jabeur, S; Yazidi, M; Ftouhi, B; Slimane, H

    2012-03-01

    McCune-Albright syndrome (MAS) consists of the triad of polyostotic fibrous dysplasia, cutaneous pigmentation, and multiple endocrine abnormalities. Type 1 diabetes mellitus is not included in MAS. We report the case of an 18-year-old girl who presented with McCune-Albright syndrome. The diagnosis was made by the presence of precocious puberty at the age of 6 years, cutaneous pigmentation, polyostotic fibrous dysplasia, and phosphate diabetes. Type 1 diabetes mellitus developed at the age of 16 years. We discuss this case, the relationship between type 1 diabetes mellitus and MAS, with a literature review.

  5. Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis.

    PubMed

    Parvanescu, Alina; Cros, Jérôme; Ronot, Maxime; Hentic, Olivia; Grybek, Virginie; Couvelard, Anne; Levy, Philippe; Chanson, Philippe; Ruszniewski, Philippe; Sauvanet, Alain; Gaujoux, Sebastien

    2014-08-01

    GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.

  6. Endothelial cells microparticle-associated protein disulfide isomerase promotes platelet activation in metabolic syndrome

    PubMed Central

    Li, Yi-hui; Song, Dai-jun; Chen, Tong-shuai; Zhang, Wei; Zhong, Ming; Zhang, Yun; Xing, Yan-qiu; Wang, Zhi-hao

    2016-01-01

    Background Metabolic syndrome (MetS) is a common challenge in the world, and the platelet activation is enhanced in MetS patients. However, the fundamental mechanism that underlies platelet activation in MetS remains incompletely understood. Endothelial cells are damaged seriously in MetS patients, then they release more endothelial microparticles (EMPs). After all, whether the EMPs participate in platelet activation is still obscure. If they were, how did they work? Results We demonstrated that the levels of EMPs, PMPs (platelet derived microparticles) and microparticle-carried-PDI activity increased in MetS patients. IR endothelial cells released more EMPs, the EMP-PDI was more activated. EMPs can enhance the activation of CD62P, GPIIb/IIIa and platelet aggregation and this process can be partly inhibited by PDI inhibitor such as RL90 and rutin. Activated platelets stimulated by EMPs expressed more PDI on cytoplasm and released more PMPs. Materials and Methods We obtained plasma from 23 MetS patients and 8 normal healthy controls. First we built insulin resistance (IR) model of human umbilical vein endothelial cells (HUVECs), and then we separated EMPs from HUVECs culture medium and used these EMPs to stimulate platelets. Levels of microparticles, P-selectin(CD62P), Glycoprotein IIb/IIIa (GPIIb/IIIa) were detected by flow cytometry and levels of EMPs were detected by enzyme-linked immunosorbent assay (ELISA). The protein disulfide isomerase (PDI) activity was detected by insulin transhydrogenase assay. Platelet aggregation was assessed by turbidimetry. Conclusion EMPs can promote the activation of GPIIb/IIIa in platelets and platelet aggregation by the PDI which is carried on the surface of EMPs. PMID:27825126

  7. EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide.

    PubMed

    Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier; Asmussen, Karsten; Jacobsen, Soren; Bartoloni, Elena; Gerli, Roberto; Bijlsma, Johannes Wj; Kruize, Aike A; Bombardieri, Stefano; Bookman, Arthur; Kallenberg, Cees; Meiners, Petra; Brun, Johan G; Jonsson, Roland; Caporali, Roberto; Carsons, Steven; De Vita, Salvatore; Del Papa, Nicoletta; Devauchelle, Valerie; Saraux, Alain; Fauchais, Anne-Laure; Sibilia, Jean; Hachulla, Eric; Illei, Gabor; Isenberg, David; Jones, Adrian; Manoussakis, Menelaos; Mandl, Thomas; Jacobsson, Lennart; Demoulins, Frederic; Montecucco, Carlomaurizio; Ng, Wan-Fai; Nishiyama, Sumusu; Omdal, Roald; Parke, Ann; Praprotnik, Sonja; Tomsic, Matjia; Price, Elizabeth; Scofield, Hal; L Sivils, Kathy; Smolen, Josef; Laqué, Roser Solans; Steinfeld, Serge; Sutcliffe, Nurhan; Sumida, Takayuki; Valesini, Guido; Valim, Valeria; Vivino, Frederick B; Vollenweider, Cristina

    2015-01-01

    The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

  8. EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide

    PubMed Central

    Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier

    2015-01-01

    The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS. PMID:26509054

  9. Obesity, Food Selectivity, and Physical Activity in Individuals with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Raspa, Melissa; Bailey, Donald B., Jr.; Bishop, Ellen; Holiday, David; Olmsted, Murrey

    2010-01-01

    National survey data from 884 families were used to examine the overall health of children and adults with fragile X syndrome. Results indicate the rate of obesity in adults with fragile X syndrome is similar to the general population (30%). Male children with fragile X syndrome, however, had higher rates of obesity (31%) when compared with…

  10. Heart Activity and Autistic Behavior in Infants and Toddlers with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Roberts, Jane E.; Tonnsen, Bridgette; Robinson, Ashley; Shinkareva, Svetlana V.

    2012-01-01

    The present study contrasted physiological arousal in infants and toddlers with fragile X syndrome to typically developing control participants and examined physiological predictors early in development to autism severity later in development in fragile X syndrome. Thirty-one males with fragile X syndrome (ages 8-40 months) and 25 age-matched…

  11. Distributed Cooperation Solution Method of Complex System Based on MAS

    NASA Astrophysics Data System (ADS)

    Weijin, Jiang; Yuhui, Xu

    To adapt the model in reconfiguring fault diagnosing to dynamic environment and the needs of solving the tasks of complex system fully, the paper introduced multi-Agent and related technology to the complicated fault diagnosis, an integrated intelligent control system is studied in this paper. Based on the thought of the structure of diagnostic decision and hierarchy in modeling, based on multi-layer decomposition strategy of diagnosis task, a multi-agent synchronous diagnosis federation integrated different knowledge expression modes and inference mechanisms are presented, the functions of management agent, diagnosis agent and decision agent are analyzed, the organization and evolution of agents in the system are proposed, and the corresponding conflict resolution algorithm in given, Layered structure of abstract agent with public attributes is build. System architecture is realized based on MAS distributed layered blackboard. The real world application shows that the proposed control structure successfully solves the fault diagnose problem of the complex plant, and the special advantage in the distributed domain.

  12. QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents.

    PubMed

    Medina Marrero, R; Marrero-Ponce, Y; Barigye, S J; Echeverría Díaz, Y; Acevedo-Barrios, R; Casañola-Martín, G M; García Bernal, M; Torrens, F; Pérez-Giménez, F

    2015-01-01

    The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.73% and 92.47%, respectively, for the training set. Additionally, these models are able to correctly classify 92.16% and 87.56% of 706 compounds in an external test set. A comparison of the statistical parameters of the QuBiLs-MAS LDA-based models with those for models reported in the literature reveals comparable to superior performance, although the latter were built over much smaller and less diverse datasets, representing fewer mechanisms of action. It may therefore be inferred that the QuBiLs-MAS method constitutes a valuable tool useful in the design and/or selection of new and broad spectrum agents against life-threatening fungal infections.

  13. Pediatric Fulminant Leptospirosis Complicated by Pericardial Tamponade, Macrophage Activation Syndrome and Sclerosing Cholangitis

    PubMed Central

    Yeşilbaş, Osman; Kıhtır, Hasan Serdar; Yıldırım, Hamdi Murat; Hatipoğlu, Nevin; Şevketoğlu, Esra

    2016-01-01

    Background: Leptospirosis is a zoonotic infectious disease caused by pathogenic spirochetes of the genus Leptospira. Although it is usually asymptomatic and self-limited, severe potentially fatal illness accompanied by multi-organ failure may occur. Case Report: Here we report an unusual case of severe leptospirosis successfully treated with continuous venovenous hemofiltration (CVVHF) and therapeutic plasma exchange (TPE). The patient presented with pericardial tamponade, renal failure and macrophage activation syndrome, and later suffered prolonged jaundice and sclerosing cholangitis during hospitalization in the pediatric intensive care unit (PICU). To the best of our knowledge, sclerosing cholangitis due to leptospirosis has not been reported in the literature. Conclusion: Leptospirosis should be kept in mind in the differential diagnosis of sepsis and septic shock with fever, thrombocytopenia, jaundice and renal failure. TPE and CVVHF should start early after the diagnosis of leptospirosis with multiorgan failure. PMID:27761292

  14. Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4.

    PubMed

    Xu, Xiaohua; Liu, Yilun

    2009-03-04

    Human RECQ helicases have been linked to distinct clinical diseases with increased cancer rates and premature ageing. All RECQ proteins, except RECQ4, have been shown to be functional helicases. Mutations in RECQ4 lead to Rothmund-Thomson syndrome (RTS), and mouse models reveal that the conserved helicase motifs are required for avoidance of RTS. Furthermore, the amino (N) terminus of RECQ4 shares homology with yeast DNA replication initiation factor, Sld2, and is vital for embryonic development. Here, in contrast to previous reports, we show that RECQ4 exhibits DNA helicase activity. Importantly, two distinct regions of the protein, the conserved helicase motifs and the Sld2-like N-terminal domain, each independently promote ATP-dependent DNA unwinding. Taken together, our data provide the first biochemical clues underlying the molecular function of RECQ4 in DNA replication and genome maintenance.

  15. Active viral B hepatitis in parenteral drug abusers with acquired immune deficiency syndrome (AIDS).

    PubMed

    Leevy, C B; Nurse, H; Kapila, R

    1989-01-01

    Eighty-percent of 47 parenteral drug abusers with hepatomegaly and acquired immunodeficiency syndrome had HBV DNA in serum, although only 27% were HBsAg or "e" antigen-positive by polyclonal radioimmunoassay. Liver biopsies from each of 37 HBV DNA seropositive patients showed HBV DNA and were HBcAg-positive. The absence of positive HBsAg and "e" antigen in HBV DNA-positive patients was attributable to the presence of immune complexes; after in vitro dissociation of these complexes there was an increase in HBsAg from 24% to 86%, and of "e" antigen from 19% to 62%. These data indicate that actively replicating hepatitis B virus is common in patients with AIDS, and that precautions should be taken to prevent its dissemination. Therapy in these patients should address both human immunodeficiency and hepatitis B virus infections.

  16. Emergency department syndromic surveillance providing early warning of seasonal respiratory activity in England.

    PubMed

    Hughes, H E; Morbey, R; Hughes, T C; Locker, T E; Pebody, R; Green, H K; Ellis, J; Smith, G E; Elliot, A J

    2016-04-01

    Seasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1-4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.

  17. Active Control of Repetitive Structural Transitions between Replication Forks and Holliday Junctions by Werner Syndrome Helicase

    PubMed Central

    Shin, Soochul; Lee, Jinwoo; Yoo, Sangwoon; Kulikowicz, Tomasz; Bohr, Vilhelm A.; Ahn, Byungchan; Hohng, Sungchul

    2016-01-01

    SUMMARY The reactivation of stalled DNA replication via fork regression invokes Holliday junction formation, branch migration, and the recovery of the replication fork after DNA repair or error-free DNA synthesis. The coordination mechanism for these DNA structural transitions by molecular motors, however, remains unclear. Here we perform single-molecule fluorescence experiments with Werner syndrome protein (WRN) and model replication forks. The Holliday junction is readily formed once the lagging arm is unwound, and migrated unidirectionally with 3.2 ± 0.03 bases/s velocity. The recovery of the replication fork was controlled by branch migration reversal of WRN, resulting in repetitive fork regression. The Holliday junction formation, branch migration, and migration direction reversal are all ATP dependent, revealing that WRN uses the energy of ATP hydrolysis to actively coordinate the structural transitions of DNA. PMID:27427477

  18. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome.

    PubMed

    Nieto-Torres, Jose L; Verdiá-Báguena, Carmina; Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Torres, Jaume; Aguilella, Vicente M; Enjuanes, Luis

    2015-11-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein-lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.

  19. Active ear acupuncture points in neonates with neonatal abstinence syndrome (NAS).

    PubMed

    Raith, Wolfgang; Kutschera, Jörg; Müller, Wilhelm; Urlesberger, Berndt

    2011-01-01

    The aim of the study was to determine the presence of acupuncture ear points in neonates with Neonatal Abstinence Syndrome (NAS). NAS occurs in the first days of life in neonates whose mothers have a history of drug abuse, and may also occur in neonates whose mothers are currently following substitution therapy. The patients are neonates with NAS admitted over one year to the Division of Neonatology at the University Hospital Graz. The examination took place on the third day after delivery (mean value 70.3 hours) and was performed by a neuronal pen (PS 3 © Silberbauer, Vienna, Austria). An integrated sound and optical signal detected the active ear points that were then placed on an ear map. We investigated six neonates (four male, two female). All investigated neonates showed the presence of active ear acupuncture points. The psychovegetative rim was the most common organic area of the children, following by a few organic points. This corresponds with the results found in healthy neonates. In all neonates with NAS, we found the presence of psychic ear points. The identified psychic ear points are the frustration-point, R-point and the psychotropic area nasal from the incisura intertragica. In all neonates with NAS, active organic and psychic ear points were detectable in both ears. In the future, it could be possible to use active ear points for diagnostic and therapeutic purposes.

  20. Reduced 11beta-hydroxysteroid dehydrogenase activity in patients with the nephrotic syndrome.

    PubMed

    Vogt, B; Dick, B; N'Gankam, V; Frey, F J; Frey, B M

    1999-02-01

    Patients with the nephrotic syndrome (NS) exhibit abnormal renal sodium retention which cannot completely explained by a secondary hyperaldosteronism due to reduced renal perfusion. As an alternative mechanism to explain this phenomenon we postulate a cortisol-mediated mineralocorticoid effect as a consequence of a reduced activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). A down-regulation of 11beta-HSD, i.e. of the shuttle of active to inactive glucocorticosteroids, has been shown to cause mineralocorticoid effects. Therefore we investigated the activity of 11beta-HSD by measuring the urinary ratio of (tetrahydrocortisol + 5alpha-tetrahydrocortisol)/tetrahydrocortisone [(THF+5alpha-THF)/THE] by gas-chromatography in 29 NS patients with biopsy-proven glomerulonephritis and 29 healthy control subjects. The ratio of (THF+5alpha-THF)/THE was higher in NS patients (median 1.49, range 0.45-4.07) than in the control subjects (0.98, 0.60-1.36; p<0.01). This ratio was increased as a consequence of a decreased urinary excretion rate of the cortisone metabolite, THE. The present data indicate that a reduced activity of 11beta-HSD is a new mechanism contributing to the exaggerated sodium retention in patients with the NS.

  1. [Autoinflammatory syndromes].

    PubMed

    Lamprecht, P; Gross, W L

    2009-06-01

    In its strict sense, the term "autoinflammatory syndromes" comprises the hereditary periodic fever syndromes (HPF), which are caused by mutations of pattern-recognition receptors (PRR) and perturbations of the cytokine balance. These include the crypyrinopathies, familial Mediterranean fever, TNF-receptor associated periodic fever syndrome (TRAPS), hyper-IgD and periodic syndrome (HIDS), pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, NALP12-HPF, and the Blau syndrome. The diseases are characterized by spontaneous activation of cells of the innate immunity in the absence of ligands. Autoantibodies are usually not found. HPF clinically present with recurrent fever episodes and inflammation, especially of serosal and synovial interfaces and the skin. Intriguingly, PRR-mediated autoinflammtory mechanisms also play a role in a number of chronic inflammatory and autoimmune diseases.

  2. Down syndrome critical region 2 protein inhibits the transcriptional activity of peroxisome proliferator-activated receptor {beta} in HEK293 cells

    SciTech Connect

    Song, Hae Jin; Park, Joongkyu; Seo, Su Ryeon; Kim, Jongsun; Paik, Seung R.; Chung, Kwang Chul

    2008-11-21

    Down syndrome is mainly caused by a trisomy of chromosome 21. The Down syndrome critical region 2 (DSCR2) gene is located within a part of chromosome 21, the Down syndrome critical region (DSCR). To investigate the function of DSCR2, we sought to identify DSCR2-interacting proteins using yeast two-hybrid assays. A human fetal brain cDNA library was screened, and DSCR2 was found to interact with a member of the nuclear receptor superfamily, peroxisome proliferator-activated receptor {beta}, (PPAR{beta}). A co-immunoprecipitation assay demonstrated that DSCR2 physically interacts with PPAR{beta} in mammalian HEK293 cells. DSCR2 also inhibited the ligand-induced transcriptional activity of PPAR{beta}. Furthermore, PPAR{beta} also decreased the solubility of DSCR2, which increased levels of insoluble DSCR2.

  3. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome.

    PubMed

    Mizuno, Kei; Kawatani, Junko; Tajima, Kanako; Sasaki, Akihiro T; Yoneda, Tetsuya; Komi, Masanori; Hirai, Toshinori; Tomoda, Akemi; Joudoi, Takako; Watanabe, Yasuyoshi

    2016-01-01

    Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

  4. Not all M&As are alike--and that matters.

    PubMed

    Bower, J L

    2001-03-01

    Despite all that's been written about mergers and acquisitions, even the experts know surprisingly little about them. The author recently headed up a year-long study sponsored by Harvard Business School on the subject of M&A activity. In-depth findings will emerge over the next few years, but the research has already revealed some interesting results. Most intriguing is the notion that, although academics, consultants, and businesspeople lump M&As together, they represent very different strategic activities. Acquisitions occur for the following reasons: to deal with overcapacity through consolidation in mature industries; to roll up competitors in geographically fragmented industries; to extend into new products and markets; as a substitute for R&D; and to exploit eroding industry boundaries by inventing an industry. The different strategic intents present distinct integration challenges. For instance, if you acquire a company because your industry has excess capacity, you have to determine which plants to shut down and which people to let go. If, on the other hand, you buy a company because it has developed an important technology, your challenge is to keep the acquisition's best engineers from jumping ship. These scenarios require the acquiring company to engage in nearly opposite managerial behaviors. The author explores each type of M&A--its strategic intent and the integration challenges created by that intent. He underscores the importance of the acquiring company's assessment of the acquired group's culture. Depending on the type of M&A, approaches to the culture in place must vary, as will the level to which culture interferes with integration. He draws from the experiences of such companies as Cisco, Viacom, and BancOne to exemplify the different kinds of M&As.

  5. Impaired Homocysteine Transmethylation and Protein-Methyltransferase Activity Reduce Expression of Selenoprotein P: Implications for Obesity and Metabolic Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity causes Metabolic Syndrome and Type-II Diabetes, disrupting hepatic function, methionine (Met)/homocysteine (Hcy) transmethylation and methyltransferase (PRMT) activities. Selenoprotein P (SEPP1), exported from the liver, is the predominate form of plasma selenium (Se) and the physiological S...

  6. Elevated soft tissue activity in early but not delayed phase of bone scan in Klippel-Trenaunay syndrome.

    PubMed

    Liu, Bin; Servaes, Sabah; Zhuang, Hongming

    2013-03-01

    Triple-phase bone scan is commonly used in the diagnosis of osteomyelitis. Elevated bone tracer activity in early but not delayed phase of the study favors cellulitis over osteomyelitis. We reported that Klippel-Trenaunay syndrome, a congenital disorder characterized by malformations of the capillary, venous, and lymphatic systems, can have images similar to cellulitis on triple-phase bone scan.

  7. Acute Effects of a Therapeutic Mobility Device on Physical Activity and Heart Rate in Children with Down Syndrome

    ERIC Educational Resources Information Center

    Hauck, Janet L.; Ulrich, Dale A.

    2015-01-01

    Purpose: The purpose of this feasibility study was to provide an opportunity to increase physical activity (PA) and heart rate (HR) for children with Down syndrome (DS) during unstructured group exercise utilizing a riding device called the Power Pumper®. Method: Twenty-four children aged 5 to 7 years old participated in this case-control study,…

  8. Selected Laws, Rules and State-Level Activities in Wisconsin Related to Acquired Immunodeficiency Syndrome. Information Memorandum 87-4.

    ERIC Educational Resources Information Center

    Sweet, Richard

    This information memorandum describes the selected laws, rules, and state-level activities in Wisconsin related to acquired immunodeficiency syndrome (AIDS) and tests for antibodies to the virus (HIV) that causes AIDS. A section on current state laws on AIDS and HIV antibody testing describes laws related to informed consent for testing,…

  9. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome.

    PubMed Central

    Schwindinger, W F; Francomano, C A; Levine, M A

    1992-01-01

    McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The diverse metabolic abnormalities seen in MAS share the involvement of cells that respond to extracellular signals through activation of the hormone-sensitive adenylyl cyclase system (EC 4.6.1.1). Mutations that lead to constitutive activation of Gs alpha, the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase activity, have been identified in a subset of human growth hormone-secreting pituitary tumors and human thyroid tumors. We report here the identification of a mutation in the gene encoding Gs alpha in a patient with MAS. Denaturing gradient gel electrophoresis was used to analyze amplified DNA fragments including exon 8 or exon 9 of the Gs alpha gene. In one subject with MAS a G-to-A transition was found in exon 8 of one of the two alleles encoding Gs alpha. This single-base substitution results in the replacement of arginine by histidine at position 201 of the mature Gs alpha protein. Semiquantitative analysis of amplified DNA indicated that the mutant allele was less prevalent than the wild-type allele in peripheral leukocytes and was present in very low levels in skin. These findings support the previous contention that the segmental distribution and variable expression of the cutaneous, skeletal, and endocrine manifestations of MAS reflect an underlying somatic mosaicism. Further, these results suggest that the molecular basis of MAS is a postzygotic mutation in Gs alpha that causes constitutive activation of adenylyl cyclase. Images PMID:1594625

  10. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000

    NASA Astrophysics Data System (ADS)

    Stoupel, Eliahu G.; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D.; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth—138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices—sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999—were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected—r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

  11. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000.

    PubMed

    Stoupel, Eliahu G; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth--138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices--sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999--were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected--r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

  12. Inflammatory cells and cellular activation in the lower respiratory tract in Churg-Strauss syndrome

    PubMed Central

    Schnabel, A.; Csernok, E.; Braun, J.; Gross, W.

    1999-01-01

    BACKGROUND—To obtain insight into the mechanisms of tissue injury in lung disease due to Churg-Strauss syndrome (CSS), the bronchoalveolar lavage (BAL) cell profile and the levels in the BAL fluid of cell products released by activated eosinophils and neutrophils were assessed.
METHODS—Thirteen patients with active progressive CSS (n = 7) or CSS in partial remission (n = 6) underwent clinical staging and bronchoalveolar lavage. The levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and peroxidase activity in the BAL fluid were determined and the results were compared with those of 19 patients with pulmonary active Wegener's granulomatosis (WG) and nine control subjects.
RESULTS—In patients with progressive CSS the BAL cell profile was dominated by eosinophils, neutrophil elevation being the exception. The eosinophilia was associated with high ECP levels (4.39 ng/ml and 0.40 ng/ml in the two CSS groups compared with unmeasurable values in the controls). Individual patients with highly active CSS also had raised MPO levels, comparable to the levels in the most active WG patients. Peroxidase activity in the BAL fluid was 1.26 U/ml and 0.10 U/ml in the two groups of patients with CSS and 0.20 U/ml in the controls. Pulmonary disease in patients with WG was characterised by an extensive increase in MPO (0.30ng/ml versus 0.13 ng/ml in the controls) together with high peroxidase activity in the BAL fluid (4.37 U/ml), but only a small increase in ECP levels was seen. No correlation was found between the ECP and MPO levels in patients with CSS which suggests that eosinophil and neutrophil activation vary independently of each other.
CONCLUSIONS—These findings suggest that, in addition to eosinophil activation, neutrophil activation is an important feature in some patients with highly active CSS. The balance of neutrophil and eosinophil involvement appears to be variable and this may be one explanation for the individually variable treatment

  13. Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

    PubMed Central

    Méndez-Hernández, Pablo; Flores, Yvonne; Siani, Carole; Lamure, Michel; Dosamantes-Carrasco, L Darina; Halley-Castillo, Elizabeth; Huitrón, Gerardo; Talavera, Juan O; Gallegos-Carrillo, Katia; Salmerón, Jorge

    2009-01-01

    Background In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. Methods The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. Results The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95) and women (OR 0.78; 95%CI 0.64–0.94) who reported an amount of ≥30 minutes/day of leisure

  14. Mega aorta syndrome: a case of thoracic and abdominal aortic aneurysm.

    PubMed

    Wu, William C; Mitchell, Christopher A; Linklater, Derek

    2010-07-01

    An 83-year-old woman presented to the emergency department (ED) via emergency medical services with the chief complaint of "strokelike symptoms." Physical examination revealed altered mental status, tachycardia, hypotension, and a large nonpulsatile periumbilical mass. Bedside ultrasound revealed a 9-cm abdominal aortic aneurysm with absent central flow. Computed tomography scan demonstrated diffuse thoracic and abdominal aortic dilation with rupture into the mediastinum along with left hemothorax. Repeat beside ultrasound demonstrated abdominal aortic aneurysm rupture not seen on the computed tomography scan. Despite aggressive resuscitation, the patient developed bradycardia, which devolved into pulseless electric activity cardiac arrest. She was unable to be resuscitated. The patient's diffuse aneurysmal dilation places her into the small category of patients with a disease entity known as mega aorta syndrome (MAS). Mega aorta syndrome is defined as aneurysmal dilation of the aorta to greater than 6 cm in diameter. Although not in our case, most cases of MAS are symptomatic before catastrophic presentation. The disease progression for these patients is slow and occurs over years. When this disease is recognized early, a surgery known as the elephant trunk procedure can be performed. This operation replaces the entire aorta in multiple stages. This gives the emergency physician a critical role in the diagnosis and outcome of these patients because they may come through the ED for an unrelated complaint early in the disease process. This case report illustrates an advanced case of MAS.

  15. Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice.

    PubMed

    Wang, Yu; Shoemaker, Robin; Powell, David; Su, Wen; Thatcher, Sean; Cassis, Lisa

    2017-03-01

    Angiotensin-(1-7) [ANG-(1-7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1-7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency (MasR(-/-) ) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type (MasR(+/+) ) and MasR(-/-) mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR(-/-) mice had reduced ejection fraction (EF) and fractional shortening than MasR(+/+) mice. Male, but not female, HF-fed MasR(+/+) mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR(-/-) mice had lower DBP than MasR(+/+) mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR(-/-) mice had higher left ventricular (LV) wall thickness than MasR(+/+) mice. Moreover, MasR(+/+) , but not MasR(-/-) , mice displayed reductions in EF from HF feeding that were reversed by ANG-(1-7) infusion. LV fibrosis was reduced in HF-fed MasR(+/+) but not MasR(-/-) ANG-(1-7)-infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1-7) in MasR(+/+) but not MasR(-/-) mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.NEW & NOTEWORTHY MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1-7) infusion restores obesity-induced cardiac dysfunction of wild

  16. Level of Physical Activity and In-Hospital Course of Patients with Acute Coronary Syndrome

    PubMed Central

    Jorge, Juliana de Goes; Santos, Marcos Antonio Almeida; Barreto Filho, José Augusto Soares; Oliveira, Joselina Luzia Menezes; de Melo, Enaldo Vieira; de Oliveira, Norma Alves; Faro, Gustavo Baptista de Almeida; Sousa, Antônio Carlos Sobral

    2016-01-01

    Background Acute coronary syndrome (ACS) is one of the main causes of morbidity and mortality in the modern world. A sedentary lifestyle, present in 85% of the Brazilian population, is considered a risk factor for the development of coronary artery disease. However, the correlation of a sedentary lifestyle with cardiovascular events (CVE) during hospitalization for ACS is not well established. Objective To evaluate the association between physical activity level, assessed with the International Physical Activity Questionnaire (IPAQ), with in-hospital prognosis in patients with ACS. Methods Observational, cross-sectional, and analytical study with 215 subjects with a diagnosis of ACS consecutively admitted to a referral hospital for cardiac patients between July 2009 and February 2011. All volunteers answered the short version of the IPAQ and were observed for the occurrence of CVE during hospitalization with a standardized assessment conducted by the researcher and corroborated by data from medical records. Results The patients were admitted with diagnoses of unstable angina (34.4%), acute myocardial infarction (AMI) without ST elevation (41.4%), and AMI with ST elevation (24.2%). According to the level of physical activity, the patients were classified as non-active (56.3%) and active (43.7%). A CVE occurred in 35.3% of the cohort. The occurrence of in-hospital complications was associated with the length of hospital stay (odds ratio [OR] = 1.15) and physical inactivity (OR = 2.54), and was independent of age, systolic blood pressure, and prior congestive heart failure. Conclusion A physically active lifestyle reduces the risk of CVE during hospitalization in patients with ACS. PMID:26690692

  17. Physical activity in infants with Down syndrome receiving a treadmill intervention.

    PubMed

    Angulo-Barroso, Rosa; Burghardt, Amy R; Lloyd, Meghann; Ulrich, Dale A

    2008-04-01

    Despite the recognized relevance of physical activity in the development and health of children, assessment of physical activity levels (PA-level) in infancy is limited, especially in infants with Down syndrome (DS). Increasing PA-level using a treadmill training (TMT) intervention may benefit infants with motor delays. The purpose of this study was to investigate whether a higher intensity, individualized TMT protocol (HI) would elicit immediate and short-term higher PA-level in infants with DS than a lower intensity, generalized training protocol (LG). Thirty infants with DS were randomly assigned to the LG or the HI group. Training was terminated when the infants could walk three steps independently. Activity monitors were placed on infants' trunks and legs for a 24-h period every other month during the intervention phase, and at set intervals 1-year post-independent walking onset. Data were analyzed to separate sedentary-to-light activity (Lowact) and moderate-to-vigorous activity (Highact). Overall our results demonstrate that infants receiving the HI TMT had higher levels of Highact than infants in the LG group, factoring out the activity produced by the intervention itself. Infants in the LG group spent more time in Lowact than the HI group. In addition, these results seemed to be retained during the post-intervention follow-up. Despite these exciting results, more work is needed to understand the relationship of the intensity of TMT on PA-level in infants with DS, and whether PA-level and TMT are related to motor milestone achievement and/or health benefits.

  18. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs.

    PubMed

    Hardaway, R M; Williams, C H; Marvasti, M; Farias, M; Tseng, A; Pinon, I; Yanez, D; Martinez, M; Navar, J

    1990-12-01

    Death from traumatic shock has been associated with loss of blood externally or internally. However, many patients die after trauma, even though blood volume restoration is adequate. Death is often due to pulmonary failure (adult respiratory distress syndrome [ARDS]). Death and ARDS have been associated with disseminated intravascular coagulation (DIC) and microclots in the lungs. Dissolution of the microclots after trauma can be achieved by activation of endogenous plasmin. Nine pigs were anesthetized for 48 h. Trauma was administered by 60 standard blows to each thigh resulting in a bruise of muscle but no skin, bone, or major vessel injury. Nutrition and respiration were maintained at normal levels. All nine pigs died with severe lung pathology and low PaO2. Ten other traumatized pigs were treated with a plasminogen activator iv 4 h after trauma. Five of these were treated with tissue plasminogen activator (tPA) and five with urokinase. All treated pigs survived 48 h and maintained a normal PaO2. Autopsy showed minimal lung pathology.

  19. Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β.

    PubMed

    Hoang, Minh-Hien; Jia, Yaoyao; Mok, Boram; Jun, Hee-jin; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2015-08-01

    Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC50 = 0.33 μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome.

  20. A Case of McCune-Albright Syndrome with Associated Multiple Endocrinopathies

    PubMed Central

    Sung, Sang Hun; Shon, Ho Sang; Kim, Hong Tae; Choi, Woo Young; Seo, Chang Jin; Lee, Joo Hyoung

    2007-01-01

    McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT). PMID:17427647

  1. 47 CFR 101.1317 - Competitive bidding procedures for mutually exclusive MAS EA applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Competitive bidding procedures for mutually exclusive MAS EA applications. 101.1317 Section 101.1317 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... License Requirements § 101.1317 Competitive bidding procedures for mutually exclusive MAS EA...

  2. A Hydrophobic Pocket in the Active Site of Glycolytic Aldolase Mediates Interactions with Wiskott-Aldrich Syndrome Protein

    SciTech Connect

    St-Jean,M.; Izard, T.; Sygusch, J.

    2007-01-01

    Aldolase plays essential catalytic roles in glycolysis and gluconeogenesis. However, aldolase is a highly abundant protein that is remarkably promiscuous in its interactions with other cellular proteins. In particular, aldolase binds to highly acidic amino acid sequences, including the C-terminus of the Wiskott-Aldrich syndrome protein, an actin nucleation promoting factor. Here we report the crystal structure of tetrameric rabbit muscle aldolase in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein. Aldolase recognizes a short, 4-residue DEWD motif (residues 498-501), which adopts a loose hairpin turn that folds about the central aromatic residue, enabling its tryptophan side chain to fit into a hydrophobic pocket in the active site of aldolase. The flanking acidic residues in this binding motif provide further interactions with conserved aldolase active site residues, Arg-42 and Arg-303, aligning their side chains and forming the sides of the hydrophobic pocket. The binding of Wiskott-Aldrich syndrome protein to aldolase precludes intramolecular interactions of its C-terminus with its active site, and is competitive with substrate as well as with binding by actin and cortactin. Finally, based on this structure a novel naphthol phosphate-based inhibitor of aldolase was identified and its structure in complex with aldolase demonstrated mimicry of the Wiskott-Aldrich syndrome protein-aldolase interaction. The data support a model whereby aldolase exists in distinct forms that regulate glycolysis or actin dynamics.

  3. Resveratrol protects against experimental induced Reye's syndrome by prohibition of oxidative stress and restoration of complex I activity.

    PubMed

    Abdin, Amany; Sarhan, Naglaa

    2014-09-01

    This study was designed to investigate whether resveratrol could provide protection against Reye's syndrome induced by 4-pentenoic acid in Wistar albino rats. Compared with rats with untreated Reye's syndrome, 1 h pretreatment by low dose resveratrol (10 mg/kg by oral gavage) resulted in marked amelioration in liver functions in the form of significant decrease in serum transaminases (AST, ALT) and plasma ammonia levels, shortening of prothrombin time, and increase in serum albumin levels. In addition, resveratrol prohibited oxidative stress markers, as indicated by a significant increase in GSH and decrease in MDA, with restoration of complex I activity in liver tissues. The classical histopathological presentation in Reye's syndrome of microvesicular steatosis by light microscope and mitochondria distortion by electron microscope has been improved by resveratrol pretreatment. The efficient protection by resveratrol was determined by normalization in serum levels of AST and albumin, as well as complex I activity, GSH, and MDA. In conclusion, pretreatment by resveratrol in low doses could protect against Reye's syndrome partially via prohibition of oxidative stress and restoration of complex I activity. This may provide the opportunity to reconsider aspirin therapy for infants and young children. However, the verification of such results in clinical practice remains a challenge.

  4. Angiotensin-(1-7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism.

    PubMed

    Cisternas, Franco; Morales, María Gabriela; Meneses, Carla; Simon, Felipe; Brandan, Enrique; Abrigo, Johanna; Vazquez, Yaneisi; Cabello-Verrugio, Claudio

    2015-03-01

    Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, an increase in myosin heavy chain (MHC) degradation and increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang-(1-7) on the skeletal muscle atrophy induced by AngII. Our results show that Ang-(1-7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels and the increase in atrogin-1 and MuRF-1. Ang-(1-7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang-(1-7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang-(1-7). Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang-(1-7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, with pathologies that present high levels of AngII.

  5. Investigation of the association between metabolic syndrome and disease activity in rheumatoid arthritis.

    PubMed

    Sahebari, Maryam; Goshayeshi, Ladan; Mirfeizi, Zahra; Rezaieyazdi, Zahra; Hatef, Mohammad R; Ghayour-Mobarhan, Majid; Akhlaghi, Saeed; Sahebkar, Amirhossein; Ferns, Gordon A

    2011-06-09

    Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.

  6. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  7. A generic, computerized nuclear materials accountability system (NucMAS) and its layered products

    SciTech Connect

    Davis, Jr, J M

    1989-01-01

    NucMAS provides a material balance area with a computerized data management system for nuclear materials accountability. NucMAS is a generic application. It handles the data management and reporting functions for different processing facilities by storing all process-specific information as data rather than procedure. A NucMAS application is configured for each facility it supports. NucMAS and its layered products are compatible with three types of data clients. Core NucMAS has a screen-oriented user interface to support the accountability clerk as a client. Accountability clerks enter data from operating logs and laboratory analyses one to three days after actual processing. Layered products support process operators and automated systems as near-real-time and real-time data clients. The core and layered products use a data-driven approach which results in software that is configurable and maintainable. 3 refs., 5 figs.

  8. Adipokines, biomarkers of endothelial activation, and metabolic syndrome in patients with ankylosing spondylitis.

    PubMed

    Genre, Fernanda; López-Mejías, Raquel; Miranda-Filloy, José A; Ubilla, Begoña; Carnero-López, Beatriz; Blanco, Ricardo; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A

    2014-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS.

  9. Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation.

    PubMed

    Batenburg, Nicole L; Thompson, Elizabeth L; Hendrickson, Eric A; Zhu, Xu-Dong

    2015-05-12

    Mutations of CSB account for the majority of Cockayne syndrome (CS), a devastating hereditary disorder characterized by physical impairment, neurological degeneration and segmental premature aging. Here we report the generation of a human CSB-knockout cell line. We find that CSB facilitates HR and represses NHEJ. Loss of CSB or a CS-associated CSB mutation abrogating its ATPase activity impairs the recruitment of BRCA1, RPA and Rad51 proteins to damaged chromatin but promotes the formation of 53BP1-Rif1 damage foci in S and G2 cells. Depletion of 53BP1 rescues the formation of BRCA1 damage foci in CSB-knockout cells. In addition, knockout of CSB impairs the ATM- and Chk2-mediated DNA damage responses, promoting a premature entry into mitosis. Furthermore, we show that CSB accumulates at sites of DNA double-strand breaks (DSBs) in a transcription-dependent manner. The kinetics of DSB-induced chromatin association of CSB is distinct from that of its UV-induced chromatin association. These results reveal novel, important functions of CSB in regulating the DNA DSB repair pathway choice as well as G2/M checkpoint activation.

  10. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome.

    PubMed

    Thorp, Alicia A; Schlaich, Markus P

    2015-01-01

    Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.

  11. Farnesoid X receptor activation improves erectile dysfunction in models of metabolic syndrome and diabetes.

    PubMed

    Morelli, Annamaria; Vignozzi, Linda; Maggi, Mario; Adorini, Luciano

    2011-08-01

    The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

  12. Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

    PubMed

    Zhong, Franklin L; Mamaï, Ons; Sborgi, Lorenzo; Boussofara, Lobna; Hopkins, Richard; Robinson, Kim; Szeverényi, Ildikó; Takeichi, Takuya; Balaji, Reshmaa; Lau, Aristotle; Tye, Hazel; Roy, Keya; Bonnard, Carine; Ahl, Patricia J; Jones, Leigh Ann; Baker, Paul; Lacina, Lukas; Otsuka, Atsushi; Fournie, Pierre R; Malecaze, François; Lane, E Birgitte; Akiyama, Masashi; Kabashima, Kenji; Connolly, John E; Masters, Seth L; Soler, Vincent J; Omar, Salma Samir; McGrath, John A; Nedelcu, Roxana; Gribaa, Moez; Denguezli, Mohamed; Saad, Ali; Hiller, Sebastian; Reversade, Bruno

    2016-09-22

    Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

  13. Chronic ethanol consumption inhibits glucokinase transcriptional activity by Atf3 and triggers metabolic syndrome in vivo.

    PubMed

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-09-26

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from -287 to -158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis.

  14. Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation

    PubMed Central

    Batenburg, Nicole L; Thompson, Elizabeth L; Hendrickson, Eric A; Zhu, Xu-Dong

    2015-01-01

    Mutations of CSB account for the majority of Cockayne syndrome (CS), a devastating hereditary disorder characterized by physical impairment, neurological degeneration and segmental premature aging. Here we report the generation of a human CSB-knockout cell line. We find that CSB facilitates HR and represses NHEJ. Loss of CSB or a CS-associated CSB mutation abrogating its ATPase activity impairs the recruitment of BRCA1, RPA and Rad51 proteins to damaged chromatin but promotes the formation of 53BP1-Rif1 damage foci in S and G2 cells. Depletion of 53BP1 rescues the formation of BRCA1 damage foci in CSB-knockout cells. In addition, knockout of CSB impairs the ATM- and Chk2-mediated DNA damage responses, promoting a premature entry into mitosis. Furthermore, we show that CSB accumulates at sites of DNA double-strand breaks (DSBs) in a transcription-dependent manner. The kinetics of DSB-induced chromatin association of CSB is distinct from that of its UV-induced chromatin association. These results reveal novel, important functions of CSB in regulating the DNA DSB repair pathway choice as well as G2/M checkpoint activation. PMID:25820262

  15. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

    PubMed Central

    Thorp, Alicia A.; Schlaich, Markus P.

    2015-01-01

    Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts. PMID:26064978

  16. Abnormal Spontaneous Brain Activity in Women with Premenstrual Syndrome Revealed by Regional Homogeneity

    PubMed Central

    Liao, Hai; Pang, Yong; Liu, Peng; Liu, Huimei; Duan, Gaoxiong; Liu, Yanfei; Tang, Lijun; Tao, Jien; Wen, Danhong; Li, Shasha; Liang, Lingyan; Deng, Demao

    2017-01-01

    Background: Previous studies have revealed that the etiologies of premenstrual syndrome (PMS) refer to menstrual cycle related brain changes. However, its intrinsic neural mechanism is still unclear. The aim of the present study was to assess abnormal spontaneous brain activity and to explicate the intricate neural mechanism of PMS using resting state functional magnetic resonance imaging (RS-fMRI). Materials and Methods: The data of 20 PMS patients (PMS group) and 21 healthy controls (HC group) were analyzed by regional homogeneity (ReHo) method during the late luteal phase of menstrual cycle. In addition, all the participants were asked to complete a daily record of severity of problems (DRSP) questionnaire. Results: Compared with HC group, the results showed that PMS group had increased ReHo mainly in the bilateral precuneus, left inferior temporal cortex (ITC), right inferior frontal cortex (IFC) and left middle frontal cortex (MFC) and decreased ReHo in the right anterior cingulate cortex (ACC) at the luteal phase. Moreover, the PMS group had higher DRSP scores, and the DRSP scores positively correlated with ReHo in left MFC and negatively correlated with ReHo in the right ACC. Conclusion: Our results suggest that abnormal spontaneous brain activity is found in PMS patients and the severity of symptom is specifically related to the left MFC and right ACC. The present findings may be beneficial to explicate the intricate neural mechanism of PMS. PMID:28243196

  17. Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation

    PubMed Central

    Guenin-Macé, Laure; Veyron-Churlet, Romain; Thoulouze, Maria-Isabel; Romet-Lemonne, Guillaume; Hong, Hui; Leadlay, Peter F.; Danckaert, Anne; Ruf, Marie-Thérèse; Mostowy, Serge; Zurzolo, Chiara; Bousso, Philippe; Chrétien, Fabrice; Carlier, Marie-France; Demangel, Caroline

    2013-01-01

    Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration. In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture. This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis. Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti–Buruli ulcer therapeutic potential. PMID:23549080

  18. Correlations of Interstitial Cystitis/Painful Bladder Syndrome with Female Sexual Activity

    PubMed Central

    Yoon, Hyun Suk

    2010-01-01

    Purpose We investigated how the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) are correlated with the sexual activity of these patients. Materials and Methods A total of 87 patients were included in this study; 18 patients were diagnosed with IC and the other 69 had PBS. The diagnosis was made on the basis of the concept of IC/PBS proposed by the ICS in 2002. Patients were asked to fill in a Bristol female lower urinary tract symptom questionnaire, and symptoms were rated on a scale of from 1 to 4 or 5. Pearson's correlation coefficient was used to analyze the correlation of pain and urinary symptoms with quality of life and sexual activity. Results The average age of the patients was 51±14.7 years (range, 28-74 years). Age and vulvodynia were positively correlated with one another (r=0.232), and there was a negative correlation between age and dyspareunia (r=-0.302). Among the items regarding IC/PBS and sexual activity, frequency showed a positive correlation with vulvodynia (r=0.258) in addition to an inhibited sex life (r=0.403). Urgency showed a positive correlation with an inhibited sex life (r=0.346). Vulvodynia showed a positive correlation with an inhibited sex life (r=0.259) and dyspareunia (r=0.401). The main symptoms of IC/PBS (frequency, urgency, and pelvic pain) showed a positive correlation with almost all items related to quality of life (p<0.05). Conclusions Frequency, urgency, and various types of pain are negatively correlated with the sexual activity of patients. This suggests that physicians should consider sexual function in the management of patients with IC/PBS. PMID:20414410

  19. Actinobacillus pleuropneumoniae Possesses an Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Labrie, Josée; Hernandez Reyes, Yenney; Burciaga Nava, Jorge A.; Gagnon, Carl A.; Jacques, Mario

    2014-01-01

    Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections. This phenomenon is known as the porcine respiratory disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC. The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections. To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI. Bacterial adherence and cell death were compared. Results showed that PRRSV pre-infection did not affect bacterial adherence to the cells. PRRSV and App co-infection produced an additive cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection. This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs. The antiviral activity might be due, at least in part, to the production of interferon γ. The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools. PMID:24878741

  20. Reduced parasympathetic activity during sleep in the symptomatic phase of severe premenstrual syndrome

    PubMed Central

    Baker, Fiona C.; Colrain, Ian M; Trinder, John

    2008-01-01

    Objective Severe premenstrual syndrome (PMS) is a common, distressing disorder in women that manifests during the premenstrual (late-luteal) phase of the ovulatory menstrual cycle. There is some evidence that altered autonomic function may be an important component of PMS but few studies have used heart rate variability (HRV), as a sensitive marker of autonomic activity, in severe PMS and findings are conflicting. Methods We investigated HRV during sleep, a state relatively free of external disruptions, in nine women with severe PMS and twelve controls. Results The normal-to-normal (NN) RR-interval was shorter during the sleep period in women with PMS than in controls in both the follicular and late-luteal phases of the menstrual cycle. The standard deviation of all NN intervals (SDNN), a measure of total variability in the inter-beat interval, was lower during the sleep period in the late-luteal phase than in the follicular phase in women with PMS. The square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD), a measure reflecting high frequency activity, showed a similar pattern. High frequency power, a marker of parasympathetic activity, was lower during non-rapid eye movement (non-REM) and REM sleep in the late-luteal phase than in the follicular phase in women with severe PMS. Controls had a shorter NN-interval, but similar HRV measures, in the late-luteal phase compared with the follicular phase. Conclusion These results suggest that women with severe PMS have decreased parasympathetic activity during sleep in association with their premenstrual symptoms compared to when they are symptom-free. PMID:18582607

  1. ACE2/Ang-(1-7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cells.

    PubMed

    Singh, Neha; Joshi, Shrinidh; Guo, Lirong; Baker, Matthew B; Li, Yan; Castellano, Ronald K; Raizada, Mohan K; Jarajapu, Yagna P R

    2015-11-15

    CD34(+) stem/progenitor cells have been identified as a promising cell population for the autologous cell-based therapies in patients with cardiovascular disease. The counter-regulatory axes of renin angiotensin system, angiotensin converting enzyme (ACE)/Ang II/angiotensin type 1 (AT1) receptor and ACE2/Ang-(1-7)/Mas receptor, play an important role in the cardiovascular repair. This study evaluated the expression and vascular repair-relevant functions of these two pathways in human CD34(+) cells. CD34(+) cells were isolated from peripheral blood mononuclear cells (MNCs), obtained from healthy volunteers. Expression of ACE, ACE2, AT1, and angiotensin type 2 and Mas receptors were determined. Effects of Ang II, Ang-(1-7), Norleu(3)-Ang-(1-7), and ACE2 activators, xanthenone (XNT) and diminazene aceturate (DIZE) on proliferation, migration, and adhesion of CD34(+) cells were evaluated. ACE2 and Mas were relatively highly expressed in CD34(+) cells compared with MNCs. Ang-(1-7) or its analog, Norleu(3)-Ang-(1-7), stimulated proliferation of CD34(+) cells that was associated with decrease in phosphatase and tensin homologue deleted on chromosome 10 levels and was inhibited by triciribin, an AKT inhibitor. Migration of CD34(+) cells was enhanced by Ang-(1-7) or Norleu(3)-Ang-(1-7) that was decreased by a Rho-kinase inhibitor, Y-27632. In the presence of Ang II, XNT or DIZE enhanced proliferation and migration that were blocked by DX-600, an ACE2 inhibitor. Treatment of MNCs with Ang II, before the isolation of CD34(+) cells, attenuated the proliferation and migration to stromal derived factor-1α. This attenuation was reversed by apocynin, an NADPH oxidase inhibitor. Adhesion of MNCs or CD34(+) cells to fibronectin was enhanced by Ang II and was unaffected by Ang-(1-7). This study suggests that ACE2/Ang-(1-7)/Mas pathway stimulates functions of CD34(+) cells that are cardiovascular protective, whereas Ang II attenuates these functions by acting on MNCs. These findings

  2. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

    PubMed

    Yu, Changhui; Tang, Wei; Wang, Yuhao; Shen, Qiang; Wang, Bin; Cai, Chunqing; Meng, Xiaojing; Zou, Fei

    2016-07-01

    The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis.

  3. Strategies to Increase the Physical Activity Participation of Young Adults with Asperger Syndrome in Community Programs

    ERIC Educational Resources Information Center

    Hamm, Jessica; Driver, Simon

    2015-01-01

    Currently one in 50 American school-age children is diagnosed with Autism. Although Asperger Syndrome is no longer acknowledged as a separate diagnosis, this article refers to high-functioning individuals with Autism as having Asperger Syndrome, since it is a culturally relevant term. One of the most challenging times for individuals with Asperger…

  4. Auditory Attraction: Activation of Visual Cortex by Music and Sound in Williams Syndrome

    ERIC Educational Resources Information Center

    Thornton-Wells, Tricia A.; Cannistraci, Christopher J.; Anderson, Adam W.; Kim, Chai-Youn; Eapen, Mariam; Gore, John C.; Blake, Randolph; Dykens, Elisabeth M.

    2010-01-01

    Williams syndrome is a genetic neurodevelopmental disorder with a distinctive phenotype, including cognitive-linguistic features, nonsocial anxiety, and a strong attraction to music. We performed functional MRI studies examining brain responses to musical and other types of auditory stimuli in young adults with Williams syndrome and typically…

  5. Noninvasive Imaging of Ventricular Activation - Application to Patients With WPW-Syndrome

    DTIC Science & Technology

    2007-11-02

    continue the validation process to the investigation of WPW-syndrome (Wolf- Parkinson - White-syndrome) [2]. The anatomical position of the acces- sory...ed., Mal - vern PA: Lea & Febiger, 1992. [3] L. Gepstein, G. Hayam, and S.A. Ben-Haim, ”A novel method for non- fluoroscopic catheter-based

  6. Patterns of acoustical activity of bats prior to and following White-nose Syndrome occurrence

    USGS Publications Warehouse

    Ford, W. Mark; Britzke, Eric R.; Dobony, Christopher A.; Rodrigue, Jane L.; Johnson, Joshua B.

    2011-01-01

    White-nose Syndrome (WNS), a wildlife health concern that has decimated cave-hibernating bat populations in eastern North America since 2006, began affecting source-caves for summer bat populations at Fort Drum, a U.S. Army installation in New York in the winter of 2007–2008. As regional die-offs of bats became evident, and Fort Drum's known populations began showing declines, we examined whether WNS-induced change in abundance patterns and seasonal timing of bat activity could be quantified using acoustical surveys, 2003–2010, at structurally uncluttered riparian–water habitats (i.e., streams, ponds, and wet meadows). As predicted, we observed significant declines in overall summer activity between pre-WNS and post-WNS years for little brown bats Myotis lucifugus, northern bats M. septentrionalis, and Indiana bats M. sodalis. We did not observe any significant change in activity patterns between pre-WNS and post-WNS years for big brown bats Eptesicus fuscus, eastern red bats Lasiurus borealis, or the small number of tri-colored bats Perimyotis subflavus. Activity of silver-haired bats Lasionycteris noctivagans increased from pre-WNS to post-WNS years. Activity levels of hoary bats Lasiurus cinereus significantly declined between pre- and post-WNS years. As a nonhibernating, migratory species, hoary bat declines might be correlated with wind-energy development impacts occurring in the same time frame rather than WNS. Intraseason activity patterns also were affected by WNS, though the results were highly variable among species. Little brown bats showed an overall increase in activity from early to late summer pre-WNS, presumably due to detections of newly volant young added to the local population. However, the opposite occurred post-WNS, indicating that reproduction among surviving little brown bats may be declining. Our data suggest that acoustical monitoring during the summer season can provide insights into species' relative abundance on the

  7. The effect of patellar taping on EMG activity of vasti muscles during squatting in individuals with patellofemoral pain syndrome.

    PubMed

    Mostamand, Javid; Bader, Dan L; Hudson, Zöe

    2011-01-01

    Although patellar taping has been shown to reduce pain in participants with patellofemoral pain syndrome, the mechanisms of pain reduction have not completely been established following its application. The purpose of this study was to evaluate EMG activity of vastus medialis and vastus lateralis following the application of patellar taping during a functional single leg squat. Both vastus medialis obliquus-vastus lateralis onset and vastus medialis obliquus/vastus lateralis amplitude of 18 participants with patellofemoral pain syndrome and 18 healthy participants as controls were measured using an EMG unit. This procedure was performed on the affected knee of participants with patellofemoral pain syndrome, before, during, and after patellar taping during unilateral squatting. The same procedure was also performed on the unaffected knees of both groups. The mean values of vastus medialis obliquus-vastus lateralis onset prior to taping (2.54 ms, s = 4.35) were decreased significantly following an immediate application of tape (-3.22 ms, s = 3.45) and after a prolonged period of taping (-6.00 ms, s = 3.40 s) (P < 0.05). There was also a significant difference between the mean values of vastus medialis obliquus-vastus lateralis onset among controls (-2.03 ms, s = 6.04) and participants with patellofemoral pain syndrome prior to taping (P < 0.05). However, there were no significant difference between the ranked values of vastus medialis obliquus/vastus lateralis amplitude of the affected and unaffected knees of participants with patellofemoral pain syndrome and controls during different conditions of taping (P > 0.05). Decreased values of vastus medialis obliquus-vastus lateralis onset may contribute to patellar realignment and explain the mechanism of pain reduction following patellar taping in participants with patellofemoral pain syndrome.

  8. Upper extremity acute compartment syndrome during tissue plasminogen activator therapy for pulmonary embolism in a morbidly obese patient

    PubMed Central

    Tuna, Serkan; Duymus, Tahir Mutlu; Mutlu, Serhat; Ketenci, Ismail Emre; Ulusoy, Ayhan

    2015-01-01

    Introduction Deep vein thrombosis (DVT) and pulmonary embolism (PE) are more frequently observed in morbidly obese patients. Tissue plasminogen activator (tPA) is a thrombolytic agent which dissolves the thrombus more rapidly than conventional heparin therapy and reduces the mortality and morbidity rates associated with PE. Compartment syndrome is a well-known and documented complication of thrombolytic treatment. In awake, oriented and cooperative patients, the diagnosis of compartment syndrome is made based on clinical findings including swelling, tautness, irrational and continuous pain, altered sensation, and severe pain due to passive stretching. These clinical findings may not be able to be adequately assessed in unconscious patients. Presentation of case In this case report, we present compartment syndrome observed, for which fasciotomy was performed on the upper right extremity of a 46-year old morbidly obese, conscious female patient who was receiving tPA due to a massive pulmonary embolism. Discussion Compartment syndrome had occurred due to the damage caused by the repeated unsuccessful catheterisation attempts to the brachial artery and the accompanying tPA treatment. Thus, the bleeding that occurred in the volar compartment of the forearm and the anterior compartment of the arm led to acute compartment syndrome (ACS). After relaxation was brought about in the volar compartment of the forearm and the anterior compartment of the arm, the circulation in the limb was restored. Conclusion As soon as the diagnosis of compartment syndrome is made, an emergency fasciotomy should be performed. Close follow-up is required to avoid wound healing problems after the fasciotomy. PMID:25618841

  9. [Association between occupational stress and aminotransferase activity in patients with metabolic syndrome].

    PubMed

    Zhao, H; Song, L; Qiang, Y; Liu, H R; Qiu, F Y; Li, X Z; Song, H

    2016-12-20

    Objective: To investigate the association between occupational stress and activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with metabolic syndrome. Methods: A case-control study was performed. According to inclusion and exclusion criteria, among the staff members of enterprises and public institutions aged 20~60 years who underwent physical examination in The Affiliated Hospital of Ningxia Medical University and The People's Hospital of Wuzhong from October 2011 to October 2012, 622 patients with metabolic syndrome who did not have a blood relationship with each other were enrolled as case group, and 600 healthy staff members who also did not have a blood relationshipwith each otherwere enrolled as control group. Questionnaire investigation, chronic occupational stress investigation, physical examination, and laboratory tests were performed for all subjects. Results: Compared with the control group, the case group had significantly higher serum levels and abnormal rates of AST and ALT (t=-4.338 and-5.485, χ(2)=11.168 and 34.302, all P<0.05) . There were no significantdifferences in the serum level and abnormal rate of AST between the subgroups with different occupational stresses in both groups (F=2.192 and 2.567, χ(2)=2.694 and 5.402, all P>0.05) , but there were significant differencesbetween the subgroups in all subjects (F=5.005, χ(2)=6.398, all P<0.05) . There were no significant differences in the serum level and abnormal rate of ALT between thesubgroups with different occupational stresses in the case group, the control group, and all subjects (F=0.845, 0.450, and 1.416, χ(2)=2.564, 1.344, and 3.147, all P>0.05) . The partial correlation analysis showed that the total score of occupational stress was positively correlated withthe serum level of AST (r=0.071, P<0.05) and was not correlated with the serum level of ALT (r=-0.044, P>0.05) , and that the serum level of AST was positively correlated with that of ALT

  10. Prevalence of metabolic syndrome and its relationship with leisure time physical activity among Peruvian adults

    PubMed Central

    Gelaye, Bizu; Tafur, Luis Revilla; Lopez, Tania; Sanchez, Sixto; Williams, Michelle A.

    2009-01-01

    Background Metabolic syndrome (MetS) is an important risk factor of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Previous studies have suggested an inverse relationship between physical activity and MetS. However, these findings were inconsistent; and few investigators have examined these associations among South Americans. We estimated the prevalence of MetS and its association with leisure time physical activity (LTPA) among Peruvian adults. Materials and methods This cross-sectional study of 1,675 individuals (619 men and 1056 women) was conducted among residents in Lima and Callao, Peru. Information about LTPA, socio-demographic, and other lifestyle characteristics were collected by interview. The presence of MetS was defined using the Adult Treatment Panel III (ATP III) criteria. Results Overall, the prevalence of MetS was 26.9% and was more common among women (29.9%) than men (21.6%). Habitual participation in LTPA was associated with a 23% reduced risk of MetS (OR=0.77; 95% CI: 0.60–1.03). There was an inverse trend of MetS risk with amount of LTPA (p=0.016). Compared with non-exercisers, those who exercised < 150 minutes/week had a 21% reduced risk of MetS (AOR= 0.79; 95% CI 0.60–1.04). Individuals who exercised ≥ 150 minutes/week, compared with non-exercisers, had a 42% reduced risk of MetS (AOR=0.58; 95% CI: 0.36–0.93). Associations of similar magnitudes were observed when men and women were studied separately. Conclusion These data document a high prevalence of MetS and suggest an association with LTPA among urban dwelling Peruvians. Further prospective studies are needed to confirm these observations and to examine interventions that may promote increased physical activity in this population. PMID:19563445

  11. Promoter-dependent activity on androgen receptor N-terminal domain mutations in androgen insensitivity syndrome.

    PubMed

    Tadokoro-Cuccaro, Rieko; Davies, John; Mongan, Nigel P; Bunch, Trevor; Brown, Rosalind S; Audi, Laura; Watt, Kate; McEwan, Iain J; Hughes, Ieuan A

    2014-01-01

    Androgen receptor (AR) mutations are associated with androgen insensitivity syndrome (AIS). Missense mutations identified in the AR-N-terminal domain (AR-NTD) are rare, and clinical phenotypes are typically mild. We investigated 7 missense mutations and 2 insertion/deletions located in the AR-NTD. This study aimed to elucidate the pathogenic role of AR-NTD mutants in AIS and to use this knowledge to further define AR-NTD function. AR-NTD mutations (Q120E, A159T, G216R, N235K, G248V, L272F, and P380R) were introduced into AR-expression plasmids. Stably expressing cell lines were established for del57L and ins58L. Transactivation was measured using luciferase reporter constructs under the control of GRE and Pem promoters. Intrinsic fluorescence spectroscopy and partial proteolysis studies were performed for mutations which showed reduced activities by using a purified AR-AF1 protein. Pem-luciferase reporter activation was reduced for A159T, N235K, and G248V but not the GRE-luciferase reporter. Protein structure analysis detected no significant change in the AR-AF1 region for these mutations. Reduced cellular expression and transactivation activity were observed for ins58L. The mutations Q120E, G216R, L272F, P380R, and del57L showed small or no detectable changes in function. Thus, clinical and experimental analyses have identified novel AR-signalling defects associated with mutations in the structurally disordered AR-NTD domain in patients with AIS.

  12. Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome.

    PubMed

    Li, Rong; Chen, Lu-zhu; Zhao, Shui-ping; Huang, Xian-sheng

    2016-01-01

    Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS) for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1) control group; (2) SA (stable angina) group; and (3) ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day) and high-statin (atorvastatin, 20 mg/kg/day) group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

  13. RAI1 transcription factor activity is impaired in mutants associated with Smith-Magenis Syndrome.

    PubMed

    Carmona-Mora, Paulina; Canales, Cesar P; Cao, Lei; Perez, Irene C; Srivastava, Anand K; Young, Juan I; Walz, Katherina

    2012-01-01

    Smith-Magenis Syndrome (SMS) is a complex genomic disorder mostly caused by the haploinsufficiency of the Retinoic Acid Induced 1 gene (RAI1), located in the chromosomal region 17p11.2. In a subset of SMS patients, heterozygous mutations in RAI1 are found. Here we investigate the molecular properties of these mutated forms and their relationship with the resulting phenotype. We compared the clinical phenotype of SMS patients carrying a mutation in RAI1 coding region either in the N-terminal or the C-terminal half of the protein and no significant differences were found. In order to study the molecular mechanism related to these two groups of RAI1 mutations first we analyzed those mutations that result in the truncated protein corresponding to the N-terminal half of RAI1 finding that they have cytoplasmic localization (in contrast to full length RAI1) and no ability to activate the transcription through an endogenous target: the BDNF enhancer. Similar results were found in lymphoblastoid cells derived from a SMS patient carrying RAI1 c.3103insC, where both mutant and wild type products of RAI1 were detected. The wild type form of RAI1 was found in the chromatin bound and nuclear matrix subcellular fractions while the mutant product was mainly cytoplasmic. In addition, missense mutations at the C-terminal half of RAI1 presented a correct nuclear localization but no activation of the endogenous target. Our results showed for the first time a correlation between RAI1 mutations and abnormal protein function plus they suggest that a reduction of total RAI1 transcription factor activity is at the heart of the SMS clinical presentation.

  14. Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome.

    PubMed

    Hamajima, Takashi; Maruwaka, Kaori; Homma, Keiko; Matsuo, Kumihiro; Fujieda, Kenji; Hasegawa, Tomonobu

    2010-01-01

    We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

  15. Dual action of neurokinin-1 antagonists on Mas-related GPCRs

    PubMed Central

    Azimi, Ehsan; Reddy, Vemuri B.; Shade, Kai-Ting C.; Anthony, Robert M.; Pereira, Paula Juliana Seadi; Lerner, Ethan A.

    2016-01-01

    The challenge of translating findings from animal models to the clinic is well known. An example of this challenge is the striking effectiveness of neurokinin-1 receptor (NK-1R) antagonists in mouse models of inflammation coupled with their equally striking failure in clinical investigations in humans. Here, we provide an explanation for this dichotomy: Mas-related GPCRs (Mrgprs) mediate some aspects of inflammation that had been considered mediated by NK-1R. In support of this explanation, we show that conventional NK-1R antagonists have off-target activity on the mouse receptor MrgprB2 but not on the homologous human receptor MRGPRX2. An unrelated tripeptide NK-1R antagonist has dual activity on MRGPRX2. This tripeptide both suppresses itch in mice and inhibits degranulation from the LAD-2 human mast cell line elicited by basic secretagogue activation of MRGPRX2. Antagonists of Mrgprs may fill the void left by the failure of NK-1R antagonists. PMID:27734033

  16. Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

    PubMed Central

    Kagota, Satomi; Maruyama, Kana; McGuire, John J.

    2016-01-01

    Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study. PMID:27006943

  17. Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

    PubMed

    Armangil, Didem; Yurdakök, Murat; Okur, Hamza; Gürgey, Aytemiz

    2011-08-01

    Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

  18. Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities

    PubMed Central

    Lozada, Enerlyn; Yi, Jingjie; Luo, Jianyuan; Orren, David K.

    2014-01-01

    Loss of WRN function causes Werner Syndrome, characterized by increased genomic instability, elevated cancer susceptibility and premature aging. Although WRN is subject to acetylation, phosphorylation and sumoylation, the impact of these modifications on WRN’s DNA metabolic function remains unclear. Here, we examined in further depth the relationship between WRN acetylation and its role in DNA metabolism, particularly in response to induced DNA damage. Our results demonstrate that endogenous WRN is acetylated somewhat under unperturbed conditions. However, levels of acetylated WRN significantly increase after treatment with certain DNA damaging agents or the replication inhibitor hydroxyurea. Use of DNA repair-deficient cells or repair pathway inhibitors further increase levels of acetylated WRN, indicating that induced DNA lesions and their persistence are at least partly responsible for increased acetylation. Notably, acetylation of WRN correlates with inhibition of DNA synthesis, suggesting that replication blockage might underlie this effect. Moreover, WRN acetylation modulates its affinity for and activity on certain DNA structures, in a manner that may enhance its relative specificity for physiological substrates. Our results also show that acetylation and deacetylation of endogenous WRN is a dynamic process, with sirtuins and other histone deacetylases contributing to WRN deacetylation. These findings advance our understanding of the dynamics of WRN acetylation under unperturbed conditions and following DNA damage induction, linking this modification not only to DNA damage persistence but also potentially to replication stalling caused by specific DNA lesions. Our results are consistent with proposed metabolic roles for WRN and genomic instability phenotypes associated with WRN deficiency. PMID:24965941

  19. Acquired immunodeficiency syndrome-related malignancies in the era of highly active antiretroviral therapy.

    PubMed

    Bernstein, Wendy B; Little, Richard F; Wilson, Wyndham H; Yarchoan, Robert

    2006-07-01

    Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, malignancies have been an important feature of this disease. Several cancers, including Kaposi sarcoma (KS), certain aggressive B-cell lymphomas, and cervical cancer, are considered AIDS-defining when they occur in patients infected with human immunodeficiency virus. Most AIDS-defining tumors are associated with one of 3 DNA viruses: KS-associated herpesvirus, Epstein-Barr virus, or human papillomavirus. With the introduction of highly active antiretroviral therapy (HAART), the incidence of KS and certain lymphomas has decreased, whereas that of other tumors, such as cervical cancer, has undergone little change. Several new drugs and therapies have been developed for KS and AIDS-related lymphomas, and these treatments, plus the development of HAART, have contributed to improvements in morbidity and mortality. At the same time, the improved overall survival of patients with HAART has contributed to an increase in the number of patients living with AIDS in developed countries such as the United States. With the development of HAART and improved prevention and treatment of opportunistic infections, an increasing percentage of the deaths in AIDS patients have been from malignancies. Strategies for prevention, screening, and therapy remain important areas of research in this developing field.

  20. Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

    PubMed Central

    Ji, Gong-Jun; Liao, Wei; Yu, Yang; Miao, Huan-Huan; Feng, Yi-Xuan; Wang, Kai; Feng, Jian-Hua; Zang, Yu-Feng

    2016-01-01

    Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS. PMID:27799898

  1. The journey of antiphospholipid antibodies from cellular activation to antiphospholipid syndrome.

    PubMed

    Willis, Rohan; Gonzalez, E B; Brasier, A R

    2015-03-01

    Pathogenic antiphospholipid antibodies (aPL) are the driving factors of recurrent pregnancy loss and thrombosis that characterize antiphospholipid syndrome (APS). Current evidence indicates that aPL induce a procoagulant phenotype in the vasculature and abnormal cellular proliferation and differentiation in placental tissues to cause the typical clinical features; however, the molecular mechanisms underlying these processes remain incompletely understood. Inflammation serves as a necessary link between the observed procoagulant phenotype and actual thrombus development and is an important mediator of the placental injury in APS patients. However, the underlying mechanisms for these events have also not been fully elucidated. In this review, we will outline the available data that give us our current understanding of the pathophysiology of APS, especially as it relates to the development of thromboembolic and obstetric pathological phenomena in these patients. We will also describe the intracellular signaling pathways activated by aPL in various cellular subtypes and outline the current evidence linking these pathways to clinical phenotypes. Finally, we will discuss the implications of distinct molecular patterns defining clinical phenotypes of APS patients.

  2. Diet and physical activity in relation to metabolic syndrome among urban Indian men and women.

    PubMed

    Miglani, Neetu; Bains, Kiran; Singh, Pritpal

    2015-01-01

    The relationship of diet and physical activity with metabolic syndrome (MS) was studied among 60 male and female (40-60 y) urban Indian MS patients. Intake of green leafy vegetables, other vegetables, fruits and milk were significantly (p ≤ .01) associated with reduced fat mass and waist circumference and increased lean body mass. Energy, carbohydrates, and fat intakes were significantly (p ≤ .01) correlated with increased body fat and waist circumference and reduced lean body mass. Energy, total and saturated fat intake were positively and significantly (p ≤ .05; .01) correlated with total cholesterol. Total fat was also significantly (p ≤ .05; .01) correlated with increased systolic blood pressure (r = 0.33), serum triglycerides (r = 0.33), LDL-C (r = 0.29) and VLDL-C (r = 0.28). Increased TDEE was significantly (p ≤ .01) associated with decreased body fat and waist circumference (r = 0.53 and 0.60) and increased lean body mass (r = 0.68).

  3. Agonists of MAS oncogene and angiotensin II type 2 receptors attenuate cardiopulmonary disease in rats with neonatal hyperoxia-induced lung injury.

    PubMed

    Wagenaar, Gerry T M; Laghmani, El Houari; Fidder, Melissa; Sengers, Rozemarijn M A; de Visser, Yvonne P; de Vries, Louwe; Rink, Rick; Roks, Anton J M; Folkerts, Gert; Walther, Frans J

    2013-09-01

    Stimulation of MAS oncogene receptor (MAS) or angiotensin (Ang) receptor type 2 (AT2) may be novel therapeutic options for neonatal chronic lung disease (CLD) by counterbalancing the adverse effects of the potent vasoconstrictor angiotensin II, consisting of arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH) and pulmonary inflammation. We determined the cardiopulmonary effects in neonatal rats with CLD of daily treatment during continuous exposure to 100% oxygen for 10 days with specific ligands for MAS [cyclic Ang-(1-7); 10-50 μg·kg(-1)·day(-1)] and AT2 [dKcAng-(1-7); 5-20 μg·kg(-1)·day(-1)]. Parameters investigated included lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression in the lungs of key genes involved in the renin-angiotensin system, inflammation, coagulation, and alveolar development. We investigated the role of nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester (25 mg·kg(-1)·day(-1)) during AT2 agonist treatment. Prophylactic treatment with agonists for MAS or AT2 for 10 days diminished cardiopulmonary injury by reducing alveolar septum thickness and medial wall thickness of small arterioles and preventing RVH. Both agonists attenuated the pulmonary influx of inflammatory cells, including macrophages (via AT2) and neutrophils (via MAS) but did not reduce alveolar enlargement and vascular alveolar leakage. The AT2 agonist attenuated hyperoxia-induced fibrin deposition. In conclusion, stimulation of MAS or AT2 attenuates cardiopulmonary injury by reducing pulmonary inflammation and preventing PAH-induced RVH but does not affect alveolar and vascular development in neonatal rats with experimental CLD. The beneficial effects of AT2 activation on experimental CLD were mediated via a NOS-independent mechanism.

  4. Angelman syndrome-associated ubiquitin ligase UBE3A/E6AP mutants interfere with the proteolytic activity of the proteasome.

    PubMed

    Tomaić, V; Banks, L

    2015-01-29

    Angelman syndrome, a severe neurodevelopmental disease, occurs primarily due to genetic defects, which cause lack of expression or mutations in the wild-type E6AP/UBE3A protein. A proportion of the Angelman syndrome patients bear UBE3A point mutations, which do not interfere with the expression of the full-length protein, however, these individuals still develop physiological conditions of the disease. Interestingly, most of these mutations are catalytically defective, thereby indicating the importance of UBE3A enzymatic activity role in the Angelman syndrome pathology. In this study, we show that Angelman syndrome-associated mutants interact strongly with the proteasome via the S5a proteasomal subunit, resulting in an overall inhibitory effect on the proteolytic activity of the proteasome. Our results suggest that mutated catalytically inactive forms of UBE3A may cause defects in overall proteasome function, which could have an important role in the Angelman syndrome pathology.

  5. Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.

    PubMed

    Zhang, Zhuo-Qian; Wang, Jing; Hoy, Zachary; Keegan, Achsah; Bhagwat, Samir; Gigliotti, Francis; Wright, Terry W

    2015-12-01

    Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.

  6. Oxidative stress in cardiomyocytes contributes to decreased SERCA2a activity in rats with metabolic syndrome.

    PubMed

    Balderas-Villalobos, Jaime; Molina-Muñoz, Tzindilu; Mailloux-Salinas, Patrick; Bravo, Guadalupe; Carvajal, Karla; Gómez-Viquez, Norma L

    2013-11-01

    Ca(+) mishandling due to impaired activity of cardiac sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) has been associated with the development of left ventricular diastolic dysfunction in insulin-resistant cardiomyopathy. However, the molecular causes underlying SERCA2a alterations induced by insulin resistance and related metabolic disorders, such as metabolic syndrome (MetS), are not completely understood. In this study, we used a sucrose-fed rat model of MetS to test the hypothesis that decreased SERCA2a activity is mediated by elevated oxidative stress produced in the MetS heart. Production of ROS and cytosolic Ca(2+) concentration were recorded in left ventricular myocytes using confocal imaging. The level of SERCA2a oxidation was determined in left ventricular homogenates by biotinylated iodoacetamide labeling. Compared with control rats, sucrose-fed rats exhibited several characteristics of MetS, including central obesity, insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Moreover, relative to myocytes from control rats, myocytes from MetS rats exhibited elevated basal production of ROS accompanied by slowed cytosolic Ca(2+) removal, reflected by prolonged Ca(2+) transients. The slowed cytosolic Ca(2+) removal was associated with a significant decrease in SERCA2a-mediated Ca(2+) reuptake and increased SERCA2a oxidation. Importantly, myocytes from MetS rats treated with the antioxidant N-acetylcysteine showed normal ROS levels and SERCA2a-mediated Ca(2+) reuptake as well as accelerated cytosolic Ca(2+) removal. These data suggest that elevated oxidative stress may induce oxidative modifications on SERCA2a leading to abnormal function of this protein in the MetS heart.

  7. Association of physical activity with risk of metabolic syndrome: findings from a cross-sectional study conducted in rural area, Nantong, China.

    PubMed

    Xiao, Jing; Wu, Chuanli; Xu, Guangfei; Huang, Jianping; Gao, Yuexia; Lu, Qingyun; Hua, Tianqi; Cai, Hui

    2016-10-01

    The prevalence of metabolic syndrome increases rapidly worldwide, and its association with physical activity (PA) varies with race and lifestyles. Little is known about the association in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6997 male participants in 2007 and 2008. Socio-demographic characteristics, and physiological and behavioural data were collected. Logistic regression model was applied to estimate associations of metabolic syndrome and its components with different PAs. The overall metabolic syndrome prevalence was 21.6% in current study. Increasing total PA or moderate-to-vigorous-intensity occupational PA was associated with decreasing 5%-60% risk of having metabolic syndrome and abnormal metabolic syndrome components in both genders. An association between leisure-time PA and blood pressure was found in men, but no associations between leisure-time PA and metabolic syndrome components were found in women. Commuting PA, such as walking and taking bus, by bicycle and walking only, was associated with decrease of 20%-45% risk of several abnormal metabolic syndrome components in women. This study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce the prevalence of metabolic syndrome and its components among rural population in China.

  8. Comparative analysis of signature genes in porcine reproductive and respiratory syndrome virus (PRRSV)-infected porcine monocyte-derived dendritic cells at differential activation statuses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Activation statuses of monocytic cells, e.g. monocytes, macrophages and dendritic cells (DCs), are critically important for antiviral immunity. In particular, some devastating viruses, including porcine reproductive and respiratory syndrome virus (PRRSV), are capable of directly infecting these cell...

  9. Activation of villous trophoblastic p38 and ERK1/2 signaling pathways in preterm preeclampsia and HELLP syndrome.

    PubMed

    Szabo, Szilvia; Mody, Meera; Romero, Roberto; Xu, Yi; Karaszi, Katalin; Mihalik, Noemi; Xu, Zhonghui; Bhatti, Gaurav; Fule, Tibor; Hupuczi, Petronella; Krenacs, Tibor; Rigo, Janos; Tarca, Adi L; Hassan, Sonia S; Chaiworapongsa, Tinnakorn; Kovalszky, Ilona; Papp, Zoltan; Than, Nandor Gabor

    2015-07-01

    Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and the release of toxic substances, which promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet unknown trigger the placenta to induce the terminal pathway. The contribution of the villous trophoblast to these pathologic events has not been fully elucidated. Here we aimed to study how stress and signaling pathways influence trophoblastic functions in various subforms of preeclampsia. Tissue microarrays (TMAs) were constructed from placentas obtained from pregnant women in the following groups: 1-2) preterm preeclampsia with (n = 8) or without (n = 7) HELLP syndrome; 3) late-onset preeclampsia (n = 8); 4-5) preterm (n = 5) and term (n = 9) controls. TMA slides were stained for phosphorylated Akt-1, ERK1/2, JNK, and p38 kinases, and trophoblastic immunostainings were semi-quantitatively evaluated. BeWo cells were kept in various stress conditions, and the expression of FLT1, GCM1, LEP, and PGF was profiled by qRT-PCR, while Akt-1, ERK1/2, JNK, and p38 kinase activities were measured with phospho-kinase immunoassays. We found that: 1) Placental LEP and FLT1 expression was up-regulated in preterm preeclampsia with or without HELLP syndrome compared to controls; 2) Mean pp38 immunoscore was higher in preterm preeclampsia, especially in cases with HELLP syndrome, than in controls. 3) Mean pERK1/2 immunoscore was higher in preterm preeclampsia with HELLP syndrome than in controls. 4) In BeWo cells, ischemia up-regulated LEP expression, and it increased JNK and decreased ERK1/2 activity. 5) Hypoxia up-regulated FLT1 and down-regulated PGF expression, and it increased ERK1/2, JNK and p38 activity. 6) IL-1β treatment down-regulated PGF expression, and it increased JNK and p38 activity. 7) The p38 signaling pathway had the most impact on LEP, FLT1 and PGF expression. In conclusion, hypoxic and ischemic stress, along

  10. BOREAS Level-2 MAS Surface Reflectance and Temperature Images in BSQ Format

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Newcomer, Jeffrey (Editor); Lobitz, Brad; Spanner, Michael; Strub, Richard; Lobitz, Brad

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Aircraft Data Acquisition Program focused on providing the research teams with the remotely sensed aircraft data products they needed to compare and spatially extend point results. The MODIS Airborne Simulator (MAS) images, along with other remotely sensed data, were collected to provide spatially extensive information over the primary study areas. This information includes biophysical parameter maps such as surface reflectance and temperature. Collection of the MAS images occurred over the study areas during the 1994 field campaigns. The level-2 MAS data cover the dates of 21-Jul-1994, 24-Jul-1994, 04-Aug-1994, and 08-Aug-1994. The data are not geographically/geometrically corrected; however, files of relative X and Y coordinates for each image pixel were derived by using the C130 navigation data in a MAS scan model. The data are provided in binary image format files.

  11. 77 FR 58996 - Multiple Award Schedule (MAS) Program Continuous Open Season-Operational Change; Extension of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-25

    ... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES ADMINISTRATION Multiple Award Schedule (MAS) Program Continuous Open Season-- Operational Change; Extension of Comment Period AGENCY: Federal Acquisition Service (FAS), General Services Administration (GSA)....

  12. Heart activity and autistic behavior in infants and toddlers with fragile X syndrome.

    PubMed

    Roberts, Jane E; Tonnsen, Bridgette; Robinson, Ashley; Shinkareva, Svetlana V

    2012-03-01

    The present study contrasted physiological arousal in infants and toddlers with fragile X syndrome to typically developing control participants and examined physiological predictors early in development to autism severity later in development in fragile X syndrome. Thirty-one males with fragile X syndrome (ages 8-40 months) and 25 age-matched control participants were included. The group with fragile X syndrome showed shorter interbeat intervals (IBIs), lower vagal tone (VT), and less modulation of IBI. Data suggested a nonlinear effect with IBI and autistic behavior; however, a linear effect with VT and autistic behavior emerged. These findings suggest that atypical physiological arousal emerges within the first year and predicts severity of autistic behavior in fragile X syndrome. These relationships are complex and dynamic, likely reflecting endogenous factors assumed to reflect atypical brain function secondary to reduced fragile X mental retardation protein. This research has important implications for the early identification and treatment of autistic behaviors in young children with fragile X syndrome.

  13. U.S. Geological Survey mineral databases; MRDS and MAS/MILS

    USGS Publications Warehouse

    McFaul, E.J.; Mason, G.T.; Ferguson, W.B.; Lipin, B.R.

    2000-01-01

    These two CD-ROM's contain the latest version of the Mineral Resources Data System (MRDS) database and the Minerals Availability System/Minerals Industry Location System (MAS/MILS) database for coverage of North America and the world outside North America. The records in the MRDS database each contain almost 200 data fields describing metallic and nonmetallic mineral resources, deposits, and commodities. The records in the MAS/MILS database each contain almost 100 data fields describing mines and mineral processing plans.

  14. Ammonia Vapor Removal by Cu3(BTC)2 and Its Characterization by MAS NMR

    DTIC Science & Technology

    2009-01-01

    further confirmation of these assignments, Soxhlet - extracted (MeOH) Cu3(BTC)2 is totally devoid of both DMF peaks, leaving only the pristine methine...samples, 1H and 13C MAS NMR spectra for solvent extracted Cu3(BTC)2 and (NH4)3BTC, Figure 15. 1H MAS NMR spectra obtained for Cu3(BTC)2 exposed to NH3

  15. Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome.

    PubMed

    Noh, Jung-Hoon; Kong, Doo-Sik; Seol, Ho Jun; Shin, Hyung Jin

    2014-09-01

    McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.

  16. A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome.

    PubMed

    Whitley, C B; Gorlin, R J; Krivit, W

    1987-09-01

    We identified a phenotypically normal obligate heterozygote for Hurler syndrome with exceedingly low levels of alpha-L-iduronidase enzyme activity. Subsequent investigation determined that low alpha-L-iduronidase activity was systemic, also characteristic of the subject's leukocytes and cultured skin fibroblasts. Residual alpha-L-iduronidase activity of cultured fibroblasts was found to have reduced catalytic activity (Vmax) against the 4-methylumbelliferone substrate, but normal substrate affinity (KM). Additional studies further characterized the residual enzyme activity in this woman who is an apparent compound heterozygote for Hurler syndrome, and for an allele with low alpha-L-iduronidase activity lacking pathologic manifestation. Such low activity "pseudodeficiency" alleles will complicate attempts at prenatal diagnosis of Hurler syndrome and related disorders in rare families.

  17. Antioxidant enzyme activities and mitochondrial fatty acids in pulmonary hypertension syndrome (PHS) in broilers.

    PubMed

    Iqbal, M; Cawthon, D; Beers, K; Wideman, R F; Bottje, W G

    2002-02-01

    Major objectives of this study were to assess antioxidant protection and fatty acid profile in lung mitochondria and whole liver in broilers with pulmonary hypertension syndrome [(PHS; with and without high dietary vitamin E (VE)] (Experiment 1) and in broilers that did not develop PHS but were genetically selected (S) or not selected (NS) for resistance to PHS (Experiment 2). In Experiment 1, lung mitochondrial glutathione peroxidase (GSH-Px) activity was elevated in broilers with PHS compared to controls, broilers fed high VE, and broilers fed high VE with PHS (VE-PHS), but there were no differences in GSH reductase (GSH-Rd) among groups. In liver tissue, GSH-Px was also elevated by PHS but was lower in VE and VE-PHS groups than in controls. There were no differences in liver GSH-Rd, superoxide dismutase (SOD), or gamma-glutamylcysteine synthetase (gamma-GCS) activities with the exception that gamma-GCS was higher in the VE-PHS group than in the other groups. In Experiment 2, S lung mitochondria exhibited lower GSH-Px and higher GSH-Rd compared to NS broilers. In the liver, there were no differences in GSH-Px, GSH-Rd, or gamma-GCS, but SOD was lower in S compared to the NS broilers. High VE increased the percentage of saturated fatty acids and decreased the percentage of unsaturated fatty acids in lung mitochondria in Experiment 1; there were no differences in fatty acid content between S and NS mitochondria in Experiment 2. Thus, it appears that GSH recycling enzyme activities are affected by PHS and high VE presumably in response to differences in oxidative stress and that genetic resistance to PHS is associated with an inherently better capability to metabolize oxidants in lung mitochondria. The increase in saturation of lung mitochondrial fatty acids with high dietary VE would presumably make them more resistant to oxidative stress and, thus, reduce the level of PHS-induced oxidative stress.

  18. Lymphocyte subpopulations and suppressor cell activity in acute polyradiculoneuritis (Guillain-Barré syndrome).

    PubMed Central

    Hughes, R A; Aslan, S; Gray, I A

    1983-01-01

    Ficoll-Triosil separated peripheral blood mononuclear (PBM) cells were analysed by fluorescent microscopy with Ortho monoclonal antisera to T cells (OKT3+) helper cells (OKT4+) and suppressor cytotoxic cells (OKT8+) and with polyclonal antiserum to surface immunoglobulin. Twenty-five normal subjects, 16 patients with acute polyradiculoneuritis (Guillain-Barré syndrome, AP) and 10 patients with other neurological diseases were studied. The percentages of OKT3+, OKT4+ and immunoglobulin bearing cells were similar in the three patient groups but the percentage of OKT8+ cells was reduced to 13.5 +/- 4.1 (mean +/- s.d.) compared with 19.4 +/- 4.9 in the normal subjects and 18.5 +/- 3.1 in the patients with other neurological diseases. The ratio of OKT4+/OKT8+ cells was correspondingly increased to 3.5 +/- 2.1 compared with 2.1 +/- 0.5 in the normal subjects and 2.1 +/- 0.4 in the patients with other neurological diseases. In one test of suppressor cell function Con A incubated mitomycin treated PBM cells were added to autologous PBM cells stimulated with Con A to compare the degree of suppression with that produced by control incubated mitomycin treated cells (Con A suppression test). In a second test of suppressor cell function short lived suppressor cell (SLS) activity was assayed by comparing PBM stimulation by Con A added at the start of culture with that produced by Con A added after 24 hr. Neither test revealed any significant differences between AP patients and control subjects. PMID:6221841

  19. Hyaluronan Contributes to Bronchiolitis Obliterans Syndrome and Stimulates Lung Allograft Rejection through Activation of Innate Immunity

    PubMed Central

    Wang, Xingan; Sugimoto, Seichiro; Kennedy, Vanessa E.; Zhang, Helen L.; Pavlisko, Elizabeth N.; Kelly, Fran L.; Huang, Howard; Kreisel, Daniel; Palmer, Scott M.

    2014-01-01

    Rationale: Although innate immunity is increasingly recognized to contribute to lung allograft rejection, the significance of endogenous innate ligands, such as hyaluronan (HA) fragments, in clinical or experimental lung transplantation is uncertain. Objectives: To determine if HA is associated with clinical bronchiolitis obliterans syndrome (BOS) in lung transplant recipients, and evaluate the effect of low- or high-molecular-weight HA on experimental lung allograft rejection, including dependence on innate signaling pathways or effector cells. Methods: HA concentrations were measured in bronchoalveolar lavage and plasma samples from lung recipients with or without established BOS. BOS and normal lung tissues were assessed for HA localization and expression of HA synthases. Murine orthotopic lung recipients with established tolerance were treated with low- or high-molecular-weight HA under varied experimental conditions, including Toll-like receptor (TLR) 2/4 and myeloid differentiation protein 88 deficiency and neutrophil depletion. Measurements and Main Results: HA localized within areas of intraluminal small airways fibrosis in BOS lung tissue. Moreover, transcripts for HA synthase enzymes were significantly elevated in BOS versus normal lung tissues and both lavage fluid and plasma HA concentrations were increased in recipients with BOS. Treatment with low-molecular-weight HA abrogated tolerance in murine orthotopic lung recipients in a TLR2/4- and myeloid differentiation protein 88–dependent fashion and drove expansion of alloantigen-specific T lymphocytes. Additionally, TLR-dependent signals stimulated neutrophilia that promoted rejection. In contrast, high-molecular-weight HA attenuated basal allograft inflammation. Conclusions: These data suggest that accumulation of HA could contribute to BOS by directly activating innate immune signaling pathways that promote allograft rejection and neutrophilia. PMID:24471427

  20. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    PubMed Central

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3–16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment. PMID:27362350

  1. Activation of necroptosis in a rat model of acute respiratory distress syndrome induced by oleic acid.

    PubMed

    Pan, Long; Yao, Dun-Chen; Yu, Yu-Zhong; Chen, Bing-Jun; Li, Sheng-Jie; Hu, Gui-He; Xi, Chang; Wang, Zi-Hui; Li, Jian-Hua; Long, Jie; Tu, Yong-Sheng

    2016-10-25

    The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit. Expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissue were determined by Western blot and immunohistochemical staining. The interaction between RIPK1 and RIPK3 was explored by immunoprecipitation. The results showed that, compared with those in control group, total white blood cells count (WBC), polymorphonuclear percentage (PMN%), total protein concentration, TNF-α level in BALF, W/D, and the alveolar-arterial oxygen tension difference (P(A-a)O2) in OA group were significantly increased at 4 h after OA injection. Western blot and immunostaining further showed remarkably increased expressions of RIPK1, RIPK3 and MLKL in lung tissue from OA group. Additionally, immunoprecipitation results indicated an enforced interaction between RIPK1 and RIPK3 in OA group. Collectively, the TNF-α level in BALF and the RIPK1-RIPK3-MLKL signaling pathway in lung tissue were found to be upregulated and activated with the process of ARDS. These findings implicate that RIPK1/RIPK3-mediated necroptosis plays a possible role in the pathogenesis of ARDS, which may provide a new idea to develop novel drugs for the therapy of ARDS.

  2. Associations between physical activity and sedentary time on components of metabolic syndrome among adults with HIV.

    PubMed

    Jaggers, Jason R; Prasad, Vivek K; Dudgeon, Wesley D; Blair, Steven N; Sui, Xuemei; Burgess, Stephanie; Hand, Gregory A

    2014-01-01

    Recent data show that people living with HIV/AIDS (PLWHA) are at a greater risk of cardiovascular disease (CVD), which could possibly be explained by an increased prevalence of metabolic syndrome (MetSyn) due to the known toxicities associated with antiretroviral therapy (ART). The purpose of this study is to examine the relationships between physical activity (PA) and components of MetSyn in a sample of PLWHA taking ART. A total of 31 males and 32 females living with HIV and currently taking ART were enrolled in a home-based PA intervention aimed to reduce risk factors for CVD. Clinical assessments included measures of resting blood pressure (BP), waist circumference, height, weight, PA levels via accelerometer, and a fasted blood draw. Components of MetSyn were divided into three clusters (1 = 0-1; 2 = 2; 3 = 3 or more). A one-way analysis of variance was used to determine differences between clusters. Multiple linear regressions were used to identify significant associations between moderate intensity PA (MPA) and sedentary time among components of MetSyn. MPA was significantly lower across MetSyn clusters (p < 0.001), whereas sedentary time was significantly higher (p = 0.01). A multiple linear regression showed MPA to be a significant predictor of waist circumference after controlling for age, race, gender, and sedentary time. Routine PA can be beneficial in helping PLWHA reduce waist circumference ultimately leading to metabolic improvements. This in turn would help PLWHA self-manage known components of MetSyn, thus reducing their risk of CVD and mortality.

  3. Associations Between Physical Activity and Sedentary Time on Components of Metabolic Syndrome Among Adults with HIV

    PubMed Central

    Jaggers, Jason R.; Prasad, Vivek K.; Dudgeon, Wesley; Blair, Steven N.; Sui, Xuemei; Burgess, Stephanie; Hand, Gregory A.

    2014-01-01

    Recent data show that people living with HIV/AIDS (PLWHA) are at a greater risk of cardiovascular disease (CVD), which could possibly be explained by an increased prevalence of metabolic syndrome (MetSyn) due to the known toxicities associated with antiretroviral therapy (ART). The purpose of this study is to examine the relationships among physical activity (PA) and components of MetSyn in a sample of PLWHA taking ART. A total of 31 males and 32 females living with HIV and currently taking ART were enrolled in a home-based PA intervention aimed to reduce risk factors for CVD. Clinical assessments included measures of resting blood pressure (BP), waist circumference, height, weight, PA levels via accelerometer, and a fasted blood draw. Components of MetSyn were divided into three clusters (1=0–1; 2 = 2; 3 = 3 or more). A one-way ANOVA was used to determine differences between clusters. Multiple linear regressions were used to identify significant associations between moderate intensity PA (MPA) and sedentary time among components of MetSyn. MPA was significantly lower across MetSyn clusters (p < 0.001), whereas sedentary time was significantly higher (p = 0.01). A multiple linear regression showed MPA to be a significant predictor of waist circumference after controlling for age, race, gender and sedentary time. Routine PA can be beneficial in helping PLWHA reduce waist circumference ultimately leading to metabolic improvements. This in turn would help PLWHA self-manage known components of MetSyn, thus reducing their risk of CVD and mortality. PMID:24861098

  4. Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension.

    PubMed

    Huggett, Robert J; Burns, Joanna; Mackintosh, Alan F; Mary, David A S G

    2004-12-01

    Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS) in which the presence of insulin resistance, glucose intolerance, abnormal lipoprotein metabolism, and central obesity all confer an increased risk. Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity, which is itself known to increase cardiovascular risk, the aim of this study was to see if MS is a state of sympathetic nerve hyperactivity and if the additional presence of EHT intensifies this hyperactivity. In 69 closely matched subjects, comprising hypertensive MS (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16), and normotensive controls without MS (NC, 18), we measured resting muscle sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in MS+EHT (76+/-3.1 impulses/100 beats) was greater (at least P<0.01) than in MS-EHT (62+/-3.2 impulses/100 beats) and in EHT (60+/-2.3 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NC (46+/-2.7 impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings suggest that MS is a state of sympathetic nerve hyperactivity and that the additional presence of hypertension further intensifies this hyperactivity. The degree of sympathetic hyperactivity seen in this study could be argued at least partly to contribute to the higher cardiovascular risk and metabolic abnormalities seen in MS+EHT patients.

  5. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome

    SciTech Connect

    Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y.

    1987-11-01

    Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.

  6. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.

    PubMed Central

    Epstein, C J; Avraham, K B; Lovett, M; Smith, S; Elroy-Stein, O; Rotman, G; Bry, C; Groner, Y

    1987-01-01

    Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. These animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes. Images PMID:2960971

  7. Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.

    PubMed

    Vaché, Christel; Besnard, Thomas; le Berre, Pauline; García-García, Gema; Baux, David; Larrieu, Lise; Abadie, Caroline; Blanchet, Catherine; Bolz, Hanno Jörn; Millan, Jose; Hamel, Christian; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

    2012-01-01

    USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified a single pathogenic alteration in one of them and a different mutation in the two affected nieces. As the patients carried a common USH2A haplotype, they likely shared a mutation not found by standard sequencing techniques. Analysis of RNA from nasal cells in one affected individual identified an additional pseudoexon (PE) resulting from a deep intronic mutation. This was confirmed by minigene assay. This is the first example in Usher syndrome (USH) with a mutation causing activation of a PE. The finding of this alteration in eight other individuals of mixed European origin emphasizes the importance of including RNA analysis in a comprehensive diagnostic service. Finally, this mutation, which would not have been found by whole-exome sequencing, could offer, for the first time in USH, the possibility of therapeutic correction by antisense oligonucleotides (AONs).

  8. Kinetic Mechanisms of Mutation-dependent Harvey Ras Activation and Their Relevance for Development of Costello Syndrome

    PubMed Central

    Wey, Michael; Lee, Jungwoon; Jeong, Soon Seog; Kim, Jungho; Heo, Jongyun

    2013-01-01

    Costello syndrome is linked to activating mutations of a residue in the p-loop or the NKCD/SAK motifs of Harvey Ras (HRas). More than 10 HRas mutants that induce Costello syndrome have been identified; G12S HRas is the most prevalent of these. However, certain HRas p-loop mutations also are linked to cancer formation that are exemplified with G12V HRas. Despite these relations, specific links between types of HRas mutations and diseases evade definition because some Costello syndrome HRas p-loop mutations, such as G12S HRas, also often cause cancer. This study established novel kinetic parameter-based equations that estimate the value of the cellular fractions of the GTP-bound active form of HRas mutant proteins. Such calculations differentiate between two basic kinetic mechanisms that populate the GTP-bound form of Ras in cells. (i) The increase in GTP-bound Ras by the HRas mutation-mediated perturbation of the intrinsic kinetic characteristics of Ras. This generates a broad spectrum of the population of the GTP-bound form of HRas that typically causes Costello syndrome. The upper end of this spectrum of HRas mutants, as exemplified by G12S HRas, can also cause cancer. (ii) The increase in GTP-bound Ras because the HRas mutations perturb the p120GAP action on Ras. This causes production of a significantly high population of the only GTP-bound form of HRas linked merely to cancer formation. The HRas mutant G12V belongs to this category. PMID:24224811

  9. 1H HR-MAS NMR of carotenoids in aqueous samples and raw vegetables.

    PubMed

    Miglietta, M L; Lamanna, R

    2006-07-01

    Carotenoids are linear C40 tetraterpenoid hydrocarbons and represent a wide category of natural pigments. They are components of the pigment system of chloroplasts and are involved in the primary light absorption and the photon canalization of photosynthesis. Moreover, they also behave as quenchers of singlet oxygen, protecting cells and organisms against lipid peroxidation. Carotenoids have a strong lipophilic character and are usually analyzed in organic solvents. However, because of their biological activity, the characterization of these compounds in an aqueous environment or in the natural matrix is very important. One of the most important dietary carotenoids is beta-carotene, which has been extensively studied both in vivo and in model systems, but because of the low concentration and strong interaction with the biological matrix, beta-carotene has never been observed by NMR in solid aqueous samples.In the present work, a model system has been developed for the detection and identification of beta-carotene in solid aqueous samples by 1H HR-MAS NMR. The efficiency of the model has led to the identification of beta-carotene in a raw vegetable matrix.

  10. Immobilization of soluble protein complexes in MAS solid-state NMR: Sedimentation versus viscosity.

    PubMed

    Sarkar, Riddhiman; Mainz, Andi; Busi, Baptiste; Barbet-Massin, Emeline; Kranz, Maximilian; Hofmann, Thomas; Reif, Bernd

    2016-01-01

    In recent years, MAS solid-state NMR has emerged as a technique for the investigation of soluble protein complexes. It was found that high molecular weight complexes do not need to be crystallized in order to obtain an immobilized sample for solid-state NMR investigations. Sedimentation induced by sample rotation impairs rotational diffusion of proteins and enables efficient dipolar coupling based cross polarization transfers. In addition, viscosity contributes to the immobilization of the molecules in the sample. Natural Deep Eutectic Solvents (NADES) have very high viscosities, and can replace water in living organisms. We observe a considerable amount of cross polarization transfers for NADES solvents, even though their molecular weight is too low to yield significant sedimentation. We discuss how viscosity and sedimentation both affect the quality of the obtained experimental spectra. The FROSTY/sedNMR approach holds the potential to study large protein complexes, which are otherwise not amenable for a structural characterization using NMR. We show that using this method, backbone assignments of the symmetric proteasome activator complex (1.1MDa), and high quality correlation spectra of non-symmetric protein complexes such as the prokaryotic ribosome 50S large subunit binding to trigger factor (1.4MDa) are obtained.

  11. Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome.

    PubMed

    Rentoukas, Elias; Tsarouhas, Konstantinos; Kaplanis, Ioannis; Korou, Eleni; Nikolaou, Maria; Marathonitis, George; Kokkinou, Stavroula; Haliassos, Alexander; Mamalaki, Avgi; Kouretas, Demetrios; Tsitsimpikou, Christina

    2012-01-01

    Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis.

  12. Association between physical activity and metabolic syndrome in older adults in Korea: analysis of data from the Korean National Health and Nutrition Examination Survey IV.

    PubMed

    Choi, Mona; Yeom, Hye-A; Jung, Dukyoo

    2013-09-01

    The prevalence of metabolic syndrome is consistently increasing among Korean adults and is reported to be particularly high among older adults in Korea. This paper reports the prevalence of metabolic syndrome and identifies the association between metabolic syndrome and physical activity in Korean older adults. Subjects of this study were 3653 older adults who participated in the fourth Korean National Health and Nutrition Examination Survey during the years 2007-2009. The prevalence of metabolic syndrome in the study population was 46.84%. The prevalences of abdominal obesity, elevated fasting glucose, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated blood pressure were 39.51, 45.53, 39.55, 48.24, and 69.14%, respectively, in the study population. Compared to subjects who reported low levels of physical activity, the odds ratios of metabolic syndrome for those who were moderately active and highly active were 0.93 and 0.63, respectively. Nurses should develop metabolic syndrome management programs that are tailored to the needs of the targeted group and that include individually adapted physical activity programs to promote health.

  13. Neonatal McCune-Albright syndrome with survival beyond two years.

    PubMed

    Pierce, Melinda; Scottoline, Brian

    2016-11-01

    McCune-Albright syndrome (MAS) is a rare disease resulting from a somatic, mosaic mutation of GNAS1 encoding the Gs α subunit of the G-protein coupled membrane receptor responsible for multiple hormonal signaling cascades. We present a patient with neonatal MAS who initially presented with neonatal diabetes and concern for congenital cardiac disease, and subsequently was found to have significant ACTH-independent neonatal Cushing syndrome. Her course included multi-system organ involvement, although she initially did not have obvious findings consistent with the MAS classic triad of café-au-lait macules, fibrous dysplasia, or peripheral precocious puberty. After medical and surgical treatment, she remains the only reported survivor of neonatal MAS. This clinical report alerts clinicians to the possibility of this disease in neonates with non-classical endocrine and non-endocrine manifestations of MAS, and demonstrates that this very early presentation is potentially survivable. © 2016 Wiley Periodicals, Inc.

  14. Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

    PubMed

    Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

    2014-03-01

    Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

  15. Sonographic assessment of carpal tunnel syndrome in rheumatoid arthritis: prevalence and correlation with disease activity.

    PubMed

    Karadag, Omer; Kalyoncu, Umut; Akdogan, Ali; Karadag, Yesim Sucullu; Bilgen, Sule Apras; Ozbakır, Senay; Filippucci, Emilio; Kiraz, Sedat; Ertenli, Ihsan; Grassi, Walter; Calgüneri, Meral

    2012-08-01

    Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). High frequency ultrasonography (US) is a sensitive and specific method in diagnosis of CTS. This study is aimed to: firstly assess diameter frequency of CTS in RA with US and compare with a control group; secondly, investigate relationship of CTS with disease activity. One hundred consecutive RA patients (women/men: 78/22) fulfilling ACR 1987 RA criteria and 45 healthy controls (women/control: 34/11) were enrolled into study. Disease activity parameters, RA and CTS patient global assessment and health assessment questionnaire (HAQ-DI) were recorded. Both patient and control group were questioned about secondary causes of CTS, and Katz hand diagram, Boston CTS questionnaire and Phalen ve Tinel tests were applied once for each hand. Wrist joint and carpal tunnel were assessed with US grey scale and power Doppler US, then cross-sectional area of median nerve (CSA) was calculated. Patients with median nerve CSA between 10.0 and 13.0 mm(2) were evaluated with electromyography (EMG). CTS was diagnosed if CSA of median nerve >13.0 mm(2) or CTS was shown with NCS. Although there was no difference between RA patients and controls in age, sex, history of DM (+) and goitre, CTS was more frequent in RA group (respectively, 17.0% vs. 4.4%, P = 0.038). In RA group with CTS, age, history of DM, disease duration, HAQ-DI score, CTS patient global score, Boston symptom severity and functional status scores were elevated compared to without CTS [respectively, 57 (36-73) vs. 50 (24-76), P = 0.041; 35.3% vs. 6.0%, P < 0.001; 108 (12-396) months vs. 72 (6-360) months, P = 0.036; 1.93 (0.75-2.87) vs. 1.125 (0-2.75), P = 0.013; 52 (1-97) vs. 25 (0-91), P = 0.001; 2.81 (1.18-4.17) vs. 2.0 (1.0-4.01), P = 0.01; 3.37 (1.37-5.0) vs. 2.25 (1.0-5.0), P = 0.008]. No difference was found between CTS (+) and (-) RA patients in acute phase reactants, disease activity and US findings

  16. Clonal Rett Syndrome cell lines to test compounds for activation of wild-type MeCP2 expression.

    PubMed

    Yu, Dongbo; Sakurai, Fuminori; Corey, David R

    2011-09-15

    Rett Syndrome is an X-linked progressive neurological disorder caused by inactivation of one allele of the MECP2 gene. There are no curative treatments, and activation of wild-type MECP2 expression is one strategy for stabilizing or reversing the disease. We isolated fibroblast clones that express exclusively either the wild-type or a 32-bp-deletion mutant form of MECP2. We developed a sensitive assay for measuring wild-type MECP2 mRNA levels and tested small molecule epigenetic activators for their ability to activate gene expression. Although our pilot screen did not identify activators of MECP2 expression, it established the value of using clonal cells and defined challenges that must be overcome.

  17. Serum 25-Hydroxyvitamin D3 and BAFF Levels Are Associated with Disease Activity in Primary Sjogren's Syndrome

    PubMed Central

    Lee, Sang Jin; Oh, Hye Jin; Choi, Byoong Yong; Jang, Yu Jin; Lee, Joo Youn; Park, Jin Kyun

    2016-01-01

    The study investigated the association between disease activity and serum 25-hydroxyvitamin D3 (25(OH)-D3), B cell activation of the tumor necrosis factor family (BAFF), or β2 microglobulin in patients with primary Sjogren's syndrome (SS). Sixty-nine primary SS patients and 22 sicca control patients were included in the study. Disease activity was measured with EULAR Sjogren's syndrome disease activity index (ESSDAI). Serum levels of 25(OH)-D3 and β2 microglobulin were measured by radioimmunoassay and BAFF was measured by an enzyme-linked immunosorbent assay. Serum levels of 25(OH)-D3 were significantly lower in SS patients compared to the sicca controls (p = 0.036). Serum levels of BAFF tended to be higher (p = 0.225) and those of β2 microglobulin were significantly higher in patients with SS than in sicca controls (p = 0.023). In univariate regression analyses, ESSDAI was significantly associated with serum levels of 25(OH)-D3, BAFF, and β2 microglobulin. After stepwise backward multivariate linear regression analyses including age and acute phase reactants, ESSDAI was associated with 25(OH)-D3 (β = −0.042, p = 0.015) and BAFF (β = 0.001, p = 0.015) in SS patients. In SS patients, ESSDAI is negatively associated with serum levels of 25(OH)-D3 and positively associated with BAFF. PMID:28074193

  18. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  19. Evidence for a Systematic Offset of -0.25 mas in the Gaia DR1 Parallaxes

    NASA Astrophysics Data System (ADS)

    Stassun, Keivan G.; Torres, Guillermo

    2016-11-01

    We test the parallaxes reported in the Gaia first data release using the sample of eclipsing binaries with accurate, empirical distances from Stassun & Torres. We find an average offset of -0.25 ± 0.05 mas in the sense of the Gaia parallaxes being too small (i.e., the distances too long). The offset does not depend strongly on obvious parameters such as color or brightness. However, we find with high confidence that the offset may depend on ecliptic latitude: the mean offset is -0.38 ± 0.06 mas in the ecliptic north and -0.05 ± 0.09 mas in the ecliptic south. The ecliptic latitude dependence may also be represented by the linear relation, {{Δ }}π ≈ -0.22(+/- 0.05)-0.003(+/- 0.001)× β mas (β in degrees). Finally, there is a possible dependence of the parallax offset on distance, with the offset becoming negligible for π ≲ 1 mas; we discuss whether this could be caused by a systematic error in the eclipsing binary distance scale, and reject this interpretation as unlikely.

  20. Time-Dependent Coupling of Lfm-Helio and MAS Models for CME Propagation

    NASA Astrophysics Data System (ADS)

    Lyon, J.; Merkin, V. G.; Lionello, R.; Linker, J.; Raouafi, N. E.

    2014-12-01

    We present initial results of coupling of the heliospheric adaptation of the Lyon-Fedder-Mobarry (LFM) magnetohydrodynamic (MHD) model — LFM-helio — with the MAS model of the solar corona. Up to now, LFM-helio has been limited to steady-state solutions dominated by corotating structures. We have developed a generalized interface for specification of time-dependent coronal boundary conditions and ingestion of MAS simulation data into the LFM model. The coupling is done by overlapping the LFM inner boundary buffer region with the outer portion of the MAS coronal grid. LFM-helio operates in the inertial rest frame, but our coupling code is sufficiently flexible that MAS solutions performed in either rotating or inertial frames can be ingested. We present results of a number of idealized coupled MAS/LFM-helio simulations — ranging from simply symmetric solar wind background to realistic including high and slow speed streams — intended to test the interface for seamless propagation of transients from the corona into the inner heliosphere domain. The transients are then tracked to larger heliocentric distances — to Earth and beyond. We specifically investigate the magnetic structure of the CMEs as they propagate through the interplanetary medium including rotation and erosion, and consider how the simulation resolution affects the results. We also developed codes for creation of synthetic white-light heliographic images which are used to help track CMEs kinematics through J-maps and put the simulations into a realistic observational context.

  1. Activities for Babies and Toddlers with Down Syndrome: A Physiotherapy Approach.

    ERIC Educational Resources Information Center

    Kelso, Rose-Anne; Price, Sue

    Children with Down Syndrome have the potential for the development of a large range and variety of postures, balance reactions, movements, and skills. Sometimes this potential remains relatively untapped resulting in unusual, inefficient, or even detrimental patterns of movement. By handling and playing with the child, he or she becomes more aware…

  2. Cognitive Behavior Therapy for Relatively Active and for Passive Chronic Fatigue Syndrome Patients

    ERIC Educational Resources Information Center

    Bazelmans, Ellen; Prins, Judith; Bleijenberg, Gijs

    2006-01-01

    In chronic fatigue syndrome (CFS), facilitating, initiating, and perpetuating factors are distinguished. Although somatic factors might have initiated symptoms in CFS, they do not explain the persistence of fatigue. Cognitive behavior therapy (CBT) for CFS focuses on factors that perpetuate and prolong symptoms. Recently it has been shown that,…

  3. Leisure Activities in Prader-Wlli Syndrome: Implications for Health, Cognition and Adaptive Functioning

    ERIC Educational Resources Information Center

    Dykens, Elisabeth M.

    2014-01-01

    Although hyperphagia and compulsivity in Prader-Willi syndrome (PWS) are well described, recreation and adaptive skills are relatively unexplored. Parents of 123 participants with PWS (4--48 years) completed measures of their child's adaptive, recreation, and problem behaviors. Offspring received cognitive testing. Watching TV was the most…

  4. Relationship between the metabolic syndrome and physical activity energy expenditure: a MONET study.

    PubMed

    Karelis, Antony D; Lavoie, Marie-Eve; Messier, Virginie; Mignault, Diane; Garrel, Dominique; Prud'homme, Denis; Rabasa-Lhoret, Rémi

    2008-04-01

    The purpose of this cross-sectional study was to examine the association between the metabolic syndrome (MetS) and physical activity energy expenditure (PAEE) in overweight and obese sedentary postmenopausal women. The study population consisted of 137 overweight and obese sedentary postmenopausal women (age, 57.7 +/- 4.8 years; BMI, 32.4 +/- 4.6 kg.m(-2)). Subjects had the MetS if 3 out of the following 5 criteria were met: visceral fat > 130 cm2, high-density lipoprotein (HDL) cholesterol < 1.29 mmol.L(-1), fasting triglycerides > or = 1.7 mmol.L(-1), blood pressure > or = 130/85 mmHg, and fasting glucose > or =5.6 mmol.L(-1). We measured (i) body composition (by dual-energy X-ray absorptiometry); (ii) visceral fat (by computed tomography); (iii) insulin sensitivity (using the hyperinsulinemic-euglycemic clamp); (iv) plasma lipids, fasting glucose, and insulin, as well as 2 h glucose during an oral glucose tolerance test; (v) resting blood pressure; (vi) peak oxygen consumption (VO2 peak); (vii) PAEE (using doubly labeled water); and (viii) lower-body muscle strength (using weight-training equipment). Forty-two women (30.7%) had the MetS in our cohort. Individuals without the MetS had significantly higher levels of PAEE (962 +/- 296 vs. 837 +/- 271 kcal.d(-1); p < 0.05), VO2 peak (18.2 +/- 3.0 vs. 16.7 +/- 3.2 mL.min(-1).kg(-1); p < 0.05), and insulin sensitivity, as well as significantly lower levels of 2 h glucose and central lean body mass. No differences in total energy expenditure, resting metabolic rate, and muscle strength between groups were observed. Logistic regression analysis showed that 2 h glucose (odds ratio (OR): 1.50 (95% CI 1.17-1.92)), central lean body mass (OR: 1.17 (95% CI 1.05-1.31)), and PAEE (OR: 0.998 (95% CI 0.997-1.000)), but not VO2 peak and (or) muscle strength, were independent predictors of the MetS. Lower levels of PAEE and higher levels of 2 h glucose, as well as central lean body mass, are independent determinants of the MetS in

  5. Induction of Alternatively Activated Macrophages Enhances Pathogenesis during Severe Acute Respiratory Syndrome Coronavirus Infection

    PubMed Central

    Page, Carly; Goicochea, Lindsay; Matthews, Krystal; Zhang, Yong; Klover, Peter; Holtzman, Michael J.; Hennighausen, Lothar

    2012-01-01

    Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1−/− mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6−/− double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA

  6. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.

    PubMed

    Page, Carly; Goicochea, Lindsay; Matthews, Krystal; Zhang, Yong; Klover, Peter; Holtzman, Michael J; Hennighausen, Lothar; Frieman, Matthew

    2012-12-01

    Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA

  7. Complete blockade of the vasorelaxant effects of angiotensin-(1–7) and bradykinin in murine microvessels by antagonists of the receptor Mas

    PubMed Central

    Peiró, Concepción; Vallejo, Susana; Gembardt, Florian; Palacios, Erika; Novella, Susana; Azcutia, Verónica; Rodríguez-Mañas, Leocadio; Hermenegildo, Carlos; Sánchez-Ferrer, Carlos F; Walther, Thomas

    2013-01-01

    The heptapeptide angiotensin-(1–7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin–angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1–7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1–7). However, it remained controversial whether an additional receptor could account for angiotensin-(1–7)-induced vasorelaxation. Here, we used two different angiotensin-(1–7) antagonists, A779 and d-Pro-angiotensin-(1–7), to address this question and also to study their influence on the vasodilatation induced by bradykinin. Isolated mesenteric microvessels from both wild-type and Mas-deficient C57Bl/6 mice were precontracted with noradrenaline, and vascular reactivity to angiotensin-(1–7) and bradykinin was subsequently studied using a small-vessel myograph. Furthermore, mechanisms for Mas effects were investigated in primary human umbilical vein endothelial cells. Both angiotensin-(1–7) and bradykinin triggered a concentration-dependent vasodilatation in wild-type microvessels, which was absent in the presence of a nitric oxide synthase inhibitor. In these vessels, the pre-incubation with the Mas antagonists A779 or d-Pro-angiotensin-(1–7) totally abolished the vasodilatory capacity of both angiotensin-(1–7) and bradykinin, which was nitric oxide mediated. Accordingly, Mas-deficient microvessels lacked the capacity to relax in response to either angiotensin-(1–7) or bradykinin. Pre-incubation of human umbilical vein endothelial cells with A779 prevented bradykinin-mediated NO generation and NO synthase phosphorylation at serine 1177. The angiotensin-(1–7) antagonists A779 and d-Pro-angiotensin-(1–7) equally block Mas, which completely controls the angiotensin-(1–7)-induced vasodilatation in mesenteric microvessels. Importantly, Mas also appears to be a critical player in NO-mediated vasodilatation induced by

  8. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome.

    PubMed

    Sullivan, Asa; Nord, Carl E; Evengård, Birgitta

    2009-01-26

    Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in the study. The patients had high fatigue severity scores and high disability scores. During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed. Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS.

  9. Neural activity in relation to empirically derived personality syndromes in depression using a psychodynamic fMRI paradigm

    PubMed Central

    Taubner, Svenja; Wiswede, Daniel; Kessler, Henrik

    2013-01-01

    Objective: The heterogeneity between patients with depression cannot be captured adequately with existing descriptive systems of diagnosis and neurobiological models of depression. Furthermore, considering the highly individual nature of depression, the application of general stimuli in past research efforts may not capture the essence of the disorder. This study aims to identify subtypes of depression by using empirically derived personality syndromes, and to explore neural correlates of the derived personality syndromes. Materials and Methods: In the present exploratory study, an individually tailored and psychodynamically based functional magnetic resonance imaging paradigm using dysfunctional relationship patterns was presented to 20 chronically depressed patients. Results from the Shedler–Westen Assessment Procedure (SWAP-200) were analyzed by Q-factor analysis to identify clinically relevant subgroups of depression and related brain activation. Results: The principle component analysis of SWAP-200 items from all 20 patients lead to a two-factor solution: “Depressive Personality” and “Emotional-Hostile-Externalizing Personality.” Both factors were used in a whole-brain correlational analysis but only the second factor yielded significant positive correlations in four regions: a large cluster in the right orbitofrontal cortex (OFC), the left ventral striatum, a small cluster in the left temporal pole, and another small cluster in the right middle frontal gyrus. Discussion: The degree to which patients with depression score high on the factor “Emotional-Hostile-Externalizing Personality” correlated with relatively higher activity in three key areas involved in emotion processing, evaluation of reward/punishment, negative cognitions, depressive pathology, and social knowledge (OFC, ventral striatum, temporal pole). Results may contribute to an alternative description of neural correlates of depression showing differential brain activation dependent

  10. CC10 reduces inflammation in meconium aspiration syndrome in newborn piglets.

    PubMed

    Angert, Robert M; Pilon, Aprile L; Chester, Darrin; Davis, Jonathan M

    2007-12-01

    Complications from meconium aspiration syndrome (MAS) remain significant despite a variety of therapeutic interventions. Clara cell protein (CC10) is a novel anti-inflammatory agent that can also inhibit phospholipase A2 (PLA2) (an important component of meconium). The present study examined whether administration of recombinant human CC10 (rhCC10) would reduce inflammation and improve lung function in a piglet model of MAS. Following meconium instillation, piglets exhibited significant physiologic dysfunction that improved significantly after surfactant administration. Analysis of tracheal aspirates revealed significant increases in both tumor necrosis factor (TNF) alpha and interleukin (IL)-8 after meconium instillation. rhCC10-treated animals had significantly lower TNF-alpha levels at 24 h (561 +/- 321 versus 1357 +/- 675 pg/mL, p < 0.05) compared with saline controls. There were no differences between rhCC10-treated and untreated groups with respect to other measured physiologic variables or inflammatory markers, including secretory PLA2 activity. Histologic analyses revealed marked inflammatory infiltrates and thickened alveolar walls, but no significant differences among rhCC10 and control animals. Newborn piglets with MAS have significant physiologic dysfunction, marked inflammatory changes and histologic abnormalities, which was partially counteracted by a single dose of exogenous surfactant and rhCC10.

  11. Deep water X-mas tree standardization -- Interchangeability approach

    SciTech Connect

    Paula, M.T.R.; Paulo, C.A.S.; Moreira, C.C.

    1995-12-31

    Aiming the rationalization of subsea operations to turn the production of oil and gas more economical and reliable, standardization of subsea equipment interfaces is a tool that can play a very important role. Continuing the program initiated some years ago, Petrobras is now harvesting the results from the first efforts. Diverless guidelineless subsea Christmas trees from four different suppliers have already been manufactured in accordance to the standardized specification. Tests performed this year in Macae (Campos Basin onshore base), in Brazil, confirmed the interchangeability among subsea Christmas trees, tubing hangers, adapter bases and flowline hubs of different manufacturers. This interchangeability, associated with the use of proven techniques, results in operational flexibility, savings in rig time and reduction in production losses during workovers. By now, 33 complete sets of subsea Christmas trees have already been delivered and successfully tested. Other 28 sets are still being manufactured by the four local suppliers. For the next five years, more than a hundred of these trees will be required for the exploration of the new discoveries. This paper describes the standardized equipment, the role of the operator in an integrated way of working with the manufacturers on the standardization activities, the importance of a frank information flow through the involved companies and how a simple manufacturing philosophy, with the use of construction jigs, has proved to work satisfactorily.

  12. Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome.

    PubMed

    Tessaris, Daniele; Matarazzo, Patrizia; Mussa, Alessandro; Tuli, Gerdi; Verna, Francesca; Fiore, Ludovica; Lala, Roberto

    2012-01-01

    McCune-Albright Syndrome (MAS) is a congenital endocrine disorder due to mosaic tissutal hyper-function. We describe a boy with a molecularly confirmed MAS, clinically evident with congenital café-au-lait spots, bone fibrous dysplasia, hyperthyroidism, and renal phosphate wasting syndrome. At 4.6 years of age he disclosed a rapid progression of peripheral puberty, so we decided to treat him with bicalutamide 25 mg/day and anastrozole 1 mg/day. Combined third generation aromatase inhibitors - competitive androgen receptor blockers were employed in familial male precocious puberty (FMPP). Combined treatment was performed for 49 months from the age of 4.6 to 6.7 years. The patient underwent clinical, laboratory, and instrumental evaluation twice a year from the first admission to the current age. This treatment caused a rapid normalization of growth velocity, subsequent reduction of penile androgenization, and stabilization of testicular volume. The therapy was well tolerated for all its duration and neither side effects, nor secondary hypothalamic activation were noted. This report provides further evidence of effectiveness and safety of combined third generation aromatase inhibitors - competitive androgen receptor blockers in male precocious peripheral puberty, firstly employed in male MAS, and contributes to expand the spectrum of disorders in which their employment may reveal promising.

  13. Multiple autoimmune syndrome with celiac disease.

    PubMed

    Harpreet, Singh; Deepak, Jain; Kiran, B

    2016-01-01

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  14. Multiple autoimmune syndrome with celiac disease

    PubMed Central

    Harpreet, Singh; Kiran, B.

    2016-01-01

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren’s syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients. PMID:28115785

  15. Technology Enhanced Learning for People with Intellectual Disabilities and Cerebral Paralysis: The MAS Platform

    NASA Astrophysics Data System (ADS)

    Colomo-Palacios, Ricardo; Paniagua-Martín, Fernando; García-Crespo, Ángel; Ruiz-Mezcua, Belén

    Education for students with disabilities now takes place in a wide range of settings, thus, including a wider range of assistive tools. As a result of this, one of the most interesting application domains of technology enhanced learning is related to the adoption of learning technologies and designs for people with disabilities. Following this unstoppable trend, this paper presents MAS, a software platform aimed to help people with severe intellectual disabilities and cerebral paralysis in their learning processes. MAS, as a technology enhanced learning platform, provides several tools that supports learning and monitoring for people with special needs, including adaptative games, data processing and monitoring tools. Installed in a special needs education institution in Madrid, Spain, MAS provides special educators with a tool that improved students education processes.

  16. Factor analysis of 27Al MAS NMR spectra for identifying nanocrystalline phases in amorphous geopolymers.

    PubMed

    Urbanova, Martina; Kobera, Libor; Brus, Jiri

    2013-11-01

    Nanostructured materials offer enhanced physicochemical properties because of the large interfacial area. Typically, geopolymers with specifically synthesized nanosized zeolites are a promising material for the sorption of pollutants. The structural characterization of these aluminosilicates, however, continues to be a challenge. To circumvent complications resulting from the amorphous character of the aluminosilicate matrix and from the low concentrations of nanosized crystallites, we have proposed a procedure based on factor analysis of (27)Al MAS NMR spectra. The capability of the proposed method was tested on geopolymers that exhibited various tendencies to crystallize (i) completely amorphous systems, (ii) X-ray amorphous systems with nanocrystalline phases, and (iii) highly crystalline systems. Although the recorded (27)Al MAS NMR spectra did not show visible differences between the amorphous systems (i) and the geopolymers with the nanocrystalline phase (ii), the applied factor analysis unambiguously distinguished these materials. The samples were separated into the well-defined clusters, and the systems with the evolving crystalline phase were identified even before any crystalline fraction was detected by X-ray powder diffraction. Reliability of the proposed procedure was verified by comparing it with (29)Si MAS NMR spectra. Factor analysis of (27)Al MAS NMR spectra thus has the ability to reveal spectroscopic features corresponding to the nanocrystalline phases. Because the measurement time of (27)Al MAS NMR spectra is significantly shorter than that of (29)Si MAS NMR data, the proposed procedure is particularly suitable for the analysis of large sets of specifically synthesized geopolymers in which the formation of the limited fractions of nanocrystalline phases is desired.

  17. Chicken parvovirus and its associations with malabsorption syndrome.

    PubMed

    Finkler, F; Lima, D A; Cerva, C; Moraes, L B; Cibulski, S P; Teixeira, T F; Santos, H F; Almeida, L L; Roehe, P M; Franco, A C

    2016-08-01

    Malabsorption syndrome (MAS) is a multifactorial syndrome which is characterized by enteric disorders and reduced growth rates of broilers. Such condition is responsible for significant economic losses to the poultry industry. A possible association between chicken parvovirus (ChPV) infections and the occurrence of MAS has been proposed. However, such association has not to date been elucidated in view that ChPV has been detected in healthy as well as in MAS-affected chickens. This study aimed to detect and quantify ChPV loads in sera and tissues of MAS-affected, as well as in healthy broilers. Fifty nine, 39-day-old broilers (50 diseased, 9 healthy birds), obtained from the same flocks, were examined. The highest ChPV DNA loads were detected in MAS-affected broilers, particularly in fecal samples and intestinal tissues (~5500 genomic copies/300ng of total DNA). The average viral genome load in serum in MAS-affected birds was 1134copies/mL, whereas no viral DNA was found in sera and thymus tissues from healthy animals. These findings reveal that MAS-affected broilers consistently carry ChPV DNA is serum, whereas healthy animals do not. In addition, viral loads in tissues (bursa of Fabricius, spleen, intestine and liver) of MAS-affected birds were significantly higher in comparison to the same tissues from healthy broilers. Although preliminary, the results obtained here indicate an association between the detection of ChPV DNA in serum, in addition to high ChPV viral loads in tissues, and the occurrence of MAS in broilers. Further experiments should be performed to confirm such results.

  18. The use of selected plasma enzyme activities for the diagnosis of fatty liver-hemorrhagic syndrome in laying hens.

    PubMed

    Diaz, G J; Squires, E J; Julian, R J

    1999-01-01

    Profiles of plasma enzymes were compared in two strains of single comb white leghorn laying hens, a normal commercial strain and strain UCD-003, which is highly susceptible to fatty liver-hemorrhagic syndrome. Plasma activity of lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) averaged 194 +/- 27, 4.0 +/- 2.8, 146 +/- 20, 1.0 +/- 1.0, and 1041 +/- 268 U/liter, respectively in normal birds. Activities of LDH, GDH, AST, and ALT, but not CK, were significantly higher in UCD-003 than in normal hens. A bimodal distribution of activities of all enzymes was found in the UCD-003 hens, with some birds showing activities comparable with those of the normal hens and others with values that were 2-10 times greater than those found in normal hens. These results are consistent with the extensive hepatic lesions observed in the UCD-003 strain of birds. Average gross hemorrhagic scores from visual inspection (scale of 0-3) were 0.28 +/- 0.45 in normal birds and 1.63 +/- 0.94 in the UCD-003 birds. Even though no clear relationship was found between plasma enzyme activities and the extent of liver hemorrhage in individual birds, the UCD-003 hens consistently had average values significantly higher for plasma enzymes that indicate liver damage. The results suggest that measurement of enzyme activities indicative of liver damage in birds, particularly AST, LDH, and GDH, is a valuable tool in the diagnosis of fatty liver-hemorrhagic syndrome in a flock of layers.

  19. Pulsed field gradient multiple-quantum MAS NMR spectroscopy of half-integer spin quadrupolar nuclei

    NASA Astrophysics Data System (ADS)

    Fyfe, C. A.; Skibsted, J.; Grondey, H.; Meyer zu Altenschildesche, H.

    1997-12-01

    Pulsed field gradients (PFGs) have been applied to select coherence transfer pathways in multiple-quantum (MQ) MAS NMR spectra of half-integer spin quadrupolar nuclei in rigid solids. 27Al triple-quantum (3Q) MAS NMR spectra of the aluminophosphate molecular sieves VPI-5 and AlPO 4-18 have been used to demonstrate the selection of the (0)→(3)→(-1) coherence transfer pathway using PFGs and no phase cycling. Compared to MQMAS experiments that employ phase cycling schemes, the main advantage of the PFG-MQMAS technique is its simplicity, which should facilitate the combination of MQMAS with other pulse sequences.

  20. Abdominal obesity, insulin resistance, and the metabolic syndrome: contribution of physical activity/exercise.

    PubMed

    Ross, Robert; Després, Jean-Pierre

    2009-12-01

    The metabolic syndrome, a constellation of metabolic abnormalities, which include abdominal obesity, insulin resistance, an atherogenic dyslipidemia, elevated blood pressure, a prothrombotic profile, and inflammation is associated with an increased risk of type 2 diabetes (1), cardiovascular disease (2), and mortality (3). The prevalence of individuals with these clustering abnormalities has been steadily increasing over the past two decades, is now estimated to affect at least a quarter of the US population, and is particularly prevalent among older adults (4). Similarly, abdominal obesity, as crudely estimated by an elevated waist circumference, is the most prevalent manifestation of the metabolic syndrome and affects 36% of men and 52% of women, according to the 1999-2000 US National Health and Nutrition Examination Study (5).

  1. Amniotic Band Syndrome, Perinatal Hospice, and Palliative Care versus Active Management

    PubMed Central

    Faye, Justin; Chadee, Annika; Gottimukkala, Sri; Upadhyay, Ruchi; Lara, Carla; Rajegowda, Benamanahalli H.; Corwin, Andrew D.; Lala, Rasila V.; Vernon, Jessica; Nuritdinova, Dilfuza; Chasen, Stephen

    2016-01-01

    Introduction. Amniotic band syndrome and sequence are a relatively rare condition in which congenital anomalies occur as a result of the adherence and entrapment of fetal parts with coarse fibrous bands of the amniotic membrane. A large percentage of reported cases have an atypical gestational history. The frequency of this obstetric complication is not affected by fetal gender, genetic abnormality, or prenatal infection. Case. A 21-year-old, G1P0 female parturient at 18 weeks and 5 days with a single intrauterine gestation during a routine ultrasound evaluation was noted to have amniotic band sequence. The pregnancy was subsequently complicated by preterm premature rupture of membranes with oligohydramnios, resulting in a surviving neonate scheduled for rehabilitative treatment. Conclusion. Amniotic band syndrome is an uncommon congenital anomaly resulting in multiple disfiguring and disabling manifestations. Several theories are proposed with most involving early rupture of the amnion and entanglement of fetal parts by amniotic bands. This syndrome can be manifested by development of multiple malformations, with the majority of the defects being limb abnormalities of a disorganized nature, as in the case we present. In the absence of a clear etiology of consequential congenital abnormalities, obstetric management guidelines should use shared decision models to focus on the quality of life for the offspring. PMID:28025631

  2. Using Video Modeling, Prompting, and Behavior-Specific Praise to Increase Moderate-to-Vigorous Physical Activity for Young Children with down Syndrome

    ERIC Educational Resources Information Center

    Adamo, Elyse K.; Wu, Jenny; Wolery, Mark; Hemmeter, Mary Louise; Ledford, Jennifer R.; Barton, Erin E.

    2015-01-01

    Children with Down syndrome may be at increased risk of problems associated with inactivity. Early intervention to increase physical activity may lead to increased participation in typical activities and long-term increases in quality of life (e.g., decreased likelihood of obesity-related illness). A multi-component intervention, including video…

  3. SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome

    PubMed Central

    Rose, Thomas; Szelinski, Franziska; Lisney, Anna; Reiter, Karin; Fleischer, Sarah J; Burmester, Gerd R; Radbruch, Andreas; Hiepe, Falk; Grützkau, Andreas; Biesen, Robert; Dörner, Thomas

    2016-01-01

    Objectives To evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS). Methods 31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjögren's syndrome disease activity index (ESSDAI). SIGLEC1 expression on monocytes was analysed using flow cytometry. IP-10 concentrations were determined using Bioplex human Cytokine 27-plex kit. Spearman rank test (SRT) was used for correlation analysis and Mann-Whitney U (MWU) to test for differences between glandular and extraglandular manifestations. Results An activated IFN system was detected by an upregulation of SIGLEC1 expression in 64.5% and by elevated serum level of IP-10 in 78.9% of our patients with pSS. In a subsequent analysis SIGLEC1 expression was found to be upregulated more frequently in patients with extraglandular manifestations (16/16, 100%) compared to patients with exclusively glandular involvement (4/15, 27%). SIGLEC1 expression could significantly discriminate between these two disease subgroups (p=0.0001, MWU) with a positive predictive value (PPV) of 80% for extraglandular disease. Moreover, the expression correlated with disease activity (p=0.005, r=0.54, SRT). Serum IP-10 levels neither differed significantly between glandular and extraglandular disease nor correlated with ESSDAI. Conclusions Our results indicate that increased SIGLEC1 expression characterises patients with systemic involvement and high disease activity. Therefore, SIGLEC1 determination might be of value for subset definition, risk stratification and differential therapeutic considerations in pSS. PMID:28123773

  4. Benefits of Omega-3 Fatty Acids Supplementation on Serum Paraoxonase 1 Activity and Lipids Ratios in Polycystic Ovary Syndrome

    PubMed Central

    Mohammadi, Elahe; Rafraf, Maryam

    2012-01-01

    Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with increased risk of cardiovascular disease. The purpose of this study was to investigate the ef¬fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Methods: This double-blind randomized controlled clinical trial was conducted on 64 PCOS pa¬tients with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks. Fasting blood samples, anthropometric measure¬ments and dietary intakes were collected at the beginning and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were measured using the enzymatic methods. LDL-C con¬centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured. Data were analyzed using SPSS software. Results: Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both) and significantly increased serum PON1 activity (P = 0.048) compared with placebo. Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively). Conclusion: Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women. PMID:24688934

  5. A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.

    PubMed

    Caratão, Nadine; Cortesão, Catarina S; Reis, Pedro H; Freitas, Raquel F; Jacob, Cristina M A; Pastorino, Antonio C; Carneiro-Sampaio, Magda; Barreto, Vasco M

    2013-08-01

    Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.

  6. Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations

    PubMed Central

    2012-01-01

    Myelodysplastic syndromes (MDS) are often accompanied by autoimmune phenomena. The underlying mechanisms for these associations remain uncertain, although T cell activation seems to be important. Human T-lymphotropic virus (HTLV-1) has been detected in patients with myelodysplastic syndromes, mostly in regions of the world which are endemic for the virus, and where association of HTLV-1 with rheumatological manifestation is not rare. We present here the case of a 58 year old man who presented with cytopenias, leukocytoclastic vasculitis of the skin and glomerulopathy, and was diagnosed as MDS (refractory anemia with excess blasts - RAEB 1). The patient also tested positive for HTLV-1 by PCR. After 8 monthly cycles of 5-azacytidine he achieved a complete hematologic remission. Following treatment, a second PCR for HTLV-1 was carried out and found to be negative. This is the first report in the literature of a HTLV-1-positive MDS with severe autoimmune manifestations, which was treated with the hypomethylating factor 5-azacitidine, achieving cytogenetic remission with concomitant resolution of the autoimmune manifestations, as well as HTLV-1-PCR negativity. HTLV-1-PCR negativity may be due to either immune mediated clearance of the virus, or a potential antiretroviral effect of 5-azacytidine. 5-azacytidine is known for its antiretroviral effects, although there is no proof of its activity against HTLV-1 infection in vivo. PMID:22214262

  7. Comparison of the White-Nose Syndrome Agent Pseudogymnoascus destructans to Cave-Dwelling Relatives Suggests Reduced Saprotrophic Enzyme Activity

    PubMed Central

    Reynolds, Hannah T.; Barton, Hazel A.

    2014-01-01

    White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans’ saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth. PMID:24466096

  8. Reduced thrombosis in Klkb1−/− mice is mediated by increased Mas receptor, prostacyclin, Sirt1, and KLF4 and decreased tissue factor

    PubMed Central

    Stavrou, Evi X.; Fang, Chao; Merkulova, Alona; Alhalabi, Omar; Grobe, Nadja; Antoniak, Silvio; Mackman, Nigel

    2015-01-01

    The precise mechanism for reduced thrombosis in prekallikrein null mice (Klkb1−/−) is unknown. Klkb1−/− mice have delayed carotid artery occlusion times on the rose bengal and ferric chloride thrombosis models. Klkb1−/− plasmas have long-activated partial thromboplastin times and defective contact activation–induced thrombin generation that partially corrects upon prolonged incubation. However, in contact activation–induced pulmonary thromboembolism by collagen/epinephrine or long-chain polyphosphate, Klkb1−/− mice, unlike F12−/− mice, do not have survival advantage. Klkb1−/− mice have reduced plasma BK levels and renal B2R mRNA. They also have increased expression of the renal receptor Mas and plasma prostacyclin. Increased prostacyclin is associated with elevated aortic vasculoprotective transcription factors Sirt1 and KLF4. Treatment of Klkb1−/− mice with the Mas antagonist A-779, COX-2 inhibitor nimesulide, or Sirt1 inhibitor splitomicin lowers plasma prostacyclin and normalizes arterial thrombosis times. Treatment of normal mice with the Mas agonist AVE0991 reduces thrombosis. Klkb1−/− mice have reduced aortic tissue factor (TF) mRNA, antigen, and activity. In sum, Klkb1−/− mice have a novel mechanism for thrombosis protection in addition to reduced contact activation. This pathway arises when bradykinin delivery to vasculature is compromised and mediated by increased receptor Mas, prostacyclin, Sirt1, and KLF4, leading to reduced vascular TF. PMID:25339356

  9. The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells.

    PubMed

    Villalobos, Laura A; San Hipólito-Luengo, Álvaro; Ramos-González, Mariella; Cercas, Elena; Vallejo, Susana; Romero, Alejandra; Romacho, Tania; Carraro, Raffaele; Sánchez-Ferrer, Carlos F; Peiró, Concepción

    2016-01-01

    Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro(7)-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  10. The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells

    PubMed Central

    Villalobos, Laura A.; San Hipólito-Luengo, Álvaro; Ramos-González, Mariella; Cercas, Elena; Vallejo, Susana; Romero, Alejandra; Romacho, Tania; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2016-01-01

    Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases. PMID:28018220

  11. 47 CFR 101.1317 - Competitive bidding procedures for mutually exclusive MAS EA applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Competitive bidding procedures for mutually exclusive MAS EA applications. 101.1317 Section 101.1317 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems...

  12. Advanced instrumentation for DNP-enhanced MAS NMR for higher magnetic fields and lower temperatures.

    PubMed

    Matsuki, Yoh; Idehara, Toshitaka; Fukazawa, Jun; Fujiwara, Toshimichi

    2016-03-01

    Sensitivity enhancement of MAS NMR using dynamic nuclear polarization (DNP) is gaining importance at moderate fields (B0<9T) and temperatures (T>90K) with potential applications in chemistry and material sciences. However, considering the ever-increasing size and complexity of the systems to be studied, it is crucial to establish DNP under higher field conditions, where the spectral resolution and the basic NMR sensitivity tend to improve. In this perspective, we overview our recent efforts on hardware developments, specifically targeted on improving DNP MAS NMR at high fields. It includes the development of gyrotrons that enable continuous frequency tuning and rapid frequency modulation for our 395 GHz-600 MHz and 460 GHz-700 MHz DNP NMR spectrometers. The latter 700 MHz system involves two gyrotrons and a quasi-optical transmission system that combines two independent sub-millimeter waves into a single dichromic wave. We also describe two cryogenic MAS NMR probe systems operating, respectively, at T ∼ 100K and ∼ 30K. The latter system utilizes a novel closed-loop helium recirculation mechanism, achieving cryogenic MAS without consuming any cryogen. These instruments altogether should promote high-field DNP toward more efficient, reliable and affordable technology. Some experimental DNP results obtained with these instruments are presented.

  13. Moderate MAS enhances local (1)H spin exchange and spin diffusion.

    PubMed

    Roos, Matthias; Micke, Peter; Saalwächter, Kay; Hempel, Günter

    2015-11-01

    Proton NMR spin-diffusion experiments are often combined with magic-angle spinning (MAS) to achieve higher spectral resolution of solid samples. Here we show that local proton spin diffusion can indeed become faster at low (<10 kHz) spinning rates as compared to static conditions. Spin diffusion under static conditions can thus be slower than the often referred value of 0.8 nm(2)/ms, which was determined using slow MAS (Clauss et al., 1993). The enhancement of spin diffusion by slow MAS relies on the modulation of the orientation-dependent dipolar couplings during sample rotation and goes along with transient level crossings in combination with dipolar truncation. The experimental finding and its explanation is supported by density matrix simulations, and also emphasizes the sensitivity of spin diffusion to the local coupling topology. The amplification of spin diffusion by slow MAS cannot be explained by any model based on independent spin pairs; at least three spins have to be considered.

  14. Considerations for Consortia as States Transition Away from AA-MAS. NCEO Brief. Number 7

    ERIC Educational Resources Information Center

    National Center on Educational Outcomes, 2014

    2014-01-01

    States with an alternate assessment based on modified achievement standards (AA-MAS) that received a flexibility waiver from some of the requirements of No Child Left Behind are required to phase out their use of this assessment. And, on August 23, 2013, the U.S. Department of Education published a proposed rollback of regulation that allowed the…

  15. Successfully Transitioning from the AA-MAS to the General Assessment. NCEO Policy Directions. Number 22

    ERIC Educational Resources Information Center

    Lazarus, Sheryl; Thurlow, Martha; Christensen, Laurene; Shyyan, Vitaliy

    2014-01-01

    Federal policy initiatives such as the flexibility waivers for accountability are requiring that states transition away from the use of an alternate assessment based on modified achievement standards (AA-MAS). It is expected that those students who had participated in that assessment will instead participate in the state's general assessment (or a…

  16. An Analysis of the Rise and Fall of the AA-MAS Policy

    ERIC Educational Resources Information Center

    Lazarus, Sheryl S.; Thurlow, Martha L.; Ysseldyke, James E.; Edwards, Lynn M.

    2015-01-01

    In 2005, to address concerns about students who might fall in the "gap" between the regular assessment and the alternate assessment based on alternate achievement standards (AA-AAS), the U.S. Department of Education announced that states could develop alternate assessments based on modified achievement standards (AA-MAS). This article…

  17. 48 CFR 538.270 - Evaluation of multiple award schedule (MAS) offers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Evaluation of multiple... and Administering Federal Supply Schedules 538.270 Evaluation of multiple award schedule (MAS) offers... determining the Government's price negotiation objectives, consider the following factors: (1)...

  18. Performance of RINEPT is amplified by dipolar couplings under ultrafast MAS conditions.

    PubMed

    Zhang, Rongchun; Ramamoorthy, Ayyalusamy

    2014-06-01

    The refocused insensitive nuclei enhanced by polarization transfer (RINEPT) technique is commonly used for heteronuclear polarization transfer in solution and solid-state NMR spectroscopy. Suppression of dipolar couplings, either by fast molecular motions in solution or by a combination of MAS and multiple pulse sequences in solids, enables the polarization transfer via scalar couplings. However, the presence of unsuppressed dipolar couplings could alter the functioning of RINEPT, particularly under fast/ultrafast MAS conditions. In this study, we demonstrate, through experiments on rigid solids complemented by numerical simulations, that the polarization transfer efficiency of RINEPT is dependent on the MAS frequency. In addition, we show that heteronuclear dipolar coupling is the dominant factor in the polarization transfer, which is strengthened by the presence of (1)H-(1)H dipolar couplings. In fact, the simultaneous presence of homonuclear and heteronuclear dipolar couplings is the premise for the polarization transfer by RINEPT, whereas the scalar coupling plays an insignificant role under ultrafast MAS conditions on rigid solids. Our results additionally reveal that the polarization transfer efficiency decreases with the increasing duration of RF pulses used in the RINEPT sequence.

  19. The Multidimensional Attitudes Scale toward Persons with Disabilities (MAS): Construction and Validation

    ERIC Educational Resources Information Center

    Findler, Liora; Vilchinsky, Noa; Werner, Shirli

    2007-01-01

    This study presents the development of a new instrument, the "Multidimensional Attitudes Scale Toward Persons With Disabilities" (MAS). Based on the multidimensional approach, it posits that attitudes are composed of three dimensions: affect, cognition, and behavior. The scale was distributed to a sample of 132 people along with a…

  20. Effects of sarin on temperature and activity of rats as a model for gulf war syndrome neuroregulatory functions.

    PubMed

    Conn, Carole A; Dokladny, Karol; Ménache, Margaret G; Barr, Edward B; Kozak, Wieslaw; Kozak, Anna; Wachulec, Maceij; Rudolph, Karin; Kluger, Matthew J; Henderson, Rogene F

    2002-10-15

    Coexposure to subclinical levels of nerve gas and to heat stress may have induced some of the clinical symptoms of the Gulf War Syndrome. We tested the hypothesis that single or repeated subclinical exposure to sarin, particularly under conditions of heat stress, would impair regulation of body temperature and locomotor activity. Male F344 rats were housed at 25 degrees C or under mild heat stress at 32 degrees C and were exposed 1 h/day for 1, 5, or 10 days to 0, 0.2, or 0.4 mg/m(3) of sarin in a nose-only exposure system. Body temperature and activity were monitored continuously by telemetry during exposure and 1 month postexposure. Exposed rats showed no clinical symptoms of toxicity such as tremors, despite evidence of reduced red blood cell cholinesterase activity. Heat stress consistently elevated body temperature in unexposed animals, particularly during the dark period when animals are most active. Inhalation of sarin gas at the two subclinical levels did not affect body temperature acutely in a biologically meaningful manner after the first exposure nor after 5 or 10 repeated exposures, either at thermoneutral ambient temperature or during chronic heat stress. There were no consistent effects of sarin or housing temperature on activity. The data suggest that subclinical levels of sarin have minimal effects on temperature regulation and locomotor activity under these observation conditions.

  1. The metabolic profile of lemon juice by proton HR-MAS NMR: the case of the PGI Interdonato Lemon of Messina.

    PubMed

    Cicero, Nicola; Corsaro, Carmelo; Salvo, Andrea; Vasi, Sebastiano; Giofré, Salvatore V; Ferrantelli, Vincenzo; Di Stefano, Vita; Mallamace, Domenico; Dugo, Giacomo

    2015-01-01

    We have studied by means of High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) the metabolic profile of the famous Sicilian lemon known as 'Interdonato Lemon of Messina PGI'. The PGI Interdonato Lemon of Messina possesses high organoleptic and healthy properties and is recognised as one of the most nutrient fruits. In particular, some of its constituents are actively studied for their chemo-preventive and therapeutic properties. In this paper, we have determined by means of HR-MAS NMR spectroscopy the molar concentration of the main metabolites constituent the juice of PGI Interdonato Lemon of Messina in comparison with that of the not-PGI Interdonato Lemon of Turkey. Our aim is to develop an analytical technique, in order to determine a metabolic fingerprint able to reveal commercial frauds in national and international markets.

  2. Milnacipran is active in models of irritable bowel syndrome and abdominal visceral pain in rodents.

    PubMed

    Depoortère, Ronan; Meleine, Mathieu; Bardin, Laurent; Aliaga, Monique; Muller, Emilie; Ardid, Denis; Newman-Tancredi, Adrian

    2011-12-15

    The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, a serotonin/noradrenalin reuptake inhibitor, has recently been approved in the USA for fibromyalgia, a chronic pathology characterized by diffused/chronic musculoskeletal pain, and a high prevalence of irritable bowel syndrome. Here, we determined its antinociceptive efficacy in two visceral pain tests in rodents: the acetic acid-induced writhing model in mice and the butyrate/colonic distension assay in rats, a model of irritable bowel syndrome. Acute milnacipran (5-40 mg/kgi.p.) significantly and dose-dependently reduced writhing (72.2 ± 3.2 versus 17.0 ± 4.1 writhes at 40 mg/kg). Following repeated administration (40 m/kgi.p. for 5 days), milnacipran preserved its ability to significantly reduce writhing (76 ± 8.3 versus 21.1 ± 6.7 writhes). Similarly, in the butyrate model, acute milnacipran (17.5 and 35 mg/kg, i.p.) significantly and dose-dependently increased cramps induction thresholds (from 45.7 ± 5.7 to 66.3 ± 4.8 and 75.6 ± 2.9 mm Hg, for 17.5 and 35 mg/kg, respectively) and reduced the number of cramps (from 3.0 ± 0.8 to 1.2 ± 0.8 and 0.3 ± 0.3 following inflation of an intra-rectal balloon. To summarise, milnacipran was efficacious in the writhing test, after acute and semi-chronic administration. This effect was confirmed after acute administration in a more specific model of colonic hypersensitivity induced by butyrate. This suggests that milnacipran has potential clinical application in the treatment of visceral pain, such as in irritable bowel syndrome, highly co-morbid with fibromyalgia.

  3. [Syndromes 2. Pfeiffer syndrome].

    PubMed

    Freihofer, H P

    1998-07-01

    Acrocephalosyndactylias are syndromes characterized by abnormalities of the head (craniosynostosis), the face (hypertelorism, retromaxillism), hands and feet (cutaneous or bony syndactyly). Inheritance is autosomal dominant, but spontaneous cases are described also. The group is divided into several syndromes with varying penetrance and expressivity. As an example of an acrocephalosyndactylia is the Pfeiffer syndrome presented.

  4. Defining global syndromes of fire and the relationship of these to biomes, climate and human activity

    NASA Astrophysics Data System (ADS)

    Lehmann, C.; Archibald, S.; Gomez-Dans, J.; Bradstock, R.

    2012-12-01

    Fire is a ubiquitous component of the Earth system that remains poorly understood. To date, global scale understanding of fire is limited largely to the annual extent of burning as detected by satellites. This is problematic because fire is multi-dimensional, and focus on individual metrics belies both the complexity and importance of fire within the Earth system. In an applied sense, the lack of a unified understanding of fire impedes estimation of GHG emissions or prediction of future fire regimes as a consequence of changing patterns of climate and land use. To address this we identified five key characteristics of fire regimes: size, frequency, intensity, season and extent. We combined new global datasets with existing datasets to examine cross-correlations among characteristics. We demonstrate that only certain combinations of fire characteristics are possible and this likely reflects fundamental energetic constraints derived from interactions between under-lying fuel types, climate and rates of re-growth post-fire. For example, very intense fires can only occur infrequently because a system requires a lengthy period to develop sufficient fuel to burn. Further, very cool fires only occur infrequently because fuels are not available to burn. Following, we applied a clustering algorithm to these data to determine whether we could identify syndromes of fire regimes. Pyromes, as global syndromes of fire are conceptually analogous to biomes (global syndromes of vegetation) where the extent of each pyrome is determined solely as a product of the fire characteristics themselves. A point of difference to biomes being that no one has previously attempted to quantify the global range of fire syndromes. We identified five pyromes, four of which we believe represent distinctions between crown, litter and grass-fuelled fires. The relationship of pyromes to biomes and climate are not deterministic as different biomes and climates may be represented within a single pyrome

  5. Thrombocytose au cours d'un syndrome d'activation macrophagique compliquant un lupus érythémateux systémique

    PubMed Central

    Lekpa, Fernando Kemta; Ndongo, Souhaïbou; Fall, Seynabou; Pouye, Abdoulaye; Ka, Mamadou Mourtalla; Moreira-Diop, Thérèse

    2014-01-01

    Le syndrome d'activation macrophagique (SAM) est une complication du lupus érythémateux systémique (LES), due à l'activation et la prolifération incontrôlée des macrophages dans la moelle osseuse. La bycytopénie voire la pancytopénie est constante. Nous rapportons un cas atypique de SAM diagnostiqué au même moment qu'un LES chez une patiente noire de 17 ans. Le tableau initial associait une fièvre, un syndrome inflammatoire, une anémie, un taux normal de leucocytes et plus surprenant, une thrombocytose. PMID:25584123

  6. The angiotensin-(1-7)/Mas axis reduces myonuclear apoptosis during recovery from angiotensin II-induced skeletal muscle atrophy in mice.

    PubMed

    Meneses, Carla; Morales, María Gabriela; Abrigo, Johanna; Simon, Felipe; Brandan, Enrique; Cabello-Verrugio, Claudio

    2015-09-01

    Angiotensin-(1-7) [Ang (1-7)] is a peptide belonging to the non-classical renin-angiotensin system (RAS). Ang (1-7), through its receptor Mas, has an opposite action to angiotensin II (Ang II), the typical peptide of the classical RAS axis. Ang II produces skeletal muscle atrophy, a pathological condition characterised by the loss of strength and muscle mass. A feature of muscle atrophy is the decrease of the myofibrillar proteins produced by the activation of the ubiquitin-proteasome pathway (UPP), evidenced by the increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. In addition, it has been described that Ang II also induces myonuclear apoptosis during muscle atrophy. We assessed the effects of Ang (1-7) and Mas participation on myonuclear apoptosis during skeletal muscle atrophy induced by Ang II. Our results show that Ang (1-7), through Mas, prevents the effects induced by Ang II in the diaphragm muscles and decreases several events associated with apoptosis in the diaphragm (increased apoptotic nuclei, increased expression of caspase-8 and caspase-9, increased caspase-3 activity and increased Bax/Bcl-2 ratio). Concomitantly, Ang (1-7) also attenuates the decrease in fibre diameter and muscle strength, and prevents the increase in atrogin-1 and MuRF-1 during the muscle wasting induced by Ang II. Interestingly, these effects of Ang (1-7) are dependent on the Mas receptor. Thus, we demonstrated for the first time that Ang (1-7) prevents myonuclear apoptosis during the recovery of skeletal muscle atrophy induced by Ang II.

  7. Docetaxel-associated myalgia–arthralgia syndrome in patients with breast cancer

    PubMed Central

    Seguin, Chelsea; Kovacevich, Natalie; Voutsadakis, Ioannis A

    2017-01-01

    Background As taxanes are increasingly used in oncology, the myalgia–arthralgia syndrome (M-AS) that represents an adverse effect of these drugs is becoming more common. Nevertheless, information regarding predisposing factors, prevention, and therapy of the syndrome is still lacking. Patients and methods Women who had received docetaxel as part of the FEC-D(T) regimen for the adjuvant treatment of breast cancer were retrospectively identified from the records of our oncology department. Data on demographics, disease specifics, adverse effects, and treatment were reviewed. Patients were divided into two groups: those who developed M-AS after docetaxel treatment and those who did not develop the syndrome. The two groups were compared to identify risk factors for M-AS. Effectiveness of drugs used for M-AS was evaluated. Results Sixty-seven patients were identified as fulfilling the inclusion criteria. Nineteen patients developed the M-AS after the first docetaxel administration. Forty-eight patients did not develop the syndrome. Three patients in this group were excluded because they had been taking gabapentin or pregabalin at the time of docetaxel administration for another indication. The remaining 45 patients constituted the control group. The two groups were similar in age, menopause status, stage of their cancer, and histology. The M-AS group had a higher median body surface area and was more likely to receive less than the three intended cycles of docetaxel. Nonsteroidal anti-inflammatory drugs, atypical antiepileptics, extended corticosteroids, and opioids were drugs used as M-AS treatments. Conclusion Docetaxel-associated M-AS is an adverse effect causing incomplete drug treatment. Possible risk factors and effectiveness of treatments for the syndrome are presented. PMID:28176956

  8. Activity Patterns in Response to Symptoms in Patients Being Treated for Chronic Fatigue Syndrome: An Experience Sampling Methodology Study

    PubMed Central

    2016-01-01

    Objective: Cognitive–behavioral models of chronic fatigue syndrome (CFS) propose that patients respond to symptoms with 2 predominant activity patterns—activity limitation and all-or-nothing behaviors—both of which may contribute to illness persistence. The current study investigated whether activity patterns occurred at the same time as, or followed on from, patient symptom experience and affect. Method: Twenty-three adults with CFS were recruited from U.K. CFS services. Experience sampling methodology (ESM) was used to assess fluctuations in patient symptom experience, affect, and activity management patterns over 10 assessments per day for a total of 6 days. Assessments were conducted within patients’ daily life and were delivered through an app on touchscreen Android mobile phones. Multilevel model analyses were conducted to examine the role of self-reported patient fatigue, pain, and affect as predictors of change in activity patterns at the same and subsequent assessment. Results: Current experience of fatigue-related symptoms and pain predicted higher patient activity limitation at the current and subsequent assessments whereas subjective wellness predicted higher all-or-nothing behavior at both times. Current pain predicted less all-or-nothing behavior at the subsequent assessment. In contrast to hypotheses, current positive affect was predictive of current activity limitation whereas current negative affect was predictive of current all-or-nothing behavior. Both activity patterns varied at the momentary level. Conclusions: Patient symptom experiences appear to be driving patient activity management patterns in line with the cognitive–behavioral model of CFS. ESM offers a useful method for examining multiple interacting variables within the context of patients’ daily life. PMID:27819461

  9. Enhanced Nitric Oxide Synthase Activation via Protease-Activated Receptor 2 Is Involved in the Preserved Vasodilation in Aortas from Metabolic Syndrome Rats.

    PubMed

    Maruyama, Kana; Kagota, Satomi; McGuire, John J; Wakuda, Hirokazu; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2015-01-01

    Endothelium-dependent vasodilation via protease-activated receptor 2 (PAR2) is preserved in mesenteric arteries from SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome even though nitric oxide (NO)-mediated vasodilation is attenuated. Therefore, we examined the PAR2 mechanisms underlying metabolic syndrome-resistant vasodilation in SHRSP.ZF aortas with ageing. In isolated aortas, the PAR2 agonist 2-furoyl-LIGRLO-amide (2fly) caused vasodilation that was sustained in male SHRSP.ZF until 18 weeks of age, but was attenuated afterwards compared with age-matched Wistar-Kyoto rats (controls) at 23 weeks. In contrast, acetylcholine-induced vasodilation was impaired in SHRSP.ZF already at 18 weeks of age. Treatments of aortas with inhibitors of NO synthase and soluble guanylate cyclase abolished the sustained 2fly- and residual acetylcholine-induced vasodilation in SHRSP.ZF at 18 weeks of age. In the aortas of SHRSP.ZF, 8-bromo-cGMP-induced vasodilation, NO production and cGMP accumulation elicited by 2fly were not different from in the controls. PAR2 agonist increased phospho-Ser1177-eNOS protein content only in SHRSP.ZF aortas. These results indicate that vasodilation mediated by PAR2 is sustained even though NO-dependent relaxation is attenuated with ageing/exposure to metabolic disorders in large-caliber arteries from SHRSP.ZF. PAR2 stimulation of NO production via an additional pathway that targets phosphorylation of Ser1177-eNOS suggests a regulatory mechanism for sustaining agonist-mediated vasodilation in metabolic syndrome.

  10. Activation of a cryptic splice site in the growth hormone receptor associated with growth hormone insensitivity syndrome in a genetic isolate of Laron Syndrome

    SciTech Connect

    Schiavi, A.; Bartlett, R.; Brown, M.

    1994-09-01

    Laron syndrome (LS) is a rare, autosomal recessive disease found worldwide. Despite various ethnic differences, all patients with LS described display classic dysmorphic features and extreme short stature due to defects in the growth hormone receptor (GHR). The vast majority of these patients are sporadic occurrences resulting from consanguineous matings; however, an Ecuadorian genetic isolate of LS has been reported. Our investigations have identified a genetic isolate of LS of Anglo Saxon origin. Seven individuals, by all clinical and biochemical criteria, have LS. As a result of extensive review of family and medical histories we have constructed a pedigree tracing the lineage of our affected patients through the 17th century. No GHR gross deletions were detected using an exon-specific PCR assay developed in our laboratory. Previous molecular analyses have identified mutations in exons 2-7 in numerous patients with classical LS. Single strand conformational polymorphism (SSCP) analysis was performed on GHR exons 2-7, and a marked conformational shift was noted in exon 7. Cycle sequencing of exon 7 from three affected individuals, and from four first-degree relatives, revealed a C{r_arrow}T transition at position 766 of the cDNA, and a heterozygous C{r_arrow}T transition at the identical position in the obligate carriers studied. This mutation is predicted to activate a cryptic donor splice site 63 base pairs upstream from the 3{prime} end of exon 7, effectively truncating the GHR cDNA without changing the reading frame. The resultant GHR protein is shortened by a proposed 21 amino acids. The identification and conformation of this mutation not only identifies a novel mutation in the GHR, and the first to be described in LS patients of English descent, but also allows for comparisons between genotypes and phenotypes in an inbred population.

  11. Hyperspectral Microwave Atmospheric Sounder (HyMAS) Architecture and Design Accommodations

    NASA Technical Reports Server (NTRS)

    Hilliard, Lawrence; Racette, Paul; Blackwell, William; Galbraith, Christopher; Thompson, Erik

    2013-01-01

    The Hyperspectral Microwave Atmospheric Sounder (HyMAS) is being developed at Lincoln Laboratories and accommodated by the Goddard Space Flight Center for a flight opportunity on a NASA research aircraft. The term "hyperspectral microwave" is used to indicate an all-weather sounding that performs equivalent to hyperspectral infrared sounders in clear air with vertical resolution of approximately 1 km. Deploying the HyMAS equipped scanhead with the existing Conical Scanning Microwave Imaging Radiometer (CoSMIR) shortens the path to a flight demonstration. Hyperspectral microwave is achieved through the use of independent RF antennas that sample the volume of the Earth s atmosphere through various levels of frequencies, thereby producing a set of dense, spaced vertical weighting functions. The simulations proposed for HyMAS 118/183-GHz system should yield surface precipitation rate and water path retrievals for small hail, soft hail, or snow pellets, snow, rainwater, etc. with accuracies comparable to those of the Advanced Technology Microwave Sounder. Further improvements in retrieval methodology (for example, polarization exploitation) are expected. The CoSMIR instrument is a packaging concept re-used on HyMAS to ease the integration features of the scanhead. The HyMAS scanhead will include an ultra-compact Intermediate Frequency Processor (IFP) module that is mounted inside the door to improve thermal management. The IFP is fabricated with materials made of Low-Temperature Co-fired Ceramic (LTCC) technology integrated with detectors, amplifiers, A/D conversion and data aggregation. The IFP will put out 52 channels of 16 bit data comprised of 4-9 channel data streams for temperature profiles and 2-8 channel streams for water vapor. With the limited volume of the existing CoSMIR scanhead and new HyMAS front end components, the HyMAS team at Goddard began preliminary layout work inside the new drum. Importing and re-using models of the shell, the scan head computer

  12. Hyperspectral Microwave Atmospheric Sounder (HyMAS) architecture and design accommodations

    NASA Astrophysics Data System (ADS)

    Hilliard, L.; Racette, P.; Blackwell, W.; Galbraith, C.; Thompson, E.

    The Hyperspectral Microwave Atmospheric Sounder (HyMAS) is being developed at Lincoln Laboratories and accommodated by the Goddard Space Flight Center for a flight opportunity on a NASA research aircraft. The term “ hyperspectral microwave” is used to indicate an all-weather sounding that performs equivalent to hyperspectral infrared sounders in clear air with vertical resolution of approximately 1 km. Deploying the HyMAS equipped scanhead with the existing Conical Scanning Microwave Imaging Radiometer (CoSMIR) shortens the path to a flight demonstration. Hyperspectral microwave is achieved through the use of independent RF antennas that sample the volume of the Earth's atmosphere through various levels of frequencies, thereby producing a set of dense, spaced vertical weighting functions. The simulations proposed for HyMAS 118/183-GHz system should yield surface precipitation rate and water path retrievals for small hail, soft hail, or snow pellets, snow, rainwater, etc. with accuracies comparable to those of the Advanced Technology Microwave Sounder. Further improvements in retrieval methodology (for example, polarization exploitation) are expected. The CoSMIR instrument is a packaging concept re-used on HyMAS to ease the integration features of the scanhead. The HyMAS scanhead will include an ultra-compact Intermediate Frequency Processor (IFP) module that is mounted inside the door to improve thermal management. The IFP is fabricated with materials made of Low-Temperature Co-fired Ceramic (LTCC) technology integrated with detectors, amplifiers, A/D conversion and data aggregation. The IFP will put out 52 channels of 16 bit data comprised of 4 - 9 channel data streams for temperature profiles and 2-8 channel streams for water vapor. With the limited volume of the existing CoSMIR scanhead and new HyMAS front end components, the HyMAS team at Goddard began preliminary layout work inside the new drum. Importing and re-using models of the shell, the s- an head

  13. Effectiveness of Anise Oil for Treatment of Mild to Moderate Depression in Patients With Irritable Bowel Syndrome: A Randomized Active and Placebo-Controlled Clinical Trial.

    PubMed

    Mosaffa-Jahromi, Maryam; Tamaddon, Ali-Mohammad; Afsharypuor, Suleiman; Salehi, Alireza; Seradj, Seyed Hassan; Pasalar, Mehdi; Jafari, Peyman; Lankarani, Kamran Bagheri

    2017-01-01

    Depression is a prevalent disorder among patients suffering from irritable bowel syndrome. The current study was performed to evaluate the effect of a traditional Persian medicine product, anise oil, in removing the symptoms of mild to moderate depression in patients with irritable bowel syndrome. In a randomized double-blinded active and placebo controlled clinical trial, 120 participants with mild to moderate depression according to the Beck Depression Inventory-II total scores were categorized into 3 equal groups and received anise oil, Colpermin, and placebo. The results at the end of trial (week 4) and follow-up (week 6) demonstrated significant priority against active and placebo groups. Although the mechanism is unknown yet, anise oil could be a promising choice of treatment for depressed patients with irritable bowel syndrome.

  14. A single amino acid deletion in the matrix protein of porcine reproductive and respiratory syndrome virus confers resistance to a polyclonal swine antibody with broadly neutralizing activity.

    PubMed

    Trible, Benjamin R; Popescu, Luca N; Monday, Nicholas; Calvert, Jay G; Rowland, Raymond R R

    2015-06-01

    Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection.

  15. Moebius Syndrome

    MedlinePlus

    ... children with Moebius syndrome have some degree of autism. There are four recognized categories of Moebius syndrome: ... children with Moebius syndrome have some degree of autism. There are four recognized categories of Moebius syndrome: ...

  16. Hydro-Methanolic Extract of Cornus Mas L. and Blood Glucose, Lipid Profile and Hematological Parameters of Male Rats

    PubMed Central

    Abdollahi, Bita; Mesgari Abbasi, Mehran; Zakeri Milani, Parvin; Nourdadgar, Ashraf Sadat; Banan Khojasteh, Seyyed Mehdi; Nejati, Vahid

    2014-01-01

    Background: Cornus mas L, an olive-shaped red-colored single-seeded fruit, is used in traditional medicine in different parts of Europe and Asia. Objectives: In the present study, 40 male Wistar rats were randomly divided into five groups, and the effects of 21 days of intraperitoneally (IP) administration of 50, 200 and 400 mg/kg body weight of C. mas hydro-methanolic extract on the rats hematological and biochemical parameters were investigated. The experimental study was carried out in Tabriz, Iran. Materials and Methods: The hematology and biochemical tests were performed by the Technicon H1 Hematology Analyzer and enzymatic methods, respectively. Results: The results indicated that all doses of the extract caused significant (P < 0.05) decreases in the hemoglobin distribution width (HDW) (2.3 ± 0.2 vs. 2.5 ± 0.2, P = 0.049) and platelet distribution width (PDW) (56.5 ± 1.8 vs. 63.9 ± 3.6, P = 0.001) of the treated groups vs. control group, whereas only high doses caused significant elevation in the mean corpuscular hemoglobin concentration (MCHC) (30.3 ± 0.8 vs. 28.6 ± 0.6, P = 0.047), mean platelet volume (MPV) (5.0 ± 0.6 vs. 4.1 ± 0.3, P = 0.002), total platelet mass (PCT) (0.33 ± 0.07 vs. 0.26 ± 0.01, P = 0.050), and significant decrease in the red cell distribution width (RDW) (13.8 ± 0.4 vs. 14.7 ± 1.3, P = 0.048) of the treated groups vs. control group. Conclusions: Decreasing effect of the extract on platelet activity might classify it as an alternative for antiplatelet therapy in cardiovascular diseases (CVD). The results of this study suggested that further investigations with higher doses of C. mas fruit extract are necessary to obtain significant protective and nonprotective changes in hematological and biochemical parameters. PMID:25031858

  17. Plasma fatty acid composition, estimated desaturase activities, and intakes of energy and nutrient in Japanese men with abdominal obesity or metabolic syndrome.

    PubMed

    Kawashima, Aiko; Sugawara, Shiori; Okita, Misako; Akahane, Takemi; Fukui, Kennichi; Hashiuchi, Maiko; Kataoka, Chieko; Tsukamoto, Ikuyo

    2009-01-01

    To examine predictive factors for abdominal obesity or metabolic syndrome, we investigated the association of plasma fatty acid composition, estimated desaturase activity, and nutrient intakes, with abdominal obesity or metabolic syndrome in Japanese males. Clinical characteristics, the fatty acid composition of plasma cholesteryl esters, and energy and nutrient intakes were analyzed in 3 groups: metabolic syndrome (MS, n=24), abdominal obesity (OB, n=43), and control (n=27). The estimated desaturase activities were calculated by the ratio of 16:1n-7/16:0, 18:3n-6/18:2n-6, and 20:4n-6/20:3n-6 in plasma cholesteryl esters as surrogates of the measure of the delta 9, delta 6, delta 5 desaturase (D9-16D, D6D and D5D) activities, respectively. Plasma fatty acid composition did not differ significantly between the OB group and the control group. The MS group had higher levels of palmitoleic, oleic, and gamma-linolenic acids, but a lower level of linoleic acid than the control. Stronger D6D activity and weaker D5D activity were observed in the OB group. A higher level of D9-16D activity as well as a higher level of D6D activity and a lower level of D5D activity was observed in the MS group. A logistic regression analysis showed that the low D5D activity and high D9-16D activity were predictive of the development of abdominal obesity from controls (odds ratio=0.39, p<0.05) and metabolic syndrome from abdominal obesity (odds ratio=2.44, p<0.05), respectively. In the multiple linear regression analysis, D5D activity positively correlated with the intake of eicosapentaenoic acid (EPA). In conclusion, the estimated D5D activity was a predictive factor for abdominal obesity and the estimated D9-16D activity was a predictive factor for developing metabolic syndrome from abdominal obesity in Japanese male subjects. Dietary intake of EPA would play an important role in preventing abdominal obesity and the development of metabolic syndrome.

  18. How do kV and mAs affect CT lesion detection performance?

    NASA Astrophysics Data System (ADS)

    Huda, W.; Ogden, K. M.; Shah, K.; Jadoo, C.; Scalzetti, E. M.; Lavallee, R. L.; Roskopf, M. L.

    2007-03-01

    The purpose of this study was to investigate how output (mAs) and x-ray tube voltage (kV) affect lesion detection in CT imaging. An adult Rando phantom was scanned on a GE LightSpeed CT scanner at x-ray tube voltages from 80 to 140 kV, and outputs from 90 to 360 mAs. Axial images of the abdomen were reconstructed and viewed on a high quality monitor at a soft tissue display setting. We measured detection of 2.5 to 12.5 mm sized lesions using a 2 Alternate Forced Choice (2-AFC) experimental paradigm that determined lesion contrast (I) corresponding to a 92% accuracy (I 92%) of lesion detection. Plots of log(I 92%) versus log(lesion size) were all approximately linear. The slope of the contrast detail curve was ~ -1.0 at 90 mAs, close to the value predicted by the Rose model, but monotonically decreased with increasing mAs to a value of ~ -0.7 at 360 mAs. Increasing the x-ray tube output by a factor of four improved lesion detection by a factor of 1.9 for the smallest lesion (2.5 mm), close to the value predicted by the Rose model, but only by a factor of 1.2 for largest lesion (12.5 mm). Increasing the kV monotonically decreased the contrast detail slopes from -1.02 at 80 kV to -0.71 at 140 kV. Increasing the x-ray tube voltage from 80 to 140 kV improved lesion detection by a factor of 2.8 for the smallest lesion (2.5 mm), but only by a factor of 1.7 for largest lesion (12.5 mm). We conclude that: (i) quantum mottle is an important factor for low contrast lesion detection in images of anthropomorphic phantoms; (ii) x-ray tube voltage has a much greater influence on lesion detection performance than x-ray tube output; (iii) the Rose model only predicts CT lesion detection performance at low x-ray tube outputs (90 mAs) and for small lesions (2.5 mm).

  19. Current Concepts in the Management of Meconium Aspiration Syndrome.

    PubMed

    Chettri, Subhash; Bhat, B Vishnu; Adhisivam, B

    2016-10-01

    In developing countries, meconium aspiration syndrome (MAS) is an important cause of morbidity and mortality among neonates. The concepts of pathophysiology and management of meconium stained amniotic fluid (MSAF) and meconium aspiration syndrome have undergone tremendous change in recent years. Routine intranatal and postnatal endotracheal suctioning of meconium in vigorous infants is no longer recommended. Recent studies have challenged its role even in non-vigorous infants. Supportive therapy like oxygen supplementation, mechanical ventilation and intravenous fluids are the cornerstone in the management of meconium aspiration syndrome. Availability of surfactant, inhaled nitric oxide, high frequency ventilators and extracorporeal membrane oxygenation has made it possible to salvage more infants with meconium aspiration syndrome. In this review the authors have discussed the current concepts in the pathophysiology and management of MAS. Drugs in trials and future therapeutic targets are also discussed briefly.

  20. Participation and Performance Reporting for the Alternate Assessment Based on Modified Achievement Standards (AA-MAS). Technical Report 58

    ERIC Educational Resources Information Center

    Albus, Deb; Thurlow, Martha L.; Lazarus, Sheryl S.

    2011-01-01

    This report examines publicly reported participation and performance data for the alternate assessment based on modified achievement standards (AA-MAS). The authors' analysis of these data included all states publicly reporting AA-MAS data, regardless of whether they had received approval to use the results for Title I accountability calculations.…

  1. States' Participation Guidelines for Alternate Assessments Based on Modified Academic Achievement Standards (AA-MAS) in 2009. Synthesis Report 75

    ERIC Educational Resources Information Center

    Lazarus, Sheryl S.; Hodgson, Jennifer; Thurlow, Martha L.

    2010-01-01

    All students, including students with disabilities, must be included in state accountability systems as required by law. In April 2007, federal regulations provided states the flexibility to offer another assessment option--an Alternate Assessment based on Modified Achievement Standards (AA-MAS) for some students with disabilities. The AA-MAS is…

  2. Role of Nijmegen Breakage Syndrome Protein in Specific T-Lymphocyte Activation Pathways

    PubMed Central

    García-Pérez, Miguel Angel; Allende, Luis M.; Corell, Alfredo; Paz-Artal, Estela; Varela, Pilar; López-Goyanes, Alberto; García-Martin, Francisco; Vázquez, Rosario; Sotoca, Amalia; Arnaiz-Villena, Antonio

    2001-01-01

    Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by immunodeficiency, microcephaly, and “bird-like” facies. NBS shares some clinical features with ataxia telangiectasia (AT), including increased sensitivity to ionizing radiation, increased spontaneous and induced chromosome fragility, and strong predisposition to lymphoid cancers. The mutated gene that results in NBS codes for a novel double-stranded DNA break repair protein, named nibrin. In the present work, a Spanish NBS patient was extensively characterized at the immunological and the molecular DNA levels. He showed low CD3+-cell numbers and an abnormal low CD4+ naive cell/CD4+ memory cell ratio, previously described in AT patients and also described in the present report in the NBS patient. The proliferative response of peripheral blood lymphocytes in vitro to mitogens is deficient in NBS patients, but the possible link among NBS mutations and the abnormal immune response is still unknown. PMID:11427422

  3. Hypothenar Hammer Syndrome Caused by Recreational Sports Activities and Muscle Anomaly in the Wrist

    SciTech Connect

    Kreitner, Karl-Friedrich; Dueber, Christoph; Mueller, Lars-Peter; Degreif, Juergen

    1996-09-15

    A 34-year-old man with digital ischemia is reported. Angiography revealed thromboembolic occlusions of the proper digital arteries of the index, middle, and ring fingers and a tortuous ulnar artery in Guyon's canal. Though hypothenar hammer syndrome was suspected, there was no relevant occupational history. Magnetic resonance imaging and magnetic resonance angiography demonstrated an anomalous muscular sling around the ulnar artery immediately adjacent to the hook of the hamate. The ulnar artery showed mural thrombi in its tortuous segment. These findings were confirmed during operative exploration. After thrombectomy and embolectomy the involved segment of the ulnar artery was replaced by an autologous vein graft. Postoperatively there was complete resolution of the symptoms. Only during convalescence did it become clear that the patient was a passionate golfer.

  4. How do sex hormones modify arrhythmogenesis in long QT syndrome? Sex hormone effects on arrhythmogenic substrate and triggered activity.

    PubMed

    Odening, Katja E; Koren, Gideon

    2014-11-01

    Gender differences in cardiac repolarization and the arrhythmogenic risk of patients with inherited and acquired long QT syndromes are well appreciated clinically. Enhancing our knowledge of the mechanisms underlying these differences is critical to improve our therapeutic strategies for preventing sudden cardiac death in such patients. This review summarizes the effects of sex hormones on the expression and function of ion channels that control cardiac cell excitation and repolarization as well as key proteins that regulate Ca(2+) dynamics at the cellular level. Moreover, it examines the role of sex hormones in modifying the dynamic spatiotemporal (regional and transmural) heterogeneities in action potential duration (eg, the arrhythmogenic substrate) and the susceptibility to (sympathetic) triggered activity at the tissue, organ, and whole animal levels. Finally, it explores the implications of these effects on the management of patients with LQTS.

  5. Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome.

    PubMed

    Tate, Elizabeth D; Pranzatelli, Michael R; Verhulst, Steven J; Markwell, Stephen J; Franz, David Neal; Graf, William D; Joseph, S Anne; Khakoo, Yasmin N; Lo, Warren D; Mitchell, Wendy G; Sivaswamy, Lalitha

    2012-07-01

    To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.

  6. Sanfilippo D syndrome: Estimation of N-acetylglucosamine-6-sulfatase activity with a radiolabeled monosulfated disaccharide substrate

    SciTech Connect

    Freeman, C.; Hopwood, J.J.

    1989-02-01

    N-Acetylglucosamine-6-sulfatase activity was assayed by incubation of the radiolabeled disaccharide O-(a-N-acetylglucosamine-6-sulfate)-(1----3)-L-(6-/sup 3/H)-idonic acid (GlcNAc6S-IdOA), with homogenates of leucocytes, cultured fibroblasts, and urine from normal individuals, patients affected with N-acetylglucosamine-6-sulfatase-deficiency (Sanfilippo D syndrome, mucopolysaccharidosis type IIID), and patients affected with other mucopolysaccharidoses and lysosomal storage disorders. The assay clearly distinguished affected homozygotes from their obligate heterozygotes and normal controls and other lysosomal storage disorders. Sulfatase activity in fibroblasts, leucocytes, and urine toward GlcNAc6S-IdOA exhibited a pH optimum at 4.2, 4.5, and 5.1, respectively. Sulfatase activity in fibroblasts had an apparent Km of 7.2 microM and was significantly inhibited by both sulfate and phosphate ions. The action of fibroblast or leucocyte N-acetylglucosamine-6-sulfatase activity toward GlcNAc6S-IdOA is recommended for the routine enzymatic detection and classification of mucopolysaccharidosis type IIID patients.

  7. Comparison of dietary intake and physical activity between women with and without polycystic ovary syndrome: a review.

    PubMed

    Lin, Annie W; Lujan, Marla E

    2014-09-01

    Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age worldwide. In addition to deleterious effects on fertility imparted by PCOS, women with PCOS are at increased risk of obesity, diabetes, cardiovascular disease, depression, and certain cancers. Hormonal and metabolic aberrations in PCOS have the potential to influence dietary intake and physical activity levels. There are emerging global data that women with PCOS have different baseline dietary energy intakes compared with women without PCOS. These alterations in diet may exacerbate clinical symptoms and compound risk of chronic disease in patients. Few studies have compared baseline physical activity levels between women with and without PCOS. Although comparisons between studies are confounded by several factors, the data point to no differences in activity levels among PCOS and non-PCOS groups. This review provides an assessment of the current literature on baseline dietary intake and physical activity levels in women with PCOS. Future recommendations to strengthen research in this area are provided, given the implications to aid in the development of effective nutrition-focused interventions for PCOS.

  8. Biochemical Activities of the Wiskott-Aldrich Syndrome Homology Region 2 Domains of Sarcomere Length Short (SALS) Protein.

    PubMed

    Tóth, Mónika Ágnes; Majoros, Andrea Kinga; Vig, Andrea Teréz; Migh, Ede; Nyitrai, Miklós; Mihály, József; Bugyi, Beáta

    2016-01-08

    Drosophila melanogaster sarcomere length short (SALS) is a recently identified Wiskott-Aldrich syndrome protein homology 2 (WH2) domain protein involved in skeletal muscle thin filament regulation. SALS was shown to be important for the establishment of the proper length and organization of sarcomeric actin filaments. Here, we present the first detailed characterization of the biochemical activities of the tandem WH2 domains of SALS (SALS-WH2). Our results revealed that SALS-WH2 binds both monomeric and filamentous actin and shifts the monomer-filament equilibrium toward the monomeric actin. In addition, SALS-WH2 can bind to but fails to depolymerize phalloidin- or jasplakinolide-bound actin filaments. These interactions endow SALS-WH2 with the following two major activities in the regulation of actin dynamics: SALS-WH2 sequesters actin monomers into non-polymerizable complexes and enhances actin filament disassembly by severing, which is modulated by tropomyosin. We also show that profilin does not influence the activities of the WH2 domains of SALS in actin dynamics. In conclusion, the tandem WH2 domains of SALS are multifunctional regulators of actin dynamics. Our findings suggest that the activities of the WH2 domains do not reconstitute the presumed biological function of the full-length protein. Consequently, the interactions of the WH2 domains of SALS with actin must be tuned in the cellular context by other modules of the protein and/or sarcomeric components for its proper functioning.

  9. Lung ultrasound findings in meconium aspiration syndrome.

    PubMed

    Piastra, Marco; Yousef, Nadya; Brat, Roselyne; Manzoni, Paolo; Mokhtari, Mostafa; De Luca, Daniele

    2014-09-01

    Meconium aspiration syndrome (MAS) is a rare and life-threatening neonatal lung injury induced by meconium in the lung and airways. Lung ultrasound (LUS) is a quick, easy and cheap imaging technique that is increasingly being used in critical care settings, also for newborns. In this paper we describe ultrasound findings in MAS. Six patients with MAS of variable severity were examined by LUS during the first hours of life. Chest X-rays were used as reference. The following dynamic LUS signs were seen in all patients: (1) B-pattern (interstitial) coalescent or sparse; (2) consolidations; (3) atelectasis; (4) bronchograms. No pattern was observed for the distribution of signs in lung areas, although the signs varied with time, probably due to the changing localisation of meconium in the lungs. LUS images corresponded well with X-ray findings. In conclusion, we provide the first formal description of LUS findings in neonates with MAS. LUS is a useful and promising tool in the diagnosis and management of MAS, providing real-time bedside imaging, with the additional potential benefit of limiting radiation exposure in sick neonates.

  10. Peroxisome Proliferator-Activated Receptor-γGene Expression and Its Association with Oxidative Stress in Patients with Metabolic Syndrome

    PubMed Central

    Hatami, Mehdi; Saidijam, Massoud; Yadegarzari, Reza; Borzuei, Shiva; Soltanian, Alireza; Arian, Marzieh Safi

    2016-01-01

    Regulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene plays an important role in controlling the metabolism of lipids and inflammatory processes. Therefore, it can be associated with the pathogenesis of metabolic syndrome (MetS). The purpose of this study was to determine the expression of this gene in peripheral blood mononuclear cells (PBMC) in patients with metabolic syndrome. Using real-time polymerase chain reaction (PCR), mRNA expression of PPAR-γ was found in PBMC from 37 subjects with MetS and 30 healthy controls. Serum levels of glucose and lipid profiles were measured. The total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) test. Malondialdehyde (MDA) was determined using a fluorimetric method. Total oxidant status (TOS) in serum was assayed according to oxidation of ferric to ferrous in the presence of methyl orange. Super oxide dismutase (SOD) activity was measured using a Randox kit. Expression of PPAR-γ gene was significantly increased in patients with MetS compared to the control subjects (p=0.002). There was no difference in serum levels of TAC, MDA and SOD between the two study groups, but a significant difference was observed in the TOS (p=0.03). Serum levels of triglycerides and glucose were significantly higher in subjects with MetS. According to the results of our study, an increase in the expression of PPAR-γ in subjects with MetS indicated a possible role of PPAR-γ in the pathogenesis of this disease. PMID:27689030

  11. Amelioration of radiation-induced hematopoietic syndrome by an antioxidant chlorophyllin through increased stem cell activity and modulation of hematopoiesis.

    PubMed

    Suryavanshi, Shweta; Sharma, Deepak; Checker, Rahul; Thoh, Maikho; Gota, Vikram; Sandur, Santosh K; Sainis, Krishna B

    2015-08-01

    Hematopoietic stem cells and progenitor cells (HSPC) are low in abundance and exhibit high radiosensitivity and their ability to divide dramatically decreases following exposure to ionizing radiation. Our earlier studies have shown antiapoptotic, immune-stimulatory, and antioxidant effects of chlorophyllin, a constituent of the over the counter drug derifil. Here we describe the beneficial effects of chlorophyllin against radiation-induced hematopoietic syndrome. Chlorophyllin administration significantly enhanced the abundance of HSPC in vivo. It induced a transient cell cycle arrest in lineage-negative cells in the bone marrow. However, the chlorophyllin-treated mice exposed to whole body irradiation (WBI) had a significantly higher proportion of actively dividing HSPC in the bone marrow as compared to only WBI-exposed mice. It significantly increased the number of colony forming units (CFUs) by bone marrow cells in vitro and spleen CFUs in irradiated mice in vivo. Pharmacokinetic study showed that chlorophyllin had a serum half-life of 141.8 min in mice. Chlorophyllin upregulated antiapoptotic genes and antioxidant machinery via activation of prosurvival transcription factors Nrf-2 and NF-κB and increased the survival and recovery of bone marrow cells in mice exposed to WBI. Chlorophyllin stimulated granulocyte production in bone marrow and increased the abundance of peripheral blood neutrophils by enhancing serum levels of granulocyte-colony stimulation factor (GCSF). Most importantly, prophylactic treatment of mice with chlorophyllin significantly abrogated radiation-induced mortality. Chlorophyllin mitigates radiation-induced hematopoietic syndrome by increasing the abundance of hematopoietic stem cells, enhancing granulopoiesis, and stimulating prosurvival pathways in bone marrow cells and lymphocytes.

  12. Flammer syndrome

    PubMed Central

    2014-01-01

    The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment. PMID:25075228

  13. Functional magnetic resonance imaging of cerebral activation during spinal cord stimulation in failed back surgery syndrome patients.

    PubMed

    Stancák, Andrej; Kozák, Jirí; Vrba, Ivan; Tintera, Jaroslav; Vrána, Jirí; Polácek, Hubert; Stancák, Marián

    2008-02-01

    Spinal cord stimulation (SCS) consisting of electrical stimulation of the dorsal spinal cord using epidural electrodes has been shown to relieve chronic neuropathic pain. To analyze the cerebral activation patterns related to SCS, and to evaluate the effects of SCS on the processing of acute experimental pain, we performed functional magnetic resonance imaging (fMRI) on eight patients suffering from failed back surgery syndrome who were also being treated with SCS for severe pain in their legs and lower back. Three types of stimulation were used, each lasting 36s: (i) SCS, (ii) heat pain (HP) applied to the leg affected by neuropathic pain, and (iii) simultaneous HP and SCS. During SCS, we found increased activation of the medial primary sensorimotor cortex somatotopically corresponding to the foot and/or perineal region, contralateral posterior insula, and the ipsilateral secondary somatosensory cortex (S2). Decreased activation was seen in the bilateral primary motor cortices and the ipsilateral primary somatosensory cortex corresponding to the shoulder, elbow and hand. Compared to separately presented HP and SCS, simultaneous HP and SCS showed statistically significant activation of the bilateral inferior temporal cortex and the ipsilateral cerebellar cortex. The activation of the primary motor cortex, insula and S2 during SCS may directly interfere with the processing of neuropathic pain. When SCS is associated with heat pain, the paralimbic association cortex and cerebellum show activation exceeding the sum of activations resulting from separate SCS and heat pain stimulation. The explanation of this could possibly rest with the continuous comparisons of simultaneous pain and somatosensory sensations occurring in a single dermatome.

  14. Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein.

    PubMed

    von Kobbe, Cayetano; Harrigan, Jeanine A; Schreiber, Valérie; Stiegler, Patrick; Piotrowski, Jason; Dawut, Lale; Bohr, Vilhelm A

    2004-01-01

    Werner syndrome (WS) is a genetic premature aging disorder in which patients appear much older than their chronological age. The gene mutated in WS encodes a nuclear protein (WRN) which possesses 3'-5' exonuclease and ATPase-dependent 3'-5' helicase activities. The genomic instability associated with WS cells and the biochemical characteristics of WRN suggest that WRN plays a role in DNA metabolic pathways such as transcription, replication, recombination and repair. Recently we have identified poly(ADP-ribose) polymerase-1 (PARP-1) as a new WRN interacting protein. In this paper, we further mapped the interacting domains. We found that PARP-1 bound to the N-terminus of WRN and to the C-terminus containing the RecQ-conserved (RQC) domain. WRN bound to the N-terminus of PARP-1 containing DNA binding and BRCA1 C-terminal (BRCT) domains. We show that unmodified PARP-1 inhibited both WRN exonuclease and helicase activities, and to our knowledge is the only known WRN protein partner that inactivates both of the WRN's catalytic activities suggesting a biologically significant regulation. Moreover, this dual inhibition seems to be specific for PARP-1, as PARP-2 did not affect WRN helicase activity and only slightly inhibited WRN exonuclease activity. The differential effect of PARP-1 and PARP-2 on WRN catalytic activity was not due to differences in affinity for WRN or the DNA substrate. Finally, we demonstrate that the inhibition of WRN by PARP-1 was influenced by the poly(ADP-ribosyl)ation state of PARP-1. The biological relevance of the specific modulation of WRN catalytic activities by PARP-1 are discussed in the context of pathways in which these proteins may function together, namely in the repair of DNA strand breaks.

  15. Physical activity and self-reported symptoms of insomnia, restless legs syndrome, and depression: the comprehensive dialysis study.

    PubMed

    Anand, Shuchi; Johansen, Kirsten L; Grimes, Barbara; Kaysen, George A; Dalrymple, Lorien S; Kutner, Nancy G; Chertow, Glenn M

    2013-01-01

    Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health-related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self-reported physical activity with self-reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health-related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self-reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two-item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.

  16. Associations between Objectively Measured Physical Activity, Cardiorespiratory Fitness and Risk Factors for Metabolic Syndrome in 12- to 15-Year-Old Tianjin City Children

    ERIC Educational Resources Information Center

    Tan, Sijie; Wang, Jianxiong; Zhang, Yibing; Zhang, Chen

    2015-01-01

    Objective: The study aim was to explore associations between daily physical activity level, cardiorespiratory fitness and metabolic syndrome among Chinese children. Design: We conducted a school-based, cross-sectional study. Setting: Participants including 112 boys and 121 girls were recruited from three schools in the urban suburbs of Tianjin…

  17. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis

    PubMed Central

    Zhang, Pei; Huang, Angela; Morales-Ruiz, Manuel; Starcher, Barry C.; Huang, Yan; Sessa, William C.; Niklason, Laura E.

    2012-01-01

    Abstract Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibility of using engineered zinc-finger protein transcription factors (ZFPs) to achieve compensatory expression of haploinsufficient genes by inducing augmented expression from the remaining wild-type allele. For complex genes with multiple splice variants, this approach could have distinct advantages over cDNA-based gene replacement strategies. Targeting the elastin gene, we show that transcriptional activation by engineered ZFPs can induce compensatory expression from the wild-type allele in the setting of classic WBS and SVAS genetic mutations, increase elastin expression in wild-type cells, induce expression of the major elastin splice variants, and recapitulate their natural stoichiometry. Further, we establish that transcriptional activation of the mutant allele in SVAS does not overcome nonsense-mediated decay, and thus ZFP-mediated transcriptional activation is not likely to induce production of a mutant protein, a crucial consideration. Finally, we show in bioengineered blood vessels that ZFP-mediated induction of elastin expression is capable of stimulating functional elastogenesis. Haploinsufficiency is a common mechanism of genetic disease. These findings have significant implications for WBS and SVAS, and establish that haploinsufficiency can be overcome by targeted transcriptional activation without inducing protein expression from the mutant allele. PMID:22891920

  18. El Proyecto Sismico "LARSE" - Trabajando Hacia un Futuro con Mas Seguridad para Los Angeles

    USGS Publications Warehouse

    Henyey, Thomas L.; Fuis, Gary S.; Benthien, Mark L.; Burdette, Thomas R.; Christofferson, Shari A.; Clayton, Robert W.; Criley, Edward E.; Davis, Paul M.; Hendley, James W.; Kohler, Monica D.; Lutter, William J.; McRaney, John K.; Murphy, Janice M.; Okaya, David A.; Ryberg, Trond; Simila, Gerald W.; Stauffer, Peter H.

    1999-01-01

    La region de Los Angeles contiene una red de fallas activas, incluyendo muchas fallas por empuje que son profundas y no rompen la superficie de la tierra. Estas fallas ocultas incluyen la falla anteriormente desconocida que fue responsable por la devastacion que ocurrio durante el terremoto de Northridge en enero de 1994, el terremoto mas costoso en la historia de los Estados Unidos. El Experimento Sismico en la Region de Los Angeles (Los Angeles Region Seismic Experiment, LARSE), esta localizando los peligros ocultos de los terremotos debajo de la region de Los Angeles para mejorar la construccion de las estructuras que pueden apoyar terremotos que son inevitables en el futuro, y que ayudaran a los cientificos determinar donde occurira el sacudimento mas fuerte y poderoso.

  19. MAS NMR of the Drug Resistant S31N M2 Proton Transporter from Influenza A

    PubMed Central

    Andreas, Loren B.; Eddy, Matthew T.; Chou, James J.; Griffin, Robert G.

    2012-01-01

    We report chemical shift assignments of the drug-resistant S31N mutant of M218-60 determined with magic angle spinning (MAS) 3D spectra acquired with a 15N-13C ZF-TEDOR transfer followed by 13C-13C mixing by RFDR. The MAS spectra reveal two sets of resonances, indicating that the tetramer assembles as a dimer of dimers, similar to the wild type channel. The two sets of chemical shifts are shown to be in close proximity at residue H37, and assignments reveal a difference in the helix torsion angles, as predicted by TALOS+, for the key resistance residue N31. In contrast to wild type M218-60, chemical shift changes are minimal with addition of the inhibitor rimantadine, suggesting that the drug does not bind to S31N. PMID:22480220

  20. Technology Development for a Hyperspectral Microwave Atmospheric Sounder (HyMAS)

    NASA Technical Reports Server (NTRS)

    Blackwell, W.; Galbraith, C.; Hilliard, L.; Racette, P.; Thompson, E.

    2014-01-01

    The Hyperspectral Microwave Atmospheric Sounder (HyMAS) is being developed at Lincoln Laboratories and accommodated by the Goddard Space Flight Center for a flight opportunity on a NASA research aircraft. The term hyperspectral microwave is used to indicate an all-weather sounding instrument that performs equivalent to hyperspectral infrared sounders in clear air with vertical resolution of approximately 1 km. Deploying the HyMAS equipped scanhead with the existing Conical Scanning Microwave Imaging Radiometer (CoSMIR) shortens the path to a flight demonstration. Hyperspectral microwave is achieved through the use of independent RF antennas that sample the volume of the Earths atmosphere through various levels of frequencies, thereby producing a set of dense, spaced vertical weighting functions.

  1. Deuterium MAS NMR studies of dynamics on multiple timescales: histidine and oxalic acid.

    PubMed

    Chan-Huot, Monique; Wimperis, Stephen; Gervais, Christel; Bodenhausen, Geoffrey; Duma, Luminita

    2015-01-12

    Deuterium ((2) H) magic-angle spinning (MAS) nuclear magnetic resonance is applied to monitor the dynamics of the exchanging labile deuterons of polycrystalline L-histidine hydrochloride monohydrate-d7 and α-oxalic acid dihydrate-d6 . Direct experimental evidence of fast dynamics is obtained from T1Z and T1Q measurements. Further motional information is extracted from two-dimensional single-quantum (SQ) and double-quantum (DQ) MAS spectra. Differences between the SQ and DQ linewidths clearly indicate the presence of motions on intermediate timescales for the carboxylic moiety and the D2 O in α-oxalic acid dihydrate, and for the amine group and the D2 O in L-histidine hydrochloride monohydrate. Comparison of the relaxation rate constants of Zeeman and quadrupolar order with the relaxation rate constants of the DQ coherences suggests the co-existence of fast and slow motional processes.

  2. Winter Activity of Coastal Plain Populations of Bat Species Affected by White-Nose Syndrome and Wind Energy Facilities.

    PubMed

    Grider, John F; Larsen, Angela L; Homyack, Jessica A; Kalcounis-Rueppell, Matina C

    2016-01-01

    Across the entire distribution of a species, populations may have variable responses to environmental perturbations. Many bat species experience mortality in large portions of their range during hibernation and along migratory paths to and from wintering grounds, from White-nose syndrome (WNS) and wind energy development, respectively. In some areas, warm temperatures may allow bats to remain active through winter, thus decreasing their susceptibility to WNS and/or mortality associated with migration to wintering grounds. These areas could act as a refugia and be important for the persistence of local populations. To determine if warmer temperatures affect bat activity, we compared year-round activity of bat populations in the Coastal Plain and Piedmont of North Carolina, USA, two regions that differ in winter temperature. We established six recording stations, four along a 295-kilometer north-south transect in the Coastal Plain, and two in the Piedmont of North Carolina. We recorded bat activity over two years. We supplemented our recordings with mist-net data. Although bat activity was lower during winter at all sites, the odds of recording a bat during winter were higher at Coastal Plain sites when compared with Piedmont sites. Further, bats in the Piedmont had a lower level of winter activity compared to summer activity than bats in the Coastal Plain that had more similar levels of activity in the winter and summer. We found high bat species richness on the Coastal Plain in winter, with winter-active species including those known to hibernate throughout most of their range and others known to be long distance migrants. In particular, two species impacted by WNS, the northern long-eared bat (Myotis septentrionalis) and tricolored bat (Perimyotis subflavus), were present year round in the Coastal Plain. The tricolored bat was also present year-round in the Piedmont. In the Coastal Plain, the long distance migratory hoary bat (Lasiurus cinereus) was active in the

  3. Winter Activity of Coastal Plain Populations of Bat Species Affected by White-Nose Syndrome and Wind Energy Facilities

    PubMed Central

    Larsen, Angela L.; Homyack, Jessica A.; Kalcounis-Rueppell, Matina C.

    2016-01-01

    Across the entire distribution of a species, populations may have variable responses to environmental perturbations. Many bat species experience mortality in large portions of their range during hibernation and along migratory paths to and from wintering grounds, from White-nose syndrome (WNS) and wind energy development, respectively. In some areas, warm temperatures may allow bats to remain active through winter, thus decreasing their susceptibility to WNS and/or mortality associated with migration to wintering grounds. These areas could act as a refugia and be important for the persistence of local populations. To determine if warmer temperatures affect bat activity, we compared year-round activity of bat populations in the Coastal Plain and Piedmont of North Carolina, USA, two regions that differ in winter temperature. We established six recording stations, four along a 295-kilometer north-south transect in the Coastal Plain, and two in the Piedmont of North Carolina. We recorded bat activity over two years. We supplemented our recordings with mist-net data. Although bat activity was lower during winter at all sites, the odds of recording a bat during winter were higher at Coastal Plain sites when compared with Piedmont sites. Further, bats in the Piedmont had a lower level of winter activity compared to summer activity than bats in the Coastal Plain that had more similar levels of activity in the winter and summer. We found high bat species richness on the Coastal Plain in winter, with winter-active species including those known to hibernate throughout most of their range and others known to be long distance migrants. In particular, two species impacted by WNS, the northern long-eared bat (Myotis septentrionalis) and tricolored bat (Perimyotis subflavus), were present year round in the Coastal Plain. The tricolored bat was also present year-round in the Piedmont. In the Coastal Plain, the long distance migratory hoary bat (Lasiurus cinereus) was active in the

  4. Modelling Lyman α forest cross-correlations with LyMAS

    NASA Astrophysics Data System (ADS)

    Lochhaas, Cassandra; Weinberg, David H.; Peirani, Sébastien; Dubois, Yohan; Colombi, Stéphane; Blaizot, Jérémy; Font-Ribera, Andreu; Pichon, Christophe; Devriendt, Julien

    2016-10-01

    We use the Lyα Mass Association Scheme (LyMAS) to predict cross-correlations at z = 2.5 between dark matter haloes and transmitted flux in the Lyα forest, and compare to cross-correlations measured for quasars and damped Lyα systems (DLAs) from the Baryon Oscillation Spectroscopic Survey (BOSS) by Font-Ribera et al. We calibrate LyMAS using Horizon-AGN hydrodynamical cosmological simulations of a (100 h- 1 Mpc)3 comoving volume. We apply this calibration to a (1 h- 1 Gpc)3 simulation realized with 20483 dark matter particles. In the 100 h- 1 Mpc box, LyMAS reproduces the halo-flux correlations computed from the full hydrodynamic gas distribution very well. In the 1 h- 1 Gpc box, the amplitude of the large-scale cross-correlation tracks the halo bias bh as expected. We provide empirical fitting functions that describe our numerical results. In the transverse separation bins used for the BOSS analyses, LyMAS cross-correlation predictions follow linear theory accurately down to small scales. Fitting the BOSS measurements requires inclusion of random velocity errors; we find best-fitting rms velocity errors of 399 and 252 {km} {s}^{-1} for quasars and DLAs, respectively. We infer bias-weighted mean halo masses of M_h/10^{12} h^{-1} M_{⊙}=2.19^{+0.16}_{-0.15} and 0.69^{+0.16}_{-0.14} for the host haloes of quasars and DLAs, with ˜0.2 dex systematic uncertainty associated with redshift evolution, intergalactic medium parameters, and selection of data fitting range.

  5. Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection.

    PubMed

    Chen, Rui; Moriya, Junji; Luo, Xianwen; Yamakawa, Jun-ichi; Takahashi, Takashi; Sasaki, Kenroh; Yoshizaki, Fumihiko

    2009-06-01

    The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups. Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.

  6. Indirect detection of infinite-speed MAS solid-state NMR spectra

    NASA Astrophysics Data System (ADS)

    Perras, Frédéric A.; Venkatesh, Amrit; Hanrahan, Michael P.; Goh, Tian Wei; Huang, Wenyu; Rossini, Aaron J.; Pruski, Marek

    2017-03-01

    Heavy spin-1/2 nuclides are known to possess very large chemical shift anisotropies that can challenge even the most advanced magic-angle-spinning (MAS) techniques. Wide manifolds of overlapping spinning sidebands and insufficient excitation bandwidths often obfuscate meaningful spectral information and force the use of static, low-resolution solid-state (SS)NMR methods for the characterization of materials. To address these issues, we have merged fast-magic-angle-turning (MAT) and dipolar heteronuclear multiple-quantum coherence (D-HMQC) experiments to obtain D-HMQC-MAT pulse sequences which enable the rapid acquisition of 2D SSNMR spectra that correlate isotropic 1H chemical shifts to the indirectly detected isotropic ;infinite-MAS; spectra of heavy spin-1/2 nuclides. For these nuclides, the combination of fast MAS and 1H detection provides a high sensitivity, which rivals the DNP-enhanced ultra-wideline SSNMR. The new pulse sequences were used to determine the Pt coordination environments in a complex mixture of decomposition products of transplatin and in a metal-organic framework with Pt ions coordinated to the linker ligands.

  7. High-resolution proton-detected NMR of proteins at very fast MAS

    NASA Astrophysics Data System (ADS)

    Andreas, Loren B.; Le Marchand, Tanguy; Jaudzems, Kristaps; Pintacuda, Guido

    2015-04-01

    When combined with high-frequency (currently ∼60 kHz) magic-angle spinning (MAS), proton detection boosts sensitivity and increases coherence lifetimes, resulting in narrow 1H lines. Herein, we review methods for efficient proton detected techniques and applications in highly deuterated proteins, with an emphasis on 100% selected 1H site concentration for the purpose of sensitivity. We discuss the factors affecting resolution and sensitivity that have resulted in higher and higher frequency MAS. Next we describe the various methods that have been used for backbone and side-chain assignment with proton detection, highlighting the efficient use of scalar-based 13C-13C transfers. Additionally, we show new spectra making use of these schemes for side-chain assignment of methyl 13C-1H resonances. The rapid acquisition of resolved 2D spectra with proton detection allows efficient measurement of relaxation parameters used as a measure of dynamic processes. Under rapid MAS, relaxation times can be measured in a site-specific manner in medium-sized proteins, enabling the investigation of molecular motions at high resolution. Additionally, we discuss methods for measurement of structural parameters, including measurement of internuclear 1H-1H contacts and the use of paramagnetic effects in the determination of global structure.

  8. High-resolution proton-detected NMR of proteins at very fast MAS.

    PubMed

    Andreas, Loren B; Le Marchand, Tanguy; Jaudzems, Kristaps; Pintacuda, Guido

    2015-04-01

    When combined with high-frequency (currently ∼60 kHz) magic-angle spinning (MAS), proton detection boosts sensitivity and increases coherence lifetimes, resulting in narrow ((1))H lines. Herein, we review methods for efficient proton detected techniques and applications in highly deuterated proteins, with an emphasis on 100% selected ((1))H site concentration for the purpose of sensitivity. We discuss the factors affecting resolution and sensitivity that have resulted in higher and higher frequency MAS. Next we describe the various methods that have been used for backbone and side-chain assignment with proton detection, highlighting the efficient use of scalar-based ((13))C-((13))C transfers. Additionally, we show new spectra making use of these schemes for side-chain assignment of methyl ((13))C-((1))H resonances. The rapid acquisition of resolved 2D spectra with proton detection allows efficient measurement of relaxation parameters used as a measure of dynamic processes. Under rapid MAS, relaxation times can be measured in a site-specific manner in medium-sized proteins, enabling the investigation of molecular motions at high resolution. Additionally, we discuss methods for measurement of structural parameters, including measurement of internuclear ((1))H-((1))H contacts and the use of paramagnetic effects in the determination of global structure.

  9. Fast and accurate MAS-DNP simulations of large spin ensembles.

    PubMed

    Mentink-Vigier, Frédéric; Vega, Shimon; De Paëpe, Gaël

    2017-02-01

    A deeper understanding of parameters affecting Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP), an emerging nuclear magnetic resonance hyperpolarization method, is crucial for the development of new polarizing agents and the successful implementation of the technique at higher magnetic fields (>10 T). Such progress is currently impeded by computational limitation which prevents the simulation of large spin ensembles (electron as well as nuclear spins) and to accurately describe the interplay between all the multiple key parameters at play. In this work, we present an alternative approach to existing cross-effect and solid-effect MAS-DNP codes that yields fast and accurate simulations. More specifically we describe the model, the associated Liouville-based formalism (Bloch-type derivation and/or Landau-Zener approximations) and the linear time algorithm that allows computing MAS-DNP mechanisms with unprecedented time savings. As a result, one can easily scan through multiple parameters and disentangle their mutual influences. In addition, the simulation code is able to handle multiple electrons and protons, which allows probing the effect of (hyper)polarizing agents concentration, as well as fully revealing the interplay between the polarizing agent structure and the hyperfine couplings, nuclear dipolar couplings, nuclear relaxation times, both in terms of depolarization effect, but also of polarization gain and buildup times.

  10. ERP correlates of object recognition memory in Down syndrome: Do active and passive tasks measure the same thing?

    PubMed

    Van Hoogmoed, A H; Nadel, L; Spanò, G; Edgin, J O

    2016-02-01

    Event related potentials (ERPs) can help to determine the cognitive and neural processes underlying memory functions and are often used to study populations with severe memory impairment. In healthy adults, memory is typically assessed with active tasks, while in patient studies passive memory paradigms are generally used. In this study we examined whether active and passive continuous object recognition tasks measure the same underlying memory process in typically developing (TD) adults and in individuals with Down syndrome (DS), a population with known hippocampal impairment. We further explored how ERPs in these tasks relate to behavioral measures of memory. Data-driven analysis techniques revealed large differences in old-new effects in the active versus passive task in TD adults, but no difference between these tasks in DS. The group with DS required additional processing in the active task in comparison to the TD group in two ways. First, the old-new effect started 150 ms later. Second, more repetitions were required to show the old-new effect. In the group with DS, performance on a behavioral measure of object-location memory was related to ERP measures across both tasks. In total, our results suggest that active and passive ERP memory measures do not differ in DS and likely reflect the use of implicit memory, but not explicit processing, on both tasks. Our findings highlight the need for a greater understanding of the comparison between active and passive ERP paradigms before they are inferred to measure similar functions across populations (e.g., infants or intellectual disability).

  11. The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

    PubMed Central

    García-Álvarez, Isabel; Garrido, Leoncio; Romero-Ramírez, Lorenzo; Nieto-Sampedro, Manuel; Fernández-Mayoralas, Alfonso; Campos-Olivas, Ramón

    2013-01-01

    The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning (1H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the 1H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death. PMID:24194925

  12. Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

    PubMed

    van Hemmen, Judy; Veltman, Dick J; Hoekzema, Elseline; Cohen-Kettenis, Peggy T; Dessens, Arianne B; Bakker, Julie

    2016-03-01

    Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure.

  13. Delayed onset of electromyographic activity of vastus medialis obliquus relative to vastus lateralis in subjects with patellofemoral pain syndrome.

    PubMed

    Cavazzuti, L; Merlo, A; Orlandi, F; Campanini, I

    2010-07-01

    Patellofemoral Pain Syndrome (PFPS) is a common musculoskeletal complaint. The presence of a delay between vastus medialis obliquus (VMO) and vastus lateralis (VL) muscle onset has been suggested in the literature as a possible cause of PFPS, with poor agreement amongst authors on the value of the delay. In this study we computed the delay in the activation of VMO and VL in 15 PFPS patients and 20 age-matched controls (Ctrls) during the following tasks: sit to stand, stand to sit, squat, step up and step down. Activation instants were detected from surface EMG data by a double-threshold statistical detector. In order to compare the muscle activity throughout the task, we computed the delay between the instants in which the VMO and VL normalised envelopes reached subsequent normalised amplitude levels, until the envelope peak. In all investigated tasks but sit to stand, the onset delay was lower or equal then 0.02s, without group differences. Similarly, no differences between Ctrls and PFPS timing were found throughout all tasks, until the peak. Our results do not support the hypothesis that an onset delay between VMO and VL can be one of the causes of PFPS.

  14. Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

    PubMed Central

    Mandel-Brehm, Caleigh; Salogiannis, John; Dhamne, Sameer C.; Rotenberg, Alexander; Greenberg, Michael E.

    2015-01-01

    Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of-function mutations in the maternally inherited copy of the UBE3A gene, and is characterized by an absence of speech, excessive laughter, cognitive delay, motor deficits, and seizures. Despite the fact that the symptoms of AS occur in early childhood, behavioral characterization of AS mouse models has focused primarily on adult phenotypes. In this report we describe juvenile behaviors in AS mice that are strain-independent and clinically relevant. We find that young AS mice, compared with their wild-type littermates, produce an increased number of ultrasonic vocalizations. In addition, young AS mice have defects in motor coordination, as well as abnormal brain activity that results in an enhanced seizure-like response to an audiogenic challenge. The enhanced seizure-like activity, but not the increased ultrasonic vocalizations or motor deficits, is rescued in juvenile AS mice by genetically reducing the expression level of the activity-regulated cytoskeleton-associated protein, Arc. These findings suggest that therapeutic interventions that reduce the level of Arc expression have the potential to reverse the seizures associated with AS. In addition, the identification of aberrant behaviors in young AS mice may provide clues regarding the neural circuit defects that occur in AS and ultimately allow new approaches for treating this disorder. PMID:25848016

  15. Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression.

    PubMed

    Mandel-Brehm, Caleigh; Salogiannis, John; Dhamne, Sameer C; Rotenberg, Alexander; Greenberg, Michael E

    2015-04-21

    Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of-function mutations in the maternally inherited copy of the UBE3A gene, and is characterized by an absence of speech, excessive laughter, cognitive delay, motor deficits, and seizures. Despite the fact that the symptoms of AS occur in early childhood, behavioral characterization of AS mouse models has focused primarily on adult phenotypes. In this report we describe juvenile behaviors in AS mice that are strain-independent and clinically relevant. We find that young AS mice, compared with their wild-type littermates, produce an increased number of ultrasonic vocalizations. In addition, young AS mice have defects in motor coordination, as well as abnormal brain activity that results in an enhanced seizure-like response to an audiogenic challenge. The enhanced seizure-like activity, but not the increased ultrasonic vocalizations or motor deficits, is rescued in juvenile AS mice by genetically reducing the expression level of the activity-regulated cytoskeleton-associated protein, Arc. These findings suggest that therapeutic interventions that reduce the level of Arc expression have the potential to reverse the seizures associated with AS. In addition, the identification of aberrant behaviors in young AS mice may provide clues regarding the neural circuit defects that occur in AS and ultimately allow new approaches for treating this disorder.

  16. Deletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells

    PubMed Central

    Baptista, Marisa A. P.; Keszei, Marton; Oliveira, Mariana; Sunahara, Karen K. S.; Andersson, John; Dahlberg, Carin I. M.; Worth, Austen J.; Liedén, Agne; Kuo, I-Chun; Wallin, Robert P. A.; Snapper, Scott B.; Eidsmo, Liv; Scheynius, Annika; Karlsson, Mikael C. I.; Bouma, Gerben; Burns, Siobhan O.; Forsell, Mattias N. E.; Thrasher, Adrian J.; Nylén, Susanne; Westerberg, Lisa S.

    2016-01-01

    Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8+ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8+ T cells at the expense of CD4+ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8+ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells. PMID:27425374

  17. Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats.

    PubMed

    Rahman, Asadur; Fujisawa, Yoshihide; Nakano, Daisuke; Hitomi, Hirofumi; Nishiyama, Akira

    2017-01-07

    Metabolic syndrome is often associated with disruption of circadian rhythm of systemic hemodynamics and cardiovascular disease. Experiments were conducted to investigate the effects of luseogliflozin, a selective SGLT2 inhibitor, on circadian rhythm of sympathetic nervous function and locomotor activity (LA) in metabolic syndrome rats. The difference in the low frequency component of systolic blood pressure between the dark and light period significantly increased in the luseogliflozin-treated SHRcp. LA also increased in the dark period compared with the light period following luseogliflozin treatment. These data suggest that circadian rhythm of sympathetic nervous function and LA is improved by luseogliflozin in metabolic syndrome rats, which may contribute to SGLT2 inhibitor-induced improvement of cardiovascular outcomes. This article is protected by copyright. All rights reserved.

  18. Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome.

    PubMed

    Cordeddu, Viviana; Yin, Jiani C; Gunnarsson, Cecilia; Virtanen, Carl; Drunat, Séverine; Lepri, Francesca; De Luca, Alessandro; Rossi, Cesare; Ciolfi, Andrea; Pugh, Trevor J; Bruselles, Alessandro; Priest, James R; Pennacchio, Len A; Lu, Zhibin; Danesh, Arnavaz; Quevedo, Rene; Hamid, Alaa; Martinelli, Simone; Pantaleoni, Francesca; Gnazzo, Maria; Daniele, Paola; Lissewski, Christina; Bocchinfuso, Gianfranco; Stella, Lorenzo; Odent, Sylvie; Philip, Nicole; Faivre, Laurence; Vlckova, Marketa; Seemanova, Eva; Digilio, Cristina; Zenker, Martin; Zampino, Giuseppe; Verloes, Alain; Dallapiccola, Bruno; Roberts, Amy E; Cavé, Hélène; Gelb, Bruce D; Neel, Benjamin G; Tartaglia, Marco

    2015-11-01

    The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.

  19. Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt

    PubMed Central

    Ali, Mohamed A; Shehata, Mahmoud M; Gomaa, Mokhtar R; Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S; El-Taweel, Ahmed N; Atea, Mohamed; Hassan, Nagla; Bagato, Ola; Moatasim, Yassmin; Mahmoud, Sara H; Kutkat, Omnia; Maatouq, Asmaa M; Osman, Ahmed; McKenzie, Pamela P; Webby, Richard J; Kayali, Ghazi

    2017-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat. PMID:28050021

  20. Phase Cycling Schemes for finite-pulse-RFDR MAS Solid State NMR Experiments

    PubMed Central

    Zhang, Rongchun; Nishiyama, Yusuke; Sun, Pingchuan; Ramamoorthy, Ayyalusamy

    2015-01-01

    The finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used in 2D homonuclear chemical shift correlation experiments under magic angle spinning (MAS). A recent study demonstrated the advantages of using a short phase cycle, XY4, and its super-cycle, XY414, for the fp-RFDR pulse sequence employed in 2D 1H/1H single-quantum/single-quantum correlation experiments under ultrafast MAS conditions. In this study, we report a comprehensive analysis on the dipolar recoupling efficiencies of XY4, XY412, XY413, XY414, and XY814 phase cycles under different spinning speeds ranging from 10 to 100 kHz. The theoretical calculations reveal the presence of second-order terms (T10T2,±2, T1,±1T2,±1, etc.) in the recoupled homonuclear dipolar coupling Hamiltonian only when the basic XY4 phase cycle is utilized, making it advantageous for proton-proton magnetization transfer under ultrafast MAS conditions. It is also found that the recoupling efficiency of fp-RFDR is quite dependent on the duty factor (τ180/τR) as well as on the strength of homonuclear dipolar couplings. The rate of longitudinal magnetization transfer increases linearly with the duty factor of fp-RFDR for all the XY-based phase cycles investigated in this study. Examination of the performances of different phase cycles against chemical shift offset and RF field in homogeneity effects revealed that XY414 is the most tolerant phase cycle, while the shortest phase cycle XY4 suppressed the RF field inhomogeneity effects most efficiently under slow spinning speeds. Our results suggest that the difference in the fp-RFDR recoupling efficiencies decreases with the increasing MAS speed, while ultrafast (>60 kHz) spinning speed is advantageous as it recouples a large amount of homonuclear dipolar couplings and therefore enable fast magnetization exchange. The effects of higher-order terms and cross terms between various interactions in the effective Hamiltonian of fp-RFDR are also analyzed

  1. Phase cycling schemes for finite-pulse-RFDR MAS solid state NMR experiments

    NASA Astrophysics Data System (ADS)

    Zhang, Rongchun; Nishiyama, Yusuke; Sun, Pingchuan; Ramamoorthy, Ayyalusamy

    2015-03-01

    The finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used in 2D homonuclear chemical shift correlation experiments under magic angle spinning (MAS). A recent study demonstrated the advantages of using a short phase cycle, XY4, and its super-cycle, XY414, for the fp-RFDR pulse sequence employed in 2D 1H/1H single-quantum/single-quantum correlation experiments under ultrafast MAS conditions. In this study, we report a comprehensive analysis on the dipolar recoupling efficiencies of XY4, XY412, XY413, XY414, and XY814 phase cycles under different spinning speeds ranging from 10 to 100 kHz. The theoretical calculations reveal the presence of second-order terms (T10T2,±2, T1,±1T2,±1, etc.) in the recoupled homonuclear dipolar coupling Hamiltonian only when the basic XY4 phase cycle is utilized, making it advantageous for proton-proton magnetization transfer under ultrafast MAS conditions. It is also found that the recoupling efficiency of fp-RFDR is quite dependent on the duty factor (τ180/τR) as well as on the strength of homonuclear dipolar couplings. The rate of longitudinal magnetization transfer increases linearly with the duty factor of fp-RFDR for all the XY-based phase cycles investigated in this study. Examination of the performances of different phase cycles against chemical shift offset and RF field inhomogeneity effects revealed that XY414 is the most tolerant phase cycle, while the shortest phase cycle XY4 suppressed the RF field inhomogeneity effects most efficiently under slow spinning speeds. Our results suggest that the difference in the fp-RFDR recoupling efficiencies decreases with the increasing MAS speed, while ultrafast (>60 kHz) spinning speed is advantageous as it recouples a large amount of homonuclear dipolar couplings and therefore enable fast magnetization exchange. The effects of higher-order terms and cross terms between various interactions in the effective Hamiltonian of fp-RFDR are also analyzed

  2. Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats

    PubMed Central

    Chen, Ming-Xian; Chen, Yu; Fu, Rui; Liu, Sai-Yue; Yang, Qin-Qin; Shen, Tang-Biao

    2016-01-01

    The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-α and IL-1β in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-α and IL-1β induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats. PMID:28078028

  3. Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats.

    PubMed

    Chen, Ming-Xian; Chen, Yu; Fu, Rui; Liu, Sai-Yue; Yang, Qin-Qin; Shen, Tang-Biao

    2016-01-01

    The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-α and IL-1β in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-α and IL-1β induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats.

  4. Anti-white spot syndrome virus activity of Ceriops tagal aqueous extract in giant tiger shrimp Penaeus monodon.

    PubMed

    Sudheer, N S; Philip, Rosamma; Bright Singh, I S

    2012-09-01

    White spot syndrome virus (WSSV), the most contagious pathogen of cultured shrimp, causes mass mortality, leading to huge economic loss to the shrimp industry. The lack of effective therapeutic or prophylactic measures has aggravated the situation, necessitating the development of antiviral agents. With this objective, the antiviral activity in the aqueous extract of a mangrove plant Ceriops tagal in Penaeus monodon was evaluated. The Ceriops tagal aqueous extract (CTAE) was non-toxic to shrimps at 50 mg/ml when injected intramuscularly at a dosage of 10 μL/animal (0.5 mg/animal) and showed a protective effect against WSSV at 30 mg/ml when mixed with WSSV suspension at a 1:1 ratio. When the extract was administered along with the diet and the animals were challenged orally, there was a dose-dependent increase in survival, culminating in 100 % survival at a concentration of 500 mg/kg body weight/day. Neither hypertrophied nuclei nor the viral envelope protein VP28 could be demonstrated in surviving shrimps using histology and indirect immunofluorescence histochemistry (IIFH), respectively. To elucidate the mode of action, the temporal expression of WSSV genes and shrimp immune genes, including antimicrobial peptides, was attempted. None of the viral genes were found to be expressed in shrimps that were fed with the extract and challenged or in those that were administered CTAE-exposed WSSV. The overall results suggest that the aqueous extract from C. tagal can protect P. monodon from white spot syndrome virus infection.

  5. Recombinase Activating Gene 1 Deficiencies Without Omenn Syndrome May Also Present With Eosinophilia and Bone Marrow Fibrosis

    PubMed Central

    Ulusoy, Ezgi; Karaca, Neslihan Edeer; Azarsiz, Elif; Berdeli, Afig; Aksu, Guzide; Kutukculer, Necil

    2016-01-01

    Background Severe combined immunodeficiency (SCID) syndromes are a heterogenous group of diseases characterized by impairment in both cellular and humoral immunity with a range of genetic disorders. Complete recombinase activating gene (RAG) deficiency is associated with classical T-B-NK+ SCID which is the most common phenotype of Turkish SCID patients. There is a broad spectrum of hypomorfic RAG mutations including Omenn syndrome, leaky or atypical SCID with expansion of γδ T cells, autoimmunity and cytomegalovirus (CMV) infections. Methods Twenty-one (44%) patients had RAG1 deficiency of all 44 SCID patients followed up by pediatric immunology department. A retrospective analysis was conducted on the medical records of all SCID patients with RAG1 deficiency. Results Eight patients were classified as T-B-NK+ SCID, five patients as T+B-NK+ SCID (three of these were Omenn phenotype), and eight patients as T+B+NK+ SCID phenotype. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were 87.7 ± 73.8 (12 - 256), 4.4 ± 8.2 (1 - 36) and 29.1 ± 56.8 (1 - 244) months, respectively. Consanguinity was present in 11 (52%) of 21 patients. Autoimmunity was found in six patients (28%). Ten patients (47%) had CMV infection, four (19%) had Epstein-Barr virus (EBV) infections and three (14%) had Bacillus Calmette-Guerin (BCG) infections. Seven patients who had refractory cytopenia (two pancytopenia and five bicytopenia) underwent bone marrow biopsy, three of whom had bone marrow fibrosis. Future evaluations must be considered about bone marrow fibrosis in RAG1 deficiency patients. Eosinophilia was observed in 10 patients, seven of whom did not have Omenn phenotype. Conclusion Non-Omenn phenotype RAG1 deficiencies can also present with eosinophilia. This report is presented to emphasize that RAG1 mutations may lead to diverse clinical phenotypes. PMID:27081423

  6. The effect of solar-geomagnetic activity during and after admission on survival in patients with acute coronary syndromes.

    PubMed

    Vencloviene, Jone; Babarskiene, Ruta; Milvidaite, Irena; Kubilius, Raimondas; Stasionyte, Jolanta

    2014-08-01

    A number of studies have established the effects of solar-geomagnetic activity on the human cardio-vascular system. It is plausible that the heliophysical conditions existing during and after hospital admission may affect survival in patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS patients who were admitted to the Hospital of Kaunas University of Medicine, Lithuania, and who survived for more than 4 days. We evaluated the associations between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after admission, and 2-year survival, based on Cox's proportional-hazards model, controlling for clinical data. After adjustment for clinical variables, active-stormy GMA on the 2nd day after admission was associated with an increased (by 1.58 times) hazard ratio (HR) of cardiovascular death (HR=1.58, 95 % CI 1.07-2.32). For women, geomagnetic storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by 3.91 times (HR=3.91, 95 % CI 1.31-11.7); active-stormy GMA during the 2nd-3rd day after admission increased the HR by over 2.5 times (HR=2.66, 95 % CI 1.40-5.03). In patients aged over 70 years, GS occurring 1 day before or 2 days after admission, increased the HR by 2.5 times, compared to quiet days; GS in conjunction with SF on the previous day, nearly tripled the HR (HR=3.08, 95 % CI 1.32-7.20). These findings suggest that the heliophysical conditions before or after the admission affect the hazard ratio of lethal outcome; adjusting for clinical variables, these effects were stronger for women and older patients.

  7. The effect of solar-geomagnetic activity during and after admission on survival in patients with acute coronary syndromes

    NASA Astrophysics Data System (ADS)

    Vencloviene, Jone; Babarskiene, Ruta; Milvidaite, Irena; Kubilius, Raimondas; Stasionyte, Jolanta

    2014-08-01

    A number of studies have established the effects of solar-geomagnetic activity on the human cardio-vascular system. It is plausible that the heliophysical conditions existing during and after hospital admission may affect survival in patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS patients who were admitted to the Hospital of Kaunas University of Medicine, Lithuania, and who survived for more than 4 days. We evaluated the associations between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after admission, and 2-year survival, based on Cox's proportional-hazards model, controlling for clinical data. After adjustment for clinical variables, active-stormy GMA on the 2nd day after admission was associated with an increased (by 1.58 times) hazard ratio (HR) of cardiovascular death (HR = 1.58, 95 % CI 1.07-2.32). For women, geomagnetic storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by 3.91 times (HR = 3.91, 95 % CI 1.31-11.7); active-stormy GMA during the 2nd-3rd day after admission increased the HR by over 2.5 times (HR = 2.66, 95 % CI 1.40-5.03). In patients aged over 70 years, GS occurring 1 day before or 2 days after admission, increased the HR by 2.5 times, compared to quiet days; GS in conjunction with SF on the previous day, nearly tripled the HR (HR = 3.08, 95 % CI 1.32-7.20). These findings suggest that the heliophysical conditions before or after the admission affect the hazard ratio of lethal outcome; adjusting for clinical variables, these effects were stronger for women and older patients.

  8. Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women With Polycystic Ovary Syndrome

    PubMed Central

    Torchen, Laura C.; Idkowiak, Jan; Fogel, Naomi R.; O'Neil, Donna M.; Shackleton, Cedric H. L.; Arlt, Wiebke

    2016-01-01

    Context: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5α-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites. Objective: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood. Design, Setting, and Participants: Twenty-one PCOS-d, 1–3 years old, and 36 control girls of comparable age were studied at an academic medical center. Main Outcome Measures: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5α-reductase and 11β-hydroxysteroid dehydrogenase activities were calculated. Results: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P = .02). PCOS-d had increased 5α-tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5α-reductase activity. There was no evidence for differences in 11β-hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight. Conclusions: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5α-reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action. PMID:26990942

  9. Anti-inflammatory treatment of meconium aspiration syndrome: benefits and risks.

    PubMed

    Mokra, Daniela; Mokry, Juraj; Tonhajzerova, Ingrid

    2013-06-01

    Meconium aspiration syndrome (MAS) is a major cause of respiratory insufficiency in the term and post-term newborns. There are several pathomechanisms participating in this disorder, particularly the airway obstruction, surfactant dysfunction, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction. Inflammatory changes resulting from meconium aspiration cause severe impairment of lung parenchyma and surfactant, and influence the reactivity of both vascular and airway smooth muscle. Therefore, anti-inflammatory drugs may be of benefit in the management of MAS. This article reviews the pharmacological actions and side effects of various anti-inflammatory drugs used up to now in the experimental models of MAS and in the treatment of newborns with meconium aspiration.

  10. Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway

    PubMed Central

    Fan, Bo-Shi; Zhang, En-Hui; Wu, Miao; Guo, Jin-Min; Su, Ding-Feng; Liu, Xia; Yu, Jian-Guang

    2016-01-01

    On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine (Ani) is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR) mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with Ani decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with Ani (20 mg/kg and 28 mg/kg respectively, i.p.) 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist) and PNU282987 (selective α7nAChR agonist), or in α7nAChR knockout mice. Effect of Ani was also appraised in C2C12 myotubes. Ani reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by Ani. Phosphorylation of Na/K-ATPase was enhanced by Ani in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of Ani on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway. PMID:27065867

  11. [Dynamics of violations of intravascular platelet activity in rats during the formation of metabolic syndrome using fructose models].

    PubMed

    Medvedev, I N

    2016-01-01

    Objective: To trace the development of disorders intravascular platelet activity in experimental form of the metabolic syndrome. The study included 61 rat male Wistar rats at the age of 2.5-3 months. Animals were divided into 2 groups: 32 rats were given free access to drink 10% solution of fructose for 8 weeks and 29 rats were the control group. The level of the total cholesterol, high density lipoprotein cholesterol (HDLD cholesterol) and triglycerides were determined using colorimetric enzymatic method. The blood plasma content of endothelin-1 was determined by radioimmunoassay, thromboxane B2 and 6-keto-prostaglandin F(1α)--by ELISA. The total content of nitrogen oxide metabolites was revealed in blood. Intravascular platelet activity was assessed using phase contrast microscopy. In terms of fructose load in rats simultaneously with the increase of body weight and the development of biochemical disorders that are characteristic for the metabolic syndrome, there comes a marked progressive increase in intravascular platelet activity [reduction of the number of discocytes from 81.0 ± 0.1 to 61.3 ± 0.2%, increase in the number of reactive platelets from 19.0 ± 0.1 to 38.7 ± 0.2%, an increase in the number of freely moving in the blood of small units from 2.4 ± 0.0 to 14.6 ± 0.1 per 100 free platelets, and of medium and large units (from 4 or more cells) from 0.1 ± 0.03 to 2.3 ± 0.06 per 100 free platelets], largely due to the increase (p < 0.01) of the synthesis of thromboxane B2 (from 145.9 ± 0.2 to 232.6 ± 0.7 pg/ml), endothelin-4 (from 6.9 ± 0.2 to 12.5 ± 0.4 pg/ml) and reduction (p < 0.01) of the generation of 6-keto-prostaglandin F1α (from 75.9 ± 0.2 to 62.3 ± 0.4 pg/ml), and the total amount of nitric oxide metabolites (from 27.9 ± 0.3 to 23.2 ± 0.1 mmol/l).

  12. Emilia sonchifolia extract activity against white spot syndrome virus and yellow head virus in shrimp cell cultures.

    PubMed

    Maikaeo, Lamai; Chotigeat, Wilaiwan; Mahabusarakam, Wilawan

    2015-07-23

    Emilia sonchifolia (L.) DC is a plant used in traditional medicine to treat several viral and bacterial diseases. The antiviral activities of selected Sephadex LH-20 column fractions and HPLC subfractions of an acetone extract of E. sonchifolia leaves were determined in shrimp Penaeus merguiensis primary lymphoid cells infected with either white spot syndrome virus (WSSV) or yellow head virus (YHV). WSSV and YHV replication was quantified using quantitative real-time PCR tests targeted to the VP19 and ORF1b gene transcripts, respectively. In lymphoid organ cells exposed to 100 µg ml⁻¹ of either the Sephadex fraction F14 or the HPLC F14 subfraction SF4, both fractions caused reduced replication, but YHV replication was reduced only by SF4. In the asthiazolyl blue mitochondrial enzyme activity assays to assess extract cytotoxicity, >60% of primary lymphoid organ cells remained viable following exposure to 100 µg ml⁻¹ of either F14 or SF4. GC-MS analysis of the HPLC F14 subfraction SF4 showed that it contained 2,4-di-tert-butylphenol. This study is the first to show that E. sonchifolia leaf extracts might be useful as bioactive agents to protect shrimp against viruses such as WSSV and YHV.

  13. Enhancement of human DNA polymerase η activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.

    PubMed

    Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K; Griffin, Wezley C; Eoff, Robert L

    2012-12-07

    We have investigated the interaction between human DNA polymerase η (hpol η) and the Werner syndrome protein (WRN). Functional assays revealed that the WRN exonuclease and RecQ C-terminal (RQC) domains are necessary for full stimulation of hpol η-catalyzed formation of correct base pairs. We find that WRN does not stimulate hpol η-catalyzed formation of mispairs. Moreover, the exonuclease activity of WRN prevents stable mispair formation by hpol η. These results are consistent with a proofreading activity for WRN during single-nucleotide additions. ATP hydrolysis by WRN appears to attenuate stimulation of hpol η. Pre-steady-state kinetic results show that k(pol) is increased 4-fold by WRN. Finally, pulldown assays reveal a bipartite physical interaction between hpol η and WRN that is mediated by the exonuclease and RQC domains. Taken together, these results are consistent with alteration of the rate-limiting step in polymerase catalysis by direct protein-protein interactions between WRN and hpol η. In summary, WRN improves the efficiency and fidelity of hpol η to promote more effective replication of DNA.

  14. Shiga Toxin Promotes Podocyte Injury in Experimental Hemolytic Uremic Syndrome via Activation of the Alternative Pathway of Complement

    PubMed Central

    Locatelli, Monica; Buelli, Simona; Pezzotta, Anna; Corna, Daniela; Perico, Luca; Tomasoni, Susanna; Rottoli, Daniela; Rizzo, Paola; Conti, Debora; Thurman, Joshua M.; Remuzzi, Giuseppe; Zoja, Carlamaria

    2014-01-01

    Shiga toxin (Stx)–producing Escherichia coli is the offending agent of postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and widespread microvascular thrombosis. We previously documented that Stx induces glomerular complement activation, generating C3a responsible for microvascular thrombosis in experimental HUS. Here, we show that the presence of C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the glomerular basement membrane is mediated by integrins, the relevance of integrin-linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte expression of ILK increased after the injection of Stx2/LPS and preceded the upregulation of Snail and downregulation of nephrin and α-actinin-4. Factor B deficiency or pretreatment with an inhibitory antibody to factor B protected mice against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and α-actinin-4 expression. In cultured podocytes, treatment with C3a reduced α-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail and cell motility. These results suggest that Stx-induced activation of the alternative pathway of complement and generation of C3a promotes ILK signaling, leading to podocyte dysfunction and loss in Stx-HUS. PMID:24578132

  15. Diet composition and physical activity in overweight and obese premenopausal women with or without polycystic ovary syndrome.

    PubMed

    Álvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

    2011-12-01

    The polycystic ovary syndrome (PCOS) is a complex polygenic disorder in which environmental factors play an important modifying role. We aimed to find differences in diet and life-style that might contribute to the development of PCOS among overweight or obese premenopausal women. We compared diet composition and self-reported physical activity among 22 patients with PCOS and 59 women without androgen excess recruited from a total of 113 consecutive premenopausal women reporting for management of weight excess. After correcting for a difference in age between women with PCOS and controls, there were no overall statistical significant differences between them in the total caloric intake, in the intake of macro- and micro-nutrients, caffeine, fiber and alcohol, in the proportion of women exercising regularly, or in the number of hours of exercise per week. The proportion of fat in the diets of the overweight and obese women irrespective of PCOS was well-above current recommendations, yet this excessive fat intake occurred at the expense of monounsaturated fatty acids mostly. In conclusion, diet composition and physical activity were apparently not decisive for the development of PCOS among overweight and obese premenopausal women.

  16. Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists.

    PubMed

    Hager, U A; Hein, A; Lennerz, J K M; Zimmermann, K; Neuhuber, W L; Reeh, P W

    2008-01-02

    A recently described family of "orphan" receptors, called Mas-related G-protein-coupled receptors (Mrg), is preferentially expressed in small nociceptive neurons of the rodent and human dorsal root ganglia (DRG). Mrg are activated by high affinity peptide fragments derived from the proenkephalin A gene, e.g. BAM22 (bovine adrenal medullary). To study the histological distribution and functional properties of these receptors, we combined confocal immunohistochemistry in rat DRG and dermis whole mounts, using new antibodies against the rat Mas-related G-protein-coupled receptor C (MrgC), with single-fiber recordings and neurochemical experiments using isolated hind-paw skin and sciatic nerve. In lumbar DRG we found cytoplasmic MrgC labeling mainly in small- and medium-sized neurons; coexpression with isolectin B4 (46%) and transient receptor potential vanilloid receptor 1 channel protein (TRPV1) (52%) occurred frequently, whereas calcitonin gene-related peptide (CGRP) was rarely colocalized with MrgC in DRG (11%) and dermal nerve fibers (6%). One of the MrgC agonists, BAM22, more than doubled the heat-induced cutaneous CGRP release from rat and mouse skin. The effect of BAM22, also known to activate opioid receptors, was further enhanced by combination with naloxone that had no effect on its own. This sensitizing effect proved to be independent of secondary prostaglandin formation, mast cell degranulation, protein kinase C (PKC) activation and independent of TRPV1. Nonetheless, the capsaicin-induced CGRP release was also sensitized. Receptive fields of 26 mechano-heat sensitive C-fibers were treated with MrgC agonists. Only one unit was strongly and repeatedly excited and showed a profound sensitization to heat upon BAM22+naloxone. Two other established MrgC agonists (gamma2-melanocyte stimulating hormone and BAM8-22) were ineffective. Thus, BAM22 sensitizes the capsaicin- and heat-induced CGRP release in an apparently MrgC-unrelated way. The sensitization to heat

  17. Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit

    PubMed Central

    Tooth, David; Garsed, Klara; Singh, Gulzar; Marciani, Luca; Lam, Ching; Fordham, Imogen; Fields, Annie; Banwait, Rawinder; Lingaya, Melanie; Layfield, Robert; Hastings, Maggie; Whorwell, Peter; Spiller, Robin

    2014-01-01

    Objectives Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. Design Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. Results Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=−0.32, p=0.005) and HV (r=−0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140–426) to 1031 (435–2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. Conclusions The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. ClinicalTrials.gov NCT00745004. PMID:23911555

  18. Dressler's Syndrome

    MedlinePlus

    ... syndrome may also be called postpericardiotomy syndrome, post-myocardial infarction syndrome and post-cardiac injury syndrome. With recent ... Dressler's syndrome. References LeWinter MM. Pericardial complications of myocardial infarction. http://www.uptodate.com/home. Accessed May 27, ...

  19. [Prolonged erythrocytic T activation, depression of blood group A and increase of fetal hemoglobin in a myelodysplastic syndrome evolving into erythroleukemia].

    PubMed

    Gioseffi, O N; Del Río, F; Pardini, P; Kitagawa, M

    1991-04-01

    T cryptantigen can be exposed on the red cell membrane as a result of removal of terminal glycosides, either by bacterial enzymes or by incomplete synthesis of the cell membrane due to somatic mutation, usually caused by a neoplasm. T-activated erythrocytes have been observed in different pathologies, but they have not been seen associated with other abnormalities of red blood cell proteins described in myelodysplastic syndromes or acute leukaemias. A patient with initial diagnosis of refractory anaemia that evolved into erythroleukaemia showed prolonged T-activation, a depressed A blood-group antigen and an increase of foetal haemoglobin, simultaneously. The evolutive pattern of T-activation suggests more an abnormal erythropoiesis than an enzymatic effect and a certain relationship with the haemolytic syndrome.

  20. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  1. Spontaneous heparin-induced thrombocytopenia syndrome without any proximate heparin exposure, infection, or inflammatory condition: Atypical clinical features with heparin-dependent platelet activating antibodies.

    PubMed

    Okata, Takuya; Miyata, Shigeki; Miyashita, Fumio; Maeda, Takuma; Toyoda, Kazunori

    2015-01-01

    Recent studies suggest that a thromboembolic disorder resembling heparin-induced thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients without any history of heparin exposure. It is likely due to anti-platelet factor 4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial surfaces and nucleic acids. We describe an atypical case of spontaneous HIT syndrome. A 70-year-old man suddenly presented with acute cerebral sinus thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for the treatment of CST, his platelet count fell precipitously and he developed deep vein thrombosis, a clinical picture consistent with rapid-onset HIT but without any proximate episodes of heparin exposure, infection, trauma, surgery, or other acute illness. Antigen assays and a washed platelet activation assay indicated that the patient already possessed anti-PF4/heparin IgG antibodies with heparin-dependent platelet activation properties on admission. Cessation of UFH and initiation of argatroban resulted in prompt recovery of his platelet count without further thromboembolic events. We identified two similar cases in the literature. However, these patients do not meet the recently proposed criteria for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or delayed diagnosis of HIT appears to be associated with worse outcomes. We propose that these atypical cases should be included in the category of spontaneous HIT syndrome.

  2. Atypical Functional Brain Activation during a Multiple Object Tracking Task in Girls with Turner Syndrome: Neurocorrelates of Reduced Spatiotemporal Resolution

    ERIC Educational Resources Information Center

    Beaton, Elliott A.; Stoddard, Joel; Lai, Song; Lackey, John; Shi, Jianrong; Ross, Judith L.; Simon, Tony J.

    2010-01-01

    Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a…

  3. Control of Muscle Mitochondria by Insulin Entails Activation of Akt2-mtNOS Pathway: Implications for the Metabolic Syndrome

    PubMed Central

    Finocchietto, Paola; Barreyro, Fernando; Holod, Silvia; Peralta, Jorge; Franco, María C.; Méndez, Carlos; Converso, Daniela P.; Estévez, Alvaro; Carreras, Maria C.; Poderoso, Juan J.

    2008-01-01

    Background In the metabolic syndrome with hyperinsulinemia, mitochondrial inhibition facilitates muscle fat and glycogen accumulation and accelerates its progression. In the last decade, nitric oxide (NO) emerged as a typical mitochondrial modulator by reversibly inhibiting citochrome oxidase and oxygen utilization. We wondered whether insulin-operated signaling pathways modulate mitochondrial respiration via NO, to alternatively release complete glucose oxidation to CO2 and H2O or to drive glucose storage to glycogen. Methodology/Principal Findings We illustrate here that NO produced by translocated nNOS (mtNOS) is the insulin-signaling molecule that controls mitochondrial oxygen utilization. We evoke a hyperinsulinemic-normoglycemic non-invasive clamp by subcutaneously injecting adult male rats with long-lasting human insulin glargine that remains stable in plasma by several hours. At a precise concentration, insulin increased phospho-Akt2 that translocates to mitochondria and determines in situ phosphorylation and substantial cooperative mtNOS activation (+4–8 fold, P<.05), high NO, and a lowering of mitochondrial oxygen uptake and resting metabolic rate (−25 to −60%, P<.05). Comparing in vivo insulin metabolic effects on gastrocnemius muscles by direct electroporation of siRNA nNOS or empty vector in the two legs of the same animal, confirmed that in the silenced muscles disrupted mtNOS allows higher oxygen uptake and complete (U-14C)-glucose utilization respect to normal mtNOS in the vector-treated ones (respectively 37±3 vs 10±1 µmolO2/h.g tissue and 13±1 vs 7.2±1 µmol 3H2O/h.g tissue, P<.05), which reciprocally restricted glycogen-synthesis by a half. Conclusions/Significance These evidences show that after energy replenishment, insulin depresses mitochondrial respiration in skeletal muscle via NO which permits substrates to be deposited as macromolecules; at discrete hyperinsulinemia, persistent mtNOS activation could contribute to mitochondrial

  4. Down Syndrome (For Kids)

    MedlinePlus

    ... teachers and others to come up with a plan for the best way for each child to learn. Kids with Down syndrome like their playtime, too. They play sports and participate in activities, such as music lessons or dance classes. Kids with Down syndrome may ...

  5. SLOW-MAS NMR METHODS TO STUDY METABOLIC PROCESSES IN VIVO AND IN VITRO

    SciTech Connect

    Wind, Robert A.; Bertram, Hanne Christine; Hu, Jian Zhi

    2005-09-25

    In vitro and in vivo 1H NMR spectroscopy is widely used to measure metabolic profiles in cells, tissues, animals, and humans and to use them, e.g., for diagnosis and therapy response evaluations. However, the spectra often suffer from poor resolution due to variations in the isotropic bulk magnetic susceptibility present in biological objects, resulting in a broadening of the NMR lines. In principle this broadening can be averaged to zero by the technique of magic angle spinning (MAS), where the sample is rotated about an axis making an angle of 54o44’ relative to the external magnetic field. However, a problem is that in a standard MAS experiment spinning speeds of a kHz or more are required in order to avoid the occurrence of spinning sidebands (SSBs) in the spectra, which renders analysis of the spectra difficult again. At these spinning speeds the large centrifugal forces cause severe structural damage in larger biological objects, so that this method cannot be used to study metabolic processes in intact samples. In solid state NMR several methods have been developed where slow MAS is combined with special radio frequency pulse sequences to eliminate spinning side bands or separate them from the isotropic spectrum so that a SSB-free high-resolution isotropic spectrum is obtained. It has been shown recently that two methods, phase-adjusted spinning sidebands (PASS) and phase-corrected magic angle turning (PHORMAT), can successfully be modified for applications in biological materials (1, 2). With PASS MAS speeds as low as 40 Hz can be employed, allowing non or minimally invasive in vitro studies of excised tissues and organs. This method was used, amongst other things, to study post mortem changes in the proton metabolite spectra in excised rabbit muscle tissue (3). With PHORMAT the NMR sensitivity is reduced and longer measuring times are required, but with this methodology the MAS speed can be reduced to ~1 Hz. This makes PHORMAT amenable for in vivo

  6. [Locomotive syndrome and frailty. Total knee arthroplasty supports active life of the elderly].

    PubMed

    Watanabe, Toshifumi; Sekiya, Ichiro; Muneta, Takeshi

    2012-04-01

    For a society with an aging population, it is important to extend healthy life expectancy. Knee arthroplasty is one of the most successful and beneficial treatments for osteoarthritic knees, helping the elderly improve their activities of daily life. Previous reports have proved health-related quality of life improves dramatically with this surgery. In particular, pain and physical functioning scores improve significantly. Although the preoperative physical activity of each patient does affect the postoperative activity level, sufficient improvements can be expected for this procedure on the elderly. These effective improvements make the number of knee arthroplasties increase year to year. The elderly have high risks of postoperative medical complications. However, long term results are comparable or superior to those in younger patients. In elderly patients, pre-existing conditions should be carefully controlled, and postoperative complications, including infection and thrombosis, should be treated prophylactically to promote safety and postoperative recovery.

  7. A 29Si MAS-NMR study of transition metal site occupancy in forsterite

    NASA Astrophysics Data System (ADS)

    Mccarty, R. J.; Palke, A.; Stebbins, J. F.; Hartman, S.

    2012-12-01

    In this study, we address the problem of transition metal site occupancy in Mg-rich olivine using solid-state magic-angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. Transition metal substitution in olivine can occur in either of the two crystallographically unique octahedral sites: the smaller, more symmetric M1 site or the larger, more distorted M2 site. Site occupancy of the transition metal is expected to correlate with ionic radius and d-orbital structure. In NMR spectroscopy the presence of paramagnetic ions, such as transition metal ions, can produce accessory peaks referred to as "contact shifts," due to the interaction between unpaired electrons on the paramagnetic ion locally associated with the resonating nucleus. The position and intensity of the contact shifts are dependent on the geometrical association such as bond distances and bond angles between the paramagnetic ion and the resonating nucleus. 29Si MAS-NMR spectra collected on synthetic forsterite (Mg2SiO4) doped with minor amounts (0.2-5%) of individual, divalent, paramagnetic, transition metal cations (Mn, Co, Ni, or Cu) substituting for Mg in the octahedral sites, reveals multiple contact shifts. An interpretation of the number of such contact shifts and their relative intensities correlated with structural information of possible 29Si-M1 and 29Si-M2 configurations, potentially allows for the assignment of specific transition metals to individual M1 or M2 sites. An analysis of the MAS-NMR data will potentially bring a new level of confidence to transition metal site occupancy in forsterite.

  8. The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort

    PubMed Central

    Grabenhenrich, Linus B.; Reich, Andreas; Fischer, Felix; Zepp, Fred; Forster, Johannes; Schuster, Antje; Bauer, Carl-Peter; Bergmann, Renate L.; Bergmann, Karl E.; Wahn, Ulrich; Keil, Thomas; Lau, Susanne

    2014-01-01

    Background A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome ‘physicians’ diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings. PMID:25536057

  9. (11)B MAS NMR and First-Principles Study of the [OBO3] Pyramids in Borates.

    PubMed

    Zhou, Bing; Sun, Wei; Zhao, Biao-Chun; Mi, Jin-Xiao; Laskowski, Robert; Terskikh, Victor; Zhang, Xi; Yang, Lingyun; Botis, Sanda M; Sherriff, Barbara L; Pan, Yuanming

    2016-03-07

    Borates are built from the [Bϕ3] planar triangles and the [Bϕ4] tetrahedral groups, where ϕ denotes O or OH. However, the [Bϕ4] groups in some borates are highly distorted to include three normal B-O bonds and one anomalously long B-O bond and, therefore, are best described as the [OBO3] pyramids. Four synthetic borates of the boracite-type structures (Mg3B7O13Br, Cu3B7O13Br, Zn3B7O13Cl, and Mg3B7O13Cl) containing a range of [OBO3] pyramids were investigated by multifield (7.05, 14.1, and 21.1 T) (11)B magic-angle spinning nuclear magnetic resonance (MAS NMR), triple quantum (3Q) MAS NMR experiments, as well as density functional theory calculations. The high-resolution (11)B MAS NMR spectra supported by theoretical predictions show that the [OBO3] pyramids are characterized by isotropic chemical shifts δiso((11)B) from 1.4(1) to 4.9(1) ppm and nuclear quadrupole parameters CQ((11)B) up to 1.3(1) MHz, both significantly different from those of the [BO4] and [BO3] groups in borates. These δiso((11)B) and CQ((11)B) values indicate that the [OBO3] pyramids represent an intermediate state between the [BO4] tetrahedra and [BO3] triangles and demonstrate that the (11)B NMR parameters of four-coordinate boron oxyanions are sensitive to local structural environments. The orientation of the calculated unique electronic field gradient tensor element Vzz of the [OBO3] pyramids is aligned approximately along the direction of the anomalously long B-O bond, corresponding to B-2pz with the lowest electron density.

  10. Paraneoplastic syndromes

    SciTech Connect

    Weller, R.E.

    1994-03-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms, or syndromes which can mimic other disease conditions encountered in veterinary medicine. Recognition of PNS is valuable for several reasons: the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor; they may allow assessment of premalignant states; they may aid in the search metastases; they may help quantify and monitor response to therapy; and, they may provide insight into the study of malignant transformation and oncogene expression. This review will concentrate on the pathophysiology, diagnosis, and treatment of some of the common PNS encountered in veterinary medicine.

  11. AIDS (Acquired Immunodeficiency Syndrome) Education: Activities Aimed at the General Public Implemented Slowly

    DTIC Science & Technology

    1988-12-01

    Budget (Fiscal Years 1984-1988) 8 Table 1.3: CDC AIDS Education Expenditure Plan by 9 Target Group /Activity (Fiscal Years 1985-1987) Table 11. 1...four target groups and various program activities within each target group , as shown in table 1.3. Page 8 GAO ItRD.S-21 AIDS Education Appeudix I CI...Xs AIDS Education Budget and Planned Expenditures (FIscal Years IlS-1US) Table 1.3: CDC AIDS Education Expenditure Plan by Target Group / Dollars in

  12. IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells.

    PubMed

    Wajner, Simone Magagnin; Goemann, Iuri Martin; Bueno, Ana Laura; Larsen, P Reed; Maia, Ana Luiza

    2011-05-01

    Nonthyroidal illness syndrome (NTIS) is a state of low serum 3,5,3' triiodothyronine (T₃) that occurs in chronically ill patients; the degree of reduction in T₃ is associated with overall prognosis and survival. Iodthyronine deiodinases are enzymes that catalyze iodine removal from thyroid hormones; type I and II deiodinase (D1 and D2, respectively) convert the prohormone thyroxine T₄ to active T₃, whereas the type III enzyme (D3) inactivates T₄ and T₃. Increased production of cytokines, including IL-6, is a hallmark of the acute phase of NTIS, but the role of cytokines in altered thyroid hormone metabolism is poorly understood. Here, we measured the effect of IL-6 on both endogenous cofactor-mediated and dithiothreitol-stimulated (DTT-stimulated) cell sonicate deiodinase activities in human cell lines. Active T₃ generation by D1 and D2 in intact cells was suppressed by IL-6, despite an increase in sonicate deiodinases (and mRNAs). N-acetyl-cysteine (NAC), an antioxidant that restores intracellular glutathione (GSH) concentrations, prevented the IL-6-induced inhibitory effect on D1- and D2-mediated T₃ production, which suggests that IL-6 might function by depleting an intracellular thiol cofactor, perhaps GSH. In contrast, IL-6 stimulated endogenous D3-mediated inactivation of T₃. Taken together, these results identify a single pathway by which IL-6-induced oxidative stress can reduce D1- and D2-mediated T₄-to-T₃ conversion as well as increasing D3-mediated T₃ (and T₄) inactivation, thus mimicking events during illness.

  13. Using heat to control the sample spinning speed in MAS NMR.

    PubMed

    Mihaliuk, Eugene; Gullion, Terry

    2011-10-01

    A new approach using temperature to control the spinning speed of a sample rotor in magic-angle spinning NMR is presented. Instead of an electro-mechanical valve that regulates the flow of drive gas to control the spinning speed in traditional MAS NMR systems, we use a small heater wire located directly in the stator. The sample spinning speed is controlled very accurately with a surprisingly low heating power of 1 W. Results on a benchtop unit demonstrate the capability of the system.

  14. Spinning sidebands from chemical shift anisotropy in 13C MAS imaging.

    PubMed

    Scheler, U; Blümich, B; Spiess, H W

    1993-07-01

    Solid state imaging by 13C MAS imaging is described. The spinning sidebands occurring at moderate spinning speeds, which disturb the images, can be suppressed by TOSS. For rigid solids the spatial resolution that can be achieved in this way is better than that of 1H images at the same spinning speed. Spatially resolved spectra with or without spinning sidebands can likewise be recorded providing information about the isotropic and the anisotropic chemical shifts which can be exploited for the study of structure, order and dynamics. The techniques are demonstrated on a phantom made with 13C-labelled glycine.

  15. Multiple-quantum cross-polarization in MAS NMR of quadrupolar nuclei

    NASA Astrophysics Data System (ADS)

    Ashbrook, Sharon E.; Brown, Steven P.; Wimperis, Stephen

    1998-05-01

    Using 27Al ( I=5/2) NMR of aluminium acetylacetonate, we show that it is possible to cross-polarize from a spin I=1/2 nucleus ( 1H) directly to the central triple-quantum transition of a half-integer quadrupolar nucleus ( 27Al) in a powdered sample under MAS conditions. The optimum conditions for this multiple-quantum cross-polarization (MQCP) are investigated experimentally and compared with existing theoretical results. The new technique is applied to the recently introduced two-dimensional MQMAS experiment for recording high-resolution NMR spectra of half-integer quadrupolar nuclei.

  16. Recent Results from the MicroMAS Global Environmental MonitoringNanosatellite Mission

    NASA Astrophysics Data System (ADS)

    Blackwell, W. J.; Cahoy, K.

    2014-12-01

    The Micro-sized Microwave Atmospheric Satellite (MicroMAS) is a dual-spinning 3U CubeSat equipped with apassive microwave radiometer that observes in nine channels near the 118.75-GHz oxygen absorption line.MicroMAS is designed to observe convective thunderstorms, tropical cyclones, and hurricanes from a midinclinationorbit. The MicroMAS flight unit was developed by MIT Lincoln Laboratory and the MIT Space SystemsLaboratory and was launched to the International Space Station on July 13, 2014, and scheduled for an earlySeptember deployment for a ~90-day mission. The payload is housed in the "lower" 1U of the dual-spinning 3UCubeSat and mechanically rotated approximately once per second as the spacecraft orbits the Earth, resulting in across-track scanned beam with a full-width half-max (FWHM) beamwidth of 2.4 degrees and an approximately 17-km diameter footprint at nadir incidence from a nominal altitude of 400 km. The relatively low cost of MicroMASenables the deployment of a constellation of sensors, spaced equally around several orbit planes. A small fleet ofMicroMAS systems could yield high-resolution global temperature and water vapor profiles, as well as cloudmicrophysical and precipitation parameters.Significant advancements were made in the Assembly, Integration, and Test phase of the project developmentlifecycle. The flight software and communications architecture was refined and tested in relevant lab facilities. Thepower subsystem was modified to include additional required inhibits for the ISS launch. Hardware in the loop testsas well as simulations of the attitude determination and control system (ADCS) were performed to validate theunique dual-spinning, local vertical, local horizontal (LVLH) stabilized flight design. ADCS algorithms were testedon a 3-axis air bearing and custom rig inside a 3-axis programmable Helmholtz cage. Finally, the integratedspacecraft underwent a series of environmental tests in order to verify the results of thermal modeling

  17. Estimation of the specific surface area of apatites in human mineralized tissues using 31P MAS NMR.

    PubMed

    Kolmas, Joanna; Slósarczyk, Anna; Wojtowicz, Andrzej; Kolodziejski, Waclaw

    2007-10-01

    Specific surface areas of apatites in whole human mineralized tissues were estimated from (31)P MAS NMR linewidths: 77 m(2)g(-1) for enamel and 94 m(2)g(-1) for dentin, dental cementum and cortical bone.

  18. Physical Activity, Dietary Intake, and the Insulin Resistance Syndrome in Nondiabetic Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Draheim, Christopher C.; Williams, Daniel P.; McCubbin, Jeffrey A.

    2002-01-01

    A study identified 145 adults with mild mental retardation and hyperinsulinemia, borderline high triglycerides, low high-density lipoprotein cholesterol, hypertension, and abdominal obesity. Those who participated in more frequent bouts of physical activity or who consumed lower dietary fat intakes were one-third as likely to have hyperinsulinemia…

  19. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  20. The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity.

    PubMed

    Mhaske, Pallavi V; Levit, Noah A; Li, Leping; Wang, Hong-Zhan; Lee, Jack R; Shuja, Zunaira; Brink, Peter R; White, Thomas W

    2013-06-15

    Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome.

  1. Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats.

    PubMed

    Mansoori, A; Oryan, S; Nematbakhsh, M

    2016-03-01

    The vasodilatory effect of angiotensin 1-7 (Ang 1-7) is exerted in the vascular bed via Mas receptor (MasR) gender dependently. However, the crosstalk between MasR and angiotensin II (Ang II) types 1 and 2 receptors (AT1R and AT2R) may change some actions of Ang 1-7 in renal circulation. In this study by blocking AT1R and AT2R, the role of MasR in kidney hemodynamics was described. In anaesthetized male and female Wistar rats, the effects of saline as vehicle and MasR blockade (A779) were tested on mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) when both AT1R and AT2R were blocked by losartan and PD123319, respectively. In male rats, when AT1R and AT2R were blocked, there was a tendency for the increase in RBF/wet kidney tissue weight (RBF/KW) to be elevated by A779 as compared with the vehicle (P=0.08), and this was not the case in female rats. The impact of MasR on renal hemodynamics appears not to be sexual dimorphism either when Ang II receptors were blocked. It seems that co-blockade of all AT1R, AT2R, and MasR may alter RBF/ KW in male more than in female rats. These findings support a crosstalk between MasR and Ang II receptors in renal circulation.

  2. Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis

    PubMed Central

    Callera, Glaucia E.; Antunes, Tayze T.; Correa, Jose W.; Moorman, Danielle; Gutsol, Alexey; He, Ying; Cat, Aurelie Nguyen Dinh; Briones, Ana M.; Montezano, Augusto C.; Burns, Kevin D.; Touyz, Rhian M.

    2016-01-01

    High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes. PMID:27612496

  3. Cushing's Syndrome

    MedlinePlus

    ... example, polycystic ovary syndrome can cause menstrual disturbances, weight gain beginning in adolescence, excess hair growth, and impaired insulin action and diabetes. Metabolic syndrome-a combination of ...

  4. Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

    PubMed

    Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

    2016-02-01

    Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticoste