Science.gov

Sample records for activation syndrome mas

  1. [Biologically active substances of cornelian cherry fruits (Cornus mas L.)].

    PubMed

    Perova, I B; Zhogova, A A; Poliakova, A V; Éller, K I; Ramenskaia, G V; Samylina, I A

    2014-01-01

    10 samples of fresh-frozen cornelian cherry fruits (Cornus mas L.), collected in the Tambov and the Caucasus regions, were investigated for the total amount and composition of the main biologically active substances (BAS): anthocyanins (AC), proanthocyanidins (OPC), dihydroxycinnamic acids (DHCA), iridoids, organic acids, mono- and disaccharides and antiradical activity in the DPPH-test in vitro. Total phenolics content determined by Folin-Ciocalteu method, was 150-400 mg/100 g fresh fruit weight. The OPC content, estimated by Bate-Smith method, varied from 20-25 mg/100 g of unripe cornelian cherries to 80-430 mg/100 g of mature cornelian cherries. Total AC amount evaluated by pH-differential spectrophotometry was minimal in unripe fruits (11,2 mg/100 g), and maximal in mature fruits (92,2 mg/100 g). Profile of individual AC was determined by HPLC with UV/Vis and ESI-TOF-MS detections. 3-galactosides of cyanidin (19,0-80,3%) and pelargonidin (15,1-75,6%) were found as main anthocyanins. An original methodology for iridoid determination based on HPLC with UV and ESI-TOF-MS detection was developed. The main iridoids were identified as loganic acid, loganin, sweroside and cornuside. Total iridoids content was 130-400 mg/100 g, and loganic acid was predominant in all samples (87,6-94,8%). Only minor amount of the DHCA derivatives (<10 mg/100 g) were found. The malic acid was predominant among organic acids, the total content of which varied from 0,4 to 2,8%. Relatively high amount of ascorbic acid (35-60 mg/100 g) was found. The carbohydrates profile of cornielian cherries was represented by fructose (2,2-3,8%) and glucose (2,5-7,0%). 70% water-ethanol extracts of Cornus mas fruits have showed pronounced antiradical activity in DPPH-test (470,5-932,0 mg TE/100 g). The data on specific minor BAS can be used in the standardization and evaluation of potential biological activity of extracts and dietary supplements based on the cornelian cherry fruits. PMID:25816631

  2. [Biologically active substances of cornelian cherry fruits (Cornus mas L.)].

    PubMed

    Perova, I B; Zhogova, A A; Poliakova, A V; Éller, K I; Ramenskaia, G V; Samylina, I A

    2014-01-01

    10 samples of fresh-frozen cornelian cherry fruits (Cornus mas L.), collected in the Tambov and the Caucasus regions, were investigated for the total amount and composition of the main biologically active substances (BAS): anthocyanins (AC), proanthocyanidins (OPC), dihydroxycinnamic acids (DHCA), iridoids, organic acids, mono- and disaccharides and antiradical activity in the DPPH-test in vitro. Total phenolics content determined by Folin-Ciocalteu method, was 150-400 mg/100 g fresh fruit weight. The OPC content, estimated by Bate-Smith method, varied from 20-25 mg/100 g of unripe cornelian cherries to 80-430 mg/100 g of mature cornelian cherries. Total AC amount evaluated by pH-differential spectrophotometry was minimal in unripe fruits (11,2 mg/100 g), and maximal in mature fruits (92,2 mg/100 g). Profile of individual AC was determined by HPLC with UV/Vis and ESI-TOF-MS detections. 3-galactosides of cyanidin (19,0-80,3%) and pelargonidin (15,1-75,6%) were found as main anthocyanins. An original methodology for iridoid determination based on HPLC with UV and ESI-TOF-MS detection was developed. The main iridoids were identified as loganic acid, loganin, sweroside and cornuside. Total iridoids content was 130-400 mg/100 g, and loganic acid was predominant in all samples (87,6-94,8%). Only minor amount of the DHCA derivatives (<10 mg/100 g) were found. The malic acid was predominant among organic acids, the total content of which varied from 0,4 to 2,8%. Relatively high amount of ascorbic acid (35-60 mg/100 g) was found. The carbohydrates profile of cornielian cherries was represented by fructose (2,2-3,8%) and glucose (2,5-7,0%). 70% water-ethanol extracts of Cornus mas fruits have showed pronounced antiradical activity in DPPH-test (470,5-932,0 mg TE/100 g). The data on specific minor BAS can be used in the standardization and evaluation of potential biological activity of extracts and dietary supplements based on the cornelian cherry fruits.

  3. [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. PMID:27071265

  4. 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

  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 a newborn infant born to a mother with autoimmune disease.

    PubMed

    Park, J H; Kim, S H; Kim, H J; Lee, S J; Jeong, D C; Kim, S Y

    2015-02-01

    Macrophage activation syndrome (MAS) is a complication of rheumatic disorders characterized by cytopenia, multiple organ dysfunction and coagulopathy associated with an inappropriate activation of macrophage. In neonatal lupus erythematosus, MAS is rare but fatal, requiring early diagnosis and treatment for optimal outcome. We report a case of MAS in a neonate born to a mother with autoimmune disease, improved by treatment with steroid, intravenous immunoglobulin and cyclosporine.

  7. Angiotensin-(1-7) through Mas receptor activation induces peripheral antinociception by interaction with adrenoreceptors.

    PubMed

    Castor, Marina G M; Santos, Robson A S; Duarte, Igor D G; Romero, Thiago R L

    2015-07-01

    Angiotensin-(1-7) [Ang-(1-7)] develops its functions interacting with Mas receptor. Mas receptor was recently identified in the DRG and its activation by Ang-(1-7) resulted in peripheral antinociception against PGE2 hyperalgesia in an opioid-independent pathway. Nevertheless, the mechanism by which Ang-(1-7) induce peripheral antinociception was not yet elucidated. Considering that endogenous noradrenaline could induce antinociceptive effects by activation of the adrenoceptors the aim of this study was verify if the Ang-(1-7) is able to induce peripheral antinociception by interacting with the endogenous noradrenergic system. Hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2μg). Ang-(1-7) was administered locally into the right hindpaw alone and after either agents, α2-adrenoceptor antagonist, yohimbine (5, 10 and 20 μg/paw), α2C-adrenoceptor antagonist rauwolscine (10, 15 and 20 μg/paw), α1-adrenoceptor antagonist prazosin (0.5, 1 and 2 μg/paw), β-adrenoceptor antagonist propranolol (150, 300 and 600 ng/paw). Noradrenaline (NA) reuptake inhibitor reboxetine (30 μg/paw) was administered prior to Ang-(1-7) low dose (20 ng) and guanetidine 3 days prior to experiment (30 mg/kg/animal, once a day), depleting NA storage. Intraplantar Ang-(1-7) induced peripheral antinociception against hyperalgesia induced by PGE2. This effect was reversed, in dose dependent manner, by intraplantar injection of yohimbine, rauwolscine, prazosin and propranolol. Reboxetine intensified the antinociceptive effects of low-dose of Ang-(1-7) and guanethidine, which depletes peripheral sympathomimetic amines, reversed almost 70% the Ang-(1-7)-induced peripheral antinociception. Then, this study provides evidence that Ang-(1-7) induce peripheral antinociception stimulating an endogenous noradrenaline release that activates peripheral adrenoceptors inducing antinociception.

  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. PMID:27596418

  9. Association of Macrophage Activating Syndrome with Castleman’s Syndrome in Systemic Lupus Erythematosus

    PubMed Central

    Shariatpanahi, Shamsa; Pourfarzam, Shahryar; Gheini, Mohammadhosein

    2016-01-01

    Macrophage Activating Syndrome (MAS) is a life-threatening disease seen in autoimmune diseases including lupus erythematosus, rheumatoid arthritis, Still's disease, polyarteritis nodosa. It is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms and high serum ferritin. A 27 yr. old female patient was admitted in shahid Mostafa Khomeini Hospital (Tehran-Iran) in May 2011 because of lower extremities edema and ascites and fever from 1.5 month ago. In physical examinations she had generalized lymphadenopathy, splenomegaly and pleural effusion. In laboratory tests she had pancytopenia, positive ANA and Anti DNA (ds), hypocomplementemia, hypertriglyceridemia and high ferritin level. Gradually she had signs of RPGN and ARDS. The patient had no skin and musculoskeletal signs of SLE and no liver failure nor coagulopathy of MAS. Her lymph node biopsy was reported as Castleman syndrome. Unlike other studies, the patient showed MAS before treatment with cytotoxic for lupus nephritis. PMID:27799976

  10. Arabidopsis MAS2, an Essential Gene That Encodes a Homolog of Animal NF-κ B Activating Protein, Is Involved in 45S Ribosomal DNA Silencing

    PubMed Central

    Sánchez-García, Ana Belén; Aguilera, Verónica; Micol-Ponce, Rosa; Jover-Gil, Sara; Ponce, María Rosa

    2015-01-01

    Ribosome biogenesis requires stoichiometric amounts of ribosomal proteins and rRNAs. Synthesis of rRNAs consumes most of the transcriptional activity of eukaryotic cells, but its regulation remains largely unclear in plants. We conducted a screen for ethyl methanesulfonate-induced suppressors of Arabidopsis thaliana ago1-52, a hypomorphic allele of AGO1 (ARGONAUTE1), a key gene in microRNA pathways. We identified nine extragenic suppressors as alleles of MAS2 (MORPHOLOGY OF AGO1-52 SUPPRESSED2). Positional cloning showed that MAS2 encodes the putative ortholog of NKAP (NF-κ B activating protein), a conserved eukaryotic protein involved in transcriptional repression and splicing in animals. The mas2 point mutations behave as informational suppressors of ago1 alleles that cause missplicing. MAS2 is a single-copy gene whose insertional alleles are embryonic lethal. In yeast two-hybrid assays, MAS2 interacted with splicing and ribosome biogenesis proteins, and fluorescence in situ hybridization showed that MAS2 colocalizes with the 45S rDNA at the nucleolar organizer regions (NORs). The artificial microRNA amiR-MAS2 partially repressed MAS2 and caused hypomethylation of 45S rDNA promoters as well as partial NOR decondensation, indicating that MAS2 negatively regulates 45S rDNA expression. Our results thus reveal a key player in the regulation of rRNA synthesis in plants. PMID:26139346

  11. Simultaneous removal of organic matter and nitrogen from milking parlor wastewater by a magnetic activated sludge (MAS) process.

    PubMed

    Ying, Chun; Umetsu, Kazutaka; Ihara, Ikko; Sakai, Yasuzo; Yamashiro, Takaki

    2010-06-01

    The magnetic activated sludge (MAS) process is a modification of the conventional activated sludge process to improve the solid-liquid separation characteristics. It was developed to reduce the production of excess sludge and the time required for the conventional activated sludge process. In this study, actual milking parlor wastewater was treated with a MAS process and no sludge was removed. The effectiveness of continuous aeration and intermittent aeration in removing organic matter and nitrogen were compared. Both processes were highly efficient at removing chemical oxygen demand (COD) (averaged 91% removal) and ammonium nitrogen (NH(4)-N) (averaged 99% removal). In marked contrast to the continuous aeration process, the 30-min aeration/90-min non-aeration cycle of the intermittent aeration process rapidly reduced the nitrate nitrogen (NO(3)-N) concentration to near-zero. This result indicates that NO(3)-N was almost completely denitrified via nitrite nitrogen (NO(2)-N) to nitrogen gas. Removal of organic material and nitrogen can be considered to have occurred simultaneously in the single tank of the MAS process.

  12. Shrimp Serine Proteinase Homologues PmMasSPH-1 and -2 Play a Role in the Activation of the Prophenoloxidase System

    PubMed Central

    Jearaphunt, Miti; Amparyup, Piti; Sangsuriya, Pakkakul; Charoensapsri, Walaiporn; Senapin, Saengchan; Tassanakajon, Anchalee

    2015-01-01

    Melanization mediated by the prophenoloxidase (proPO) activating system is a rapid immune response used by invertebrates against intruding pathogens. Several masquerade-like and serine proteinase homologues (SPHs) have been demonstrated to play an essential role in proPO activation in insects and crustaceans. In a previous study, we characterized the masquerade-like SPH, PmMasSPH1, in the black tiger shrimp Penaeus monodon as a multifunctional immune protein based on its recognition and antimicrobial activity against the Gram-negative bacteria Vibrio harveyi. In the present study, we identify a novel SPH, known as PmMasSPH2, composed of an N-terminal clip domain and a C-terminal SP-like domain that share high similarity to those of other insect and crustacean SPHs. We demonstrate that gene silencing of PmMasSPH1 and PmMasSPH2 significantly reduces PO activity, resulting in a high number of V. harveyi in the hemolymph. Interestingly, knockdown of PmMasSPH1 suppressed not only its gene transcript but also other immune-related genes in the proPO system (e.g., PmPPAE2) and antimicrobial peptides (e.g., PenmonPEN3, PenmonPEN5, crustinPm1 and Crus-likePm). The PmMasSPH1 and PmMasSPH2 also show binding activity to peptidoglycan (PGN) of Gram-positive bacteria. Using a yeast two-hybrid analysis and co-immunoprecipitation, we demonstrate that PmMasSPH1 specifically interacted with the final proteinase of the proPO cascade, PmPPAE2. Furthermore, the presence of both PmMasSPH1 and PmPPAE2 enhances PGN-induced PO activity in vitro. Taken together, these results suggest the importance of PmMasSPHs in the activation of the shrimp proPO system. PMID:25803442

  13. 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.

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

    PubMed

    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

  15. The protective effect of the Cornus mas fruits (cornelian cherry) on hypertriglyceridemia and atherosclerosis through PPARα activation in hypercholesterolemic rabbits.

    PubMed

    Sozański, T; Kucharska, A Z; Szumny, A; Magdalan, J; Bielska, K; Merwid-Ląd, A; Woźniak, A; Dzimira, S; Piórecki, N; Trocha, M

    2014-11-15

    Cornelian cherry (Cornus mas L.) fruits have been used in traditional cuisine and in folk medicine in various countries. This study was conducted to evaluate the constituents and impact of cornelian cherry (C. mas L.) fruits lyophilisate on lipid levels, PPARα protein expression, atheromatous changes in the aorta, oxido-redox state, and proinflammatory cytokines in hypercholesterolemic rabbits. The HPLC-MS method was used for determining active constituents in cornelian cherry. In a subsequent in vivo study the protective effect of the cornelian cherry on diet-induced hyperlipidemia was studied using a rabbit model fed 1% cholesterol. Cornelian cherry (100mg/kg b.w.) or simvastatin (5mg/kg b.w.) were administered orally for 60 days. Two iridoids - loganic acid and cornuside - and five anthocyanins were identified as the main constituents of the cornelian cherry. The administering of the cornelian cherry led to a 44% significant decrease in serum triglyceride levels, as well as prevented development of atheromatous changes in the thoracic aorta. Cornelian cherry significantly increased PPARα protein expression in the liver, indicating that its hypolipidemic effect may stem from enhanced fatty acid catabolism. Simvastatin treatment did not affect PPAR-α expression. Moreover, the cornelian cherry had a significant protective effect on diet-induced oxidative stress in the liver, as well as restored upregulated proinflammatory cytokines serum levels. In conclusion, we have shown loganic acid to be the main iridoid constituent in the European cultivar of the cornelian cherry, and proven that the cornelian cherry could have protective effects on diet-induced hypertriglicerydemia and atherosclerosis through enhanced PPARα protein expression and via regulating oxidative stress and inflammation. PMID:25444446

  16. Characterization of active phosphorus surface sites at synthetic carbonate-free fluorapatite using single-pulse 1H, 31P, and 31P CP MAS NMR.

    PubMed

    Jarlbring, Mathias; Sandström, Dan E; Antzutkin, Oleg N; Forsling, Willis

    2006-05-01

    The chemically active phosphorus surface sites defined as PO(x), PO(x)H, and PO(x)H2, where x = 1, 2, or 3, and the bulk phosphorus groups of PO4(3-) at synthetic carbonate-free fluorapatite (Ca5(PO4)3F) have been studied by means of single-pulse 1H,31P, and 31P CP MAS NMR. The changes in composition and relative amounts of each surface species are evaluated as a function of pH. By combining spectra from single-pulse 1H and 31P MAS NMR and data from 31P CP MAS NMR experiments at varying contact times in the range 0.2-3.0 ms, it has been possible to distinguish between resonance lines in the NMR spectra originating from active surface sites and bulk phosphorus groups and also to assign the peaks in the NMR spectra to the specific phosphorus species. In the 31P CP MAS NMR experiments, the spinning frequency was set to 4.2 kHz; in the single-pulse 1H MAS NMR experiments, the spinning frequency was 10 kHz. The 31P CP MAS NMR spectrum of fluorapatite at pH 5.9 showed one dominating resonance line at 2.9 ppm assigned to originate from PO4(3-) groups and two weaker shoulder peaks at 5.4 and 0.8 ppm which were assigned to the unprotonated PO(x) (PO, PO2-, and PO3(2-)) and protonated PO(x)H (PO2H and PO3H-) surface sites. At pH 12.7, the intensity of the peak representing unprotonated PO(x) surface sites has increased 1.7% relative to the bulk peak, while the intensity of the peaks of the protonated species PO(x)H have decreased 1.4% relative to the bulk peak. At pH 3.5, a resonance peak at -4.5 ppm has appeared in the 31P CP MAS NMR spectrum assigned to the surface species PO(x)H2 (PO3H2). The results from the 1H MAS and 31P CP MAS NMR measurements indicated that H+, OH-, and physisorbed H2O at the surface were released during the drying process at 200 degrees C.

  17. MAS and MI+ Comparison.

    ERIC Educational Resources Information Center

    Grice, Ila M.

    1991-01-01

    Compares the compact disc read-only-memory (CD-ROM) Magazine Article Summaries (MAS) and Magazine Index Plus Backfile (MI+) in terms of system hardware, index coverage, searching capabilities, citation display, printing citations, local holdings, and miscellaneous features and costs. Finds in favor of MAS. (DMM)

  18. 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.

  19. Macrophage activation syndrome induced by A/H1N1 influenza in cystic fibrosis.

    PubMed

    Casciaro, Rosaria; Cresta, Federico; Favilli, Federica; Naselli, Aldo; De Alessandri, Alessandra; Minicucci, Laura

    2014-02-01

    Bacterial respiratory infections have an important impact on the development and progression of pulmonary disease in cystic fibrosis (CF). Viral infections are possible triggers of acute deterioration in the clinical status of CF patients. Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disease characterized by pancytopenia, hepatitis, hyperferritinemia, coagulopathy, and neurologic symptoms. This syndrome is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Here, we report the case of a boy affected by CF who developed MAS triggered by pandemic H1N1 influenza; good clinical response was obtained through high dose prednisone treatment. PMID:23401277

  20. Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease: A Case-Based Review.

    PubMed

    Watanabe, Eri; Sugawara, Hitoshi; Yamashita, Takeshi; Ishii, Akira; Oda, Aya; Terai, Chihiro

    2016-01-01

    We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS. PMID:27688774

  1. Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease: A Case-Based Review

    PubMed Central

    Watanabe, Eri; Yamashita, Takeshi; Ishii, Akira; Oda, Aya; Terai, Chihiro

    2016-01-01

    We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS. PMID:27688774

  2. Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease: A Case-Based Review

    PubMed Central

    Watanabe, Eri; Yamashita, Takeshi; Ishii, Akira; Oda, Aya; Terai, Chihiro

    2016-01-01

    We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS.

  3. Diminazene aceturate, an angiotensin-converting enzyme II activator, prevents gastric mucosal damage in mice: Role of the angiotensin-(1-7)/Mas receptor axis.

    PubMed

    Souza, Luan Kelves M; Nicolau, Lucas A D; Sousa, Nayara A; Araújo, Thiago S L; Sousa, Francisca Beatriz M; Costa, Douglas S; Souza, Fabiana M; Pacífico, Dvison M; Martins, Conceição S; Silva, Renan O; Souza, Marcellus H L P; Cerqueira, Gilberto S; Medeiros, Jand Venes R

    2016-07-15

    The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent. PMID:27241079

  4. 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

  5. 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.

  6. [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.

  7. Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats.

    PubMed

    Wang, Dongmei; Xue, Yaping; Chen, Yajuan; Ruan, Liqin; Hong, Yanguo

    2016-04-01

    Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) at 1 or 10nmol attenuated mechanical allodynia one day after L5 spinal nerve ligation (SNL) surgery. I.t. BAM8-22 (10 nmol) inhibited SNL-induced microglia activation in the spinal dorsal horn on day 2 post-SNL. The BAM8-22 treatment also abolished SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) in the dorsal root ganglia (DRG). On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.

  8. 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.

  9. 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

  10. 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.

  11. Macrophage Activation Syndrome-Associated Markers in Severe Dengue

    PubMed Central

    Ab-Rahman, Hasliana Azrah; Rahim, Hafiz; AbuBakar, Sazaly; Wong, Pooi-Fong

    2016-01-01

    Hemophagocytosis, a phenomenon of which activated macrophages phagocytosed hematopoietic elements was reportedly observed in severe dengue patients. In the present study, we investigated whether markers of macrophage activation syndrome (MAS) can be used as differential diagnostic markers of severe dengue. Two hundred and eight confirmed dengue patients were recruited for the study. Sandwich ELISA was used to determine serum ferritin, soluble CD163 (sCD163), and soluble CD25 (sCD25) levels. The population of circulating CD163 (mCD163) monocytes was determined using flow cytometry. Receiver operating characteristic (ROC) analysis was plotted to determine the predictive validity of the biomarkers. Serum ferritin and sCD163 were found significantly increased in severe dengue patients compared to dengue fever patients (P = 0.003). A fair area under ROC curves (AUC) at 0.72 with a significant P value of 0.004 was observed for sCD163. sCD25 and mCD163 levels were not significantly different between severe dengue and dengue fever patients. Our findings suggest that in addition to serum ferritin, sCD163 can differentiate severe dengue from that of dengue fever patients. Hence, sCD163 level can be considered for use as a predictive marker for impending severe dengue. PMID:26941578

  12. 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

  13. Interferon-γ mediates anemia but is dispensable for Fulminant Toll-Like Receptor 9-induced Macrophage Activation Syndrome and Hemophagocytosis

    PubMed Central

    Canna, Scott W.; Wrobel, Julia; Chu, Niansheng; Kreiger, Portia A.; Paessler, Michele; Behrens, Edward M.

    2013-01-01

    Objective Macrophage Activation Syndrome (MAS) is a devastating cytokine storm syndrome complicating many inflammatory diseases and characterized by fever, pancytopenia, and systemic inflammation. It is clinically similar to Hemophagocytic Lymphohistiocytosis (HLH), which is caused by viral infection of a host with impaired cellular cytotoxicity. Murine models of MAS and HLH illustrate Interferon-γ (IFN-γ) as the driving stimulus for hemophagocytosis and immunopathology. We sought to understand the inflammatory contributors to a murine model of Toll-like Receptor 9 (TLR9)-induced fulminant MAS. Methods Wild-type (WT), transgenic, and cytokine-inhibited mice were treated with an IL-10 receptor blocking antibody and TLR9 agonist, and parameters of MAS were evaluated. Results Fulminant MAS was characterized by dramatic elevations in IFN-γ, IL-12, and IL-6. Serum IFN-γ correlated with enhanced IFN-γ production within some hepatic populations, but fewer IFN-γ+ cells. Surprisingly, IFN-γKO mice developed immunopathology and hemophagocytosis comparably to WT mice. However, IFN-γKO mice did not become anemic and had greater numbers of splenic erythroid precursors. IL-12 neutralization phenocopied disease in IFN-γKO mice. Interestingly, Type I interferons contributed to the severity of hypercytokinemia and weight loss, but their absence did not otherwise affect MAS manifestations. Conclusion These data demonstrate that both fulminant MAS and hemophagocytosis can arise independently of IFN-γ, IL-12, or Type I interferons. They also suggest that IFN-γ-mediated dyserythropoiesis, not hemophagocytosis, is the dominant cause of anemia in fulminant TLR9-MAS. Thus, our data establish a novel mechanism for the acute anemia of inflammation, but suggest that a variety of triggers can result in hemophagocytic disease. PMID:23553372

  14. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome.

    PubMed

    Villanueva, Joyce; Lee, Susan; Giannini, Edward H; Graham, Thomas B; Passo, Murray H; Filipovich, Alexandra; Grom, Alexei A

    2005-01-01

    Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have previously reported that, as in HLH, patients with MAS have profoundly decreased NK activity, suggesting that this abnormality might be relevant to the pathogenesis of the syndrome. Here we examined the extent of NK dysfunction across the spectrum of diseases that comprise juvenile rheumatoid arthritis (JRA). Peripheral blood mononuclear cells (PBMC) were collected from patients with pauciarticular (n = 4), polyarticular (n = 16), and systemic (n = 20) forms of JRA. NK cytolytic activity was measured after co-incubation of PBMC with the NK-sensitive K562 cell line. NK cells (CD56+/T cell receptor [TCR]-alphabeta-), NK T cells (CD56+/TCR-alphabeta+), and CD8+ T cells were also assessed for perforin and granzyme B expression by flow cytometry. Overall, NK cytolytic activity was significantly lower in patients with sJRA than in other JRA patients and controls. In a subgroup of patients with predominantly sJRA, NK cell activity was profoundly decreased: in 10 of 20 patients with sJRA and in only 1 of 20 patients with other JRA, levels of NK activity were below two standard deviations of pediatric controls (P = 0.002). Some decrease in perforin expression in NK cells and cytotoxic T lymphocytes was seen in patients within each of the JRA groups with no statistically significant differences. There was a profound decrease in the proportion of circulating CD56bright NK cells in three sJRA patients, a pattern similar to that previously observed in MAS and HLH. In conclusion, a subgroup of patients with JRA who have not yet had an episode of MAS showed decreased NK function and an absence of circulating CD56bright population, similar to the abnormalities observed

  15. 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 ...

  16. Effects of Children with Down Syndrome on Parents' Activities.

    ERIC Educational Resources Information Center

    Barnett, W. Steven; Boyce, Glenna C.

    1995-01-01

    Daily activities were investigated of 237 mothers and 134 fathers of children with Down syndrome and 216 mothers and 174 fathers of children without Down syndrome. Compared to controls, parents of children with Down syndrome devoted more time to child care and spent less time in social activities. (Author/SW)

  17. McCune-Albright Syndrome (MAS)

    MedlinePlus

    ... with questions about grants, contracts & research areas Training, Education & Career Development Support for Training at Universities & Other Institutions Extramural training, fellowships & career development opportunities Training at ...

  18. Sensitivity of Neurospora crassa to a Marine-Derived Aspergillus tubingensis Anhydride Exhibiting Antifungal Activity That Is Mediated by the MAS1 Protein

    PubMed Central

    Koch, Liat; Lodin, Anat; Herold, Inbal; Ilan, Micha; Carmeli, Shmuel; Yarden, Oded

    2014-01-01

    The fungus Aspergillus tubingensis (strain OY907) was isolated from the Mediterranean marine sponge Ircinia variabilis. Extracellular extracts produced by this strain were found to inhibit the growth of several fungi. Among the secreted extract components, a novel anhydride metabolite, tubingenoic anhydride A (1) as well as the known 2-carboxymethyl-3-hexylmaleic acid anhydride, asperic acid, and campyrone A and C were purified and their structure elucidated. Compound 1 and 2-carboxymethyl-3-hexylmaleic acid anhydride inhibited Neurospora crassa growth (MIC = 330 and 207 μM, respectively) and affected hyphal morphology. We produced a N. crassa mutant exhibiting tolerance to 1 and found that a yet-uncharacterized gene, designated mas-1, whose product is a cytosolic protein, confers sensitivity to this compound. The ∆mas-1 strain showed increased tolerance to sublethal concentrations of the chitin synthase inhibitor polyoxin D, when compared to the wild type. In addition, the expression of chitin synthase genes was highly elevated in the ∆mas-1 strain, suggesting the gene product is involved in cell wall biosynthesis and the novel anhydride interferes with its function. PMID:25257783

  19. 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

  20. A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

    PubMed Central

    Wunderlich, Mark; Devarajan, Mahima; Ravishankar, Navin; Sexton, Christina; Kumar, Ashish R.; Mizukawa, Benjamin; Mulloy, James C.

    2016-01-01

    Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6. The BM becomes strikingly hypocellular, and spleens are significantly enlarged with evidence of extramedullary hematopoiesis and activated macrophages engaged in hemophagocytosis. This manifestation of MAS does not respond to lymphocyte-suppressive therapies such as steroids, i.v. immunoglobulin, or antibody-mediated ablation of human B and T cells, demonstrating a lymphocyte-independent mechanism of action. In contrast, elimination of human myeloid cells using gemtuzumab ozogamicin (anti-CD33) completely reversed the disease. Additionally, the IL-6R antibody tocilizumab delayed progression and prolonged lifespan. This new model of MAS provides an opportunity for investigation of the mechanisms driving this disease and for the testing of directed therapies in a humanized mouse.

  1. A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

    PubMed Central

    Wunderlich, Mark; Devarajan, Mahima; Ravishankar, Navin; Sexton, Christina; Kumar, Ashish R.; Mizukawa, Benjamin; Mulloy, James C.

    2016-01-01

    Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6. The BM becomes strikingly hypocellular, and spleens are significantly enlarged with evidence of extramedullary hematopoiesis and activated macrophages engaged in hemophagocytosis. This manifestation of MAS does not respond to lymphocyte-suppressive therapies such as steroids, i.v. immunoglobulin, or antibody-mediated ablation of human B and T cells, demonstrating a lymphocyte-independent mechanism of action. In contrast, elimination of human myeloid cells using gemtuzumab ozogamicin (anti-CD33) completely reversed the disease. Additionally, the IL-6R antibody tocilizumab delayed progression and prolonged lifespan. This new model of MAS provides an opportunity for investigation of the mechanisms driving this disease and for the testing of directed therapies in a humanized mouse. PMID:27699249

  2. 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 ...

  3. 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…

  4. 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. PMID:26714690

  5. 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.

  6. Mediators of sympathetic activation in metabolic syndrome obesity.

    PubMed

    Straznicky, Nora E; Eikelis, Nina; Lambert, Elisabeth A; Esler, Murray D

    2008-12-01

    The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. beta-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympathoinhibition remains an important goal in the therapeutic management of the metabolic syndrome.

  7. An activating G{sub s}{alpha} mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome

    SciTech Connect

    Shenker, A.; Weinstein, L.S.; Spiegel, A.M.; Sweet, D.E.

    1994-09-01

    McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, cafe-au-lait spots, and multiple endocrinopathies. The etiology of fibrous dysplasia is unknown. Activating mutations of codon 201 in the gene encoding the {alpha}-subunit of G{sub s}, the G-protein that stimulates adenylyl cyclase, have been found in all affected MAS tissues that have been studied. Initial attempts to amplify DNA from decalcified paraffin-embedded bone specimens from frozen surgical bone specimens from five MAS patients using polymerase chain reaction and allele-specific oligonucleotide hybridization. Most of the cells in four specimens of dysplastic bone contained a heterozygous mutation encoding substitution of Arg{sup 201} of G{sub s}{alpha} with His, but the mutation was barely detectable in peripheral blood specimens from the patients. Only a small amount of mutant allele was detected in a specimen of normal cortical bone from the fifth patient, although this patients had a high proportion of mutation in other, affected tissues. The mosaic distribution of mutant alleles is consistent with an embryological somatic cell mutation of the G{sub s}{alpha} gene in MAS. The presence of an activating mutation of G{sub s}{alpha} in osteoblastic progenitor cells may cause them to exhibit increased proliferation and abnormal differentiation, thereby producing the lesions of fibrous dysplasia. 43 refs., 2 figs.

  8. Effects of children with Down syndrome on parents' activities.

    PubMed

    Barnett, W S; Boyce, G C

    1995-09-01

    Effects of children with Down syndrome on parents' daily activities were investigated. Data on the allocation of time to daily activities were obtained from time diaries provided by two samples of parents with at least one child under age 17. Parents in one sample had a child with Down syndrome and parents in the other sample did not. Comparison of time allocations by sample indicated that parents of children with Down syndrome differed substantially from other parents in their patterns of time use. Both parents of a child with Down syndrome devoted more time to child care and spent less time in social activities. Mothers of children with Down syndrome allocated less time to paid employment.

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

    PubMed Central

    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. PMID:27407277

  10. 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.

  11. 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.

  12. 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

  13. 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…

  14. Mas Oncogene Signaling and Transformation Require the Small GTP-Binding Protein Rac

    PubMed Central

    Zohn, Irene E.; Symons, Marc; Chrzanowska-Wodnicka, Magdalena; Westwick, John K.; Der, Channing J.

    1998-01-01

    The Mas oncogene encodes a novel G-protein-coupled receptor that was identified originally as a transforming protein when overexpressed in NIH 3T3 cells. The mechanism and signaling pathways that mediate Mas transformation have not been determined. We observed that the foci of transformed NIH 3T3 cells caused by Mas were similar to those caused by activated Rho and Rac proteins. Therefore, we determined if Mas signaling and transformation are mediated through activation of a specific Rho family protein. First, we observed that, like activated Rac1, Mas cooperated with activated Raf and caused synergistic transformation of NIH 3T3 cells. Second, both Mas- and Rac1-transformed NIH 3T3 cells retained actin stress fibers and showed enhanced membrane ruffling. Third, like Rac, Mas induced lamellipodium formation in porcine aortic endothelial cells. Fourth, Mas and Rac1 strongly activated the JNK and p38, but not ERK, mitogen-activated protein kinases. Fifth, Mas and Rac1 stimulated transcription from common DNA promoter elements: NF-κB, serum response factor (SRF), Jun/ATF-2, and the cyclin D1 promoter. Finally, Mas transformation and some of Mas signaling (SRF and cyclin D1 but not NF-κB activation) were blocked by dominant negative Rac1. Taken together, these observations suggest that Mas transformation is mediated in part by activation of Rac-dependent signaling pathways. Thus, Rho family proteins are common mediators of transformation by a diverse variety of oncogene proteins that include Ras, Dbl family, and G-protein-coupled oncogene proteins. PMID:9488437

  15. 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…

  16. 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. PMID:26073599

  17. 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.

  18. 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.

  19. Millimeter-Wave Atmospheric Sounder (MAS)

    NASA Technical Reports Server (NTRS)

    Hartmann, G. K.

    1988-01-01

    MAS is a remote sensing instrument for passive sounding (limb sounding) of the earth's atmosphere from the Space Shuttle. The main objective of the MAS is to study the composition and dynamic structure of the stratosphere, mesosphere, and lower thermosphere in the height range 20 to 100 km, the region known as the middle atmosphere. The MAS will be flown on the Atmospheric Laboratory for Applications and Science (ATLAS 1) NASA mission scheduled for late 1990. The Millimeter-Wave Atmospheric Sounder will provide, for the first time, information obtained simultaneously on the temperature and on ozone concentrations in the 20 to 90 km altitude region. The information will cover a large area of the globe, will have high accuracy and high vertical resolution, and will cover both day and night times. Additionally, data on the two important molecules, H2O and ClO, will also be provided.

  20. Using Stable Isotopes to Assess Reduced Physical Activity of Individuals with Prader-Willi Syndrome.

    ERIC Educational Resources Information Center

    Davies, Peter S. W.; Joughlin, C.

    1993-01-01

    This study found that the physical activity levels of 10 children with Prader-Willi syndrome were significantly reduced in comparison to children without the syndrome. Increasing activity levels in children with Prader-Willi syndrome is suggested as a way to raise total energy expenditure and control weight gain. (Author/JDD)

  1. An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

    PubMed Central

    Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

    2016-01-01

    Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

  2. How Do Adults With Down Syndrome Perceive Physical Activity?

    PubMed

    Love, Adam; Agiovlasitis, Stamatis

    2016-07-01

    Adults with Down syndrome (DS) tend to have low physical activity levels, which may relate to how they perceive participation in physical activities. The current study entailed interviews with 30 adults with DS (age 18-71 yr, 18 women) to examine how they perceived physical activity, exercise, and sport. Through qualitative analysis informed by grounded theory, the investigators found that adults with DS have positive perceptions of physical activity that center on enjoyment. Three facets of enjoyment were identified: interaction, achievement, and process. Interaction reflected enjoyment of social contact with others including relatives, peers, caregivers, and animals. Achievement involved enjoyment of achieving particular ends including accomplishment of tasks, material rewards, formation of athletic identities, and improvement of health. Process represented enjoyment from performing a particular activity itself. This multifaceted enjoyment expressed by adults with DS may facilitate physical activity and should be considered when developing programs to improve their well-being. PMID:27623609

  3. 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.

  4. 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

  5. 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

  6. Ganser-like syndrome after loss of psychic self-activation syndrome: psychogenic or organic?

    PubMed

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

    2014-11-01

    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.

  7. 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,…

  8. Ultra-low temperature MAS-DNP

    NASA Astrophysics Data System (ADS)

    Lee, Daniel; Bouleau, Eric; Saint-Bonnet, Pierre; Hediger, Sabine; De Paëpe, Gaël

    2016-03-01

    Since the infancy of NMR spectroscopy, sensitivity and resolution have been the limiting factors of the technique. Regular essential developments on this front have led to the widely applicable, versatile, and powerful spectroscopy that we know today. However, the Holy Grail of ultimate sensitivity and resolution is not yet reached, and technical improvements are still ongoing. Hence, high-field dynamic nuclear polarization (DNP) making use of high-frequency, high-power microwave irradiation of electron spins has become very promising in combination with magic angle sample spinning (MAS) solid-state NMR experiments. This is because it leads to a transfer of the much larger polarization of these electron spins under suitable irradiation to surrounding nuclei, greatly increasing NMR sensitivity. Currently, this boom in MAS-DNP is mainly performed at minimum sample temperatures of about 100 K, using cold nitrogen gas to pneumatically spin and cool the sample. This Perspective deals with the desire to improve further the sensitivity and resolution by providing "ultra"-low temperatures for MAS-DNP, using cryogenic helium gas. Different designs on how this technological challenge has been overcome are described. It is shown that stable and fast spinning can be attained for sample temperatures down to 30 K using a large cryostat developed in our laboratory. Using this cryostat to cool a closed-loop of helium gas brings the additional advantage of sample spinning frequencies that can greatly surpass those achievable with nitrogen gas, due to the differing fluidic properties of these two gases. It is shown that using ultra-low temperatures for MAS-DNP results in substantial experimental sensitivity enhancements and according time-savings. Access to this temperature range is demonstrated to be both viable and highly pertinent.

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

    DOE PAGES

    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,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

  10. 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.

  11. Quantitative evaluation of erythropoietic activity in dysmyelopoietic syndromes.

    PubMed

    Cazzola, M; Barosi, G; Berzuini, C; Dacco, M; Orlandi, E; Stefanelli, M; Ascari, E

    1982-01-01

    Based on the morphological appearances of the bone marrow and peripheral blood, 43 patients with dysmyelopoietic syndromes were categorized into four types: refractory anaemia with excess of blasts, chronic myelomonocytic leukaemia, primary acquired sideroblastic anaemia and refractory anaemia with cellular marrow, without excess of blasts and/or ring sideroblasts. Ferrokinetics allowed three distinct groups of patients to be defined. All cases of refractory anaemia with excess of blasts and chronic myelomonocytic leukaemia were classified in the same group. They were characterized by relative marrow failure and had a high likelihood of developing acute leukaemia. At the other end of the spectrum, individuals with primary acquired sideroblastic anaemia had high erythropoietic activity which was largely ineffective. They had a benign clinical course without evidence of leukaemic transformation. In the middle group, in terms of erythropoietic activity, lay patients with refractory anaemia with cellular marrow and a few individuals with primary acquired sideroblastic anaemia. Their clinical course and risk of developing acute leukaemia were intermediate between the other two groups. These findings indicate that separate entities may exist within the spectrum of dysmyelopoietic syndromes. In clinical practice, they may be recognized by morphological studies and other simple laboratory means.

  12. Altered myoelectric activity in the experimental blind loop syndrome.

    PubMed

    Justus, P G; Fernandez, A; Martin, J L; King, C E; Toskes, P P; Mathias, J R

    1983-09-01

    Nutrient malabsorption and diarrhea are characteristic of the blind loop syndrome. Alterations in motility have been implicated as a cause of bacterial overgrowth, but the possibility that altered motility may result from alterations in the flora has not been explored. The purpose of this study was to characterize the myoelectric activity of the small intestine in the blind loop rat model. Eight groups of rats were studied: rats with self-filling blind loops, which develop bacterial overgrowth; rats with self-emptying blind loops, which are surgical controls that do not develop overgrowth; unoperated litter mates; rats with self-filling blind loops and unoperated controls treated with chloramphenicol, 200 mg/d i.p.; rats with surgically removed self-filling blind loops; operated control rats; and gnotobiotic rats with self-filling blind loops. In the untreated rats with self-filling blind loops, there was altered myoelectric activity characterized by an increased percentage of slow waves occupied by action potentials and by organized activity similar to the migrating action potential complex. Migrating action potential complex activity and percentage of slow waves occupied by action potentials were significantly decreased with chloramphenicol therapy; that decrease correlated with a decrease in aerobes and anaerobes. Migrating action potential complex activity was abolished in rats with surgically removed self-filling blind loops; they also showed a significant decrease in percentage of slow waves occupied by action potentials. Gnotobiotic rats with self-filling blind loops showed no alteration in myoelectric activity. These data indicate: (a) bacterial overgrowth is associated with a significant increase in percentage of slow waves occupied by action potentials and migrating action potential complex activity; (b) chloramphenicol significantly reduced both percentage of slow waves occupied by action potentials and migrating action potential complex activity; and (c

  13. Oocyte maturation. Basic and clinical aspects of in vitro maturation (IVM) with special emphasis of the role of FF-MAS.

    PubMed

    Grøndahl, Christian

    2008-02-01

    treatment of human infertility is being discussed, including both the safety and efficacy issues that need to be addressed. It is being reviewed how FF-MAS and related MAS analogues by our group and other scientific groups have been observed to mediate a dose-dependant response on both the nuclear maturation and especially the cytoplasmic maturation during oocyte maturation In Vitro thus giving rise to pre-embryos of higher developmental potential. Studies are reviewed regarding the family of meiosis activating sterols, its In Vivo regulation by gonadotropins (especially LH) and suggestions to the signaling pathways as the putative MAS receptor eliciting the important cytoplasmic maturation signaling cascade that involves mos/MAP kinase. The pharmacological effect of synthetic FF-MAS has been observed in various models and species, including murine, porcine and humane oocytes. Finally, the chromosome status of IVM human oocytes has been the focus of a large prospective clinical trial, documenting that FF-MAS acting on human oocytes during In Vitro maturation presents a safe procedure evaluated on numerical chromosome aberration rates in metaphase-II oocytes. In conclusion the In Vitro maturation of human oocytes is already now a valuable clinical treatment alternative for a subset of infertile patients, especially the Polycystic Ovarian Syndrome (PCOS) patients. IVM has the promise of being tomorrow's gold standard in treatment of human infertility if most of the important components of oocyte maturation are understood and can be adequately addressed In Vitro. Considering the present low frequency of successful fertilization and pre-implantation development following In Vitro maturation of human oocytes, the addition of FF-MAS or MAS analogues to the maturation medium to improve the cytoplasmic maturation and to yield higher quality pre-embryos may prove highly beneficial.

  14. 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.

  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. 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.

  17. 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…

  18. 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…

  19. 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

  20. Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes.

    PubMed

    Martín, M; de Paz, R; Jiménez-Yuste, V; Fernández Bello, I; García Arias Salgado, E; Alvarez, M T; Butta, N V

    2013-05-01

    Patients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected. PMID:23407717

  1. [A case of Isaac's syndrome--continuous muscle fiber activity syndrome].

    PubMed

    Kuwasaki, N; Shoji, H; Tominaga, H; Kaji, M; Nonaka, K

    1986-06-01

    A 34-year-old woman noted difficulty of gait initiation, then dilated finger opening and hyperhidrosis appeared. Her stature was a muscular habitus, and muscle stiffness and myokymia were found in all muscles of the extremities. Her stiffness persisted during sleep. Her calf muscles were large and a contracture was noticed in ankle joints. There was no evidence of wasting and weakness. A remarkable delay in voluntary relaxation of the contracted muscles without percussion myotonia was recognized. Tendon reflexes of lower extremities were absent. Laboratory examination revealed elevation of CPK, LDH, myoglobulin, aldolase and basal metabolic rate (BMR). An extraband of CPK isoenzyme between MB and MM fraction was observed. The thin layer gel filtration technique and immunofixation technique showed that this extraband was complexes of CPK and IgA, and light chain of the CPK linked IgA was lambda type. All other laboratory tests were normal for the following: urinalysis, ESR, a blood count, liver function, kidney function, glucose, rheumatoid factor, CRP, thyroid function, parathyroid function, serum electrolytes, ECG, EEG, cranial CT, without slight elevation of IgA, and CSF protein. In needle EMG and surface EMG spontaneous discharges were recorded at rest. These discharges consist of normal motor unit potentials, doublets, and triplets in needle EMG. The discharges were markedly reduced after the median nerve block with xylocaine. In needle EMG, myotonic discharge was not observed. Nerve conduction velocities were within normal ranges. According to these data, she was diagnosed as having Issacs' syndrome (continuous muscle fiber activity syndrome). Carbamazepine, 200 mg daily was administrated and showed a dramatic reversal of the symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3730194

  2. 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

  3. 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

  4. 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.

  5. Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid.

    PubMed

    Olivon, V C; Aires, R D; Santiago, L B; Ramalho, L Z N; Cortes, S F; Lemos, V S

    2015-09-01

    Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response. PMID:26256416

  6. 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

  7. 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. PMID:23953425

  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. Platelet and endothelial activation in catastrophic and quiescent antiphospholipid syndrome.

    PubMed

    Bontadi, A; Ruffatti, A; Falcinelli, E; Giannini, S; Marturano, A; Tonello, M; Hoxha, A; Pengo, V; Punzi, L; Momi, S; Gresele, P

    2013-05-01

    Antiphospholipid antibodies (aPL) seem to induce a prothrombotic state by activating endothelium and platelets, but no studies have evaluated systematically the effects of aPL from patients with the antiphospholipid syndrome (APS) in quiescent versus catastrophic phase. Our aims were to evaluate the in vitro effects on platelet activation of anti-β2 glycoprotein I (anti-β2GPI) antibodiesisolated from APS patientin either quiescent or catastrophic phase and to investigate ex vivo platelet and endothelial activation in patients with quiescent or catastrophic APS. Anti-β2GPI antibodies were isolated from plasma of a pregnant woman in two different stages of APS (quiescent and catastrophic, respectively). They were co-incubated with washed platelets from healthy controls that were then challenged with TRAP-6 (thrombin receptor activating peptide 6) and the expression of P- selectin (P-sel) on platelets was assessed by flow cytometry. Moreover, plasma samples from six patients with quiescent, four with catastrophic APS and 10 controls were assessed for several markers of platelet and endothelial activation. The results showed that purified anti-β2GPI antibodies co-incubated with platelets enhanced TRAP-6- induced platelet P-sel expression. Notably, anti-β2GPI antibodies isolated during the catastrophic phase enhanced platelet P-sel expression more than antibodies isolated from the same patient in the quiescent stage of disease. Moreover, APS patients had significantly higher plasma levels of soluble (s) Psel, sCD40 ligand, soluble vascular cell adhesion molecule 1 and monocyte chemoattractant protein 1 than control subjects. In addition, sP-sel and von Willebrand factor activity were significantly higher during catastrophic than in quiescent phase. PMID:23572134

  10. 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. PMID:26559277

  11. Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways

    PubMed Central

    Pastori, Silvia; Virzì, Grazia Maria; Brocca, Alessandra; de Cal, Massimo; Cantaluppi, Vincenzo; Castellani, Chiara; Fedrigo, Marny; Thiene, Gaetano; Valente, Maria Luisa; Angelini, Annalisa; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    Cardiorenal syndrome type 1 (CRS1) pathophysiology is complex, and immune-mediated damage, including alterations in the immune response with monocyte apoptosis and cytokine release, has been reported as a potential mechanism. In this study, we examined the putative role of renal tubular epithelial cell (RTC) apoptosis as a pathogenic mechanism in CRS1. In particular, we investigated the caspase pathways involved in induced apoptosis. We enrolled 29 patients with acute heart failure (AHF), 11 patients with CRS1, and 15 controls (CTR) without AHF or acute kidney injury (AKI). Patients who had AKI prior to the episode of AHF or who had any other potential causes of AKI were excluded. Plasma from different groups was incubated with RTCs for 24 h. Subsequently, cell apoptosis, DNA fragmentation, and caspase-3, −8, and −9 activities were investigated in RTCs incubated with AHF, CRS1, and CTR plasma. A p value <0.5 was considered statistically significant. A quantitative analysis of apoptosis showed significantly higher apoptosis rates in CRS1 patients compared to AHF patients and CTR (p < 0.01). This increase in apoptosis was strongly confirmed by caspase-3 levels (ρ = 0.73). Caspase-8 and −9 were significantly higher in CRS1 patients compared to AHF patients and CTR (p < 0.01). Furthermore, caspase-3 levels showed a significantly positive correlation with caspase-8 (ρ = 0.57) and −9 (ρ = 0.47; p < 0.001). This study demonstrated the significantly heightened presence of dual apoptotic disequilibrium in CRS1. Our findings indicated that apoptosis may have a central role in the mechanism of CRS1, and it could be a potential therapeutic target in this syndrome. PMID:26648947

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

    PubMed

    Azhar, Salman

    2010-09-01

    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/ß 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. 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…

  14. 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…

  15. Brattleboro Rats as the Model of Blood Hyperviscosity Syndrome for Testing Substances with Hemorheological Activity.

    PubMed

    Plotnikov, M B; Vasil'ev, A S; Aliev, O I; Zibareva, L N

    2015-09-01

    Hyperviscosity syndrome was described in Brattleboro rats. The aim of this study was to investigate the possibility of Brattleboro rats using, as a test system for the study of agents with hemorheological activity. Under conditions of this model of high blood viscosity syndrome in Brattleboro rats, Lychnis chalcedonica L. extract (150 mg/kg) administered intragastrically for 10 days exhibited hemorheological activity by modulating macro- (plasma viscosity, fibrinogen concentration) and microrheological (erythrocyte aggregation and deformability parameters. Hence, Brattleboro rats are an adequate model of hyperviscosity syndrome that can be used for search and testing of substances with hemorheological activity. PMID:26463056

  16. 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. PMID

  17. 48 CFR 538.272 - MAS price reductions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false MAS price reductions. 538... Schedules 538.272 MAS price reductions. (a) Section 552.238-75, Price Reductions, requires the contractor to maintain during the contract period the negotiated price/discount relationship (and/or term and...

  18. 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.

  19. 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

  20. 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…

  1. Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

    PubMed Central

    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. PMID:24250786

  2. Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to activated protein C clotting inhibitor.

    PubMed

    Gambaro, G; Patrassi, G; Pittarello, F; Nardellotto, A; Checchetto, S; D'Angelo, A

    1998-10-01

    It has long been known that patients with nephrotic syndrome have a hypercoagulable state, which explains the association between nephrotic syndrome, renal vein thrombosis, and thromboembolism. However, the Budd-Chiari syndrome has never been reported in nephrotic patients. This is the first report of such an association that, most likely, depended on a primary resistance to activated protein C.

  3. 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…

  4. 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…

  5. 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

  6. Expression of the Mas receptor is upregulated in skeletal muscle wasting.

    PubMed

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

    2015-02-01

    Skeletal muscle atrophy during sepsis, immobilization, and chronic diseases is characterized by an increase in expression and activity of the muscle-specific ubiquitin 3 ligases atrogin-1 and MuRF-1. The classical renin-angiotensin system (RAS), by high level of circulating angiotensin II (AngII) is directly involved in skeletal muscle wasting associated with cardiac and renal failure. Ang (1-7), a peptide belonging to the non-classical RAS system, produces effects that are opposite to AngII. The actions of Ang (1-7) are mediated by its binding and signalling through the Mas receptor. Our purpose is to assess the effects of atrophic stimuli AngII, lipopolysaccharide (LPS), and immobilization on the expression of the Mas receptor in skeletal muscle. For that we used gastrocnemius and tibialis anterior muscles of C57BL10 mice treated with AngII, LPS or subjected to unilateral hindlimb immobilization by casting. In addition, we used C2C12 myotubes incubated with AngII or LPS. We evaluated Mas expression by quantitative real-time PCR, Western blot immunohistochemical analysis. Skeletal muscle atrophy was corroborated by the expression of atrogin-1 and MuRF-1 and the fibre diameter. Our results show that Mas receptor expression was increased by AngII or LPS in vitro and in vivo, and upregulated by immobilization. The increase of the Mas expression was concomitantly with the upregulation of atrogin-1 and MuRF-1 and the reduction of the fibre diameter. These results from studies in vitro and in vivo demonstrate for the first time that the Mas receptor is increased under atrophic stimulus and suggest that the non-classical RAS system could have an important role in muscle wasting.

  7. An electromagnetic PIC code on the MasPar

    SciTech Connect

    MacNeice, P.

    1993-12-31

    A 3D electromagnetic particle-in-cell code has been rewritten to run on the MasPar. The original code; known as TRISTAN which was written by Oscar Buneman was rewritten in MPL and its data structure altered to suit the MasPar architecture and exploit the fully local property of the algorithm. We discuss the significant issues associated with porting the code and present a comparative analysis of the code run times on the MasPar and on the CRAY YMP and C90. Results of a simulation of the interaction of the solar wind with the earth`s magnetosphere are shown.

  8. Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.

    PubMed

    Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Akter, Shamima; Hayashi, Takeshi; Mizoue, Tetsuya

    2016-09-01

    Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for <7.5, 7.5 to <16.5, and ≥16.5 metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

  9. 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

    2016-01-01

    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.

  10. 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…

  11. Active Smoking and Risk of Metabolic Syndrome: A Meta-Analysis of Prospective Studies

    PubMed Central

    Ning, Guang

    2012-01-01

    Background Epidemiological evidence suggests that smoking has been associated with emergence of metabolic syndrome. However, data on this issue are inconsistent and controversial. We therefore conducted a meta-analysis to examine the association between smoking and metabolic syndrome. Methodology and Principal Findings We searched the Medline, Embase and the Cochrane Library database up to March 2012 to identify prospective cohort studies related to smoking and metabolic syndrome. Reference lists of retrieved articles were also reviewed. Summary effect estimates were derived using a random-effects model and stratified by gender, smoking dose, follow-up duration and geographical area. Primary analysis of 13 studies involving 56,691 participants and 8,688 cases detected a significant positive association between active smoking and risk of metabolic syndrome (pooled relative risk [RR] 1.26, 95% CI: 1.10–1.44). Estimates of effects were substantially consistent in the stratified analyses. In the dose-response analysis, risk of metabolic syndrome was stronger for active male smokers (pooled RR 1.34, 95% CI: 1.20–1.50) than it was for former male smokers (pooled RR 1.19, 95% CI: 1.00–1.42), and greater for heavy smokers (pooled RR 1.42, 95% CI: 1.27–1.59) compared with light smokers (pooled RR 1.10, 95% CI: 0.90–1.35). No evidence of statistical publication bias was found (Egger' s test P = 0.227, Begg' s test P = 0.113). Conclusions Active smoking is associated with development of metabolic syndrome. Smoking cessation appears to reduce the risk of metabolic syndrome. PMID:23082217

  12. The roles of peroxisome proliferator-activated receptors in the metabolic syndrome.

    PubMed

    Mansour, Mahmoud

    2014-01-01

    The epidemic of obesity and its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X, is one of the most challenging health problems facing industrialized countries. The nuclear receptors, peroxisome proliferator-activated receptors (PPARs alpha (α), beta (β) also known as delta (δ), and gamma (γ)), have well-documented roles in lipid and glucose metabolism. Pharmacologically, PPARα is activated by fibrate hypolipidemic drugs, whereas PPARγ is activated by insulin sensitizers thiazolidinediones (TZDs). No marketed drug is yet available for PPARβ(δ). The identification of fibrates and TZDs as respective ligands for PPARα and PPARγ was a groundbreaking finding that sparked notable pharmaceutical interest in PPARs as potential drug targets for treatment of the metabolic syndrome. Limiting side effects associated with clinical use of TZDs have emerged in recent years. New and novel PPAR drugs with broad safety margins and therapeutic potentials for the metabolic syndrome are in development. These include partial, dual, or pan PPAR agonists; PPAR antagonists; and selective PPAR modulators. The objective of this chapter is to highlight the therapeutic benefits of targeting more than one PPAR subtype in the treatment of the metabolic syndrome. The pros and cons observed during clinical use of TZDs and the strategies and progress made in the production of new generations of safe and effective PPAR ligands are discussed. PMID:24373239

  13. A Drosophila model of GSS syndrome suggests defects in active zones are responsible for pathogenesis of GSS syndrome.

    PubMed

    Choi, Jin-Kyu; Jeon, Yong-Chul; Lee, Dae-Weon; Oh, Jae-Min; Lee, Hyun-Pil; Jeong, Byung-Hoon; Carp, Richard I; Koh, Young Ho; Kim, Yong-Sun

    2010-11-15

    We have established a Drosophila model of Gerstmann-Sträussler-Scheinker (GSS) syndrome by expressing mouse prion protein (PrP) having leucine substitution at residue 101 (MoPrP(P101L)). Flies expressing MoPrP(P101L), but not wild-type MoPrP (MoPrP(3F4)), showed severe defects in climbing ability and early death. Expressed MoPrP(P101L) in Drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains. We found that behavioral defects and early death of MoPrP(P101L) flies were not due to Caspase 3-dependent programmed cell death signaling. In addition, we found that Type 1 glutamatergic synaptic boutons in larval neuromuscular junctions of MoPrP(P101L) flies showed significantly increased numbers of satellite synaptic boutons. Furthermore, the amount of Bruchpilot and Discs large in MoPrP(P101L) flies was significantly reduced. Brains from scrapie-infected mice showed significantly decreased ELKS, an active zone matrix marker compared with those of age-matched control mice. Thus, altered active zone structures at the molecular level may be involved in the pathogenesis of GSS syndrome in Drosophila and scrapie-infected mice.

  14. Intensity of bouted and sporadic physical activity and the metabolic syndrome in adults

    PubMed Central

    Robson, Jordan

    2015-01-01

    Background. Physical activity guidelines for adults only recognize the health benefits of accumulating bouted moderate-to-vigorous physical activity (MVPA), or MVPA occurring over at least 10 consecutive minutes. There is a lack of evidence supporting the health benefits of other patterns and intensities of activity including sporadic MVPA (i.e., MVPA occurring in periods of fewer than 10 consecutive minutes) and light intensity physical activity (LIPA). The objective of this study was to examine the health benefits associated with physical activity that does not meet the physical activity guidelines criteria for bouted MVPA. Specifically, we examined the association between sporadic MVPA and bouted and sporadic LIPA with the metabolic syndrome. Methods. We studied a representative cross-sectional sample of 1,974 adults aged 20 years and older from the 2003–2006 US National Health and Nutrition Examination Survey. Physical activity was measured over 7 days using Actigraph AM-7164 accelerometers. Each minute over the 7-day measurement period was classified as being of a sedentary, light, or moderate-to-vigorous intensity. A 10 min threshold differentiated bouted activity from sporadic activity. Average minutes/day of sporadic LIPA, sporadic MVPA, bouted LIPA, bouted MVPA, and embedded MVPA (MVPA occurring within bouts of primarily LIPA) were calculated. Metabolic syndrome status was determined using established criteria. Associations were examined using logistic regression and controlled for relevant covariates. Results. For every 30 min/day of physical activity, the odds ratio (95% confidence interval) of the metabolic syndrome was reduced by 4% (1–7%) for bouted LIPA, 64% (51–71%) for bouted MVPA, and 57% (45–67%) for embedded MVPA. Sporadic LIPA was not independently associated with the metabolic syndrome. We could not examine the association between sporadic MVPA and the metabolic syndrome because participants accumulated such a marginal amount of this

  15. UPLC-TOF-MS Characterization and Identification of Bioactive Iridoids in Cornus mas Fruit

    PubMed Central

    West, Brett J.; Jensen, C. Jarakae

    2013-01-01

    Cornus mas L. is indigenous to Europe and parts of Asia. Although Cornus is widely considered to be an iridoid rich genera, only two iridoids have been previously found in this plant. The lack of information on taxonomically and biologically active iridoids prompted us to develop and optimize an analytical method for characterization of additional phytochemicals in C. mas fruit. An ultra performance liquid chromatography (UPLC) coupled with photodiode array spectrophotometry (PDA) and electrospray time-of-flight mass spectrometry (ESI-TOF-MS) was employed and mass parameters were optimized. Identification was made by elucidating the mass spectral data and further confirmed by comparing retention times and UV spectra of target peaks with those of reference compounds. Primary DNA damage and antigenotoxicity tests in E. coli PQ37 were used to screen the iridoids for biological activity. As a result, ten phytochemicals were identified, including iridoids loganic acid, loganin, sweroside, and cornuside. Nine of these were reported for the first time from C. mas fruit. The iridoids did not induce SOS repair of DNA, indicating a lack of genotoxic activity in E. coli PQ37. However, loganin, sweroside, and cornuside did reduce the amount of DNA damage caused by 4-nitroquinoline 1-oxide, suggesting potential antigenotoxic activity. PMID:24228188

  16. Fine Motor Activities Program to Promote Fine Motor Skills in a Case Study of Down's Syndrome.

    PubMed

    Lersilp, Suchitporn; Putthinoi, Supawadee; Panyo, Kewalin

    2016-01-01

    Children with Down's syndrome have developmental delays, particularly regarding cognitive and motor development. Fine motor skill problems are related to motor development. They have impact on occupational performances in school-age children with Down's syndrome because they relate to participation in school activities, such as grasping, writing, and carrying out self-care duties. This study aimed to develop a fine motor activities program and to examine the efficiency of the program that promoted fine motor skills in a case study of Down's syndrome. The case study subject was an 8 -year-old male called Kai, who had Down's syndrome. He was a first grader in a regular school that provided classrooms for students with special needs. This study used the fine motor activities program with assessment tools, which included 3 subtests of the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) that applied to Upper-limb coordination, Fine motor precision and Manual dexterity; as well as the In-hand Manipulation Checklist, and Jamar Hand Dynamometer Grip Test. The fine motor activities program was implemented separately and consisted of 3 sessions of 45 activities per week for 5 weeks, with each session taking 45 minutes. The results showed obvious improvement of fine motor skills, including bilateral hand coordination, hand prehension, manual dexterity, in-hand manipulation, and hand muscle strength. This positive result was an example of a fine motor intervention program designed and developed for therapists and related service providers in choosing activities that enhance fine motor skills in children with Down's syndrome. PMID:27357876

  17. 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…

  18. Physical activity, physical fitness, gross motor coordination, and metabolic syndrome: focus of twin research in Portugal.

    PubMed

    Maia, José António Ribeiro; Santos, Daniel; de Freitas, Duarte Luis; Thomis, Martine

    2013-02-01

    A very brief history of Portuguese twin research in sport and human movement sciences is presented. Recruitment procedures, zygosity determination, and phenotypes are given for twins and their parents from the mainland, and Azores and Madeira archipelagos. Preliminary findings are mostly related to physical activity, health-related physical fitness, gross motor coordination, neuromotor development, and metabolic syndrome traits.

  19. 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…

  20. 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…

  1. 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. PMID:26851244

  2. 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

  3. 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.

  4. 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.

  5. Increased sleep spindle activity in patients with Costello syndrome (HRAS gene mutation).

    PubMed

    Della Marca, Giacomo; Leoni, Chiara; Dittoni, Serena; Battaglia, Domenica; Losurdo, Anna; Testani, Elisa; Colicchio, Salvatore; Gnoni, Valentina; Gambardella, Maria L; Mariotti, Paolo; Alfieri, Paolo; Tartaglia, Marco; Zampino, Giuseppe

    2011-06-01

    Costello syndrome is a congenital disorder because of HRAS gene mutation, frequently associated with neurologic impairment and sleep disorders. The aims of the study were to evaluate the sleep EEG, and particularly the sleep spindles, in a population of patients with Costello syndrome and to compare them with those characterizing unaffected subjects. Eleven subjects (5 men and 6 women) with Costello syndrome were included in the study; age ranged between 18 months and 31 years (mean, 9.6 ± 9.4 years). The diagnosis was posed on the basis of established clinical criteria and confirmed molecularly. Sleep EEG was studied by means of full-night, laboratory-based video-polysomnography, performed overnight, during hospitalization. Sleep activity was quantified by means of power spectral analysis. Patients heterozygous for an HRAS mutation exhibited increased EEG power in 12- to 15-Hz activity band compared with age-matched control subjects. In conclusion, the authors observed a consistent increase in the amplitude of cortical sleep spindles in all our subjects with an HRAS mutation. These "giant" spindles were not associated with any evidence of structural damage of the cortex or the thalami and should be considered as phenotypic feature of sleep EEG activity in Costello syndrome because of HRAS mutation.

  6. The effect of FF-MAS on porcine cumulus-oocyte complex maturation, fertilization and pronucleus formation in vitro.

    PubMed

    Faerge, Inger; Strejcek, Frantisek; Laurincik, Jozef; Rath, Detlef; Niemann, Heiner; Schellander, Karl; Rosenkranz, Christine; Hyttel, Poul Maddox; Grøndahl, Christian

    2006-08-01

    Follicular fluid meiosis-activating sterol (FF-MAS) has been isolated from the follicular fluid (FF) of several species including man. FF-MAS increases the quality of in vitro oocyte maturation, and thus the developmental potential of oocytes exposed to FF-MAS during in vitro maturation is improved. The aim of the present study was to investigate the effects of FF-MAS on porcine oocyte maturation and pronucleus formation in vitro. Porcine cumulus-oocyte complexes (COCs) were isolated from abattoir ovaries and in vitro matured for 48 h in NCSU 37 medium supplemented with 1 mg/l cysteine, 10 ng/ml epidermal growth factor and 50 microM 2-mercaptoethanol with or without 10% porcine follicular fluid (pFF). For the first 22 h, 1 mM db-cAMP and 10 I.E PMSG/hCG was added. The medium was supplemented with 1 microM, 3 microM, 10 microM, 30 microM or 100 microM FF-MAS dissolved in ethanol. After maturation the COCs were denuded mechanically using a fine glass pipette under constant pH and in vitro fertilized with fresh semen (5 x 10(5) spermatozoa/ml). The presumptive zygotes were evaluated 18 h after fertilization. The addition of pFF increased the monospermic as well as the polyspermic penetration of oocytes. In the absence of pFF, the addition of FF-MAS decreased the polyspermic penetration rate, whereas FF-MAS in combination with pFF decreased monospermic and increased polyspermic penetration. The degeneration rate of ova decreased in the presence of FF-MAS irrespective of the presence or absence of pFF. In the absence of pFF, FF-MAS at 3-10 microM increased the number of zygotes with advanced maternal pronuclear stages. In supraphysiological doses, i.e. 30-100 microM, FF-MAS dose-dependently and reversibly inhibited nuclear maturation in the absence of pFF.

  7. Rho-Associated Kinase Activity Is an Independent Predictor of Cardiovascular Events in Acute Coronary Syndrome

    PubMed Central

    Kajikawa, Masato; Noma, Kensuke; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Matsumoto, Takeshi; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Aibara, Yoshiki; Chayama, Kazuaki; Sasaki, Shota; Kato, Masaya; Dote, Keigo; Goto, Chikara; Liao, James K.; Higashi, Yukihito

    2016-01-01

    Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98–11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome. PMID:26283039

  8. Verification of the MAS TMM by infrared TB/TV testing methods

    NASA Astrophysics Data System (ADS)

    Szigetvari, Z.

    1990-09-01

    The structural/Thermal Mathematical Model (TMM) of the remote sensing instrument MAS (Microwave Atmospheric Sounder) was successfully TB/TV tested in a space simulation chamber. MAS is thermally characterized by strongly varying orbital heat loads and multiple solar reflections when situated in the orbiter cargo bay. Due to the complicated orbital environment and to budget limitations, the test objectives were simplified and achieved by infrared TB/TV testing methods. The simulation of the external radiative heat loads from Sun, Earth and orbiter cargo bay walls was realized by controlling the test chamber shroud temperatures at desired levels. The activities during preparation, completion and evaluation of the conducted infrared TB/TV tests are described and among others the implemented test data evaluation system DIANA is highlighted.

  9. High-temperature MAS-NMR at high spinning speeds.

    PubMed

    Kirchhain, Holger; Holzinger, Julian; Mainka, Adrian; Spörhase, Andreas; Venkatachalam, Sabarinathan; Wixforth, Achim; van Wüllen, Leo

    2016-09-01

    A low cost version to enable high temperature MAS NMR experiments at temperatures of up to 700°C and spinning speeds of up to 10kHz is presented. The method relies on inductive heating using a metal coated rotor insert. The metal coating is accomplished via a two step process involving physical vapor deposition and galvanization.

  10. 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. PMID:1533951

  11. 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.

  12. The syndrome of continuous muscle fibre activity following gold therapy.

    PubMed

    Grisold, W; Mamoli, B

    1984-01-01

    A 72-year-old man suffering from arthritis received a total dose of 500 mg sodium aurothiomalate during a period of 5 months. His clinical state then deteriorated and he had to be hospitalized. Upon admission he was bedridden, his level of consciousness was slightly impaired, he was confused and respiration was laboured. Continuous muscle activity was noted on all extremities and at first, erroneously, fasciculations were diagnosed. The EMG exhibited continuous muscle fibre activity consisting of duplets, triplets and multiplets. The discharges occurred in an irregular pattern; when various muscles were examined at the same time no synchronicity could be observed between muscle discharges. In the left m. deltoideus an increased percentage of polyphasic potentials was found, whereas mean duration of motor unit potentials was normal. Spontaneous activity remained unchanged during sleep and administration of intravenous diazepam or phenytoin. Blocking of ulnar nerve at either elbow or wrist level did not stop spontaneous activity in m. abductor digiti quinti. Ischaemia increased the amount of discharges after 7 min. Within 4 months after termination of gold therapy the patient's condition improved and he was discharged from hospital. Regular EMG follow-up after 8 months showed complete cessation of abnormal spontaneous activities. Nerve conduction velocities were normal except for markedly reduced compound action potential in peroneal nerves. Continuous muscle fibre activity as a side-effect of gold therapy is described. PMID:6440953

  13. Oral Pigmentation in McCune-Albright Syndrome

    PubMed Central

    Pichard, Dominique C.; Boyce, Alison M.; Collins, Michael T.; Cowen, Edward W.

    2016-01-01

    IMPORTANCE The differential diagnosis for oral lentigines includes several syndromes with important associated systemic findings. McCune-Albright syndrome (MAS), a mosaic condition associated with café au lait pigmentation, is not typically considered a mucosal lentiginosis syndrome. The clinical phenotype of MAS is variable because of mosaicism, but oral pigmentation developing in mid-childhood to early adulthood should be recognized as a clinical feature of MAS. OBSERVATIONS We present 4 patients with MAS who developed oral mucosal pigmentation during childhood or early adulthood. All patients had other characteristic findings of MAS including hyperfunctioning endocrinopathies, polyostotic fibrous dysplasia, and café au lait pigmentation. CONCLUSIONS AND RELEVANCE Oral pigmentation is an underrecognized finding in MAS and presents later in development compared with the other mucosal lentiginosis syndromes. The diagnosis of MAS is most commonly a clinical diagnosis because mutational analysis is challenging in mosaic conditions. Expanding the cutaneous phenotype to include oral pigmentation further characterizes the clinical findings in this mosaic condition, broadens the differential diagnosis of syndromes with oral pigmentation, and in some cases may aid in earlier diagnosis of MAS. PMID:24671640

  14. 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.

  15. The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities.

    PubMed

    Amendt, B A; Sutherland, L B; Semina, E V; Russo, A F

    1998-08-01

    Rieger syndrome is an autosomal-dominant developmental disorder that includes glaucoma and mild craniofacial dysmorphism in humans. Mutations in the Pitx2 homeobox gene have been linked to Rieger syndrome. We have characterized wild type and mutant Pitx2 activities using electrophoretic mobility shift assays, protein binding, and transient transfection assays. Pitx2 preferentially binds the bicoid homeodomain binding site and transactivates reporter genes containing this site. The combination of Pitx2 and another homeodomain protein, Pit-1, yielded a synergistic 55-fold activation of the prolactin promoter in transfection assays. Addition of Pit-1 increased Pitx2 binding to the bicoid element in electrophoretic mobility shift assays. Furthermore, we demonstrate specific binding of Pit-1 to Pitx2 in vitro. Thus, wild type Pitx2 DNA binding activity is modulated by protein-protein interactions. We next studied two Rieger mutants. A threonine to proline mutation (T68P) in the second helix of the homeodomain retained DNA binding activity with the same apparent KD and only about a 2-fold reduction in the Bmax. However, this mutant did not transactivate reporter genes containing the bicoid site. The mutant Pitx2 protein binds Pit-1, but there was no detectable synergism on the prolactin promoter. A second mutation (L54Q) in a highly conserved residue in helix 1 of the homeodomain yielded an unstable protein. Our results provide insights into the potential mechanisms underlying the developmental defects in Rieger syndrome. PMID:9685346

  16. 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.

  17. Processing of CP MAS kinetics: Towards NMR crystallography for complex solids

    NASA Astrophysics Data System (ADS)

    Dagys, Laurynas; Klimavicius, Vytautas; Balevicius, Vytautas

    2016-09-01

    Variable temperature and high data point density measurements of 1H-31P cross-polarization kinetics in the powdered ammonium dihydrogen phosphate (ADP) have been carried out in the range of -40 °C to +90 °C upon 7 and 10 kHz MAS. The advanced route of processing CP MAS kinetic data has been developed. It is based on reducing the incoherent far range order spin couplings and extracting the CP oscillatory term with the sequent mathematical treatment. The proper replica has been found, which allowed to reduce the Fourier-Bessel (Hankel) transform calculating the angularly averaged and purely distance-depending spin distribution profile to the routine Fourier transform. The shortest 31P-1H distances determined by CP MAS kinetics get between the values obtained by neutron and X-ray diffraction, whereas those for more remote protons are slightly larger. The changes in P⋯H distances are hardly noticeable, though a certain trend to increase upon the heating can be deduced. The clearly pronounced effect was the increase of the spin-diffusion rate constant upon heating. It allows to state that the communication between interacting spins is the process extremely easy to activate.

  18. [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. PMID:22342516

  19. 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

  20. Longitudinal assessment of leg motor activity and sleep patterns in infants with and without Down syndrome.

    PubMed

    McKay, Sandra M; Angulo-Barroso, Rosa M

    2006-04-01

    Whether infants with Down syndrome (DS) perform leg movements with the same frequency and quality as their typical development (TD) counterparts is equivocal. Furthermore, the relationship between these early leg movements and later onset of locomotor milestones has only been partially explored. The aims of this study were two-fold: (1) to describe the longitudinal leg activity in infants with and without DS (3-6 months), and (2) to examine sleeping patterns and leg activity during the night. In addition, the relationships between leg activities and sleep patterns with locomotor development were explored. An activity monitor was placed monthly on the infant's ankle for 48 h. Data were analyzed to separate day-night, high-low activity, and sleep fragmentation. The results indicate that infants with DS produced more low intensity activity and more fragmented sleep. These findings are discussed in relation to the influence of early motor activity on achievement of functional motor behavior.

  1. Cross ambiguity functions on the MasPar MP-2

    SciTech Connect

    Carlson, D.A.; Pryor, D.V.; Frock, C.K.

    1995-12-01

    In a signal processing environment, cross ambiguity functions are often used to detect when one signal is a time and/or frequency shift of another. They consist of multiple cross-correlations, which can be computed efficiently using complex valued FFTs. This paper discusses the implementation of cross ambiguity functions on the MasPar MP-2, a SIMD processor array. Two different implementations are developed. The first computes each cross ambiguity function serially, using FFT code that parallelizes across the complete set of processors. The second uses the MasPar IORAM to realign the data so that the cross ambiguity functions can be computed in parallel. In this case, multiple FFTs are executed in parallel on subsets of the processors, which lowers the overall amount of communication required.

  2. 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.

  3. Triple trouble--macrophage activation syndrome in a case of severe leptospirosis and scrub typhus co-infection.

    PubMed

    Diwan, A G; Shewale, Rahul; Iyer, Shivakumar; Nisal, Amit; Agrawa, Prakhar

    2014-01-01

    Macrophage activation syndrome is a potentially life threatening phenomenon characterised by aggressive proliferation of macrophages and T lymphocytes leading to haemophagocytosis of other blood cells and multi organ failure. Here we present a very unusual combination of leptospirosis and scrub typhus infection leading to macrophage activation syndrome. Scrub typhus associated with macrophage activation syndrome has rarely been reported in India. A 40 year old female presented with high grade fever, seizures, bodyache, arthralgia and severe breathlessness. Investigations revealed persistent thrombocytopenia, impaired liver function tests, renal dysfunction, leptospiral IgM ELISA positive and a positive Weil Felix test. There was evidence of haemophagocytosis in bone marrow. Macrophage activation syndrome if left untreated has been associated with rapidly fatal outcome and early treatment can help us save that one precious thing..called life..! PMID:25327097

  4. Activated STING in a Vascular and Pulmonary Syndrome

    PubMed Central

    Yang, D.; Ramsey, S.E.; Sanchez, G.A. Montealegre; Tenbrock, K.; Wittkowski, H.; Jones, O.Y.; Kuehn, H.S.; Lee, C.-C.R.; DiMattia, M.A.; Cowen, E.W.; Gonzalez, B.; Palmer, I.; DiGiovanna, J.J.; Biancotto, A.; Kim, H.; Tsai, W.L.; Trier, A.M.; Huang, Y.; Stone, D.L.; Hill, S.; Kim, H.J.; Hilaire, C. St.; Gurprasad, S.; Plass, N.; Chapelle, D.; Horkayne-Szakaly, I.; Foell, D.; Barysenka, A.; Candotti, F.; Holland, S.M.; Hughes, J.D.; Mehmet, H.; Issekutz, A.C.; Raffeld, M.; McElwee, J.; Fontana, J.R.; Minniti, C.P.; Moir, S.; Kastner, D.L.; Gadina, M.; Steven, A.C.; Wingfield, P.T.; Brooks, S.R.; Rosenzweig, S.D.; Fleisher, T.A.; Goldbach-Mansky, R.

    2014-01-01

    BACKGROUND The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-β, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mono-nuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibro-blasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients’ lymphocytes was

  5. 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…

  6. The syndrome of continuous muscle fiber activity. Evidence to suggest proximal neurogenic causation.

    PubMed

    Irani, P F; Purohit, A V; Wadia, N H

    1977-04-01

    Four patients with the syndrome of continuous muscle fiber activity were seen in a period of 6 years. Young females predominated. Remarkable improvement followed phenytoin sodium and carbamazepine administration in three patients, one of whom was "cured" within 4 years. In the remaining patient the response was inconstant. Electromyography showed abnormal spontaneous activity with diphasic and triphasic potentials appearing as doublets and multiplets. Waxing and waning was observed. D-tubocurarine and succinylcholine abolished the spontaneous activity excluding the muscle and the myoneural junction as its source. Spinal anesthesia, thiopental sodium, sleep and baclofen had no effect on it, ruling out a central source. In three patients, nerve blocks at the knee and elbow or wrist abolished this activity pointing to a proximal site of origin in the nerve somewhere between the spinal cord and the nerve block. In the remaining patient such a block significantly reduced but did not abolished the activity suggesting a dual source above and below the block. Finally successive examinations in one of our patients led us to believe that this activity may arise from different sites at varying times. It appears that regardless of the site of origin of the activity in the motor axon the counter part clinical syndrome remains the same. PMID:857572

  7. 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.

  8. 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

  9. Possible C1q bypass loop activation in the haemolytic uraemic syndrome.

    PubMed Central

    Nolin, L; O'Regan, S; Pelletier, M; Rivard, G E; Mongeau, J G; Robitaille, P

    1979-01-01

    Ultrastructural and immunofluorescent microscopic studies were performed on renal tissue obtained from nine patients during the acute and convalescent phase of the haemolytic uraemic syndrome (HUS). All had glomerular deposits of IgM in the absence of circulating immune complexes. This was associated with deposition of C1q during the acute phase, and properdin and C3 during the convalescent phase. C4 was consistently absent. Since such a pattern of complement deposition does not fulfil criteria either for alternate or classical pathway activation, the possibility of C1q bypass loop activation by IgM is suggested. PMID:371879

  10. [Bioelectric activity of cervix uteri in normal menstrual cycle and in the syndrome of sclerocystic ovaries].

    PubMed

    Rymashevskiĭ, V K; Kozhin, A A; Chzhan Chun'; Gorchakov, L A

    1974-10-01

    34 20-26 year old women with anovulatory cycles with the Stein syndrome and 5 women with normal menstrual cycles were studied in regard to bioelectric cervical activity by means of a vaginal probe and the micrograph ''Medicore.'' In the control group, an increase of progesterone in the 2nd phase of the cycle led to a decrease in the electromyographic (EMG) amplitude. In the anovulatory cycle, the extended activity of estrogens and minimal amount of progesterone stimulated a high tone of uterine impulses, which was substantiated by a high EMG proved to be effective and useful in the diagnosis of gynecological patients. PMID:4440834

  11. Thoracic outlet syndrome of pectoralis minor etiology mimicking cardiac symptoms on activity: a case report

    PubMed Central

    Fitzgerald, Gary

    2012-01-01

    Thoracic outlet syndrome is the result of compression or irritation of neurovascular bundles as they pass from the lower cervical spine into the arm, via the axilla. If the pectoralis minor muscle is involved the patient may present with chest pain, along with pain and paraesthesia into the arm. These symptoms are also commonly seen in patients with chest pain of a cardiac origin. In this case, a patient presents with a history of left sided chest pain with pain and paraesthesia into the left upper limb, which only occurs whilst running. The symptoms were reproduced on both digital pressure over the pectoralis minor muscle and on provocative testing for thoracic outlet syndrome. The patient’s treatment therefore focused on the pectoralis minor muscle, with a complete resolution of symptoms. This illustrates that not all cases of chest pain with associated arm symptoms that occur on physical activity are of cardiac origin. PMID:23204575

  12. MECHANISMS IN ENDOCRINOLOGY: Tissue-specific activation of cortisol in Cushing's syndrome.

    PubMed

    Morgan, Stuart A; Hassan-Smith, Zaki K; Lavery, Gareth G

    2016-08-01

    Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have 'Cushingoid' side effects including visceral obesity, muscle myopathy, hypertension, insulin resistance, type 2 diabetes mellitus, osteoporosis, and hepatic steatosis. These features are replicated in patients with much rarer endogenous glucocorticoid (GC) excess (Cushing's syndrome), which has devastating consequences if left untreated. Current medical therapeutic options that reverse the tissue-specific consequences of hypercortisolism are limited. In this article, we review the current evidence that local GC metabolism via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a central role in mediating the adverse metabolic complications associated with circulatory GC excess - challenging our current view that simple delivery of active GCs from the circulation represents the most important mode of GC action. Furthermore, we explore the potential for targeting this enzyme as a novel therapeutic strategy for the treatment of both endogenous and exogenous Cushing's syndrome.

  13. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

    PubMed

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

    2014-05-01

    Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence. PMID:24788150

  14. The Relationship Between Diabetes, Metabolic Syndrome, and Platelet Activity as Measured by Mean Platelet Volume

    PubMed Central

    Shah, Binita; Sha, Daohang; Xie, Dawei; Mohler, Emile R.; Berger, Jeffrey S.

    2012-01-01

    OBJECTIVE The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control. RESEARCH DESIGN AND METHODS This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression. RESULTS MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control. CONCLUSIONS Mean platelet volume is strongly and independently associated with the presence and severity of diabetes. PMID:22410814

  15. Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

    PubMed

    Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

    2002-01-01

    Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue. PMID:12199350

  16. 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

  17. A general protocol for temperature calibration of MAS NMR probes at arbitrary spinning speeds.

    PubMed

    Guan, Xudong; Stark, Ruth E

    2010-01-01

    A protocol using (207)Pb 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

  18. 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

  19. Radioiodine treatment in McCune–Albright syndrome with hyperthyroidism

    PubMed Central

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

    2012-01-01

    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. PMID:22837937

  20. Impairment in Instrumental Activities of Daily Living and the Geriatric Syndrome of Self-Neglect

    PubMed Central

    Naik, Aanand D.; Burnett, Jason; Pickens-Pace, Sabrina; Dyer, Carmel B.

    2010-01-01

    Purpose We sought to characterize self-neglect definitively as a geriatric syndrome by identifying an association with functional impairment. Design and Methods We performed a cross-sectional home evaluation of 100 community-living older adults referred by Adult Protective Services for geriatric self-neglect and 100 matched adults from a community geriatrics clinic. We made our assessments by using two manual muscle tests, a timed-gait test, a modified Physical Performance Test (mPPT), and the Kohlman Evaluation of Living Skills (KELS). Results Participants in the self-neglect group had impaired mPPT (p < .077) and KELS (p < .001) scores compared with community-controls. Using analysis of covariance models, we found that self-neglect referral explained a significant proportion of the variance in KELS scores (32%; p < .001) but not in mPPT scores (22%; p = .49). Implications The geriatric syndrome of self-neglect is associated with increased morbidity and mortality and appears to be independently associated with impairments in instrumental activities of daily living. The evaluation and treatment of geriatric self-neglect should be consistent with that of other geriatric syndromes. PMID:18591364

  1. 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.

  2. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome?

    PubMed

    Fowler, C J; Christmas, T J; Chapple, C R; Parkhouse, H F; Kirby, R S; Jacobs, H S

    1988-12-01

    A potential association between abnormal electromyographic activity--that is, decelerating bursts and complex repetitive discharges--of the urethral sphincter and difficulty in voiding was examined in 57 women with urinary retention. Abnormal electromyographic activity was found in 33. Ultrasonography of the ovaries in 22 of the 33 women showed that 14 had polycystic ovaries. Of the other eight women, two had had oophorectomies, one had shrunken ovaries and ovarian failure, and one had previously undergone oophorectomy and the other ovary could not be seen; in one neither ovary could be seen, and three had ovaries of normal appearance, although two of these women were taking the contraceptive pill. Thirteen of the group had endocrine symptoms and signs characteristic of the polycystic ovary syndrome. Videocystometrography in 17 of the women who were examined by ultrasonography showed low flow rates and high residual volumes of urine after micturition in 12 women who could void, the other five having chronic urinary retention. A speculative hypothesis for the observed association of impaired voiding, abnormal electromyographic activity of the urinary sphincter, and polycystic ovaries is advanced, based on the relative progesterone deficiency that characterises the polycystic ovary syndrome. Progesterone stabilises membranes, and its depletion might permit ephaptic transmission of impulses between muscle fibres in the muscle of the urethral sphincter, giving rise to the abnormal electromyographic activity. This may impair relaxation of the sphincter, resulting in low flow rates of urine, incomplete emptying of the bladder, and, finally, urinary retention.

  3. A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome.

    PubMed

    Mimura, Masaru; Hoeft, Fumiko; Kato, Motoichiro; Kobayashi, Nobuhisa; Sheau, Kristen; Piggot, Judith; Mills, Debra; Galaburda, Albert; Korenberg, Julie R; Bellugi, Ursula; Reiss, Allan L

    2010-01-26

    Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. METHODS: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS. PMID:21304831

  4. Assessment of coagulation disorders and cancer procoagulant activity in patients with myelodysplastic syndromes.

    PubMed

    Chojnowski, K; Treliński, J; Wawrzyniak, E; Sobolewska, M; Mielicki, W

    2002-01-01

    Hemostatic disorders mainly due to thrombocytopenia represent an important clinical problem in patients with myelodysplastic syndromes (MDS). Much less is known about the possible coagulation abnormalities. Thirty patients with MDS were studied. Activity of cancer procoagulant (CP), concentrations of activation markers of coagulation and fibrinolysis such as thrombin-antithrombin complexes (TAT), prothrombin fragment 1+2 (F1+2) and D-dimers (DD) as well as standard coagulation tests were determined. Coagulation abnormalities concerned mainly patients with RAEB and RAEB-t. In this group the mean values of TATand F1+2 concentrations were significantly higher than in control indicating chronic coagulation activation similar to that observed in acute leukemias. CP activity in MDS patients did not differ from the control group.

  5. Multinuclear MAS NMR investigation of zeolites reacted with chlorofluorocarbons

    NASA Astrophysics Data System (ADS)

    Hannus, I.; Kónya, Z.; Lentz, P.; Nagy, J. B.; Kiricsi, I.

    1999-05-01

    Multinuclear ( 23Na, 27Al, 29Si, 13C) MAS NMR techniques were used for investigation of surface reaction of Y-type zeolites with CFCs (CCl 4, CCl 3F, CCl 2F 2, CClF 3, CF 4) and HCFC (CHClF 2). The hydrogen containing derivative reacts slowly. Those possessing more than 2 F atoms can be regarded as stable unreactive materials. CCl 4, CCl 3F, CCl 2F 2 react strongly with the zeolites. The reaction of HCFC with zeolites has a different mechanism to the other CFCs tested. On the basis of multinuclear NMR results a mechanism is given for the decomposition of HCFC.

  6. Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome

    PubMed Central

    Dong, Chen; Zhou, Hui; Shen, Chong; Yu, Lu-Gang; Ding, Yi; Zhang, Yong-Hong; Guo, Zhi-Rong

    2015-01-01

    Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are the serious public health problems worldwide. Moreover, it is estimated that MetS patients have about five-fold greater risk of the T2DM development compared with people without the syndrome. Peroxisome proliferator-activated receptors are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of MetS and T2DM. All three members of the peroxisome proliferator-activated receptor (PPAR) nuclear receptor subfamily, PPARα, PPARβ/δ and PPARγ are critical in regulating insulin sensitivity, adipogenesis, lipid metabolism, and blood pressure. Recently, more and more studies indicated that the gene polymorphism of PPARs, such as Leu162Val and Val227Ala of PPARα, +294T > C of PPARβ/δ, Pro12Ala and C1431T of PPARγ, are significantly associated with the onset and progressing of MetS and T2DM in different population worldwide. Furthermore, a large body of evidence demonstrated that the glucose metabolism and lipid metabolism were influenced by gene-gene interaction among PPARs genes. However, given the complexity pathogenesis of metabolic disease, it is unlikely that genetic variation of a single locus would provide an adequate explanation of inter-individual differences which results in diverse clinical syndromes. Thus, gene-gene interactions and gene-environment interactions associated with T2DM and MetS need future comprehensive studies. PMID:25987964

  7. Hand ischemia in active patients: detecting and treating hypothenar hammer syndrome.

    PubMed

    Rowan, L J

    1998-01-01

    Occlusion of the palmar arch vessels is rare, but it can occur in athletes and workers who subject their hands to repeated blunt trauma or gripping activities. A case report examines a baseball player who presented with classic symptoms of hypothenar hammer syndrome (occlusion of the ulnar artery due to repetitive blunt trauma); evaluation also identified radial artery occlusion. Occlusive symptoms include pain, cold intolerance, and numbness. The diagnosis rests on evaluating the patency of the palmar arches. Conservative treatment involves rest, tobacco avoidance, and medications. Patients who have severe arterial compromise require resection and reconstruction.

  8. Antinociceptive Activity and Effect of Methanol Extracts of Three Salvia Spp. on Withdrawal Syndrome in Mice

    PubMed Central

    Karami, Mohammad; Shamerani, Mohammad Mehdi; Hossini, Ebrahim; Gohari, Ahmad Reza; Ebrahimzadeh, Mohammad Ali; Nosrati, Anahita

    2013-01-01

    Purpose: There are several reports about effects of Salvia spp. on CNS. The present experiment is undertaken to study effect of S. limbata, S. hypoleuca and S. macrosiphon on withdrawal syndrome in mice. Methods: Antinociceptive activities of aerial parts of Salvia spp. is investigated using hot plate method. In addition, the effect of its aerial parts on morphine dependence is investigated in mice. After induction of morphine dependency, different concentrations of plant extract are injected. To assess morphine withdrawal, naloxone (5 mg kg-1, i.p.) are injected into mice on the 5th day. Withdrawal syndrome is assessed by placing each mouse in a glass box 30 cm in height and recording the incidence of escape jumps for 60 minutes. Results: A decrease in incidence of escape jumps is observed in morphine dependence mice. S. limbata and S. hypoleuca extracts produced a statistically significant inhibition of pain induced by hot plate latency at (500, 1000 and 1500 mg kg-1) i.p. A significant increase in pain threshold is observed after 30 and 60 minutes (p < 0.001). The activity was comparable to that of morphine (30 mg kg-1, i.p., p > 0.05). The antinociceptive activity increased up to 60 minutes. Conclusion: S. limbataand S. hypolecuca extracts produced statistically significant inhibition of pain and development of morphine dependence in mice. PMID:24312878

  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. Leisure activities in Prader-Wili syndrome: implications for health, cognition and adaptive functioning.

    PubMed

    Dykens, Elisabeth M

    2014-02-01

    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 frequent recreational activity, and was associated with compulsivity and skin picking. BMIs were negatively correlated with physical play, and highest in those who watched TV and played computer games. Computer games and physical activities were associated with higher IQ and adaptive scores. People with PWS and other disabilities need to watch less TV and be more engaged in physical activities, games, and leisure pursuits that are fun, and may bring cognitive or adaptive advantages.

  11. Type IX Ehlers-Danlos syndrome and Menkes syndrome: the decrease in lysyl oxidase activity is associated with a corresponding deficiency in the enzyme protein.

    PubMed Central

    Kuivaniemi, H; Peltonen, L; Kivirikko, K I

    1985-01-01

    Type IX of the Ehlers-Danlos syndrome (E-D IX) and the Menkes syndrome are X-linked recessively inherited disorders characterized by abnormalities in copper metabolism. These abnormalities are associated with a severe reduction in the activity of lysyl oxidase, the extracellular copper enzyme that initiates crosslinking of collagens and elastin. No increase in this deficient enzyme activity was obtained when culture media from fibroblasts of patients with E-D IX or the Menkes syndrome were incubated with copper under various conditions in vitro. A distinct, although small, increase in lysyl oxidase activity was obtained, however, when copper-supplemented media were used during culturing of the fibroblasts, although even under these conditions, the enzyme activity in the media from the affected cells remained markedly below that of the controls. Immunoprecipitation, dot-blotting, and immunoperoxidase staining experiments with antisera to human lysyl oxidase indicated that fibroblasts from patients with E-D IX or the Menkes syndrome do not secrete into their medium, or contain inside the cell, any significant amounts of a copper-deficient, catalytically inactive lysyl oxidase protein. These findings appear to be consistent with the hypothesis that synthesis of the lysyl oxidase protein itself is impaired. The possibility is not excluded, however, that a copper-deficient enzyme protein may be synthesized in normal amounts but become degraded very rapidly inside the cell. The failure to obtain any large increase in the deficient lysyl oxidase activity upon various forms of copper administration suggests that it may not be possible to obtain any significant improvement in the connective tissue manifestations of these disorders by copper therapy. Images Fig. 1 Fig. 2 PMID:9556668

  12. 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.

  13. 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. PMID:27492469

  14. 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

  15. 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

  16. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

    PubMed

    Kundur, Avinash R; Singh, Indu; Bulmer, Andrew C

    2015-03-01

    Gilbert's syndrome (GS) is a relatively common condition, inducing a benign, non-hemolytic, unconjugated hyperbilirubinemia. Gilbert's Syndrome is associated with mutation in the Uridine Glucuronosyl Transferase 1A1 (UGT1A1) gene promoter, reducing UGT1A1 activity, which normally conjugates bilirubin allowing its elimination from the blood. Individuals with GS demonstrate mildly elevated plasma antioxidant capacity caused by elevated levels of unconjugated bilirubin (UCB), reduced thiols and glutathione. Interestingly, the development of, and risk of mortality from, cardiovascular disease is remarkably reduced in GS individuals. An explanation for this protection may be explained by bilirubin's ability to inhibit multiple processes that induce platelet hyper-reactivity and thrombosis, thus far under-appreciated in the literature. Reactive oxygen species are produced continuously via metabolic processes and have the potential to oxidatively modify proteins and lipids within cell membranes, which may encourage the development of thrombosis and CVDs. Oxidative stress induced platelet hyper-reactivity significantly increases the risk of thrombosis, which can potentially lead to tissue infarction. Here, we discuss the possible mechanisms by which increased antioxidant status might influence platelet function and link this to cardiovascular protection in GS. In summary, this is the first article to discuss the possible role of bilirubin as an anti-thrombotic agent, which inhibits platelet activation and potentially, organ infarction, which could contribute to the reduced mortality rate in mildly hyperbilirbinemic individuals. PMID:25576848

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

    PubMed

    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

  18. Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

    PubMed Central

    Thornbrough, Joshua M.; Jha, Babal K.; Yount, Boyd; Goldstein, Stephen A.; Li, Yize; Elliott, Ruth; Sims, Amy C.; Baric, Ralph S.; Silverman, Robert H.

    2016-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention. PMID:27025250

  19. Evaluation of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis: single center experience over a one-year period

    PubMed Central

    Barut, Kenan; Yücel, Gözde; Sinoplu, Ada Bulut; Şahin, Sezgin; Adroviç, Amra; Kasapçopur, Özgür

    2015-01-01

    Aim: This study aimed to evaluate the demographic, clinical, laboratory properties of patients with macrophage activation syndrome and treatment outcomes. Material and Methods: The data of the patients who were diagnosed with macrophage activation syndrome secondary to systemic juvenile idiopathic arthritis between June 2013–May 2014 were evaluated by screening patient records. Results: Ten patients with macrophage activation syndrome were followed up in one year. The mean age at the time of diagnosis was found to be 7.6±4.5 years. The most common clinical finding at presentation (80%) was increased body temperature. Hepatosplenomegaly was found in half of the patients. The most common hematological finding (90%) was anemia. The mean erythrocyte sedimentation rate was found to be 71.8±36.2 mm/h, whereas it was measured to be lower (31.2±25.2 mm/h) at the time of the diagnosis of macrophage activation syndrome. Increased ferritin level was found in all of our patients (the mean ferritin level was found to be 23 957±15 525 ng/mL). Hypertriglyceridemia was found in nine patients (90%). The mean triglyceride level was found to be 397±332 mg/dL. Systemic steroid treatment was administered to all patients. Cyclosporine A was given to eight patients (80%), canakinumab was given to four patients (40%) and anakinra was given to five patients (50%). Plasmapheresis was performed in two patients. Improvement was found in all patients except for one patient. The patient in whom no improvement was observed showed a chronic course. Conclusions: The diagnosis of macrophage activation syndrome should be considered in presence of sudden disturbance in general condition, resistant high fever and systemic inflammation findings in children with active rheumatic disease. Complete recovery can be provided with early and efficient treatment in macrophage activation syndrome which develops secondary to systemic juvenil idiopathic arthritis. PMID:26884689

  20. 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

  1. 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.

  2. 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.

  3. Auditory Attraction: Activation of visual cortex by music and sound in Williams syndrome

    PubMed Central

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

    2009-01-01

    Williams syndrome (WS) is a genetic neurodevelopmental disorder with a distinctive phenotype including cognitive-linguistic features, non-social 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 WS and typically-developing controls. In Study 1, the WS group exhibited unforeseen activations of the visual cortex to musical stimuli, and it was this novel finding that became the focus of two subsequent studies. Using retinotopy, color localizers and additional sound conditions, we identified specific visual areas in WS subjects that were activated by both musical and non-musical auditory stimuli. The results, similar to synesthetic-like experiences, have implications for cross-modal sensory processing in typical and atypical neurodevelopment. PMID:20440382

  4. 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.

  5. A girl with increased writing and painting activities associated with Turner's syndrome and autistic spectrum disorder.

    PubMed

    Ahouee, Shohreh Mohseni; Shooshtari, Mitra Hakim; Bidaki, Reza

    2015-01-01

    This report describes the findings on the evaluation of a 9-year-old girl with disabling and pronounced increased writing and painting activities associated with Turner's syndrome and autistic spectrum disorder. She spent most of the time doing these activities which affected not only her academic performance, but also social relationships. A comprehensive treatment plan consists of both biological and psychological aspects, is the main point of this case. Low dose of risperidone (0.5 mg/day) was started to decrease the patient's stereotypic behaviors. Sertraline (12.5 mg/day) was prescribed for her phobia. She was also referred to an occupational therapist in order to improve her social skills.

  6. DYRK1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model.

    PubMed

    Kurabayashi, Nobuhiro; Nguyen, Minh Dang; Sanada, Kamon

    2015-11-01

    Down syndrome (DS) arises from triplication of genes on human chromosome 21 and is associated with anomalies in brain development such as reduced production of neurons and increased generation of astrocytes. Here, we show that differentiation of cortical progenitor cells into astrocytes is promoted by DYRK1A, a Ser/Thr kinase encoded on human chromosome 21. In the Ts1Cje mouse model of DS, increased dosage of DYRK1A augments the propensity of progenitors to differentiate into astrocytes. This tendency is associated with enhanced astrogliogenesis in the developing neocortex. We also find that overexpression of DYRK1A upregulates the activity of the astrogliogenic transcription factor STAT in wild-type progenitors. Ts1Cje progenitors exhibit elevated STAT activity, and depletion of DYRK1A in these cells reverses the deregulation of STAT. In sum, our findings indicate that potentiation of the DYRK1A-STAT pathway in progenitors contributes to aberrant astrogliogenesis in DS. PMID:26373433

  7. DYRK1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model.

    PubMed

    Kurabayashi, Nobuhiro; Nguyen, Minh Dang; Sanada, Kamon

    2015-11-01

    Down syndrome (DS) arises from triplication of genes on human chromosome 21 and is associated with anomalies in brain development such as reduced production of neurons and increased generation of astrocytes. Here, we show that differentiation of cortical progenitor cells into astrocytes is promoted by DYRK1A, a Ser/Thr kinase encoded on human chromosome 21. In the Ts1Cje mouse model of DS, increased dosage of DYRK1A augments the propensity of progenitors to differentiate into astrocytes. This tendency is associated with enhanced astrogliogenesis in the developing neocortex. We also find that overexpression of DYRK1A upregulates the activity of the astrogliogenic transcription factor STAT in wild-type progenitors. Ts1Cje progenitors exhibit elevated STAT activity, and depletion of DYRK1A in these cells reverses the deregulation of STAT. In sum, our findings indicate that potentiation of the DYRK1A-STAT pathway in progenitors contributes to aberrant astrogliogenesis in DS.

  8. 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.

  9. 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.

  10. Anode consumption on a subsea X-mas tree

    SciTech Connect

    Lye, R.E.

    1998-12-31

    Anode consumption and coating breakdown on a X-mas tree installed at the Troll Field in the Norwegian North Sea was investigated after 5 years. A comparison with a spare tree and one tree being exposed for only 3--4 months was done. The epoxy coating has several blisters, in particular on stainless steel surfaces. Water inside the blisters has a pH of 13-14 indicating that the cathodic reaction occurs inside them. The anode dimensions indicate an overall anode consumption of approximately 20%, while the design allows 27% after 5 years. This indicates that the original design is quite conservative. If the design had been done according to present day design rules, the conservatism would be reduced; an overall anode consumption of 23% is then likely (still less than allowed 27%).

  11. Multinuclear MAS NMR studies of sodalitic framework materials

    SciTech Connect

    Johnson, G.M.; Mead, P.J.; Dann, S.E.; Weller, M.T.

    2000-02-24

    A wide range of sodalite framework materials, M{sub 8}[TT{prime}O{sub 4}]{sub 6}X{sub 2} where T = Al, Ga, Si, T{prime} = Be, Al, Si, Ge, have been characterized using {sup 27}Al, {sup 29}Si, and {sup 71}Ga magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. Structural parameters, such as functions of the framework T{single{underscore}bond}O{single{underscore}bond}T{prime} angle, correlate linearly with the determined chemical shift values and provide relationships, as a function of T{prime}, which will facilitate characterization of more complex zeolitic compounds containing such species. The effects of changing a particular neighboring framework cation on the resonance position is controlled by variations in both framework bond angles/distances and electrostatic effects; these contributions are resolved.

  12. 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

  13. 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

  14. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.

    PubMed

    Subissi, Lorenzo; Posthuma, Clara C; Collet, Axelle; Zevenhoven-Dobbe, Jessika C; Gorbalenya, Alexander E; Decroly, Etienne; Snijder, Eric J; Canard, Bruno; Imbert, Isabelle

    2014-09-16

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3'-5' exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5'-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  15. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

    PubMed Central

    Subissi, Lorenzo; Posthuma, Clara C.; Collet, Axelle; Zevenhoven-Dobbe, Jessika C.; Gorbalenya, Alexander E.; Decroly, Etienne; Snijder, Eric J.; Canard, Bruno; Imbert, Isabelle

    2014-01-01

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3′-5′ exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5′-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  16. 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.

  17. 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

  18. 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).

  19. 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…

  20. 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…

  1. 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. PMID:26509054

  2. 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.

  3. Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome.

    PubMed

    Orth, Dorothea; Khan, Abdul Basit; Naim, Asma; Grif, Katharina; Brockmeyer, Jens; Karch, Helge; Joannidis, Michael; Clark, Simon J; Day, Anthony J; Fidanzi, Sonja; Stoiber, Heribert; Dierich, Manfred P; Zimmerhackl, Lothar B; Würzner, Reinhard

    2009-05-15

    Infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of hemolytic uremic syndrome (HUS). Shiga toxins (Stxs), especially Stx2, are believed to represent major virulence factors of EHEC, contributing to HUS pathogenesis. Beside EHEC-associated HUS, there are hereditary atypical forms of HUS, which are mostly caused by mutations of complement regulators. The aim of the present study was to investigate whether or not complement is also involved in the pathogenesis of EHEC-induced typical HUS, by being activated either directly or indirectly by involvement of its inhibitors. Purified Stx2 markedly activated complement via the alternative pathway and was found to bind to factor H (FH), however, only when it was active. No apparent cleavage or destruction of FH was visible, and cofactor activity in fluid phase was unaffected, but clearly delayed for surface-attached FH, where it is essential for host cell protection. Binding studies using FH constructs revealed that Stx2 binds to short consensus repeats (SCRs) 6-8 and SCRs18-20, but not to SCRs16-17, i.e., to regions involved in the surface recognition function of FH. In conclusion, complement, and in particular FH, not only plays an important role in atypical HUS, but most probably also in EHEC-induced HUS.

  4. Menstrual cycle phase does not affect sympathetic neural activity in women with postural orthostatic tachycardia syndrome

    PubMed Central

    Stickford, Abigail SL; VanGundy, Tiffany B; Levine, Benjamin D; Fu, Qi

    2015-01-01

    Abstract Patients with the postural orthostatic tachycardia syndrome (POTS) are primarily premenopausal women, which may be attributed to female sex hormones. We tested the hypothesis that hormonal fluctuations of the menstrual cycle alter sympathetic neural activity and orthostatic tolerance in POTS women. Ten POTS women were studied during the early follicular (EF) and mid-luteal (ML) phases of the menstrual cycle. Haemodynamics and muscle sympathetic nerve activity (MSNA) were measured when supine, during 60 deg upright tilt for 45 min or until presyncope, and during the cold pressor test (CPT) and Valsalva manoeuvres. Blood pressure and total peripheral resistance were higher during rest and tilting in the ML than EF phase; however, heart rate, stroke volume and cardiac output were similar between phases. There were no mean ± SD differences in MSNA burst frequency (8 ± 8 EF phase vs. 10 ± 10 bursts min–1 ML phase at rest; 34 ± 15 EF phase vs. 36 ± 16 bursts min–1 ML phase at 5 min tilt), burst incidence or total activity, nor any differences in the cardiovagal and sympathetic baroreflex sensitivities between phases under any condition. The incidence of presyncope was also the same between phases. There were no differences in haemodynamic or sympathetic responses to CPT or Valsalva. These results suggest that the menstrual cycle does not affect sympathetic neural activity but modulates blood pressure and vasoconstriction in POTS women during tilting. Thus, factors other than sympathetic neural activity are probably responsible for the symptoms of orthostatic intolerance across the menstrual cycle in women with POTS. Key points Women with the postural orthostatic tachycardia syndrome (POTS) report fluctuations in orthostatic tolerance throughout the menstrual cycle. The mechanism(s) underlying blood pressure control across the menstrual cycle in women with POTS are unknown. The findings of the present study indicate that the menstrual

  5. Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

    PubMed

    Schnackenberg, Christine G; Costell, Melissa H; Krosky, Daniel J; Cui, Jianqi; Wu, Charlene W; Hong, Victor S; Harpel, Mark R; Willette, Robert N; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  6. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    PubMed Central

    Schnackenberg, Christine G.; Costell, Melissa H.; Krosky, Daniel J.; Cui, Jianqi; Wu, Charlene W.; Hong, Victor S.; Harpel, Mark R.; Willette, Robert N.; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome. PMID:23586038

  7. Effects of an Internet physical activity intervention in adults with metabolic syndrome.

    PubMed

    Bosak, Kelly A; Yates, Bernice; Pozehl, Bunny

    2010-02-01

    The Internet is a relatively new method of delivering strategies for health behavior change. The purpose of this study was to determine the feasibility of delivering a physical activity intervention by the Internet to improve outcomes in adults with the metabolic syndrome. Twenty-two participants (16 males; 6 females) were recruited from a cardiology clinic database, age range 32-66 years. Participants were randomly assigned to the Internet intervention (n = 12) or the usual care ( n = 10) group. The mean total dose, in terms of the time the intervention Web site was accessed was 2 hours over 6 weeks, which was greater than the time spent delivering usual care. Overall, participants' evaluations of the Internet intervention were positive. The costs of development and delivery of the Internet intervention were less than that of a consultation and follow-up in the cardiology clinic for this sample. The Internet intervention appears feasible for testing in a larger study.

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

    PubMed

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

    2016-08-01

    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.

  9. White-Nose Syndrome: Human Activity in the Emergence of an Extirpating Mycosis.

    PubMed

    Reynolds, Hannah T; Barton, Hazel A

    2013-12-01

    In winter 2006, the bat population in Howe Cave, in central New York State, USA, contained a number of bats displaying an unusual white substance on their muzzles. The following year, numerous bats in four surrounding caves displayed unusual winter hibernation behavior, including day flying and entrance roosting. A number of bats were found dead and dying, and all demonstrated a white, powdery substance on their muzzles, ears, and wing membranes, which was later identified as the conidia of a previously undescribed fungal pathogen, Geomyces destructans. The growth of the conidia gave infected bats the appearance of having dunked their faces into powdered sugar. The disease was named white-nose syndrome and represents an emerging zoonotic mycosis, likely introduced through human activities, which has led to a precipitous decline in North American bat species. PMID:26184962

  10. 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

  11. 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.

  12. MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

    PubMed Central

    Taggart, James; Ho, Tzu-Chieh; Amin, Elianna; Xu, Haiming; Barlowe, Trevor S.; Perez, Alexendar R.; Durham, Benjamin H.; Tivnan, Patrick; Okabe, Rachel; Chow, Arthur; Vu, Ly; Park, Sun Mi; Prieto, Camila; Famulare, Christopher; Patel, Minal; Lengner, Christopher J.; Verma, Amit; Roboz, Gail; Guzman, Monica; Klimek, Virginia M.; Abdel-Wahab, Omar; Leslie, Christina; Nimer, Stephen D.; Kharas, Michael G.

    2016-01-01

    Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia and stem cell function, but its role in MDS is unknown. Here, we demonstrate that elevated MSI2 expression correlates with poor survival in MDS. Conditional deletion of Msi2 in a mouse model of MDS results in a rapid loss of MDS haematopoietic stem and progenitor cells (HSPCs) and reverses the clinical features of MDS. Inversely, inducible overexpression of MSI2 drives myeloid disease progression. The MDS HSPCs remain dependent on MSI2 expression after disease initiation. Furthermore, MSI2 expression expands and maintains a more activated (G1) MDS HSPC. Gene expression profiling of HSPCs from the MSI2 MDS mice identifies a signature that correlates with poor survival in MDS patients. Overall, we identify a role for MSI2 in MDS representing a therapeutic target in this disease. PMID:26898884

  13. Brain mapping of epileptic activity in a case of idiopathic occipital lobe epilepsy (Panayiotopoulos syndrome).

    PubMed

    Leal, Alberto J R; Nunes, Sofia; Martins, António; Secca, Mário Forjaz; Jordão, Constança

    2007-06-01

    The Panayiotopoulos type of occipital lobe epilepsy has generated great interest, but the particular brain areas involved in the peculiar seizure manifestations have not been established. We studied a patient with the syndrome, using high-resolution EEG and simultaneous EEG and functional magnetic resonance imaging (fMRI). Resolution of the scalp EEG was improved using a realistic spline Laplacian algorithm, and produced a complex distribution of current sinks and sources over the occipital lobe. The spike-related blood oxygen level dependent (BOLD) effect was multifocal, with clusters in lateral and inferior occipital lobe and lateral and anterior temporal lobe. We also performed regional dipole seeding in BOLD clusters to determine their relative contribution to generation of scalp spikes. The integrated model of the neurophysiologic and vascular data strongly suggests that the epileptic activity originates in the lateral occipital area, spreading to the occipital pole and lateral temporal lobe.

  14. The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome.

    PubMed

    Suharti, Catharina; van Gorp, Eric C M; Setiati, Tatty E; Dolmans, Wil M V; Djokomoeljanto, Robert J; Hack, C Erik; ten, Cate Hugo; van der Meer, Jos W M

    2002-01-01

    In a prospective clinical study of 50 patients with Dengue Shock Syndrome (DSS), we investigated the association of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), and IL-6 with activation markers of coagulation (F1+2 and TATc) and fibrinolysis (t-PA, PAPc, and D-dimer). We found that TNF-alpha, IL-1beta and Il-1Ra, but not IL-6, concentrations were elevated in the circulation during the early stage of infection and at discharge from hospital. TNF-alpha was significantly associated with D-dimer, an activation marker of fibrinolysis (p < 0.003), but not with activation markers of coagulation. IL-1beta was significantly associated with t-PA (p < 0.03). IL-1Ra was significantly associated with F1+2, TATc (p < 0.04 and p < 0.02, respectively), whereas IL-6 was significantly associated with both, activation markers of coagulation (F1+2; p < 0.03) and fibrinolysis (PAPc; p = 0.002). Our data are in line with studies in bacterial sepsis. In severe dengue virus infection the same cytokines are involved in the onset and regulation of hemostasis.

  15. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome.

    PubMed

    Cruz, Josiane C; Flôr, Atalia F L; França-Silva, Maria S; Balarini, Camille M; Braga, Valdir A

    2015-01-01

    The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS. PMID:26779026

  16. AKT activation promotes PTEN hamartoma tumor syndrome-associated cataract development.

    PubMed

    Sellitto, Caterina; Li, Leping; Gao, Junyuan; Robinson, Michael L; Lin, Richard Z; Mathias, Richard T; White, Thomas W

    2013-12-01

    Mutations in the human phosphatase and tensin homolog (PTEN) gene cause PTEN hamartoma tumor syndrome (PHTS), which includes cataract development among its diverse clinical pathologies. Currently, it is not known whether cataract formation in PHTS patients is secondary to other systemic problems, or the result of the loss of a critical function of PTEN within the lens. We generated a mouse line with a lens-specific deletion of Pten (PTEN KO) and identified a regulatory function for PTEN in lens ion transport. Specific loss of PTEN in the lens resulted in cataract. PTEN KO lenses exhibited a progressive age-related increase in intracellular hydrostatic pressure, along with, increased intracellular sodium concentrations, and reduced Na+/K+-ATPase activity. Collectively, these defects lead to lens swelling, opacities and ultimately organ rupture. Activation of AKT was highly elevated in PTEN KO lenses compared to WT mice. Additionally, pharmacological inhibition of AKT restored normal Na+/K+-ATPase activity in primary cultured lens cells and reduced lens pressure in intact lenses from PTEN KO animals. These findings identify a direct role for PTEN in the regulation of lens ion transport through an AKT-dependent modulation of Na+/K+-ATPase activity, and provide a new animal model to investigate cataract development in PHTS patients. PMID:24270425

  17. 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.

  18. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  19. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors.

    PubMed

    Dubuis, Eric; Thompson, Victoria; Leite, Maria Isabella; Blaes, Franz; Maihöfner, Christian; Greensmith, David; Vincent, Angela; Shenker, Nicolas; Kuttikat, Anoop; Leuwer, Martin; Goebel, Andreas

    2014-11-01

    Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P<0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with α-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the α-1a receptor, CRPS-IgG was applied to α-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to α-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.

  20. 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.

  1. Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome.

    PubMed

    Ge, Hong-You; Nie, Hongling; Madeleine, Pascal; Danneskiold-Samsøe, Bente; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

    2009-12-15

    The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients and healthy controls (n=22 each, age- and gender-matched) were recruited. The surface area over the upper trapezius muscle on each side was divided into 13 sub-areas (points) of 1cm in diameter for each point. Pressure pain threshold (PPT) and the local and referred pain pattern induced by manual palpation at 13 points bilaterally in the upper trapezius were recorded. Results showed that PPT levels at all measured points were significantly lower in FMS than controls. Multiple active MTrPs (7.4+/-2.2) were identified bilaterally in the muscle in FMS patients, but no active MTrPs were found in controls. The mid-fiber region of the muscle had the lowest PPT level with the largest number of active MTrPs in FMS and with the largest number of latent MTrPs in controls. The local and referred pain pattern induced from active MTrPs bilaterally in the upper trapezius muscle were similar to the ongoing pain pattern in the neck and shoulder region in FMS. In conclusion, active MTrPs bilaterally in the upper trapezius muscle contribute to the neck and shoulder pain in FMS. Active MTrPs may serve as one of the sources of noxious input leading to the sensitization of spinal and supraspinal pain pathways in FMS.

  2. Regulation of alveolar epithelial cell survival by the ACE-2/angiotensin 1–7/Mas axis

    PubMed Central

    Li, Xiaopeng; Xue, Anita; Gao, Xu; Abdul-Hafez, Amal

    2011-01-01

    Earlier work from this laboratory demonstrated that apoptosis of alveolar epithelial cells (AECs) requires autocrine generation of angiotensin (ANG) II. More recent studies showed that angiotensin converting enzyme-2 (ACE-2), which degrades ANGII to form ANG1–7, is protective but severely downregulated in human and experimental lung fibrosis. Here it was theorized that ACE-2 and its product ANG1–7 might therefore regulate AEC apoptosis. To evaluate this hypothesis, the AEC cell line MLE-12 and primary cultures of rat AECs were exposed to the profibrotic apoptosis inducers ANGII or bleomycin (Bleo). Markers of apoptosis (caspase-9 or -3 activation and nuclear fragmentation), steady-state ANGII and ANG1–7, and JNK phosphorylation were measured thereafter. In the absence of Bleo, inhibition of ACE-2 by small interfering RNA or by a competitive inhibitor (DX600 peptide) caused a reciprocal increase in autocrine ANGII and corresponding decrease in ANG1–7 in cell culture media (both P < 0.05) and, moreover, induced AEC apoptosis. At baseline (without inhibitor), ANG1–7 in culture media was 10-fold higher than ANGII (P < 0.01). Addition of purified ANGII or bleomycin-induced caspase activation, nuclear fragmentation, and JNK phosphorylation in cultured AECs. However, preincubation with ANG1–7 (0.1 μM) prevented JNK phosphorylation and apoptosis. Moreover, pretreatment with A779, a specific blocker of the ANG1–7 receptor mas, prevented ANG1–7 blockade of JNK phosphorylation, caspase activation, and nuclear fragmentation. These data demonstrate that ACE-2 regulates AEC survival by balancing the proapoptotic ANGII and its antiapoptotic degradation product ANG1–7. They also suggest that ANG1–7 inhibits AEC apoptosis through the ANG1–7 receptor mas. PMID:21665960

  3. 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,…

  4. 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...

  5. 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,…

  6. Mas5, a homologue of bacterial DnaJ, is indispensable for the host infection and environmental adaptation of a filamentous fungal insect pathogen.

    PubMed

    Wang, Jie; Ying, Sheng-Hua; Hu, Yue; Feng, Ming-Guang

    2016-03-01

    Mas5, a yeast heat shock protein classified to the Hsp40 group, is homologous to bacterial archetype DnaJ but functionally unexplored in filamentous fungi. Here we identify a Mas5 homologue (46.86 kDa) in Beauveria bassiana and show its indispensability for host infection and environmental adaptation of the fungal insect pathogen. The deletion of mas5 caused severe defects in aerial conidiation, conidial germination and submerged blastospore production (mimic to host haemocoel). The deletion mutant lost 100% virulence to Galleria mellonella larvae through normal cuticular penetration (topical inoculation) and 50% through cuticle-bypassing infection (intrahaemocoel injection). It formed no blastospore in vivo after inoculation or only a very few after injection. Its extracellular (cuticle degrading) enzymes and virulence-relating Pr1 proteases were 62% and 32% less active respectively. It became more sensitive to high osmolarity, oxidation, cell-wall perturbation, heat shock and UV-B irradiation. These concurred with reduced contents of intracellular mannitol and trehalose, decreased activities of antioxidant enzymes, impaired cell walls and suppressed transcripts of stress-responsive and virulence-relating genes. All the changes were restored by targeted mas5 complementation. All together, Mas5 is indispensable for the in vitro and in vivo life cycle of B. bassiana by targeting many sets of enzymes/proteins at transcriptional and post-transcriptional levels.

  7. Antioxidant capacity of cornelian cherry (Cornus mas L.) - comparison between permanganate reducing antioxidant capacity and other antioxidant methods.

    PubMed

    Popović, Boris M; Stajner, Dubravka; Slavko, Kevrešan; Sandra, Bijelić

    2012-09-15

    Ethanol extracts (80% in water) of 10 cornelian cherry (Cornus mas L.) genotypes were studied for antioxidant properties, using methods including DPPH(), ()NO, O(2)(-) and ()OH antiradical powers, FRAP, total phenolic and anthocyanin content (TPC and ACC) and also one relatively new, permanganate method (permanganate reducing antioxidant capacity-PRAC). Lipid peroxidation (LP) was also determined as an indicator of oxidative stress. The data from different procedures were compared and analysed by multivariate techniques (correlation matrix calculation and principal component analysis (PCA)). Significant positive correlations were obtained between TPC, ACC and DPPH(), ()NO, O(2)(-), and ()OH antiradical powers, and also between PRAC and TPC, ACC and FRAP. PCA found two major clusters of cornelian cherry, based on antiradical power, FRAP and PRAC and also on chemical composition. Chemometric evaluation showed close interdependence between PRAC method and FRAP and ACC. There was a huge variation between C. mas genotypes in terms of antioxidant activity. PMID:23107685

  8. 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. PMID:26567876

  9. 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.

  10. 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

  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. 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.

  13. Cockayne syndrome group B protein has novel strand annealing and exchange activities.

    PubMed

    Muftuoglu, Meltem; Sharma, Sudha; Thorslund, Tina; Stevnsner, Tinna; Soerensen, Martin M; Brosh, Robert M; Bohr, Vilhelm A

    2006-01-01

    Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by UV sensitivity, severe neurological abnormalities and prageroid symptoms. The CS complementation group B (CSB) protein is involved in UV-induced transcription coupled repair (TCR), base excision repair and general transcription. CSB also has a DNA-dependent ATPase activity that may play a role in remodeling chromatin in vivo. This study reports the novel finding that CSB catalyzes the annealing of complementary single-stranded DNA (ssDNA) molecules with high efficiency, and has strand exchange activity. The rate of CSB-catalyzed annealing of complementary ssDNA is 25-fold faster than the rate of spontaneous ssDNA annealing under identical in vitro conditions and the reaction occurs with a high specificity in the presence of excess non-homologous ssDNA. The specificity and intrinsic nature of the reaction is also confirmed by the observation that it is stimulated by dephosphorylation of CSB, which occurs after UV-induced DNA damage, and is inhibited in the presence of ATPgammaS. Potential roles of CSB in cooperation with strand annealing and exchange activities for TCR and homologous recombination are discussed. PMID:16410611

  14. Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial

    PubMed Central

    van Eupen, Inge; Meirte, Jill; Van Cauwenbergh, Deborah; Moorkens, Greta; Meeus, Mira; Nijs, Jo

    2015-01-01

    OBJECTIVE. The objective of this study was to evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS). METHOD. A total of 33 women with CFS (age 41.1 ± 11.2 yr) were randomly allocated to APSM (experimental group; n = 16) or relaxation (control group; n = 17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS). RESULTS. COPM scores changed significantly over time in both groups (p = .03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size = 0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p < .01). CONCLUSION. APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required. PMID:26356665

  15. Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome.

    PubMed

    Blassberg, Robert; Macrae, James I; Briscoe, James; Jacob, John

    2016-02-15

    Smith-Lemli-Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium.

  16. Reduced cholesterol levels impair Smoothened activation in Smith–Lemli–Opitz syndrome

    PubMed Central

    Blassberg, Robert; Macrae, James I.; Briscoe, James; Jacob, John

    2016-01-01

    Smith–Lemli–Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID:26685159

  17. Chaenomeles japonica, Cornus mas, Morus nigra fruits characteristics and their processing potential.

    PubMed

    Tarko, Tomasz; Duda-Chodak, Aleksandra; Satora, Paweł; Sroka, Paweł; Pogoń, Piotr; Machalica, Justyna

    2014-12-01

    The aim of this study was to determine the suitability of Japanese quince (Chaenomeles japonica), cornelian cherry (Cornus mas) and black mulberry (Morus nigra) fruits as raw materials for processing. All analyzed fruits were characterized by high antioxidant activity and total phenolic content. Fruits of Japanese quince and cornelian cherry had also high acidity. Products such as fruit wines and liquors were prepared from the tested fruits. In respect of soluble solid content and reducing sugars content the obtained wine should be classified as dry wines. All analyzed liquors were characterized by similar alcohol content and the soluble solid content. Moreover, liquors made from Japanese quince and cornelian cherry were characterized by high total acidity and antioxidant capacity. The results of sensory analysis showed high commercial potential of the examined fruits. PMID:25477663

  18. How do people with chronically painful joint hypermobility syndrome make decisions about activity?

    PubMed Central

    Schmidt, Anne; Corcoran, Kelley; Grahame, Rodney

    2015-01-01

    Background: The model of activity avoidance prompted by fear of increased pain and/or harm dominates understanding and research into activity limitation in chronic pain. Yet, the accounts of people with chronic pain on decisions about activity limitation are rarely heard beyond the confines of fear and avoidance questionnaires. Methods: We used semi-structured interviews to explore the decisions of 11 women attending a pain management clinic with chronically painful Joint Hypermobility Syndrome (JHS). Results: Six themes emerged from Interpretative Phenomenological Analysis: the overall aim of keeping pain to a manageable level, considering whether the planned activity was worth it and, running through all judgements, the influence of pain intensity. The decision was tipped towards avoidance by unpredictability of pain and by high emotional cost and towards going ahead with the activity by the wish to exert control and by low emotional cost. Many accounts described a specifiable cost–benefit analysis of individual decisions, weighing the importance of each activity against its potential aversive consequences, which only in a minority of cases was dominated by fear of pain or injury. Conclusion: Assumptions of fear as the basis of activity avoidance should not be used uncritically in clinical settings. Decisions about activity should explore beyond pain expectancy, incorporating goals, values, and decision processes. Summary points The model of fear of pain or re/injury and associated avoidance, an important insight that has generated effective therapeutic interventions, risks being over-applied and assumed rather than demonstrated. Patients’ own accounts, using qualitative analysis of interview in 11 women with long term chronic pain associated with joint hypermobility, give a more nuanced description of complex decision-making around activity. While a few activities were unquestionably avoided because of such fears, others were undertaken when benefits

  19. AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.

    PubMed

    McCarty, Mark F

    2005-01-01

    The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C. This endothelial "lipotoxicity" can be alleviated by very-low-fat diets and by appropriate weight loss. In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase. These considerations may rationalize the superior impact of metformin therapy on the macrovascular health of diabetics. More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome. PMID:15823720

  20. 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.

  1. 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. PMID:11246927

  2. 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.

  3. Receptor MAS protects mice against hypothermia and mortality induced by endotoxemia.

    PubMed

    Souza, Laura L; Duchene, Johan; Todiras, Mihail; Azevedo, Luciano C P; Costa-Neto, Claudio M; Alenina, Natalia; Santos, Robson A; Bader, Michael

    2014-04-01

    The renin-angiotensin (Ang) system is involved in maintaining cardiovascular function by regulating blood pressure and electrolyte homeostasis. More recently, alternative pathways within the renin-angiotensin system have been described, such as the ACE-2/Ang-(1-7)/Mas axis, with opposite effects to the ones of the ACE/Ang-II/AT1 axis. Correspondingly, our previous work reported that Ang-(1-7) via its receptor Mas inhibits the mRNA expression of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α increased by lipopolysaccharide (LPS) in mouse peritoneal macrophages. These data led us to investigate the functional role of the Ang-(1-7)/Mas axis in an in vivo LPS model. In this work, we present evidence that Ang-(1-7) via Mas significantly reduced the LPS-increased production of circulating cytokines, such as IL-6, IL-12, and CXCL-1. This inhibitory effect was mediated by Mas because it was not detectable in Mas-deficient (Mas) mice. Accordingly, IL-6, CXCL-1, and CXCL-2 levels were higher after LPS treatment in the absence of Mas. Mas mice were less resistant to LPS-induced endotoxemia, their survival rate being 50% compared with 95% in wild-type mice. Telemetric analyses showed that Mas mice presented more pronounced LPS-induced hypothermia with a 3°C lower body temperature compared with wild-type mice. Altogether, our findings suggest that Ang-(1-7) and Mas inhibit LPS-induced cytokine production and hypothermia and thereby protect mice from the fatal consequences of endotoxemia. PMID:24430551

  4. Mas receptor deficiency exacerbates lipopolysaccharide-induced cerebral and systemic inflammation in mice.

    PubMed

    Oliveira-Lima, Onésia C; Pinto, Mauro C X; Duchene, Johan; Qadri, Fatimunnisa; Souza, Laura L; Alenina, Natalia; Bader, Michael; Santos, Robson A S; Carvalho-Tavares, Juliana

    2015-12-01

    Beyond the classical actions of the renin-angiotensin system on the regulation of cardiovascular homeostasis, several studies have shown its involvement in acute and chronic inflammation. The G protein-coupled receptor Mas is a functional binding site for the angiotensin-(1-7); however, its role in the immune system has not been fully elucidated. In this study, we evaluated the effect of genetic deletion of Mas receptor in lipopolysaccharide (LPS)-induced systemic and cerebral inflammation in mice. Inflammatory response was triggered in Mas deficient (Mas(-/-)) and C57BL/6 wild-type (WT) mice (8-12 weeks-old) by intraperitoneal injection of LPS (5 mg/kg). Mas(-/-) mice presented more intense hypothermia compared to WT mice 24 h after LPS injection. Systemically, the bone marrow of Mas(-/-) mice contained a lower number of neutrophils and monocytes 3 h and 24 h after LPS injection, respectively. The plasma levels of inflammatory mediators KC, MCP-1 and IL-10 were higher in Mas(-/-) mice 24 h after LPS injection in comparison to WT. In the brain, Mas(-/-) animals had a significant increase in the number of adherent leukocytes to the brain microvasculature compared to WT mice, as well as, increased number of monocytes and neutrophils recruited to the pia-mater. The elevated number of adherent leukocytes on brain microvasculature in Mas(-/-) mice was associated with increased expression of CD11b - the alpha-subunit of the Mac-1 integrin - in bone marrow neutrophils 3h after LPS injection, and with increased brain levels of chemoattractants KC, MIP-2 and MCP-1, 24 h later. In conclusion, we demonstrated that Mas receptor deficiency results in exacerbated inflammation in LPS-challenged mice, which suggest a potential role for the Mas receptor as a regulator of systemic and brain inflammatory response induced by LPS.

  5. Is Xanthine oxidase activity in polycystic ovary syndrome associated with inflammatory and cardiovascular risk factors?

    PubMed

    Isık, Hatice; Aynıoglu, Oner; Tımur, Hakan; Sahbaz, Ahmet; Harma, Muge; Can, Murat; Guven, Berrak; Alptekin, Husnu; Kokturk, Furuzan

    2016-08-01

    The aim of this study is to examine women with polycystic ovary syndrome (PCOS) to determine the relationship between xanthine oxidase (XO) and oxidative stress, inflammatory status, and various clinical and biochemical parameters. In this cross-sectional study a total of 83 women including 45 PCOS patients and 38 healthy women were enrolled. We collected blood samples for XO and superoxide dismutase (SOD) activity, hormone levels, cholesterol values, and inflammatory markers. Body mass index (BMI) , waist-to-hip ratio (WHR), and blood pressure were assessed. Blood samples were taken for hormonal levels, cholesterol levels, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostatic model assessment-insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), C-reactive protein (CRP), white blood cell and neutrophil counts, XO and SOD activities. The basal hormone levels, triglyceride (TG) levels, TG/HDL-C (high density lipoprotein-cholesterol) ratios FPG, FPI and HOMA-IR levels were higher in PCOS patients compared to controls (p<0.05). Platelet and plateletcrit (PCT) values, CRP, and XO activity were significantly increased, however SOD activity was decreased in PCOS patients (p<0.001). XO activity was positively correlated with LH/FSH and TG/HDL ratios, CRP, PCT, FPG, FPI, and HOMA-IR, and negatively correlated with QUICKI levels. In conclusion, XO is a useful marker to assess oxidative stress in PCOS patients. Positive correlations between XO and inflammatory markers and cardiovascular disease risk factors suggest that XO plays an important role in the pathogenesis of PCOS and its metabolic complications. PMID:27295433

  6. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects

    PubMed Central

    Johannesson, Elisabet; Ringström, Gisela; Abrahamsson, Hasse; Sadik, Riadh

    2015-01-01

    AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms. PMID:25593485

  7. 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

  8. Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6.

    PubMed

    Little, Hayley J; Rorick, Nicholas K; Su, Ling-I; Baldock, Clair; Malhotra, Saimon; Jowitt, Tom; Gakhar, Lokesh; Subramanian, Ramaswamy; Schutte, Brian C; Dixon, Michael J; Shore, Paul

    2009-02-01

    Cleft lip and cleft palate (CLP) are common disorders that occur either as part of a syndrome, where structures other than the lip and palate are affected, or in the absence of other anomalies. Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant disorders characterized by combinations of cleft lip, CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6). IRF6 belongs to a family of transcription factors that share a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain. To date, mutation analyses have suggested a broad genotype-phenotype correlation in which missense and nonsense mutations occurring throughout IRF6 may cause VWS; in contrast, PPS-causing mutations are highly associated with the DNA-binding domain, and appear to preferentially affect residues that are predicted to interact directly with the DNA. Nevertheless, this genotype-phenotype correlation is based on the analysis of structural models rather than on the investigation of the DNA-binding properties of IRF6. Moreover, the effects of mutations in the protein interaction domain have not been analysed. In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6. In addition, we have demonstrated that IRF6 functions as a co-operative transcriptional activator and that mutations in the protein interaction domain of IRF6 disrupt this activity. PMID:19036739

  9. Brown's syndrome.

    PubMed

    Wilson, M E; Eustis, H S; Parks, M M

    1989-01-01

    Brown's syndrome is a well-recognized clinical disorder of ocular motility manifesting most notably a restriction of active and passive elevation in adduction. The original name, "superior oblique tendon sheath syndrome," is no longer appropriate, since it has been shown that the tissue surrounding the anterior superior oblique tendon is blameless as a restrictive force. "True" and "simulated" as descriptive modifiers should also be discarded, as they relate to the disproven sheath concept. Brown's syndrome occurs as a congenital or acquired, constant or intermittent condition; the common link is restriction of free movement through the trochlea pulley mechanism. The various etiologic theories are reviewed and the spectrum of medical and surgical treatments are described and evaluated. Evidence suggests that subtypes of Brown's syndrome lie on a single continuum and that spontaneous resolution occurs in each group, probably more often than previously recognized. A simplified classification scheme is encouraged and possible future directions in Brown's syndrome research are introduced.

  10. Segmental basal cell naevus syndrome caused by an activating mutation in smoothened.

    PubMed

    Khamaysi, Z; Bochner, R; Indelman, M; Magal, L; Avitan-Hersh, E; Sarig, O; Sprecher, E; Bergman, R

    2016-07-01

    Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited. PMID:26822128

  11. Chronic Ethanol Consumption Inhibits Glucokinase Transcriptional Activity by Atf3 and Triggers Metabolic Syndrome in Vivo*

    PubMed Central

    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

    2014-01-01

    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. PMID:25074928

  12. 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

  13. Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis

    PubMed Central

    Gaspar, Paulo; Kallemeijn, Wouter W.; Strijland, Anneke; Scheij, Saskia; Van Eijk, Marco; Aten, Jan; Overkleeft, Herman S.; Balreira, Andrea; Zunke, Friederike; Schwake, Michael; Sá Miranda, Clara; Aerts, Johannes M. F. G.

    2014-01-01

    Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the GBA gene. While GD is characterized by the presence of glucosylceramide-laden macrophages, AMRF patients do not show these. We studied the fate of GBA in relation to LIMP2 deficiency by employing recently designed activity-based probes labeling active GBA molecules. We demonstrate that GBA is almost absent in lysosomes of AMRF fibroblasts. However, white blood cells contain considerable amounts of residual enzyme. Consequently, AMRF patients do not acquire lipid-laden macrophages and do not show increased plasma levels of macrophage markers, such as chitotriosidase, in contrast to GD patients. We next investigated the consequences of LIMP2 deficiency with respect to plasma glycosphingolipid levels. Plasma glucosylceramide concentration was normal in the AMRF patients investigated as well as in LIMP2-deficient mice. However, a marked increase in the sphingoid base, glucosylsphingosine, was observed in AMRF patients and LIMP2-deficient mice. Our results suggest that combined measurements of chitotriosidase and glucosylsphingosine can be used for convenient differential laboratory diagnosis of GD and AMRF. PMID:24212238

  14. 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. PMID:27662089

  15. A familial syndrome of susceptibility to chronic active Epstein-Barr virus infection.

    PubMed Central

    Joncas, J. H.; Ghibu, F.; Blagdon, M.; Montplaisir, S.; Stefanescu, I.; Menezes, J.

    1984-01-01

    In two members of a family (daughter and father) active Epstein-Barr virus (EBV) infections persisted over periods of 4 and 3 years respectively (possibly 10 years in the father). Both had persistent splenomegaly and occasional bouts of unexplained fever but lived otherwise normal lives. The other members of the family (mother and son) were healthy. The titres of antibody to the EBV viral capsid antigen (VCA) and early antigen (EA) were extremely high in the daughter's blood, whereas the titres of antibody to the Epstein-Barr nuclear antigen were low in the daughter's blood and undetectable in the father's. Target cells of the EBV infection that were obtained from the daughter's blood were established in culture with great difficulty and showed increased expression of VCA and EA. Other immunologic investigations in the two patients revealed that the ratio of helper to suppressor T lymphocytes was inverted, natural killer-cell activity was abnormally low, lymphocyte responses to certain mitogens were depressed and there was a serum factor blocking mitogen-induced transformation. The possibility that the patients' unusual susceptibility to EBV infection represented an inherited syndrome (perhaps X-linked) is discussed. PMID:6318944

  16. Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model.

    PubMed

    Barth, Lydia; Sütterlin, Rosmarie; Nenniger, Markus; Vogt, Kaspar E

    2014-01-01

    Neurodevelopmental diseases such as the Rett syndrome (RTT) have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind RTT pathophysiology.

  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 award schedule (MAS) offers. 538.270 Section 538.270 Federal Acquisition Regulations System GENERAL... and Administering Federal Supply Schedules 538.270 Evaluation of multiple award schedule (MAS)...

  18. Psychometric Comparison of the Motivation Assessment Scale (MAS) and the Questions about Behavioral Function (QABF)

    ERIC Educational Resources Information Center

    Koritsas, S.; Iacono, T.

    2013-01-01

    Background: The Motivation Assessment Scale (MAS) and the Questions About Behavioral Function (QABF) are frequently used to assess the learned function of challenging behaviour in people with intellectual disability (ID). The aim was to explore and compare the psychometric properties of the MAS and the QABF. Method: Seventy adults with ID and…

  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. Effects of a recreational physical activity summer camp on body composition, metabolic syndrome and physical fitness in obese children.

    PubMed

    Roriz DE Oliveira, Mafalda S; Teixeira Seabra, André F; Ribeiro Maia, José A

    2016-01-01

    This study sought to examine the effects of a recreational physical activity summer camp on body composition, metabolic syndrome, and physical fitness in obese children. Forty-eight children (8-10 years; Body Mass Index ≥85th percentile) completed 4-weeks of a structured recreational physical activity program summer camp (5 hours/day, 5 days/week). Over the 4-weeks, significant reductions (P<0.05) in weight, waist circumference, Body Mass Index, percentage of body fat, and systolic and diastolic blood pressure were observed. Additionally, a significant increase was observed in HDL-cholesterol, handgrip, trunk lift, and shuttle run (P<0.05). These findings suggest that a 4-week recreational physical activity summer camp yields several body-composition, metabolic-syndrome, and physical fitness benefits in obese children and should represent an effective support for their health development.

  1. Antiviral activity and underlying molecular mechanisms of Matrine against porcine reproductive and respiratory syndrome virus in vitro.

    PubMed

    Sun, Na; Wang, Zhi-Wei; Wu, Cai-Hong; Li, E; He, Jun-Ping; Wang, Shao-Yu; Hu, Yuan-Liang; Lei, Hai-Min; Li, Hong-Quan

    2014-04-01

    Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is an acute infectious disease. The prevalence of PRRS has made swine industry suffered huge financial losses. Matrine, a natural compound, has been demonstrated to possess anti-PRRSV activity in Marc-145 cells. However, the underlying molecular mechanisms were still unknown. The main objective of our study was to discuss the effect of Matrine on PRRSV N protein expression and PRRSV induced apoptosis. Indirect immunofluorescence assay (IFA) and Western blot were used to assess the effect of Matrine on N protein expression. Apoptosis was analyzed by fluorescence staining. In addition, the effect of Matrine on caspase-3 activation was investigated by Western blot. Indirect immunofluorescence assay and Western blot analysis demonstrated that Matrine could inhibit N protein expression in Marc-145 cells. And Matrine was found to be able to impair PRRSV-induced apoptosis by inhibiting caspase-3 activation.

  2. 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.

  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. [The most common overuse injury syndromes of the upper extremity associated with work activity].

    PubMed

    Krapac, L

    2001-12-01

    Repetitive use of upper extremities, non-physiological body posture, especially of cervical spine, shoulders, lower arms, and fists are still present in modern technological processes. Innate deformities, weakness of connective tissue, accompanying morbidity (radicular symptoms, neuropathies, superior thoracic aperture syndrome, vasopathies and neuroses) are significant pathogenic overuse syndromes. Other causes of overuse syndromes are non-ergonomic tools, musical instruments, furniture, or keyboards. Lack of training for jobs involving repetitive movements, as well as job dissatisfaction are additional aggravating factors of the overuse syndrome. Polypragmasy with drug and physical therapy, insufficient rehabilitation, and questionable medical prognosis of working capacity are challenges to public health of even in richer societies. This paper describes the most common overuse syndromes of upper extremities. The aetiology of reflex dystrophy syndrome, carpal tunnel, and myofascial painful syndrome are still insufficiently explained. The paper also presents data collected in a group of 40 metal workers exposed to significant shoulder strain. They more often reported pain in the cervical spine than the control group of workers under moderate strain (45% v. 7.5%; P < 0.01), as well as pain in the shoulders (12.5% v. 5.0%) and stiffened hand (22.5%:7.5%). Symptoms were significantly more frequent in the dominant hand. A common diagnosis in a sample of 110 musicians was a change in the shoulder joint, which was more distinct in the right shoulder (10%) than in the left (7%) and comparable in the elbows (8%). The paper proceeds with cases of advanced overuse syndrome in a textile worker and cases of dissimulation in a physician and a guitarist. The paper stresses the importance of quantification of morphological and functional changes in overuse syndromes and discusses the necessity of prevention, education, early diagnosis, pharmacological and physical therapy, and

  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. 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.

  8. 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.

  9. 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

  10. RAI1 Transcription Factor Activity Is Impaired in Mutants Associated with Smith-Magenis Syndrome

    PubMed Central

    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. PMID:23028815

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

    PubMed

    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

  12. 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

  13. 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

  14. Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone.

    PubMed

    Armanini, Decio; Bordin, Luciana; Donà, Gabriella; Sabbadin, Chiara; Bakdounes, Leila; Ragazzi, Eugenio; Giorgino, Francesco L; Fiore, Cristina

    2012-05-01

    A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk. PMID:22387621

  15. Recombinant human soluble thrombomodulin is active against hemophagocytic lymphohistiocytosis associated with acquired immunodeficiency syndrome.

    PubMed

    Chi, SungGi; Ikezoe, Takayuki; Takeuchi, Asako; Takaoka, Masato; Yokoyama, Akihito

    2013-11-01

    A 39-year-old man was admitted to our hospital to initiate highly active anti-retroviral therapy (HAART) for documented acquired immune deficiency syndrome. The HIV load was 2.5 million copies/mL and the CD4-positive lymphocyte count was only 52 cells/µL at presentation. The HAART regimen consisted of lamivudine and abacavir as the backbone, plus raltegravir and lopinavir/ritonavir as the base. The day after initiating HAART, his body temperature rose to 102.4 °F (39.1 °C), accompanied by elevated levels of liver enzymes, neutropenia, coagulopathies, and an extremely high serum ferritin level, prompting us to suspect hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC). To correct the coagulation abnormalities, recombinant thrombomodulin (rTM) was initiated at 375 U/kg. Surprisingly, fever resolved almost immediately, in parallel with dramatic decreases in serum levels of ferritin and liver enzymes and prompt normalization of coagulopathy with only two doses of rTM. The patient subsequently developed amebiasis, which was successfully treated using metronidazole. In summary, the use of rTM dramatically improved not only DIC, but also HLH, suggesting potent anti-inflammatory effects of the agent. Although further clinical reports and trials are needed, rTM appears to provide an additional therapeutic option in the management of HLH.

  16. 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).

  17. A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70.

    PubMed

    Chan, Alice Y; Punwani, Divya; Kadlecek, Theresa A; Cowan, Morton J; Olson, Jean L; Mathes, Erin F; Sunderam, Uma; Fu, Shu Man; Srinivasan, Rajgopal; Kuriyan, John; Brenner, Steven E; Weiss, Arthur; Puck, Jennifer M

    2016-02-01

    A brother and sister developed a previously undescribed constellation of autoimmune manifestations within their first year of life, with uncontrollable bullous pemphigoid, colitis, and proteinuria. The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome. Both children required allogeneic hematopoietic cell transplantation (HCT), which resolved their autoimmunity. The early onset, severity, and distinctive findings suggested a single gene disorder underlying the phenotype. Whole-exome sequencing performed on five family members revealed the affected siblings to be compound heterozygous for two unique missense mutations in the 70-kD T cell receptor ζ-chain associated protein (ZAP-70). Healthy relatives were heterozygous mutation carriers. Although pre-HCT patient T cells were not available, mutation effects were determined using transfected cell lines and peripheral blood from carriers and controls. Mutation R192W in the C-SH2 domain exhibited reduced binding to phosphorylated ζ-chain, whereas mutation R360P in the N lobe of the catalytic domain disrupted an autoinhibitory mechanism, producing a weakly hyperactive ZAP-70 protein. Although human ZAP-70 deficiency can have dysregulated T cells, and autoreactive mouse thymocytes with weak Zap-70 signaling can escape tolerance, our patients' combination of hypomorphic and activating mutations suggested a new disease mechanism and produced previously undescribed human ZAP-70-associated autoimmune disease. PMID:26783323

  18. Thalamocortical network activity enables chronic tic detection in humans with Tourette syndrome.

    PubMed

    Shute, Jonathan B; Okun, Michael S; Opri, Enrico; Molina, Rene; Rossi, P Justin; Martinez-Ramirez, Daniel; Foote, Kelly D; Gunduz, Aysegul

    2016-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Deep brain stimulation (DBS) is an emerging therapy for severe cases of TS. We studied two patients with TS implanted with bilateral Medtronic Activa PC + S DBS devices, capable of chronic recordings, with depth leads in the thalamic centromedian-parafascicular complex (CM-PF) and subdural strips over the precentral gyrus. Low-frequency (1-10 Hz) CM-PF activity was observed during tics, as well as modulations in beta rhythms over the motor cortex. Tics were divided into three categories: long complex, complex, and simple. Long complex tics, tics involving multiple body regions and lasting longer than 5 s, were concurrent with a highly detectable thalamocortical signature (average recall [sensitivity] 88.6%, average precision 96.3%). Complex tics were detected with an average recall of 63.9% and precision of 36.6% and simple tics an average recall of 39.3% and precision of 37.9%. The detections were determined using data from both patients. PMID:27419067

  19. Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome.

    PubMed

    White, Andrea T; Light, Alan R; Hughen, Ronald W; Bateman, Lucinda; Martins, Thomas B; Hill, Harry R; Light, Kathleen C

    2010-07-01

    Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L). In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex. Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.

  20. 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

  1. EPHA4 is overexpressed but not functionally active in Sézary syndrome

    PubMed Central

    Hameetman, Liesbeth; van der Fits, Leslie; Zoutman, Willem H.; Out-Luiting, Jacoba J.; Siegal, Gregg; de Esch, Iwan J.P.; Vermeer, Maarten H.; Tensen, Cornelis P.

    2015-01-01

    EPHA4 belongs to the largest subfamily of receptor tyrosine kinases. In addition to its function during development, overexpression of EPHA4 in tumors has been correlated with increased proliferation, migration and poor survival. Several genome-wide transcription profiling studies have demonstrated high EPHA4 expression in Sézary syndrome (SS), a leukemic variant of cutaneous CD4+ T-cell lymphoma (CTCL) with an aggressive clinical course and poor prognosis. In this study we set out to explore the functional role of EPHA4 in SS. Both high EPHA4 mRNA and protein expression was found in circulating SS-cells of patients compared to healthy CD4+ T-cells. However, using a phosphospecific EPHA4 antibody, phosphorylation of the EPHA4 kinase domain was not detected in either circulating or skin residing SS cells. Moreover, treatment with the phosphatase inhibitor pervanadate did not result in detectable phosphorylation of the EPHA4 kinase domain, in either SS cells or in healthy CD4+ T-cells. Thus, the results from our study confirm high EPHA4 expression in SS cells both on the mRNA and protein levels, making EPHA4 a good diagnostic marker. However, the overexpressed EPHA4 does not appear to be functionally active and its overexpression might be secondary to other oncogenic drivers in SS, like STAT3 and TWIST1. PMID:26376612

  2. A novel technique based on a PNA hybridization probe and FRET principle for quantification of mutant genotype in fibrous dysplasia/McCune–Albright syndrome

    PubMed Central

    Karadag, Abdullah; Riminucci, Mara; Bianco, Paolo; Cherman, Natasha; Kuznetsov, Sergei A.; Nguyen, Nga; Collins, Michael T.; Robey, Pamela G.; Fisher, Larry W.

    2004-01-01

    Somatic mutations are present in various proportions in numerous developmental pathologies. Somatic activating missense mutations of the GNAS gene encoding the Gsα protein have previously been shown to be the cause of fibrous dysplasia of bone (FD)/McCune-Albright syndrome (MAS). Because in MAS patients, tissues as diverse as melanocytes, gonads and bone are affected, it is generally accepted that the GNAS mutation in this disease must have occurred early in development. Interestingly, it has been shown that the development of an active FD lesion may require both normal and mutant cells. Studies of the somatic mosaic states of FD/MAS and many other somatic diseases need an accurate method to determine the ratio of mutant to normal cells in a given tissue. A new method for quantification of the mutant:normal ratio of cells using a PNA hybridization probe-based FRET technique was developed. This novel technique, with a linear sensitivity of 2.5% mutant alleles, was used to detect the percentage mutant cells in a number of tissue and cell culture samples derived from FD/MAS lesions and could easily be adapted for the quantification of mutations in a large spectrum of diseases including cancer. PMID:15096559

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

    PubMed

    Tomaić, V; Banks, L

    2015-01-01

    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. PMID:25633294

  4. Cardiac and Sympathetic Activation are Reduced in Children with Down Syndrome and Sleep Disordered Breathing

    PubMed Central

    O’Driscoll, Denise M.; Horne, Rosemary S.C.; Davey, Margot J.; Hope, Sarah A.; Anderson, Vicki; Trinder, John; Walker, Adrian M.; Nixon, Gillian M.

    2012-01-01

    Study Objectives: Sleep disordered breathing (SDB) occurs at an increased incidence in children with Down Syndrome (DS) compared to the general pediatric population. We hypothesized that, compared with typically developing (TD) children with SDB, children with DS have a reduced cardiovascular response with delayed reoxygenation after obstructive respiratory events, and reduced sympathetic drive, providing a potential explanation for their increased risk of pulmonary hypertension. Design: Beat-by-beat heart rate (HR) was analyzed over the course of obstructive events (pre, early, late, post-event) and compared between groups. Also compared were the time for oxygen resaturation post-event and overnight urinary catecholamines. Setting: Pediatric sleep laboratory. Patients: Sixty-four children aged 2-17 y referred for investigation of SDB (32 DS; 32 TD) matched for age and obstructive apnea/hypopnea index. Measurement and Results: Children underwent overnight polysomnography with overnight urine collection. Compared to TD children, those with DS had significantly reduced HR changes post-event during NREM (DS: 21.4% ± 1.8%, TD: 26.6% ± 1.6%, change from late to post-event, P < 0.05). The time to resaturation post-event was significantly increased in the DS group (P < 0.05 for both NREM and REM sleep). Children with DS had significantly reduced overnight urinary noradrenaline (P < 0.01), adrenaline (P < 0.05) and dopamine levels (P < 0.01) compared with TD children. Conclusion: Children with DS and SDB exhibit a compromised acute cardio-respiratory response and dampened sympathetic response to SDB compared with TD children with SDB. These data may reflect autonomic dysfunction in children with DS that may place them at increased risk for cardiovascular complications such as pulmonary hypertension. Citation: O’Driscoll DM; Horne RSC; Davey MJ; Hope SA; Anderson V; Trinder J; Walker AM; Nixon GM. Cardiac and sympathetic activation are reduced in children with down

  5. The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer.

    PubMed

    Hartung, Anne-Mette; Swensen, Jeff; Uriz, Inaki E; Lapin, Morten; Kristjansdottir, Karen; Petersen, Ulrika S S; Bang, Jeanne Mari V; Guerra, Barbara; Andersen, Henriette Skovgaard; Dobrowolski, Steven F; Carey, John C; Yu, Ping; Vaughn, Cecily; Calhoun, Amy; Larsen, Martin R; Dyrskjøt, Lars; Stevenson, David A; Andresen, Brage S

    2016-05-01

    Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE) and creation of an Exonic Splicing Silencer (ESS). We show that this vulnerability of HRAS exon 2 is caused by a weak 3' splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS- causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping.

  6. Mucosal permeability and immune activation as potential therapeutic targets of probiotics in irritable bowel syndrome.

    PubMed

    Barbara, Giovanni; Zecchi, Lisa; Barbaro, Raffaella; Cremon, Cesare; Bellacosa, Lara; Marcellini, Marco; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2012-10-01

    There is increasingly convincing evidence supporting the participation of the gut microenvironment in the pathophysiology of irritable bowel syndrome (IBS). Studies particularly suggest an interplay between luminal factors (eg, foods and bacteria residing in the intestine), the epithelial barrier, and the mucosal immune system. Decreased expression and structural rearrangement of tight junction proteins in the small bowel and colon leading to increased intestinal permeability have been observed, particularly in postinfectious IBS and in IBS with diarrhea. These abnormalities are thought to contribute to the outflow of antigens through the leaky epithelium, causing overstimulation of the mucosal immune system. Accordingly, subsets of patients with IBS show higher numbers and an increased activation of mucosal immunocytes, particularly mast cells. Immune factors, released by these cells, including proteases, histamine, and prostanoids, participate in the perpetuation of the permeability dysfunction and contribute to the activation of abnormal neural responses involved in abdominal pain perception and changes in bowel habits. All these mechanisms represent new targets for therapeutic approaches in IBS. Probiotics are an attractive therapeutic option in IBS given their recognized safety and by virtue of positive biological effects they can exert on the host. Of importance for the IBS pathophysiology is that preclinical studies have shown that selective probiotic strains exhibit potentially useful properties including anti-inflammatory effects, improvement of mucosal barrier homeostasis, beneficial effects on intestinal microbiota, and a reduction of visceral hypersensitivity. The effect of probiotics on IBS is positive in most randomized, controlled studies, although the gain over the placebo is small. Identifying tailored probiotic approaches for subgroups of IBS patients represents a challenge for the future.

  7. Thyroid Hormone Levels and TSH Activity in Patients with Obstructive Sleep Apnea Syndrome.

    PubMed

    Bielicki, P; Przybyłowski, T; Kumor, M; Barnaś, M; Wiercioch, M; Chazan, R

    2016-01-01

    Obstructive sleep apnea syndrome (OSAS) is characterized by complete cessation of inspiratory flow (apnea) or upper airway airflow limitation (hypopnea) with increased respiratory muscle activity, which is repeatedly observed during sleep. Hypothyroidism has been described as a rare cause of OSAS, but it is considered to be the main cause of breathing disorders during sleep in patients in whom an improvement of OSAS is observed after thyroid hormone replacement therapy. Nevertheless, euthyreosis due to thyroxine replacement in patients with OSAS often does not improve the breathing disorder and treatment with continuous positive airway pressure is usually applied. The aim of this study was to assess thyroid function in patients with OSAS. We studied 813 patients in whom severe OSAS was diagnosed; the mean apnea-hypopnea index was 44.0. Most of the patients were obese (mean BMI 33.1 ± 6.6 kg/m2) and had excessive daytime sleepiness (ESS 12.8 ± 6.6). With the thyroid stimulating hormone (TSH) concentration as the major criterion, hypothyroidism was diagnosed in 38 (4.7%) and hyperthyroidism was diagnosed in 31 (3.8%) patients. Analysis of basic anthropometric data, selected polysomnography results, and TSH, fT3, and fT4 values did not reveal any significant correlations. In conclusion, the incidence of thyroid function disorders seems to be no different in OSAS than that in the general population. We did not find correlations between TSH activity and the severity of breathing disorders during sleep. PMID:26542600

  8. The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer

    PubMed Central

    Kristjansdottir, Karen; Petersen, Ulrika S. S.; Bang, Jeanne Mari V.; Guerra, Barbara; Andersen, Henriette Skovgaard; Dobrowolski, Steven F.; Carey, John C.; Yu, Ping; Calhoun, Amy; Larsen, Martin R.; Dyrskjøt, Lars; Stevenson, David A.; Andresen, Brage S.

    2016-01-01

    Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE) and creation of an Exonic Splicing Silencer (ESS). We show that this vulnerability of HRAS exon 2 is caused by a weak 3’ splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS- causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping. PMID:27195699

  9. 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. PMID:26853182

  10. 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.

  11. MasABK Proteins Interact with Proteins of the Type IV Pilin System to Affect Social Motility of Myxococcus xanthus

    PubMed Central

    Fremgen, Sarah; Williams, Amanda; Furusawa, Gou; Dziewanowska, Katarzyna; Settles, Matthew; Hartzell, Patricia

    2013-01-01

    Gliding motility is critical for normal development of spore-filled fruiting bodies in the soil bacterium Myxococcus xanthus. Mutations in mgl block motility and development but one mgl allele can be suppressed by a mutation in masK, the last gene in an operon adjacent to the mgl operon. Deletion of the entire 5.5 kb masABK operon crippled gliding and fruiting body development and decreased sporulation. Expression of pilAGHI, which encodes type IV pili (TFP) components essential for social (S) gliding, several cryptic pil genes, and a LuxR family protein were reduced significantly in the Δmas mutant while expression of the myxalamide operon was increased significantly. Localization and two-hybrid analysis suggest that the three Mas proteins form a membrane complex. MasA-PhoA fusions confirmed that MasA is an integral cytoplasmic membrane protein with a ≈100 amino acid periplasmic domain. Results from yeast two-hybrid assays showed that MasA interacts with the lipoprotein MasB and MasK, a protein kinase and that MasB and MasK interact with one another. Additionally, yeast two-hybrid analysis revealed a physical interaction between two gene products of the mas operon, MasA and MasB, and PilA. Deletion of mas may be accompanied by compensatory mutations since complementation of the Δmas social gliding and developmental defects required addition of both pilA and masABK. PMID:23342171

  12. 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

  13. The neuroprotective effect of cornus MAS on brain tissue of Wistar rats.

    PubMed

    Francik, Renata; Kryczyk, Jadwiga; Krośniak, Mirosław; Berköz, Mehmet; Sanocka, Ilona; Francik, Sławomir

    2014-01-01

    Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer's disease) or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet). This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  14. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    PubMed Central

    Francik, Renata; Kryczyk, Jadwiga; Krośniak, Mirosław; Berköz, Mehmet; Sanocka, Ilona; Francik, Sławomir

    2014-01-01

    Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer's disease) or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet). This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma. PMID:25401157

  15. The neuroprotective effect of cornus MAS on brain tissue of Wistar rats.

    PubMed

    Francik, Renata; Kryczyk, Jadwiga; Krośniak, Mirosław; Berköz, Mehmet; Sanocka, Ilona; Francik, Sławomir

    2014-01-01

    Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer's disease) or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet). This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma. PMID:25401157

  16. 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...

  17. 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

  18. Kounis syndrome.

    PubMed

    Ntuli, P M; Makambwa, E

    2015-10-01

    Kounis syndrome is characterised by a group of symptoms that manifest as unstable vasospastic or non-vasospastic angina secondary to a hypersensitivity reaction. It was first described by Kounis and Zavras in 1991 as the concurrence of an allergic response with an anaphylactoid or anaphylactic reaction and coronary artery spasm or even myocardial infarction. Since then, this condition has evolved to include a number of mast cell activation disorders associated with acute coronary syndrome. There are many triggering factors, including reactions to multiple medications, exposure to radiological contrast media, poison ivy, bee stings, shellfish and coronary stents. In addition to coronary arterial involvement, Kounis syndrome comprises other arterial systems with similar physiologies, such as mesenteric and cerebral circulation resulting in ischaemia/infarction of the vital organs. The incidence of this condition is difficult to establish owing to the number of potential instigating factors and its relatively infrequent documentation in the literature.We report the case of an HIV-negative 39-year-old man with no coronary risk factors or family history of premature coronary artery disease, who developed Kounis syndrome after the administration of fluoroquinolone for dysuria. However, to the best of our knowledge,no data on the incidence and prevalence of Kounis syndrome in South Africa have ever been reported in the literature. The recent understanding of Kounis syndrome has led to the condition being classified into three syndrome variants.

  19. Meconium aspiration syndrome and neonatal outcome in a developing country.

    PubMed

    Malik, A S; Hillman, D

    1994-01-01

    The outcome in 148 inborn meconium-stained neonates was studied prospectively over a 5-month period. Fifty-three infants (38.5%) developed meconium aspiration syndrome (MAS). There was a significantly higher rate of MAS (p < 0.001), mechanical ventilation (p < 0.016) and hospital stay (p < 0.016) in neonates with meconium in the trachea than in neonates with no meconium in the oropharynx. The incidence of MAS was significantly higher and the duration of hospital stay longer in outborn than in inborn infants (p < 0.022).

  20. Acrogigantism and facial asymmetry: McCune-Albright syndrome.

    PubMed

    Subbiah, Sridhar; Palikhe, Gaurav; Bhadada, Sanjay Kumar; Mukherjee, Kanchan Kumar; Bhansali, Anil

    2011-01-01

    McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery. PMID:22145488

  1. 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

  2. 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

  3. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.

    PubMed Central

    Gregory, T J; Longmore, W J; Moxley, M A; Whitsett, J A; Reed, C R; Fowler, A A; Hudson, L D; Maunder, R J; Crim, C; Hyers, T M

    1991-01-01

    Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant pellet was analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, and minimum surface tension (STmin). PL was decreased in both AR and A (3.48 +/- 0.61 and 2.47 +/- 0.40 mumol/ml, respectively) compared to N (7.99 +/- 0.60 mumol/ml). Phosphatidylcholine was decreased in A (62.64 +/- 2.20% PL) compared to N (76.27 +/- 2.05% PL). Phosphatidylglycerol was 11.58 +/- 1.21% PL in N and was decreased to 6.48 +/- 1.43% PL in A. SP-A was 123.64 +/- 20.66 micrograms/ml in N and was decreased to 49.28 +/- 21.68 micrograms/ml in AR and to 29.88 +/- 8.49 micrograms/ml in A. SP-B was 1.28 +/- 0.33 micrograms/ml in N and was decreased to 0.57 +/- 0.24 micrograms/ml in A. STmin was increased in AR (15.1 +/- 2.53 dyn/cm) and A (29.04 +/- 2.05 dyn/cm) compared to N (7.44 +/- 1.61 dyn/cm). These data demonstrate that the chemical composition and functional activity of surfactant is altered in ARDS. Several of these alterations also occur in AR, suggesting that these abnormalities occur early in the disease process. PMID:1752956

  4. 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.

  5. Citron and lemon under the lens of HR-MAS NMR spectroscopy.

    PubMed

    Mucci, Adele; Parenti, Francesca; Righi, Valeria; Schenetti, Luisa

    2013-12-01

    High Resolution Magic Angle Spinning (HR-MAS) is an NMR technique that can be applied to semi-solid samples. Flavedo, albedo, pulp, seeds, and oil gland content of lemon and citron were studied through HR-MAS NMR spectroscopy, which was used directly on intact tissue specimens without any physicochemical manipulation. HR-MAS NMR proved to be a very suitable technique for detecting terpenes, sugars, organic acids, aminoacids and osmolites. It is valuable in observing changes in sugars, principal organic acids (mainly citric and malic) and ethanol contents of pulp specimens and this strongly point to its use to follow fruit ripening, or commercial assessment of fruit maturity. HR-MAS NMR was also used to derive the molar percentage of fatty acid components of lipids in seeds, which can change depending on the Citrus species and varieties. Finally, this technique was employed to elucidate the metabolic profile of mold flavedo. PMID:23871074

  6. 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.

  7. Cornelian cherry (cornus MAS L.) juice as a potential source of biological compounds.

    PubMed

    Gąstoł, Maciej; Krośniak, Mirosław; Derwisz, Małgorzata; Dobrowolska-Iwanek, Justyna

    2013-08-01

    Cornelian cherry (Cornus mas L.), apple (Malus domestica Borkh. cultivars Jonagold and Red Boskoop), pear (Pyrus communis cv. Conference), and plum (Prunus domestica L. cv. Common Plum) juices were assayed for their quality, organic acids, polyphenol content, and antioxidant activity (determined as a ferric-reducing antioxidant power [FRAP]). Cornelian cherry juice revealed the highest titratable acidity-2.58 g malic acid/100 g. The highest polyphenol content was also noted for Cornelian cherry-45.6 mg gallic acid (GA)/g. The medium level of polyphenols was proved for Jonagold apple (22.8 mg GA1/g). The lowest level was recorded for Common Plum (9.60 mg GA/g), followed by Conference pear and Red Boskoop apple (12.3 and 21.3 mg GA/g, respectively). The FRAP values were 1.97 mmol Fe/L for Common Plum juice, 2.37 mmol Fe/L for Conference pear juice, and 3.92 mmol Fe/L for both Red Boskoop and Jonagold apple juices. However, the obtained data indicated outstanding antioxidant properties for Cornelian cherry juice. In this case, FRAP reached 23.5 mmol Fe/L. The calculated correlation coefficient FRAP versus polyphenols indicates that the antioxidant status for Cornelian cherry is not only correlated with polyphenols but also with other biological compounds. The obtained results indicated that Cornelian cherry is a valuable source of substances with a high antioxidant activity.

  8. Cornelian cherry (cornus MAS L.) juice as a potential source of biological compounds.

    PubMed

    Gąstoł, Maciej; Krośniak, Mirosław; Derwisz, Małgorzata; Dobrowolska-Iwanek, Justyna

    2013-08-01

    Cornelian cherry (Cornus mas L.), apple (Malus domestica Borkh. cultivars Jonagold and Red Boskoop), pear (Pyrus communis cv. Conference), and plum (Prunus domestica L. cv. Common Plum) juices were assayed for their quality, organic acids, polyphenol content, and antioxidant activity (determined as a ferric-reducing antioxidant power [FRAP]). Cornelian cherry juice revealed the highest titratable acidity-2.58 g malic acid/100 g. The highest polyphenol content was also noted for Cornelian cherry-45.6 mg gallic acid (GA)/g. The medium level of polyphenols was proved for Jonagold apple (22.8 mg GA1/g). The lowest level was recorded for Common Plum (9.60 mg GA/g), followed by Conference pear and Red Boskoop apple (12.3 and 21.3 mg GA/g, respectively). The FRAP values were 1.97 mmol Fe/L for Common Plum juice, 2.37 mmol Fe/L for Conference pear juice, and 3.92 mmol Fe/L for both Red Boskoop and Jonagold apple juices. However, the obtained data indicated outstanding antioxidant properties for Cornelian cherry juice. In this case, FRAP reached 23.5 mmol Fe/L. The calculated correlation coefficient FRAP versus polyphenols indicates that the antioxidant status for Cornelian cherry is not only correlated with polyphenols but also with other biological compounds. The obtained results indicated that Cornelian cherry is a valuable source of substances with a high antioxidant activity. PMID:23905648

  9. Carbon-13 CP-MAS nuclear magnetic resonance studies of teas.

    PubMed

    Martínez-Richa, Antonio; Joseph-Nathan, Pedro

    2003-05-01

    13C CP-MAS NMR spectra of green and black tea were obtained and assigned based on the solid-state NMR spectra of tropolone, (+)-catechin hydrate, gallic acid, caffeine and flavone derivatives. The peak shape and chemical shifts observed for carbonyl carbons in CP-MAS spectra of teas indicate the existence of different chemical species, mainly free phenollic acids and ester derivatives of flavonoids. The peak patterns allow to establish differences between both teas.

  10. The Consistency of the Pandemic Simulations between the SEIR Model and the MAS Model

    NASA Astrophysics Data System (ADS)

    Toyosaka, Yuki; Hirose, Hideo

    There are two main methods for pandemic simulations: the SEIR model and the MAS model. The SEIR model can deal with simulations quickly for many homogeneous populations with simple ordinary differential equations; however, the model cannot accommodate many detailed conditions. The MAS model, the multi-agent simulation, can deal with detailed simulations under the many kinds of initial and boundary conditions with simple social network models. However, the computing cost will grow exponentially as the population size becomes larger. Thus, simulations in the large-scale model would hardly be realized unless supercomputers are available. By combining these two methods, we may perform the pandemic simulations in the large-scale model with lower costs. That is, the MAS model is used in the early stage of a pandemic simulation to determine the appropriate parameters to be used in the SEIR model. With these obtained parameters, the SEIR model may then be used. To investigate the validity of this combined method, we first compare the simulation results between the SEIR model and the MAS model. Simulation results of the MAS model and the SEIR model that uses the parameters obtained by the MAS model simulation are found to be close to each other.

  11. 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.

  12. Does metformin increase paraoxonase activity in patients with the metabolic syndrome? Additional data from the MEFISTO study.

    PubMed

    Meaney, Eduardo; Sierra-Vargas, Patricia; Meaney, Alejandra; Guzmán-Grenfell, Martín; Ramírez-Sánchez, Israel; Hicks, Juan Jose; Olivares-Corichi, Ivonne; Ceballos, Guillermo

    2012-06-01

    In a subanalysis on the metformin, arterial function, intima-media thickness, and nitroxidation in the metabolic syndrome (MEFISTO)(8) (an open-label fashion, with 1 year of 850 mg daily of metformin) subjects' samples, we measured the paraoxonase 1 (PON1) activity in 39 patients that finished the study and relate values with high density lipoprotein (HDL). The comparative PON1 activities at the beginning and at the end of the study were 5.528 ± 0.588 and 4.743 ± 0.619 nmol/mg protein/min (NS) for control group and 3.229 ± 0.403 and 5.135 ± 0.585 nmol/mg protein/min (p < 0.02) for the metformin group. Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration. Our results point out that there is a relationship among PON1 activity and the reduction of carotideal intima-media thickness.

  13. Neither Classical nor Alternative Macrophage Activation Is Required for Pneumocystis Clearance during Immune Reconstitution Inflammatory Syndrome

    PubMed Central

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

    2015-01-01

    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 Pc

  14. [Foetal therapy for Down syndrome: a pro-active ethical reflection].

    PubMed

    de Wert, G M W R; Dondorp, W J

    2016-01-01

    Prenatal screening for Down syndrome has to date focused on facilitating the informed choice to continue or not with a pregnancy. The non-invasive prenatal test (NIPT) for Down syndrome does potentially offer the option to apply foetal neurocognitive therapy for Down syndrome (FTDS). Current research in animal models looks promising and therefore a proactive ethical reflection in relation to clinical trials is urgently needed. This discussion includes an exploration of the ethical aspects of FTDS. There seem to be no convincing a priori objections on the basis of the social model of disability. Arguments in terms of (respect for) autonomy, wellbeing and justice seem to in principle support such therapy. Still, both the conditions for sound clinical trials and the implications of possible effective therapy for current prenatal screening need further scrutiny. PMID:27334087

  15. 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

  16. [The active search for occupational diseases in the engineering industries. Diseases associated with exposure to welding activities in optical radiation: dry eye syndrome].

    PubMed

    Messineo, A; Leone, M; Sanna, S; Arrigoni, E; Teodori, C; Pecorella, I; Imperatore, A; Villarini, S; Macchiaroli, S

    2011-01-01

    In the project of active research of occupational diseases was conducted a study on 45 welders in the engineering companies, with particular attention to the hazards of exposure to the optical radiation. The protocol used involved the execution of Breack Up test, Schirmer test, corneal staining and scraping cytology. It revealed that more than half of the welders had ocular lesions referable to their work activity as well as some permanent functional damages with the characters of dry eye syndrome. None of these diseases, which could alert for medical-legal and insurance, was highlighted by the occupational health physician.

  17. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome.

    PubMed

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique; Cassis, Lisa A

    2012-03-15

    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.

  18. 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

  19. Activity of proximal promoter of the human beta(1)-integrin gene was increased in Sézary syndrome.

    PubMed

    Paulin, Y; Boukhelifa, M; Derappe, C; Giner, M; Font, J; Aubery, M

    2001-06-01

    Changes in beta1-integrin expression have been involved in abnormal cellular interactions between malignant lymphocytes from Sézary (Sz) patients and keratinocytes. In this paper, we compare the activity of both distal and proximal promoters of the beta1-integrin gene in malignant lymphocytes from Sz patients with human normal lymphocytes. Activity of both beta1-integrin promoters was also analysed in human normal keratinocytes. Northern blot analysis shows that beta1-integrin mRNA expression is higher in malignant Sz lymphocytes than in normal lymphocytes. CAT assays show that the activity of proximal beta1-integrin promoter is markedly increased (up to 6-fold) in malignant lymphocytes from Sz patients, in comparison to normal lymphocytes. These results suggest that changes in activity of the proximal promoter of beta1-integrin subunit could be, in part, responsible for the abnormal cellular interactions between malignant lymphocytes and keratinocytes observed in Sz syndrome.

  20. 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. PMID:27017576

  1. 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.

  2. 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. PMID:27473992

  3. 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,…

  4. 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…

  5. 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…

  6. Impairment in Instrumental Activities of Daily Living and the Geriatric Syndrome of Self-Neglect

    ERIC Educational Resources Information Center

    Naik, Aanand D.; Burnett, Jason; Pickens-Pace, Sabrina; Dyer, Carmel B.

    2008-01-01

    Purpose: We sought to characterize self-neglect definitively as a geriatric syndrome by identifying an association with functional impairment. Design and Methods: We performed a cross-sectional home evaluation of 100 community-living older adults referred by Adult Protective Services for geriatric self-neglect and 100 matched adults from a…

  7. 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

  8. McCune-Albright syndrome: radiological and MR findings.

    PubMed

    Yongjing, G; Huawei, L; Zilai, P; Bei, D; Hao, J; Kemin, C

    2001-01-01

    McCune-Albright syndrome (MAS) is a non-inherited disorder due to the GNAS1 gene mutation. The syndrome is characterized with the triad of polyostotic fibrous dysplasia, pigmented skin lesions, endocrinopathy, and precocious puberty. We report the case of a 14-year-old boy, presenting with sclerotic type of polyostotic fibrous dysplasia. Radiological methods including plain X-ray film, MR and whole body bone scintigraphy suggested the diagnosis of MAS. MRI provided more directly perceived images and it was more sensitive in demonstrating the lesion: its shape, contents, especially the size of the affected region. Histopathological study and the identification of mutant gene finally confirmed the diagnostic result.

  9. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome

    PubMed Central

    Sullivan, Åsa; Nord, Carl E; Evengård, Birgitta

    2009-01-01

    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. PMID:19171024

  10. 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

  11. 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

    2009-01-01

    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. PMID:19171024

  12. A randomised, double-blind, vehicle-controlled study to evaluate the efficacy and safety of MAS063D (Atopiclair) in the treatment of mild to moderate atopic dermatitis.

    PubMed

    Belloni, G; Pinelli, S; Veraldi, S

    2005-01-01

    MAS063D (Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis (AD). The putative active ingredients of MAS063D are hyaluronic acid, telmesteine, Vitis vinifera, glycyrrhetinic acid. A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control. MAS063D improved the total body area affected (17.2% --> 13.2%, p < 0.001), itch score (2.7 --> 1.3 on a 10-point scale, p = 0.001) and EASI score (28.3 --> 24.3, p = 0.024) after 22 days treatment compared to baseline. The patients' opinion of MAS063D (patient's view of itch control, and view of study substance) was rated by participating patients as significantly better than control (p = 0.008, p = 0.042 respectively). Based on these preliminary results in a small scale study, it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD. PMID:15701590

  13. Blocking of Exchange Proteins Directly Activated by cAMP Leads to Reduced Replication of Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Tao, Xinrong; Mei, Feng; Agrawal, Anurodh; Peters, Clarence J.; Ksiazek, Thomas G.

    2014-01-01

    The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections and diseases represents a potential threat for worldwide spread and requires development of effective therapeutic strategies. In this study, we revealed a novel positive function of an exchange protein directly activated by cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication. Specifically, we have shown that Epac-specific inhibitor treatment or silencing Epac-1 gene expression rendered cells resistant to viral infection. We believe Epac-1 inhibitors deserve further study as potential therapeutic agents for MERS-CoV infection. PMID:24453361

  14. Magnesium Silicate Dissolution Investigated by 29Si MAS, 1H-29Si CP MAS, 25Mg QCPMG, and 1H-25Mg CP QCPMG NMR

    SciTech Connect

    Davis, Michael C.; Brouwer, William J.; Wesolowski, David J.; Anovitz, Lawrence M.; Lipton, Andrew S.; Mueller, Karl T.

    2009-08-01

    Olivine has been the subject of frequent investigation in the earth sciences because of its simple structure and rapid dissolution kinetics. Several studies have observed a preferential release of magnesium with respect to silica during weathering under acidic conditions, which has been correlated to the formation of a silicon rich leached layer. While leached layer formation has been inferred through the changing solution chemistry, a thorough spectroscopic investigation of olivine reacted under acidic conditions has not been conducted. In particular, the fate of magnesium in the system is not understood and spectroscopic interrogations through nuclear magnetic resonance can elucidate the changing magnesium coordination and bonding environment. In this study, we combine analysis of the changing solution chemistry with advanced spectroscopic techniques (29Si MAS, 1H-29Si CP MAS, 25Mg QCPMG, and 1H-25Mg 2 CP QCPMG NMR) to probe leached layer formation and possible secondary phase precipitation during the dissolution of forsterite at 150 oC.

  15. Plasma fatty acids profile and estimated elongase and desaturases activities in Tunisian patients with the metabolic syndrome.

    PubMed

    Sethom, M M; Fares, S; Feki, M; Hadj-Taieb, S; Elasmi, M; Omar, S; Sanhaji, H; Jemaa, R; Kaabachi, N

    2011-01-01

    This study aimed to determine plasma fatty acids pattern and to estimate desaturases activities in Tunisian subjects with metabolic syndrome (MetS). A total of 1975 adults were randomly selected from the Great Tunis region (Tunisia). MetS was defined according to the International Diabetes Federation criteria. Saturated and monounsaturated fatty acids levels and delta 9 desaturase activity were increased, but polyunsaturated fatty acids (PUFA) levels and delta 5 desaturase activity were decreased in patients with MetS. Using multivariate analysis, MetS was found inversely associated with PUFA; compared to first quartile, multi-adjusted odd ratios (95% confidence interval) of MetS were 0.80 (0.54-1.17), 0.47 (0.27-0.81) and 0.32 (0.15-0.68) for second, third and fourth quartiles of PUFA, respectively. Altered fatty acids pattern in MetS is likely related to both dietary and metabolic changes. PMID:21782403

  16. In Silico Design for Adenosine Monophosphate-Activated Protein Kinase Agonist from Traditional Chinese Medicine for Treatment of Metabolic Syndromes

    PubMed Central

    Tang, Hsin-Chieh

    2014-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) acts as a master mediator of metabolic homeostasis. It is considered as a significant millstone to treat metabolic syndromes including obesity, diabetes, and fatty liver. It can sense cellular energy or nutrient status by switching on the catabolic pathways. Investigation of AMPK has new findings recently. AMPK can inhibit cell growth by the way of autophagy. Thus AMPK has become a hot target for small molecular drug design of tumor inhibition. Activation of AMPK must undergo certain extent change of the structure. Through the methods of structure-based virtual screening and molecular dynamics simulation, we attempted to find out appropriate small compounds from the world's largest TCM Database@Taiwan that had the ability to activate the function of AMPK. Finally, we found that two TCM compounds, eugenyl_beta-D-glucopyranoside and 6-O-cinnamoyl-D-glucopyranose, had the qualification to be AMPK agonist. PMID:24899913

  17. The clinical significance of activated lymphocytes in patients with myelodysplastic syndromes: a single centre study of 131 patients.

    PubMed

    Meers, Stef; Vandenberghe, Peter; Boogaerts, Marc; Verhoef, Gregor; Delforge, Michel

    2008-07-01

    We studied the immune compartment in patients with myelodysplastic syndromes. We show increased surface expression of activation markers (HLA-DR(+), CD57(+), CD28(-), CD62L(-)) on T lymphocytes in blood and bone marrow (n=131). T cell activation was not restricted to any relevant clinical subgroup (FAB, IPSS, cytogenetics) and did not correlate with blood counts or need for treatment. In vitro clonogenic growth of marrow mononuclear cells (n=18) was not influenced by T cells expressing these markers. In addition, using X-chromosome inactivation analysis (n=12) we demonstrate clonal involvement of NK and B cells in half of these patients. We conclude that although activated T lymphocytes can be found in MDS, their role in disease pathogenesis remains unclear in the majority of patients.

  18. Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension.

    PubMed

    Toft, I; Bønaa, K H; Ingebretsen, O C; Nordøy, A; Birkeland, K I; Jenssen, T

    1997-03-01

    Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose (r = .41, P = .002), insulin sensitivity (r = -.35, P = .01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r = -.43, P = .007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index (r = .62, P = .0005), waist-to-hip ratio (r = .75, P = .0001), plasma glucose (r = .50, P = .007), insulin (r = .49, P = .009), proinsulin (r = .57, P = .002), C-peptide (r = .60, P = .0009), insulin sensitivity (r = -.74, P = .0001), NEFA suppression (r = -.64, P = .003), and triglycerides (r = .58, P = .001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.

  19. 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.

  20. Residue specific hydration of primary cell wall potato pectin identified by solid-state 13C single-pulse MAS and CP/MAS NMR spectroscopy.

    PubMed

    Larsen, Flemming H; Byg, Inge; Damager, Iben; Diaz, Jerome; Engelsen, Søren B; Ulvskov, Peter

    2011-05-01

    Hydration of rhamnogalacturonan-I (RG-I) derived from potato cell wall was analyzed by (13)C single-pulse (SP) magic-angle-spinning (MAS) and (13)C cross-polarization (CP) MAS nuclear magnetic resonance (NMR) and supported by (2)H SP/MAS NMR experiments. The study shows that the arabinan side chains hydrate more readily than the galactan side chains and suggests that the overall hydration properties can be controlled by modifying the ratio of these side chains. Enzymatic modification of native (NA) RG-I provided samples with reduced content of arabinan (sample DA), galactan (sample DG), or both side chains (sample DB). Results of these samples suggested that hydration properties were determined by the length and character of the side chains. NA and DA exhibited similar hydration characteristics, whereas DG and DB were difficult to hydrate because of the less hydrophilic properties of the rhamnose-galacturonic acid (Rha-GalA) backbone in RG-I. Potential food ingredient uses of RG-I by tailoring of its structure are discussed.

  1. Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line.

    PubMed Central

    Zembowicz, A; Vane, J R

    1992-01-01

    Toxic shock syndrome toxin 1 (TSST-1) is a Mr 22,000 protein produced by Staphylococcus aureus. It is thought to be the cause of toxic shock syndrome. We investigated the hypothesis that TSST-1 induces nitric oxide (NO) synthase and that the NO formed may be involved in the pathogenesis of toxic shock syndrome. We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1 and also expresses NO synthase activity upon immunological stimulation. J774.2 macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown product of NO, and induced concentration-dependent elevations of cGMP in the pig kidney epithelial cell line (LLC-PK1). This latter effect was due to the generation of L-arginine-derived NO for it was (i) abolished by oxyhemoglobin (10 microM), a scavenger of NO, or by methylene blue (10 microM), an inhibitor of NO-activated guanylate cyclase; (ii) potentiated by superoxide dismutase (100 units/ml), which prolongs the life of NO; (iii) inhibited by NG-monomethyl-L-arginine (0.3 mM), an inhibitor of NO synthase; (iv) significantly decreased when L-arginine (0.4 mM) in the medium was replaced by D-arginine (0.4 mM). Moreover, TSST-1 (100 nM) enhanced the activity of cytosolic NO synthase in J774.2 cells. Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1. The effects of hydrocortisone were partially reversed by coincubation with RU 486 (1 microM), an antagonist of glucocorticoid receptors. Thus, TSST-1 and perhaps other exotoxins produced by Gram-positive bacteria induce NO synthase and the increased NO formation may contribute to toxic shock syndrome and possibly to changes in the immune responses that accompany infection. PMID:1372433

  2. Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A 13C MAS NMR Study

    PubMed Central

    Ciesielski, Filip; Griffin, David C.; Loraine, Jessica; Rittig, Michael; Delves-Broughton, Joss; Bonev, Boyan B.

    2016-01-01

    The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B. PMID:27379235

  3. 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.

  4. 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…

  5. 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

  6. Comparison of the white-nose syndrome agent Pseudogymnoascus destructans to cave-dwelling relatives suggests reduced saprotrophic enzyme activity.

    PubMed

    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

  7. 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

  8. Premenstrual syndrome.

    PubMed

    Parker, P D

    1994-11-01

    Premenstrual syndrome is characterized by an array of somatic, cognitive, affective and behavioral disturbances that recur in cyclic fashion during the luteal phase of the menstrual cycle. The goal of management is to control symptoms well enough that the patient can function appropriately at all stages of the menstrual cycle. Both the patient and the physician must acknowledge that premenstrual syndrome is a complex reproductive disorder with a large number of possible manifestations; therefore, they must be willing to consider more than one strategy, and they must allow sufficient time to seek out successful therapeutic options. The patient must play an active role in all stages of management. Although no specific cure for premenstrual syndrome currently exists, most patients experience significant reduction of symptoms and improvement of quality of life when a rational individualized approach is used. Management may involve pharmacologic, nutritional and psychosocial interventions. PMID:7942429

  9. 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.

  10. Muscle attachment site (MAS) patterns for species determination in European species of Lucilia (Diptera: Calliphoridae).

    PubMed

    Niederegger, Senta; Szpila, Krzysztof; Mall, Gita

    2015-03-01

    Species identification is generally assessed to be more difficult in larval stages than in adult forms. Especially closely related species such as Lucilia caesar and Lucilia illustris are difficult to identify. The aim of this study was to simplify species determination in Lucilia larvae for entomological and forensic purposes. Muscle attachment site (MAS) patterns were previously found to be a good tool for species determination in blowfly larvae. Here, distinctive MAS patterns are presented for European Lucilia ampullacea, L. caesar, L. illustris, L. richardsi, L. sericata, and L. silvarum. A joint pattern for the genus Lucilia is provided for a quick classification of a larva to the genus.

  11. 29Si and 27Al MAS NMR spectra of mullites from different kaolinites.

    PubMed

    He, Hongping; Guo, Jiugao; Zhu, Jianxi; Yuan, Peng; Hu, Cheng

    2004-04-01

    Mullites synthesized from four kaolinites with different random defect densities have been studied by 27Al and 29Si magic angle spinning nuclear magnetic resonance spectroscopy (MAS NMR) and X-ray diffraction (XRD). All these mullites show the same XRD pattern. However, 29Si and 27Al MAS NMR spectra reveal that the mullites derived from kaolinites with high defect densities, have a sillimanite-type Al/Si ordering scheme and are low in silica, whereas those mullites derived from kaolinites with low defect densities, consist of both sillimanite- and mullite-type Al/Si ordering schemes and are rich in silica. PMID:15084323

  12. Auriculotemporal Syndrome (Frey Syndrome).

    PubMed

    Motz, Kevin M; Kim, Young J

    2016-04-01

    Frey syndrome is a common sequela of parotidectomy, and although it is not frequently manifested clinically, it can cause significant morbidity for those affected. Frey syndrome results from synkinetic autonomic reinnervation by transected postganglionic parasympathetic nerve fiber within the parotid gland to the overlying sweat glands of the skin. Many surgical techniques have been proposed to prevent the development of Frey syndrome. For those who develop clinical symptoms of Frey syndrome, objective testing can be performed with a Minor starch-iodine test. Some of the current methods to prevent and treat symptomatic Frey syndrome are reviewed. PMID:26902982

  13. Tourette syndrome

    MedlinePlus

    Gilles de la Tourette syndrome; Tic disorders - Tourette syndrome ... Tourette syndrome is named for Georges Gilles de la Tourette, who first described this disorder in 1885. The disorder is likely passed down through families. The syndrome may be linked to ...

  14. Contribution of fructose-6-phosphate to glucocorticoid activation in the endoplasmic reticulum: possible implication in the metabolic syndrome.

    PubMed

    Senesi, Silvia; Legeza, Balázs; Balázs, Zoltán; Csala, Miklós; Marcolongo, Paola; Kereszturi, Eva; Szelényi, Péter; Egger, Christine; Fulceri, Rosella; Mandl, József; Giunti, Roberta; Odermatt, Alex; Bánhegyi, Gábor; Benedetti, Angelo

    2010-10-01

    Both fructose consumption and increased intracellular glucocorticoid activation have been implicated in the pathogenesis of the metabolic syndrome. Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) depends on hexose-6-phosphate dehydrogenase (H6PD), which physically interacts with 11β-HSD1 at the luminal surface of the endoplasmic reticulum (ER) membrane and generates reduced nicotinamide adenine dinucleotide phosphate for the reduction of glucocorticoids. The reducing equivalents for the reaction are provided by glucose-6-phosphate (G6P) that is transported by G6P translocase into the ER. Here, we show that fructose-6-phosphate (F6P) can substitute for G6P and is sufficient to maintain reductase activity of 11β-HSD1 in isolated microsomes. Our findings indicate that the mechanisms of F6P and G6P transport across the ER membrane are distinct and provide evidence that F6P is converted to G6P in the ER lumen, thus yielding substrate for H6PD-dependent reduced nicotinamide adenine dinucleotide phosphate generation. Using the purified enzyme, we show that F6P cannot be directly dehydrogenated by H6PD, and we also excluded H6PD as a phosphohexose isomerase. Therefore, we postulate the existence of an ER luminal hexose-phosphate isomerase different from the cytosolic enzyme. The results suggest that cytosolic F6P promotes prereceptor glucocorticoid activation in white adipose tissue, which might have a role in the pathophysiology of the metabolic syndrome.

  15. 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

  16. Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.

    PubMed

    Kanamarlapudi, Venkateswarlu; Gordon, Uma D; López Bernal, Andrés

    2016-06-01

    Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. PMID:27061682

  17. 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.

  18. Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine.

    PubMed

    Liu, Yue; Yin, Huijun; Chen, Keji

    2013-11-01

    The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases. Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs. The study of blood stasis syndrome (BSS) and activated blood circulation of traditional Chinese medicine (TCM) is one of the most active fields where the integration of TCM and western medicine in China has been successful. Activated blood circulation herbs (ABC herbs) of Chinese medicine are often used in the treatment of BSS. Most ABC herbs have antiplatelet and anti-atherosclerosis activity, but knowledge about their targets is lacking. Coronary heart disease (CHD), BSS, and platelet activation are closely related. By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD, platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs. In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.

  19. 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.

  20. 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.

  1. Sealed Rotors for In Situ High Temperature High Pressure MAS NMR†

    PubMed Central

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

    2015-01-01

    Here we present the design of reusable and perfectly-sealed all-zircornia MAS rotors. The rotors are used to study AlPO4-5 molecular sieve crystallization under hydrothermal conditions, high temperature high pressure cyclohexanol dehydration reaction, and low temperature metabolomics of intact biological tissue. PMID:26171928

  2. Understanding the symmetric line shape in the 17O MAS spectra for hexagonal ice

    NASA Astrophysics Data System (ADS)

    Yamada, Kazuhiko; Oki, Shinobu; Deguchi, Kenzo; Shimizu, Tadashi

    2016-06-01

    Solid-state 17O Magic-Angle Spinning (MAS) nuclear magnetic resonance (NMR) spectra of 17O-enriched hexagonal ice, [17O]-Ih, between 173 and 253 K were presented. Marked changes in the line shape were clearly observed, indicating water molecular reorientation in the crystal structure. At 173 K, molecular motions were considered to be frozen and analysis of the 1D MAS spectrum yielded the following parameters: quadrupole coupling constant (CQ) = 6.6 ± 0.2 MHz and asymmetry parameter (ηQ) = 0.95 ± 0.05. At 232 K and above, contrary to the conventional explanation, pseudo-symmetric line shapes appeared in the 17O MAS NMR spectra arising from the contribution of second-order quadrupole interactions. As a chemical exchange model to describe these isotropic 17O MAS NMR spectra, a modified Ratcliffe model, which consider the effects of proton disorder, was proposed, and the resulting theoretical spectra could well reproduce the experimental spectra.

  3. 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...

  4. 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…

  5. 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…

  6. 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…

  7. 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.

  8. 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 self-esteem…

  9. Advanced instrumentation for DNP-enhanced MAS NMR for higher magnetic fields and lower temperatures

    NASA Astrophysics Data System (ADS)

    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 < 9 T) and temperatures (T > 90 K) 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 ∼100 K and ∼30 K. 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.

  10. 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. PMID:26920836

  11. Genome Sequence of Streptococcus agalactiae Strain 09mas018883, Isolated from a Swedish Cow.

    PubMed

    Zubair, S; de Villiers, E P; Fuxelius, H H; Andersson, G; Johansson, K-E; Bishop, R P; Bongcam-Rudloff, E

    2013-01-01

    We announce the complete genome sequence of Streptococcus agalactiae strain 09mas018883, isolated from the milk of a cow with clinical mastitis. The availability of this genome may allow identification of candidate genes, leading to discovery of antigens that might form the basis for development of a vaccine as an alternative means of mastitis control. PMID:23846269

  12. Specific Alterations in Complement Protein Activity of Little Brown Myotis (Myotis lucifugus) Hibernating in White-Nose Syndrome Affected Sites

    PubMed Central

    Moore, Marianne S.; Reichard, Jonathan D.; Murtha, Timothy D.; Zahedi, Bita; Fallier, Renee M.; Kunz, Thomas H.

    2011-01-01

    White-nose syndrome (WNS) is the most devastating condition ever reported for hibernating bats, causing widespread mortality in the northeastern United States. The syndrome is characterized by cutaneous lesions caused by a recently identified psychrophilic and keratinophylic fungus (Geomyces destructans), depleted fat reserves, atypical behavior, and damage to wings; however, the proximate cause of mortality is still uncertain. To assess relative levels of immunocompetence in bats hibernating in WNS-affected sites compared with levels in unaffected bats, we describe blood plasma complement protein activity in hibernating little brown myotis (Myotis lucifugus) based on microbicidal competence assays using Escherichia coli, Staphylococcus aureus and Candida albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected sites had higher bactericidal ability against E. coli and S. aureus, but lower fungicidal ability against C. albicans when compared with blood plasma from bats collected at unaffected sites. Within affected sites during mid-hibernation, we observed no difference in microbicidal ability between bats displaying obvious fungal infections compared to those without. Bactericidal ability against E. coli decreased significantly as hibernation progressed in bats collected from an affected site. Bactericidal ability against E. coli and fungicidal ability against C. albicans were positively correlated with body mass index (BMI) during late hibernation. We also compared complement activity against the three microbes within individuals and found that the ability of blood plasma from hibernating M. lucifugus to lyse microbial cells differed as follows: E. coli>S. aureus>C. albicans. Overall, bats affected by WNS experience both relatively elevated and reduced innate immune responses depending on the microbe tested, although the cause of observed immunological changes remains unknown. Additionally, considerable trade-offs may exist between energy

  13. Specific alterations in complement protein activity of little brown myotis (Myotis lucifugus) hibernating in white-nose syndrome affected sites.

    PubMed

    Moore, Marianne S; Reichard, Jonathan D; Murtha, Timothy D; Zahedi, Bita; Fallier, Renee M; Kunz, Thomas H

    2011-01-01

    White-nose syndrome (WNS) is the most devastating condition ever reported for hibernating bats, causing widespread mortality in the northeastern United States. The syndrome is characterized by cutaneous lesions caused by a recently identified psychrophilic and keratinophylic fungus (Geomyces destructans), depleted fat reserves, atypical behavior, and damage to wings; however, the proximate cause of mortality is still uncertain. To assess relative levels of immunocompetence in bats hibernating in WNS-affected sites compared with levels in unaffected bats, we describe blood plasma complement protein activity in hibernating little brown myotis (Myotis lucifugus) based on microbicidal competence assays using Escherichia coli, Staphylococcus aureus and Candida albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected sites had higher bactericidal ability against E. coli and S. aureus, but lower fungicidal ability against C. albicans when compared with blood plasma from bats collected at unaffected sites. Within affected sites during mid-hibernation, we observed no difference in microbicidal ability between bats displaying obvious fungal infections compared to those without. Bactericidal ability against E. coli decreased significantly as hibernation progressed in bats collected from an affected site. Bactericidal ability against E. coli and fungicidal ability against C. albicans were positively correlated with body mass index (BMI) during late hibernation. We also compared complement activity against the three microbes within individuals and found that the ability of blood plasma from hibernating M. lucifugus to lyse microbial cells differed as follows: E. coli>S. aureus>C. albicans. Overall, bats affected by WNS experience both relatively elevated and reduced innate immune responses depending on the microbe tested, although the cause of observed immunological changes remains unknown. Additionally, considerable trade-offs may exist between energy

  14. Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors.

    PubMed

    Yumuk, Volkan D

    2006-11-01

    The three peroxisome-proliferator-activated receptor (PPAR) subtypes PPAR-alpha, PPAR-gamma, and PPAR-delta are ligand-activated transcription factors of the nuclear receptor family. PPARs form obligate heterodimers with the retinoid X receptor, which bind to peroxisome-proliferator-response elements (PPREs). PPAR-alpha is expressed mainly in liver, brown fat, kidney, heart, and skeletal muscle; PPAR-gamma in intestine and adipose tissue; PPAR-alpha and PPAR-gamma are both expressed in vascular endothelium, smooth muscle cells, macrophages, and foam cells; PPAR-delta in skeletal muscle, human embryonic kidney, intestine, heart, adipose tissue, developing brain, and keratinocytes. Intense interest in the development of drugs with new mechanisms of action for the metabolic syndrome has focused attention on nuclear receptors, such as PPARs that function as regulators of energy homeostasis. Agonists of PPAR-alpha and PPAR-gamma are currently used to treat diabetic dyslipidemia and type 2 diabetes. Dual PPAR-alpha/gamma agonists and PPAR-alpha/gamma/delta pan-agonists are under investigation for treatment of cardiovascular disease and the metabolic syndrome. Selective PPAR modulators (SPPARMs) are PPAR ligands that possess desirable efficacy and improved tolerance. Efforts are being made to identify novel partial agonists or antagonists for PPAR-gamma in order to combine their antidiabetic and antiobesity effects. Glucocorticoids are major mediators of the stress response and could be the link between stress and PPAR activator signaling and thus may affect the downstream metabolic pathways involved in fuel homeostasis. PMID:17148746

  15. 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

  16. Various shrug exercises can change scapular kinematics and scapular rotator muscle activities in subjects with scapular downward rotation syndrome.

    PubMed

    Lee, Ji-Hyun; Cynn, Heon-Seock; Choi, Woo-Jeong; Jeong, Hyo-Jung; Yoon, Tae-Lim

    2016-02-01

    Scapular dyskinesis, characterized by scapular downward rotation syndrome (SDRS) affects scapula-humeral rhythm and results in shoulder dysfunction. Previous study has led to the recommendation of standard shrug exercise to contend with SDRS and strengthen the upper trapezius (UT) muscle. However, few researchers have examined which shrug exercise is most effective. The aim of this research was to compare scapular kinematic changes and scapular rotator muscles activity across three different shrug exercises in SDRS. The amounts of scapular downward rotation were measured by a caliper and the scapular upward rotation angle was measured using two digital inclinometers. Surface electromyography was used to measure EMG amplitude from the UT, lower trapezius (LT), serratus anterior (SA), and levator scapula (LS). Seventeen subjects with SDRS were recruited for this study. The subjects performed three shrug exercises with 30° shoulder abduction (preferred shrug, frontal shrug, and stabilization shrug). The stabilization shrug showed a significantly greater scapular upward rotation angle compared with the preferred shrug (P=0.004) and frontal shrug (P=0.006). The UT activity was significantly greater in the frontal shrug than in the preferred shrug (P=0.002). The UT/LS muscle activity ratio was also significantly greater in the frontal shrug than in the preferred shrug (P=0.004). The stabilization shrug should be preferred to enhance the upward rotation angle. In addition, the frontal shrug can be used as an effective method to increase UT activity and to decrease LS activity in SDRS. PMID:26625348

  17. Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Malinge, Sebastien; Ben-Abdelali, Raouf; Settegrana, Catherine; Radford-Weiss, Isabelle; Debre, Marianne; Beldjord, Kheira; Macintyre, Elizabeth A; Villeval, Jean-Luc; Vainchenker, William; Berger, Roland; Bernard, Olivier A; Delabesse, Eric; Penard-Lacronique, Virginie

    2007-03-01

    Activation of tyrosine kinase genes is a frequent event in human hematologic malignancies. Because gene activation could be associated with gene dysregulation, we attempted to screen for activating gene mutation based on high-level gene expression. We focused our study on the Janus kinase 2 (JAK2) gene in 90 cases of acute leukemia. This strategy led to the identification of a novel JAK2-acquired mutation in a patient with Down syndrome (DS) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This mutation involves a 5-amino acid deletion within the JH2 pseudokinase domain (JAK2DeltaIREED). Expression of JAK2DeltaIREED in Ba/F3 cells induced constitutive activation of the JAK-STAT pathway and growth factor-independent cell proliferation. These results highlight the JAK2 pseudokinase domain as an oncogenic hot spot and indicate that activation of the JAK-STAT pathway may contribute to lymphoid malignancies and hematologic disorders observed in children with DS.

  18. A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome.

    PubMed

    Scheibye-Knudsen, Morten; Mitchell, Sarah J; Fang, Evandro F; Iyama, Teruaki; Ward, Theresa; Wang, James; Dunn, Christopher A; Singh, Nagendra; Veith, Sebastian; Hasan-Olive, Md Mahdi; Mangerich, Aswin; Wilson, Mark A; Mattson, Mark P; Bergersen, Linda H; Cogger, Victoria C; Warren, Alessandra; Le Couteur, David G; Moaddel, Ruin; Wilson, David M; Croteau, Deborah L; de Cabo, Rafael; Bohr, Vilhelm A

    2014-11-01

    Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csb(m/m) mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csb(m/m) mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD(+) supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD(+), through the deacetylase SIRT1 and suggests possible interventions for CS.

  19. A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome.

    PubMed

    Scheibye-Knudsen, Morten; Mitchell, Sarah J; Fang, Evandro F; Iyama, Teruaki; Ward, Theresa; Wang, James; Dunn, Christopher A; Singh, Nagendra; Veith, Sebastian; Hasan-Olive, Md Mahdi; Mangerich, Aswin; Wilson, Mark A; Mattson, Mark P; Bergersen, Linda H; Cogger, Victoria C; Warren, Alessandra; Le Couteur, David G; Moaddel, Ruin; Wilson, David M; Croteau, Deborah L; de Cabo, Rafael; Bohr, Vilhelm A

    2014-11-01

    Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csb(m/m) mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csb(m/m) mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD(+) supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD(+), through the deacetylase SIRT1 and suggests possible interventions for CS. PMID:25440059

  20. Pain acceptance-based coping in complex regional pain syndrome Type I: daily relations with pain intensity, activity, and mood.

    PubMed

    Cho, Sungkun; McCracken, Lance M; Heiby, Elaine M; Moon, Dong-Eon; Lee, Jang-Han

    2013-10-01

    This study aimed to examine the temporal patterning of pain acceptance-based coping, activity, and mood in patients with complex regional pain syndrome Type I (CRPS-I), by using a daily diary method. A total of 30 patients with CRPS-I seeking treatment in a tertiary pain management center located in Seoul, Korea participated in the study. Multilevel random effects analyses indicated that (a) engagement in pain acceptance-based coping was significantly associated with lower same-day pain and negative mood and greater same-day activity and positive mood; (b) pain acceptance-based coping predicted increases in activity on the following day; (c) greater pain intensity was significantly associated with lower same-day pain acceptance-based coping and activity and greater same-day negative mood; and (d) pain intensity did not predict pain acceptance-based coping, activity, or mood on the following day. These findings suggest that patients with CRPS-I may benefit from responding to pain with acceptance. Further study and eventual application of this process in CRPS-I may improve upon the success of current approaches to this problem. PMID:22854886

  1. 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.

  2. Overexpressed Down Syndrome Cell Adhesion Molecule (DSCAM) Deregulates P21-Activated Kinase (PAK) Activity in an In Vitro Neuronal Model of Down Syndrome: Consequences on Cell Process Formation and Extension.

    PubMed

    Pérez-Núñez, Ramón; Barraza, Natalia; Gonzalez-Jamett, Arlek; Cárdenas, Ana Maria; Barnier, Jean-Vianney; Caviedes, Pablo

    2016-07-01

    In humans, Down syndrome (DS) is caused by the presence of an extra copy of autosome 21. The most striking finding in DS patients is intellectual disability and the onset of Alzheimer's disease (AD)-like neuropathology in adulthood. Gene overdose is most likely to underlie both developmental impairments, as well as altered neuronal function in DS. Lately, the disruption of cellular signaling and regulatory pathways has been implicated in DS pathophysiology, and many of such pathways may represent common targets for diverse DS-related genes, which could in turn represent attractive therapeutical targets. In this regard, one DS-related gene Down Syndrome Cell Adhesion Molecule (DSCAM), has important functions in neuronal proliferation, maturation, and synaptogenesis. p21-associated kinases (PAKs) appear as a most interesting possibility for study, as DSCAM is known to regulate the PAKs pathway. Hence, in DS, overexpressed DSCAM could deregulate PAKs activity and affect signaling pathways that regulate synaptic plasticity such as dendritic spine dynamics and axon guidance and growth. In the present work, we used an immortalized cell line derived from the cerebral cortex of an animal model of DS such as the trisomy 16 (Ts16) fetal mouse (named CTb), and a similar cell line established from a normal littermate (named CNh), to study the effect of DSCAM in the PAKs pathway. The present study shows that DSCAM is overexpressed in CTb cells by approximately twofold, compared to CNh cells. Congruently, PAK1, as well as its downstream effectors LIMK and cofilin, stay phosphorylated for longer periods after DSCAM activation in the CTb cells, leading to an altered actin dynamics, expressed as an increased basal F/G ratio and reduced neurite growth, in the trisomic condition. The present work presents the correlation between DSCAM gene overexpression and a dysregulation of the PAK pathway, resulting in altered morphological parameters of neuronal plasticity in the trisomic cell

  3. 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.

  4. Genetics Home Reference: cardiofaciocutaneous syndrome

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions cardiofaciocutaneous syndrome cardiofaciocutaneous syndrome Enable ...

  5. Differential activation of the amygdala and the 'social brain' during fearful face-processing in Asperger Syndrome.

    PubMed

    Ashwin, Chris; Baron-Cohen, Simon; Wheelwright, Sally; O'Riordan, Michelle; Bullmore, Edward T

    2007-01-01

    Impaired social cognition is a core feature of autism. There is much evidence showing people with autism use a different cognitive style than controls for face-processing. We tested if people with autism would show differential activation of social brain areas during a face-processing task. Thirteen adults with high-functioning autism or Asperger Syndrome (HFA/AS) and 13 matched controls. We used fMRI to investigate 'social brain' activity during perception of fearful faces. We employed stimuli known to reliably activate the amygdala and other social brain areas, and ROI analyses to investigate brain areas responding to facial threat as well as those showing a linear response to varying threat intensities. We predicted: (1) the HFA/AS group would show differential activation (as opposed to merely deficits) of the social brain compared to controls and (2) that social brain areas would respond to varied intensity of fear in the control group, but not the HFA/AS group. Both predictions were confirmed. The controls showed greater activation in the left amygdala and left orbito-frontal cortex, while the HFA/AS group showed greater activation in the anterior cingulate gyrus and superior temporal cortex. The control group also showed varying responses in social brain areas to varying intensities of fearful expression, including differential activations in the left and right amygdala. This response in the social brain was absent in the HFA/AS group. HFA/AS are associated with different patterns of activation of social brain areas during fearful emotion processing, and the absence in the HFA/AS brain of a response to varying emotional intensity.

  6. 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.

  7. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized.

  8. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized. PMID:27660746

  9. 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.

  10. Dietary folic acid activates AMPK and improves insulin resistance and hepatic inflammation in dietary rodent models of the metabolic syndrome.

    PubMed

    Buettner, R; Bettermann, I; Hechtl, C; Gäbele, E; Hellerbrand, C; Schölmerich, J; Bollheimer, L C

    2010-10-01

    The AMP activated kinase plays an important role in metabolic control, and pharmacologic enhancement of AMPK activity is used to improve insulin resistance. We hypothesized that high dose of folic acid supplementation might improve insulin sensitivity and hepatic inflammation and examined this by a dietary intervention in (a) the high fat fed rat model of the metabolic syndrome, which shows sole hepatic steatosis as well as (b) in rats fed with a high cholesterol, high cholate diet inducing nonalcoholic steatohepatitis (NASH). Male Wistar rats were fed with folic acid supplemented (40 mg/kg) high fat diet [based on lard, fat content 25% (wt/wt)] or NASH inducing diet (containing 15% fat, 1.25% cholesterol, 0.5% sodium cholate). Metabolic profiling was performed by measuring the animals' visceral fat pads, fasting plasma glucose, insulin, and adipokines as well as in vivo insulin tolerance tests. Hepatic steatosis and inflammation were analyzed semiquantitatively by histological analysis. Folic acid supplementation reduced visceral obesity and improved plasma adiponectin levels. In vivo insulin sensitivity was improved, and in HF-FA rats folic acid increased activation of hepatic AMPK. Further, folic acid supplementation improved hepatic inflammation in animals fed with NASH-inducing diet. Dietary folic acid improved parameters of insulin resistance and hepatic inflammation in rodent models. This might be due to an increased AMK activation.

  11. 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

    2016-01-01

    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.

  12. Erythrocyte catechol-O-methyltransferase activity: genetic analysis in nuclear families with one child affected by Down syndrome.

    PubMed

    Brahe, C; Serra, A; Morton, N E

    1985-06-01

    Erythrocyte catechol-O-methyltransferase (COMT) activity was measured in 142 members of 32 nuclear families in which one child had Down syndrome (DS). The mean activity in subjects with trisomy 21 appears higher than in parents and sibs, though not significantly so. However, this fact does not seem to modify the properties expected for a trait genetically controlled in a diploid population. The commingling analysis of the COMT activity in the whole group, and in each subgroup of relatives, suggests a mixture of two or, more likely, three components, the latter being in agreement with a transmission model of genes without dominance. The most parsimonious hypothesis supported by the mixed model segregation analysis is that of an additive major locus (d = 0.5) with an estimated frequency of 0.40 +/- 0.03 for the COMTH gene, to which a small polygenic effect (H = 0.067) can be added. This hypothesis is supported further by the analysis of family resemblance, r = 0.45 +/- 0.12 being the maximum likelihood estimator of the intraclass correlation among sibs. The higher COMT activity in DS subjects may reflect a situation of general enzyme disorder only indirectly connected with trisomy of chromosome 21. PMID:3160238

  13. 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.

  14. 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

  15. Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome?

    PubMed

    Lin, Jin-Ding; Lin, Lan-Ping; Hsu, Shang-Wei; Chen, Wen-Xiu; Lin, Fu-Gong; Wu, Jia-Ling; Chu, Cordia

    2014-11-13

    This study aims to answer the research question of "Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome (DS)?" A cross-sectional survey was employed to recruit 216 individuals with DS over 15 years of age in the analyses. A structured questionnaire included demographic data, brief self-reported aging conditions, Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) and activity of daily living (ADL) scales were completed by the primary caregivers who were well-suited for providing information on the functioning conditions of the DS individuals. Results showed that the most five frequent aging conditions (sometimes, usually and always) included frailty (20.2%), vision problem (15.8%), loss of language ability (15.3%), sleep problem (14.9%) and memory impairment (14.5%). Other onset aging conditions included more chronic diseases (13.9%), hearing loss (13%), chewing ability and tooth loss (12.5%), incontinence (11.1%), depressive syndrome (7.7%), falls and gait disorder (7.2%), loss of taste and smell (7.2%). The data also showed scores of DSQIID, onset aging conditions and ADL has significant relationships each other in Pearson's correlation tests. Finally, multiple linear regression analyses indicated onset aging conditions (β=-0.735, p<0.001) can significantly predicted the variation in ADL scores after adjusting other factors (R(2)=0.381). This study suggests that the authority should initiate early intervention programs aim to improve healthy aging and ADL functions for people with DS. PMID:25462513

  16. Peroxisome Proliferator-Activated Receptor-γGene Expression and Its Association with Oxidative Stress in Patients with Metabolic Syndrome.

    PubMed

    Hatami, Mehdi; Saidijam, Massoud; Yadegarzari, Reza; Borzuei, Shiva; Soltanian, Alireza; Arian, Marzieh Safi; Goodarzi, Mohammad Taghi

    2016-09-01

    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

  17. 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.

  18. "Café-au-lait spots" caused by vitiligo in McCune-Albright syndrome.

    PubMed

    Whyte, M P; Podgornik, M N; Zerega, J; Reinus, W R

    2000-12-01

    Café-au-lait spots, fibrous dysplasia of bone, and endocrine gland hyperactivity are the principal features of McCune-Albright syndrome (MAS). Café-au-lait spots appear at, or soon after, birth. We illustrate "café-au-lait spots" acquired during middle age in a patient with MAS that are an illusion caused by vitiligo. This 64-year-old woman is the oldest patient reported with this disorder. PMID:11127218

  19. 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

  20. 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

  1. 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

  2. Physical Activity and Self-reported Symptoms of Insomnia, Restless Legs Syndrome and Depression: the Comprehensive Dialysis Study

    PubMed Central

    Anand, Shuchi; Johansen, Kirsten L.; Grimes, Barbara; Kaysen, George A.; Dalrymple, Lorien S.; Kutner, Nancy G.; Chertow, Glenn M.

    2012-01-01

    Background 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. Methods 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 2-item Patient Health Questionnaire. Results 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. Conclusion 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. PMID:22812496

  3. Reduced Ovarian Glyoxalase-I Activity by Dietary Glycotoxins and Androgen Excess: A Causative Link to Polycystic Ovarian Syndrome

    PubMed Central

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-01-01

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (rs = 0.533, p < 0.001), estradiol (rs = 0.326, p = 0.033) and progesterone levels (rs = 0.500, p < 0.001). A negative correlation was observed between GLO-I activity and AGE expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (rs = −0.263, p = 0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS. PMID:22859292

  4. 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…

  5. 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

    Zhang, Pei; Huang, Angela; Morales-Ruiz, Manuel; Starcher, Barry C; Huang, Yan; Sessa, William C; Niklason, Laura E; Giordano, Frank J

    2012-11-01

    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.

  6. Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression.

    PubMed

    Tanno, Tomohiro; Tomita, Hirofumi; Narita, Ikuyo; Kinjo, Takahiko; Nishizaki, Kimitaka; Ichikawa, Hiroaki; Kimura, Yoshihiro; Tanaka, Makoto; Osanai, Tomohiro; Okumura, Ken

    2016-06-01

    Enhanced renin-angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1-7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of blood pressure, and evaluated the potential mechanisms. The 3- to 4-month-old male mice overexpressing renin in the liver (Ren-Tg) were given Olm (5 mg/kg/d) and hydralazine (Hyd) (3.5 mg/kg/d) orally for 2 months. Systolic blood pressure was higher in the Ren-Tg mice than in wild-type littermates. Olm and Hyd treatments lowered systolic blood pressure to the same degree. However, cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression, was inhibited by only Olm treatment, but not by Hyd. Olm treatment reversed decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibited enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species, whereas Hyd treatment had no influence on them. These findings indicate that Olm treatment inhibits cardiac hypertrophy independently of blood pressure, not only through its original AT1R blockade but partly through enhancement of ACE2/Ang(1-7)/Mas axis and suppression of Nox4 expression. PMID:26886190

  7. Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas).

    PubMed

    Jayaprakasam, Bolleddula; Olson, L Karl; Schutzki, Robert E; Tai, Mei-Hui; Nair, Muraleedharan G

    2006-01-11

    Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes-related disorders in Asia. In this study, the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, were purified, and their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high-fat diet was evaluated. Mice were initially fed a high-fat diet for 4 weeks and then switched to a high-fat diet containing anthocyanins (1 g/kg of high-fat diet) and ursolic acid (500 mg/kg of high-fat diet) for an additional 8 weeks. The high-fat diet induced glucose intolerance, and this was prevented by anthocyanins and ursolic acid. The anthocyanin-treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver, including a significant decrease in liver triacylglycerol concentration. Anthocyanin and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity. PMID:16390206

  8. 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…

  9. 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.…

  10. Activation of the mTOR pathway by the amino acid (L)-leucine in the 5q- syndrome and other ribosomopathies.

    PubMed

    Boultwood, Jacqueline; Yip, Bon Ham; Vuppusetty, Chaitanya; Pellagatti, Andrea; Wainscoat, James S

    2013-01-01

    Patients with the 5q- syndrome and Diamond-Blackfan anemia (DBA) suffer from a severe macrocytic anemia. The 5q- syndrome and DBA are disorders of aberrant ribosome biogenesis (ribosomopathies) and haploinsufficiency of the ribosomal protein genes RPS14 and RPS19, respectively, underlies the anemia found in these disorders. Erythroblasts obtained from patients with the 5q- syndrome and DBA show impaired mRNA translation and this defect in translation may represent a potential therapeutic target in these ribosomopathies. There are some indications that the amino acid l-leucine, a translation enhancer, may have some efficacy in this group of disorders. Recent studies have shown that l-leucine treatment of zebrafish and murine models of the 5q- syndrome and DBA results in a marked improvement in the anemia. l-leucine treatment of RPS14-deficient and RPS19-deficient erythroblasts and erythroblasts from patients with the 5q- syndrome has been shown to result in an increase in cell proliferation, erythroid differentiation and mRNA translation in culture. l-leucine has been shown to improve hemoglobin levels and transfusion independence in a patient with DBA. l-leucine activates the mTOR (mammalian target of rapamycin) signaling pathway that controls cell growth and mRNA translation. There is evidence to suggest that the promotion of translation via the mTOR pathway by l-leucine is the mechanism that underlies the enhanced erythroid progenitor cell growth and differentiation observed in animal and cellular models of the 5q- syndrome and DBA treated with this amino acid. These data support the rationale for clinical trials of l-leucine as a therapeutic agent for the 5q- syndrome and DBA. PMID:23031788

  11. Transactivation, dimerization, and DNA-binding activity of white spot syndrome virus immediate-early protein IE1.

    PubMed

    Liu, Wang-Jing; Chang, Yun-Shiang; Wang, Hao-Ching; Leu, Jiann-Horng; Kou, Guang-Hsiung; Lo, Chu-Fang

    2008-11-01

    Immediate-early proteins from many viruses function as transcriptional regulators and exhibit transactivation activity, DNA binding activity, and dimerization. In this study, we investigated these characteristics in white spot syndrome virus (WSSV) immediate-early protein 1 (IE1) and attempted to map the corresponding functional domains. Transactivation was investigated by transiently expressing a protein consisting of the DNA binding domain of the yeast transactivator GAL4 fused to full-length IE1. This GAL4-IE1 fusion protein successfully activated the Autographa californica multicapsid nucleopolyhedrovirus p35 basal promoter when five copies of the GAL4 DNA binding site were inserted upstream of the TATA box. A deletion series of GAL4-IE1 fusion proteins suggested that the transactivation domain of WSSV IE1 was carried within its first 80 amino acids. A point mutation assay further showed that all 12 of the acidic residues in this highly acidic domain were important for IE1's transactivation activity. DNA binding activity was confirmed by an electrophoresis mobility shift assay using a probe with (32)P-labeled random oligonucleotides. The DNA binding region of WSSV IE1 was located in its C-terminal end (amino acids 81 to 224), but mutation of a putative zinc finger motif in this C-terminal region suggested that this motif was not directly involved in the DNA binding activity. A homotypic interaction between IE1 molecules was demonstrated by glutathione S-transferase pull-down assay and a coimmunoprecipitation analysis. A glutaraldehyde cross-linking experiment and gel filtration analysis showed that this self-interaction led to the formation of stable IE1 dimers. PMID:18768963

  12. Differential Regulation of Proinflammatory Mediators following LPS- and ATP-Induced Activation of Monocytes from Patients with Antiphospholipid Syndrome

    PubMed Central

    Martirosyan, Anush; Petrek, Martin; Navratilova, Zdenka; Blbulyan, Armen; Boyajyan, Anna; Manukyan, Gayane

    2015-01-01

    Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent thrombosis and pregnancy morbidity in association with the presence of antiphospholipid antibodies. Growing evidence supports the involvement of monocytes in APS pathogenesis. Inflammatory activation of monocytes promotes thrombus formation and other APS complications. However, mechanisms underlying their activation are poorly investigated. We aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS + adenosine triphosphate (ATP) using comparative qRT-PCR. The results showed that LPS significantly increased transcriptional levels of TLR2, IL-23, CCL2, CXCL10, IL-1β, and IL-6 in APS cells, while, in cells from healthy donors, LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of the cells resulted in decreased mRNA levels of NLRP3 in monocytes isolated from healthy donors and CCL2, IL-1β in APS cells. By contrast, TLR2 mRNAs were elevated in both investigated groups after culture of the cells with LPS + ATP. Thus, the findings indicate increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes. Low concentrations of ATP diminish LPS-induced inflammatory state of APS monocytes which might be a potential mechanism which regulates inflammatory state of the cells. PMID:25785264

  13. 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

  14. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice.

    PubMed

    Navani, Dipesh M; Sirohi, Sunil; Madia, Priyanka A; Yoburn, Byron C

    2011-10-01

    On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, low doses of 6β-naltrexol antagonized naltrexone precipitated withdrawal while high doses acted additively. All doses of naltrexone increased 6β-naltrexol's potency to precipitate withdrawal. The next experiment examined changes in antagonist potency to precipitate withdrawal with increasing morphine dependence. Mice were exposed to morphine for 1-6 days and then withdrawal was precipitated. Naltrexone was more potent than 6β-naltrexol at all the time points. The ED(50) of both drugs decreased at the same rate suggesting that increased dependence produced no change in constitutive opioid receptor activity. Taken together these results indicate that the functional efficacy of 6β-naltrexol is dose-dependent and that constitutive opioid receptor activity did not change as opioid dependence increased from 1 to 6 days. PMID:21736895

  15. 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

  16. Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.

    PubMed

    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

    2016-07-18

    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.

  17. 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.

  18. 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. PMID:25848016

  19. Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.

    PubMed

    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

  20. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice.

    PubMed

    Navani, Dipesh M; Sirohi, Sunil; Madia, Priyanka A; Yoburn, Byron C

    2011-10-01

    On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, low doses of 6β-naltrexol antagonized naltrexone precipitated withdrawal while high doses acted additively. All doses of naltrexone increased 6β-naltrexol's potency to precipitate withdrawal. The next experiment examined changes in antagonist potency to precipitate withdrawal with increasing morphine dependence. Mice were exposed to morphine for 1-6 days and then withdrawal was precipitated. Naltrexone was more potent than 6β-naltrexol at all the time points. The ED(50) of both drugs decreased at the same rate suggesting that increased dependence produced no change in constitutive opioid receptor activity. Taken together these results indicate that the functional efficacy of 6β-naltrexol is dose-dependent and that constitutive opioid receptor activity did not change as opioid dependence increased from 1 to 6 days.

  1. CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway.

    PubMed

    Cathomas, Flurin; Fuertig, Rene; Sigrist, Hannes; Newman, Gregory N; Hoop, Vanessa; Bizzozzero, Manuela; Mueller, Andreas; Luippold, Andreas; Ceci, Angelo; Hengerer, Bastian; Seifritz, Erich; Fontana, Adriano; Pryce, Christopher R

    2015-11-01

    The similarity between sickness behavior syndrome (SBS) in infection and autoimmune disorders and certain symptoms in major depressive disorder (MDD), and the high co-morbidity of autoimmune disorders and MDD, constitutes some of the major evidence for the immune-inflammation hypothesis of MDD. CD40 ligand-CD40 immune-activation is important in host response to infection and in development of autoimmunity. Mice given a single intra-peritoneal injection of CD40 agonist antibody (CD40AB) develop SBS for 2-3days characterized by weight loss and increased sleep, effects that are dependent on the cytokine, tumor necrosis factor (TNF). Here we report that CD40AB also induces behavioral effects that extend beyond acute SBS and co-occur with but are not mediated by kynurenine pathway activation and recovery. CD40AB led to decreased saccharin drinking (days 1-7) and decreased Pavlovian fear conditioning (days 5-6), and was without effect on physical fatigue (day 5). These behavioral effects co-occurred with increased plasma and brain levels of kynurenine and its metabolites (days 1-7/8). Co-injection of TNF blocker etanercept with CD40AB prevented each of SBS, reduced saccharin drinking, and kynurenine pathway activation in plasma and brain. Repeated oral administration of a selective indoleamine 2,3-dioxygenase (IDO) inhibitor blocked activation of the kynurenine pathway but was without effect on SBS and saccharin drinking. This study provides novel evidence that CD40-TNF activation induces deficits in saccharin drinking and Pavlovian fear learning and activates the kynurenine pathway, and that CD40-TNF activation of the kynurenine pathway is not necessary for induction of the acute or extended SBS effects.

  2. 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. PMID:22643833

  3. Solid-state 29Si MAS NMR studies of diatoms: structural characterization of biosilica deposits.

    PubMed

    Bertermann, R; Kröger, N; Tacke, R

    2003-03-01

    Four different diatom species (Chaetoceros debilis, Chaetoceros didymum, Cylindrotheca fusiformis, Nitzschia angularis) were studied by solid-state (29)Si MAS NMR spectroscopy. To determine the Q(2):Q(3):Q(4) ratios in the biosilica deposits of the diatoms, quantitative (29)Si MAS NMR experiments were performed. This analysis did not reveal any differences regarding the molecular architecture of the silica (i.e. the degree of condensation of the SiOH units (2 identical with SiOH --> identical with Si-O-Si identical with + H(2)O)) from the different diatom species. However, complete cells showed significantly smaller Q(4):Q(3) ratios (1.8-1.9) than extracted cell walls (2.5-2.8), indicating the existence of intracellular pools of less condensed silica.

  4. 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.

  5. 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.

  6. Cornelian cherry (cornus MAS L.) juices as a source of minerals in human diet.

    PubMed

    Krośniak, M; Gastoł, M; Szałkowski, M; Zagrodzki, P; Derwisz, M

    2010-01-01

    The aim of this study was to determine the mineral content of Cornelian cherry (Cornus mas L.), as this fruit and its preservatives may be considered as important nutritional supplements. Potassium (K), calcium (Ca), sodium (Na), iron (Fe), zinc (Zn), manganese (Mn), and copper (Cu) were present in Cornelian cherry juice as measured by atomic absorption. Compared to other juices obtained from plum, pear, and apple, Cornelian cherry juice contained high levels of Ca, reaching 10-fold higher (323 mg/L) levels than other juices (14-77 mg/L). With respect to the remaining elements, K, Na, Fe, Zn, and Mn, the levels noted for Cornus mas juice were also higher than in other juices studied. The reverse was true for Cu, for which levels were lower. Data indicate that Cornelian cherry juices are rich in various essential elements and might be considered as an important dietary mineral supplementation for individuals deficient in nutritional elements. PMID:20706938

  7. OptiMAS: a decision support tool to conduct marker-assisted selection programs.

    PubMed

    Valente, Fabio; Gauthier, Franck; Bardol, Nicolas; Blanc, Guylaine; Joets, Johann; Charcosset, Alain; Moreau, Laurence

    2014-01-01

    Ongoing major advances in plant genotyping and phenotyping lead to a better understanding of genetic architecture of agronomical traits. In this context, it is important to develop decision support tools to help breeders in implementing marker-assisted selection (MAS) projects to assemble new allele combinations. Algorithms have been developed within an interactive graphical interface to (a) trace parental QTL alleles throughout selection generations, (b) propose strategies to select the best plants based on estimated molecular scores, and (c) efficiently intermate them depending on the expected value of their progenies. By investigating multi-allelic context and diverse pedigree structure, OptiMAS enables to assemble favorable alleles issued from diverse parents and further accelerate genetic gain.

  8. The angiotensin-converting enzyme 2/angiotensin (1-7)/Mas axis protects the function of pancreatic β cells by improving the function of islet microvascular endothelial cells.

    PubMed

    Lu, Chun-Li; Wang, Ying; Yuan, Li; Li, Yang; Li, Xiao-Ya

    2014-11-01

    In the diabetic state, the local rennin-angiotensin system (RAS) is activated in the pancreas, and is strongly associated with islet dysfunction. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis is a protective, negative regulator of the classical renin-angiotensin system. In this study, we assessed the role of the ACE2/Ang(1‑7)/Mas axis in pancreatic β cell survival and function. ACE2 knockout and wild-type mice were fed a high-fat diet for 16 weeks. We then performed terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and determined the expression levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in the pancreatic islets. The effects of Ang(1-7) or Mas receptor silencing on endothelial function were assessed in MS-1 cells. MIN6 cells were then co-cultured with the MS-1 cells to evaluate the effects of ACE2 on insulin secretion. The ACE2 knockout mice were more susceptible than the wild-type mice to high-fat diet-induced β cell dysfunction. The TUNEL-positive area of the pancreatic islets and the expression levels of IL-1β and iNOS were markedly increased in the ACE2 knockout mice compared with their wild-type littermates. The Mas-silenced MS-1 cells were more sensitive to palmitate-induced dysfunction and apoptosis in vitro. Ang(1-7) increased the activity of the Akt/endothelial NOS/nitric oxide (NO) pathway in the MS-1 cells, protected MIN6 cells against palmitate-induced apoptosis, and improved MIN6 insulin secretory function in the co-culture system. In conclusion, this study demonstrates that the ACE2/Ang(1-7)/Mas axis is a potential target for protecting the funcion of β cells by improving the function of islet microvascular endothelial cells. PMID:25175177

  9. The multiple autoimmune syndromes. A clue for the autoimmune tautology.

    PubMed

    Anaya, Juan-Manuel; Castiblanco, John; Rojas-Villarraga, Adriana; Pineda-Tamayo, Ricardo; Levy, Roger A; Gómez-Puerta, José; Dias, Carlos; Mantilla, Ruben D; Gallo, Juan Esteban; Cervera, Ricard; Shoenfeld, Yehuda; Arcos-Burgos, Mauricio

    2012-12-01

    The multiple autoimmune syndromes (MAS) consist on the presence of three or more well-defined autoimmune diseases (ADs) in a single patient. The aim of this study was to analyze the clinical and genetic characteristics of a large series of patients with MAS. A cluster analysis and familial aggregation analysis of ADs was performed in 84 patients. A genome-wide microsatellite screen was performed in MAS families, and associated loci were investigated through the pedigree disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered. Three main clusters were established. Aggregation for type 1 diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with MAS were observed harboring autoimmunity genes. The MAS represent the best example of polyautoimmunity as well as the effect of a single genotype on diverse phenotypes. Its study provides important clues to elucidate the common mechanisms of ADs (i.e., autoimmune tautology).

  10. 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. PMID:26971503

  11. 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.

  12. Investigation of multiaxial molecular dynamics by 2H MAS NMR spectroscopy.

    PubMed

    Kristensen, J H; Hoatson, G L; Vold, R L

    1998-11-01

    The technique of 2H MAS NMR spectroscopy is presented for the investigation of multiaxial molecular dynamics. To evaluate the effects of discrete random reorientation a Lie algebraic formalism based on the stochastic Liouville-von Neumann equation is developed. The solution to the stochastic Liouville-von Neumann equation is obtained both in the presence and absence of rf irradiation. This allows effects of molecular dynamics to be evaluated during rf pulses and extends the applicability of the formalism to arbitrary multiple pulse experiments. Theoretical methods are presented for the description of multiaxial dynamics with particular emphasis on the application of vector parameters to represent molecular rotations. Numerical time and powder integration algorithms are presented that are both efficient and easy to implement computationally. The applicability of 2H MAS NMR spectroscopy for investigating molecular dynamics is evaluated from theoretical spectra. To demonstrate the potential of the technique the dynamics of thiourea-2H4 is investigated experimentally. From a series of variable temperature MAS and quadrupole echo spectra it has been found that the dynamics can be described by composite rotation about the CS and CN bonds. Both experiments are sensitive to the fast CS rotation which is shown to be described by the Arrhenius parameters E(CS) = 46.4 +/- 2.3 kJ mol(-1) and ln(A(CS))= 32.6 +/- 0.9. The MAS experiment represents a significant improvement by simultaneously allowing the dynamics of the slow CN rotation to be fully characterized in terms of E(CN) = 56.3 +/- 3.4 kJ mol(-1) and ln(A(CN)) = 25.3 +/- 1.1. PMID:9875600

  13. Elucidating proline dynamics in spider dragline silk fibre using 2H-13C HETCOR MAS NMR.

    PubMed

    Shi, Xiangyan; Yarger, Jeffery L; Holland, Gregory P

    2014-05-14

    (2)H-(13)C HETCOR MAS NMR is performed on (2)H/(13)C/(15)N-Pro enriched A. aurantia dragline silk. Proline dynamics are extracted from (2)H NMR line shapes and T1 in a site-specific manner to elucidate the backbone and side chain molecular dynamics for the MaSp2 GPGXX β-turn regions for spider dragline silk in the dry and wet, supercontracted states.

  14. 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.

  15. 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.

  16. 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

  17. 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. PMID:24018849

  18. 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

  19. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    PubMed

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS. PMID:16789626

  20. [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). PMID:27228700

  1. 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

  2. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? Some children with Brown syndrome have poor binocular ... In the congenital form of Brown syndrome, the eye movement problem is usually constant and unlikely to resolve ...

  3. Dravet Syndrome

    MedlinePlus

    ... NINDS Dravet Syndrome Information Page Synonym(s): Severe Myoclonic Epilepsy of Infancy (SMEI) Table of Contents (click to ... Dravet Syndrome? Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), is a severe form of ...

  4. Fahr's Syndrome

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Fahr's Syndrome Information Page Synonym(s): Familial Idiopathic Basal Ganglia ... is being done? Clinical Trials Organizations What is Fahr's Syndrome? Fahr's Syndrome is a rare, genetically dominant, ...

  5. Cushing syndrome

    MedlinePlus

    Hypercortisolism; Cortisol excess ... The most common cause of Cushing syndrome is taking too much glucocorticosteroid medicine. This form of Cushing syndrome is called exogenous Cushing syndrome . Prednisone, dexamethasone, and prednisolone are ...

  6. Williams syndrome

    MedlinePlus

    Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. Parents may not have any family history of the condition. However, people with Williams syndrome have a 50% chance of passing the ...

  7. 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.

  8. Proteolytic activation cascade of the Netherton syndrome-defective protein, LEKTI, in the epidermis: implications for skin homeostasis.

    PubMed

    Fortugno, Paola; Bresciani, Alberto; Paolini, Chantal; Pazzagli, Chiara; El Hachem, May; D'Alessio, Marina; Zambruno, Giovanna

    2011-11-01

    Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is the defective protein of the ichthyosiform condition Netherton syndrome (NS). Strongly expressed in the most differentiated epidermal layers, LEKTI is a serine protease inhibitor synthesized as three different high-molecular-weight precursors, which are rapidly processed into shorter fragments and secreted extracellularly. LEKTI polypeptides interact with several proteases to regulate skin barrier homeostasis as well as inflammatory and/or immunoallergic responses. Here, by combining antibody mapping, N-terminal sequencing, and site-specific mutagenesis, we defined the amino-acid sequence of most of the LEKTI polypeptides physiologically generated in human epidermis. We also identified three processing intermediates not described so far. Hence, a proteolytic cascade model for LEKTI activation is proposed. We then pinpointed the most effective fragments against the desquamation-related kallikreins (KLKs) and we proved that LEKTI is involved in stratum corneum shedding as some of its polypeptides inhibit the KLK-mediated proteolysis of desmoglein-1. Finally, we quantified the individual LEKTI fragments in the uppermost epidermis, showing that the ratios between LEKTI polypeptides and active KLK5 are compatible with a fine-tuned inhibition. These findings are relevant both to the understanding of skin homeostasis regulation and to the design of novel therapeutic strategies for NS.

  9. Neutrophils from patients with myelodysplastic syndromes: relationship between impairment of granular contents, complement receptors, functional activities and disease status.

    PubMed

    Moretti, S; Lanza, F; Spisani, S; Latorraca, A; Rigolin, G M; Giuliani, A L; Castoldi, G L; Traniello, S

    1994-05-01

    Myelodysplastic syndromes (MDS) are stem cell disorders of clonal origin in which infections and leukemic transformation are quite frequent. Neutrophils from 28 patients with MDS were analysed by flow cytometry for the expression of the two complement receptors CR1 and CR3, the antigenic reactivity of some granule constituents--myeloperoxidase, lysozyme, elastase, lactoferrin--and functional activities, such as locomotion, respiratory burst and cytotoxicity. The results were correlated with the FAB disease subtypes, grouped as low risk (RA) and high risk patients (RAEB, RAEB-t, CMML) and with 30 healthy subjects. A significant reduction in the percentage of neutrophil CR1, CR3 positivity and chemotaxis induced by endotoxin-activated serum was detected in the high risk group when compared with the low risk group and healthy controls. Furthermore, the high risk group also showed a low amount of myeloperoxidase, elastase, lysozyme and superoxide anion, but both low and high risk groups displayed reduced cellular cytotoxicity in comparison with the control. This work indicates that MDS patients belonging to the more advanced FAB categories frequently show multiple abnormalities in the expression of neutrophil complement receptors, and granular components (> 3), as well as in cell functions, suggesting the possibility of using these phenotypic abnormalities in the monitoring of disease progression. PMID:8069192

  10. Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome.

    PubMed

    Le Goff, Carine; Rogers, Curtis; Le Goff, Wilfried; Pinto, Graziella; Bonnet, Damien; Chrabieh, Maya; Alibeu, Olivier; Nistchke, Patrick; Munnich, Arnold; Picard, Capucine; Cormier-Daire, Valérie

    2016-08-01

    Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. Whole-exome sequencing identified heterozygous MAP3K7 mutations in six distinct CSCF-affected individuals from four families and ranging in age from 5 to 37 years. MAP3K7 encodes transforming growth factor β (TGF-β)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway. MAPK-p38 signaling was markedly altered when expression of non-canonical TGF-β-driven target genes was impaired. These findings support the loss of transcriptional control of the TGF-β-MAPK-p38 pathway in fibroblasts obtained from affected individuals. Surprisingly, although TAK1 is located at the crossroad of inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder affecting mainly cartilage, bone, and heart. PMID:27426734

  11. 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

  12. Phase cycling schemes for finite-pulse-RFDR MAS solid state NMR experiments.

    PubMed

    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, XY4(1)4, for the fp-RFDR pulse sequence employed in 2D (1)H/(1)H 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, XY4(1)2, XY4(1)3, XY4(1)4, and XY8(1)4 phase cycles under different spinning speeds ranging from 10 to 100 kHz. The theoretical calculations reveal the presence of second-order terms (T(10)T(2,±2), T(1,±1)T(2,±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 XY4(1)4 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

  13. Light optical precision measurements of the active and inactive Prader-Willi syndrome imprinted regions in human cell nuclei.

    PubMed

    Rauch, Joachim; Knoch, Tobias A; Solovei, Irina; Teller, Kathrin; Stein, Stefan; Buiting, Karin; Horsthemke, Bernhard; Langowski, Jörg; Cremer, Thomas; Hausmann, Michael; Cremer, Christoph

    2008-01-01

    Despite the major advancements during the last decade with respect to both knowledge of higher order chromatin organization in the cell nucleus and the elucidation of epigenetic mechanisms of gene control, the true three-dimensional (3D) chromatin structure of endogenous active and inactive gene loci is not known. The present study was initiated as an attempt to close this gap. As a model case, we compared the chromatin architecture between the genetically active and inactive domains of the imprinted Prader-Willi syndrome (PWS) locus in human fibroblast and lymphoblastoid cell nuclei by 3D fluorescence in situ hybridization and quantitative confocal laser scanning microscopy. The volumes and 3D compactions of identified maternal and paternal PWS domains were determined in stacks of light optical serial sections using a novel threshold-independent approach. Our failure to detect volume and compaction differences indicates that possible differences are below the limits of light optical resolution. To overcome this limitation, spectral precision distance microscopy, a method of localization microscopy at the nanometer scale, was used to measure 3D distances between differentially labeled probes located both within the PWS region and in its neighborhood. This approach allows the detection of intranuclear differences between 3D distances down to about 70-90 nm, but again did not reveal clearly detectable differences between active and inactive PWS domains. Despite this failure, a comparison of the experimental 3D distance measurements with computer simulations of chromatin folding strongly supports a non-random higher order chromatin configuration of the PWS locus and argues against 3D configurations based on giant chromatin loops. Our results indicate that the search for differences between endogenous active and inactive PWS domains must be continued at still smaller scales than hitherto possible with conventional light microscopic procedures. The possibilities to

  14. A failure of TNFAIP3 negative regulation maintains sustained NF-κB activation in Sjögren's syndrome.

    PubMed

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario Domenico; Ingravallo, Giuseppe; Maiorano, Eugenio; D'Amore, Massimo

    2011-06-01

    Sjögren's syndrome (SS) is characterized by the features of systemic autoimmunity and exocrine gland dysfunction and inflammation. Deregulated cytokine production is known to contribute to the etiology of SS but the underlying molecular mechanism is still remains to be unclear. TNF-α-induced protein 3 or TNFAIP3 is involved in the negative feedback regulation of nuclear factor-κB (NF-κB) signaling in response to specific pro-inflammatory stimuli in different cell types. To define the contribution of TNFAIP3 to SS, the levels of TNFAIP3 expression in human salivary gland epithelial cells (SGEC) derived from active primary SS patients were analyzed. Histological analysis was performed on paraffin-embedded human Sjögren's samples and healthy tissues. In separate experiments, immunofluorescence staining, western blot analysis and quantitative real-time PCR for TNFAIP3 was conducted in SGEC from SS and healthy subjects. Our findings clearly demonstrate changes in levels of the protein and gene expression between healthy controls and SS patients, depicting a very weak positivity for TNFAIP3 in SS samples. TNFAIP3 was found down-regulated in SGECs derived from SS patients in comparison with controls, and the cells with down-regulated TNFAIP3 expression exhibited enhanced NF-κB activities. In addition, to investigate the role of TNFAIP3 in the activation of NF-κB, we depleted TNFAIP3 expression by siRNA in healthy SGEC after treatment with or without TNF-α. Intriguingly, the silencing of TNFAIP3 by its siRNA in healthy SGEC increased NF-κB activation that could explain the deregulated cytokines production observed in SS.

  15. 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

  16. Beneficial effect of brewers' yeast extract on daily activity in a murine model of chronic fatigue syndrome.

    PubMed

    Takahashi, Takashi; Yu, Fei; Zhu, Shi-Jie; Moriya, Junji; Sumino, Hiroyuki; Morimoto, Shigeto; Yamaguchi, Nobuo; Kanda, Tsugiyasu

    2006-03-01

    The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

  17. Protective Effect of Cornus mas Fruits Extract on Serum Biomarkers in CCl4-Induced Hepatotoxicity in Male Rats

    PubMed Central

    Alavian, Seyed Moayed; Banihabib, Nafiseh; Es. Haghi, Masoud; Panahi, Farid

    2014-01-01

    Background: Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties. Objectives: The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats. Materials and Methods: Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity. Results: Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content. Conclusions: Cornus mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders. PMID:24829584

  18. 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…

  19. 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

  20. Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

    PubMed

    Lackner, Jeffrey M; Lou Coad, Mary; Mertz, Howard R; Wack, David S; Katz, Leonard A; Krasner, Susan S; Firth, Rebecca; Mahl, Thomas C; Lockwood, Alan H

    2006-05-01

    This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.

  1. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation.

    PubMed

    Robertson, Stacy; Martínez, Gonzalo J; Payet, Cloe A; Barraclough, Jennifer Y; Celermajer, David S; Bursill, Christina; Patel, Sanjay

    2016-07-01

    Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β.

  2. The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

    PubMed

    Schwingshackl, Andreas

    2016-09-01

    Mechanical ventilation (MV) and oxygen therapy (hyperoxia; HO) comprise the cornerstones of life-saving interventions for patients with acute respiratory distress syndrome (ARDS). Unfortunately, the side effects of MV and HO include exacerbation of lung injury by barotrauma, volutrauma, and propagation of lung inflammation. Despite significant improvements in ventilator technologies and a heightened awareness of oxygen toxicity, besides low tidal volume ventilation few if any medical interventions have improved ARDS outcomes over the past two decades. We are lacking a comprehensive understanding of mechanotransduction processes in the healthy lung and know little about the interactions between simultaneously activated stretch-, HO-, and cytokine-induced signaling cascades in ARDS. Nevertheless, as we are unraveling these mechanisms we are gathering increasing evidence for the importance of stretch-activated ion channels (SACs) in the activation of lung-resident and inflammatory cells. In addition to the discovery of new SAC families in the lung, e.g., two-pore domain potassium channels, we are increasingly assigning mechanosensing properties to already known Na(+), Ca(2+), K(+), and Cl(-) channels. Better insights into the mechanotransduction mechanisms of SACs will improve our understanding of the pathways leading to ventilator-induced lung injury and lead to much needed novel therapeutic approaches against ARDS by specifically targeting SACs. This review 1) summarizes the reasons why the time has come to seriously consider SACs as new therapeutic targets against ARDS, 2) critically analyzes the physiological and experimental factors that currently limit our knowledge about SACs, and 3) outlines the most important questions future research studies need to address. PMID:27521425

  3. 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.

  4. 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…

  5. Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition.

    PubMed

    Soundararajan, Meera; Roos, Annette K; Savitsky, Pavel; Filippakopoulos, Panagis; Kettenbach, Arminja N; Olsen, Jesper V; Gerber, Scott A; Eswaran, Jeyanthy; Knapp, Stefan; Elkins, Jonathan M

    2013-06-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key roles in brain development, regulation of splicing, and apoptosis, and are potential drug targets for neurodegenerative diseases and cancer. We present crystal structures of one representative member of each DYRK subfamily: DYRK1A with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA and DH (DYRK homology) box regions. The current activation model suggests that DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the activation loop YxY motif during protein translation. The structures explain the roles of this tyrosine and of the DH box in DYRK activation and provide a structural model for DYRK substrate recognition. Phosphorylation of a library of naturally occurring peptides identified substrate motifs that lack proline in the P+1 position, suggesting that DYRK1A is not a strictly proline-directed kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity. PMID:23665168

  6. Structures of Down Syndrome Kinases, DYRKs, Reveal Mechanisms of Kinase Activation and Substrate Recognition

    PubMed Central

    Soundararajan, Meera; Roos, Annette K.; Savitsky, Pavel; Filippakopoulos, Panagis; Kettenbach, Arminja N.; Olsen, Jesper V.; Gerber, Scott A.; Eswaran, Jeyanthy; Knapp, Stefan; Elkins, Jonathan M.

    2013-01-01

    Summary Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key roles in brain development, regulation of splicing, and apoptosis, and are potential drug targets for neurodegenerative diseases and cancer. We present crystal structures of one representative member of each DYRK subfamily: DYRK1A with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA and DH (DYRK homology) box regions. The current activation model suggests that DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the activation loop YxY motif during protein translation. The structures explain the roles of this tyrosine and of the DH box in DYRK activation and provide a structural model for DYRK substrate recognition. Phosphorylation of a library of naturally occurring peptides identified substrate motifs that lack proline in the P+1 position, suggesting that DYRK1A is not a strictly proline-directed kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity. PMID:23665168

  7. Paraneoplastic syndromes

    SciTech Connect

    Weller, R.E.

    1986-10-01

    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. Various types of PNS, singly or in multiples, may be associated with either benign or malignant tumors and may involve almost every organ system, directly or indirectly. These disorders can precede the discovery of the tumor by weeks, months, or even years, and many are good diagnostic and prognostic indicators. The true incidence of PNS in animal cancer patients is unknown, although approximately 75% of all human cancer patients, at some time during the tumor-bearing part of their lives, suffer from one or more of these disorders. Recognition of PNS is valuable because the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor, because they may allow assessment of premalignant states, because they may aid in the search for metastases, because they may help quantify and monitor response to therapy, and because they may provide insight into the study of malignant transformations and oncogene expression. Recognition of these syndromes is relevant to the diagnosis and treatment of many problems in veterinary cancer medicine. 22 refs., 2 tabs.

  8. 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

  9. 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.

  10. Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene.

    PubMed

    Känsäkoski, Johanna; Jääskeläinen, Jarmo; Jääskeläinen, Tiina; Tommiska, Johanna; Saarinen, Lilli; Lehtonen, Rainer; Hautaniemi, Sampsa; Frilander, Mikko J; Palvimo, Jorma J; Toppari, Jorma; Raivio, Taneli

    2016-01-01

    Mutations in the X-linked androgen receptor (AR) gene underlie complete androgen insensitivity syndrome (CAIS), the most common cause of 46,XY sex reversal. Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who show normal coding region of AR. Here, we describe a novel mechanism of AR disruption leading to CAIS in two 46,XY sisters. We analyzed whole-genome sequencing data of the patients for pathogenic variants outside the AR coding region. Patient fibroblasts from the genital area were used for AR cDNA analysis and protein quantification. Analysis of the cDNA revealed aberrant splicing of the mRNA caused by a deep intronic mutation (c.2450-118A>G) in the intron 6 of AR. The mutation creates a de novo 5' splice site and a putative exonic splicing enhancer motif, which leads to the preferential formation of two aberrantly spliced mRNAs (predicted to include a premature stop codon). Patient fibroblasts contained no detectable AR protein. Our results show that patients with CAIS and normal AR coding region need to be examined for deep intronic mutations that can lead to pseudoexon activation. PMID:27609317

  11. Mothers and Fathers at Play with their Children with Down Syndrome: Influence on Child Exploratory and Symbolic Activity

    PubMed Central

    de Falco, Simona; Esposito, Gianluca; Venuti, Paola; Bornstein, Marc H.

    2012-01-01

    Background Through play children exercise their emerging mental abilities, and for their part, when in collaborative play, caregivers often adjust their behaviours to assist their children’s progress. In this study, we focused on comparisons between play of Down Syndrome (DS) children with their two parents as well as on comparisons between the two parents’ play behaviours. Method Altogether 40 parent–child dyads participated: 20 children with DS (M age = 36.14 months) with their mothers and separately with their fathers. We coded participants’ play behaviours during child solitary and mother–child and father–child collaborative sessions. Results Although children increased exploratory play from solitary to collaborative sessions with both parents, symbolic play increased only during joint play with fathers. Fathers displayed less symbolic and more exploratory activity compared to mothers. Mothers and fathers alike were attuned to their children, although fathers showed a higher degree of attunement. Conclusions This study shows that maternal and paternal contributions to DS child play skills are positive but different. During collaborative play children received specific and nonoverlapping scaffolding from their two parents, and fathers’ contributions were unique. PMID:23275758

  12. 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 corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder.

  13. The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26.

    PubMed

    Davoodi, Jamshid; Kelly, John; Gendron, Nathalie H; MacKenzie, Alex E

    2007-06-01

    Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition shown to be the result of deletions of the glypican-3 (GPC3) gene. GPC3 is a proteoglycan localized to the cell membrane via a glycosylphosphatidyl-inositol (GPI) anchor. To further elucidate the GPC3 function(s), we have screened various cell lines for proteins that interact with GPC3, resulting in the isolation of a 115 kDa protein, identified as CD26. The interaction occurred with both the glycosylated and unglycosylated forms of GPC3 and led to the inhibition of CD26 peptidase activity. Moreover, introduction of CD26 into Cos-1 cells was accompanied by the up-regulation of cell growth, while inclusion of recombinant GPC3 in the media reduced the growth of CD26 transfected Cos-1 cells, drastically. Furthermore, HepG2 C3A cells containing CD26 underwent apoptosis in the presence of recombinant GPC3 in both concentration and time-dependant manner. In light of the fact that inhibition of CD26 reduces the rate of cell proliferation, we propose that a number of physical findings observed in SGBS patients may be a consequence of a direct interaction of GPC3 with CD26. Furthermore, GPC3 without the GPI anchor is capable of inducing apoptosis indicating that neither the GPI anchor nor the membrane attachment is required for apoptosis induction.

  14. Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene

    PubMed Central

    Känsäkoski, Johanna; Jääskeläinen, Jarmo; Jääskeläinen, Tiina; Tommiska, Johanna; Saarinen, Lilli; Lehtonen, Rainer; Hautaniemi, Sampsa; Frilander, Mikko J.; Palvimo, Jorma J.; Toppari, Jorma; Raivio, Taneli

    2016-01-01

    Mutations in the X-linked androgen receptor (AR) gene underlie complete androgen insensitivity syndrome (CAIS), the most common cause of 46,XY sex reversal. Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who show normal coding region of AR. Here, we describe a novel mechanism of AR disruption leading to CAIS in two 46,XY sisters. We analyzed whole-genome sequencing data of the patients for pathogenic variants outside the AR coding region. Patient fibroblasts from the genital area were used for AR cDNA analysis and protein quantification. Analysis of the cDNA revealed aberrant splicing of the mRNA caused by a deep intronic mutation (c.2450-118A>G) in the intron 6 of AR. The mutation creates a de novo 5′ splice site and a putative exonic splicing enhancer motif, which leads to the preferential formation of two aberrantly spliced mRNAs (predicted to include a premature stop codon). Patient fibroblasts contained no detectable AR protein. Our results show that patients with CAIS and normal AR coding region need to be examined for deep intronic mutations that can lead to pseudoexon activation. PMID:27609317

  15. Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation*

    PubMed Central

    Lee, Eun Hye; Kim, Seon Sook; Lee, Seul; Baek, Kwan-Hyuck; Seo, Su Ryeon

    2015-01-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous functions, including development, differentiation, and survival, and various aspects of learning and memory. Here we report that PACAP induces the expression of regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome patients. Increased RCAN1 expression is accompanied by activation of the PKA-cAMP response element-binding protein pathways. EMSA and ChIP analyses demonstrate the presence of a functional cAMP response element in the RCAN1 promoter. Moreover, we show that PACAP-dependent neuronal differentiation is significantly disturbed by improper RCAN1 expression. Our data provide the first evidence of RCAN1, a Down syndrome-related gene, as a novel target for control of the neurotrophic function of PACAP. PMID:26157140

  16. The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome.

    PubMed

    Chuansumrit, Ampaiwan; Tangnararatchakit, Kanchana; Lektakul, Yujinda; Pongthanapisith, Viroj; Nimjaroenniyom, Nuntaporn; Thanarattanakorn, Pattra; Wongchanchailert, Malai; Komwilaisak, Patcharee

    2004-06-01

    To report the use of recombinant activated factor VII (rFVIIa) in controlling life-threatening bleeding episodes in patients with grades III and IV Dengue Hemorrhagic Fever (DHF), also known as Dengue Shock Syndrome. Fifteen patients (seven boys, eight girls), whose median age was 8 years, were enrolled in the study. They were divided into two groups. Group 1 included nine patients, mainly grade III, waiting for platelet concentrate, and group 2 included six patients, mainly grade IV, who had already received platelet concentrate with unresponsiveness. A single dose or repeated doses of 100 microg/kg rFVIIa was/were given at intervals of 4 h according to the bleeding symptoms. The median times from the onset of bleeding to rFVIIa initiation were 6.5 and 29.8 h in groups 1 and 2, respectively. Each patient received one to three doses. An effective response was found in eight patients (53.3%), including six patients in group 1 and two patients in group 2. They had complete cessation of bleeding without recurrence for 48 h. An ineffective response was found in seven patients (46.7%) including three patients in group 1 and four patients in group 2 for which the bleeding recurred (n = 2), temporarily slowed down (n = 3), continued (n = 1) or occurred at a new site (n = 1). These included three patients in profound shock 24-48 h before referral to comprehensive treatment centers, two patients receiving ibuprofen before hospitalization, one patient with extensive volume overloading, and one patient requiring surgical intervention to ligate the torn intercostal artery and vein. The platelet concentrate was promptly transfused to stop bleeding in patients with ineffective responses. The results revealed that the earlier initiation of rFVIIa in the mainly grade III DHF in group 1 yielded a higher effective response (66.7%) than the delayed initiation in the mainly grade IV DHF in group 2 (33.3%). Moreover, patients previously receiving ibuprofen or volume expander of low

  17. Chronic Fatigue Syndrome

    MedlinePlus

    Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that ... activities. The main symptom of CFS is severe fatigue that lasts for 6 months or more. You ...

  18. 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

  19. TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch.

    PubMed

    Wilson, Sarah R; Gerhold, Kristin A; Bifolck-Fisher, Amber; Liu, Qin; Patel, Kush N; Dong, Xinzhong; Bautista, Diana M

    2011-05-01

    Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. In many cases, pathological itch is insensitive to antihistamine treatment. Recent studies have identified members of the Mas-related G protein-coupled receptor (Mrgpr) family that are activated by mast cell mediators and promote histamine-independent itch. MrgprA3 and MrgprC11 act as receptors for the pruritogens chloroquine and BAM8-22, respectively. However, the signaling pathways and transduction channels activated downstream of these pruritogens are largely unknown. We found that TRPA1 is the downstream target of both MrgprA3 and MrgprC11 in cultured sensory neurons and heterologous cells. TRPA1 is required for Mrgpr-mediated signaling, as sensory neurons from TRPA1-deficient mice exhibited markedly diminished responses to chloroquine and BAM8-22. Similarly, TRPA1-deficient mice displayed little to no scratching in response to these pruritogens. Our findings indicate that TRPA1 is an essential component of the signaling pathways that promote histamine-independent itch.

  20. 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

  1. Muscle attachment site (MAS) patterns for species determination in five species of Sarcophaga (Diptera: Sarcophagidae).

    PubMed

    Niederegger, Senta; Szpila, Krzysztof; Mall, Gita

    2016-01-01

    To further establish species determination using the muscle attachment site (MAS) pattern method, third instar larvae of five forensically important species of Sarcophaga Meigen were investigated: Sarcophaga argyrostoma (Robineau-Desvoidy), Sarcophaga caerulescens Zetterstedt, Sarcophaga melanura Meigen, Sarcophaga albiceps Meigen and Sarcophaga similis Meade. As in the previously investigated Calliphoridae, patterns were found to be species specific. The main feature of the Sarcophaga patterns is the divided central horizontal row of segment four. A genus pattern was established to be used as base for comparison in further species determination. PMID:26391172

  2. MAS Equipped with Ant Colony Applied into Dynamic Job Shop Scheduling

    NASA Astrophysics Data System (ADS)

    Kang, Kai; Zhang, Ren Feng; Yang, Yan Qing

    This paper presents a methodology adopting the new structure of MAS(multi-agent system) equipped with ACO(ant colony optimization) algorithm for a better schedule in dynamic job shop. In consideration of the dynamic events in the job shop arriving indefinitely schedules are generated based on tasks with ant colony algorithm. Meanwhile, the global objective is taken into account for the best solution in the actual manufacturing environment. The methodology is tested on a simulated job shop to determine the impact with the new structure.

  3. Muscle attachment site (MAS) patterns for species determination in five species of Sarcophaga (Diptera: Sarcophagidae).

    PubMed

    Niederegger, Senta; Szpila, Krzysztof; Mall, Gita

    2016-01-01

    To further establish species determination using the muscle attachment site (MAS) pattern method, third instar larvae of five forensically important species of Sarcophaga Meigen were investigated: Sarcophaga argyrostoma (Robineau-Desvoidy), Sarcophaga caerulescens Zetterstedt, Sarcophaga melanura Meigen, Sarcophaga albiceps Meigen and Sarcophaga similis Meade. As in the previously investigated Calliphoridae, patterns were found to be species specific. The main feature of the Sarcophaga patterns is the divided central horizontal row of segment four. A genus pattern was established to be used as base for comparison in further species determination.

  4. MAS: Malware Analysis System Based on Hardware-Assisted Virtualization Technology

    NASA Astrophysics Data System (ADS)

    Kim, Taehyoung; Kim, Inhyuk; Min, Changwoo; Eom, Young Ik

    There are many analysis techniques in order to analyze malicious codes. However, recently malicious codes often evade detection using stealthy obfuscation techniques, and attack computing systems. We propose an enhanced dynamic binary instrumentation using hardware-assisted virtualization technology. As a machine-level analyzer, our system can be isolated from almost the whole threats of malware, and provides single step analysis environment. Proposed system also supports rapid system call analysis environment. We implement our malware analysis system (referred as MAS) on the KVM hypervisor with Intel VT-x virtualization support. Our experiments with benchmarks show that the proposed system provides efficient analysis environment with low overhead.

  5. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy.

    PubMed

    Chong, Jessica X; Caputo, Viviana; Phelps, Ian G; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T; Ishak, Gisele E; Ardern-Holmes, Simone; Richmond, Zara; Bamshad, Michael J; Ortiz-Gonzalez, Xilma R; Tartaglia, Marco; Chopra, Maya; Doherty, Dan

    2016-04-01

    Infantile encephalopathies are a group of clinically and biologically heterogeneous disorders for which the genetic basis remains largely unknown. Here, we report a syndromic neonatal encephalopathy characterized by profound developmental disability, severe hypotonia, seizures, diminished respiratory drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently identified by whole-exome sequencing as the cause of this condition in four unrelated families. Matching these families was facilitated by the sharing of phenotypic profiles and WES data in a recently released web-based tool (Geno2MP) that links phenotypic information to rare variants in families with Mendelian traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of the Rab family and has been shown to control cell growth and proliferation, actin-cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T [p.Arg126(∗)] and c.1363A>T [p.Lys455(∗)]) are predicted to truncate the protein, and loss of the major TBCK isoform was confirmed in primary fibroblasts from one affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a conserved residue within the TBC1 domain. Structural analysis implicated Arg511 as a required residue for Rab-GAP function, and in silico homology modeling predicted impaired GAP function in the corresponding mutant. These results suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In contrast to other disorders caused by dysregulated mTOR signaling associated with focal or global brain overgrowth, impaired TBCK function results in progressive loss of brain volume. PMID:27040692

  6. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy

    PubMed Central

    Chong, Jessica X.; Caputo, Viviana; Phelps, Ian G.; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C.; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T.; Ishak, Gisele E.; Ardern-Holmes, Simone; Richmond, Zara; Bamshad, Michael J.; Ortiz-Gonzalez, Xilma R.; Tartaglia, Marco; Chopra, Maya; Doherty, Dan

    2016-01-01

    Infantile encephalopathies are a group of clinically and biologically heterogeneous disorders for which the genetic basis remains largely unknown. Here, we report a syndromic neonatal encephalopathy characterized by profound developmental disability, severe hypotonia, seizures, diminished respiratory drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently identified by whole-exome sequencing as the cause of this condition in four unrelated families. Matching these families was facilitated by the sharing of phenotypic profiles and WES data in a recently released web-based tool (Geno2MP) that links phenotypic information to rare variants in families with Mendelian traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of the Rab family and has been shown to control cell growth and proliferation, actin-cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T [p.Arg126∗] and c.1363A>T [p.Lys455∗]) are predicted to truncate the protein, and loss of the major TBCK isoform was confirmed in primary fibroblasts from one affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a conserved residue within the TBC1 domain. Structural analysis implicated Arg511 as a required residue for Rab-GAP function, and in silico homology modeling predicted impaired GAP function in the corresponding mutant. These results suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In contrast to other disorders caused by dysregulated mTOR signaling associated with focal or global brain overgrowth, impaired TBCK function results in progressive loss of brain volume. PMID:27040692

  7. Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome?

    PubMed Central

    Zea, Arnold H.; Stewart, Tyrus; Ascani, Jeannine; Tate, David J.; Finkel-Jimenez, Beatriz; Wilk, Anna; Reiss, Krzysztof; Smoyer, William E.; Aviles, Diego H.

    2016-01-01

    The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS) have increased IL-2 production. We hypothesized that podocytes express an IL-2 receptor (IL-2R) and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were stimulated with IL-2 in vitro, to study signaling events via the JAK/STAT pathway. The results showed that stimulation with IL-2 resulted in increased mRNA and protein expression of STAT 5a, phosphorylated STAT 5, JAK 3, and phosphorylated JAK 3. We then investigated for signs of cellular injury and the data showed that pro-apoptotic markers Bax and cFLIP were significantly increased following IL-2 exposure, whereas LC3 II was decreased. Furthermore, mitochondrial depolarization and apoptosis were both significantly increased following activation of the IL-2R. We used a paracellular permeability assay to monitor the structural integrity of a podocyte monolayer following IL-2 exposure. The results showed that podocytes exposed to IL-2 have increased albumin leakage across the monolayer. We conclude that murine podocytes express the IL-2R, and that activation through the IL-2R results in podocyte injury. PMID:27389192

  8. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy.

    PubMed

    Chong, Jessica X; Caputo, Viviana; Phelps, Ian G; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T; Ishak, Gisele E; Ardern-Holmes, Simone; Richmo