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Sample records for subtype mediated physiologies

  1. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

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    Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

    2006-06-01

    The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

  2. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

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    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  3. Physiological blushing in social anxiety disorder patients with and without blushing complaints: Two subtypes?

    NARCIS (Netherlands)

    Voncken, M.J.; Bogels, S.M.

    2009-01-01

    This study investigates whether social anxiety disorder (SAD) patients with blushing complaints show heightened physiological blushing and arousability in social situations than SAD patients without blushing complaints and healthy controls. SAD blushers (n = 32), SAD non-blushers (n = 34), and

  4. The analgesic effect of clonixine is not mediated by 5-HT3 subtype receptors.

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    Paeile, C; Bustamante, S E; Sierralta, F; Bustamante, D; Miranda, H F

    1995-10-01

    1. The analgesic effect of clonixinate of L-lysine (Clx) in the nociceptive C-fiber reflex in rat and in the writhing test in mice is reported. 2. Clx was administered by three routes, i.v., i.t. and i.c.v., inducing a dose-dependent antinociception. 3. The antinociceptive effect of Clx was 40-45% with respect to the control integration values in the nociceptive C-fiber reflex method. 4. The writhing test yielded ED50 values (mg/kg) of 12.0 +/- 1.3 (i.p.), 1.8 +/- 0.2 (i.t.) and 0.9 +/- 0.1 (i.c.v.) for Clx administration. 5. Ondansetron was not able to antagonize the antinociception response of Clx in the algesiometric tests used. 6. Chlorophenilbiguanide did not produce any significative change in the analgesic effect of Clx in the nociceptive C-fiber reflex method. 7. It is suggested that the mechanism of action of the central analgesia of Clx is not mediated by 5-HT3 subtype receptors.

  5. HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

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    Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

    2018-03-01

    HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

  6. Effects of LHRH and ANG II on prolactin stimulation are mediated by hypophysial AT1 receptor subtype.

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    Becú-Villalobos, D; Lacau-Mengido, I M; Thyssen, S M; Díaz-Torga, G S; Libertun, C

    1994-02-01

    We have used the nonpeptide angiotensin II (ANG II) receptor antagonists losartan (receptor subtype AT1) and PD-123319 (AT2) to determine the participation of ANG II receptor subtypes in luteinizing hormone-releasing hormone (LHRH)-induced prolactin release in a perifusion study using intact pituitaries in vitro. LHRH (1.85 x 10(-7) M) released prolactin consistently, whereas losartan (10(-5) M) abolished prolactin response without modifying basal prolactin or luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. PD-123319 (10(-5) M) had no effect on basal or LHRH-induced prolactin, LH, or FSH release. We also determined that the effect of ANG II on prolactin release was mediated by the same receptor subtype. In adenohypophysial cells dispersed in vitro ANG II (10(-8) M) released prolactin. Losartan (10(-7) and 10(-6) M), but not PD-123319, inhibited this effect. We conclude that in intact hypophyses of 15-day-old female rats the effect of LHRH on prolactin release is readily demonstrated. LHRH-induced prolactin release appears to be mediated by ANG II acting in a paracrine manner on AT1 receptors located on lactotrophs.

  7. The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients.

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    Gall, Lewis S; Vulliamy, Paul; Gillespie, Scarlett; Jones, Timothy F; Pierre, Rochelle S J; Breukers, Sabine E; Gaarder, Christine; Juffermans, Nicole P; Maegele, Marc; Stensballe, Jakob; Johansson, Pär I; Davenport, Ross A; Brohi, Karim

    2018-03-19

    To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell

  8. The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients

    DEFF Research Database (Denmark)

    Gall, Lewis S; Vulliamy, Paul; Gillespie, Scarlett

    2018-01-01

    OBJECTIVE: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group...

  9. Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.

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    Owaki, Hiroyuki; Sadahiro, Sotaro; Takaki, Miyako

    2015-04-01

    Human internal anal sphincter (IAS) is contracted by α1-adrenoceptor stimulation and thus α1-adrenoceptor agonists may be useful in treating fecal incontinence. This study characterizes the contribution of α1-adrenoceptor subtypes in contraction of human IAS and to investigate the age-related risk of patients with fecal incontinence. IAS and inferior mesenteric artery (IMA), as a predictor of systemic arterial pressure, were obtained from 11 patients. Both muscle strips were assessed by isometric-contraction experiments using phenylephrine, further in IAS, in the presence of various subtype selective α1-adrenoceptor antagonists. Immunohistochemistry and gene expression studies were performed in the same samples. The mean pEC50 values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC50 change of IAS was observed between age IAS, rightward shift of the concentration-response curves of phenylephrine was observed with three α1-adrenoceptor antagonists. Each pKB value of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKB values and gene expression studies indicated that α1A-adrenoceptor subtypes predominantly contributed to human IAS contraction. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  10. Functional characterization of estrogen receptor subtypes, ERα and ERβ, mediating vitellogenin production in the liver of rainbow trout

    International Nuclear Information System (INIS)

    Leanos-Castaneda, Olga; Kraak, Glen van der

    2007-01-01

    The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ERα and ERβ, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ERα selective agonist, methyl-piperidino-pyrazole (MPP) an ERα selective antagonist, and diarylpropionitrile (DPN) an ERβ selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbow trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [ 3 H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ERα could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ERβ. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ERα. On the other hand, once blocked ERα with MPP, the only manifestation of agonist activity of estradiol would be achieved via ERβ. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ERβ, implying, furthermore

  11. Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

    Science.gov (United States)

    Lai, H; Carino, M A

    1992-07-01

    Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

  12. Mindfulness, Resilience, and Burnout Subtypes in Primary Care Physicians: The Possible Mediating Role of Positive and Negative Affect.

    Science.gov (United States)

    Montero-Marin, Jesús; Tops, Mattie; Manzanera, Rick; Piva Demarzo, Marcelo M; Álvarez de Mon, Melchor; García-Campayo, Javier

    2015-01-01

    Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect) in primary care physicians, taking into account the potential mediating role of negative and positive affect. A cross-sectional design was used. Six hundred and twenty-two Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS), Connor-Davidson Resilience Scale (CD-RISC), Positive and Negative Affect Schedule (PANAS), and Burnout Clinical Subtype Questionnaire (BCSQ-12) questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares (ULS) method was used for developing structural equation modeling. Mindfulness and resilience presented moderately high associations (φ = 0.46). Links were found between mindfulness and overload (γ = -0.25); resilience and neglect (γ = -0.44); mindfulness and resilience, and negative affect (γ = -0.30 and γ = -0.35, respectively); resilience and positive affect (γ = 0.70); negative affect and overload (β = 0.36); positive affect and lack of development (β = -0.16). The links between the burnout types reached high and positive values between overload and lack of development (β = 0.64), and lack of development and neglect (β = 0.52). The model was a very good fit to the data (GFI = 0.96; AGFI = 0.96; RMSR = 0.06; NFI = 0.95; RFI = 0.95; PRATIO = 0.96). Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for treating its advanced stages.

  13. Mindfulness, resilience, and burnout subtypes in primary care physicians: the possible mediating role of positive and negative affect

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    Jesus eMontero-Marin

    2015-12-01

    Full Text Available AbstractPurpose: Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect in primary care physicians, taking into account the potential mediating role of negative and positive affect.Methods: A cross-sectional design was used. 622 Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS, Connor-Davidson Resilience Scale (CD-RISC, Positive and Negative Affect Schedule (PANAS and Burnout Clinical Subtype Questionnaire (BCSQ-12 questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares method was used for developing structural equation modelling. Results: Mindfulness and resilience presented moderately high associations (φ=0.46. Links were found between mindfulness and overload (γ=-0.25; resilience and neglect (γ=-0.44; mindfulness and resilience, and negative affect (γ=-0.30 and γ=-0.35 respectively; resilience and positive affect (γ=0.70; negative affect and overload (β=0.36; positive affect and lack of development (β=-0.16. The links between the burnout types reached high and positive values between overload and lack of development (β=0.64, and lack of development and neglect (β=0.52. The model was a very good fit to the data (GFI=0.96; AGFI=0.96; RMSR=0.06; NFI=0.95; RFI=0.95; PRATIO=0.96.Conclusions: Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for treating its advanced stages.

  14. Different AMPA receptor subtypes mediate the distinct kinetic components of a biphasic EPSC in hippocampal interneurons

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    Todd eStincic

    2015-05-01

    Full Text Available CA1 hippocampal interneurons at the border between stratum radiatum and stratum lacunosum-moleculare have AMPA receptor (AMPAR-mediated excitatory postsynaptic currents (EPSCs that consist of two distinct phases: a typical fast component (FC, and a highly unusual slow component (SC that persists for hundreds of milliseconds. To determine whether these kinetically distinct components of the EPSC are mediated by distinct AMPAR subpopulations, we examined the relative contributions of GluA2-containing and –lacking AMPARs to the SC. GluA2-containing AMPARs mediated the majority of the FC whereas GluA2-lacking AMPARs preferentially generated the SC. When glutamate uptake through the glial glutamate transporter EAAT1 was inhibited, spill over-mediated AMPAR activation recruited an even slower third kinetic component that persisted for several seconds; however, this spillover-mediated current was mediated predominantly by GluA2-containing AMPARs and therefore was clearly distinct from the SC when uptake is intact. Thus, different AMPAR subpopulations that vary in GluA2 content mediate the distinct components of the AMPAR EPSC. The SC is developmentally downregulated in mice, declining after the second postnatal week. This downregulation affects both GluA2-containing and GluA2-lacking AMPARs mediating the SC, and is not accompanied by developmental changes in the GluA2 content of AMPARs underlying the FC. Thus, the downregulation of the SC appears to be independent of synaptic GluA2 expression, suggesting the involvement of another AMPAR subunit or an auxiliary protein. Our results therefore identify GluA2-dependent and GluA2-independent determinants of the SC: GluA2-lacking AMPARs preferentially contribute to the SC, while the developmental downregulation of the SC is independent of GluA2 content.

  15. Violence Exposure Subtypes Differentially Mediate the Relation between Callous-Unemotional Traits and Adolescent Delinquency.

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    Oberth, Carla; Zheng, Yao; McMahon, Robert J

    2017-11-01

    Research with children and adolescents has established a link between callous-unemotional (CU) traits and delinquency, as well as a link between violence exposure (witnessing and direct victimization) and diverse negative and antisocial outcomes. Little attention has been paid to investigating the association among CU traits, violence exposure, and various forms of delinquency. Using a sample of 753 adolescents (male =58%; African American =46%), the current study aimed to elucidate the mediating role of violence exposure (measured in grades 7, 8, 10, 11) on the relationship between CU traits measured in grade 7 and later delinquency (i.e., property, violent, drug, and sexual) assessed in grade 12. Total violence exposure (witnessing and direct victimization) mediated the association between CU traits and all forms of delinquency. When looking at witnessing and direct victimization separately, however, only witnessing violence mediated the relationship between CU traits and all forms of delinquency. These results highlight the importance of violence exposure in the CU-delinquency link, and showed the differential roles of indirect and direct forms of violence exposure on the association. Witnessing and direct victimization may involve different underlying mechanisms influencing developmental outcomes in youth. These findings have important implications for understanding developmental models of violence exposure, CU traits, and delinquency, as well as interventions for youth who have experienced both indirect and direct forms of violence.

  16. Physiological stress mediates the honesty of social signals.

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    Gary R Bortolotti

    Full Text Available Extravagant ornaments used as social signals evolved to advertise their bearers' quality. The Immunocompetence Handicap Hypothesis proposes that testosterone-dependent ornaments reliably signal health and parasite resistance; however, empirical studies have shown mixed support. Alternatively, immune function and parasite resistance may be indirectly or directly related to glucocorticoid stress hormones. We propose that an understanding of the interplay between the individual and its environment, particularly how they cope with stressors, is crucial for understanding the honesty of social signals.We analyzed corticosterone deposited in growing feathers as an integrated measure of hypothalamic-pituitary-adrenal activity in a wild territorial bird, the red grouse Lagopus lagopus scoticus. We manipulated two key, interrelated components, parasites and testosterone, which influence both ornamentation and fitness. Birds were initially purged of parasites, and later challenged with parasites or not, while at the same time being given testosterone or control implants, using a factorial experimental design. At the treatment level, testosterone enhanced ornamentation, while parasites reduced it, but only in males not implanted with testosterone. Among individuals, the degree to which both parasites and testosterone had an effect was strongly dependent on the amount of corticosterone in the feather grown during the experiment. The more stressors birds had experienced (i.e., higher corticosterone, the more parasites developed, and the less testosterone enhanced ornamentation.With this unique focus on the individual, and a novel, integrative, measure of response to stressors, we show that ornamentation is ultimately a product of the cumulative physiological response to environmental challenges. These findings lead toward a more realistic concept of honesty in signaling as well as a broader discussion of the concept of stress.

  17. Characterization of the effect of penehyclidine hydrochloride on muscarinic receptor subtypes mediating the contraction of guinea-pig isolated gastrointestinal smooth muscle.

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    Xiao, Hong-Tao; Liao, Zhi; Meng, Xian-Min; Yan, Xiao-Yan; Chen, Shu-Jie; Mo, Zheng-Ji

    2009-07-01

    The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes. Radioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes. The results indicated that the relaxing effect of penehyclidine hydrochloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 mumol/l. The results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.

  18. Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex

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    Gigout Sylvain

    2012-04-01

    Full Text Available Abstract Background Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode and field potential recordings. Results CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M1/M4 mAChRs antagonist but not by AF-DX 116 (M2/M4 mAChRs antagonist. Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABAA and GABAB receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M1/M4 mAChRs agonist, yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition. Conclusions These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M1 mAChR, decrease of inhibition by M2 mAChR and depression of excitatory transmission by M4 mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the

  19. 5-HT receptor subtypes as key targets in mediating pigment dispersion within melanophores of teleost, Oreochromis mossambicus.

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    Salim, Saima; Ali, Ayesha S; Ali, Sharique A

    2013-02-01

    The presence of distinct class of 5-HT receptors in the melanophores of tilapia (Oreochromis mossambicus) is reported. The cellular responses to 5-HT (5-hydroxytryptamine), 5-HT(1), and 5-HT(2), agonists on isolated scale melanophores were observed with regard to pigment translocation within the cells. It was found that 5-HT exerted rapid and strong concentration dependent pigment granule dispersion within the melanophores. The threshold pharmacological dose of 5-HT that could elicit a measurable response was as low as 4.7×10(-12) M/L. Selective 5-HT(1) and 5-HT(2) agonists, sumatriptan and myristicin were investigated and resulted in dose-dependent pigment dispersion. The dispersing effects were effectively antagonized by receptor specific antagonists. It is suggested that 5-HT-induced physiological effects are mediated via distinct classes of receptors that possibly participate in modulation of pigmentary responses of the fish. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Seminal Fluid-Mediated Inflammation in Physiology and Pathology of the Female Reproductive Tract

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    Anthonio O. Adefuye

    2016-01-01

    Full Text Available Inflammation is a multifaceted process involving a host of resident and recruited immune cells that eliminate the insult or injury and initiate tissue repair. In the female reproductive tract (FMRT, inflammation-mediated alterations in epithelial, vascular, and immune functions are important components of complex physiological processes and many local and systemic pathologies. It is well established that intracoital and postcoital function of seminal fluid (SF goes beyond nutritive support for the spermatozoa cells. SF, in particular, the inflammatory bioactive lipids, and prostaglandins present in vast quantities in SF, have a role in localized immune modulation and regulation of pathways that can exacerbate inflammation in the FMRT. In sexually active women SF-mediated inflammation has been implicated in physiologic processes such as ovulation, implantation, and parturition while also enhancing tumorigenesis and susceptibility to infection. This review highlights the molecular mechanism by which SF regulates inflammatory pathways in the FMRT and how alterations in these pathways contribute to physiology and pathology of the female reproductive function. In addition, based on findings from TaqMan® 96-Well Plate Arrays, on neoplastic cervical cells treated with SF, we discuss new findings on the role of SF as a potent driver of inflammatory and tumorigenic pathways in the cervix.

  1. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

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    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-07-08

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection*

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-01-01

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. PMID:27226547

  4. Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle.

    Science.gov (United States)

    Chino, Daisuke; Sone, Tomoyo; Yamazaki, Kumi; Tsuruoka, Yuri; Yamagishi, Risa; Shiina, Shunsuke; Obara, Keisuke; Yamaki, Fumiko; Higai, Koji; Tanaka, Yoshio

    2018-01-01

    Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10 -7 M). Atenolol (a selective β 1 -AR antagonist; 3 × 10 -7 -10 -6  M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA 2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β 2 -AR antagonist) at 10 -9 -10 -8  M, but was competitively antagonized by 10 -7 -3 × 10 -7  M, with a pA 2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10 -7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA 2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β 1 -AR and β 3 -AR.

  5. Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice

    Science.gov (United States)

    Smith, Kiersten S.; Engin, Elif; Meloni, Edward G.; Rudolph, Uwe

    2012-01-01

    GABAA receptor modulating drugs such as benzodiazepines (BZs) have been used to treat anxiety disorders for over five decades. In order to determine whether the same or different GABAA receptor subtypes are necessary for the anxiolytic-like action of BZs in unconditioned anxiety and conditioned fear models, we investigated the role of different GABAA receptor subtypes by challenging wild type, α1(H101R), α2(H101R) and α3(H126R) mice bred on the C57BL/6J background with diazepam or chlordiazepoxide in the elevated plus maze and the fear-potentiated startle paradigms. Both drugs significantly increased open arm exploration in the elevated plus maze in wild type, α1(H101R) and α3(H126R), but this effect was abolished in α2(H101R) mice; these were expected results based on previous published results. In contrast, while administration of diazepam and chlordiazepoxide significantly attenuated fear-potentiated startle (FPS) in wild type mice and α3(H126R) mice, the fear-reducing effects of these drugs were absent in both α1(H101R) and α2(H101R) point mutants, indicating that both α1- and α2-containing GABAA receptors are necessary for BZs to exert their effects on conditioned fear responses.. Our findings illustrate both an overlap and a divergence between the GABAA receptor subtype requirements for the impact of BZs, specifically that both α1- and α2-containing GABAA receptors are necessary for BZs to reduce conditioned fear whereas only α2-containing GABAA receptors are needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises the possibility that GABAergic pharmacological interventions for specific anxiety disorders can be differentially tailored. PMID:22465203

  6. Microenvironment-Mediated Mechanisms of Resistance to HER2 Inhibitors Differ between HER2+ Breast Cancer Subtypes.

    Science.gov (United States)

    Watson, Spencer S; Dane, Mark; Chin, Koei; Tatarova, Zuzana; Liu, Moqing; Liby, Tiera; Thompson, Wallace; Smith, Rebecca; Nederlof, Michel; Bucher, Elmar; Kilburn, David; Whitman, Matthew; Sudar, Damir; Mills, Gordon B; Heiser, Laura M; Jonas, Oliver; Gray, Joe W; Korkola, James E

    2018-03-28

    Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental signals influence resistance, we monitored TKI-treated breast cancer cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations of 56 soluble and 46 matrix microenvironmental proteins on basal-like HER2+ (HER2E) or luminal-like HER2+ (L-HER2+) cells treated with the TKIs lapatinib or neratinib. In HER2E cells, hepatocyte growth factor, a ligand for MET, induced resistance that could be reversed with crizotinib, an inhibitor of MET. In L-HER2+ cells, neuregulin1-β1 (NRG1β), a ligand for HER3, induced resistance that could be reversed with pertuzumab, an inhibitor of HER2-HER3 heterodimerization. The subtype-specific responses were also observed in 3D cultures and murine xenografts. These results, along with bioinformatic pathway analysis and siRNA knockdown experiments, suggest different mechanisms of resistance specific to each HER2+ subtype: MET signaling for HER2E and HER2-HER3 heterodimerization for L-HER2+ cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Development of a reverse transcription loop-mediated isothermal amplification method for the rapid detection of avian influenza virus subtype H7.

    Science.gov (United States)

    Bao, Hongmei; Wang, Xiurong; Zhao, Yuhui; Sun, Xiaodong; Li, Yanbing; Xiong, Yongzhong; Chen, Hualan

    2012-01-01

    A rapid and sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of the H7 avian influenza virus (H7 AIV) isotype was developed. The minimum detection limit of the RT-LAMP assay was 0.1-0.01 PFU per reaction for H7 AIV RNA, making this assay 100-fold more sensitive than the conventional RT-PCR method. This RT-LAMP assay also has the capacity to detect both high- and low-pathogenic H7 AIV strains. Using a pool of RNAs extracted from influenza viruses corresponding to all 15 HA subtypes (in addition to other avian pathogenic viruses), the RT-LAMP system was confirmed to amplify only H7 AIV RNA. Furthermore, specific pathogen free (SPF) chickens were infected artificially with H7 AIV, throat and cloacal swabs were collected, and viral shedding was examined using viral isolation, RT-PCR and RT-LAMP. Shedding was detected following viral isolation and RT-LAMP one day after infection, whereas viral detection using RT-PCR was effective only on day 3 post-infection. These results indicate that the RT-LAMP method could facilitate epidemiological surveillance and the rapid diagnosis of the avian influenza subtype H7. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Anxiety and Depression: Mouse Genetics and Pharmacological Approaches to the Role of GABAA Receptor Subtypes

    Science.gov (United States)

    Smith, Kiersten S.; Rudolph, Uwe

    2012-01-01

    GABAA receptors mediate fast synaptic inhibitory neurotransmission throughout the central nervous system. Recent work indicates a role for GABAA receptors in physiologically modulating anxiety and depression levels. In this review, we summarize research that led to the identification of the essential role of GABAA receptors in counteracting trait anxiety and depression-related behaviors, and research aimed at identifying individual GABAA receptor subtypes involved in physiological and pharmacological modulation of emotions. PMID:21810433

  9. Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

    Science.gov (United States)

    Fasano, Alessio

    2008-01-01

    The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields. PMID:18832585

  10. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    Science.gov (United States)

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P 1 , S1P 2 , and S1P 3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to G q . We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα 13 but not Gα 12 , Gα q , or Gα i . Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P 3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P 3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P 3 KO mouse heart. CYM-51736, an S1P 3 -specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P 3 receptor- and Gα 13 -mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Harsh parenting and peer acceptance in Chinese early adolescents: Three child aggression subtypes as mediators and child gender as moderator.

    Science.gov (United States)

    Wang, Mingzhong

    2017-01-01

    This study examined the mediating roles of three types of child aggression in the relation between harsh parenting and Chinese early adolescents' peer acceptance as well as the moderating role of child gender on this indirect relation. 833 children (mean age=13.58, 352 girls) with their parents were recruited as participants from two junior high schools in Shandong Province, People's Republic of China. The results showed that paternal harsh parenting was only associated with boys' aggressive behaviors and maternal harsh parenting was only associated with boys' and girls' verbal aggression. Adolescents' verbal and relational aggressions were negatively associated with their peer acceptance. Verbal aggression was more strongly and negatively associated with girls' peer acceptance. The results imply that in the Chinese cultural context, paternal harsh parenting may compromise boys' peer acceptance through boys' verbal and relational aggression as mediators, whereas maternal harsh parenting may impair children's peer acceptance through children's verbal aggression as a mediator, especially for girls. These results provide a theoretical basis for ameliorating the negative effect of harsh parenting on early adolescents' peer acceptance by reducing their aggressive behaviors, with different strategies between boys and girls. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

    Science.gov (United States)

    Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

    2015-02-27

    The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Maternal Elaborative Reminiscing Mediates the Effect of Child Maltreatment on Behavioral and Physiological Functioning

    Science.gov (United States)

    Valentino, Kristin; Hibel, Leah C; Cummings, E. Mark; Nuttall, Amy K.; Comas, Michelle; McDonnell, Christina G.

    2016-01-01

    Theoretical and empirical evidence suggest that the way in which parents discuss everyday emotional experiences with their young children (i.e., elaborative reminiscing) has significant implications for child cognitive and socio-emotional functioning, and that maltreating parents have a particularly difficult time in engaging in this type of dialogue. This dyadic interactional exchange, therefore, has the potential to be an important process variable linking child maltreatment to developmental outcomes at multiple levels of analysis. The current investigation evaluated the role of maternal elaborative reminiscing in associations between maltreatment and child cognitive, emotional, and physiological functioning. Participants included 43 maltreated and 49 nonmaltreated children (aged 3–6) and their mothers. Dyads participated in a joint reminiscing task about four past emotional events, and children participated in assessments of receptive language and emotion knowledge. Child salivary cortisol was also collected from children three times a day (waking, midday, and bedtime) on two consecutive days to assess daily levels and diurnal decline. Results indicated that maltreating mothers engaged in significantly less elaborative reminiscing than nonmaltreating mothers. Maternal elaborative reminiscing mediated associations between child maltreatment and child receptive language and child emotion knowledge. Additionally, there was support for an indirect pathway between child maltreatment and child cortisol diurnal decline through maternal elaborative reminiscing. Directions for future research are discussed and potential clinical implications are addressed. PMID:26535941

  14. Listening to music and physiological and psychological functioning: the mediating role of emotion regulation and stress reactivity.

    Science.gov (United States)

    Thoma, M V; Scholz, U; Ehlert, U; Nater, U M

    2012-01-01

    Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.

  15. Development of a Reverse Transcription Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Subtype H7N9 Avian Influenza Virus

    Directory of Open Access Journals (Sweden)

    Hongmei Bao

    2014-01-01

    Full Text Available A novel influenza A (H7N9 virus has emerged in China. To rapidly detect this virus from clinical samples, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP method for the detection of the H7N9 virus. The minimum detection limit of the RT-LAMP assay was 0.01 PFU H7N9 virus, making this method 100-fold more sensitive to the detection of the H7N9 virus than conventional RT-PCR. The H7N9 virus RT-LAMP assays can efficiently detect different sources of H7N9 influenza virus RNA (from chickens, pigeons, the environment, and humans. No cross-reactive amplification with the RNA of other subtype influenza viruses or of other avian respiratory viruses was observed. The assays can effectively detect H7N9 influenza virus RNA in drinking water, soil, cloacal swab, and tracheal swab samples that were collected from live poultry markets, as well as human H7N9 virus, in less than 30 min. These results suggest that the H7N9 virus RT-LAMP assays were efficient, practical, and rapid diagnostic methods for the epidemiological surveillance and diagnosis of influenza A (H7N9 virus from different resource samples.

  16. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    OpenAIRE

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D.; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G.; Joyner, Michael J.; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBR...

  17. Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y

    OpenAIRE

    Nishida, Yuichiro; Adati, Naoki; Ozawa, Ritsuko; Maeda, Aasami; Sakaki, Yoshiyuki; Takeda, Tadayuki

    2008-01-01

    Abstract Background SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA), but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K) is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E), each of which show a different phenotype during RA-mediated differentiation. Findings SH-SY5Y-A cells diffe...

  18. A novel bZIP gene from Tamarix hispida mediates physiological responses to salt stress in tobacco plants.

    Science.gov (United States)

    Wang, Yucheng; Gao, Caiqiu; Liang, Yenan; Wang, Chao; Yang, Chuanping; Liu, Guifeng

    2010-02-15

    Basic leucine zipper proteins (bZIPs) are transcription factors that bind abscisic acid (ABA)-responsive elements (ABREs) and enable plants to withstand adverse environmental conditions. In the present study, a novel bZIP gene, ThbZIP1 was cloned from Tamarix hispida. Expression studies in T. hispida showed differential regulation of ThbZIP1 in response to treatment with NaCl, polyethylene glycol (PEG) 6000, NaHCO(3), and CdCl(2), suggesting that ThbZIP1 is involved in abiotic stress responses. To identify the physiological responses mediated by ThbZIP1, transgenic tobacco plants overexpressing exogenous ThbZIP1 were generated. Various physiological parameters related to salt stress were measured and compared between transgenic and wild type (WT) plants. Our results indicate that overexpression of ThbZIP1 can enhance the activity of both peroxidase (POD) and superoxide dismutase (SOD), and increase the content of soluble sugars and soluble proteins under salt stress conditions. These results suggest that ThbZIP1 contributes to salt tolerance by mediating signaling through multiple physiological pathways. Furthermore, ThbZIP1 confers stress tolerance to plants by enhancing reactive oxygen species (ROS) scavenging, facilitating the accumulation of compatible osmolytes, and inducing and/or enhancing the biosynthesis of soluble proteins. Copyright 2009 Elsevier GmbH. All rights reserved.

  19. Assessing the performance of a Loop Mediated Isothermal Amplification (LAMP) assay for the detection and subtyping of high-risk suptypes of Human Papilloma Virus (HPV) for Oropharyngeal Squamous Cell Carcinoma (OPSCC) without DNA purification.

    Science.gov (United States)

    Rohatensky, Mitchell G; Livingstone, Devon M; Mintchev, Paul; Barnes, Heather K; Nakoneshny, Steven C; Demetrick, Douglas J; Dort, Joseph C; van Marle, Guido

    2018-02-08

    Oropharyngeal Squamous Cell Carcinoma (OPSCC) is increasing in incidence despite a decline in traditional risk factors. Human Papilloma Virus (HPV), specifically subtypes 16, 18, 31 and 35, has been implicated as the high-risk etiologic agent. HPV positive cancers have a significantly better prognosis than HPV negative cancers of comparable stage, and may benefit from different treatment regimens. Currently, HPV related carcinogenesis is established indirectly through Immunohistochemistry (IHC) staining for p16, a tumour suppressor gene, or polymerase chain reaction (PCR) that directly tests for HPV DNA in biopsied tissue. Loop mediated isothermal amplification (LAMP) is more accurate than IHC, more rapid than PCR and is significantly less costly. In previous work we showed that a subtype specific HPV LAMP assay performed similar to PCR on purified DNA. In this study we examined the performance of this LAMP assay without DNA purification. We used LAMP assays using established primers for HPV 16 and 18, and new primers for HPV 31 and 35. LAMP reaction conditions were tested on serial dilutions of plasmid HPV DNA to confirm minimum viral copy number detection thresholds. LAMP was then performed directly on different human cell line samples without DNA purification. Our LAMP assays could detect 10 5 , 10 3 , 10 4 , and 10 5 copies of plasmid DNA for HPV 16, 18, 31, and 35, respectively. All primer sets were subtype specific, with no cross-amplification. Our LAMP assays also reliably amplified subtype specific HPV DNA from samples without requiring DNA isolation and purification. The high risk OPSCC HPV subtype specific LAMP primer sets demonstrated, excellent clinically relevant, minimum copy number detection thresholds with an easy readout system. Amplification directly from samples without purification illustrated the robust nature of the assay, and the primers used. This lends further support HPV type specific LAMP assays, and these specific primer sets and assays

  20. water stress mediated changes in growth, physiology and secondary metabolites of desi ajwain (trachyspermum ammi l.)

    International Nuclear Information System (INIS)

    Azhar, N.; Hussain, B.; Abbasi, K.Y.

    2011-01-01

    Biotic and abiotic stresses exert a considerable influence on the production of several secondary metabolites in plants; water stress is one of the most important abiotic stress factors. This study was carried out to elucidate the effect of drought stress on growth, physiology and secondary metabolite production in desi ajwain (Trachyspermum ammi L.). Plants were grown in pots and three drought levels (100%, 80% and 60%) of field capacity were created. The experiment was laid out in complete randomized design (CRD) with three replicates. Data on growth, physiological and biochemical parameters were recorded and analyzed statistically. Physiological parameters like transpiration rate and stomatal conductance decreased concentration increased. The photosynthetic rate showed significantly with increasing water stress levels, but internal CO/sub 2/ non-significant reduction from 100% field capacity to 80% field capacity but increased at 60% field capacity. Growth parameters including plant height, herb fresh and dry weights were reduced significantly with increasing stress levels, while total phenolic contents and chlorophyll contents increased under water stress conditions. These results suggest that cultivation of medicinal plants like desi ajwain under drought stress could enhance the production of secondary metabolites. (author)

  1. Directional Change Mediates the Physiological Response to High-Intensity Shuttle Running in Professional Soccer Players

    Directory of Open Access Journals (Sweden)

    Remy Tang

    2018-04-01

    Full Text Available The purpose of this study was to investigate the influence that different frequencies of deceleration and acceleration actions had on the physiological demands in professional soccer players. Thirteen players were monitored via microelectromechanical devices during shuttle running protocols which involved one, three, or seven 180 degree directional changes. Heart rate exertion (HRE (1.1 ± 0.7 and rating of perceived exertion (RPE (5 ± 1 were significantly higher for the protocol which included seven directional changes when compared to the protocols which included one (HRE 0.5 ± 0.3, ES = 1.1, RPE 3 ± 0, ES = 2.7 or three (HRE 0.5 ± 0.2, ES = 1.1, RPE 3 ± 1, ES = 1.9 directional changes (p < 0.05. The gravitational force (g-force as measured through accelerometry (ACC also showed a similar trend when comparing the seven (8628.2 ± 1630.4 g to the one (5888.6 ± 1159.1 g, ES = 1.9 or three (6526.9 ± 1257.6 g, ES = 1.4 directional change protocols (p < 0.05. The results of this study suggest that increasing the frequency of decelerations and accelerations at a high intensity running (HIR speed alters the movement demands and elevates the physiological responses in professional players. This data has implications for the monitoring of physical performance and implementation of training drills.

  2. Energetic Physiology Mediates Individual Optimization of Breeding Phenology in a Migratory Arctic Seabird.

    Science.gov (United States)

    Hennin, Holly L; Bêty, Jöel; Legagneux, Pierre; Gilchrist, H Grant; Williams, Tony D; Love, Oliver P

    2016-10-01

    The influence of variation in individual state on key reproductive decisions impacting fitness is well appreciated in evolutionary ecology. Rowe et al. (1994) developed a condition-dependent individual optimization model predicting that three key factors impact the ability of migratory female birds to individually optimize breeding phenology to maximize fitness in seasonal environments: arrival condition, arrival date, and ability to gain in condition on the breeding grounds. While empirical studies have confirmed that greater arrival body mass and earlier arrival dates result in earlier laying, no study has assessed whether individual variation in energetic management of condition gain effects this key fitness-related decision. Using an 8-year data set from over 350 prebreeding female Arctic common eiders (Somateria mollissima), we tested this component of the model by examining whether individual variation in two physiological traits influencing energetic management (plasma triglycerides: physiological fattening rate; baseline corticosterone: energetic demand) predicted individual variation in breeding phenology after controlling for arrival date and body mass. As predicted by the optimization model, individuals with higher fattening rates and lower energetic demand had the earliest breeding phenology (shortest delays between arrival and laying; earliest laying dates). Our results are the first to empirically determine that individual flexibility in prebreeding energetic management influences key fitness-related reproductive decisions, suggesting that individuals have the capacity to optimally manage reproductive investment.

  3. Allelopatic Potential of Dittrichia viscosa (L. W. Greuter Mediated by VOCs: A Physiological and Metabolomic Approach.

    Directory of Open Access Journals (Sweden)

    Fabrizio Araniti

    Full Text Available Dittrichia viscosa (L. W. Greuter is a pioneer species belonging to the Compositae family. It is widespread in the Mediterranean basin, where it is considered invasive. It is a source of secondary metabolites, playing an important ecological role. D. viscosa plant extracts showed a phytotoxic activity on several physiological processes of different species. In the current study, the allelopathic potential of D. viscosa VOCs, released by its foliage, was evaluated on seed germination and root growth of lettuce. The VOCs effect was also studied on lettuce adult plants in microcosm systems, which better mimicked the open field conditions. D. viscosa VOCs inhibited both seed germination and root growth of lettuce. The VOCs composition revealed a large presence of terpenoids, responsible of the effects observed. Moreover, D. viscosa VOCs caused an alteration on plant water status accompanied by oxidative damages and photoinhibition on lettuce adult plants.

  4. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall.

    Science.gov (United States)

    Fasano, Alessio

    2008-11-01

    The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields.

  5. Transcriptomic underpinning of toxicant-mediated physiological function alterations in three terrestrial invertebrate taxa: A review

    Energy Technology Data Exchange (ETDEWEB)

    Brulle, Franck [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France); Morgan, A. John [Cardiff School of Biosciences, Cardiff University, P.O. Box 915, Cardiff, CF10 3US Wales (United Kingdom); Cocquerelle, Claude [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France); Vandenbulcke, Franck, E-mail: franck.vandenbulcke@univ-lille1.f [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France)

    2010-09-15

    Diverse anthropogenic activities often lead to the accumulation of inorganic and organic residues in topsoils. Biota living in close contact with contaminated soils may experience stress at different levels of biological organisation throughout the continuum from the molecular-genetic to ecological and community levels. To date, the relationship between changes at the molecular (mRNA expression) and biochemical/physiological levels evoked by exposures to chemical compounds has been partially established in a limited number of terrestrial invertebrate species. Recently, the advent of a family of transcriptomic tools (e.g. Real-time PCR, Subtractive Suppressive Hybridization, Expressed Sequence Tag sequencing, pyro-sequencing technologies, Microarray chips), together with supporting informatic and statistical procedures, have permitted the robust analyses of global gene expression changes within an ecotoxicological context. This review focuses on how transcriptomics is enlightening our understanding of the molecular-genetic responses of three contrasting terrestrial macroinvertebrate taxa (nematodes, earthworms, and springtails) to inorganics, organics, and agrochemicals. - Environmental toxicology and transcriptomics in soil macroinvertebrates.

  6. Transcriptomic underpinning of toxicant-mediated physiological function alterations in three terrestrial invertebrate taxa: A review

    International Nuclear Information System (INIS)

    Brulle, Franck; Morgan, A. John; Cocquerelle, Claude; Vandenbulcke, Franck

    2010-01-01

    Diverse anthropogenic activities often lead to the accumulation of inorganic and organic residues in topsoils. Biota living in close contact with contaminated soils may experience stress at different levels of biological organisation throughout the continuum from the molecular-genetic to ecological and community levels. To date, the relationship between changes at the molecular (mRNA expression) and biochemical/physiological levels evoked by exposures to chemical compounds has been partially established in a limited number of terrestrial invertebrate species. Recently, the advent of a family of transcriptomic tools (e.g. Real-time PCR, Subtractive Suppressive Hybridization, Expressed Sequence Tag sequencing, pyro-sequencing technologies, Microarray chips), together with supporting informatic and statistical procedures, have permitted the robust analyses of global gene expression changes within an ecotoxicological context. This review focuses on how transcriptomics is enlightening our understanding of the molecular-genetic responses of three contrasting terrestrial macroinvertebrate taxa (nematodes, earthworms, and springtails) to inorganics, organics, and agrochemicals. - Environmental toxicology and transcriptomics in soil macroinvertebrates.

  7. Elevated atmospheric CO2 negatively impacts photosynthesis through radiative forcing and physiology-mediated climate feedback

    Science.gov (United States)

    Zhu, Peng; Zhuang, Qianlai; Ciais, Philippe; Welp, Lisa; Li, Wenyu; Xin, Qinchuan

    2017-02-01

    Increasing atmospheric CO2 affects photosynthesis involving directly increasing leaf carboxylation rates, stomatal closure, and climatic effects. The direct effects are generally thought to be positive leading to increased photosynthesis, while its climatic effects can be regionally positive or negative. These effects are usually considered to be independent from each other, but they are in fact coupled through interactions between land surface exchanges of gases and heat and the physical climate system. In particular, stomatal closure reduces evapotranspiration and increases sensible heat emissions from ecosystems, leading to decreased atmospheric moisture and precipitation and local warming. We use a coupled earth system model to attribute the influence of the increase in CO2 on gross primary productivity (GPP) during the period of 1930-2011. In our model, CO2 radiative effects cause climate change that has only a negligible effect on global GPP (a reduction of 0.9 ± 2% during the last 80 years) because of opposite responses between tropical and northern biomes. On the other hand, CO2 physiological effects on GPP are both positive, by increased carboxylation rates and water use efficiency (7.1 ± 0.48% increase), and negative, by vegetation-climate feedback reducing precipitation, as a consequence of decreased transpiration and increased sensible heat in areas without water limitation (2.7 ± 1.76% reduction).When considering the coupled atmosphere-vegetation system, negative climate feedback on photosynthesis and plant growth due to the current level of CO2 opposes 29-38% of the gains from direct fertilization effects.

  8. Physiological and cognitive mediators for the association between self-reported depressed mood and impaired choice stepping reaction time in older people.

    NARCIS (Netherlands)

    Kvelde, T.; Pijnappels, M.A.G.M.; Delbaere, K.; Close, J.C.; Lord, S.R.

    2010-01-01

    Background. The aim of the study was to use path analysis to test a theoretical model proposing that the relationship between self-reported depressed mood and choice stepping reaction time (CSRT) is mediated by psychoactive medication use, physiological performance, and cognitive ability.A total of

  9. Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y

    Directory of Open Access Journals (Sweden)

    Sakaki Yoshiyuki

    2008-10-01

    Full Text Available Abstract Background SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA, but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E, each of which show a different phenotype during RA-mediated differentiation. Findings SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells. Conclusion We identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.

  10. Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y.

    Science.gov (United States)

    Nishida, Yuichiro; Adati, Naoki; Ozawa, Ritsuko; Maeda, Aasami; Sakaki, Yoshiyuki; Takeda, Tadayuki

    2008-10-28

    SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA), but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K) is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E), each of which show a different phenotype during RA-mediated differentiation. SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF) for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells. We identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.

  11. RNAi-mediated downregulation of poplar plasma membrane intrinsic proteins (PIPs) changes plasma membrane proteome composition and affects leaf physiology.

    Science.gov (United States)

    Bi, Zhen; Merl-Pham, Juliane; Uehlein, Norbert; Zimmer, Ina; Mühlhans, Stefanie; Aichler, Michaela; Walch, Axel Karl; Kaldenhoff, Ralf; Palme, Klaus; Schnitzler, Jörg-Peter; Block, Katja

    2015-10-14

    Plasma membrane intrinsic proteins (PIPs) are one subfamily of aquaporins that mediate the transmembrane transport of water. To reveal their function in poplar, we generated transgenic poplar plants in which the translation of PIP genes was downregulated by RNA interference investigated these plants with a comprehensive leaf plasma membrane proteome and physiome analysis. First, inhibition of PIP synthesis strongly altered the leaf plasma membrane protein composition. Strikingly, several signaling components and transporters involved in the regulation of stomatal movement were differentially regulated in transgenic poplars. Furthermore, hormonal crosstalk related to abscisic acid, auxin and brassinosteroids was altered, in addition to cell wall biosynthesis/cutinization, the organization of cellular structures and membrane trafficking. A physiological analysis confirmed the proteomic results. The leaves had wider opened stomata and higher net CO2 assimilation and transpiration rates as well as greater mesophyll conductance for CO2 (gm) and leaf hydraulic conductance (Kleaf). Based on these results, we conclude that PIP proteins not only play essential roles in whole leaf water and CO2 flux but have important roles in the regulation of stomatal movement. Copyright © 2015. Published by Elsevier B.V.

  12. Current concepts on the physiology and genetics of neurotransmitters-mediating enzyme-aromatic L-amino acid decarboxylase

    International Nuclear Information System (INIS)

    Rahman, M.K.

    1993-03-01

    Two most important neurotransmitters, dopamine and serotonin are mediated by the enzyme aromatic L-amino acid decarboxylase (AADC). Because of their importance in the regulation of neuronal functions, behaviour and emotion of higher animals, many researchers are working on this enzyme to elucidate its physiological properties, structure and genetic aspects. We have discovered this enzyme in the mammalian blood, we established sensitive assay methods for the assay of the activities of this enzyme. We have made systematic studies on this enzyme in the tissues and brains of rats, and human subjects. We have found an endogenous inhibitor of this enzyme in the monkey's blood. The amino acid sequences of human AADC has been compared to rat or bovine. A full-length cDNA clone encoding human AADC has been isolated. Very recently the structure of human AADC gene including 5'-flaking region has been characterized and the transcriptional starting point has been determined. The human AADC gene assigned to chromosome 7. Up-to-date research data have shown that AADC is encoded by a single gene. Recently two patients with AADC deficiency were reported. This paper describes the systematic up-to-date review studies on AADC. (author). 62 refs, 5 figs, 8 tabs

  13. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans.

    Science.gov (United States)

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G; Joyner, Michael J; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions ( n = 8), and during progressive loss of 1 L blood ( n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result

  14. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  15. AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

    Science.gov (United States)

    Virts, Elizabeth L; Jankowska, Anna; Mackay, Craig; Glaas, Marcel F; Wiek, Constanze; Kelich, Stephanie L; Lottmann, Nadine; Kennedy, Felicia M; Marchal, Christophe; Lehnert, Erik; Scharf, Rüdiger E; Dufour, Carlo; Lanciotti, Marina; Farruggia, Piero; Santoro, Alessandra; Savasan, Süreyya; Scheckenbach, Kathrin; Schipper, Jörg; Wagenmann, Martin; Lewis, Todd; Leffak, Michael; Farlow, Janice L; Foroud, Tatiana M; Honisch, Ellen; Niederacher, Dieter; Chakraborty, Sujata C; Vance, Gail H; Pruss, Dmitry; Timms, Kirsten M; Lanchbury, Jerry S; Alpi, Arno F; Hanenberg, Helmut

    2015-09-15

    Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene. © The Author 2015. Published by Oxford University Press.

  16. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    NARCIS (Netherlands)

    Silvani, A.; Calandra-Buonaura, G.; Johnson, B.D.; Helmond, N. van; Barletta, G.; Cecere, A.G.; Joyner, M.J.; Cortelli, P.

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological

  17. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  18. Plant Survival and Mortality during Drought Can be Mediated by Co-occurring Species' Physiological and Morphological Traits: Results from a Model

    Science.gov (United States)

    Tai, X.; Mackay, D. S.

    2015-12-01

    Interactions among co-occurring species are mediated by plant physiology, morphology and environment. Without proper mechanisms to account for these factors, it remains difficult to predict plant mortality/survival under changing climate. A plant ecophysiological model, TREES, was extended to incorporate co-occurring species' belowground interaction for water. We used it to examine the interaction between two commonly co-occurring species during drought experiment, pine (Pinus edulis) and juniper (Juniperus monosperma), with contrasting physiological traits (vulnerability to cavitation and leaf water potential regulation). TREES was parameterized and validated using field-measured plant physiological traits. The root architecture (depth, profile, and root area to leaf area ratio) of juniper was adjusted to see how root morphology could affect the survival/mortality of its neighboring pine under both ambient and drought conditions. Drought suppressed plant water and carbon uptake, as well increased the average percentage loss of conductivity (PLC). Pine had 59% reduction in water uptake, 48% reduction in carbon uptake, and 38% increase in PLC, while juniper had 56% reduction in water uptake, 50% reduction in carbon and 29% increase in PLC, suggesting different vulnerability to drought as mediated by plant physiological traits. Variations in juniper root architecture further mediated drought stress on pine, from negative to positive. Different juniper root architecture caused variations in response of pine over drought (water uptake reduction ranged 0% ~63%, carbon uptake reduction ranged 0% ~ 70%, and PLC increase ranged 2% ~ 91%). Deeper or more uniformly distributed roots of juniper could effectively mitigate stress experienced by pine. In addition, the total water and carbon uptake tended to increase as the ratio of root area to leaf area increased while PLC showed non-monotonic response, suggesting the potential trade-off between maximizing resource uptake and

  19. Morphologic Subtypes of Hepatocellular Carcinoma.

    Science.gov (United States)

    Torbenson, Michael S

    2017-06-01

    Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti.

    Directory of Open Access Journals (Sweden)

    Jason S Lehmann

    Full Text Available Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-, and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+ and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56- T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that

  1. Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition

    Directory of Open Access Journals (Sweden)

    Ambele Melvin A

    2012-10-01

    Full Text Available Abstract Background The malaria parasite disposes of host-derived ferrihaem (iron(IIIprotoporphyrin IX, Fe(IIIPPIX by conversion to crystalline haemozoin in close association with neutral lipids. Lipids mediate synthetic haemozoin (β-haematin formation very efficiently. However, the effect on reaction rates of concentrations of lipid, Fe(IIIPPIX and physiologically relevant ions and biomolecules are unknown. Methods Lipid emulsions containing Fe(IIIPPIX were prepared in aqueous medium (pH 4.8, 37°C to mediate β-haematin formation. The reaction was quenched at various times and free Fe(IIIPPIX measured colorimetrically as a pyridine complex and the kinetics and yields analysed. Products were also characterized by FTIR, TEM and electron diffraction. Autofluorescence was also used to monitor β-haematin formation by confocal microscopy. Results At fixed Fe(IIIPPIX concentration, β-haematin yields remained constant with decreasing lipid concentration until a cut-off ratio was reached whereupon efficiency decreased dramatically. For the haemozoin-associated neutral lipid blend (NLB and monopalmitoylglycerol (MPG, this occurred below a lipid/Fe(IIIPPIX (L/H ratio of 0.54. Rate constants were found to increase with L/H ratio above the cut-off. At 16 μM MPG, Fe(IIIPPIX concentration could be raised until the L/H ratio reached the same ratio before a sudden decline in yield was observed. MPG-mediated β-haematin formation was relatively insensitive to biologically relevant cations (Na+, K+, Mg2+, Ca2+, or anions (H2PO4−, HCO3−, ATP, 2,3-diphosphoglycerate, glutathione. Confocal microscopy demonstrated β-haematin formation occurs in association with the lipid particles. Conclusions Kinetics of β-haematin formation have shown that haemozoin-associated neutral lipids alone are capable of mediating β-haematin formation at adequate rates under physiologically realistic conditions of ion concentrations to account for haemozoin formation.

  2. The social transmission of risk: Maternal stress physiology, synchronous parenting, and well-being mediate the effects of war exposure on child psychopathology.

    Science.gov (United States)

    Halevi, Galit; Djalovski, Amir; Kanat-Maymon, Yaniv; Yirmiya, Karen; Zagoory-Sharon, Orna; Koren, Lee; Feldman, Ruth

    2017-11-01

    While chronic early stress increases child susceptibility to psychopathology, risk and resilience trajectories are shaped by maternal social influences whose role requires much further research in longitudinal studies. We examined the social transmission of risk by assessing paths leading from war-exposure to child symptoms as mediated by 3 sources of maternal social influence; stress physiology, synchronous parenting, and psychiatric disorder. Mothers and children living in a zone of continuous war were assessed in early childhood (1.5-5 years) and the current study revisited families in late (9-11years) childhood (N = 177; N = 101 war-exposed; N = 76 controls). At both time-points, maternal and child's salivary cortisol (SC), social behavior, and externalizing and internalizing symptoms were assessed. In late childhood, hair cortisol concentrations (HCC) were also measured and mother and child underwent psychiatric diagnosis. The social transmission model was tested against 2 alternative models; 1 proposing direct impact of war on children without maternal mediation, the other predicting late-childhood symptoms from early childhood variables, not change trajectories. Path analysis controlling for early childhood variables supported our conceptual model. Whereas maternal psychopathology was directly linked with child symptoms, defining direct mediation, the impact of maternal stress hormones was indirect and passed through stress contagion mechanisms involving coupling between maternal and child's HCC and SC. Similarly, maternal synchrony linked with child social engagement as the pathway to reduced symptomatology. Findings underscore the critical role of maternal stress physiology, attuned behavior, and well-being in shaping child psychopathology amid adversity and specify direct and indirect paths by which mothers stand between war and the child. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  4. Complement-coagulation cross-talk: a potential mediator of the physiological activation of complement by low pH

    Directory of Open Access Journals (Sweden)

    Hany Ibrahim Kenawy

    2015-05-01

    Full Text Available The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross talk between the contact system and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD accompanied by metabolic acidosis, in which therapeutic alkalinisation of urine has been shown significantly to reduce tubular complement activation products, an effect which may have important implications for slowing progression of CKD.

  5. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  6. Influenza A Subtyping

    Science.gov (United States)

    Kaul, Karen L.; Mangold, Kathy A.; Du, Hongyan; Pesavento, Kristen M.; Nawrocki, John; Nowak, Jan A.

    2010-01-01

    Influenza virus subtyping has emerged as a critical tool in the diagnosis of influenza. Antiviral resistance is present in the majority of seasonal H1N1 influenza A infections, with association of viral strain type and antiviral resistance. Influenza A virus subtypes can be reliably distinguished by examining conserved sequences in the matrix protein gene. We describe our experience with an assay for influenza A subtyping based on matrix gene sequences. Viral RNA was prepared from nasopharyngeal swab samples, and real-time RT-PCR detection of influenza A and B was performed using a laboratory developed analyte-specific reagent-based assay that targets a conserved region of the influenza A matrix protein gene. FluA-positive samples were analyzed using a second RT-PCR assay targeting the matrix protein gene to distinguish seasonal influenza subtypes based on differential melting of fluorescence resonance energy transfer probes. The novel H1N1 influenza strain responsible for the 2009 pandemic showed a melting profile distinct from that of seasonal H1N1 or H3N2 and compatible with the predicted melting temperature based on the published novel H1N1 matrix gene sequence. Validation by comparison with the Centers for Disease Control and Prevention real-time RT-PCR for swine influenza A (novel H1N1) test showed this assay to be both rapid and reliable (>99% sensitive and specific) in the identification of the novel H1N1 influenza A virus strain. PMID:20595627

  7. Subtyping adolescents with bulimia nervosa.

    Science.gov (United States)

    Chen, Eunice Y; Le Grange, Daniel

    2007-12-01

    Cluster analyses of eating disorder patients have yielded a "dietary-depressive" subtype, typified by greater negative affect, and a "dietary" subtype, typified by dietary restraint. This study aimed to replicate these findings in an adolescent sample with bulimia nervosa (BN) from a randomized controlled trial and to examine the validity and reliability of this methodology. In the sample of BN adolescents (N=80), cluster analysis revealed a "dietary-depressive" subtype (37.5%) and a "dietary" subtype (62.5%) using the Beck Depression Inventory, Rosenberg Self-Esteem Scale and Eating Disorder Examination Restraint subscale. The "dietary-depressive" subtype compared to the "dietary" subtype was significantly more likely to: (1) report co-occurring disorders, (2) greater eating and weight concerns, and (3) less vomiting abstinence at post-treatment (all p'sreliability of the subtyping scheme, a larger sample of adolescents with mixed eating and weight disorders in an outpatient eating disorder clinic (N=149) was subtyped, yielding similar subtypes. These results support the validity and reliability of the subtyping strategy in two adolescent samples.

  8. Exploring transcriptional signalling mediated by OsWRKY13, a potential regulator of multiple physiological processes in rice

    Directory of Open Access Journals (Sweden)

    Li Xianghua

    2009-06-01

    Full Text Available Abstract Background Rice transcription regulator OsWRKY13 influences the functioning of more than 500 genes in multiple signalling pathways, with roles in disease resistance, redox homeostasis, abiotic stress responses, and development. Results To determine the putative transcriptional regulation mechanism of OsWRKY13, the putative cis-acting elements of OsWRKY13-influenced genes were analyzed using the whole genome expression profiling of OsWRKY13-activated plants generated with the Affymetrix GeneChip Rice Genome Array. At least 39 transcription factor genes were influenced by OsWRKY13, and 30 of them were downregulated. The promoters of OsWRKY13-upregulated genes were overrepresented with W-boxes for WRKY protein binding, whereas the promoters of OsWRKY13-downregulated genes were enriched with cis-elements putatively for binding of MYB and AP2/EREBP types of transcription factors. Consistent with the distinctive distribution of these cis-elements in up- and downregulated genes, nine WRKY genes were influenced by OsWRKY13 and the promoters of five of them were bound by OsWRKY13 in vitro; all seven differentially expressed AP2/EREBP genes and six of the seven differentially expressed MYB genes were suppressed by in OsWRKY13-activated plants. A subset of OsWRKY13-influenced WRKY genes were involved in host-pathogen interactions. Conclusion These results suggest that OsWRKY13-mediated signalling pathways are partitioned by different transcription factors. WRKY proteins may play important roles in the monitoring of OsWRKY13-upregulated genes and genes involved in pathogen-induced defence responses, whereas MYB and AP2/EREBP proteins may contribute most to the control of OsWRKY13-downregulated genes.

  9. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

    International Nuclear Information System (INIS)

    Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

    1991-01-01

    The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

  10. Appreciating HIV-1 diversity: subtypic differences in ENV

    Energy Technology Data Exchange (ETDEWEB)

    Gnanakaran, S [Los Alamos National Laboratory; Shen, Tongye [Los Alamos National Laboratory; Lynch, Rebecca M [NON LANL; Derdeyn, Cynthia A [NON LANL

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) group M is responsible for the current AIDS pandemic and exhibits exceedingly high levels of viral genetic diversity around the world, necessitating categorization of viruses into distinct lineages, or subtypes. These subtypes can differ by around 35% in the envelope (Env) glycoproteins of the virus, which are displayed on the surface of the virion and are targets for both neutralizing antibody and cell-mediated immune responses. This diversity reflects the remarkable ability of the virus to adapt to selective pressures, the bulk of which is applied by the host immune response, and represents a serious obstacle for developing an effective vaccine with broad coverage. Thus, it is important to understand the underlying biological consequences of inter-subtype diversity. Recent studies have revealed that the HIV-1 subtypes exhibit phenotypic differences that result from subtle differences in Env structure, particularly within the highly immunogenic V3 domain, which participates directly in viral entry. This review will therefore explore current research that describes subtypic differences in Env at the genetic and phenotypic level, focusing in particular on V3, and highlighting recent discoveries about the unique features of subtype C Env, which is the most prevalent subtype globally.

  11. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress.

    Science.gov (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  12. Transcriptome classification reveals molecular subtypes in psoriasis

    Directory of Open Access Journals (Sweden)

    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  13. Ocean acidification stimulates alkali signal pathway: A bicarbonate sensing soluble adenylyl cyclase from oyster Crassostrea gigas mediates physiological changes induced by CO2 exposure.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Wang, Hao; Jiang, Shuai; Chen, Hao; Wang, Lingling; Song, Linsheng

    2016-12-01

    Ocean acidification (OA) has been demonstrated to have severe effects on marine organisms, especially marine calcifiers. However, the impacts of OA on the physiology of marine calcifiers and the underlying mechanisms remain unclear. Soluble adenylyl cyclase (sAC) is an acid-base sensor in response to [HCO 3 - ] and an intracellular source of cyclic AMP (cAMP). In the present study, an ortholog of sAC was identified from pacific oyster Crassostrea gigas (designated as CgsAC) and the catalytic region of CgsAC was cloned and expressed. Similar to the native CgsAC from gill tissues, the recombinant CgsAC protein (rCgsAC) exhibited [HCO 3 - ] mediated cAMP-forming activity, which could be inhibited by a small molecule KH7. After 16days of CO 2 exposure (pH=7.50), the mRNA transcripts of CgsAC increased in muscle, mantle, hepatopancreas, gill, male gonad and haemocytes, and two truncated CgsAC forms of 45kD and 20kD were produced. Cytosolic CgsAC could be translocated from the cytoplasm and nuclei to the membrane in response to CO 2 exposure. Besides, CO 2 exposure could increase the production of cAMP and intracellular pH of haemocytes, which was regulated by CgsAC (pocean acidification on marine calcifiers. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Pure type systems with subtyping

    NARCIS (Netherlands)

    Zwanenburg, J.; Girard, J.-Y.

    1999-01-01

    We extend the framework of Pure Type Systems with subtyping, as found in F = ¿ . This leads to a concise description of many existing systems with subtyping, and also to some new interesting systems. We develop the meta-theory for this framework, including Subject Reduction and Minimal Typing. The

  15. Cockroach GABAB receptor subtypes: molecular characterization, pharmacological properties and tissue distribution.

    Science.gov (United States)

    Blankenburg, S; Balfanz, S; Hayashi, Y; Shigenobu, S; Miura, T; Baumann, O; Baumann, A; Blenau, W

    2015-01-01

    γ-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the central nervous system (CNS). Its effects are mediated by either ionotropic GABAA receptors or metabotropic GABAB receptors. GABAB receptors regulate, via Gi/o G-proteins, ion channels, and adenylyl cyclases. In humans, GABAB receptor subtypes are involved in the etiology of neurologic and psychiatric disorders. In arthropods, however, these members of the G-protein-coupled receptor family are only inadequately characterized. Interestingly, physiological data have revealed important functions of GABAB receptors in the American cockroach, Periplaneta americana. We have cloned cDNAs coding for putative GABAB receptor subtypes 1 and 2 of P. americana (PeaGB1 and PeaGB2). When both receptor proteins are co-expressed in mammalian cells, activation of the receptor heteromer with GABA leads to a dose-dependent decrease in cAMP production. The pharmacological profile differs from that of mammalian and Drosophila GABAB receptors. Western blot analyses with polyclonal antibodies have revealed the expression of PeaGB1 and PeaGB2 in the CNS of the American cockroach. In addition to the widespread distribution in the brain, PeaGB1 is expressed in salivary glands and male accessory glands. Notably, PeaGB1-like immunoreactivity has been detected in the GABAergic salivary neuron 2, suggesting that GABAB receptors act as autoreceptors in this neuron. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  17. Pulmonary emphysema subtypes on computed tomography: the MESA COPD study.

    Science.gov (United States)

    Smith, Benjamin M; Austin, John H M; Newell, John D; D'Souza, Belinda M; Rozenshtein, Anna; Hoffman, Eric A; Ahmed, Firas; Barr, R Graham

    2014-01-01

    Pulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ≥ 10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Twenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P emphysema, was associated with reduced body mass index (-5 kg/m(2); P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Pulmonary Emphysema Subtypes on Computed Tomography in Smokers

    Science.gov (United States)

    Smith, Benjamin M.; Austin, John H.M.; Newell, John D.; D’Souza, Belinda M.; Rozenshtein, Anna; Hoffman, Eric A.; Ahmed, Firas; Barr, R. Graham

    2013-01-01

    Background Pulmonary emphysema is divided into three major subtypes at autopsy: centrilobular, paraseptal and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well-defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. Methods The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years with ≥10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Results Twenty-seven percent of 318 smokers had emphysema on CT. Inter-rater reliability of emphysema subtype was substantial (K:0.70). Compared to participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with PSE were similar to controls, except for male predominance. Centrilobular but not panlobular or paraseptal emphysema was associated with greater smoking history (+21 pack-years Pemphysema was associated with reduced body mass index (−5 kg/m2;P=0.01). Other than for dyspnea, these findings were independent of the forced expiratory volume in one second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Conclusions Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema but not paraseptal emphysema have considerable symptomatic and physiological consequences. PMID:24384106

  19. Rice Physiology

    Science.gov (United States)

    P.A. Counce; Davidi R. Gealy; Shi-Jean Susana Sung

    2002-01-01

    Physiology occurs tn physical space through chemical reactions constrained by anatomy and morphology, yet guided by genetics. Physiology has been called the logic of life. Genes encode structural and fimcdonal proteins. These proteins are subsequently processed to produce enzymes that direct and govern the biomechanical processes involved in the physiology of the...

  20. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  1. Motor subtype changes in early Parkinson's disease.

    Science.gov (United States)

    Eisinger, Robert S; Hess, Christopher W; Martinez-Ramirez, Daniel; Almeida, Leonardo; Foote, Kelly D; Okun, Michael S; Gunduz, Aysegul

    2017-10-01

    Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Classification of alpha 1-adrenoceptor subtypes

    NARCIS (Netherlands)

    Michel, M. C.; Kenny, B.; Schwinn, D. A.

    1995-01-01

    Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been detected in various tissues by pharmacological techniques, and three distinct cDNAs encoding alpha 1-adrenoceptor subtypes have been cloned. The profile of an increasing number of subtype-selective compounds at cloned and endogenous

  3. Subtypes of nonmedical prescription drug misuse

    Science.gov (United States)

    McCabe, Sean Esteban; Boyd, Carol J.; Teter, Christian J.

    2010-01-01

    This study used three characteristics (i.e., motive, route of administration, and co-ingestion with alcohol) of nonmedical prescription drug misuse across four separate classes (i.e., pain, sedative/anxiety, sleeping and stimulant medications) to examine subtypes and drug related problems. A Web survey was self-administered by a randomly selected sample of 3,639 undergraduate students attending a large Midwestern 4-year U.S. university. Self-treatment subtypes were characterized by motives consistent with the prescription drug's pharmaceutical main indication, oral only routes of administration, and no co-ingestion with alcohol. Recreational subtypes were characterized by recreational motives, oral or non-oral routes, and co-ingestion. Mixed subtypes consisted of other combinations of motives, routes, and co-ingestion. Among those who reported nonmedical prescription drug misuse, approximately 13% were classified into the recreational subtype, while 39% were in the self-treatment subtype, and 48% were in the mixed subtype. There were significant differences in the subtypes in terms of gender, race and prescription drug class. Approximately 50% of those in subtypes other than self-treatment screened positive for drug abuse. The odds of substance use and abuse were generally lower among self-treatment subtypes than other subtypes. The findings indicate subtypes should be considered when examining nonmedical prescription drug misuse, especially for pain medication. PMID:19278795

  4. Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

    Science.gov (United States)

    Santollo, Jessica; Daniels, Derek

    2015-12-01

    Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood. An obvious step toward addressing this open question is identifying which estrogen receptor subtypes are involved and what intracellular processes are involved. This question, however, is complicated not only by the variety of estrogen receptor subtypes that exist, but also because many subtypes have multiple locations of action (i.e. in the nucleus or in the plasma membrane). This review will highlight our current understanding of the roles that specific estrogen receptor subtypes play in mediating estradiol's anorexigenic and anti-dipsogenic effects along with highlighting the many open questions that remain. This review will also describe recent work being performed by our laboratory aimed at answering these open questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Gene specific actions of thyroid hormone receptor subtypes.

    Directory of Open Access Journals (Sweden)

    Jean Z Lin

    Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

  6. Plant physiological responses to hydrologically mediated changes in nitrogen supply on a boreal forest floodplain: a mechanism explaining the discrepancy in nitrogen demand and supply

    Science.gov (United States)

    Lina Koyama; Knut. Kielland

    2011-01-01

    A discrepancy between plant demand and soil supply of nitrogen (N) has been observed in early successional stages of riparian vegetation in interior Alaska. We hypothesized that a hydrologically mediated N supply serves as a mechanism to balance this apparent deficiency of plant N supply. To test this hypothesis, we conducted a tracer experiment and measured the...

  7. Diabetes and Breast Cancer Subtypes.

    Directory of Open Access Journals (Sweden)

    Heleen K Bronsveld

    Full Text Available Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes.This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years, women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR, HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211 and women without diabetes (n = 101, irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55, HER2-negative (OR = 2.84(95%CI:1.11-7.22, and basal-like (OR = 3.14(95%CI:1.03-9.60 tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45 and triple negative (OR = 2.60(95%CI:0.88-7.67 tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general.We found no compelling evidence that women with diabetes

  8. Diabetes and Breast Cancer Subtypes.

    Science.gov (United States)

    Bronsveld, Heleen K; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersen, Morten; Vestergaard, Peter; Schmidt, Marjanka K

    2017-01-01

    Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55)), HER2-negative (OR = 2.84(95%CI:1.11-7.22)), and basal-like (OR = 3.14(95%CI:1.03-9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45)) and triple negative (OR = 2.60(95%CI:0.88-7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general. We found no compelling evidence that women with diabetes, treated

  9. The tremorolytic action of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is mediated by beta-adrenoceptors located in a deep peripheral compartment.

    Science.gov (United States)

    Abila, B; Wilson, J F; Marshall, R W; Richens, A

    1985-10-01

    The effects of intravenous propranolol 100 micrograms kg-1, sotalol 500 micrograms kg-1, timolol 7.8 micrograms kg-1, atenolol 125 micrograms kg-1 and placebo on essential, physiological and isoprenaline-induced tremor were studied. These beta-adrenoceptor blocker doses produced equal reduction of standing-induced tachycardia in essential tremor patients. Atenolol produced significantly less reduction of essential and isoprenaline-induced tremor than the non-selective drugs, confirming the importance of beta 2-adrenoceptor blockade in these effects. Propranolol and sotalol produced equal maximal inhibition of isoprenaline-induced tremor but propranolol was significantly more effective in reducing essential tremor. The rate of development of the tremorolytic effect was similar in essential, physiological and isoprenaline-induced tremors but all tremor responses developed significantly more slowly than the heart rate responses. It is proposed that these results indicate that the tremorolytic activity of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is exerted via the same beta 2-adrenoceptors located in a deep peripheral compartment which is thought to be in the muscle spindles.

  10. Motoric subtypes of delirium in geriatric patients

    Directory of Open Access Journals (Sweden)

    Sandeep Grover

    2014-01-01

    Results: On amended DMSS, hyperactive subtype (N = 45; 45.9% was the most common motoric subtype of delirium, followed by hypoactive subtype (N = 23; 23.5%, and mixed subtype (N = 21; 21.4%. On DRS-R-98, all patients fulfilled the criteria of ′acute (temporal onset of symptoms′, ′presence of an underlying physical disorder′ and ′difficulty in attention′. In the total sample, >90% of the patients had disturbances in sleep-wake cycle, orientation and fluctuation of symptoms. The least common symptoms were delusions, visuospatial disturbances and motor retardation. When compared to hypoactive group, significantly higher proportion of patients with hyperactive subtype had delusions, perceptual disturbances, and motor agitation. Whereas, compared to hyperactive subtype, significantly higher proportion of patients with hypoactive subtype had thought process abnormality and motor retardation. When the hyperactive and mixed motoric subtype groups were compared, patients with mixed subtype group had significantly higher prevalence of thought process abnormality and motor retardation. Comparison of hypoactive and mixed subtype revealed significant differences in the frequency of perceptual disturbances, delusions and motor agitation and all these symptoms being found more commonly in patients with the mixed subtype. Severity of symptoms were found to be significantly different across the various motoric subtypes for some of the non-cognitive symptoms, but significant differences were not seen for the cognitive symptoms as assessed on DRS-R-98. Conclusion: In elderly patients, motor subtypes of delirium differ from each other on non-cognitive symptom profile in terms of frequency and severity.

  11. Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes.

    Science.gov (United States)

    Avula, Leela Rani; Buckinx, Roeland; Favoreel, Herman; Cox, Eric; Adriaensen, Dirk; Van Nassauw, Luc; Timmermans, Jean-Pierre

    2013-05-01

    Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and

  12. Physiological parameters

    International Nuclear Information System (INIS)

    Natera, E.S.

    1998-01-01

    The physiological characteristics of man depend on the intake, metabolism and excretion of stable elements from food, water, and air. The physiological behavior of natural radionuclides and radionuclides from nuclear weapons testing and from the utilization of nuclear energy is believed to follow the pattern of stable elements. Hence information on the normal physiological processes occurring in the human body plays an important role in the assessment of the radiation dose received by man. Two important physiological parameters needed for internal dose determination are the pulmonary function and the water balance. In the Coordinated Research Programme on the characterization of Asian population, five participants submitted data on these physiological characteristics - China, India, Japan, Philippines and Viet Nam. During the CRP, data on other pertinent characteristics such as physical and dietary were simultaneously being collected. Hence, the information on the physiological characteristics alone, coming from the five participants were not complete and are probably not sufficient to establish standard values for the Reference Asian Man. Nonetheless, the data collected is a valuable contribution to this research programme

  13. Identification of cDNA encoding an additional α subunit of a human GTP-binding protein: Expression of three αi subtypes in human tissues and cell lines

    International Nuclear Information System (INIS)

    Kim, S.; Ang, S.L.; Bloch, D.B.; Bloch, K.D.; Kawahara, Y.; Tolman, C.; Lee, R.; Seidman, J.G.; Neer, E.J.

    1988-01-01

    The guanine nucleotide-binding proteins (G proteins), which mediate hormonal regulation of many membrane functions, are composed of α, β, and γ subunits. The authors have cloned and characterized cDNA from a human T-cell library encoding a form of α i that is different from the human α i subtypes previously reported. α i is the α subunit of a class of G proteins that inhibits adenylate cyclase and regulates other enzymes and ion channels. This cDNA encodes a polypeptide of 354 amino acids and is assigned to encode the α i-3 subtype of G proteins on the basis of its similarity to other α i -like cDNAs and the presence of a predicted site for ADP ribosylation by pertussis toxin. They have determined the expression of mRNA for this and two other subtypes of human α i (α i-1 and α i-2 ) in a variety of human fetal tissues and in human cell lines. All three α i subtypes were present in the tissues tested. However, analysis of individual cell types reveals specificity of α i-1 expression. mRNA for α i-1 is absent in T cells, B cells, and monocytes but is present in other cell lines. The finding of differential expression of α i-1 genes may permit characterization of distinct physiological roles for this α i subunit. mRNA for α i-2 and α i-3 was found in all the primary and transformed cell lines tested. Thus, some cells contain all three α i subtypes. This observation raises the question of how cells prevent cross talk among receptors that are coupled to effectors through such similar α proteins

  14. Hypertension Subtypes among Hypertensive Patients in Ibadan

    OpenAIRE

    Abiodun M. Adeoye; Adewole Adebiyi; Bamidele O. Tayo; Babatunde L. Salako; Adesola Ogunniyi; Richard S. Cooper

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% fema...

  15. P-glycoprotein mediated efflux limits the transport of the novel anti-Parkinson's disease candidate drug FLZ across the physiological and PD pathological in vitro BBB models.

    Directory of Open Access Journals (Sweden)

    Qian Liu

    Full Text Available FLZ, a novel anti-Parkinson's disease (PD candidate drug, has shown poor blood-brain barrier (BBB penetration based on the pharmacokinetic study using rat brain. P-glycoprotein (P-gp and breast cancer resistance protein (BCRP are two important transporters obstructing substrates entry into the CNS as well as in relation to PD neuropathology. However, it is unclear whether P-gp and BCRP are involved in low BBB permeability of FLZ and what the differences of FLZ brain penetration are between normal and Parkinson's conditions. For this purpose, in vitro BBB models mimicking physiological and PD pathological-related BBB properties were constructed by C6 astroglial cells co-cultured with primary normal or PD rat cerebral microvessel endothelial cells (rCMECs and in vitro permeability experiments of FLZ were carried out. High transepithelial electrical resistance (TEER and low permeability for sodium fluorescein (NaF confirmed the BBB functionality of the two models. Significantly greater expressions of P-gp and BCRP were detected in PD rCMECs associated with the lower in vitro BBB permeability of FLZ in pathological BBB model compared with physiological model. In transport studies only P-gp blocker effectively inhibited the efflux of FLZ, which was consistent with the in vivo permeability data. This result was also confirmed by ATPase assays, suggesting FLZ is a substrate for P-gp but not BCRP. The present study first established in vitro BBB models reproducing PD-related changes of BBB functions in vivo and demonstrated that poor brain penetration of FLZ and low BBB permeability were due to the P-gp transport.

  16. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  17. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  18. Physiological pseudomyopia.

    Science.gov (United States)

    Jones, R

    1990-08-01

    Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia.

  19. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.

    Science.gov (United States)

    Light, Alan R; Hughen, Ronald W; Zhang, Jie; Rainier, Jon; Liu, Zhuqing; Lee, Jeewoo

    2008-09-01

    The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

  20. Several Hfq-dependent alterations in physiology of Yersinia enterocolitica O:3 are mediated by derepression of the transcriptional regulator RovM.

    Science.gov (United States)

    Leskinen, Katarzyna; Pajunen, Maria I; Varjosalo, Markku; Fernández-Carrasco, Helena; Bengoechea, José A; Skurnik, Mikael

    2017-03-01

    In bacteria, the RNA chaperone Hfq enables pairing of small regulatory RNAs with their target mRNAs and therefore is a key player of post-transcriptional regulation network. As a global regulator, Hfq is engaged in the adaptation to external environment, regulation of metabolism and bacterial virulence. In this study we used RNA-sequencing and quantitative proteomics (LC-MS/MS) to elucidate the role of this chaperone in the physiology and virulence of Yersinia enterocolitica serotype O:3. This global approach revealed the profound impact of Hfq on gene and protein expression. Furthermore, the role of Hfq in the cell morphology, metabolism, cell wall integrity, resistance to external stresses and pathogenicity was evaluated. Importantly, our results revealed that several alterations typical for the hfq-negative phenotype were due to derepression of the transcriptional factor RovM. The overexpression of RovM caused by the loss of Hfq chaperone resulted in extended growth defect, alterations in the lipid A structure, motility and biofilm formation defects, as well as changes in mannitol utilization. Furthermore, in Y. enterocolitica RovM only in the presence of Hfq affected the abundance of RpoS. Finally, the impact of hfq and rovM mutations on the virulence was assessed in the mouse infection model. © 2016 John Wiley & Sons Ltd.

  1. Ruminative subtypes and impulsivity in risk for suicidal behavior.

    Science.gov (United States)

    Valderrama, Jorge; Miranda, Regina; Jeglic, Elizabeth

    2016-02-28

    Rumination has been previously linked to negative psychological outcomes, including depression and suicidal behavior. However, there has been conflicting research on whether or not two different subtypes of rumination - brooding and reflection - are more or less maladaptive. The present research sought to (1) examine whether individuals high in brooding but lower in reflection would show higher trait and behavioral impulsivity, relative to individuals low in brooding and low in reflection; and (2) examine impulsivity as a mediator of the relation between ruminative subtypes and suicidal ideation. In Study 1, participants (N=78) were recruited based on high, average, and low scores on a measure of brooding and reflective rumination. Individuals who scored high in brooding and average in reflection scored significantly higher in negative urgency, that is, in the tendency to act rashly in an attempt to reduce negative affect, than did those who scored low in brooding and low in reflection. Study 2 (N=1638) examined the relationship between ruminative subtypes, impulsivity, and suicide risk. We found an indirect relationship between brooding and suicide risk through lack of premeditation and lack of perseverance, independently of reflection. These findings are discussed in relation to cognitive risk for suicide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  3. Transsexual subtypes : Clinical and theoretical significance

    NARCIS (Netherlands)

    Smith, YLS; van Goozen, SHM; Kuiper, AJ; Cohen-Kettenis, PT

    2005-01-01

    The present study was designed to investigate whether transsexuals can be validly subdivided into subtypes on the basis of sexual orientation, and whether differences between subtypes of transsexuals are similar for male-to-female (ME) and female-to-male transsexuals (FMs). Within a large

  4. Environmental physiology

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Summaries of research projects conducted during 1978 and 1979 are presented. Subject areas include: the effects of environmental pollutants on homeostasis of the hematopoietic system; pollutant effects on steroid metabolism; pollutant effects on pulmonary macrophages; effects of toxic gases on lung cells; the development of immunological methods for assessing lung damage at the cellular level; the response of erythropoietin concentration to various physiological changes; and the study of actinide metabolism in monkey skeletons

  5. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  6. Resistance of Subtype C HIV-1 Strains to Anti-V3 Loop Antibodies

    Directory of Open Access Journals (Sweden)

    David Almond

    2012-01-01

    Full Text Available HIV-1’s subtype C V3 loop consensus sequence exhibits increased resistance to anti-V3 antibody-mediated neutralization as compared to the subtype B consensus sequence. The dynamic 3D structure of the consensus C V3 loop crown, visualized by ab initio folding, suggested that the resistance derives from structural rigidity and non-β-strand secondary protein structure in the N-terminal strand of the β-hairpin of the V3 loop crown, which is where most known anti-V3 loop antibodies bind. The observation of either rigidity or non-β-strand structure in this region correlated with observed resistance to antibody-mediated neutralization in a series of chimeric pseudovirus (psV mutants. The results suggest the presence of an epitope-independent, neutralization-relevant structural difference in the antibody-targeted region of the V3 loop crown between subtype C and subtype B, a difference that we hypothesize may contribute to the divergent pattern of global spread between these subtypes. As antibodies to a variable loop were recently identified as an inverse correlate of risk for HIV infection, the structure-function relationships discussed in this study may have relevance to HIV vaccine research.

  7. Molecular subtypes of Alzheimer's disease.

    Science.gov (United States)

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

    2018-02-19

    Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

  8. Verified Subtyping with Traits and Mixins

    Directory of Open Access Journals (Sweden)

    Asankhaya Sharma

    2014-07-01

    Full Text Available Traits allow decomposing programs into smaller parts and mixins are a form of composition that resemble multiple inheritance. Unfortunately, in the presence of traits, programming languages like Scala give up on subtyping relation between objects. In this paper, we present a method to check subtyping between objects based on entailment in separation logic. We implement our method as a domain specific language in Scala and apply it on the Scala standard library. We have verified that 67% of mixins used in the Scala standard library do indeed conform to subtyping between the traits that are used to build them.

  9. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  10. Intragroup emotions: physiological linkage and social presence

    Directory of Open Access Journals (Sweden)

    Simo eJärvelä

    2016-02-01

    Full Text Available We investigated how technologically mediating two different components of emotion – communicative expression and physiological state – to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression and visualization of group level physiological heart rates and their dyadic linkage (physiology was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member’s physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  11. Intragroup Emotions: Physiological Linkage and Social Presence.

    Science.gov (United States)

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    We investigated how technologically mediating two different components of emotion-communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  12. Intragroup Emotions: Physiological Linkage and Social Presence

    Science.gov (United States)

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

  13. The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses

    DEFF Research Database (Denmark)

    Guetg, Nicole; Seddik, Riad; Vigot, Réjan

    2009-01-01

    )) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce...... a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.......GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed...

  14. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Directory of Open Access Journals (Sweden)

    Abiodun M. Adeoye

    2014-01-01

    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  15. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  17. posttraumatic stress disorder: a theoretical model of the hyperarousal subtype

    Directory of Open Access Journals (Sweden)

    Charles Stewart Weston

    2014-04-01

    Full Text Available Posttraumatic stress disorder (PTSD is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC, and medial orbitofrontal cortex (mOFC, to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework

  18. Differential expression of muscarinic acetylcholine receptor subtypes in Jurkat cells and their signaling.

    Science.gov (United States)

    Alea, Mileidys Perez; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Fuxe, Kjell; Garriga, Pere

    2011-08-15

    Muscarinic acetylcholine receptors expression and signaling in the human Jurkat T cell line were investigated. Semiquantitative real-time PCR and radioligand binding studies, using a wide set of antagonist compounds, showed the co-existence of M(3), M(4), and M(5) subtypes. Stimulation of these subpopulations caused a concentration and time- dependent activation of second messengers and ERK signaling pathways, with a major contribution of the M(3) subtype in a G(q/11)-mediated response. In addition, we found that T-cell stimulation leads to increased expression of M(3) and M(5) both at transcriptional and protein levels in a PLC/PKCθ dependent manner. Our data clarifies the functional role of AChR subtypes in Jurkat cells and pave the way to future studies on the potential cross-talk among these subpopulations and their regulation of T lymphocytes immune function. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  20. Blockade of alcohol's amnestic activity in humans by an alpha5 subtype benzodiazepine receptor inverse agonist.

    Science.gov (United States)

    Nutt, David J; Besson, Marie; Wilson, Susan J; Dawson, Gerard R; Lingford-Hughes, Anne R

    2007-12-01

    Alcohol produces many subjective and objective effects in man including pleasure, sedation, anxiolysis, plus impaired eye movements and memory. In human volunteers we have used a newly available GABA-A/benzodiazepine receptor inverse agonist that is selective for the alpha5 subtype (a5IA) to evaluate the role of this subtype in mediating these effects of alcohol on the brain. After pre-treatment with a5IA, we found almost complete blockade of the marked impairment caused by alcohol (mean breath concentration 150mg/100ml) of word list learning and partial but non-significant reversal of subjective sedation without effects on other measures such as intoxication, liking, and slowing of eye movements. This action was not due to alterations in alcohol kinetics and so provides the first proof of concept that selectively decreasing GABA-A receptor function at a specific receptor subtype can offset some actions of alcohol in humans. It also supports growing evidence for a key role of the alpha5 subtype in memory. Inverse agonists at other GABA-A receptor subtypes may prove able to reverse other actions of alcohol, and so offer a new approach to understanding the actions of alcohol in the human brain and in the treatment of alcohol related disorders in humans.

  1. Precise subtyping for synchronous multiparty sessions

    Directory of Open Access Journals (Sweden)

    Mariangiola Dezani-Ciancaglini

    2016-02-01

    Full Text Available The notion of subtyping has gained an important role both in theoretical and applicative domains: in lambda and concurrent calculi as well as in programming languages. The soundness and the completeness, together referred to as the preciseness of subtyping, can be considered from two different points of view: operational and denotational. The former preciseness has been recently developed with respect to type safety, i.e. the safe replacement of a term of a smaller type when a term of a bigger type is expected. The latter preciseness is based on the denotation of a type which is a mathematical object that describes the meaning of the type in accordance with the denotations of other expressions from the language. The result of this paper is the operational and denotational preciseness of the subtyping for a synchronous multiparty session calculus. The novelty of this paper is the introduction of characteristic global types to prove the operational completeness.

  2. Antisocial personality disorder--stable and unstable subtypes.

    Science.gov (United States)

    Ullrich, Simone; Coid, Jeremy

    2010-04-01

    There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.

  3. Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

    Science.gov (United States)

    Rodgers, Stephanie; Vandeleur, Caroline L; Ajdacic-Gross, Vladeta; Aleksandrowicz, Aleksandra A; Strippoli, Marie-Pierre F; Castelao, Enrique; Glaus, Jennifer; Lasserre, Aurélie M; Müller, Mario; Rössler, Wulf; Angst, Jules; Preisig, Martin

    2016-01-15

    Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. The use of cross-sectional data does not allow causal conclusions. This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression.

    Science.gov (United States)

    Kiguoya, Marion W; Mann, Jaclyn K; Chopera, Denis; Gounder, Kamini; Lee, Guinevere Q; Hunt, Peter W; Martin, Jeffrey N; Ball, T Blake; Kimani, Joshua; Brumme, Zabrina L; Brockman, Mark A; Ndung'u, Thumbi

    2017-07-01

    HIV-1 Gag-protease-driven replication capacity correlates with the replication capacity of whole virus isolates. We further show that subtype B displays a significantly higher Gag-protease-mediated replication capacity than does subtype C, and we identify a major genetic determinant of these differences. Moreover, in two independent East African cohorts we demonstrate a reproducible hierarchy of Gag-protease-driven replicative capacity, whereby recombinants exhibit the greatest replication, followed by subtype D, followed by subtypes A and C. Our data identify Gag-protease as a major determinant of subtype differences in disease progression among HIV-1 subtypes; furthermore, we propose that the poorer viral replicative capacity of subtypes A and C may paradoxically contribute to their more efficient spread in sub-Saharan Africa. Copyright © 2017 American Society for Microbiology.

  5. Genetic contributions to subtypes of aggression

    NARCIS (Netherlands)

    Ligthart, R.S.L.; Bartels, M.; Hoekstra, R.A.; Hudziak, J.; Boomsma, D.I.

    2005-01-01

    Boys and girls may display different styles of aggression. The aim of this study was to identify subtypes of aggression within the Child Behavior Checklist (CBCL) aggression scale, and determine their characteristics for both sexes. Maternal CBCL ratings of 7449 7-year-old twin pairs were analyzed

  6. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv...

  7. Parkinson's disease motor subtypes and mood.

    Science.gov (United States)

    Burn, David J; Landau, Sabine; Hindle, John V; Samuel, Michael; Wilson, Kenneth C; Hurt, Catherine S; Brown, Richard G

    2012-03-01

    Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals. Copyright © 2011 Movement Disorder Society.

  8. Subtyping can have a simple semantics

    NARCIS (Netherlands)

    Balsters, H.; Fokkinga, M.M.

    1991-01-01

    Consider a first order typed language, with semantics $S$ for expressions and types. Adding subtyping means that a partial order $<$; on types is defined and that the typing rules are extended to the effect that expression $e$ has type $t$ whenever $e$ has type $s$ and $s

  9. Subtypes of children with attention disabilities.

    NARCIS (Netherlands)

    Brand, E.F.J.M.; Das-Smaal, E.A.; Jong, de P.F.

    1996-01-01

    Subtypes of children with attentional problems were investigated using cluster analysis. Subjects were 9-year-old-elementary school children (N = 443). The test battery administered to these children comprised a comprehensive set of common attention tests, covering different aspects of attentional

  10. Network Physiology: How Organ Systems Dynamically Interact.

    Science.gov (United States)

    Bartsch, Ronny P; Liu, Kang K L; Bashan, Amir; Ivanov, Plamen Ch

    2015-01-01

    We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems.

  11. Network Physiology: How Organ Systems Dynamically Interact

    Science.gov (United States)

    Bartsch, Ronny P.; Liu, Kang K. L.; Bashan, Amir; Ivanov, Plamen Ch.

    2015-01-01

    We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems. PMID:26555073

  12. Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure.

    Science.gov (United States)

    George, Jeffy; Mattapallil, Joseph J

    2018-01-01

    Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus. Interferon-α (IFN-α) is an innate cytokine that has been shown to activate intracellular defenses capable of restricting and controlling HIV. IFN-α, however, harbors numerous functional subtypes that have been reported to display different binding affinities and potency. Recent studies have suggested that certain subtypes such as IFN-α8 and IFN-α14 have potent anti-HIV activity with little or no immune activation, whereas other subtypes such as IFN-α4, IFN-α5, and IFN-α14 activate NK cells. Could these subtypes be used in combination with other strategies to reduce the latent viral reservoir? Here, we review the role of IFN-α subtypes in HIV infection and discuss the possibility that certain subtypes could be potential adjuncts to a "shock and kill" or therapeutic vaccination strategy leading to better control of the latent reservoir and subsequent functional cure.

  13. Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.

    Science.gov (United States)

    Sarvagalla, Sailu; Coumar, Mohane Selvaraj

    2015-01-01

    Aurora kinase A, B and C, are key regulators of mitosis and are over expressed in many of the human cancers, making them an ideal drug target for cancer chemotherapy. Currently, over a dozen of Aurora kinase inhibitors are in various phases of clinical development. The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective. Despite the intensive research efforts in the past decade, no Aurora kinase inhibitor has reached the market. Recent evidence suggests that the sub-type selective Aurora kinase A inhibitor could possess advantages over pan-selective Aurora inhibitors, by avoiding Aurora B mediated neutropenia. However, sub-type selective Aurora kinase A inhibitor design is very challenging due to the similarity in the active site among the isoforms. Structural biology and computational aspects pertaining to the design of Aurora kinase inhibitors were analyzed and found that a possible means to develop sub-type selective inhibitor is by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. Particularly, a useful strategy for the design of sub-type selective Aurora A inhibitor could be by targeting Thr217 residue as in the case of MLN8054. Further preclinical and clinical studies with the sub-type selective Aurora inhibitors could help bring them to the market for the treatment of cancer.

  14. Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

    Directory of Open Access Journals (Sweden)

    Mingshun Zhang

    Full Text Available Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

  15. Muscarinic acetylcholine receptor subtypes: localization and structure/function

    DEFF Research Database (Denmark)

    Brann, M R; Ellis, J; Jørgensen, H

    1993-01-01

    Based on the sequence of the five cloned muscarinic receptor subtypes (m1-m5), subtype selective antibody and cDNA probes have been prepared. Use of these probes has demonstrated that each of the five subtypes has a markedly distinct distribution within the brain and among peripheral tissues...... are described, as well as the implied structures of these functional domains....

  16. Subtypes of depression in cancer patients : An empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, Adelita V; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J

    PURPOSE: This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

  17. Subtypes of depression in cancer patients: an empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, A.V.; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J.

    2016-01-01

    Purpose This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

  18. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

    DEFF Research Database (Denmark)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

    2016-01-01

    studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian...

  19. Influence of childhood abuse and neglect subtypes on late-life suicide risk beyond depression.

    Science.gov (United States)

    Behr Gomes Jardim, Gabriel; Novelo, Marta; Spanemberg, Lucas; von Gunten, Armin; Engroff, Paula; Nogueira, Eduardo Lopes; Cataldo Neto, Alfredo

    2018-06-01

    The association of childhood maltreatment and suicide has been extensively examined within the population. Depression figures as a main cause for the elevated suicide rate in advanced ages and is often related to childhood maltreatment. The purpose of the present study was to examine the relationship between childhood maltreatment subtypes and suicide risk, testing geriatric depression as a moderator. This is a cross-sectional study looking at a sample of 449 individuals 60 year s old or older from the Multidimensional Study of the Elderly of Porto Alegre Family Health Strategy, Brazil (EMI-SUS/POA). Childhood maltreatment (Childhood Trauma Questionnaire), geriatric depressive symptoms (Geriatric Depression Scale), and suicide risk (Mini International Neuropsychiatric Interview) were assessed. The subtypes of childhood abuse and neglect were significantly associated with suicide risk. In the multivariate analysis, controlling for age, gender, income, marital status, ethnicity, smoking, and geriatric depression symptoms, all trauma subtypes remained associated with suicide risk with the exception of physical neglect (EA = 3.65; PA = 3.16; SA = 5.1; EN = 2.43; PN = 1.76). The present study showed that childhood maltreatment subtypes predicted suicide risk, and geriatric depression does not directly mediate this relation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

    Directory of Open Access Journals (Sweden)

    Miroslav M. Savic

    2005-01-01

    Full Text Available Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α5 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states.

  1. Comparison of symptoms of delirium across various motoric subtypes.

    Science.gov (United States)

    Grover, Sandeep; Sharma, Akhilesh; Aggarwal, Munish; Mattoo, Surendra K; Chakrabarti, Subho; Malhotra, Savita; Avasthi, Ajit; Kulhara, Parmanand; Basu, Debasish

    2014-04-01

    The aim of this study was to determine the correlation between delirium motor subtypes and other symptoms of delirium. Three hundred and twenty-one (n = 321) consecutive patients referred to consultation-liaison psychiatry services were evaluated on Delirium Rating scale-Revised-98 version and amended Delirium Motor Symptom Scale. Half of the patients had hyperactive subtype (n = 161; 50.15%) delirium. One-quarter of the study sample met the criteria for mixed subtype (n = 79; 24.61%), about one-fifth of the study sample met the criteria for hypoactive delirium subtype (n = 64; 19.93%), and only very few patients (n = 17; 5.29%) did not meet the required criteria for any of these three subtypes and were categorized as 'no subtype'. When the hyperactive and hypoactive subtypes were compared, significant differences were seen in the prevalence of perceptual disturbances, delusions, lability of affect, thought process abnormality, motor agitation and motor retardation. All the symptoms were more common in the hyperactive subtype except for thought process abnormality and motor retardation. Compared to hyperactive subtype, the mixed subtype had significantly higher prevalence of thought process abnormality and motor retardation. Significant differences emerged with regard to perceptual disturbances, delusions, lability of affect and motor agitation when comparing the patients with mixed subtype with those with hypoactive subtype. All these symptoms were found to be more common in the mixed subtype. No significant differences emerged for the cognitive symptoms as assessed on Delirium Rating scale-Revised-98 across the different motoric subtypes. Different motoric subtypes of delirium differ on non-cognitive symptoms. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  2. Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation

    KAUST Repository

    AbuElela, Ayman

    2017-12-01

    During tumor progression and development of distant metastases, a subset of cancer cells undergoes transformation programs, such as epithelial-mesenchymal transition (EMT), to acquire enhanced migratory attributes to commence the metastatic cascade with the intension of achieving an active cell adhesion molecule-mediated organ-specific homing. Similarly, naive T cells reform the assemblage of their surface adhesion molecules during differentiation to activated T cells in order to successfully home to sites of inflammation and other extra-lymphoid organs for surveillance purposes. Sialyl-Lewis X (sLex) is well-known for mediating the homing of epithelial circulating tumor cellss (CTCs) and activated T cells to target sites through the interaction with endothelial selectins. Since glycan structures are not directly encoded by the genome, their expression is dependent on the glycosyltransferase (GT) expression and activity. Yet, the modulation of GTs during breast cancer transformation and in different molecular subtypes is still unknown. In addition, although the regulation of GTs during T cell activation is well-understood, the regulation at the epigenetic level is lacking. O-glycan-type sLex expression and E-selectin binding under static and flow conditions varies among molecular subtypes of breast cancer and upon the induction of EMT which is linked to the expression patterns of GTs. GTs displayed a significant prognostic value of in the association with the patients\\' survival profiles and in the ability to predict the breast cancer molecular subtypes from the expression data of a random patient sample. Also, GTs were able to differentiate between tumor and their normal counterparts as well as cancer types and glioblastoma subtypes. On the other hand, we studied the regulation of GTs in human CD4+ memory T cells compared to the naive cells at the epigenetic level. Memory T cell subsets demonstrated differential chromatin accessibility and histone marks within

  3. A taxometric investigation of developmental dyslexia subtypes.

    Science.gov (United States)

    O'Brien, Beth A; Wolf, Maryanne; Lovett, Maureen W

    2012-02-01

    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with severe reading disorders. Latent characteristics of the sample are assessed in regard to posited subtypes with phonological deficits and naming speed deficits, thus extending prior work by addressing whether these deficits embody separate classes of individuals. Findings support separate taxa of dyslexia with and without phonological deficits. Different latent structure for naming speed deficits was found depending on the definitional criterion used to define dyslexia. Non-phonologically based forms of dyslexia showed particular difficulty with naming speed and reading fluency. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  5. Agonist discrimination between AMPA receptor subtypes

    DEFF Research Database (Denmark)

    Coquelle, T; Christensen, J K; Banke, T G

    2000-01-01

    The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H...

  6. Global DNA methylation of ischemic stroke subtypes.

    Directory of Open Access Journals (Sweden)

    Carolina Soriano-Tárraga

    Full Text Available Ischemic stroke (IS, a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA, small-artery disease (SAD, and cardio-aortic embolism (CE. A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204 were included, distributed across 3 IS subtypes: LAA (78/281, 59/204, SAD (97/281, 53/204, and CE (106/281, 89/204. In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

  7. Subtyping borderline personality disorder by suicidal behavior.

    Science.gov (United States)

    Soloff, Paul H; Chiappetta, Laurel

    2012-06-01

    Course and outcome of Borderline Personality Disorder (BPD) are favorable for the vast majority of patients; however, up to 10% die by suicide. This discrepancy begs the question of whether there is a high lethality subtype in BPD, defined by recurrent suicidal behavior and increasing attempt lethality over time. In a prospective, longitudinal study, we sought predictors of high lethality among repeat attempters, and defined clinical subtypes by applying trajectory analysis to consecutive lethality scores. Criteria-defined subjects with BPD were assessed using standardized instruments and followed longitudinally. Suicidal behavior was assessed on the Columbia Suicide History, Lethality Rating Scale, and Suicide Intent Scale. Variables discriminating single and repeat attempters were entered into logistic regression models to define predictors of high and low lethality attempts. Trajectory analysis using three attempt and five attempt models identified discrete patterns of Lethality Rating Scale scores. A high lethality trajectory was associated with inpatient recruitment, and poor psychosocial function, a low lethality trajectory with greater Negativism, Substance Use Disorders, Histrionic and/or Narcissistic PD co-morbidity. Illness severity, older age, and poor psychosocial function are characteristics of a poor prognosis subtype related to suicidal behavior.

  8. Expression of SPIG1 reveals development of a retinal ganglion cell subtype projecting to the medial terminal nucleus in the mouse.

    Directory of Open Access Journals (Sweden)

    Keisuke Yonehara

    Full Text Available Visual information is transmitted to the brain by roughly a dozen distinct types of retinal ganglion cells (RGCs defined by a characteristic morphology, physiology, and central projections. However, our understanding about how these parallel pathways develop is still in its infancy, because few molecular markers corresponding to individual RGC types are available. Previously, we reported a secretory protein, SPIG1 (clone name; D/Bsp120I #1, preferentially expressed in the dorsal region in the developing chick retina. Here, we generated knock-in mice to visualize SPIG1-expressing cells with green fluorescent protein. We found that the mouse retina is subdivided into two distinct domains for SPIG1 expression and SPIG1 effectively marks a unique subtype of the retinal ganglion cells during the neonatal period. SPIG1-positive RGCs in the dorsotemporal domain project to the dorsal lateral geniculate nucleus (dLGN, superior colliculus, and accessory optic system (AOS. In contrast, in the remaining region, here named the pan-ventronasal domain, SPIG1-positive cells form a regular mosaic and project exclusively to the medial terminal nucleus (MTN of the AOS that mediates the optokinetic nystagmus as early as P1. Their dendrites costratify with ON cholinergic amacrine strata in the inner plexiform layer as early as P3. These findings suggest that these SPIG1-positive cells are the ON direction selective ganglion cells (DSGCs. Moreover, the MTN-projecting cells in the pan-ventronasal domain are apparently composed of two distinct but interdependent regular mosaics depending on the presence or absence of SPIG1, indicating that they comprise two functionally distinct subtypes of the ON DSGCs. The formation of the regular mosaic appears to be commenced at the end of the prenatal stage and completed through the peak period of the cell death at P6. SPIG1 will thus serve as a useful molecular marker for future studies on the development and function of ON DSGCs.

  9. Molecular subtypes and imaging phenotypes of breast cancer

    International Nuclear Information System (INIS)

    Cho, Nariya

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

  10. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  11. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  12. Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection.

    Directory of Open Access Journals (Sweden)

    Kathrin Gibbert

    Full Text Available The innate immune response mediated by cells such as natural killer (NK cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-α11 during Friend retrovirus infection (FV significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-α11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-α11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-α11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-α11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-α11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-α11.

  13. Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

    Science.gov (United States)

    Cauli, Alberto; Mathieu, Alessandro; Tedeschi, Valentina; Caristi, Silvana; Sorrentino, Rosa; Böckmann, Rainer A.; Fiorillo, Maria Teresa

    2012-01-01

    The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype. PMID:22403718

  14. Nitric oxide: a physiologic messenger.

    Science.gov (United States)

    Lowenstein, C J; Dinerman, J L; Snyder, S H

    1994-02-01

    To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

  15. Differential appearance of placentomes and expression of prostaglandin H synthase type 2 in placentome subtypes after betamethasone treatment of sheep late in gestation.

    Science.gov (United States)

    Braun, T; Li, S; Moss, T J M; Connor, K L; Doherty, D A; Nitsos, I; Newnham, J P; Challis, J R G; Sloboda, D M

    2011-04-01

    Inappropriate fetal exposure to maternal glucocorticoid (GC) has been proposed as a mechanism for fetal programming where the effects of GC may be mediated by the placenta. However, the consequences of maternal GC on placental morphology and enzyme expression are unclear. We used betamethasone (BET) to determine effects on placentome subtype distribution and expression of prostaglandin H synthase type 2 (PGHS-2) enzyme. Pregnant sheep carrying male fetuses were randomized to receive injections of saline (n = 30) or one (104 days of gestation, (dG); n = 6), two (104, 111 dG; n = 6) or three (104, 111, 118 dG; n = 11) doses of BET (0.5 mg/kg). Placental tissue was collected prior to (75, 84, 101 dG), during (109, 116 dG) and after BET (122, 132, 146 dG). Total number of placentomes was not different between gestational ages. A- and B-subtypes were most affected by prenatal BET exposure; numbers of A-subtypes were increased and numbers of B-subtypes were decreased compared to controls at 116 dG. At term numbers of A-subtypes were lower after BET, but the weight range distribution was similar to controls. In controls, placental PGHS-2 protein levels increased with gestational age and PGHS-2 localized primarily to uninuclear trophoblast cells. After BET, PGHS-2 protein in C-subtypes at term was significantly increased compared to A-subtypes. Maternal BET treatment in late gestation affects the proportions of placentome subtypes and their differential expression of PGHS-2. Our data do not support previous hypotheses that A-subtypes develop into B-, C- and D-subtypes over the course of gestation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Allosteric ligands and their binding sites define γ-aminobutyric acid (GABA) type A receptor subtypes.

    Science.gov (United States)

    Olsen, Richard W

    2015-01-01

    GABAA receptors (GABA(A)Rs) mediate rapid inhibitory transmission in the brain. GABA(A)Rs are ligand-gated chloride ion channel proteins and exist in about a dozen or more heteropentameric subtypes exhibiting variable age and brain regional localization and thus participation in differing brain functions and diseases. GABA(A)Rs are also subject to modulation by several chemotypes of allosteric ligands that help define structure and function, including subtype definition. The channel blocker picrotoxin identified a noncompetitive channel blocker site in GABA(A)Rs. This ligand site is located in the transmembrane channel pore, whereas the GABA agonist site is in the extracellular domain at subunit interfaces, a site useful for low energy coupled conformational changes of the functional channel domain. Two classes of pharmacologically important allosteric modulatory ligand binding sites reside in the extracellular domain at modified agonist sites at other subunit interfaces: the benzodiazepine site and the high-affinity, relevant to intoxication, ethanol site. The benzodiazepine site is specific for certain GABA(A)R subtypes, mainly synaptic, while the ethanol site is found at a modified benzodiazepine site on different, extrasynaptic, subtypes. In the transmembrane domain are allosteric modulatory ligand sites for diverse chemotypes of general anesthetics: the volatile and intravenous agents, barbiturates, etomidate, propofol, long-chain alcohols, and neurosteroids. The last are endogenous positive allosteric modulators. X-ray crystal structures of prokaryotic and invertebrate pentameric ligand-gated ion channels, and the mammalian GABA(A)R protein, allow homology modeling of GABA(A)R subtypes with the various ligand sites located to suggest the structure and function of these proteins and their pharmacological modulation. © 2015 Elsevier Inc. All rights reserved.

  17. Subtype distribution of Blastocystis isolates from synanthropic and zoo animals and identification of a new subtype

    DEFF Research Database (Denmark)

    Stensvold, C. R.; Alfellani, M. A.; Nørskov-Lauritsen, S.

    2009-01-01

    Blastocystis isolates from 56 Danish synanthropic and zoo animals, 62 primates primarily from United Kingdom (UK) collections and 16 UK primate handlers were subtyped by PCR, sequencing and phylogenetic analysis. A new subtype (ST) from primates and artiodactyls was identified and designated...... infections from primates by their handlers had occurred in these cases. Data from published studies of non-human primates, other mammals and birds were collected and interpreted to generate a comprehensive overview on the ST distribution in such animals. On the basis of information on 438 samples...

  18. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  19. Immunohistochemical visualization of mouse interneuron subtypes

    DEFF Research Database (Denmark)

    Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon

    2014-01-01

    , and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies...... of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location...

  20. Avian metapneumovirus subtype A in China and subtypes A and B in Nigeria.

    Science.gov (United States)

    Owoade, A A; Ducatez, M F; Hübschen, J M; Sausy, A; Chen, H; Guan, Y; Muller, C P

    2008-09-01

    In order to detect and characterize avian metapneumovirus, organs or swabs were collected from 697 chicken and 110 turkeys from commercial farms in Southwestern Nigeria and from 107 chickens from live bird markets in Southeastern China. In Nigeria, 15% and 6% of the chicken and turkey samples, respectively, and 39% of the chicken samples from China, were positive for aMPV genome by PCR. The sequence of a 400 nt fragment of the attachment protein gene (G gene) revealed the presence of aMPV subtype A in both Nigeria and Southeastern China. Essentially identical subtype A viruses were found in both countries and were also previously reported from Brazil and the United Kingdom, suggesting a link between these countries or a common source of this subtype. In Nigeria, subtype B was also found, which may be a reflection of chicken importations from most major poultry-producing countries in Europe and Asia. In order to justify countermeasures, further studies are warranted to better understand the metapneumoviruses and their impact on poultry production.

  1. Chewing Over Physiology Integration

    Science.gov (United States)

    Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

    2005-01-01

    An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

  2. Plant Physiology in Greenhouses

    NARCIS (Netherlands)

    Heuvelink, E.; Kierkels, T.

    2015-01-01

    Since 2004 Ep Heuvelink and Tijs Kierkels have been writing a continuing series of plant physiology articles for the Dutch horticultural journal Onder Glas and the international edition In Greenhouses. The book Plant Physiology in Greenhouses consists of 50 of their plant physiology articles. The

  3. Liposarcoma : MR findings in the histologic subtypes

    International Nuclear Information System (INIS)

    Lee, Jeong Hoon; Sohn, Jeong Eun; Chung, Soo Jeong; Kim, Kie Hwan; Chin, Soo Yil

    1999-01-01

    To evaluate the MR imaging findings of liposarcomas of different histologic subtypes. We evaluated MR images of 21 patients (5 men and 16 women, mean age, 55 years) with liposarcoma and correlated the findings with the results of histopathology. In the study group seven liposarcomas were well-differentiated, seven were myxoid, three were mixed, two were pleomorphic, and one was round cell. On T1-and T2-weighted images, six of seven well-differentiated liposarcomas showed signal intensity equal to the fat and hypointense septa, while the other showed low signal intensity on a T1-weighted image, heterogeneous high signal intensity on a T2-weighted image, heterogeneous enhancement after the administration of contrast media and was dedifferentiate. Nine masses in seven patients with myxoid liposarcoma showed low signal intensity on T1-weighted images, six of the nine showed lace-like foci of high signal intensity. On T2-weighted images, all masses showed homogeneous high signal intensity. After administration of contrast media, five of seven masses showed heterogeneous enhancement. Two of three mixed form were well-differentiated and myxoid types, and two subtypes were separable on MR. Pleomorphic, round cell, mixed type myxoid and pleomorphic and unclassified cases showed low signal intensity on T1-weighted images, heterogeneous high signal intensity on T2-weighted and heterogeneous enhancement. Using MR imaging, well-differentiated and myxoid liposcarcomas may be differentiated from other types

  4. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Rostgaard, K; Glaser, S L

    2013-01-01

    The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes....

  5. Salmonella source attribution based on microbial subtyping

    DEFF Research Database (Denmark)

    Barco, Lisa; Barrucci, Federica; Olsen, John Elmerdahl

    2013-01-01

    Source attribution of cases of food-borne disease represents a valuable tool for identifying and prioritizing effective food-safety interventions. Microbial subtyping is one of the most common methods to infer potential sources of human food-borne infections. So far, Salmonella microbial subtyping...... source attribution through microbial subtyping approach. It summarizes the available microbial subtyping attribution models and discusses the use of conventional phenotypic typing methods, as well as of the most commonly applied molecular typing methods in the European Union (EU) laboratories...

  6. Doppler radar physiological sensing

    CERN Document Server

    Lubecke, Victor M; Droitcour, Amy D; Park, Byung-Kwon; Singh, Aditya

    2016-01-01

    Presents a comprehensive description of the theory and practical implementation of Doppler radar-based physiological monitoring. This book includes an overview of current physiological monitoring techniques and explains the fundamental technology used in remote non-contact monitoring methods. Basic radio wave propagation and radar principles are introduced along with the fundamentals of physiological motion and measurement. Specific design and implementation considerations for physiological monitoring radar systems are then discussed in detail. The authors address current research and commercial development of Doppler radar based physiological monitoring for healthcare and other applications.

  7. Physiological stress reactivity in human pregnancy--a review.

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary

  8. Physiological stress reactivity in human pregnancy - a review

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary

  9. Molecular Subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal▿

    Science.gov (United States)

    Castro, R.; Prieto, E.; Águas, M. J.; Manata, M. J.; Botas, J.; Martins Pereira, F.

    2009-01-01

    The objectives of this study were to evaluate the reproducibility of a molecular method for the subtyping of Treponema pallidum subsp. pallidum and to discriminate strains of this microorganism from strains from patients with syphilis. We studied 212 specimens from a total of 82 patients with different stages of syphilis (14 primary, 7 secondary and 61 latent syphilis). The specimens were distributed as follows: genital ulcers (n = 9), skin and mucosal lesions (n = 7), blood (n = 82), plasma (n = 82), and ear lobe scrapings (n = 32). The samples were assayed by a PCR technique to amplify a segment of the polymerase gene I (polA). Positive samples were typed on the basis of the analysis of two variable genes, tpr and arp. Sixty-two of the 90 samples positive for polA yielded typeable Treponema pallidum DNA. All skin lesions in which T. pallidum was identified (six of six [100%]) were found to contain enough DNA for typing of the organism. It was also possible to type DNA from 7/9 (77.7%) genital ulcer samples, 13/22 (59.1%) blood samples, 20/32 (62.5%) plasma samples, and 16/21 (76.2%) ear lobe scrapings. The same subtype was identified in all samples from the same patient. Five molecular subtypes (subtypes 10a, 14a, 14c, 14f, and 14g) were identified, with the most frequently found subtype being subtype 14a and the least frequently found subtype being subtype 10a. In conclusion, the subtyping technique used in this study seems to have good reproducibility. To our knowledge, subtype 10a was identified for the first time. Further studies are needed to explain the presence of this subtype in Portugal, namely, its relationship to the Treponema pallidum strains circulating in the African countries where Portuguese is spoken. PMID:19494073

  10. Difference of achalasia subtypes based on clinical symptoms, radiographic findings, and stasis scores

    Directory of Open Access Journals (Sweden)

    A. Meillier

    2018-01-01

    Conclusions: Achalasia subtypes had similar clinical symptoms, except for increased vomiting severity in subtype i. The maximum esophageal diameter in subtype ii was significantly greater than in subtype iii. Esophageal stasis scores were similar. Thus, high-resolution esophageal manometry remains essential in assessing achalasia subtypes.

  11. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  12. Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

    Science.gov (United States)

    Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

    2016-01-01

    The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

  13. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

    van Hoeken, Daphne; Veling, Wim; Sinke, Sjoukje; Mitchell, James E.; Hoek, Hans W.

    Objective: To review the evidence for the validity and utility of subtyping bulimia nervosa (BN) into a purging (BN-P) and a nonpurging subtype (BN-NP), and of distinguishing BN-NP from binge eating disorder (BED), by comparing course, complications, and treatment. Method: A literature search of

  14. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

    van Hoeken, Daphne; Veling, Wim; Sinke, Sjoukje; Mitchell, James E.; Hoek, Hans W.

    2009-01-01

    Objective: To review the evidence for the validity and utility of subtyping bulimia nervosa (BN) into a purging (BN-P) and a nonpurging subtype (BN-NP), and of distinguishing BN-NP from binge eating disorder (BED), by comparing course, complications, and treatment. Method: A literature search of

  15. ADHD subtype differences in reinforcement sensitivity and visuospatial working memory

    NARCIS (Netherlands)

    Dovis, S.; van der Oord, S.; Wiers, R.W.; Prins, P.J.M.

    2015-01-01

    Both cognitive and motivational deficits are thought to give rise to the problems in the combined (ADHD-C) and inattentive subtype (ADHD-I) of attention-deficit hyperactivity disorder (ADHD). In both subtypes one of the most prominent cognitive weaknesses appears to be in visuospatial working memory

  16. The Association between Physical Morbidity and Subtypes of Severe Depression

    DEFF Research Database (Denmark)

    Østergaard, Søren Dinesen; Petrides, Georgio; Dinesen, Peter Thisted

    2013-01-01

    Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype...... of severe depression....

  17. Stroke subtypes and factors associated with ischemic stroke in ...

    African Journals Online (AJOL)

    Stroke subtypes assessed four OCSP (Oxfordshire Communi-. African Health Sciences Vol 15 Issue 1, March 2015. 68. 69 ty Stroke Project Classification) subtypes classification. 13 was used with lacunar circulation infarct (LACI) and total anterior (TACI), partial anterior (PACI), posterior. (POCI) circulation infarcts as non ...

  18. Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

    Science.gov (United States)

    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-01-01

    Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

  19. Ethnic variation of the histological subtypes of renal cell carcinoma ...

    African Journals Online (AJOL)

    E.V. Ezenwa

    The content of the data obtained included the ethnicity categorized as Chinese, Malays, Indians and others (Indonesians, Vietnamese and other minor groups). Other data collected included age, gender and the histological subtype categorized as clear cell, papillary, chromophobe, collecting duct and unclassified subtypes.

  20. Tubal ligation and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  1. Integrative subtype discovery in glioblastoma using iCluster.

    Directory of Open Access Journals (Sweden)

    Ronglai Shen

    Full Text Available Large-scale cancer genome projects, such as the Cancer Genome Atlas (TCGA project, are comprehensive molecular characterization efforts to accelerate our understanding of cancer biology and the discovery of new therapeutic targets. The accumulating wealth of multidimensional data provides a new paradigm for important research problems including cancer subtype discovery. The current standard approach relies on separate clustering analyses followed by manual integration. Results can be highly data type dependent, restricting the ability to discover new insights from multidimensional data. In this study, we present an integrative subtype analysis of the TCGA glioblastoma (GBM data set. Our analysis revealed new insights through integrated subtype characterization. We found three distinct integrated tumor subtypes. Subtype 1 lacks the classical GBM events of chr 7 gain and chr 10 loss. This subclass is enriched for the G-CIMP phenotype and shows hypermethylation of genes involved in brain development and neuronal differentiation. The tumors in this subclass display a Proneural expression profile. Subtype 2 is characterized by a near complete association with EGFR amplification, overrepresentation of promoter methylation of homeobox and G-protein signaling genes, and a Classical expression profile. Subtype 3 is characterized by NF1 and PTEN alterations and exhibits a Mesenchymal-like expression profile. The data analysis workflow we propose provides a unified and computationally scalable framework to harness the full potential of large-scale integrated cancer genomic data for integrative subtype discovery.

  2. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand; Osteoklastische Fingerarthrose - Subtyp der Handpolyarthrose

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W. [Radiologische Praxis, Hamburg-Barmbek (Germany); Dihlmann, A. [Berufsgenossenschaftliches Unfallkrankenhaus Hamburg (Germany)

    1998-02-01

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [Deutsch] Ziel: Beschreibung eines Subtyps der Arthrosis deformans an der Hand, der als osteoklastische Arthrose bezeichnet wird. Patienten und Methode: Retrospektive Analyse der Handroentgenaufnahmen von 150 Frauen und 100 Maennern mit Roentgenbefunden der Arthrosis deformans. Ergebnisse: 5% der Frauen und 2% der maennlichen Patienten des durchgesehenen Krankenguts zeigten an mindestens einem Fingergelenk eine Arthrose mit subchondralen Osteolysen an einem oder beiden artikulierenden Knochen, die mindestens ein Drittel der Phalanxlaenge erfasst hatten. Diese subchondralen Osteolysen gehen ueber die Groesse und Form der arthrotischen Geroellzysten, die lediglich im knoechernen (epiphysaeren) Gelenksockel sitzen, weit hinaus. Sie koennen innerhalb eines Jahres entstehen. Schlussfolgerung: Die osteoklastische Arthrose der Finger ist ein Subtyp der Handpolyarthrose. Nach Verlaufsbeobachtungen wird vermutet, dass eine

  3. Salmonella Source Attribution in Japan by a Microbiological Subtyping Approach

    DEFF Research Database (Denmark)

    Toyofuku, Hajime; Pires, Sara Monteiro; Hald, Tine

    2011-01-01

    In order to estimate the number of human Salmonella infections attributable to each of major animal-food source, and help identifying the best Salmonella intervention strategies, a microbial subtyping approach for source attribution was applied. We adapted a Bayesian model that attributes illnesses......-food sources, subtype-related factors, and source-related factors. National-surveillance serotyping data from 1998 to 2007 were applied to the model. Results suggested that the relative contribution of the sources to salmonellosis varied during the 10 year period, and that eggs are the most important source...... to specific sources and allows for the estimation of the differences in the ability of Salmonella subtypes and food types to result in reported salmonellosis. The number of human cases caused by different Salmonella subtypes is estimated as a function of the prevalence of these subtypes in the animal...

  4. Sensory Subtypes in Preschool Aged Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Tomchek, Scott D; Little, Lauren M; Myers, John; Dunn, Winnie

    2018-06-01

    Given the heterogeneity of autism spectrum disorder (ASD), research has investigated how sensory features elucidate subtypes that enhance our understanding of etiology and tailored treatment approaches. Previous studies, however, have not integrated core developmental behaviors with sensory features in investigations of subtypes in ASD. Therefore, we used latent profile analysis to examine subtypes in a preschool aged sample considering sensory processing patterns in combination with social-communication skill, motor performance, and adaptive behavior. Results showed four subtypes that differed by degree and quality of sensory features, age and differential presentation of developmental skills. Findings partially align with previous literature on sensory subtypes and extends our understanding of how sensory processing aligns with other developmental domains in young children with ASD.

  5. Molecular Subtyping of Tumors from Patients with Familial Glioma.

    Science.gov (United States)

    Ruiz, Vanessa Y; Praska, Corinne E; Armstrong, Georgina; Kollmeyer, Thomas M; Yamada, Seiji; Decker, Paul A; Kosel, Matthew L; Eckel-Passow, Jeanette E; Consortium, The Gliogene; Lachance, Daniel H; Bainbridge, Matthew N; Melin, Beatrice S; Bondy, Melissa L; Jenkins, Robert B

    2017-10-10

    Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on IDH mutation and 1p/19q co-deletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas, and that tumors in the same family should have the same molecular subtype. Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded (FFPE) tumor was obtained for a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation (CNV) data was obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wild type, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q-codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (p=0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ=0.59): 3 IDH-mutant non-codeleted, 2 IDH-wild type, and 2 IDH-mutant and 1p/19q-codeleted gliomas. Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight about the distribution of molecular subtypes in FG. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Dehydration: physiology, assessment, and performance effects.

    Science.gov (United States)

    Cheuvront, Samuel N; Kenefick, Robert W

    2014-01-01

    This article provides a comprehensive review of dehydration assessment and presents a unique evaluation of the dehydration and performance literature. The importance of osmolality and volume are emphasized when discussing the physiology, assessment, and performance effects of dehydration. The underappreciated physiologic distinction between a loss of hypo-osmotic body water (intracellular dehydration) and an iso-osmotic loss of body water (extracellular dehydration) is presented and argued as the single most essential aspect of dehydration assessment. The importance of diagnostic and biological variation analyses to dehydration assessment methods is reviewed and their use in gauging the true potential of any dehydration assessment method highlighted. The necessity for establishing proper baselines is discussed, as is the magnitude of dehydration required to elicit reliable and detectable osmotic or volume-mediated compensatory physiologic responses. The discussion of physiologic responses further helps inform and explain our analysis of the literature suggesting a ≥ 2% dehydration threshold for impaired endurance exercise performance mediated by volume loss. In contrast, no clear threshold or plausible mechanism(s) support the marginal, but potentially important, impairment in strength, and power observed with dehydration. Similarly, the potential for dehydration to impair cognition appears small and related primarily to distraction or discomfort. The impact of dehydration on any particular sport skill or task is therefore likely dependent upon the makeup of the task itself (e.g., endurance, strength, cognitive, and motor skill). © 2014 American Physiological Society.

  7. Functional Genomic investigation of Peroxisome Proliferator-Activated Receptor Gamma (PPARG mediated transcription response in gastric cancer

    Directory of Open Access Journals (Sweden)

    Karthikeyan Selvarasu

    2017-10-01

    Full Text Available Cancer is a complex and progressive multi-step disorder that results from the transformation of normal cells to malignant derivatives. Several oncogenic signaling pathways are involved in this transformation. PPARG (Peroxisome proliferator-activated receptor gamma mediated transcription and signaling is involved in few cancers. We have investigated the PPARG in gastric tumors. The objective of the present study was to investigate the PPARG mediated transcriptional response in gastric tumors. Gene-set based and pathway focused gene-set enrichment analysis of available PPARG signatures in gastric tumor mRNA profiles shows that PPARG mediated transcription is highly activated in intestinal sub-type of gastric tumors. Further, we have derived the PPARG associated genes in gastric cancer and their expression was identified for the association with the better survival of the patients. Analysis of the PPARG associated genes reveals their involvement in mitotic cell cycle process, chromosome organization and nuclear division. Towards identifying the association with other oncogenic signaling process, E2F regulated genes were found associated with PPARG mediated transcription. The current results reveal the possible stratification of gastric tumors based on the PPARG gene expression and the possible development of PPARG targeted gastric cancer therapeutics. The identified PPARG regulated genes were identified to be targetable by pioglitazone and rosiglitazone. The identification of PPARG genes also in the normal stomach tissues reveal the possible involvement of these genes in the normal physiology of stomach and needs to be investigated.

  8. Advances in physiological computing

    CERN Document Server

    Fairclough, Stephen H

    2014-01-01

    This edited collection will provide an overview of the field of physiological computing, i.e. the use of physiological signals as input for computer control. It will cover a breadth of current research, from brain-computer interfaces to telemedicine.

  9. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  10. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  11. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

    Olshan, Andrew F; Kuo, Tzy-Mey; Meyer, Anne-Marie; Nielsen, Matthew E; Purdue, Mark P; Rathmell, W Kimryn

    2013-01-01

    In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies. Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology

  12. HIV-1 subtype A gag variability and epitope evolution.

    Science.gov (United States)

    Abidi, Syed Hani; Kalish, Marcia L; Abbas, Farhat; Rowland-Jones, Sarah; Ali, Syed

    2014-01-01

    The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  13. HIV-1 subtype A gag variability and epitope evolution.

    Directory of Open Access Journals (Sweden)

    Syed Hani Abidi

    Full Text Available OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  14. An Overview of Achalasia and Its Subtypes

    Science.gov (United States)

    Patel, Dhyanesh A.; Lappas, Brian M.

    2017-01-01

    Achalasia is one of the most studied esophageal motility disorders. However, the pathophysiology and reasons that patients develop achalasia are still unclear. Patients often present with dysphagia to solids and liquids, regurgitation, and varying degrees of weight loss. There is significant latency prior to diagnosis, which can have nutritional implications. The diagnosis is suspected based on clinical history and confirmed by esophageal high-resolution manometry testing. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Recent data presented in abstract form suggest that patients with type II achalasia may be most likely, and patients with type III achalasia may be least likely, to report weight loss compared to patients with type I achalasia. Although achalasia cannot be permanently cured, palliation of symptoms is possible in over 90% of patients with the treatment modalities currently available (pneumatic dilation, Heller myotomy, or peroral endoscopic myotomy). This article reviews the clinical presentation, diagnosis, and management options in patients with achalasia, as well as potential insights into histopathologic differences and nutritional implications of the subtypes of achalasia. PMID:28867969

  15. (Re-)programming of subtype specific cardiomyocytes.

    Science.gov (United States)

    Hausburg, Frauke; Jung, Julia Jeannine; Hoch, Matti; Wolfien, Markus; Yavari, Arash; Rimmbach, Christian; David, Robert

    2017-10-01

    Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ischemic stroke subtype is associated with outcome in thrombolyzed patients

    DEFF Research Database (Denmark)

    Schmitz, Marie Louise; Simonsen, Claus Ziegler; Svendsen, M L

    2017-01-01

    OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients...... patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes....

  17. Prevalence and methodologies for detection, characterization and subtyping of Listeria monocytogenes and L. ivanovii in foods and environmental sources

    Directory of Open Access Journals (Sweden)

    Jin-Qiang Chen

    2017-09-01

    Full Text Available Listeria monocytogenes, one of the most important foodborne pathogens, can cause listeriosis, a lethal disease for humans. L. ivanovii, which is closely related to L. monocytogenes, is also widely distributed in nature and infects mainly warm-blooded ruminants, causing economic loss. Thus, there are high priority needs for methodologies for rapid, specific, cost-effective and accurate detection, characterization and subtyping of L. monocytogenes and L. ivanovii in foods and environmental sources. In this review, we (A described L. monocytogenes and L. ivanovii, world-wide incidence of listeriosis, and prevalence of various L. monocytogenes strains in food and environmental sources; (B comprehensively reviewed different types of traditional and newly developed methodologies, including culture-based, antigen/antibody-based, LOOP-mediated isothermal amplification, matrix-assisted laser desorption ionization-time of flight-mass spectrometry, DNA microarray, and genomic sequencing for detection and characterization of L. monocytogenes in foods and environmental sources; (C comprehensively summarized different subtyping methodologies, including pulsed-field gel electrophoresis, multi-locus sequence typing, ribotyping, and phage-typing, and whole genomic sequencing etc. for subtyping of L. monocytogenes strains from food and environmental sources; and (D described the applications of these methodologies in detection and subtyping of L. monocytogenes in foods and food processing facilities.

  18. Bioactive lipids in kidney physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Daria Sałata

    2014-01-01

    Full Text Available Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

  19. CRISPR-cas subtype I-Fb in Acinetobacter baumannii: evolution and utilization for strain subtyping.

    Science.gov (United States)

    Karah, Nabil; Samuelsen, Ørjan; Zarrilli, Raffaele; Sahl, Jason W; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii.

  20. CRISPR-cas Subtype I-Fb in Acinetobacter baumannii: Evolution and Utilization for Strain Subtyping

    Science.gov (United States)

    Karah, Nabil; Samuelsen, Ørjan; Zarrilli, Raffaele; Sahl, Jason W.; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii. PMID:25706932

  1. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay

    International Nuclear Information System (INIS)

    Zinkernagel, R.M.; Haenseler, E.; Leist, T.; Cerny, A.; Hengartner, H.; Althage, A.

    1986-01-01

    A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens

  2. Interpersonal subtypes in social phobia: diagnostic and treatment implications.

    Science.gov (United States)

    Cain, Nicole M; Pincus, Aaron L; Grosse Holtforth, Martin

    2010-11-01

    Interpersonal assessment may provide a clinically useful way to identify subtypes of social phobia. In this study, we examined evidence for interpersonal subtypes in a sample of 77 socially phobic outpatients. A cluster analysis based on the dimensions of dominance and love on the Inventory of Interpersonal Problems-Circumplex Scales (Alden, Wiggins, & Pincus, 1990) found 2 interpersonal subtypes of socially phobic patients. These subtypes did not differ on pretreatment global symptom severity as measured by the Brief Symptom Inventory (Derogatis, 1993) or diagnostic comorbidity but did exhibit differential responses to outpatient psychotherapy. Overall, friendly-submissive social phobia patients had significantly lower scores on measures of social anxiety and significantly higher scores on measures of well-being and satisfaction at posttreatment than cold-submissive social phobia patients. We discuss the results in terms of interpersonal theory and the clinical relevance of assessment of interpersonal functioning prior to beginning psychotherapy with socially phobic patients.

  3. New paradigms for Salmonella source attribution based on microbial subtyping.

    NARCIS (Netherlands)

    Mughini-Gras, Lapo; Franz, Eelco; van Pelt, Wilfrid

    Microbial subtyping is the most common approach for Salmonella source attribution. Typically, attributions are computed using frequency-matching models like the Dutch and Danish models based on phenotyping data (serotyping, phage-typing, and antimicrobial resistance profiling). Herewith, we

  4. Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

  5. α1A-Subtype adrenergic agonist therapy for the failing right ventricle.

    Science.gov (United States)

    Cowley, Patrick M; Wang, Guanying; Joshi, Sunil; Swigart, Philip M; Lovett, David H; Simpson, Paul C; Baker, Anthony J

    2017-12-01

    Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α 1 -adrenergic receptors (α 1 -ARs), in particular the α 1A -subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α 1A -subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg -1 ·day -1 ). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α 1A -subtype is a potential therapeutic target to treat the failing RV. NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α 1A -adrenergic receptor subtype

  6. Anxiety After Stroke: The Importance of Subtyping.

    Science.gov (United States)

    Chun, Ho-Yan Yvonne; Whiteley, William N; Dennis, Martin S; Mead, Gillian E; Carson, Alan J

    2018-03-01

    Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. © 2018 The Authors.

  7. Reproduction, physiology and biochemistry

    Science.gov (United States)

    This chapter summarizes fundamental knowledge and recent discoveries about the reproduction, physiology and biochemistry of plant-parasitic nematodes. Various types of reproduction are reviewed, including sexual reproduction and mitotic and meiotic parthenogenesis. Although much is known about the p...

  8. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  9. Molecular subtypes of glioblastoma are relevant to lower grade glioma.

    Directory of Open Access Journals (Sweden)

    Xiaowei Guan

    Full Text Available Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas.Gene expression array, single nucleotide polymorphism (SNP array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson. Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP was assigned using prediction models by Fine et al.Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.

  10. Progranulin expression in breast cancer with different intrinsic subtypes.

    Science.gov (United States)

    Li, Li Qin; Min, Li Shan; Jiang, Qun; Ping, Jin Liang; Li, Jing; Dai, Li Cheng

    2012-04-15

    Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. We found that high progranulin expression was associated with higher breast carcinoma angiogenesis, reflected by increased vascular endothelial growth factor expression and higher microvessel density. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathological features in different intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to investigate the progranulin expression profiles in the intrinsic subtypes of breast carcinomas and their relevance to histopathological and clinicopathological features. Tissue blocks containing 264 cases of breast carcinomas from 2006 to 2009 were classified as different intrinsic subtypes. Tissues of four intrinsic subtypes were immunostained for progranulin, vascular endothelial growth factor and CD105. Their relevance to histopathological and clinicopathological features was also analyzed. Twenty tissue samples from breast fibroadenomas were included in this study. Progranulin expression showed no significant differences in different intrinsic subtypes, although an increasing tendency could be found in the triple-negative breast cancer (TNBC) subgroup (χ(2)=5.00, df=3, p=0.17). However, differences were significant when pathologically node metastasis-positive (pN(+)) TNBC were excluded (χ(2)=17.84, df=3, pprogranulin in pathologically node metastasis-negative (pN(-)) TNBC. It was noted that the EGFR expression level of the pN(-) TNBC subtype was significantly higher in cases with strong progranulin expression than in cases with weak progranulin expression (χ(2)=11.26, df=1, pprogranulin in pN(-) TNBC suggests that progranulin is a promising new target for pN(-) TNBC treatment. Strong expression of progranulin correlates with positive EGFR expression in the pN(-) TNBC subtype. The close relationship between

  11. Biophysics and cell physiology

    International Nuclear Information System (INIS)

    Mazur, P.

    1975-01-01

    Progress is reported on research activities in the fields of physiology and low-temperature biology of mammalian embryos; effects of sub-zero temperatures on eggs and embryos of sea urchins; survival of frozen-thawed human red cells; effects of radiation on physiology of Escherichia coli; transfer of triplet electronic energy in dinucleotides; effects of x radiation on DNA degradation; energy deposition by neutrons; photosynthesis; excision repair of uv-induced pyrimidine dimers in DNA of plant cells

  12. Physiology of Ramadan fasting

    OpenAIRE

    Shokoufeh Bonakdaran

    2016-01-01

    Considering the emphasis of Islam on the importance of fasting, Muslims attempt to fast from dawn until sunset during the holy month of Ramadan. Fasting is associated with several benefits for normal and healthy individuals. However, it could pose high risks to the health of diabetic patients due to certain physiological changes. This study aimed to compare the physiological changes associated with fasting in healthy individuals and diabetic patients during Ramadan. Furthermore, we reviewed t...

  13. Epidemic dynamics of two coexisting hepatitis C virus subtypes.

    Science.gov (United States)

    Jiménez-Hernández, Nuria; Torres-Puente, Manuela; Bracho, Maria Alma; García-Robles, Inmaculada; Ortega, Enrique; del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

    2007-01-01

    Hepatitis C virus (HCV) infection affects about 3% of the human population. Phylogenetic analyses have grouped its variants into six major genotypes, which have a star-like distribution and several minor subtypes. The most abundant genotype in Europe is the so-called genotype 1, with two prevalent subtypes, 1a and 1b. In order to explain the higher prevalence of subtype 1b over 1a, a large-scale sequence analysis (100 virus clones) has been carried out over 25 patients of both subtypes in two regions of the HCV genome: one comprising hypervariable region 1 and another including the interferon sensitivity-determining region. Neither polymorphism analysis nor molecular variance analysis (attending to intra- and intersubtype differences, age, sex and previous history of antiviral treatment) was able to show any particular difference between subtypes that might account for their different prevalence. Only the demographic history of the populations carrying both subtypes and analysis of molecular variance (AMOVA) for risk practice suggested that the route of transmission may be the most important factor to explain the observed difference.

  14. [Human immunodeficiency virus type 1 subtypes in Djibouti].

    Science.gov (United States)

    Abar, A Elmi; Jlizi, A; Darar, H Youssouf; Ben Nasr, M; Abid, S; Kacem, M Ali Ben Hadj; Slim, A

    2012-01-01

    The authors had for aim to study the distribution of HIV-1 subtypes in a cohort of HIV positive patients in the hospital General Peltier of Djibouti. An epidemiological study was made on 40 HIV-1 positive patients followed up in the Infectious Diseases Department over three months. All patients sample were subtyped by genotyping. Thirty-five patients (15 men and 20 women) were found infected by an HIV-1 strain belonging to the M group. Genotyping revealed that - 66% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. In fact, Subtype C prevalence has been described in the Horn of Africa and a similar prevalence was previously reported in Djibouti. However our study describes the subtype B in Djibouti for the first time. It is the predominant subtype in the Western world. The detection of CRF02_AG strains indicates that they are still circulating in Djibouti, the only country in East Africa in which this recombinant virus was found. CRF02_AG recombinant isolates were primarily described in West and Central Africa. The presence of this viral heterogeneity, probably coming from the mixing of populations in Djibouti, which is an essential economic and geographical crossroads, incites us to vigilance in the surveillance of this infection.

  15. Subtyping pathological gamblers based on impulsivity, depression, and anxiety.

    Science.gov (United States)

    Ledgerwood, David M; Petry, Nancy M

    2010-12-01

    This study examined putative subtypes of pathological gamblers (PGs) based on the Pathways model, and it also evaluated whether the subtypes would benefit differentially from treatment. Treatment-seeking PGs (N = 229) were categorized into Pathways subtypes based on scores from questionnaires assessing anxiety, depression, and impulsivity. The Addiction Severity Index-Gambling assessed severity of gambling problems at baseline, posttreatment, and 12-month follow-up. Compared with behaviorally conditioned (BC) gamblers, emotionally vulnerable (EV) gamblers had higher psychiatric and gambling severity, and were more likely to have a parent with a psychiatric history. Antisocial impulsive (AI) gamblers also had elevated gambling and psychiatric severity relative to BC gamblers. They were more likely to have antisocial personality disorder and had the highest legal and family/social severity scores. They were also most likely to have a history of substance abuse treatment, history of inpatient psychiatric treatment, and a parent with a substance use or gambling problem. AI and EV gamblers experienced greater gambling severity throughout treatment than BC gamblers, but all three subtypes demonstrated similar patterns of treatment response. Thus, the three Pathways subtypes differ on some baseline characteristics, but subtyping did not predict treatment outcomes beyond a simple association with problem gambling severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  16. Personalized physiological medicine.

    Science.gov (United States)

    Ince, Can

    2017-12-28

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant changes in the pathophysiology and regulation of various organ systems and their cellular and subcellular constituents. I propose that personalized physiological medicine is composed of four pillars relevant to the critically ill patient. Pillar 1 is defined by the frailty and fitness of the patient and their physiological reserve to cope with the stress of critical illness and therapy. Pillar 2 involves monitoring of the key physiological variables of the different organ systems and their response to disease and therapy. Pillar 3 concerns the evaluation of the success of resuscitation by assessment of the hemodynamic coherence between the systemic and microcirculation and parenchyma of the organ systems. Finally, pillar 4 is defined by the integration of the physiological and clinical data into a time-learning adaptive model of the patient to provide feedback about the function of organ systems and to guide and assess the response to disease and therapy. I discuss each pillar and describe the challenges to research and development that will allow the realization of personalized physiological medicine to be practiced at the bedside for critically ill patients.

  17. Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior: study 3--the effects on amygdala efferent physiology of block of NMDA receptors prior to injection of FG-7142 and its relationship to behavioral change.

    Science.gov (United States)

    Adamec, R E

    1998-01-01

    The findings of this study support the hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate the initiation of long-term potentiation (LTP) and behavioral changes induced by the anxiogenic beta-carboline, FG-7142. Unlike previous work, this study examined the effects of FG-7142 on LTP of amygdala efferents in both hemispheres. 7-amino-phosphono-heptanoic acid (AP7), a competitive NMDA receptor blocker, given prior to administration of FG-7142, prevented LTP in amygdala efferent transmission to the medial hypothalamus and periacqueductal gray (PAG). When given FG-7142 alone, cats showed lasting behavioral changes accompanied by LTP in all pathways studied. Duration of LTP, and its relationship to behavioral change, depended on the pathway and the hemisphere of the pathway. Correlation and covariance analyses indicate that LTP in the left amygdalo-ventromedial hypothalamic pathway mediates initiation, but not maintenance, of increased defensiveness. This finding replicates previous work. A new finding is that increased local excitability in the right basal amygdala (reduced threshold for evoked response), and LTP in the right amygdalo-PAG pathway, may be important for maintenance of increases in defensive behavior. Furthermore, the effects of flumazenil, a benzodiazepine receptor antagonist, on behavior and physiology single out the importance of right amygdalo-PAG LTP as a critical mediator of increased defensiveness. Flumazenil reversed the increase in defensiveness produced by FG-7142 in a drug-dependent manner as described in Adamec (1998a). Moreover, flumazenil reversed LTP only in the right amygdalo-PAG pathway. The findings of the present study suggest that response to FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety, especially in view of the recent data in humans implicating right hemispheric function in persisting negative affective states.

  18. Fearful imagery in social phobia: generalization, comorbidity, and physiological reactivity.

    Science.gov (United States)

    McTeague, Lisa M; Lang, Peter J; Laplante, Marie-Claude; Cuthbert, Bruce N; Strauss, Cyd C; Bradley, Margaret M

    2009-03-01

    Social phobia has been characterized as a disorder of exaggerated fear of social threat and heightened sensitivity to imagery of social failure. To assess the physiological basis of this description, social phobia patients (n=75) and demographically matched control participants (n=75) imagined neutral and fearful events while acoustic startle probes were occasionally presented and eye-blink responses (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed. In addition to comparing control participants and social phobia patients, the influences of diagnostic subtype (circumscribed, generalized), comorbid depression, and chronicity were assessed. Patients exceeded control participants in startle reflex and autonomic responding during imagery of social threat, whereas the groups evinced commensurate reactivity to contents depicting commonly shared fears (survival threat). Individuals with circumscribed performance phobia were similar to control participants, with the exception of more robust reactions to idiographic, performance fear imagery. In contrast, generalized phobic patients were characterized by longer disorder chronicity and demonstrated heightened sensitivity to a broader range of fear contents. Those with generalized phobia plus comorbid depression showed attenuation of fear-potentiated startle and reported the most protracted social anxiety. Subtypes of social phobia can be objectively distinguished in patterns of physiological reactivity. Furthermore, subtypes vary systematically in chronicity and defensive engagement with the shortest disorder duration (circumscribed phobia) associated with the most robust and focal physiological reactivity, followed by broader defensive sensitivity in more chronic generalized phobia, and finally attenuation of the formerly exaggerated fear potentiation in the comorbidly depressed, the most chronic form.

  19. Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm.

    Science.gov (United States)

    Gaillard, Trudy R; Osei, Kwame

    2016-03-01

    The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5-2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora.

  20. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  1. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  2. Is PIGD a legitimate motor subtype in Parkinson disease?

    Science.gov (United States)

    Kotagal, Vikas

    2016-06-01

    Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

  3. Ultrasonographic Features of Papillary Thyroid Carcinomas According to Their Subtypes

    Directory of Open Access Journals (Sweden)

    Hye Jin Baek

    2018-05-01

    Full Text Available BackgroundThe ultrasonographic characteristics and difference for various subtypes of papillary thyroid carcinoma (PTC are still unclear. The aim of this study was to compare the ultrasonographic features of PTC according to its subtype in patients undergoing thyroid surgery.MethodsIn total, 140 patients who underwent preoperative thyroid ultrasonography (US and thyroid surgery between January 2016 and December 2016 were included. The ultrasonographic features and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS category of each thyroid nodule were retrospectively evaluated by a single radiologist, and differences in ultrasonographic features according to the PTC subtype were assessed.ResultsAccording to histopathological analyses, there were 97 classic PTCs (62.2%, 34 follicular variants (21.8%, 5 tall cell variants (3.2%, 2 oncocytic variants (1.3%, 1 Warthin-like variant (0.6%, and 1 diffuse sclerosing variant (0.6%. Most PTCs were classified under K-TIRADS category 5. Among the ultrasonographic features, the nodule margin and the presence of calcification were significantly different among the PTC subtypes. A spiculated/microlobulated margin was the most common type of margin, regardless of the PTC subtype. In particular, all tall cell variants exhibited a spiculated/microlobulated margin. The classic PTC group exhibited the highest prevalence of intranodular calcification, with microcalcification being the most common. The prevalence of multiplicity and nodal metastasis was high in the tall cell variant group.ConclusionThe majority of PTCs in the present study belonged to K-TIRADS category 5, regardless of the subtype. Our findings suggest that ultrasonographic features are not useful for distinguishing PTC subtypes.

  4. Human physiology in space

    Science.gov (United States)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  5. Plant Physiology and Development

    DEFF Research Database (Denmark)

    Taiz, Lincoln; Zeiger, Eduardo; Møller, Ian Max

    Throughout its twenty-two year history, the authors of Plant Physiology have continually updated the book to incorporate the latest advances in plant biology and implement pedagogical improvements requested by adopters. This has made Plant Physiology the most authoritative, comprehensive......, and widely used upper-division plant biology textbook. In the Sixth Edition, the Growth and Development section (Unit III) has been reorganized and expanded to present the complete life cycle of seed plants from germination to senescence. In recognition of this enhancement, the text has been renamed Plant...... Physiology and Development. As before, Unit III begins with updated chapters on Cell Walls and Signals and Signal Transduction. The latter chapter has been expanded to include a discussion of major signaling molecules, such as calcium ions and plant hormones. A new, unified chapter entitled Signals from...

  6. The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

    Science.gov (United States)

    2008-06-19

    al., 1995; Roger et al., 2004]. We have found that nootropics also enhance GABA -mediated inhibitory events, which would serve to dampen excess... schizophrenia , epilepsy, or even sleep-deprivation. Specific Aims Electrophysiology and histology experiments were used to assess cortical physiology...2005], we hypothesized that IDRA 21 may increase GABA -mediated synaptic inhibition by enhancing AMPAR-mediated, synaptic activation of GABAergic

  7. Sex differences in the physiology of eating

    Science.gov (United States)

    Asarian, Lori

    2013-01-01

    Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating. PMID:23904103

  8. Diagnosis and subtypes of adolescent antisocial personality disorder.

    Science.gov (United States)

    Jones, Meredith; Westen, Drew

    2010-04-01

    The present study examined the application of the Antisocial Personality Disorder (APD) diagnosis to adolescents and investigated the possibility of subtypes of APD adolescents. As part of a broader study of adolescent personality in clinically-referred patients, experienced clinicians provided personality data on a randomly selected patient in their care using the SWAP-II-A personality pathology instrument. Three hundred thirteen adolescents met adult DSM-IV diagnostic criteria for APD. To characterize adolescents with the disorder, we aggregated the data to identify the items most descriptive and distinctive of APD adolescents relative to other teenagers in the sample (N = 950). Q-factor analysis identified five personality subtypes: psychopathic-like, socially withdrawn, impulsive-histrionic, emotionally dysregulated, and attentionally dysregulated. The five subtypes differed in predictable ways on a set of external criteria related to global adaptive functioning, childhood family environment, and family history of psychiatric illness. Both the APD diagnosis and the empirically derived APD subtypes provided incremental validity over and above the DSM-IV disruptive behavior disorders in predicting global adaptive functioning, number of arrests, early-onset severe externalizing pathology, and quality of peer relationships. Although preliminary, these results provide support for the use of both APD and personality-based subtyping systems in adolescents.

  9. Clinically-inspired automatic classification of ovarian carcinoma subtypes

    Directory of Open Access Journals (Sweden)

    Aicha BenTaieb

    2016-01-01

    Full Text Available Context: It has been shown that ovarian carcinoma subtypes are distinct pathologic entities with differing prognostic and therapeutic implications. Histotyping by pathologists has good reproducibility, but occasional cases are challenging and require immunohistochemistry and subspecialty consultation. Motivated by the need for more accurate and reproducible diagnoses and to facilitate pathologists′ workflow, we propose an automatic framework for ovarian carcinoma classification. Materials and Methods: Our method is inspired by pathologists′ workflow. We analyse imaged tissues at two magnification levels and extract clinically-inspired color, texture, and segmentation-based shape descriptors using image-processing methods. We propose a carefully designed machine learning technique composed of four modules: A dissimilarity matrix, dimensionality reduction, feature selection and a support vector machine classifier to separate the five ovarian carcinoma subtypes using the extracted features. Results: This paper presents the details of our implementation and its validation on a clinically derived dataset of eighty high-resolution histopathology images. The proposed system achieved a multiclass classification accuracy of 95.0% when classifying unseen tissues. Assessment of the classifier′s confusion (confusion matrix between the five different ovarian carcinoma subtypes agrees with clinician′s confusion and reflects the difficulty in diagnosing endometrioid and serous carcinomas. Conclusions: Our results from this first study highlight the difficulty of ovarian carcinoma diagnosis which originate from the intrinsic class-imbalance observed among subtypes and suggest that the automatic analysis of ovarian carcinoma subtypes could be valuable to clinician′s diagnostic procedure by providing a second opinion.

  10. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

    Directory of Open Access Journals (Sweden)

    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  11. Nigerian Journal of Physiological Sciences

    African Journals Online (AJOL)

    Nigerian Journal of Physiological Sciences (Niger. J. Physiol. Sci.) is a biannual publication of the Physiological Society of Nigeria. It covers diverse areas of research in physiological sciences, publishing reviews in current research areas and original laboratory and clinical research in physiological sciences. Other websites ...

  12. Regulation of metabolism by the Mediator complex.

    Science.gov (United States)

    Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

    2016-01-01

    The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

  13. Effect of amino acid sequence variations at position 149 on the fusogenic activity of the subtype B avian metapneumovirus fusion protein.

    Science.gov (United States)

    Yun, Bingling; Gao, Yanni; Liu, Yongzhen; Guan, Xiaolu; Wang, Yongqiang; Qi, Xiaole; Gao, Honglei; Liu, Changjun; Cui, Hongyu; Zhang, Yanping; Gao, Yulong; Wang, Xiaomei

    2015-10-01

    The entry of enveloped viruses into host cells requires the fusion of viral and cell membranes. These membrane fusion reactions are mediated by virus-encoded glycoproteins. In the case of avian metapneumovirus (aMPV), the fusion (F) protein alone can mediate virus entry and induce syncytium formation in vitro. To investigate the fusogenic activity of the aMPV F protein, we compared the fusogenic activities of three subtypes of aMPV F proteins using a TCSD50 assay developed in this study. Interestingly, we found that the F protein of aMPV subtype B (aMPV/B) strain VCO3/60616 (aMPV/vB) was hyperfusogenic when compared with F proteins of aMPV/B strain aMPV/f (aMPV/fB), aMPV subtype A (aMPV/A), and aMPV subtype C (aMPV/C). We then further demonstrated that the amino acid (aa) residue 149F contributed to the hyperfusogenic activity of the aMPV/vB F protein. Moreover, we revealed that residue 149F had no effect on the fusogenic activities of aMPV/A, aMPV/C, and human metapneumovirus (hMPV) F proteins. Collectively, we provide the first evidence that the amino acid at position 149 affects the fusogenic activity of the aMPV/B F protein, and our findings will provide new insights into the fusogenic mechanism of this protein.

  14. Simulated Exercise Physiology Laboratories.

    Science.gov (United States)

    Morrow, James R., Jr.; Pivarnik, James M.

    This book consists of a lab manual and computer disks for either Apple or IBM hardware. The lab manual serves as "tour guide" for the learner going through the various lab experiences. The manual contains definitions, proper terminology, and other basic information about physiological principles. It is organized so a step-by-step procedure may be…

  15. Physiology Flies with Time.

    Science.gov (United States)

    Sehgal, Amita

    2017-11-30

    The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the circadian clock. From studies beginning in fruit flies, we now know that circadian regulation pervades most biological processes and has strong ties to human health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Personalized physiological medicine

    NARCIS (Netherlands)

    Ince, Can

    2017-01-01

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant

  17. Physiological responses to hypothermia.

    Science.gov (United States)

    Wood, Thomas; Thoresen, Marianne

    2015-04-01

    Therapeutic hypothermia is the only treatment currently recommended for moderate or severe encephalopathy of hypoxic‒ischaemic origin in term neonates. Though the effects of hypothermia on human physiology have been explored for many decades, much of the data comes from animal or adult studies; the latter originally after accidental hypothermia, followed by application of controlled hypothermia after cardiac arrest or trauma, or during cardiopulmonary bypass. Though this work is informative, the effects of hypothermia on neonatal physiology after perinatal asphyxia must be considered in the context of a prolonged hypoxic insult that has already induced a number of significant physiological sequelae. This article reviews the effects of therapeutic hypothermia on respiratory, cardiovascular, and metabolic parameters, including glycaemic control and feeding requirements. The potential pitfalls of blood‒gas analysis and overtreatment of physiological changes in cardiovascular parameters are also discussed. Finally, the effects of hypothermia on drug metabolism are covered, focusing on how the pharmacokinetics, pharmacodynamics, and dosing requirements of drugs frequently used in neonatal intensive care may change during therapeutic hypothermia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The Face of Physiology

    Directory of Open Access Journals (Sweden)

    Paul White

    2008-10-01

    Full Text Available This article explores the relationship between the physiology of the emotions and the display of character in Victorian Britain. Charles Bell and others had begun to link certain physiological functions, such as respiration, with the expression of feelings such as fear, regarding the heart and other internal organs as instruments by which the emotions were made visible. But a purely functional account of the emotions, which emerged through the development of reflex physiology during the second half of the century, would dramatically alter the nature of feelings and the means of observing them. At the same time, instinctual or acquired sympathy, which had long underpinned the accurate reading of expressions, became a problem to be surmounted by new 'objectively'. Graphic recording instruments measuring a variety of physiological functions and used with increasing frequency in clinical diagnostics became of fundamental importance for tracing the movement of feelings during the period prior to the development of cinematography. They remained, in the form of devices such as the polygraph, a crucial and controversial means of measuring affective states, beneath the potentially deceptive surface of the body.

  19. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  20. The spectrum of aphasia subtypes and etiology in subacute stroke.

    Science.gov (United States)

    Hoffmann, Michael; Chen, Ren

    2013-11-01

    Aphasia is one of the most common stroke syndrome presentations, yet little is known about the spectrum of different subtypes or their stroke mechanisms. Yet, subtypes and etiology are known to influence the prognosis and recovery. Our aim is to analyze aphasia subtypes and etiology in a large subacute stroke population. Consecutive patients from a dedicated cognitive stroke registry were accrued. A validated cognitive screening examination was administered during the first month of stroke presentation, which enabled a diagnosis of 14 different aphasic subtypes. The evolution from one subtype to another in the acute and subacute period, at times, resulted in more than 1 subtype being diagnosed. Etiology of stroke was determined by the modified Trial of Org 10172 in Acute Stroke Treatment criteria that included intracerebral hemorrhage. Exclusions included dementia, chronic medical illness, substance abuse, and severe depression. Of 2389 stroke patients, after exclusions (n=593), aphasias numbered 625 (625 of 1796; 34.8%), and the subtype frequencies included Broca aphasia (n=170; 27.2%), anomic aphasia (n=165; 26.4%), global aphasia (n=119; 19.04%), and subcortical aphasia (n=57; 9.12%). Less frequent subtypes (total n=40; 6.7%) included transcortical aphasia (n=11), Wernicke aphasia (n=10), conduction aphasia (n=7), aphemia (n=3), semantic aphasia (n=3), crossed aphasia (n=3), pure word deafness (n=2), and foreign accent syndrome (n=1). Aphasia subtypes and etiologies had some significant associations (chi-square: 855.8, P valueaphasia had a significant association with small-vessel disease (SVD) (odds ratio [OR]=2.0254, 95% confidence interval [CI]: 1.3820-2.9681), and global aphasia patients mostly had cardioembolic (CE) causes (OR=2.3589, 95% CI: 1.5506-3.5885) and less likely SVD (OR=.2583, 95% CI: .1444-.4654). Other notable inferences were included. Wernicke aphasia was caused by either CE (6 of 12; 50%) or hemorrhage (4 of 12; 33.3%) in a combined 83% of

  1. Parkinson's disease severity and motor subtype influence physical capacity components

    Directory of Open Access Journals (Sweden)

    Marcelo Pinto Pereira

    2013-09-01

    Full Text Available The severity of Parkinson's disease (PD and PD's motor subtypes influence the components of physical capacity. The aim of this study was to investigate the impact of both PD severity and motor subtype in the performance of these components. Thirty-six PD patients were assigned into four groups: Tremor (TD initial and TD mild, akinetic-rigid (AR initial, and AR mild. Patients' strength, balance, coordination, mobility and aerobic capacity were evaluated and groups were compared using a two-way ANOVA (severity and subtype as factors. AR presents a poorer performance than TD in almost all tests. Also this performance was worsened with the advance of the disease in AR, contrary to TD. We conclude that AR and TD subgroups are different about their performance on physical capacity components, moreover, this performance worsens with the advance of the disease of the AR group, but not for TD.

  2. HLA-B27 subtypes among the Chukotka native groups

    International Nuclear Information System (INIS)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I.; Reveille, J.D.; Arnett, F.C.

    1995-01-01

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter's syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs

  3. Fixation Characteristics of Severe Amblyopia Subtypes: Which One is Worse?

    Science.gov (United States)

    Koylu, Mehmet Talay; Ozge, Gokhan; Kucukevcilioglu, Murat; Mutlu, Fatih Mehmet; Ceylan, Osman Melih; Akıncıoglu, Dorukcan; Ayyıldız, Onder

    2017-01-01

    To determine differences in macular sensitivity and fixation patterns in different subtypes of severe amblyopia. This case-control study enrolled a total of 73 male adults, including 18 with pure strabismic severe amblyopia, 19 with pure anisometropic severe amblyopia, 18 with mixed (strabismic plus anizometropic) severe amblyopia, and 18 healthy controls. MP-1 microperimetry was used to evaluate macular sensitivity, location of fixation, and stability of fixation. Mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in all amblyopia subtypes when compared with healthy controls. Intergroup comparisons between amblyopia subtypes revealed that mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in pure strabismic and mixed amblyopic eyes when compared with pure anisometropic amblyopic eyes. Strabismus seems to be a worse prognostic factor in severe amblyopia than anisometropia in terms of fixation characteristics and retinal sensitivity.

  4. HLA-B27 subtypes among the Chukotka native groups

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center

    1995-12-31

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  5. Avian reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Gibbons, Edward F.; Durrant, Barbara S.; Demarest, Jack

    1995-01-01

    Knowledge of the many physiological factors associated with egg production , fertility, incubation, and brooding in nondomestic birds is limited. Science knows even less about reproduction in most of the 238 endangered or threatened birds. This discussion uses studies of nondomestic and, when necessary, domestic birds to describe physiological control of reproduction. Studies of the few nondomestic avian species show large variation in physiological control of reproduction. Aviculturists, in order to successfully propagate an endangered bird, must understand the bird's reproductive peculiarities. First, investigators can do studies with carefully chosen surrogate species, but eventually they need to confirm the results in the target endangered bird. Studies of reproduction in nondomestic birds increased in the last decade. Still, scientists need to do more comparative studies to understand the mechanisms that control reproduction in birds. New technologies are making it possible to study reproductive physiology of nondomestic species in less limiting ways. These technologies include telemetry to collect information without inducing stress on captives (Howey et al., 1987; Klugman, 1987), new tests for most of the humoral factors associated with reproduction, and the skill to collect small samples and manipulate birds without disrupting the physiological mechanisms (Bercovitz et al., 1985). Managers are using knowledge from these studies to improve propagation in zoological parks, private and public propagation facilities, and research institutions. Researchers need to study the control of ovulation, egg formation, and oviposition in the species of nondomestic birds that lay very few eggs in a season, hold eggs in the oviduct for longer intervals, or differ in other ways from the more thoroughly studied domestic birds. Other techniques that would enhance propagation for nondomestlc birds include tissue culture of cloned embryonic cells, cryopreservation of embryos

  6. Therapeutic response to benzodiazepine in panic disorder subtypes

    Directory of Open Access Journals (Sweden)

    Alexandre Martins Valença

    Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

  7. Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes.

    Science.gov (United States)

    Chen, Juan; Xu, Juan; Li, Yongsheng; Zhang, Jinwen; Chen, Hong; Lu, Jianping; Wang, Zishan; Zhao, Xueying; Xu, Kang; Li, Yixue; Li, Xia; Zhang, Yan

    2017-02-07

    Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.

  8. Identification of Multiple Subtypes of Campylobacter jejuni in Chicken Meat and the Impact on Source Attribution

    Directory of Open Access Journals (Sweden)

    John A. Hudson

    2013-09-01

    Full Text Available Most source attribution studies for Campylobacter use subtyping data based on single isolates from foods and environmental sources in an attempt to draw epidemiological inferences. It has been suggested that subtyping only one Campylobacter isolate per chicken carcass incurs a risk of failing to recognise the presence of clinically relevant, but numerically infrequent, subtypes. To investigate this, between 21 and 25 Campylobacter jejuni isolates from each of ten retail chicken carcasses were subtyped by pulsed-field gel electrophoresis (PFGE using the two restriction enzymes SmaI and KpnI. Among the 227 isolates, thirteen subtypes were identified, the most frequently occurring subtype being isolated from three carcasses. Six carcasses carried a single subtype, three carcasses carried two subtypes each and one carcass carried three subtypes. Some subtypes carried by an individual carcass were shown to be potentially clonally related. Comparison of C. jejuni subtypes from chickens with isolate subtypes from human clinical cases (n = 1248 revealed seven of the thirteen chicken subtypes were indistinguishable from human cases. None of the numerically minor chicken subtypes were identified in the human data. Therefore, typing only one Campylobacter isolate from individual chicken carcasses may be adequate to inform Campylobacter source attribution.

  9. The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype ionotropic glutamate receptors.

    Science.gov (United States)

    Wang, Rui; Mellem, Jerry E; Jensen, Michael; Brockie, Penelope J; Walker, Craig S; Hoerndli, Frédéric J; Hauth, Linda; Madsen, David M; Maricq, Andres V

    2012-09-06

    The neurotransmitter glutamate mediates excitatory synaptic transmission by gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and memory. We previously discovered two classes of AMPAR auxiliary proteins in C. elegans that modify receptor kinetics and thus change synaptic transmission. Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein that associates with both the related auxiliary subunit SOL-1 and with the GLR-1 AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in trans can rescue sol-1 mutants, and this rescue depends on in cis expression of SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the adult nervous system to control AMPAR-mediated currents. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Value of subtyping in studies of irradiation and human leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Darby, S C

    1985-01-01

    The two largest studies of the effects of irradiation on humans in postnatal life are described. These are 1) the Ankylosing Spondylitis Study(ASS) carried out on patients given X-ray therapy as treatment for spondylitis in the UK and 2) the Life Span Study(LSS) carried out on the survivors of the atomic bombings of Hiroshima and Nagasaki. From these studies, a limited degree of subtyping of leukemias is indicated. Chronic lymphatic leukemia is much less readily induced by radiation than the other major subtypes. The inducibility of acute myeloid leukemia increases with age at exposure.

  11. Parent stress across molecular subtypes of children with Angelman syndrome.

    Science.gov (United States)

    Miodrag, N; Peters, S

    2015-09-01

    Parenting stress has been consistently reported among parents of children with developmental disabilities. However, to date, no studies have investigated the impact of a molecular subtype of Angelman syndrome (AS) on parent stress, despite distinct phenotypic differences among subtypes. Data for 124 families of children with three subtypes of AS: class I and II deletions (n = 99), imprinting centre defects (IC defects; n = 11) and paternal uniparental disomy (UPD; n = 14) were drawn from the AS Rare Diseases Clinical Research Network (RDCRN) database and collected from five research sites across the Unites States. The AS study at the RDCRN gathered health information to understand how the syndrome develops and how to treat it. Parents completed questionnaires on their perceived psychological stress, the severity of children's aberrant behaviour and children's sleep patterns. Children's adaptive functioning and developmental levels were clinically evaluated. Child-related stress reached clinical levels for 40% of parents of children with deletions, 100% for IC defects and 64.3% for UPD. Sleep difficulties were similar and elevated across subtypes. There were no differences between molecular subtypes for overall child and parent-related stress. However, results showed greater isolation and lack of perceived parenting skills for parents of children with UPD compared with deletions. Better overall cognition for children with deletions was significantly related to more child-related stress while their poorer adaptive functioning was associated with more child-related stress. For all three groups, the severity of children's inappropriate behaviour was positively related to different aspects of stress. How parents react to stress depends, in part, on children's AS molecular subtype. Despite falling under the larger umbrella term of AS, it is important to acknowledge the unique aspects associated with children's molecular subtype. Identifying these factors can

  12. The whole-genome landscape of medulloblastoma subtypes

    DEFF Research Database (Denmark)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana

    2017-01-01

    actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target...... KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive...

  13. Physiological Actions of Fibroblast Growth Factor-23

    Directory of Open Access Journals (Sweden)

    Reinhold G. Erben

    2018-05-01

    Full Text Available Fibroblast growth factor-23 (FGF23 is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney. At physiological concentrations of the hormone, the endocrine actions of FGF23 in the kidney are αKlotho-dependent, because high-affinity binding of FGF23 to FGF receptors requires the presence of the co-receptor αKlotho on target cells. It is well established that excessive concentrations of intact FGF23 in the blood lead to phosphate wasting in patients with normal kidney function. Based on the importance of diseases associated with gain of FGF23 function such as phosphate-wasting diseases and chronic kidney disease, a large body of literature has focused on the pathophysiological consequences of FGF23 excess. Less emphasis has been put on the role of FGF23 in normal physiology. Nevertheless, during recent years, lessons we have learned from loss-of-function models have shown that besides the paramount physiological roles of FGF23 in the control of 1α-hydroxylase expression and of apical membrane expression of sodium-phosphate co-transporters in proximal renal tubules, FGF23 also is an important stimulator of calcium and sodium reabsorption in distal renal tubules. In addition, there is an emerging role of FGF23 as an auto-/paracrine regulator of alkaline phosphatase expression and mineralization in bone. In contrast to the renal actions of FGF23, the FGF23-mediated suppression of alkaline phosphatase in bone is αKlotho-independent. Moreover, FGF23 may be a physiological suppressor of differentiation of hematopoietic stem cells into the erythroid lineage in the bone microenvironment. At present, there is little evidence for a physiological role of FGF23 in organs other than kidney and bone. The purpose of this mini-review is to highlight the current knowledge about the complex physiological functions of FGF23.

  14. Assessing the Differences in Public Health Impact of Salmonella Subtypes Using a Bayesian Microbial Subtyping Approach for Source Attribution

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Hald, Tine

    2010-01-01

    Salmonella is a major cause of human gastroenteritis worldwide. To prioritize interventions and assess the effectiveness of efforts to reduce illness, it is important to attribute salmonellosis to the responsible sources. Studies have suggested that some Salmonella subtypes have a higher health...... impact than others. Likewise, some food sources appear to have a higher impact than others. Knowledge of variability in the impact of subtypes and sources may provide valuable added information for research, risk management, and public health strategies. We developed a Bayesian model that attributes...... illness to specific sources and allows for a better estimation of the differences in the ability of Salmonella subtypes and food types to result in reported salmonellosis. The model accommodates data for multiple years and is based on the Danish Salmonella surveillance. The number of sporadic cases caused...

  15. Bulimia nervosa-nonpurging subtype: closer to the bulimia nervosa-purging subtype or to binge eating disorder?

    Science.gov (United States)

    Jordan, Jennifer; McIntosh, Virginia V W; Carter, Janet D; Rowe, Sarah; Taylor, Kathryn; Frampton, Christopher M A; McKenzie, Janice M; Latner, Janet; Joyce, Peter R

    2014-04-01

    DSM-5 has dropped subtyping of bulimia nervosa (BN), opting to continue inclusion of the somewhat contentious diagnosis of BN-nonpurging subtype (BN-NP) within a broad BN category. Some contend however that BN-NP is more like binge eating disorder (BED) than BN-P. This study examines clinical characteristics, eating disorder symptomatology, and Axis I comorbidity in BN-NP, BN-P, and BED groups to establish whether BN-NP more closely resembles BN-P or BED. Women with BN-P (n = 29), BN-NP (n = 29), and BED (n = 54) were assessed at baseline in an outpatient psychotherapy trial for those with binge eating. Measures included the Structured Clinical Interviews for DSM-IV, Eating Disorder Examination, and Eating Disorder Inventory-2. The BN-NP subtype had BMIs between those with BN-P and BED. Both BN subtypes had higher Restraint and Drive for Thinness scores than BED. Body Dissatisfaction was highest in BN-NP and predicted BN-NP compared to BN-P. Higher Restraint and lower BMI predicted BN-NP relative to BED. BN-NP resembled BED with higher lifetime BMIs; and weight-loss clinic than eating disorder clinic attendances relative to the BN-P subtype. Psychiatric comorbidity was comparable except for higher lifetime cannabis use disorder in the BN-NP than BN-P subtype These results suggest that BN-NP sits between BN-P and BED however the high distress driving inappropriate compensatory behaviors in BN-P requires specialist eating disorder treatment. These results support retaining the BN-NP group within the BN category. Further research is needed to determine whether there are meaningful differences in outcome over follow-up. Copyright © 2013 Wiley Periodicals, Inc.

  16. Food, physiology and drug delivery.

    Science.gov (United States)

    Varum, F J O; Hatton, G B; Basit, A W

    2013-12-05

    Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Identification of Receptor Ligands and Receptor Subtypes Using Antagonists in a Capillary Electrophoresis Single-Cell Biosensor Separation System

    Science.gov (United States)

    Fishman, Harvey A.; Orwar, Owe; Scheller, Richard H.; Zare, Richard N.

    1995-08-01

    A capillary electrophoresis system with single-cell biosensors as a detector has been used to separate and identify ligands in complex biological samples. The power of this procedure was significantly increased by introducing antagonists that inhibited the cellular response from selected ligand-receptor interactions. The single-cell biosensor was based on the ligand-receptor binding and G-protein-mediated signal transduction pathways in PC12 and NG108-15 cell lines. Receptor activation was measured as increases in cytosolic free calcium ion concentration by using fluorescence microscopy with the intracellular calcium ion indicator fluo-3 acetoxymethyl ester. Specifically, a mixture of bradykinin (BK) and acetylcholine (ACh) was fractionated and the components were identified by inhibiting the cellular response with icatibant (HOE 140), a selective antagonist to the BK B_2 receptor subtype (B_2BK), and atropine, an antagonist to muscarinic ACh receptor subtypes. Structurally related forms of BK were also identified based on inhibiting B_2BK receptors. Applications of this technique include identification of endogenous BK in a lysate of human hepatocellular carcinoma cells (Hep G2) and screening for bioactivity of BK degradation products in human blood plasma. The data demonstrate that the use of antagonists with a single-cell biosensor separation system aids identification of separated components and receptor subtypes.

  18. Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially Patterned Stress and Genetic Expression

    Directory of Open Access Journals (Sweden)

    Erin Linnenbringer

    2017-11-01

    Full Text Available Hormone receptor negative (HR- breast cancer subtypes are etiologically distinct from the more common, less aggressive, and more treatable form of estrogen receptor positive (ER+ breast cancer. Numerous population-based studies have found that, in the United States, Black women are 2 to 3 times more likely to develop HR- breast cancer than White women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing genetic factors associated with African ancestry. This approach fails to acknowledge that racial stratification shapes a wide range of environmental and social exposures over the life course. Human stress genomics considers the role of individual stress perceptions on gene expression. Yet, the role of structurally rooted biopsychosocial processes that may be activated by the social patterning of stressors in an historically unequal society, whether perceived by individual black women or not, could also impact cellular physiology and gene expression patterns relevant to HR- breast cancer etiology. Using the weathering hypothesis as our conceptual framework, we develop a structural perspective for examining racial disparities in breast cancer subtypes, integrating important findings from the stress biology, breast cancer epidemiology, and health disparities literatures. After integrating key findings from these largely independent literatures, we develop a theoretically and empirically guided framework for assessing potential multilevel factors relevant to the development of HR- breast cancer disproportionately among Black women in the US. We hypothesize that a dynamic interplay among socially patterned psychosocial stressors, physiological & behavioral responses, and genomic pathways contribute to the increased risk of HR- breast cancer among Black women. This work provides a basis for exploring potential alternative pathways linking the lived experience of race to the risk of HR

  19. Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially Patterned Stress and Genetic Expression.

    Science.gov (United States)

    Linnenbringer, Erin; Gehlert, Sarah; Geronimus, Arline T

    2017-01-01

    Hormone receptor negative (HR-) breast cancer subtypes are etiologically distinct from the more common, less aggressive, and more treatable form of estrogen receptor positive (ER+) breast cancer. Numerous population-based studies have found that, in the United States, Black women are 2 to 3 times more likely to develop HR- breast cancer than White women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing genetic factors associated with African ancestry. This approach fails to acknowledge that racial stratification shapes a wide range of environmental and social exposures over the life course. Human stress genomics considers the role of individual stress perceptions on gene expression. Yet, the role of structurally rooted biopsychosocial processes that may be activated by the social patterning of stressors in an historically unequal society, whether perceived by individual black women or not, could also impact cellular physiology and gene expression patterns relevant to HR- breast cancer etiology. Using the weathering hypothesis as our conceptual framework, we develop a structural perspective for examining racial disparities in breast cancer subtypes, integrating important findings from the stress biology, breast cancer epidemiology, and health disparities literatures. After integrating key findings from these largely independent literatures, we develop a theoretically and empirically guided framework for assessing potential multilevel factors relevant to the development of HR- breast cancer disproportionately among Black women in the US. We hypothesize that a dynamic interplay among socially patterned psychosocial stressors, physiological & behavioral responses, and genomic pathways contribute to the increased risk of HR- breast cancer among Black women. This work provides a basis for exploring potential alternative pathways linking the lived experience of race to the risk of HR- breast cancer, and

  20. Renal phosphate handling: Physiology

    Directory of Open Access Journals (Sweden)

    Narayan Prasad

    2013-01-01

    Full Text Available Phosphorus is a common anion. It plays an important role in energy generation. Renal phosphate handling is regulated by three organs parathyroid, kidney and bone through feedback loops. These counter regulatory loops also regulate intestinal absorption and thus maintain serum phosphorus concentration in physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor 23 (FGF23 and klotho coreceptor are the key regulators of phosphorus balance in body.

  1. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  2. Ethnic differences in ischemic stroke subtypes in young-onset stroke: the Stroke Prevention in Young Adults Study.

    Science.gov (United States)

    Trivedi, Megh M; Ryan, Kathleen A; Cole, John W

    2015-10-29

    Prior studies indicate that young African-Americans (AA) have a greater frequency of ischemic stroke than similarly aged European-Americans (EA). We hypothesized that differences in stroke subtype frequency mediated through sex and differing risk factor profiles may play a role in ethnicity-specific stroke. Utilizing our biracial young-onset stroke population, we explored these relationships. Fifty nine hospitals in the Baltimore-Washington area participated in a population-based study of young-onset stroke in men (218-AA, 291-EA) and women (219-AA, 222-EA) aged 16-49. Data on age, sex, ethnicity and stroke risk factors (hypertension (HTN) and smoking) were gathered through standardized interview. A pair of vascular neurologists adjudicated each case to determine TOAST subtype. Logistic regression analyses evaluating for differences in stroke risk factors by TOAST subtype were performed. Analyses controlling for age and sex demonstrated that AA were more likely to have a lacunar stroke than EA (OR = 1.61; 95% CI = 1.12-2.32; p = 0.011) when utilizing the other TOAST subtypes as the reference group. This effect was mediated by HTN, which increases the risk of lacunar stroke (OR = 2.03; 95% CI = 1.38-2.98; p = 0.0003) and large artery stroke (OR = 1.70; 95% CI = 1.01-2.88; p = 0.048) when controlling for sex, ethnicity, and age. Cases below age 40 were more likely to have a cardioembolic stroke than those above age 40 (OR = 1.62; 95% CI = 1.15-2.27; p = 0.006), controlling for sex and ethnicity. Lastly, current smokers were more likely to have a large artery stroke than non-smokers (OR = 1.79; 95% CI = 1.08-2.98; p = 0.024). Our population-based data demonstrate ethnic differences in ischemic stroke subtypes. These findings may help clarify mechanisms of stroke in young adults which may in part be driven by ethnic-specific differences in early-onset traditional risk factors, thereby indicating differing emphasis on workup and prevention.

  3. Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

    Science.gov (United States)

    Hillman, Kristin L; Doze, Van A; Porter, James E

    2005-08-01

    Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists

  4. Applied physiology of triathlon.

    Science.gov (United States)

    O'Toole, M L; Douglas, P S

    1995-04-01

    The triathlon is a 3-event endurance sport in which athletes compete sequentially in swimming, cycling and running. The primary determinant of success is the ability to sustain a high rate of energy expenditure for prolonged periods of time. Exercise training-induced physiological adaptations in virtually all systems of the body allow the athlete to accomplish this. Aerobic capacity (measured as maximal oxygen uptake, VO2max), economy of motion (submaximal VO2) and fractional utilisation of maximal capacity (%VO2max) reflect the integrated responses of these physiological adaptations. Numerous studies have reported relatively high mean VO2max values for various groups of triathletes that are comparable to those reported for athletes in single-event endurance sports and clearly above those reported for untrained individuals. In shorter distance triathlons and in studies using recreational (rather than elite) triathletes, VO2max is related to performance in the corresponding event of the triathlon (e.g. tethered swimming VO2max with swim time). In longer events and with more elite triathletes, VO2max correlates less well with performance. The physiological adaptations that correspond to and facilitate improved VO2max occur centrally in the cardiovascular system, centred on increased maximal cardiac output, and peripherally in the metabolic systems, centred around increased arterio-venous O2 (a-v O2) difference. While a high VO2max in individuals is clearly of importance to triathlon performance, energy output must be sustained for long periods of time, making economy of motion also very important. Studies suggests that competitive swimmers have better swimming economy than triathletes. However, since many triathletes have previously been competitive swimmers this finding is questionable. The finding suggests that triathletes from nonswimming backgrounds would benefit from improving swimming technique rather than concentrating training workouts solely on distance. In

  5. Brain neurodevelopmental markers related to the deficit subtype of schizophrenia.

    Science.gov (United States)

    Takahashi, Tsutomu; Takayanagi, Yoichiro; Nishikawa, Yumiko; Nakamura, Mihoko; Komori, Yuko; Furuichi, Atsushi; Kido, Mikio; Sasabayashi, Daiki; Noguchi, Kyo; Suzuki, Michio

    2017-08-30

    Deficit schizophrenia is a homogeneous subtype characterized by a trait-like feature of primary and prominent negative symptoms, but the etiologic factors related to this specific subtype remain largely unknown. This magnetic resonance imaging study aimed to examine gross brain morphology that probably reflects early neurodevelopment in 38 patients with deficit schizophrenia, 37 patients with non-deficit schizophrenia, and 59 healthy controls. Potential brain neurodevelopmental markers investigated in this study were the adhesio interthalamica (AI), cavum septi pellucidi (CSP), and surface morphology (i.e., olfactory sulcus depth, sulcogyral pattern, and number of orbital sulci) of the orbitofrontal cortex (OFC). The subtype classification of schizophrenia patients was based on the score of Proxy for the Deficit Syndrome. The deficit schizophrenia group had a significantly shorter AI compared with the non-deficit group and controls. The deficit group, but not the non-deficit group, was also characterized by an altered distribution of the OFC sulcogyral pattern, as well as fewer posterior orbital sulcus compared with controls. Other neurodevelopmental markers did not differentiate the deficit and non-deficit subgroups. These results suggest that the deficit subtype of schizophrenia and its clinical manifestation may be at least partly related to prominent neurodevelopmental pathology. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Outcomes of treatment for achalasia depend on manometric subtype

    NARCIS (Netherlands)

    Rohof, Wout O.; Salvador, Renato; Annese, Vito; Bruley des Varannes, Stanislas; Chaussade, Stanislas; Costantini, Mario; Elizalde, J. Ignasi; Gaudric, Marianne; Smout, Andre J.; Tack, Jan; Busch, Olivier R.; Zaninotto, Giovanni; Boeckxstaens, Guy E.

    2013-01-01

    Patients with achalasia are treated with either pneumatic dilation (PD) or laparoscopic Heller myotomy (LHM), which have comparable rates of success. We evaluated whether manometric subtype was associated with response to treatment in a large population of patients treated with either PD or LHM (the

  7. Social Withdrawal Subtypes during Early Adolescence in India

    Science.gov (United States)

    Bowker, Julie C.; Raja, Radhi

    2011-01-01

    The overarching goal of this study was to examine the associations between three social withdrawal subtypes (shyness, unsociability, avoidance), peer isolation, peer difficulties (victimization, rejection, exclusion, low acceptance), and loneliness in India during early adolescence. Participants were 194 adolescents in Surat, India (M age=13.35…

  8. Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes

    NARCIS (Netherlands)

    Taguchi, K.; Saitoh, M.; Sato, S.; Asano, M.; Michel, M. C.

    1997-01-01

    We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin

  9. Psychosocial and Adaptive Deficits Associated with Learning Disability Subtypes

    Science.gov (United States)

    Backenson, Erica M.; Holland, Sara C.; Kubas, Hanna A.; Fitzer, Kim R.; Wilcox, Gabrielle; Carmichael, Jessica A.; Fraccaro, Rebecca L.; Smith, Amanda D.; Macoun, Sarah J.; Harrison, Gina L.; Hale, James B.

    2015-01-01

    Children with specific learning disabilities (SLD) have deficits in the basic psychological processes that interfere with learning and academic achievement, and for some SLD subtypes, these deficits can also lead to emotional and/or behavior problems. This study examined psychosocial functioning in 123 students, aged 6 to 11, who underwent…

  10. The global spread of HIV-1 subtype B epidemic

    NARCIS (Netherlands)

    Magiorkinis, Gkikas; Angelis, Konstantinos; Mamais, Ioannis; Katzourakis, Aris; Hatzakis, Angelos; Albert, Jan; Lawyer, Glenn; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Gomes, Perpétua; Camacho, Ricardo J.; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Anders; Kostrikis, Leondios G.; Lepej, Snjezana J.; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elizabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Stylianou, Dora C.; Boucher, Charles A B; Nikolopoulos, Georgios; Vasylyeva, Tetyana; Friedman, Samuel R.; van de Vijver, David; Angarano, Gioacchino; Chaix, Marie Laure; de Luca, Andrea; Korn, Klaus; Loveday, Clive; Soriano, Vincent; Yerly, Sabine; Zazzi, Mauricio; Vandamme, Anne Mieke; Paraskevis, Dimitrios

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti

  11. Cognitive Profiling and Preliminary Subtyping in Chinese Developmental Dyslexia

    Science.gov (United States)

    Ho, Connie Suk-Han; Chan, David Wai-Ock; Lee, Suk-Han; Tsang, Suk-Man; Luan, Vivian Hui

    2004-01-01

    The present study examined the cognitive profile and subtypes of developmental dyslexia in a nonalphabetic script, Chinese. One hundred and forty-seven Chinese primary school children with developmental dyslexia were tested on a number of literacy and cognitive tasks. The results showed that rapid naming deficit and orthographic deficit were the…

  12. Longitudinal Stability of Phonological and Surface Subtypes of Developmental Dyslexia

    Science.gov (United States)

    Peterson, Robin L.; Pennington, Bruce F.; Olson, Richard K.; Wadsworth, Sally J.

    2014-01-01

    Limited evidence supports the external validity of the distinction between developmental phonological and surface dyslexia. We previously identified children ages 8 to 13 meeting criteria for these subtypes (Peterson, Pennington, & Olson, 2013) and now report on their reading and related skills approximately 5 years later. Longitudinal…

  13. Brief Report: Further Evidence of Sensory Subtypes in Autism

    Science.gov (United States)

    Lane, Alison E.; Dennis, Simon J.; Geraghty, Maureen E.

    2011-01-01

    Distinct sensory processing (SP) subtypes in autism have been reported previously. This study sought to replicate the previous findings in an independent sample of thirty children diagnosed with an Autism Spectrum Disorder. Model-based cluster analysis of parent-reported sensory functioning (measured using the Short Sensory Profile) confirmed the…

  14. Sensory Processing Subtypes in Autism: Association with Adaptive Behavior

    Science.gov (United States)

    Lane, Alison E.; Young, Robyn L.; Baker, Amy E. Z.; Angley, Manya T.

    2010-01-01

    Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes…

  15. Distinct Response Time Distributions in Attention Deficit Hyperactivity Disorder Subtypes

    Science.gov (United States)

    Querne, Laurent; Berquin, Patrick

    2009-01-01

    Objective: To address the issue of response time (RT) profiles in hyperactive-impulsive (ADHD-HI), inattentive (ADHD-IA), and combined (ADHD-C) subtypes of ADHD. We hypothesized that children with ADHD-HI should respond more rapidly than children without ADHD and children with ADHD-IA and ADHD-C should respond more slowly than children without…

  16. Breast cancer molecular subtype classifier that incorporates MRI features.

    Science.gov (United States)

    Sutton, Elizabeth J; Dashevsky, Brittany Z; Oh, Jung Hun; Veeraraghavan, Harini; Apte, Aditya P; Thakur, Sunitha B; Morris, Elizabeth A; Deasy, Joseph O

    2016-07-01

    To use features extracted from magnetic resonance (MR) images and a machine-learning method to assist in differentiating breast cancer molecular subtypes. This retrospective Health Insurance Portability and Accountability Act (HIPAA)-compliant study received Institutional Review Board (IRB) approval. We identified 178 breast cancer patients between 2006-2011 with: 1) ERPR + (n = 95, 53.4%), ERPR-/HER2 + (n = 35, 19.6%), or triple negative (TN, n = 48, 27.0%) invasive ductal carcinoma (IDC), and 2) preoperative breast MRI at 1.5T or 3.0T. Shape, texture, and histogram-based features were extracted from each tumor contoured on pre- and three postcontrast MR images using in-house software. Clinical and pathologic features were also collected. Machine-learning-based (support vector machines) models were used to identify significant imaging features and to build models that predict IDC subtype. Leave-one-out cross-validation (LOOCV) was used to avoid model overfitting. Statistical significance was determined using the Kruskal-Wallis test. Each support vector machine fit in the LOOCV process generated a model with varying features. Eleven out of the top 20 ranked features were significantly different between IDC subtypes with P machine-learning-based predictive model using features extracted from MRI that can distinguish IDC subtypes with significant predictive power. J. Magn. Reson. Imaging 2016;44:122-129. © 2016 Wiley Periodicals, Inc.

  17. Molecular Subtypes and Clinical Outcomes of Breast Cancer

    African Journals Online (AJOL)

    2010-01-04

    Jan 4, 2010 ... Some early work has started in earnest at both the. AKUH(N) and Kijabe Hospitals to try and stratify our breast cancer patients to those mentioned subtypes to help in both diagnosis and treatment. The limiting fac- tors are small numbers of patients expense to undertake the tests and lack of both internal ...

  18. [Distorted cognition of bodily sensations in subtypes of social anxiety].

    Science.gov (United States)

    Kanai, Yoshihiro; Sasaki, Shoko; Iwanaga, Makoto; Seiwa, Hidetoshi

    2010-02-01

    The purpose of this study was to investigate the relationship between subtypes of social anxiety and distorted cognition of bodily sensations. The package of questionnaires including the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) was administered to 582 undergraduate students. To identify subtypes of social anxiety, cluster analysis was conducted using scores of the SPS and SIAS. Five clusters were identified and labeled as follows: Generalized type characterized by intense anxiety in most social situations, Non-anxious type characterized by low anxiety levels in social situations, Averaged type whose anxiety levels are averaged, Interaction anxiety type who feels anxiety mainly in social interaction situations, and Performance anxiety type who feels anxiety mainly in performance situations. Results of an ANOVA indicated that individuals with interaction type fear the negative evaluation from others regarding their bodily sensations whereas individuals with performance type overestimate the visibility of their bodily sensations to others. Differences in salient aspects of cognitive distortion among social anxiety subtypes may show necessity to select intervention techniques in consideration of subtypes.

  19. A study of symptom profile and clinical subtypes of delirium

    OpenAIRE

    Meagher, David

    2012-01-01

    Delineating delirium phenomenology facilitates detection, understanding neuroanatomical endophenotypes, and patient management. This compendium reflects an integrated research plan executed over a five year period, employing detailed, standardized phenomenological assessments cross-sectionally and longitudinally. Motor activity studies were controlled and included both subjective and objective measures, aimed at identifying a new approach to defining this clinical subtype as a more pure motor...

  20. Central Timing Deficits in Subtypes of Primary Speech Disorders

    Science.gov (United States)

    Peter, Beate; Stoel-Gammon, Carol

    2008-01-01

    Childhood apraxia of speech (CAS) is a proposed speech disorder subtype that interferes with motor planning and/or programming, affecting prosody in many cases. Pilot data (Peter & Stoel-Gammon, 2005) were consistent with the notion that deficits in timing accuracy in speech and music-related tasks may be associated with CAS. This study…

  1. Preoperative subtyping of meningiomas by perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao [University Medical Center Groningen, University of Groningen (Netherlands); Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China); Department of Radiology, University of Groningen (Netherlands); Roediger, Lars A.; Oudkerk, Matthijs [University Medical Center Groningen, University of Groningen (Netherlands); Department of Radiology, University of Groningen (Netherlands); Shen, Tianzhen [Fudan University Huashan Hospital, Department of Radiology, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China)

    2008-10-15

    This paper aims to evaluate the value of perfusion magnetic resonance (MR) imaging in the preoperative subtyping of meningiomas by analyzing the relative cerebral blood volume (rCBV) of three benign subtypes and anaplastic meningiomas separately. Thirty-seven meningiomas with peritumoral edema (15 meningothelial, ten fibrous, four angiomatous, and eight anaplastic) underwent perfusion MR imaging by using a gradient echo echo-planar sequence. The maximal rCBV (compared with contralateral normal white matter) in both tumoral parenchyma and peritumoral edema of each tumor was measured. The mean rCBVs of each two histological subtypes were compared using one-way analysis of variance and least significant difference tests. A p value less than 0.05 indicated a statistically significant difference. The mean rCBV of meningothelial, fibrous, angiomatous, and anaplastic meningiomas in tumoral parenchyma were 6.93{+-}3.75, 5.61{+-}4.03, 11.86{+-}1.93, and 5.89{+-}3.85, respectively, and in the peritumoral edema 0.87{+-}0.62, 1.38{+-}1.44, 0.87{+-}0.30, and 3.28{+-}1.39, respectively. The mean rCBV in tumoral parenchyma of angiomatous meningiomas and in the peritumoral edema of anaplastic meningiomas were statistically different (p<0.05) from the other types of meningiomas. Perfusion MR imaging can provide useful functional information on meningiomas and help in the preoperative diagnosis of some subtypes of meningiomas. (orig.)

  2. Detection and subtyping avian metapneumovirus from turkeys in Iran.

    Science.gov (United States)

    Mayahi, Mansour; Momtaz, Hassan; Jafari, Ramezan Ali; Zamani, Pejman

    2017-01-01

    Avian metapneumovirus (aMPV) causes diseases like rhinotracheitis in turkeys, swollen head syndrome in chickens and avian rhinotracheitis in other birds. Causing respiratory problems, aMPV adversely affects production and inflicts immense economic losses and mortalities, especially in turkey flocks. In recent years, several serological and molecular studies have been conducted on this virus, especially in poultry in Asia and Iran. The purpose of the present study was detecting and subtyping aMPV by reverse transcriptase polymerase chain reaction (RT-PCR) from non-vaccinated, commercial turkey flocks in Iran for the first time. Sixty three meat-type unvaccinated turkey flocks from several provinces of Iran were sampled in major turkey abattoirs. Samples were tested by RT-PCR for detecting and subtyping aMPV. The results showed that 26 samples from three flocks (4.10%) were positive for viral RNA and all of the viruses were found to be subtype B of aMPV. As a result, vaccination especially against subtype B of aMPV should be considered in turkey flocks in Iran to control aMPV infections.

  3. Racial Differences by Ischemic Stroke Subtype: A Comprehensive Diagnostic Approach

    Directory of Open Access Journals (Sweden)

    Sarah Song

    2012-01-01

    Full Text Available Background. Previous studies have suggested that black populations have more small-vessel and fewer cardioembolic strokes. We sought to analyze racial differences in ischemic stroke subtype employing a comprehensive diagnostic workup with magnetic resonance-imaging-(MRI- based evaluation including diffusion-weighted imaging (DWI. Methods. 350 acute ischemic stroke patients admitted to an urban hospital with standardized comprehensive diagnostic evaluations were retrospectively analyzed. Ischemic stroke subtype was determined by three Trial of Org 10172 in Acute Stroke Treatment (TOAST classification systems. Results. We found similar proportions of cardioembolic and lacunar strokes in the black and white cohort. The only subtype category with a significant difference by race was “stroke of other etiology,” more common in whites. Black stroke patients were more likely to have an incomplete evaluation, but this did not reach significance. Conclusions. We found similar proportions by race of cardioembolic and lacunar strokes when employing a full diagnostic evaluation including DWI MRI. The relatively high rate of cardioembolism may have been underappreciated in black stroke patients when employing a CT approach to stroke subtype diagnosis. Further research is required to better understand the racial differences in frequency of “stroke of other etiology” and explore disparities in the extent of diagnostic evaluations.

  4. The global spread of HIV-1 subtype B epidemic

    NARCIS (Netherlands)

    G. Magiorkinis (Gkikas); K. Angelis (Konstantinos); I. Mamais (Ioannis); Katzourakis, A. (Aris); A. Hatzakis (Angelos); J. Albert (Jan); Lawyer, G. (Glenn); O. Hamouda (Osamah); D. Struck (Daniel); J. Vercauteren (Jurgen); A. Wensing (Amj); I. Alexiev (Ivailo); B. Åsjö (Birgitta); C. Balotta (Claudia); Gomes, P. (Perpétua); R.J. Camacho (Ricardo Jorge); S. Coughlan (Suzie); A. Griskevicius (Algirdas); Z. Grossman (Zehava); Horban, A. (Anders); L.G. Kostrikis (Leondios); Lepej, S.J. (Snjezana J.); K. Liitsola (Kirsi); M. Linka (Marek); C. Nielsen; D. Otelea (Dan); R. Paredes (Roger); M. Poljak (Mario); E. Puchhammer-Stöckl (Elisabeth); J.C. Schmit; A. Sonnerborg (Anders); D. Stanekova (Danica); M. Stanojevic (Maja); Stylianou, D.C. (Dora C.); C.A.B. Boucher (Charles); Nikolopoulos, G. (Georgios); Vasylyeva, T. (Tetyana); Friedman, S.R. (Samuel R.); D.A.M.C. van de Vijver (David); G. Angarano (Guiseppe); M.L. Chaix (Marie Laure); A. de Luca (Andrea); K. Korn (Klaus); Loveday, C. (Clive); V. Soriano (Virtudes); S. Yerly (Sabine); M. Zazzi; A.M. Vandamme (Anne Mieke); D. Paraskevis (Dimitrios)

    2016-01-01

    textabstractHuman immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa

  5. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Kirstin B. Langer

    2018-04-01

    Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

  6. Role of Dopamine Receptors Subtypes, D1-Like and D2-Like, within the Nucleus Accumbens Subregions, Core and Shell, on Memory Consolidation in the One-Trial Inhibitory Avoidance Task

    Science.gov (United States)

    Manago, Francesca; Castellano, Claudio; Oliverio, Alberto; Mele, Andrea; De Leonibus, Elvira

    2009-01-01

    Recent evidence demonstrated that dopamine within the nucleus accumbens mediates consolidation of both associative and nonassociative memories. However, the specific contribution of the nucleus accumbens subregions, core and shell, and of D1 and D2 receptors subtypes has not been yet clarified. The aim of this study was, therefore, to directly…

  7. The subtype of VSD and the angiographic differentiation

    International Nuclear Information System (INIS)

    Choe, Kyu Ok; Sul, Jun Hee; Lee, Sung Kyu; Cho, Bum Koo; Hong, Sung Nok

    1985-01-01

    VSD is the most common congenital cardiac malformation and the natural history depends not only on the age of patients and the size of defect but the subtype of VSD as well, important factor in clinical management of those patients. In 110 patients, with surgically repaired VSD in Yonsei Medical Center in 1984, the subtype of VSDs evaluated by surgical observation were correlated with LV angiogram findings to verify the incidence of subtype in Korean and the diagnostic accuracy to predict the subtype by angiogram. 1. 110 patients included 64 boys and 46 girls, the age ranged from 3 months to 14 years (average 4.6 years old). 2. Angiographic findings were interpreted as follows; a. Perimembranous defects were profiled in LAO 60 .deg. LV angiogram and located below the aortic valve. In inlet excavation the shunted blood opacified the recess between septal leaflet of tricuspid valve and interventricular septum in early phase, in infundibular excavation opacified the recess between anterior leaflet of TV and anterior free wall of RV and in trabecular excavation the shunted blood traversed anterior portion of TV ring, opacified trabecular portion of RV cavity. b. Subarterial types were profiled in RAO 30 .deg. LV angiogram, just below aortic valve as well as pulmonic valve. Total infundibular defects were profiled in RAO 30 .deg. and LAO 60 .deg. LV angiogram subaortic in location in both views. c. In muscular VSD the profiled angle was varied according to the subtype but the defects were separated from the aortic valve as muscular septum interposed between the aortic valve and the defect. 3. The incidence of subtype of VSDs evaluated by surgical observation were as follows. Subarterial type : 32 cases (29.1%) Total infundibular defect : 5 cases (4.5%) Perimembranous type : 73 cases (66.3%) Infundibular excavation : 32 cases (29.2%) Trabecular excavation : 28 cases (25.5%) Inlet excavation : 10 cases (9.1%) Mixed : 3 cases (2.7%) Muscular type : 1 cases (0.9%) Total 63

  8. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

    Directory of Open Access Journals (Sweden)

    S. I. Shkrobot

    2018-02-01

    Full Text Available Objectives. The aim of the present study was to clarify clinical neurological characteristics and different ischemic stroke subtypes unfavorable course predictors in acute phase. Material and Methods. 482 patients with different ischemic stroke subtypes were observed. Among them there were 125 (25.9 % with cardioembolic infarct (CEI, 119 (24.7 % with large artery atherosclerosis (LAAS infarct, 122 (25.3 % with lacunar stroke (LAC, 116 (24.1 % with stroke of undetermined etiology (UDE. The comparative analysis of clinical picture was performed. The predictors of unfavorable course of acute phase were established. Results. We have found out that severe neurological deficit, high mortality and the worst functional outcome during the first 14 days were observed in patients with CEI and LAAS. The highest frequency of early neurological deterioration (END was detected at LAC (in 22.7 % of patients. There was a relationship between END and presence of transient ischemic attack (TIA in past medical history, the level of systolic blood pressure (SBP at the beginning of the disease and the degree of carotid arteries stenosis on the side of lesion. The patients with LAC had mild neurological deficit and better prognosis compared with other ischemic stroke subtypes. Among the clinical factors that have impact on the CEI, LAAS and UDE acute phase course were: the size of lesion, the level of consciousness on the 1st day, the baseline SBP, patient’s age. At LAAS, the presence of transient ischemic attack (TIA in past medical history and low SBP in the onset of the disease (less than140 mm Hg has an additional prognostic value for an unfavorable functional outcome. The severity of LAC in acute period depended on its localization and size. Localization of LAC in the internal capsule, thalamus and pons were characterized by the highest severity. Conclusions. Clinical neurological features of ischemic stroke depend on its subtype and have some prognostic value

  9. Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

    Science.gov (United States)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

    2018-05-23

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  10. Breast cancer molecular subtype classification using deep features: preliminary results

    Science.gov (United States)

    Zhu, Zhe; Albadawy, Ehab; Saha, Ashirbani; Zhang, Jun; Harowicz, Michael R.; Mazurowski, Maciej A.

    2018-02-01

    Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

  11. Comparing two basic subtypes in OCD across three large community samples: a pure compulsive versus a mixed obsessive-compulsive subtype.

    Science.gov (United States)

    Rodgers, Stephanie; Ajdacic-Gross, Vladeta; Kawohl, Wolfram; Müller, Mario; Rössler, Wulf; Hengartner, Michael P; Castelao, Enrique; Vandeleur, Caroline; Angst, Jules; Preisig, Martin

    2015-12-01

    Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.

  12. Association between endometriosis and risk of histological subtypes of ovarian cancer

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne

    2012-01-01

    Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes...

  13. Neurocognitive Impairments Are More Severe in the Binge-Eating/Purging Anorexia Nervosa Subtype Than in the Restricting Subtype.

    Science.gov (United States)

    Tamiya, Hiroko; Ouchi, Atushi; Chen, Runshu; Miyazawa, Shiho; Akimoto, Yoritaka; Kaneda, Yasuhiro; Sora, Ichiro

    2018-01-01

    Objective: To evaluate cognitive function impairment in patients with anorexia nervosa (AN) of either the restricting (ANR) or binge-eating/purging (ANBP) subtype. Method: We administered the Japanese version of the MATRICS Consensus Cognitive Battery to 22 patients with ANR, 18 patients with ANBP, and 69 healthy control subjects. Our participants were selected from among the patients at the Kobe University Hospital and community residents. Results: Compared to the healthy controls, the ANR group had significantly lower visual learning and social cognition scores, and the ANBP group had significantly lower processing speed, attention/vigilance, visual learning, reasoning/problem-solving, and social cognition scores. Compared to the ANR group, the ANBP group had significantly lower attention/vigilance scores. Discussion: The AN subtypes differed in cognitive function impairments. Participants with ANBP, which is associated with higher mortality rates than ANR, exhibited greater impairment severities, especially in the attention/vigilance domain, confirming the presence of impairments in continuous concentration. This may relate to the impulsivity, an ANBP characteristic reported in the personality research. Future studies can further clarify the cognitive impairments of each subtype by addressing the subtype cognitive functions and personality characteristics.

  14. The emergence of Applied Physiology within the discipline of Physiology.

    Science.gov (United States)

    Tipton, Charles M

    2016-08-01

    Despite the availability and utilization of the physiology textbooks authored by Albrecht von Haller during the 18th century that heralded the modern age of physiology, not all physicians or physiologists were satisfied with its presentation, contents, or application to medicine. Initial reasons were fundamental disagreements between the "mechanists," represented by Boerhaave, Robinson, and von Haller, and the "vitalists," represented by the faculty and graduates of the Montpellier School of Medicine in France, notably, Bordeu and Barthez. Subsequently, objections originated from Europe, United Kingdom, and the United States in publications that focused not only on the teaching of physiology to medical and secondary students, but on the specific applications of the content of physiology to medicine, health, hygiene, pathology, and chronic diseases. At the turn of the 20th century, texts began to appear with applied physiology in their titles and in 1926, physician Samson Wright published a textbook entitled Applied Physiology that was intended for both medical students and the medical profession. Eleven years later, physicians Best and Taylor published The Physiological Basis of Medical Practice: A University of Toronto Texbook in Applied Physiology Although both sets of authors defined the connection between applied physiology and physiology, they failed to define the areas of physiology that were included within applied physiology. This was accomplished by the American Physiological Society (APS) Publications Committee in 1948 with the publication of the Journal of Appplied Physiology, that stated the word "applied" would broadly denote human physiology whereas the terms stress and environment would broadly include work, exercise, plus industrial, climatic and social factors. NIH established a study section (SS) devoted to applied physiology in 1964 which remained active until 2001 when it became amalgamated into other SSs. Before the end of the 20th century when

  15. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  16. Physiological mechanisms underlying animal social behaviour.

    Science.gov (United States)

    Seebacher, Frank; Krause, Jens

    2017-08-19

    Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

  17. Physiology of woody plants

    CERN Document Server

    Hazewinkel, Michiel; Pallardy, Stephen G

    1996-01-01

    This completely revised classic volume is an up-to-date synthesis of the intensive research devoted to woody plants. Intended primarily as a text for students and a reference for researchers, this interdisciplinary book should be useful to a broad range of scientists from agroforesters, agronomists, and arborists to plant pathologists, ecophysiologists, and soil scientists. Anyone interested in plant physiology will find this text invaluable. Key Features * Includes supplementary chapter summaries and lists of general references * Provides a solid foundation of reference information * Thoroughly updated classic text/reference.

  18. Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Maike Marczenke

    2017-07-01

    Full Text Available The ultrarapid delayed rectifier K+ current (IKur, mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF. Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout. This model as well as isogenic wild-type control hiPSCs could selectively be differentiated into ventricular or atrial cardiomyocytes at high efficiency, based on the specific manipulation of retinoic acid signaling. Investigation of electrophysiological properties in Kv1.5-deficient cardiomyocytes compared to isogenic controls revealed a strictly atrial-specific disease phentoype, characterized by cardiac subtype-specific field and action potential prolongation and loss of 4-aminopyridine sensitivity. Atrial Kv1.5-deficient cardiomyocytes did not show signs of arrhythmia under adrenergic stress conditions or upon inhibiting additional types of K+ current. Exposure of bulk cultures to carbachol lowered beating frequencies and promoted chaotic spontaneous beating in a stochastic manner. Low-frequency, electrical stimulation in single cells caused atrial and mutant-specific early afterdepolarizations, linking the loss of KCNA5 function to a putative trigger mechanism in familial AF. These results clarify for the first time the role of Kv1.5 in atrial hiPSC-cardiomyocytes and demonstrate the feasibility of cardiac subtype-specific disease modeling using engineered hiPSCs.

  19. The Shifting Subtypes of ADHD: Classification Depends on How Symptom Reports Are Combined

    Science.gov (United States)

    Rowland, Andrew S.; Skipper, Betty; Rabiner, David L.; Umbach, David M.; Stallone, Lil; Campbell, Richard A.; Hough, Richard L.; Naftel, A. J.; Sandler, Dale P.

    2008-01-01

    Research on the correlates of ADHD subtypes has yielded inconsistent findings, perhaps because the procedures used to define subtypes vary across studies. We examined this possibility by investigating whether the ADHD subtype distribution in a community sample was sensitive to different methods for combining informant data. We conducted a study to…

  20. Empirically Derived Learning Disability Subtypes: A Replication Attempt and Longitudinal Patterns over 15 Years.

    Science.gov (United States)

    Spreen, Otfried; Haaf, Robert G.

    1986-01-01

    Test scores of two groups of learning disabled children (N=63 and N=96) were submitted to cluster analysis in an attempt to replicate previously described subtypes. All three subtypes (visuo-perceptual, linguistic, and articulo-graphomotor types) were identified along with minimally and severely impaired subtypes. Similar clusters in the same…

  1. 1 original article diverse genetic subtypes of hiv-1 among female sex

    African Journals Online (AJOL)

    boaz

    Keywords: Diverse, HIV, subtypes, Female Sex workers and Vaccine ... significant probability that infection with this subtype occurred with a short incubation period (p< 0.05). Conclusion: This study .... regression was used to adjust for potential cofounders. .... TABLE 2: DISTRIBUTION OF HIV-1 SUBTYPES AMONG FSWS.

  2. Starting physiology: bioelectrogenesis.

    Science.gov (United States)

    Baptista, Vander

    2015-12-01

    From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic. Copyright © 2015 The American Physiological Society.

  3. Physiology of bile secretion.

    Science.gov (United States)

    Esteller, Alejandro

    2008-10-07

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

  4. Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

    Science.gov (United States)

    Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

    2013-03-01

    Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA 500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

  5. KHYG-1 and NK-92 represent different subtypes of LFA-1-mediated NK cell adhesiveness.

    Science.gov (United States)

    Suck, Garnet; Tan, Suet-Mien; Chu, Sixian; Niam, Madelaine; Vararattanavech, Ardcharaporn; Lim, Tsyr Jong; Koh, Mickey B C

    2011-01-01

    Novel cancer cellular therapy approaches involving long-term ex vivo IL-2 stimulated highly cytotoxic natural killer (NK) cells are emerging. However, adhesion properties of such NK cells are not very well understood. Herein, we describe the novel observation of permanently activated alphaLbeta2 integrin leukocyte function-associated antigen (LFA)-1 adhesion receptor in long-term IL-2 activated NK cells and the permanent NK cell lines KHYG-1 and NK-92. We show that such cytokine activated NK effectors constitutively adhered to the LFA-1-ligand ICAM-1, whereas binding to the lower affinity ligand ICAM-3 required additional exogenous activating conditions. The results demonstrate an extended conformation and an intermediate affinity state for the LFA-1 population expressed by the NK cells. Interestingly, adhesion to ICAM-1 or K562 induced pronounced cell spreading in KHYG-1, but not in NK-92, and partially in long-term IL-2 stimulated primary NK cells. It is conceivable that such differential adhesion characteristics may impact motility potential of such NK effectors with relevance to clinical tumor targeting. KHYG-1 could be a useful model in planning future targeted therapeutic approaches involving NK effectors with augmented functions.

  6. HIV subtype, epidemiological and mutational correlations in patients from Paraná, Brazil.

    Science.gov (United States)

    Silva, Monica Maria Gomes da; Telles, Flavio Queiroz; da Cunha, Clovis Arns; Rhame, Frank S

    2010-01-01

    Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. Patients with complete medical charts were selected (n = 191). Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%), 41 subtype C (21.5%), 10 subtype F (5.2%), 7 BF (3.7%) and 1 CF (0.5%). Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161) intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses, such as 65R and 106M, were uncommon in our study. Mutations 63P and 36I, previously reported as common in HIV-1 subtypes B and C from Brazil, respectively, were common. There is a significant frequency of HIV-1 non-B infections in Paraná state, with isolates classified as subtypes C, F, BF and BC. Patients with subtype C infection were more frequently female, heterosexual and had a longer average time of HIV diagnosis.

  7. Workplace Re-organization and Changes in Physiological Stress Markers

    DEFF Research Database (Denmark)

    Carlsson, Rikke Hinge; Hansen, Åse Marie; Kristiansen, Jesper

    2014-01-01

    The aim of this study was to investigate changes in physiological stress markers as a consequence of workplace reorganization. Moreover, we aimed to investigate changes in the psychosocial work environment (job strain, effortreward imbalance (ERI), in psychological distress (stress symptoms......, perceived stress) and the mediating effect of these factors on changes in physiological stress markers. We used data from a longitudinal study that studied the health consequences of a major reorganization of non-state public offices executed in Denmark on 1 January 2007. Collection of clinical...... and questionnaire data was in 2006 and 2008, and in this sub-study we included 359 participants. To reflect stress reactions of the autonomic nervous system, the endocrine system and the immune system, we included 13 physiological markers. We observed significant change in several physiological stress markers...

  8. Structural features of subtype-selective EP receptor modulators.

    Science.gov (United States)

    Markovič, Tijana; Jakopin, Žiga; Dolenc, Marija Sollner; Mlinarič-Raščan, Irena

    2017-01-01

    Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances.

    Science.gov (United States)

    Goadsby, Peter J

    2015-08-01

    The medical aphorism that common things happen commonly makes unique (and less common) migraine subtypes especially appropriate to review for the general neurologist. This article also identifies some rare headache disorders and other disturbances, and offers strategies to manage them. This article discusses migraine with brainstem aura, which is troublesome clinically and has had a change in terminology in the International Classification of Headache Disorders, Third Edition, beta version (ICHD-3 beta), and hemiplegic migraine, which is also troublesome in practice. The rare headache disorder hypnic headache and the exploding head syndrome are also discussed. When hypnic headache is recognized, it is eminently treatable, while exploding head syndrome is a benign condition with no reported consequences. Unique migraine subtypes, rare headache disorders, and other disturbances present to neurologists. When recognized, they can often be managed very well, which offers significant benefits to patients and practice satisfaction to neurologists.

  10. Etiologic stroke subtypes: updated definition and efficient workup strategies.

    Science.gov (United States)

    Mehndiratta, Prachi; Chapman Smith, Sherita; Worrall, Bradford B

    2015-01-01

    Stroke affects approximately 16.9 million individuals per year worldwide and is the second leading cause of death. Stroke represents a family of related, but distinct subtypes. Classifying stroke subtypes must take into account various aspects of a standardized stroke workup to allow optimization of treatment and prevention strategies. Secondary prevention and pharmacologic treatment is tailored based on stroke mechanism. Additionally prognostication and recurrent risk also depends on stroke etiology. Efficient workup of stroke relies on a thorough history, clinical examination, imaging studies, and putative mechanism of stroke that lead the treating physician to a particular etiological path. Here , we provide the reader with updated definitions of etiologic ischemic stroke types as well as efficient workup strategies.

  11. Reproductive profiles and risk of breast cancer subtypes

    DEFF Research Database (Denmark)

    Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka

    2017-01-01

    Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods: We used...... pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer...... the risk for TNBC (OR = 0.78, CI 0.70-0.88, p diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC....

  12. The whole-genome landscape of medulloblastoma subtypes

    Science.gov (United States)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Groebner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

    2018-01-01

    Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients. PMID:28726821

  13. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Directory of Open Access Journals (Sweden)

    Michael W. Peck

    2017-01-01

    Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

  14. Home geriatric physiological measurements.

    Science.gov (United States)

    Tamura, Toshiyo

    2012-10-01

    In an ageing society, the elderly can be monitored with numerous physiological, physical and passive devices. Sensors can be installed in the home for continuous mobility assistance and unobtrusive disease prevention. This review presents several modern sensors, which improve the quality of life and assist the elderly, disabled people and their caregivers. The main concept of geriatric sensors is that they are capable of providing assistance without limiting or disturbing the subject's daily routine, giving him or her greater comfort, pleasure and well-being. Furthermore, this review includes associated technologies of wearable/implantable monitoring systems and the 'smart-house' project. This review concludes by discussing future challenges of the future aged society.

  15. Home geriatric physiological measurements

    International Nuclear Information System (INIS)

    Tamura, Toshiyo

    2012-01-01

    In an ageing society, the elderly can be monitored with numerous physiological, physical and passive devices. Sensors can be installed in the home for continuous mobility assistance and unobtrusive disease prevention. This review presents several modern sensors, which improve the quality of life and assist the elderly, disabled people and their caregivers. The main concept of geriatric sensors is that they are capable of providing assistance without limiting or disturbing the subject's daily routine, giving him or her greater comfort, pleasure and well-being. Furthermore, this review includes associated technologies of wearable/implantable monitoring systems and the ‘smart-house’ project. This review concludes by discussing future challenges of the future aged society. (topical review)

  16. Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

    Science.gov (United States)

    Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

    2018-03-01

    Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

  17. Maltreatment and psychopathy subtypes in high-risk adolescent females

    OpenAIRE

    Coupland, Ruth Louise

    2011-01-01

    Psychopathy is often viewed as a unitary construct, however, research with adults and adolescent males has revealed two heterogeneous subtypes. Primary psychopathy is presumed to have biological underpinnings and is associated with low levels of anxiety and psychological distress. In contrast, secondary psychopathy is believed to result from exposure to adversity, including childhood maltreatment, and is associated with emotional reactivity, impulsivity, and comorbid psychological problems. T...

  18. Somatostatin receptor subtype expression in human thyroid tumours.

    Science.gov (United States)

    Klagge, A; Krause, K; Schierle, K; Steinert, F; Dralle, H; Fuhrer, D

    2010-04-01

    Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues. Georg Thieme Verlag KG Stuttgart New York.

  19. Major depressive disorder subtypes to predict long-term course

    Science.gov (United States)

    van Loo, Hanna M.; Cai, Tianxi; Gruber, Michael J.; Li, Junlong; de Jonge, Peter; Petukhova, Maria; Rose, Sherri; Sampson, Nancy A.; Schoevers, Robert A.; Wardenaar, Klaas J.; Wilcox, Marsha A.; Al-Hamzawi, Ali Obaid; Andrade, Laura Helena; Bromet, Evelyn J.; Bunting, Brendan; Fayyad, John; Florescu, Silvia E.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Levinson, Daphna; Medina-Mora, Maria Elena; Nakane, Yoshibumi; Posada-Villa, Jose; Scott, Kate M.; Xavier, Miguel; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Background Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data. PMID:24425049

  20. Multiple Receptor Subtypes for the CGRP Super-Family

    Directory of Open Access Journals (Sweden)

    R. Quirion

    2001-01-01

    Full Text Available Molecular evidence for the existence of multiple receptors for CGRP has been rather difficult to obtain. Over 10 years after suggesting the existence of at least two classes (CGRP1 and CGRP2 of CGRP receptors on the basis of pharmacological data[1], molecular data on the CGRP2 receptor subtype are still lacking as well as potent and selective antagonists. The situation is somewhat different for the functional CGRP1 subtype which is likely composed of diverse subunits CRLR, RAMP1 and possibly RCP[2]. Moreover, BIBN 4096BS was recently reported as the first nonpeptide highly potent CGRP1 receptor antagonist[3]. However, in situ hybridization and receptor autoradiographic data have clearly shown the existence of major mismatches (e.g., cerebellum between the discrete localization of CRLR, RAMP1, and specific CGRP binding sites supporting the existence of CGRP receptor subtypes. Functional studies have also provided evidence in that regard (for a recent review: [4]. Accordingly, additional studies aiming at cloning additional CGRP receptors are certainly warranted. Similarly, recent evidence from various laboratories including ours suggests the existence of more than one class (CRLR and RAMP2 of adrenomedullin receptors at least in the rat brain. In contrast, most evidence suggests the existence of a single class of amylin receptors. In brief, it appears that multiple receptors or receptor complexes do exist for CGRP and related peptides but their composition is apparently unique among the GPCR super-family and additional data are needed to fully establish the molecular organization of each subtype. Supported by CIHR of Canada.

  1. Refining developmental coordination disorder subtyping with multivariate statistical methods

    Directory of Open Access Journals (Sweden)

    Lalanne Christophe

    2012-07-01

    Full Text Available Abstract Background With a large number of potentially relevant clinical indicators penalization and ensemble learning methods are thought to provide better predictive performance than usual linear predictors. However, little is known about how they perform in clinical studies where few cases are available. We used Random Forests and Partial Least Squares Discriminant Analysis to select the most salient impairments in Developmental Coordination Disorder (DCD and assess patients similarity. Methods We considered a wide-range testing battery for various neuropsychological and visuo-motor impairments which aimed at characterizing subtypes of DCD in a sample of 63 children. Classifiers were optimized on a training sample, and they were used subsequently to rank the 49 items according to a permuted measure of variable importance. In addition, subtyping consistency was assessed with cluster analysis on the training sample. Clustering fitness and predictive accuracy were evaluated on the validation sample. Results Both classifiers yielded a relevant subset of items impairments that altogether accounted for a sharp discrimination between three DCD subtypes: ideomotor, visual-spatial and constructional, and mixt dyspraxia. The main impairments that were found to characterize the three subtypes were: digital perception, imitations of gestures, digital praxia, lego blocks, visual spatial structuration, visual motor integration, coordination between upper and lower limbs. Classification accuracy was above 90% for all classifiers, and clustering fitness was found to be satisfactory. Conclusions Random Forests and Partial Least Squares Discriminant Analysis are useful tools to extract salient features from a large pool of correlated binary predictors, but also provide a way to assess individuals proximities in a reduced factor space. Less than 15 neuro-visual, neuro-psychomotor and neuro-psychological tests might be required to provide a sensitive and

  2. Memory Processes in Learning Disability Subtypes of Children Born Preterm

    OpenAIRE

    McCoy, Thomasin E.; Conrad, Amy L.; Richman, Lynn C.; Nopoulos, Peg C.; Bell, Edward F.

    2012-01-01

    The purpose of this study was to evaluate immediate auditory and visual memory processes in learning disability subtypes of 40 children born preterm. Three subgroups of children were examined: (a) primary language disability group (n = 13), (b) perceptual-motor disability group (n = 14), and (c) no learning disability diagnosis group without identified language or perceptual-motor learning disability (n = 13). Between-group comparisons indicate no significant differences in immediate auditory...

  3. Anatomic mapping of molecular subtypes in diffuse glioma.

    Science.gov (United States)

    Tang, Qisheng; Lian, Yuxi; Yu, Jinhua; Wang, Yuanyuan; Shi, Zhifeng; Chen, Liang

    2017-09-15

    Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background. We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well. Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes. Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

  4. Physiology for engineers applying engineering methods to physiological systems

    CERN Document Server

    Chappell, Michael

    2016-01-01

    This book provides an introduction to qualitative and quantitative aspects of human physiology. It looks at biological and physiological processes and phenomena, including a selection of mathematical models, showing how physiological problems can be mathematically formulated and studied. It also illustrates how a wide range of engineering and physics topics, including electronics, fluid dynamics, solid mechanics and control theory can be used to describe and understand physiological processes and systems. Throughout the text there are introductions to measuring and quantifying physiological processes using both signal and imaging technologies. Physiology for Engineers describes the basic structure and models of cellular systems, the structure and function of the cardiovascular system, the electrical and mechanical activity of the heart and provides an overview of the structure and function of the respiratory and nervous systems. It also includes an introduction to the basic concepts and applications of reacti...

  5. Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

    DEFF Research Database (Denmark)

    Walter, Brandon L; Armitage, Andrew E; Graham, Stephen C

    2009-01-01

    BACKGROUND: Despite the existence of over 50 subtypes and circulating recombinant forms of HIV-1, subtype C dominates the heterosexual pandemic causing approximately 56% of all infections. OBJECTIVE: To evaluate whether viral genetic factors may contribute to the observed subtype-C predominance. ....... CONCLUSION: As CD4-CCR5-T cells are key targets for genital HIV infection and cervical selection can favor compact V1-V2 loops and 316T, which increase viral infectivity, we propose that these conserved subtype-C motifs may contribute to transmission and spread of this subtype....

  6. Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities

    Directory of Open Access Journals (Sweden)

    Ana L. Miranda-Vilela

    2009-01-01

    Full Text Available Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp*1 and Hp*2 alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp*1 allele has two subtypes, Hp*1F and Hp*1S, that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56, Kalunga Afro-descendants (n = 70 and an urban population (n = 132 were determined by allele-specific PCR. The Hp*1F allele frequency was highest in Kalunga (29.3% and lowest in Kayabi (2.6%. The Hp*1F/Hp*1S allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp*1F allele. However, despite the large variation in Hp*1F frequencies, results of FST (0.0291 indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp *1F and Hp*1S frequencies among non-Amerindian Brazilians.

  7. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition.

    Science.gov (United States)

    Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M; Leung, Samuel; Baker, Jennifer H; Lebovitz, Chandra; Dragowska, Wieslawa H; Go, Nancy E; Bally, Marcel B; Minchinton, Andrew I; Gelmon, Karen A; Gorski, Sharon M

    2016-10-11

    Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies.

  8. Differential immune microenvironments and response to immune checkpoint blockade amongst molecular subtypes of murine medulloblastoma

    Science.gov (United States)

    Pham, Christina D.; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M.; Yearley, Jennifer H.; Sayour, Elias J.; Pei, Yanxin; Moore, Colin; McLendon, Roger E.; Huang, Jianping; Sampson, John H.; Wechsler-Reya, Robert; Mitchell, Duane A.

    2016-01-01

    PURPOSE Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1+ peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3+ T cells within the tumor microenvironment. CONCLUSIONS This is the first immunologic characterization of preclinical models of molecular subtypes of MB and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. PMID:26405194

  9. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

    Science.gov (United States)

    Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

    2016-02-01

    Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

  10. Association of Blastocystis subtypes with diarrhea in children

    Science.gov (United States)

    Zulfa, F.; Sari, I. P.; Kurniawan, A.

    2017-08-01

    Blastocystis hominis is an intestinal zoonotic protozoa that epidemiological surveys have shown, is highly prevalent among children and may cause chronic diarrhea. This study aimed to identify Blastocystis subtypes among children and associate those subtypes to pathology. The study’s population was children aged 6-12 years old divided into asymptomatic and symptomatic (diarrhea) groups. The asymptomatic samples were obtained from primary school students in the Bukit Duri area of South Jakarta, while the symptomatic samples were obtained from patients who visited nearby primary health centers (Puskesmas). Symptomatic stool samples were examined inParasitology Laboratory FKUI. Microscopic examination of the stool samples was performed to screen for single Blastocystic infection, followed by culture, PCR of 18S rRNA, and sequencing. In the study, 53.2% of children (n = 156) harbored intestinal parasites, Blastocysts sp. A single infection of Blastocystis sp. was present in 69 (44.23%) samples, comprised of 36 symptomatic and 33 asymptomatic participants. The Blastocystis subtypes (STs) identified in this study were STs 1-4 ST3 was the most dominant and was observed with statistically significant higher frequency in the symptomatic group. ST4 was only found in one sample in the symptomatic group. While ST1 and ST2 were found more frequently in the asymptomatic group, no statistical association was observed. ST3 is more likely to be associated with clinical symptoms than ST1 and ST2.

  11. Somatoform disorders and the subtypes: do differences exist?

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2015-07-01

    Full Text Available Background: Psychiatric diagnoses, especially somatoform disorders, are based on phenomenology, i.e. the subjective experience of the symptoms by the patient. The concept of “medically unexplained symptoms” (MUS is now getting away with much focus on the symptoms per se rather than its explanation by some medical illness. Aim of the study: To study the symptom profile of somatoform disorders and to see its variability in relation to different subtypes of the disorder. Materials and methods: Hundred consecutive patients of somatoform disorders, diagnosed clinically based on the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10 criteria, were chosen after applying various inclusion and exclusion criteria.The Post Graduate Institute of Medical Education and Research (PGI Health Questionnaire N-2 was used to evaluate symptoms of the patients. Data was analysed with chi-square test. Result: Patients of somatization disorder (SD have significantly higher prevalence of symptoms related to eyes (p=.0412 and higher complaints of hot sensation in the body (p=.0007as compared to undifferentiated somatoform (UD disorder and other somatoform disorders. Hypochondriacal ideas are significantly less in UD and SD. Conclusion: Although traditionally, subtypes of somatoform disorders are supposed to have differences in the phenomenology, there is considerable overlap between them in clinical practice. It may mean that all somatoform disorders are virtually same and there may be no need to have many subtypes.

  12. The global spread of HIV-1 subtype B epidemic.

    Science.gov (United States)

    Magiorkinis, Gkikas; Angelis, Konstantinos; Mamais, Ioannis; Katzourakis, Aris; Hatzakis, Angelos; Albert, Jan; Lawyer, Glenn; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Gomes, Perpétua; Camacho, Ricardo J; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Anders; Kostrikis, Leondios G; Lepej, Snjezana J; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elizabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Stylianou, Dora C; Boucher, Charles A B; Nikolopoulos, Georgios; Vasylyeva, Tetyana; Friedman, Samuel R; van de Vijver, David; Angarano, Gioacchino; Chaix, Marie-Laure; de Luca, Andrea; Korn, Klaus; Loveday, Clive; Soriano, Vincent; Yerly, Sabine; Zazzi, Mauricio; Vandamme, Anne-Mieke; Paraskevis, Dimitrios

    2016-12-01

    Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Stroke subtype classification by geometrical descriptors of lesion shape.

    Directory of Open Access Journals (Sweden)

    Bastian Cheng

    Full Text Available Inference of etiology from lesion pattern in acute magnetic resonance imaging is valuable for management and prognosis of acute stroke patients. This study aims to assess the value of three-dimensional geometrical lesion-shape descriptors for stroke-subtype classification, specifically regarding stroke of cardioembolic origin.Stroke Etiology was classified according to ASCOD in retrospectively selected patients with acute stroke. Lesions were segmented on diffusion-weighed datasets, and descriptors of lesion shape quantified: surface area, sphericity, bounding box volume, and ratio between bounding box and lesion volume. Morphological measures were compared between stroke subtypes classified by ASCOD and between patients with embolic stroke of cardiac and non-cardiac source.150 patients (mean age 77 years; 95% CI, 65-80 years; median NIHSS 6, range 0-22 were included. Group comparison of lesion shape measures demonstrated that lesions caused by small-vessel disease were smaller and more spherical compared to other stroke subtypes. No significant differences of morphological measures were detected between patients with cardioembolic and non-cardioembolic stroke.Stroke lesions caused by small vessel disease can be distinguished from other stroke lesions based on distinctive morphological properties. However, within the group of embolic strokes, etiology could not be inferred from the morphology measures studied in our analysis.

  14. Association of human herpesvirus 6 subtypes with symptomatic apical periodontitis.

    Science.gov (United States)

    Hernádi, Katinka; Csoma, Eszter; Adám, Balázs; Szalmás, Anita; Gyöngyösi, Eszter; Veress, György; Ildikó-Márton; Kónya, József

    2011-09-01

    The occurrence of human herpesvirus (HHV) 6 subtypes A and B in apical periodontitis was determined. The relationship of HHV-6 subtypes to other disease associated herpesviruses, i.e., Epstein-Barr virus (EBV) and human cytomegalovirus, was also investigated. Forty apical periodontitis samples (17 symptomatic and 23 asymptomatic) and 40 healthy pulp control samples were collected. Nested polymerase chain reaction was used to detect HHV-6 DNA. HHV-6 DNA was observed in significantly higher frequencies in apical periodontitis samples than in control samples (20% vs. 2.5%; P = .03). Further classification of apical lesions revealed that subtype B of HHV-6 was significantly associated with large-sized and symptomatic lesions (P apical lesions (77%) harbored ≥1 of the tested herpesviruses: EBV was the most frequent herpesvirus (72.5%) in apical periodontitis, followed by HHV-6 (20%). Our findings suggest that EBV and HHV-6B infections can be associated with symptomatic apical periodontitis. Copyright © 2011 Mosby, Inc. All rights reserved.

  15. Clinical investigation of set-shifting subtypes in anorexia nervosa.

    Science.gov (United States)

    Abbate-Daga, Giovanni; Buzzichelli, Sara; Marzola, Enrica; Amianto, Federico; Fassino, Secondo

    2014-11-30

    While evidence continues to accumulate on the relevance of cognitive inflexibility in anorexia nervosa (AN), its clinical correlates remain unclear. We aimed at examining the relationship between set-shifting and clinical variables (i.e., eating psychopathology, depression, and personality) in AN. Ninety-four individuals affected by AN and 59 healthy controls (HC) were recruited. All participants were assessed using: Eating Disorders Inventory-2 (EDI-2), Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). The AN group scored worse than HCs on set-shifting. According to their neuropsychological performances, AN patients were split into two groups corresponding to poor (N=30) and intact (N=64) set-shifting subtypes. Interoceptive awareness, impulse regulation, and maturity fears on the EDI-2 and depression on the BDI differed across all groups (HC, intact, and poor set-shifting subtype). Self-directedness on the TCI differed significantly among all groups. Cooperativeness and reward dependence differed instead only between HC and AN poor set-shifting subtype. After controlling for depression, only interoceptive awareness remained significant with reward dependence showing a trend towards statistical significance. These findings suggest that multiple clinical variables may be correlated with set-shifting performances in AN. The factors contributing to impaired cognitive inflexibility could be more complex than heretofore generally considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Strategies for subtyping influenza viruses circulating in the Danish pig population

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    2010-01-01

    in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays......Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...... were specific when applied on Danish influenza positive samples, whereas the N2 assay consistently showed several unspecific PCR products. A subset of positive influenza samples detected by the real time RT-PCR screening assay could not be subtyped using these assays. Therefore, new influenza subtyping...

  17. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    International Nuclear Information System (INIS)

    Cunha, L.K.H.; Kashima, S.; Amarante, M.F.C.; Haddad, R.; Rodrigues, E.S.; Silva, K.L.T.; Lima, T.A.; Castro, D.B.; Brito, F.C.; Almeida, E.G.; Covas, D.T.; Malheiro, A.

    2012-01-01

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization

  18. Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

    Science.gov (United States)

    Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

    2017-10-01

    A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, L.K.H. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Kashima, S.; Amarante, M.F.C.; Haddad, R.; Rodrigues, E.S. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, K.L.T.; Lima, T.A.; Castro, D.B.; Brito, F.C.; Almeida, E.G. [Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil); Covas, D.T. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Malheiro, A. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil)

    2012-01-20

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization.

  20. Subtypes of Patients Experiencing Exacerbations of COPD and Associations with Outcomes

    Science.gov (United States)

    Arostegui, Inmaculada; Esteban, Cristobal; García-Gutierrez, Susana; Bare, Marisa; Fernández-de-Larrea, Nerea; Briones, Eduardo; Quintana, José M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify

  1. Procedures of Exercise Physiology Laboratories

    Science.gov (United States)

    Bishop, Phillip A.; Fortney, Suzanne; Greenisen, Michael; Siconolfi, Steven F.; Bamman, Marcas M.; Moore, Alan D., Jr.; Squires, William

    1998-01-01

    This manual describes the laboratory methods used to collect flight crew physiological performance data at the Johnson Space Center. The Exercise Countermeasures Project Laboratory is a standard physiology laboratory; only the application to the study of human physiological adaptations to spaceflight is unique. In the absence of any other recently published laboratory manual, this manual should be a useful document staffs and students of other laboratories.

  2. Conservation physiology of marine fishes

    DEFF Research Database (Denmark)

    Jørgensen, Christian; Peck, Myron A.; Antognarelli, Fabio

    2012-01-01

    At the end of May, 17 scientists involved in an EU COST Action on Conservation Physiology of Marine Fishes met in Oristano, Sardinia, to discuss how physiology can be better used in modelling tools to aid in management of marine ecosystems. Current modelling approaches incorporate physiology...... to different extents, ranging from no explicit consideration to detailed physiological mechanisms, and across scales from a single fish to global fishery resources. Biologists from different sub-disciplines are collaborating to rise to the challenge of projecting future changes in distribution and productivity...

  3. Change of expression of renal alpha1-adrenergic receptor and angiotensin II receptor subtypes with aging in rats.

    Science.gov (United States)

    Li, Yan-Fang; Cao, Xiao-Jing; Bai, Xue-Yuan; Lin, Shu-Peng; Shi, Shu-Tian

    2010-04-01

    It has been considered that the functional decline of renal vasoconstriction during senescence is associated with an alteration in renal alpha1-adrenergic receptor (alpha1-AR) expression. While alterations in renal angiotensin II receptor (ATR) expression was considered to have an effect on renal structure and function, until now little information has been available concerning alpha1-AR and ATR expression variations over the entire aging continuum. The present study was undertaken to examine the expression levels of alpha1-AR and ATR subtypes in renal tissue during the spectrum running from young adulthood, to middle age, to the presenium, and to the senium. Semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot were used to quantify the messenger RNA (mRNA) and protein levels of alpha1-AR and ATR subtypes in renal tissue in 3-month-old (young adult), 12-month-old (middle age), 18-month-old (presenium) and 24-month-old (senium) Wistar rats. alpha1A-AR expression decreased gradually with aging: it was decreased during middle age, the presenium and the senium, compared, respectively, with young adult values (page and in the senium with respect to the presenium. alpha1B-AR and alpha1D-AR expression were unmodified during senescence. AT1R expression was unaffected by aging during young adulthood and middle age, but exhibited a remarkable downregulation in the presenium and senium periods (prenal alpha1-AR and ATR subtypes during aging. alpha1A-AR expression downregulation may account for the reduced reactivity of renal alpha1-AR to vasoconstrictors and to renal function decline in the senium. Both the downregulation of AT1R and the upregulation of AT2R may be influential in maintaining normal physiological renal function during aging.

  4. Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

    Science.gov (United States)

    Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

  5. Superficial basal cell carcinoma: A comparison of superficial only subtype with superficial combined with other subtypes by age, sex and anatomic site in 3150 cases.

    Science.gov (United States)

    Pyne, John H; Myint, Esther; Barr, Elizabeth M; Clark, Simon P; David, Michael; Na, Renua; Hou, Ruihang

    2017-08-01

    Basal cell carcinoma (BCC) may present as superficial subtype alone (sBCC) or superficial combined with other subtypes. The objective of this study was to compare sBCC without or with other BCC subtypes by age, sex and anatomic site. We retrospectively collected superficial BCC with the above characteristics from an Australian center during 2009 to 2014. We recorded 1528 sBCC and 1622 superficial BCC combined with other BCC subtype cases. Males numbered 2007 and females 1140. On males, head sites (forehead, cheek, nose and ear combined) compared to limb plus trunk sites displayed a higher incidence of superficial BCC combined with either nodular and or aggressive BCC subtypes (OR 13.15 CI 95% 8.9-19.5 P < .0001). On females a similar comparison also found a higher incidence of superficial BCC combined with solid subtype BCC on head sites compared to trunk and limb sites (OR 9.66 CI 95% 5.8-16.1 P < .0001). Superficial BCC alone is more likely on younger females on trunk and limb sites. Small partial biopsies reported as sBCC may miss other BCC subtypes present with higher risk on facial sites for males and females. Males had smaller proportions of superficial only subtype BCC on facial and ear sites compared to females. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The Region of Difference Four is a Robust Genetic Marker for Subtyping Mycobacterium caprae Isolates and is Linked to Spatial Distribution of Three Subtypes.

    Science.gov (United States)

    Rettinger, A; Broeckl, S; Fink, M; Prodinger, W M; Blum, H; Krebs, S; Domogalla, J; Just, F; Gellert, S; Straubinger, R K; Büttner, M

    2017-06-01

    Alpine Mycobacterium caprae isolates found in cattle and red deer display at least three genetic variations in the region of difference four (RD4) that can be used for further differentiation of the isolates into the subtypes 'Allgäu', 'Karwendel' and 'Lechtal'. Each genomic subtype is thereby characterized by a specific nucleotide deletion pattern in the 12.7-kb RD4 region. Even though M. caprae infections are frequently documented in cattle and red deer, little is known about the transmission routes. Hence, robust markers for M. caprae subtyping are needed to gain insight into the molecular epidemiology. For this reason, a rapid and robust multiplex PCR was developed for the simultaneous detection of three M. caprae RD4 subtypes and was used to subtype a total number of 241 M. caprae isolates from animals (145 cattle, 95 red deer and one fox) from Bavaria and Austria. All three subtypes occur spatially distributed and are found in cattle and in red deer suggesting transmission between the two species. As subtypes are genetically stable in both species it is hypothesized that the described genetic variations developed within the host due to 'within-host replication'. The results of this study recommend the genomic RD4 region as a reliable diagnostic marker for M. caprae subtype differentiation. © 2015 Blackwell Verlag GmbH.

  7. Smolt physiology and endocrinology

    Science.gov (United States)

    McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  8. Polyamines in plant physiology

    Science.gov (United States)

    Galston, A. W.; Sawhney, R. K.

    1990-01-01

    The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.

  9. Clinical physiology grand rounds.

    Science.gov (United States)

    Richards, Jeremy; Schwartzstein, Richard; Irish, Julie; Almeida, Jacqueline; Roberts, David

    2013-04-01

    Clinical Physiology Grand Rounds (CPGR) is an interactive, case-based conference for medical students designed to: (1) integrate preclinical and clinical learning; (2) promote inductive clinical reasoning; and (3) emphasise students as peer teachers. CPGR specifically encourages mixed learning level student interactions and emphasises the use of concept mapping. We describe the theoretical basis and logistical considerations for an interactive, integrative, mixed-learner environment such as CPGR. In addition, we report qualitative data regarding students' attitudes towards and perceptions of CPGR. Medical students from first to fourth year participate in a monthly, interactive conference. The CPGR was designed to bridge gaps and reinforce linkages between basic science and clinical concepts, and to incorporate interactive vertical integration between preclinical and clinical students. Medical education and content experts use Socratic, interactive teaching methods to develop real-time concept maps to emphasise the presence and importance of linkages across curricula. Student focus groups were held to assess attitudes towards and perceptions of the mixed-learner environment and concept maps in CPGR. Qualitative analyses of focus group transcripts were performed to develop themes and codes describing the students' impressions of CPGR. CPGR is a case-based, interactive conference designed to help students gain an increased appreciation of linkages between basic science and clinical medicine concepts, and an increased awareness of clinical reasoning thought processes. Success is dependent upon explicit attention being given to goals for students' integrated learning. © Blackwell Publishing Ltd 2013.

  10. TMPRSS12 Is an Activating Protease for Subtype B Avian Metapneumovirus.

    Science.gov (United States)

    Yun, Bingling; Zhang, Yao; Liu, Yongzhen; Guan, Xiaolu; Wang, Yongqiang; Qi, Xiaole; Cui, Hongyu; Liu, Changjun; Zhang, Yanping; Gao, Honglei; Gao, Li; Li, Kai; Gao, Yulong; Wang, Xiaomei

    2016-12-15

    The entry of avian metapneumovirus (aMPV) into host cells initially requires the fusion of viral and cell membranes, which is exclusively mediated by fusion (F) protein. Proteolysis of aMPV F protein by endogenous proteases of host cells allows F protein to induce membrane fusion; however, these proteases have not been identified. Here, we provide the first evidence that the transmembrane serine protease TMPRSS12 facilitates the cleavage of subtype B aMPV (aMPV/B) F protein. We found that overexpression of TMPRSS12 enhanced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. Subsequently, knockdown of TMPRSS12 with specific small interfering RNAs (siRNAs) reduced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. We also found a cleavage motif in the aMPV/B F protein (amino acids 100 and 101) that was recognized by TMPRSS12. The histidine, aspartic acid, and serine residue (HDS) triad of TMPRSS12 was shown to be essential for the proteolysis of aMPV/B F protein via mutation analysis. Notably, we observed TMPRSS12 mRNA expression in target organs of aMPV/B in chickens. Overall, our results indicate that TMPRSS12 is crucial for aMPV/B F protein proteolysis and aMPV/B infectivity and that TMPRSS12 may serve as a target for novel therapeutics and prophylactics for aMPV. Proteolysis of the aMPV F protein is a prerequisite for F protein-mediated membrane fusion of virus and cell and for aMPV infection; however, the proteases used in vitro and vivo are not clear. A combination of analyses, including overexpression, knockdown, and mutation methods, demonstrated that the transmembrane serine protease TMPRSS12 facilitated cleavage of subtype B aMPV (aMPV/B) F protein. Importantly, we located the motif in the aMPV/B F protein recognized by TMPRSS12 and the catalytic triad in TMPRSS12 that facilitated proteolysis of the aMPV/B F protein. This is the first report on TMPRSS12 as a protease for proteolysis of viral envelope

  11. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    Directory of Open Access Journals (Sweden)

    Hsu Hui-Chi

    2011-04-01

    Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

  12. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

    2011-01-01

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  13. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  14. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  15. The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico

    Directory of Open Access Journals (Sweden)

    Pablo López

    2015-12-01

    Full Text Available HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B. However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945 were obtained from our “HIV Genotyping” test file, which has been generated over a period of 14 years (2001–2014. REGA subtyping tool found the following subtypes: B (90%, B-like (3%, B/D recombinant (6%, and D/B recombinant (0.6%. Though there were fewer cases, the following subtypes were also found (in the given proportions: A1B (0.3%, BF1 (0.2%, subtype A (01-AE (0.1%, subtype A (A2 (0.1%, subtype F (12BF (0.1%, CRF-39 BF-like (0.1%, and others (0.1%. Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

  16. The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico.

    Science.gov (United States)

    López, Pablo; Rivera-Amill, Vanessa; Rodríguez, Nayra; Vargas, Freddie; Yamamura, Yasuhiro

    2015-12-23

    HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B). However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945) were obtained from our "HIV Genotyping" test file, which has been generated over a period of 14 years (2001-2014). REGA subtyping tool found the following subtypes: B (90%), B-like (3%), B/D recombinant (6%), and D/B recombinant (0.6%). Though there were fewer cases, the following subtypes were also found (in the given proportions): A1B (0.3%), BF1 (0.2%), subtype A (01-AE) (0.1%), subtype A (A2) (0.1%), subtype F (12BF) (0.1%), CRF-39 BF-like (0.1%), and others (0.1%). Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

  17. [Clinical subtypes of essential tremor and their electrophysiological and pharmacological differences].

    Science.gov (United States)

    Koguchi, Y; Nakajima, M; Kawamura, M; Hirayama, K

    1995-02-01

    We divided 19 patients with essential tremor into two subtypes according to clinical characteristics of the tremor. Ten patients had pure postural tremor distributed in the hand(s), head, and face (group A). Nine patients had tremor extending to the voice or leg(s), associated with resting tremor and/or hyperkinesie volitionnelle of the hand(s) (group B). Their ages, the age of onset, and the duration of illness were not different between the two groups. Electrophysiologically, the tremor of group A patients had higher frequencies than that of group B patients, and had synchronized activities for antagonistic muscles. Four of group B patients had reciprocal antagonistic activities of the tremor. Inactive phase of tremor induced by an electrically-evoked muscle twitch was invariably within the range of the physiological silent period for group A patients, and prolonged beyond the range for four of group B patients. Pharmacologically, 78% of group A patients responded well to beta-blocker, which was effective for 25% of group B patients. Sixty per cent of beta-blocker-resistant group B patients responded well to phenobarbital. In conclusion, a peripheral mechanism, presumably beta-adrenergic drive, is important for the tremor in group A patients, while central pathogenic mechanisms are more important for the tremor of group B patients.

  18. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

    Science.gov (United States)

    Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

    2015-12-01

    Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. © FASEB.

  19. Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study.

    Science.gov (United States)

    Morandi, Alessandro; Di Santo, Simona G; Cherubini, Antonio; Mossello, Enrico; Meagher, David; Mazzone, Andrea; Bianchetti, Angelo; Ferrara, Nicola; Ferrari, Alberto; Musicco, Massimo; Trabucchi, Marco; Bellelli, Giuseppe

    2017-10-01

    To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to report the prevalence and clinical profile of subtypes of delirium in a multicenter study. This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes. Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9). The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

    Directory of Open Access Journals (Sweden)

    Thomas P Stricker

    2017-03-01

    Full Text Available Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+ subtype and fourteen triple negative (TN subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  1. Physiologic effects of bowel preparation

    DEFF Research Database (Denmark)

    Holte, Kathrine; Nielsen, Kristine Grubbe; Madsen, Jan Lysgård

    2004-01-01

    PURPOSE: Despite the universal use of bowel preparation before colonoscopy and colorectal surgery, the physiologic effects have not been described in a standardized setting. This study was designed to investigate the physiologic effects of bowel preparation. METHODS: In a prospective study, 12...

  2. Comparative Digestive Physiology

    Science.gov (United States)

    Karasov, William H.; Douglas, Angela E.

    2015-01-01

    In vertebrates and invertebrates, morphological and functional features of gastrointestinal (GI) tracts generally reflect food chemistry, such as content of carbohydrates, proteins, fats, and material(s) refractory to rapid digestion (e.g., cellulose). The expression of digestive enzymes and nutrient transporters approximately matches the dietary load of their respective substrates, with relatively modest excess capacity. Mechanisms explaining differences in hydrolase activity between populations and species include gene copy number variations and single-nucleotide polymorphisms. Transcriptional and posttranscriptional adjustments mediate phenotypic changes in the expression of hydrolases and transporters in response to dietary signals. Many species respond to higher food intake by flexibly increasing digestive compartment size. Fermentative processes by symbiotic microorganisms are important for cellulose degradation but are relatively slow, so animals that rely on those processes typically possess special enlarged compartment(s) to maintain a microbiota and other GI structures that slow digesta flow. The taxon richness of the gut microbiota, usually identified by 16S rRNA gene sequencing, is typically an order of magnitude greater in vertebrates than invertebrates, and the interspecific variation in microbial composition is strongly influenced by diet. Many of the nutrient transporters are orthologous across different animal phyla, though functional details may vary (e.g., glucose and amino acid transport with K+ rather than Na+ as a counter ion). Paracellular absorption is important in many birds. Natural toxins are ubiquitous in foods and may influence key features such as digesta transit, enzymatic breakdown, microbial fermentation, and absorption PMID:23720328

  3. Induction of local and systemic immune reactions following infection of turkeys with avian Metapneumovirus (aMPV) subtypes A and B.

    Science.gov (United States)

    Liman, Martin; Rautenschlein, Silke

    2007-02-15

    Most of the studies regarding the immunopathogenesis of avian Metapneumovirus (aMPV) have been done with subtype C of aMPV. Not much is known about the immunopathogenesis of aMPV subtypes A and B in turkeys. Specifically, local immune reactions have not been investigated yet. We conducted two experiments in commercial turkeys. We investigated local and systemic humoral and cell mediated immune reactions following infection with an attenuated vaccine strain of aMPV subtype B (Experiment I) and virulent strains of aMPV subtypes A and B (Experiment II). Turkeys infected with virulent aMPV strains developed mild respiratory signs while birds inoculated with the attenuated aMPV did not show any clinical signs. Virus neutralizing antibodies were detected locally in tracheal washes and systemically in serum as soon as 5-7 days post aMPV infection (PI) independent of the strain used. Virus neutralizing antibody titres peaked at 7 days PI and then antibody levels declined. The peak of serum ELISA antibody production varied between infected groups and ranged from 14 and 28 days PI. All aMPV strains induced an increase in the percentage of CD4+ T cell populations in spleen and Harderian gland at days 7 or 14 PI. Furthermore, as shown in Experiment I, infection with the attenuated aMPV-B strain stimulated spleen leukocytes to release significantly higher levels of interferons (IFNs), interleukin-6 and nitric oxide in ex vivo culture in comparison to virus-free controls up to 7 days PI (P<0.05). As detected by quantitative real time RT-PCR in Experiment II, infection with virulent aMPV induced an increased IFNgamma expression in the Harderian gland in comparison to virus-free controls. IFNgamma expression in the spleen varied between aMPV strains and days PI. Overall, our study demonstrates that aMPV subtypes A and B infection induced humoral and cell mediated immune reactions comparable to subtype C infections. We observed only temporary stimulation of serum virus neutralizing

  4. Changes in insomnia subtypes in early Parkinson disease.

    Science.gov (United States)

    Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

    2017-01-24

    To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

  5. Rate of renal cell carcinoma subtypes in different races

    Directory of Open Access Journals (Sweden)

    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  6. OCD with comorbid OCPD: a subtype of OCD?

    Science.gov (United States)

    Coles, Meredith E; Pinto, Anthony; Mancebo, Maria C; Rasmussen, Steven A; Eisen, Jane L

    2008-03-01

    The current study examined the validity of using comorbid obsessive-compulsive personality disorder (OCPD) to identify a subtype of individuals with obsessive-compulsive disorder (OCD). Data for the current study were drawn from an ongoing, longitudinal study of the course of OCD and include intake assessments for 238 subjects with primary and current DSM-IV OCD who were treatment seeking. More than one fourth of the subjects (N=65, 27%) met criteria for comorbid OCPD. As compared to OCD-OCPD subjects, the OCD+OCPD subjects had a significantly younger age at onset of first OC symptoms (p=0.013), and a higher rate of symmetry and hoarding obsessions, and cleaning, ordering, repeating, and hoarding compulsions (all p'sOCPD had higher rates of comorbid anxiety disorders (p=0.007) and avoidant personality disorder (p=0.006). The OCD+OCPD subjects also had significantly lower ratings of global functioning (p=0.001) and more impaired social functioning (p=0.004), despite a lack of significant differences on overall severity of OCD symptoms. Our findings indicate that individuals with both OCD and OCPD have distinct clinical characteristics in terms of age at onset of initial OC symptoms, the types of obsessions and compulsions they experience, and psychiatric comorbidity. Our findings, coupled with data from family studies showing a higher than expected frequency of OCPD in first degree relatives of OCD probands, suggest that OCD associated with OCPD may represent a specific subtype of OCD. Additional research is warranted to further establish the validity of this subtype.

  7. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Science.gov (United States)

    2016-08-26

    Each neurotoxin subtype within a serotype cleaves its target substrate at the same single conserved peptide bond, except for BoNT/F5 (Table 2) [55...common for strains of C. botulinum Group III to form a chimeric or hybrid protein that combines elements of BoNT/C and BoNT/D neurotoxin, rather than a...Approved for public release; distribution is unlimited. UNCLASSIFIED 15 reported as BoNT/CD or BoNT/DC chimeric toxins [22]. Two exotoxins

  8. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

    Directory of Open Access Journals (Sweden)

    Isabel Cubero-Millán

    2014-09-01

    Full Text Available The vast majority of Attention-deficit/hyperactivity disorder (ADHD patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1 the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2 the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria were divided into subgroups using the “Children’s Depression Inventory” (CDI. Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

  9. The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

    Science.gov (United States)

    Perez-Aso, M; Segura, V; Montó, F; Barettino, D; Noguera, M A; Milligan, G; D'Ocon, P

    2013-10-01

    We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting β-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by β-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on β-arrestin 2 mediated internalization. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Physiological basis of tingling paresthesia evoked by hydroxy-α-sanshool

    Science.gov (United States)

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-01-01

    Hydroxy-α-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-α-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultra-sensitive light touch receptors in the skin, and targets novel populations of Aβ and C-fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury. PMID:20335471

  11. Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool.

    Science.gov (United States)

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-03-24

    Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.

  12. Physiology of Sedentary Behavior and Its Relationship to Health Outcomes

    Science.gov (United States)

    Thyfault, John P; Du, Mengmeng; Kraus, William E; Levine, James A; Booth, Frank W

    2014-01-01

    Purpose This paper reports on the findings and recommendations of the “Physiology of Sedentary Behavior and its Relationship to Health Outcomes” group, a part of a larger workshop entitled Sedentary Behavior: Identifying Research Priorities sponsored by the National Heart, and Lung and Blood Institute and the National Institute on Aging, which aimed to establish sedentary behavior research priorities. Methods The discussion within our workshop lead to the formation of critical physiological research objectives related to sedentary behaviors, that if appropriately researched would greatly impact our overall understanding of human health and longevity. Results and Conclusions Primary questions are related to physiological “health outcomes” including the influence of physical activity vs. sedentary behavior on function of a number of critical physiological systems (aerobic capacity, skeletal muscle metabolism and function, telomeres/genetic stability, and cognitive function). The group also derived important recommendations related to the “central and peripheral mechanisms” that govern sedentary behavior and how energy balance has a role in mediating these processes. General recommendations for future sedentary physiology research efforts include that studies of sedentary behavior, including that of sitting time only, should focus on the physiological impact of a “lack of human movement” in contradistinction to the effects of physical movement and that new models or strategies for studying sedentary behavior induced adaptations and links to disease development are needed to elucidate underlying mechanism(s). PMID:25222820

  13. Cassava biology and physiology.

    Science.gov (United States)

    El-Sharkawy, Mabrouk A

    2004-11-01

    Cassava or manioc (Manihot esculenta Crantz), a perennial shrub of the New World, currently is the sixth world food crop for more than 500 million people in tropical and sub-tropical Africa, Asia and Latin America. It is cultivated mainly by resource-limited small farmers for its starchy roots, which are used as human food either fresh when low in cyanogens or in many processed forms and products, mostly starch, flour, and for animal feed. Because of its inherent tolerance to stressful environments, where other food crops would fail, it is often considered a food-security source against famine, requiring minimal care. Under optimal environmental conditions, it compares favorably in production of energy with most other major staple food crops due to its high yield potential. Recent research at the Centro Internacional de Agricultura Tropical (CIAT) in Colombia has demonstrated the ability of cassava to assimilate carbon at very high rates under high levels of humidity, temperature and solar radiation,which correlates with productivity across all environments whether dry or humid. When grown on very poor soils under prolonged drought for more than 6 months, the crop reduce both its leaf canopy and transpiration water loss, but its attached leaves remain photosynthetically active, though at greatly reduced rates. The main physiological mechanism underlying such a remarkable tolerance to drought was rapid stomatal closure under both atmospheric and edaphic water stress, protecting the leaf against dehydration while the plant depletes available soil water slowly during long dry periods. This drought tolerance mechanism leads to high crop water use efficiency values. Although the cassava fine root system is sparse, compared to other crops, it can penetrate below 2 m soil,thus enabling the crop to exploit deep water if available. Leaves of cassava and wild Manihot possess elevated activities of the C4 enzyme PEP carboxylase but lack the leaf Kranz anatomy typical of C4

  14. Physiology of cell volume regulation in vertebrates

    DEFF Research Database (Denmark)

    Hoffmann, Else K; Lambert, Ian H; Pedersen, Stine F

    2009-01-01

    and their regulation by, e.g., membrane deformation, ionic strength, Ca(2+), protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate...... organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.......The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most...

  15. Phosphodiesterases in endocrine physiology and disease.

    Science.gov (United States)

    Vezzosi, Delphine; Bertherat, Jérôme

    2011-08-01

    The cAMP-protein kinase A pathway plays a central role in the development and physiology of endocrine tissues. cAMP mediates the intracellular effects of numerous peptide hormones. Various cellular and molecular alterations of the cAMP-signaling pathway have been observed in endocrine diseases. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. Indeed, PDEs are the only known mechanism for inactivation of cAMP by catalysis to 5'-AMP. It has been suggested that disruption of PDEs could also have a role in the pathogenesis of many endocrine diseases. This review summarizes the most recent advances concerning the role of the PDEs in the physiopathology of endocrine diseases. The potential significance of this knowledge can be easily envisaged by the development of drugs targeting specific PDEs.

  16. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    OpenAIRE

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  17. Evidence of multiple introductions of HIV-1 subtype C in Angola.

    Science.gov (United States)

    Afonso, Joana Morais; Morgado, Mariza G; Bello, Gonzalo

    2012-10-01

    HIV-1 subtype C is the most prevalent group M clade in southern Africa and some eastern African countries. Subtype C is also the most frequent subtype in Angola (southwestern Africa), with an estimated prevalence of 10-20%. In order to better understand the origin of the HIV-1 subtype C strains circulating in Angola, 31 subtype C pol sequences of Angolan origin were compared with 1950 subtype C pol sequences sampled in other African countries. Phylogenetic analyses reveal that the Angolan subtype C sequences were distributed in 16 different lineages that were widely dispersed among other African strains. Ten subtype C Angolan lineages were composed by only one sequence, while the remaining six clades contain between two and seven sequences. Bayesian phylogeographic analysis indicates that most Angolan clades probably originated in different southern African countries with the exception of one lineage that most likely originated in Burundi. Evolutionary analysis suggests that those Angolan subtype C clades composed by ≥ 2 sequences were introduced into the country between the late 1970s and the mid 2000s. The median estimated time frame for the origin of those Angolan lineages coincides with periods of positive migration influx in Angola that were preceded by phases of negative migratory outflow. These results demonstrate that the Angolan subtype C epidemic resulted from multiple introductions of subtype C viruses mainly imported from southern African countries over the last 30years, some of which have been locally disseminated establishing several autochthonous transmission networks. This study also suggests that population mobility between Angola and southern African countries during civil war (1974-2002) may have played a key role in the emergence of the Angolan subtype C epidemic. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. All Fatigue is Not Created Equal: The Association of Fatigue and Its Subtypes on Pain Interference in Orofacial Pain.

    Science.gov (United States)

    Boggero, Ian A; Rojas-Ramirez, Marcia V; Carlson, Charles R

    2017-03-01

    Fatigue is known to be a pathway through which depression, psychological distress, pain intensity, and sleep disturbance influence pain interference, but the independent effects of fatigue on pain interference after controlling for these variables remains unknown. In addition, no study to date has tested whether fatigue subtypes of general fatigue, mental fatigue, emotional fatigue, physical fatigue, or vigor differentially predict pain interference. The current study tested these associations using archival medical data of 2133 chronic orofacial pain patients, who completed a battery of psychological questionnaires at the time of their first appointment at an orofacial pain clinic. Hierarchical linear regression analysis revealed that after controlling for depression, psychological distress, sleep disturbance, pain intensity, and demographic variables, fatigue predicted higher pain interference (B=0.70, SE=0.17, Ppain interference after controlling for the aforementioned variables. The findings suggest that fatigue is an important independent predictor of pain interference and not merely a mediator. These findings also suggest that not all fatigue is created equal. Interventions aimed at reducing pain interference should target specific fatigue symptoms of physical fatigue and vigor. Future research investigating the independent associations of fatigue subtypes on pain outcomes may help clarify the nature of the interrelationships between pain and fatigue.

  19. The Mediator complex and transcription regulation

    Science.gov (United States)

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  20. Efficacy of zolpidem for dystonia: a study among different subtypes

    Directory of Open Access Journals (Sweden)

    Yoshimichi eMiyazaki

    2012-04-01

    Full Text Available Although there are some newly-developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1(ω1 , was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5-20mg in 34 patients suffering from miscellaneous types of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS. Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous 2 successive visits. After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2±7.9 to 5.5±5.0 (P=0.042. Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8%, 17.8% and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome and hand dystonia including musician’s. Drowsiness was the dose-limiting factor.

  1. CT assessment of subtypes of pulmonary emphysema in females

    International Nuclear Information System (INIS)

    Togami, Taro; Yamamoto, Yuka; Kameyama, Reiko; Murota, Makiko; Kimura, Naruhide; Nishiyama, Yoshihiro; Satoh, Katashi

    2011-01-01

    We performed a retrospective study examining the prevalence and subtypes of pulmonary emphysema (PE) identified by computed tomography (CT) in females. We reviewed the records of 1,687 female subjects who had undergone CT. They were divided into the following 2 age groups: group A (<50 years) and group B (≥50 years). PE was diagnosed by the presence of low-attenuation areas using visual assessment (grades 0-3) on CT images. Two subtypes of PE were observed: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). PE was divided into the following 3 categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). PE was found in 64 of 274 smokers (23.3%) and 54 of 1,413 non-smokers (3.8%). In smoking subjects, when grades 1 and 2 were grouped together as mild PE, the mean age for CT grade 3 (severe PE) was significantly higher than that for mild PE. In group A, category III predominated, whereas category I was more prevalent in group B, in both smoking and non-smoking subjects. A high incidence of PE was found in smoking subjects as compared with non-smoking subjects. PSE predominated in younger subjects, whereas CLE predominated in older subjects. (author)

  2. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  3. Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

    It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

  4. Cognitive process-based subtypes of developmental coordination disorder (DCD).

    Science.gov (United States)

    Asonitou, Katerina; Koutsouki, Dimitra

    2016-06-01

    The purpose of the study was to identify the cognitive subtypes demonstrated by children with developmental coordination disorder (DCD) using the Planning-Attention-Simultaneous-Successive Processing (PASS) theory and the Cognitive Assessment System (D-N CAS). Participants were 108 children aged 5- and 6-years old, 54 with DCD and 54 without DCD, all attending typical kindergartens. They were examined on 31 cognitive-motor variables. Hierarchical-agglomerative and iterative partitioning cluster analyses including 9 motor and 7 cognitive variables revealed the following six subtypes: o C1 = children at risk (having considerable difficulty with jumping and minor difficulty with manual dexterity and simultaneous coding); o C2 = children on the mean (all cognitive-motor scores close to the mean); o C3 = free from cognitive-motor problems (all scores above average); o C4 = manual dexterity, planning and simultaneous coding difficulties; o C5 = manual dexterity, dynamic balance, and planning difficulties; o C6 = generalized cognitive-motor dysfunction (all scores considerably below average). It is well known that DCD is a heterogeneous condition. However, whenever cognitive processes were lower than average, cognitive-motor relationship was evident in subgroups C1, C4, C5 and C6. Early identification of task-specific cognitive-motor difficulties may be essential for early educational intervention practices in order to anticipate and improve learning, academic and performing difficulties. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

    Science.gov (United States)

    Miyazaki, Yoshimichi; Sako, Wataru; Asanuma, Kotaro; Izumi, Yuishin; Miki, Tetsuro; Kaji, Ryuji

    2012-01-01

    Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor. PMID:22529836

  6. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand

    International Nuclear Information System (INIS)

    Dihlmann, W.; Dihlmann, A.

    1998-01-01

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [de

  7. Relationship between EDNOS and its subtypes and borderline personality disorder.

    Science.gov (United States)

    Marino, M F; Zanarini, M C

    2001-04-01

    The purpose of this study was to assess the prevalence of eating disorder not otherwise specified (EDNOS) and four well-defined subtypes of this disorder found in a sample of female borderline patients. The lifetime prevalence of EDNOS and its various subtypes among 233 female borderline patients and 46 female Axis II comparison subjects was assessed using the Structured Clinical Interview for DSM-III-R Axis I disorders. Thirty-three percent of female borderline patients met DSM-III-R criteria for EDNOS at some point in their lives. Of these 76 women, 20% reported a pattern of restricting without low weight, 37% reported a pattern of binging without purging, 37% reported a pattern of purging without binging, and 33% reported a pattern of low weight without loss of menses. However, less than 25% of these 76 borderline women had ever met criteria for anorexia nervosa or bulimia nervosa. The results of this study suggest that EDNOS is a separate cluster of eating disorders among borderline women, rather than a prodromal or residual form of a more clear-cut case of anorexia or bulimia nervosa. Copyright 2001 by John Wiley & Sons, Inc.

  8. [Neuropsychological subtypes of the inattention and hyperactivity syndrome].

    Science.gov (United States)

    Etchepareborda, M C

    1999-02-01

    One of the commonest neurological development disorders is the syndrome of inattention with hyperactivity, ADHD. The complex neurobiological network which intervenes in paying attention permits us to maintain a basal state of alertness, to focalize and maintain attention for long periods, select the stimulus-signal required and analyze its components, and also to simultaneously carry out processes of input-output and performance (tutorial, controlling). Damage to the various systems participating in 'paying attention' leads to a syndrome of inattention, with or without hyperactivity. The distinction into clinical sub-types (combined, mainly lacking attention or mainly hyperactive and impulsive) gives a primary differentiation of the syndrome. However, from the neuropsychological point of view, some degree of heterogeneity within the groups which defines academic behaviour and conduct may also be recognized. This type of study permits a more specific neuro-cognitive and pharmacological approach. Some clinical characteristics of the syndrome of inattention improve with different drugs, such as the state of alterness (methylphenidate), impulsivity (pipamperone) and selective attention (tiapride). However, this treatment is symptomatic and in most cases is useful to accompany the ultimate biological development of the neocortical control mechanisms. A neuro-cognitive approach which permits acquisition of habits of control, functional strategies, sequential planning of activities and per- and post-functional surveillance is fundamental. The EFE programme for training executive functions is directed towards working with the damaged processing mechanisms in each neuropsychological subtype.

  9. Complete nucleotide sequences of avian metapneumovirus subtype B genome.

    Science.gov (United States)

    Sugiyama, Miki; Ito, Hiroshi; Hata, Yusuke; Ono, Eriko; Ito, Toshihiro

    2010-12-01

    Complete nucleotide sequences were determined for subtype B avian metapneumovirus (aMPV), the attenuated vaccine strain VCO3/50 and its parental pathogenic strain VCO3/60616. The genomes of both strains comprised 13,508 nucleotides (nt), with a 42-nt leader at the 3'-end and a 46-nt trailer at the 5'-end. The genome contains eight genes in the order 3'-N-P-M-F-M2-SH-G-L-5', which is the same order shown in the other metapneumoviruses. The genes are flanked on either side by conserved transcriptional start and stop signals and have intergenic sequences varying in length from 1 to 88 nt. Comparison of nt and predicted amino acid (aa) sequences of VCO3/60616 with those of other metapneumoviruses revealed higher homology with aMPV subtype A virus than with other metapneumoviruses. A total of 18 nt and 10 deduced aa differences were seen between the strains, and one or a combination of several differences could be associated with attenuation of VCO3/50.

  10. Physiologically assessed hot flashes and endothelial function among midlife women.

    Science.gov (United States)

    Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

    2017-08-01

    Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

  11. Eicosanoid-mediated immunity in insects

    Science.gov (United States)

    Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are ...

  12. Investigating the dissociative subtype of posttraumatic stress disorder in a sample of traumatized detained youth.

    Science.gov (United States)

    Bennett, Diana C; Modrowski, Crosby A; Kerig, Patricia K; Chaplo, Shannon D

    2015-09-01

    In this study, we tested the validity of a dissociative subtype in a sample of 225 detained adolescents (142 boys, 83 girls) likely meeting full or partial criteria for posttraumatic stress disorder (PTSD). Competing theories of dissociation pose controversy regarding dissociation as a taxon versus a continuum, and results of the current study contribute to this debate by providing evidence of distinct group differences between those high and low in dissociation. Mixture modeling revealed 2 groups of youth with differing levels of depersonalization/derealization dissociative symptoms. Differences between the 2 groups of youth were investigated regarding trauma exposure and several posttraumatic reactions: posttraumatic stress symptoms (PTSS), emotion dysregulation, and emotional numbing. Compared with youth classified in the low-dissociation group, youth who exhibited high levels of dissociation demonstrated higher levels of total PTSS, posttraumatic symptom clusters of emotional numbing, intrusion, and associated features, as well as reporting more difficulties with emotion dysregulation. To test theory regarding the factors that increase the likelihood of persistent dissociation, bootstrapped regression analyses were performed to examine the possibility of an indirect effect of peritraumatic dissociation. Results consistent with statistical mediation suggested that the presence of peritraumatic dissociation at the time of trauma may contribute to the continuation of dissociative symptoms as a more generalized pattern. The results of the current study have implications for clinical treatment with traumatized youth. (c) 2015 APA, all rights reserved).

  13. Conotoxins Targeting Neuronal Voltage-Gated Sodium Channel Subtypes: Potential Analgesics?

    Directory of Open Access Journals (Sweden)

    Jeffrey R. McArthur

    2012-11-01

    Full Text Available Voltage-gated sodium channels (VGSC are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins from the μ- and μO-families that act on neuronal VGSCs. Examples of how these conotoxins target various pharmacologically important neuronal ion channels, as well as potential problems with the development of drugs from conotoxins, will be discussed.

  14. Cutaneous and Mucosal Lichen Planus: A Comprehensive Review of Clinical Subtypes, Risk Factors, Diagnosis, and Prognosis

    Science.gov (United States)

    2014-01-01

    Lichen planus (LP) is a chronic inflammatory disorder that most often affects middle-aged adults. LP can involve the skin or mucous membranes including the oral, vulvovaginal, esophageal, laryngeal, and conjunctival mucosa. It has different variants based on the morphology of the lesions and the site of involvement. The literature suggests that certain presentations of the disease such as esophageal or ophthalmological involvement are underdiagnosed. The burden of the disease is higher in some variants including hypertrophic LP and erosive oral LP, which may have a more chronic pattern. LP can significantly affect the quality of life of patients as well. Drugs or contact allergens can cause lichenoid reactions as the main differential diagnosis of LP. LP is a T-cell mediated immunologic disease but the responsible antigen remains unidentified. In this paper, we review the history, epidemiology, and clinical subtypes of LP. We also review the histopathologic aspects of the disease, differential diagnoses, immunopathogenesis, and the clinical and genetic correlations. PMID:24672362

  15. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability.

    Science.gov (United States)

    Frielink, N; Schuengel, C; Embregts, P

    2017-07-01

    According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic motivation for people with intellectual disability (ID) due to their cognitive limitations. The current study challenges this proposal by testing whether the four subtypes of extrinsic motivation can be differentiated among people with ID as well. The subtypes of extrinsic motivation were measured using two adapted versions of the Self-Regulation Questionnaire, one regarding exercise and one regarding support. In total, 186 adults with mild to borderline ID participated in the study. Results supported the distinction between the four subtypes of extrinsic motivation regarding both exercise and support. In addition, the correlation coefficients supported a quasi-simplex pattern of correlations among the subtypes, indicating that adjacent subtypes were more closely related than non-adjacent subtypes. Moreover, the study showed sufficient Cronbach's alphas and test-retest reliabilities for early stage research. Overall, the results of the current study provide initial evidence for the universality of the four subtypes of extrinsic motivation across populations with and without ID. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

  16. The dissociative subtype of posttraumatic stress disorder: rationale, clinical and neurobiological evidence, and implications.

    Science.gov (United States)

    Lanius, Ruth A; Brand, Bethany; Vermetten, Eric; Frewen, Paul A; Spiegel, David

    2012-08-01

    Clinical and neurobiological evidence for a dissociative subtype of posttraumatic stress disorder (PTSD) has recently been documented. A dissociative subtype of PTSD is being considered for inclusion in the forthcoming Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to address the symptoms of depersonalization and derealization found among a subset of patients with PTSD. This article reviews research related to the dissociative subtype including antecedent, concurrent, and predictive validators as well as the rationale for recommending the dissociative subtype. The relevant literature pertaining to the dissociative subtype of PTSD was reviewed. Latent class analyses point toward a specific subtype of PTSD consisting of symptoms of depersonalization and derealization in both veteran and civilian samples of PTSD. Compared to individuals with PTSD, those with the dissociative subtype of PTSD also exhibit a different pattern of neurobiological response to symptom provocation as well as a differential response to current cognitive behavioral treatment designed for PTSD. We recommend that consideration be given to adding a dissociative subtype of PTSD in the revision of the DSM. This facilitates more accurate analysis of different phenotypes of PTSD, assist in treatment planning that is informed by considering the degree of patients' dissociativity, will improve treatment outcome, and will lead to much-needed research about the prevalence, symptomatology, neurobiology, and treatment of individuals with the dissociative subtype of PTSD. © 2012 Wiley Periodicals, Inc.

  17. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

    Directory of Open Access Journals (Sweden)

    Xinxin Peng

    2018-04-01

    Full Text Available Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism

  18. Complete genome of a European hepatitis C virus subtype 1g isolate: phylogenetic and genetic analyses.

    Science.gov (United States)

    Bracho, Maria A; Saludes, Verónica; Martró, Elisa; Bargalló, Ana; González-Candelas, Fernando; Ausina, Vicent

    2008-06-05

    Hepatitis C virus isolates have been classified into six main genotypes and a variable number of subtypes within each genotype, mainly based on phylogenetic analysis. Analyses of the genetic relationship among genotypes and subtypes are more reliable when complete genome sequences (or at least the full coding region) are used; however, so far 31 of 80 confirmed or proposed subtypes have at least one complete genome available. Of these, 20 correspond to confirmed subtypes of epidemic interest. We present and analyse the first complete genome sequence of a HCV subtype 1g isolate. Phylogenetic and genetic distance analyses reveal that HCV-1g is the most divergent subtype among the HCV-1 confirmed subtypes. Potential genomic recombination events between genotypes or subtype 1 genomes were ruled out. We demonstrate phylogenetic congruence of previously deposited partial sequences of HCV-1g with respect to our sequence. In light of this, we propose changing the current status of its subtype-specific designation from provisional to confirmed.

  19. Complete genome of a European hepatitis C virus subtype 1g isolate: phylogenetic and genetic analyses

    Directory of Open Access Journals (Sweden)

    Bargalló Ana

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus isolates have been classified into six main genotypes and a variable number of subtypes within each genotype, mainly based on phylogenetic analysis. Analyses of the genetic relationship among genotypes and subtypes are more reliable when complete genome sequences (or at least the full coding region are used; however, so far 31 of 80 confirmed or proposed subtypes have at least one complete genome available. Of these, 20 correspond to confirmed subtypes of epidemic interest. Results We present and analyse the first complete genome sequence of a HCV subtype 1g isolate. Phylogenetic and genetic distance analyses reveal that HCV-1g is the most divergent subtype among the HCV-1 confirmed subtypes. Potential genomic recombination events between genotypes or subtype 1 genomes were ruled out. We demonstrate phylogenetic congruence of previously deposited partial sequences of HCV-1g with respect to our sequence. Conclusion In light of this, we propose changing the current status of its subtype-specific designation from provisional to confirmed.

  20. Clinical Manifestations of Cryptosporidiosis and Identification of a New Cryptosporidium Subtype in Patients From Sonora, Mexico.

    Science.gov (United States)

    Urrea-Quezada, Alejandro; González-Díaz, Mariana; Villegas-Gómez, Isaac; Durazo, María; Hernández, Jesús; Xiao, Lihua; Valenzuela, Olivia

    2018-05-01

    The aim of this study was to identify the clinical manifestations of cryptosporidiosis and the distribution of Cryptosporidium spp. and subtypes in children in Sonora, Mexico. Two subtypes of C. parvum, including IIaA15G2R1 and IIcA5G3a, and 6 subtypes of Cryptosporidium hominis, including IaA14R3, IaA15R3, IbA12G3, IdA23, IeA11G3T3, and a new subtype IaA14R11, were identified. Cryptosporidium as an etiologic agent for acute gastroenteritis is discussed.

  1. Subtype and pathway specific responses to anticancer compounds in breast cancer.

    Science.gov (United States)

    Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

    2012-02-21

    Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

  2. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  3. Rumination and Avoidance as Mediators of the Relationship Between Self-Compassion and Depression in Adolescents

    OpenAIRE

    Start, Rebecca

    2015-01-01

    Background This study sought to investigate the mediating effects of rumination and cognitivebehavioural avoidance in the relationship between self-compassion and depression amongst adolescents. Method Ninety nonclinical adolescents completed self-report measures of self-compassion, depressive symptomatology, rumination (reflection and brooding subtypes) and cognitive-behavioural avoidance. Results Results showed that for the relationship between self-compassion and...

  4. Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

    NARCIS (Netherlands)

    Michel, M. C.; Hanft, G.; Gross, G.

    1990-01-01

    We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol

  5. Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.

    Science.gov (United States)

    Sun, Min-Yu; Izumi, Yukitoshi; Benz, Ann; Zorumski, Charles F; Mennerick, Steven

    2016-03-01

    N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptors mediating excitatory transmission throughout the central nervous system (CNS), play critical roles in governing brain function and cognition. Because NMDAR dysfunction contributes to the etiology of neurological and psychiatric disorders including stroke and schizophrenia, NMDAR modulators are potential drug candidates. Our group recently demonstrated that the major brain cholesterol metabolite, 24S-hydroxycholesterol (24S-HC), positively modulates NMDARs when exogenously administered. Here, we studied whether endogenous 24S-HC regulates NMDAR activity in hippocampal slices. In CYP46A1(-/-) (knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR-to-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic current (EPSC) ratio, was reduced. This difference translated into more NMDAR-driven spiking in wild-type (WT) slices compared with KO slices. Application of SGE-301, a 24S-HC analog, had comparable potentiating effects on NMDAR EPSCs in both WT and KO slices, suggesting that endogenous 24S-HC does not saturate its NMDAR modulatory site in ex vivo slices. KO slices did not differ from WT slices in either spontaneous neurotransmission or in neuronal intrinsic excitability, and exhibited LTP indistinguishable from WT slices. However, KO slices exhibited higher resistance to persistent NMDAR-dependent depression of synaptic transmission induced by oxygen-glucose deprivation (OGD), an effect restored by SGE-301. Together, our results suggest that loss of positive NMDAR tone does not elicit compensatory changes in excitability or transmission, but it protects transmission against NMDAR-mediated dysfunction. We expect that manipulating this endogenous NMDAR modulator may offer new treatment strategies for neuropsychiatric dysfunction. Copyright © 2016 the American Physiological Society.

  6. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  7. Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

    Science.gov (United States)

    Liu, Yansong; Yu, Xinnian; Yang, Bixiu; Zhang, Fuquan; Zou, Wenhua; Na, Aiguo; Zhao, Xudong; Yin, Guangzhong

    2017-03-21

    Overgeneral autobiographical memory has been identified as a risk factor for the onset and maintenance of depression. However, little is known about the underlying mechanisms that might explain overgeneral autobiographical memory phenomenon in depression. The purpose of this study was to test the mediation effects of rumination on the relationship between overgeneral autobiographical memory and depressive symptoms. Specifically, the mediation effects of brooding and reflection subtypes of rumination were examined in patients with major depressive disorder. Eighty-seven patients with major depressive disorder completed the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Bootstrap mediation analysis for simple and multiple mediation models through the PROCESS macro was applied. Simple mediation analysis showed that rumination significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Multiple mediation analyses showed that brooding, but not reflection, significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Our results indicate that global rumination partly mediates the relationship between overgeneral autobiographical memory and depressive symptoms in patients with major depressive disorder. Furthermore, the present results suggest that the mediating role of rumination in the relationship between overgeneral autobiographical memory and depression is mainly due to the maladaptive brooding subtype of rumination.

  8. Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease

    DEFF Research Database (Denmark)

    Dencker, Ditte; Thomsen, Morgane; Wörtwein, Gitta

    2011-01-01

    's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based...... site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess...... the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS....

  9. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    2005-04-01

    Full Text Available The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80% of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

  10. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    International Nuclear Information System (INIS)

    Demirci, Senem; Broadwater, Gloria; Marks, Lawrence B.; Clough, Robert; Prosnitz, Leonard R.

    2012-01-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985–2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18–89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  11. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, Senem, E-mail: senem.demirci@ege.edu.tr [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir (Turkey); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC (United States); Cancer and Leukemia Group B Statistical Center, Duke Cancer Institute, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Clough, Robert; Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  12. HIV subtype, epidemiological and mutational correlations in patients from Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Monica Maria Gomes da Silva

    Full Text Available OBJECTIVE: Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. METHODS: Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. RESULTS: Patients with complete medical charts were selected (n = 191. Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%, 41 subtype C (21.5%, 10 subtype F (5.2%, 7 BF (3.7% and 1 CF (0.5%. Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161 intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses, such as 65R and 106M, were uncommon in our study. Mutations 63P and 36I, previously reported as common in HIV-1 subtypes B and C from Brazil, respectively, were common. CONCLUSION: There is a significant frequency of HIV-1 non-B infections in Paraná state, with isolates classified as subtypes C, F, BF and BC. Patients with subtype C infection were more frequently female, heterosexual and had a longer average time of HIV diagnosis

  13. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)

    2016-01-15

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  14. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

    Directory of Open Access Journals (Sweden)

    Ireen E Kiwelu

    Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

  15. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

    Science.gov (United States)

    Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

    2008-08-15

    The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

  16. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O.; Tumpey, Terrence M.; Pushko, Peter

    2016-01-01

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  17. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

    Directory of Open Access Journals (Sweden)

    Hongshuai Sui

    Full Text Available The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05. Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05. All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

  18. Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties

    Directory of Open Access Journals (Sweden)

    López de Victoria Aliana

    2012-02-01

    Full Text Available Abstract Background The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes. Results Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N6X7T8|S8X9 sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution. Conclusions We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3

  19. Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties

    International Nuclear Information System (INIS)

    López de Victoria, Aliana; Kieslich, Chris A; Rizos, Apostolos K; Krambovitis, Elias; Morikis, Dimitrios

    2012-01-01

    The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes. Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N 6 X 7 T 8 |S 8 X 9 sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution. We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge

  20. Role of alpha2C-adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the alpha2C-adrenoceptor gene.

    Science.gov (United States)

    Tanila, H; Mustonen, K; Sallinen, J; Scheinin, M; Riekkinen, P

    1999-02-01

    The role of the alpha2C-adrenoceptor subtype in mediating the beneficial effect of alpha2-adrenoceptor agonists on spatial working memory was studied in adult mice with targeted inactivation of the alpha2C-receptor gene (KO) and their wild-type controls (WT). A delayed alternation task was run in a T-maze with mixed delays varying from 20 s to 120 s. Dexmedetomidine, a specific but subtype nonselective alpha2-adrenoceptor agonist, dose-dependently decreased the total number of errors. The effect was strongest at the dose of 5 microg/kg (s.c.), and was observed similarly in KO and WT mice. KO mice performed inferior to WT mice due to a higher number of perseverative errors. Dexmedetomidine slowed initiation of the motor response in the start phase at lower doses in WT mice than in KO mice but no such difference was observed in the return phase of the task, suggesting involvement of alpha2C-adrenoceptors in the cognitive aspect of response preparation or in response sequence initiation. According to these findings, enhancement of spatial working memory is best achieved with alpha2-adrenoceptor agonists which have neither agonistic nor antagonistic effects at the alpha2C-adrenoceptor subtype.

  1. Characterization of muscarinic receptor subtypes in human tissues

    International Nuclear Information System (INIS)

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

    1988-01-01

    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

  2. Groin hernia subtypes are associated in patients with bilateral hernias

    DEFF Research Database (Denmark)

    Burcharth, Jakob; Andresen, Kristoffer; Pommergaard, Hans-Christian

    2015-01-01

    repair (89.9% males) were registered, and of those were 12,041 persons operated bilaterally (94.9% males). Females and males operated for a unilaterally direct inguinal hernia (DIH) had increased Hazard Ratios (HR) of 3.85 (CI 95% 2.14-6.19) and 4.46 (CI 95% 2.57-7.88) of being contralaterally operated...... for a DIH. Females and males operated for a unilaterally indirect inguinal hernia (IIH) had HRs of 6.93 (CI 95% 3.66-13.11) and 1.89 (CI95% 1.24-2.88) for being contralaterally operated for an IIH. The same tendency was seen for femoral hernias. CONCLUSIONS: All hernia subtypes were bilaterally associated...

  3. Diagnostic subtypes of bipolar disorder in older versus younger adults

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2006-01-01

    OBJECTIVE: To investigate differences in diagnostic subtypes of bipolar disorder as according to ICD-10 between patients whose first contact with psychiatric health care occurs late in life (over 50 years of age) and patients who have first contact earlier in life (50 years of age or below......). METHODS: From 1994 to 2002 all patients who received a diagnosis of a manic episode or bipolar disorder at initial contact with the mental healthcare system, whether outpatient or inpatient, were identified in Denmark's nationwide register. RESULTS: A total of 852 (49.6%) patients, who were over age 50......, and 867 patients, who were 50 or below, received a diagnosis of a manic episode or bipolar disorder at the first contact ever. Older inpatients presented with psychotic symptoms (35.4%) significantly less than younger inpatients (42.6%) due specifically to a lower prevalence of manic episodes...

  4. Do neurocognitive deficits in decision making differentiate conduct disorder subtypes?

    Science.gov (United States)

    Fanti, Kostas A; Kimonis, Eva R; Hadjicharalambous, Maria-Zoe; Steinberg, Laurence

    2016-09-01

    The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well-validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay-Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior.

  5. Diversity of Blastocystis subtypes in dogs in different geographical settings

    DEFF Research Database (Denmark)

    Wang, Wenqi; Cuttell, Leigh; Bielefeldt-Ohmann, Helle

    2013-01-01

    Background: Blastocystis is a ubiquitous, globally distributed intestinal protist infecting humans and a wide range of animals. Several studies have shown that Blastocystis is a potentially zoonotic parasite. A 1996 study reported a 70% Blastocystis prevalence in Brisbane pound dogs while another...... study found that pet dogs/cats of 11 symptomatic Blastocystis infected patients harboured at least one Blastocystis subtype (ST) in common with the patient. These results raised the possibility that dogs might be natural hosts of Blastocystis. In this study, we aimed to investigate this hypothesis...... by estimating the prevalence of Blastocystis carriage and characterising the diversity of STs in dogs from three different environmental settings and comparing these STs with the range that humans harbour. Methods: Two hundred and forty faecal samples from dogs from three different geographical regions...

  6. Incidence of dementia and major subtypes in Europe

    DEFF Research Database (Denmark)

    Fratiglioni, L; Launer, L J; Andersen, K

    2000-01-01

    The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42......,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men....... There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries...

  7. Subtyping Ageism: Policy Issues in Succession and Consumption.

    Science.gov (United States)

    North, Michael S; Fiske, Susan T

    2013-01-01

    Ageism research tends to lump "older people" together as one group, as do policy matters that conceptualize everyone over-65 as "senior." This approach is problematic primarily because it often fails to represent accurately a rapidly growing, diverse, and healthy older population. In light of this, we review the ageism literature, emphasizing the importance of distinguishing between the still-active "young-old" and the potentially more impaired "old-old" (Neugarten, 1974). We argue that ageism theory has disproportionately focused on the old-old and differentiate the forms of age discrimination that apparently target each elder subgroup. In particular, we highlight the young-old's plights predominantly in the workplace and tensions concerning succession of desirable resources; by contrast, old-old predicaments likely center on consumption of shared resources outside of the workplace. For both social psychological researchers and policymakers, accurately subtyping ageism will help society best accommodate a burgeoning, diverse older population.

  8. [Cognitive performance in schizophrenia (paranoid vs residual subtype)].

    Science.gov (United States)

    Dillon, Carol; Taragano, Fernando; Sarasola, Diego; Iturry, Mónica; Serrano, Cecilia; Raczkowski, Amalia; Allegri, Ricardo

    2007-01-01

    Several studies refer to the relationship between schizophrenia and cognitive dysfunctions. The most frequent disturbances accepted are the deficits in the executive, memory and verbal tests. However, there are few comparative data about the cognitive functioning of the different subtypes of schizophrenia. Analyze and compare the neuropsychological disturbances present in patients with paranoid and residual schizophrenia. Eleven patients with paranoid schizophrenia, eleven patients with residual schizophrenia (DSM-IV criteria), and thirty one normal subjects matched by age, educational level, and general cognitive level (Mini Mental State Examination (Folstein, 1975), were assessed with a semistructured psychiatric examination and an extensive neuropsychological battery. Significant differences were found in memory, language, and executive functions when schizophrenics were compared with normal subjects. Differences in similarities were found between paranoid and residual schizophrenics. Residual schizophrenics had more disturbances in neuropsychological tests in comparison with paranoid schizophrenics. Schizophrenics demonstrated disturbances in memory, language, executive functions and attention. Residual schizophrenics had more impairment in neuropsychological tests than paranoid schizophrenics.

  9. Granulomatous slack skin: a rare subtype of mycosis fungoides.

    Science.gov (United States)

    Motta, Letícia Marra da; Soares, Cleverson Teixeira; Nakandakari, Sadamitsu; Silva, Gardênia Viana da; Nigro, Maria Helena Mazzi Freire; Brandão, Leticia Stella Gardini

    2017-01-01

    We report a case of granulomatous slack skin, a rare and indolent subtype of mycosis fungoides. It affects mainly men between the third and fourth decades. It is characterized by hardened and erithematous plaques that mainly affect flexural areas and become pedunculated after some years. Histological examination shows a dense infiltrate of small atypical lymphocytes involving the dermis (and sometimes the subcutaneous tissue) associated with histiocytic and multinucleated giant cells containing lymphocytes and elastic fibers (lymphophagocytosis and elastophagocytosis, respectively). Patients affected by this entity can develop secondary lymphomas. There are several but little effective therapeutic modalities described. Despite the indolent behavior of granulomatous slack skin, its early recognition and continuous monitoring by a dermatologist becomes essential for its management and prevention of an unfavorable outcome.

  10. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias

    2018-01-01

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...

  11. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Rosa Dolz-Marco

    2014-01-01

    Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

  12. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Science.gov (United States)

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

    2014-01-01

    Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

  13. Subtypes of depressive episodes according to ICD-10

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2003-01-01

    a period from 1994 to 1999 were identified. The risk of relapse leading to readmission and the risk of committing suicide were compared for patients discharged with an ICD-10 diagnosis of a single depressive episode with and without melancholic syndrome and for patients with and without psychotic symptoms......BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of depression with melancholic syndrome and depression with psychosis has not been investigated. SAMPLING AND METHODS: All patients in Denmark who had a diagnosis of a single depressive episode at their first ever discharge during......, respectively. RESULTS: In all, 1,639 patients had a diagnosis of depressive episode without psychotic symptoms, 1,275 patients a diagnosis with psychotic symptoms, 293 a diagnosis without melancholic syndrome, and 248 a diagnosis with melancholic symptoms at first discharge. The risk of relapse leading...

  14. Neurocognitive impairment in the deficit subtype of schizophrenia.

    Science.gov (United States)

    Fervaha, Gagan; Agid, Ofer; Foussias, George; Siddiqui, Ishraq; Takeuchi, Hiroyoshi; Remington, Gary

    2016-08-01

    Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

  15. Conservation physiology of animal migration

    Science.gov (United States)

    Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  16. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    NARCIS (Netherlands)

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  17. Analysis of HIV subtypes and the phylogenetic tree in HIV-positive samples from Saudi Arabia

    International Nuclear Information System (INIS)

    Al-Zahrani, Alhusain J.

    2008-01-01

    Objective was to assess the prevalence of HIV-1 genetic subtypes in Saudi Arabia in samples that are serologically positive for HIV-1 and compare the HIV-1 genetic subtypes prevalent in Saudi Arabia with the subtypes prevalent in other countries. Thirty-nine HIV-1 positive samples were analyzed for HIV-1 subtypes using molecular techniques. The study is retrospective study that was conducted in Dammam, Kingdom of Saudi Arabia and in Abbott laboratories (United States of America) from2004 to 2007. All samples were seropositive for HIV-1 group M. Of the 39 seropositive samples, only 12 were polymerase chain reaction positive. Subtype C is the most common virus strain as it occurred in 58% of these samples; subtype B occurred in 17%; subtypes A, D and G were found in 8% each. The phylogenetic tree was also identified for the isolates. Detection of HIV subtypes is important for epidemiological purposes and may help in tracing the source of HIV infections in the Kingdom of Saudi Arabia. (author)

  18. The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mélanie Busby

    2018-02-01

    Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

  19. Classification and Validation of Behavioral Subtypes of Learning-Disabled Children.

    Science.gov (United States)

    Speece, Deborah L.; And Others

    1985-01-01

    Using the Classroom Behavior Inventory, teachers rated the behaviors of 63 school-identified, learning-disabled first and second graders. Hierarchical cluster analysis techniques identified seven distinct behavioral subtypes. Internal validation techniques indicated that the subtypes were replicable and had profile patterns different from a sample…

  20. Relationship between Self-Typicality and the In-Group Subtypes Effect.

    Science.gov (United States)

    Wallace, David S.; And Others

    1995-01-01

    Examined whether group members differ in the number of in-group subtype distinctions that they draw. Drawing on results of two studies, found that members of groups whose primary function is intragroup interaction (fraternities, sororities, athletic teams) draw more subtype distinctions within their own group than within other groups. (RJM)

  1. Genetic recombination and Cryptosporidium hominis virulent subtype IbA10G2.

    Science.gov (United States)

    Li, Na; Xiao, Lihua; Cama, Vitaliano A; Ortega, Ynes; Gilman, Robert H; Guo, Meijin; Feng, Yaoyu

    2013-10-01

    Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and recombination analyses only limited genetic recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in genetic recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.

  2. Folic acid supplementation influences the distribution of neural tube defect subtypes : A registry-based study

    NARCIS (Netherlands)

    Bergman, J. E. H.; Otten, E.; Verheij, J. B. G. M.; de Walle, H. E. K.

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs

  3. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    OpenAIRE

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background: According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic ...

  4. Distribution And Clinicopathological Features Of Breast Cancer Histological Subtypes In Latvia

    Directory of Open Access Journals (Sweden)

    Srebnijs Andrejs

    2015-04-01

    Full Text Available Breast cancer is a heterogenous disease. It consists of several histological subtypes that can be separated by morphology and immunohistochemistry. The aim of our study was to determine the distribution of breast cancer histological and molecular subtypes, and their relationship with clinical and pathological characteristics. A total of 561 patients who underwent breast carcinoma surgical treatment from January 2003 till December 2012 were enrolled in the study. In total, invasive ductal carcinomas not otherwise specified (IDC-NOS plus invasive ductal carcinomas no special type (IDC-NST were observed in 430 patients (76.65% of cases, medullar carcinoma in 14 patients (2.45%, other rare ductal carcinoma subtypes in 13 patients (2.31%, lobular carcinoma in 81 patients (14.4% and tubulolobular carcinoma in 23 patients (4.19%. Ductal carcinoma, lobular and tubulolobular carcinoma had predominantly luminal A and B subtype, whereas medullar carcinoma had HER2-positive and triple-negative (TN subtype. Tubular, cribriform, mucinous, papillary, and apocrine carcinomas had predominantly luminal A subtype. Significant differences between breast cancer histological subtypes and clinicopathological characteristics were observed. Our study for the first time reported the distribution and characteristics of breast cancer histological subtypes in Latvian women and relationship to clinical and tumour histopathological characteristics.

  5. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review

    NARCIS (Netherlands)

    de Rooij, S. E.; Schuurmans, M. J.; van der Mast, R. C.; Levi, M. [=Marcel M.

    2005-01-01

    Background Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The

  6. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    A.M. Valença

    2002-07-01

    Full Text Available The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2 challenge test of panic disorder (PD patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1 35% CO2 and 65% O2, and 2 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7% respiratory PD subtype patients and 5 of 11 (43.4% nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test. Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

  7. Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts

    NARCIS (Netherlands)

    Castaldi, Peter J; Benet, Marta; Petersen, Hans; Rafaels, Nicholas; Finigan, James; Paoletti, Matteo; Marike Boezen, H; Vonk, Judith M; Bowler, Russell; Pistolesi, Massimo; Puhan, Milo A; Anto, Josep; Wauters, Els; Lambrechts, Diether; Janssens, Wim; Bigazzi, Francesca; Camiciottoli, Gianna; Cho, Michael H; Hersh, Craig P; Barnes, Kathleen; Rennard, Stephen; Boorgula, Meher Preethi; Dy, Jennifer; Hansel, Nadia N; Crapo, James D; Tesfaigzi, Yohannes; Agusti, Alvar; Silverman, Edwin K; Garcia-Aymerich, Judith

    Background COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there

  8. Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment.

    Science.gov (United States)

    An, Yang; Wang, Shuzhen; Li, Songlin; Zhang, Lulu; Wang, Dayong; Wang, Haojie; Zhu, Shibai; Zhu, Wan; Li, Yongqiang; Chen, Wenwu; Ji, Shaoping; Guo, Xiangqian

    2017-09-11

    Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood. Expression profiling data were used to determine the possibility and optimal number of ULMS molecular subtypes. Next, clinicopathological characters and molecular pathways were analyzed in each subtype to prospect the clinical applications and progression mechanisms of ULMS. Two distinct molecular subtypes of ULMS were defined based on different gene expression signatures. Subtype I ULMS recapitulated low-grade ULMS, the gene expression pattern of which resembled normal smooth muscle cells, characterized by overexpression of smooth muscle function genes such as LMOD1, SLMAP, MYLK, MYH11. In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6, MAPK13 and HOXA1. We identified two distinct molecular subtypes of ULMS responding differently to chemotherapy treatment. Our findings provide a better understanding of ULMS intrinsic molecular subtypes, and will potentially facilitate the development of subtype-specific diagnosis biomarkers and therapy strategies for these tumors.

  9. Avian metapneumovirus subtypes circulating in Brazilian vaccinated and nonvaccinated chicken and turkey farms.

    Science.gov (United States)

    Chacón, Jorge Luis; Mizuma, Matheus; Vejarano, Maria P; Toquín, Didier; Eterradossi, Nicolas; Patnayak, Devi P; Goyal, Sagar M; Ferreira, Antonio J Piantino

    2011-03-01

    Avian metapneumovirus (AMPV) causes turkey rhinotracheitis and is associated with swollen head syndrome in chickens, which is usually accompanied by secondary infections that increase mortality. AMPVs circulating in Brazilian vaccinated and nonvaccinated commercial chicken and turkey farms were detected using a universal reverse transcriptase (RT)-PCR assay that can detect the four recognized subtypes of AMPV. The AMPV status of 228 farms with respiratory and reproductive disturbances was investigated. AMPV was detected in broiler, hen, breeder, and turkey farms from six different geographic regions of Brazil. The detected viruses were subtyped using a nested RT-PCR assay and sequence analysis of the G gene. Only subtypes A and B were detected in both vaccinated and nonvaccinated farms. AMPV-A and AMPV-B were detected in 15 and 23 farms, respectively, while both subtypes were simultaneously found in one hen farm. Both vaccine and field viruses were detected in nonvaccinated farms. In five cases, the detected subtype was different than the vaccine subtype. Field subtype B virus was detected mainly during the final years of the survey period. These viruses showed high molecular similarity (more than 96% nucleotide similarity) among themselves and formed a unique phylogenetic group, suggesting that they may have originated from a common strain. These results demonstrate the cocirculation of subtypes A and B in Brazilian commercial farms.

  10. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

    Science.gov (United States)

    Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

    2018-01-01

    Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

  11. HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

    Science.gov (United States)

    Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

    2008-01-01

    Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

  12. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  13. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  14. Physiology of fish endocrine pancreas.

    Science.gov (United States)

    Plisetskaya, E M

    1989-06-01

    From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined.

  15. CRISPR typing and subtyping for improved laboratory surveillance of Salmonella infections.

    Directory of Open Access Journals (Sweden)

    Laëtitia Fabre

    Full Text Available Laboratory surveillance systems for salmonellosis should ideally be based on the rapid serotyping and subtyping of isolates. However, current typing methods are limited in both speed and precision. Using 783 strains and isolates belonging to 130 serotypes, we show here that a new family of DNA repeats named CRISPR (clustered regularly interspaced short palindromic repeats is highly polymorphic in Salmonella. We found that CRISPR polymorphism was strongly correlated with both serotype and multilocus sequence type. Furthermore, spacer microevolution discriminated between subtypes within prevalent serotypes, making it possible to carry out typing and subtyping in a single step. We developed a high-throughput subtyping assay for the most prevalent serotype, Typhimurium. An open web-accessible database was set up, providing a serotype/spacer dictionary and an international tool for strain tracking based on this innovative, powerful typing and subtyping tool.

  16. Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study.

    Science.gov (United States)

    Auger, Nathalie; Le, Thi Uyen Nhi; Park, Alison L; Luo, Zhong-Cheng

    2011-10-04

    Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at PTBs. The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system.

  17. Specific trauma subtypes improve the predictive validity of the Harvard Trauma Questionnaire in Iraqi refugees.

    Science.gov (United States)

    Arnetz, Bengt B; Broadbridge, Carissa L; Jamil, Hikmet; Lumley, Mark A; Pole, Nnamdi; Barkho, Evone; Fakhouri, Monty; Talia, Yousif Rofa; Arnetz, Judith E

    2014-12-01

    Trauma exposure contributes to poor mental health among refugees, and exposure often is measured using a cumulative index of items from the Harvard Trauma Questionnaire (HTQ). Few studies, however, have asked whether trauma subtypes derived from the HTQ could be superior to this cumulative index in predicting mental health outcomes. A community sample of recently arrived Iraqi refugees (N = 298) completed the HTQ and measures of posttraumatic stress disorder (PTSD) and depression symptoms. Principal components analysis of HTQ items revealed a 5-component subtype model of trauma that accounted for more item variance than a 1-component solution. These trauma subtypes also accounted for more variance in PTSD and depression symptoms (12 and 10%, respectively) than did the cumulative trauma index (7 and 3%, respectively). Trauma subtypes provided more information than cumulative trauma in the prediction of negative mental health outcomes. Therefore, use of these subtypes may enhance the utility of the HTQ when assessing at-risk populations.

  18. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  19. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Breast cancer subtypes: two decades of journey from cell culture to patients.

    Science.gov (United States)

    Zhao, Xiangshan; Gurumurthy, Channabasavaiah Basavaraju; Malhotra, Gautam; Mirza, Sameer; Mohibi, Shakur; Bele, Aditya; Quinn, Meghan G; Band, Hamid; Band, Vimla

    2011-01-01

    Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.

  1. Sleep and daytime function in adults with attention-deficit/hyperactivity disorder: subtype differences.

    Science.gov (United States)

    Yoon, Sun Young Rosalia; Jain, Umesh Ravi; Shapiro, Colin Michael

    2013-07-01

    Although sleep disorders have been reported to affect more than half of adults with attention-deficit/hyperactivity disorder (ADHD), the association between sleep and ADHD is poorly understood. The aims of our study were to investigate sleep-related variables in adults with ADHD and to assess if any differences exist between ADHD of the predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes. We used the Epworth sleepiness scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the fatigue severity scale (FSS) to collect data on daytime sleepiness, sleep quality, and fatigue in 126 subjects (45 ADHD-I and 81 ADHD-C subjects). Approximately 85% of subjects reported excessive daytime sleepiness or poor sleep quality. The most common sleep concerns were initial insomnia, interrupted sleep, and feeling too hot. When examining ADHD subtype differences, ADHD-I subtypes reported poorer sleep quality and more fatigue than ADHD-C subtypes. Partial correlation analyses revealed that interrelationships between sleep quality, daytime sleepiness, and fatigue differ between ADHD subtypes; in ADHD-I subtypes fatigue was associated with sleep quality, while in the ADHD-C subtypes fatigue was associated with both sleep quality and daytime sleepiness. There also appears to be a subtype×gender interaction that affects the perception of fatigue, as subjective fatigue was markedly higher in ADHD-I women than in ADHD-C women. Altogether our data indicate that the interplay of variables associated with daytime function and sleep varies between ADHD subtypes. This finding may have considerable relevance in the management and pathophysiologic understanding of ADHD, and thus lead to tailored treatments for ADHD subtypes. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  2. Origin and dynamics of HIV-1 subtype C infection in India.

    Directory of Open Access Journals (Sweden)

    Chengli Shen

    Full Text Available To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India.Ninety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008 were employed to determine the origin of HIV infection in India.Phylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models.The majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78-1981.52. Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India.Indian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic.

  3. Excluded and behaving unethically: social exclusion, physiological responses, and unethical behavior.

    Science.gov (United States)

    Kouchaki, Maryam; Wareham, Justin

    2015-03-01

    Across 2 studies, we investigated the ethical consequences of physiological responses to social exclusion. In Study 1, participants who were socially excluded were more likely to engage in unethical behavior to make money and the level of physiological arousal experienced during exclusion--measured using galvanic skin response--mediated the effects of exclusion on unethical behavior. Likewise, in Study 2, results from a sample of supervisor-subordinate dyads revealed a positive relationship between experience of workplace ostracism and unethical behaviors as rated by the immediate supervisors. This relationship was mediated by employees' reports of experienced physiological arousal. Together, the results of these studies demonstrate that physiological arousal accompanies social exclusion and provides an explanatory mechanism for the increased unethical behavior in both samples. Theoretical implications of these findings for research on ethical behavior and social exclusion in the workplace are discussed. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  4. Stimulating Student Interest in Physiology: The Intermedical School Physiology Quiz

    Science.gov (United States)

    Cheng, Hwee-Ming

    2010-01-01

    The Intermedical School Physiology Quiz (IMSPQ) was initiated in 2003 during the author's last sabbatical from the University of Malaya. At this inaugural event, there were just seven competing teams from Malaysian medical schools. The challenge trophy for the IMSPQ is named in honor of Prof. A. Raman, who was the first Malaysian Professor of…

  5. From Physiology to Prevention: Further remarks on a physiological imperative

    Directory of Open Access Journals (Sweden)

    B Jouanjean

    2012-05-01

    Full Text Available Physiology, is the fundamental and functional expression of life. It is the study of all the representative functions of Man in all his capacities, and in particular, his capacity to work. It is very possible to establish a link between a physiological and physiopathological state, the capacity of work and the economy, which can be understood as the articulation between the physiological capacities of Man and the production of work. If these functions are innately acquired by Man they are likewise maintained by regulatory functions throughout life. The stability of these regulatory mechanisms represent the state of good health. The management of this state, constitutes Primary Prevention where both chronic and acute physiopathology defines an alteration in these regulatory mechanisms. We deduce from this reasoning that a tripartite management adapted to the physiological situation is viable and that by choosing parameters specific to individual and collective behavior, it is possible to inject, and combine, at each level and to each demand in order to budget a healthcare system in a more balanced and equitable way. 

  6. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  7. Cognitive subtypes in non-affected siblings of schizophrenia patients: characteristics and profile congruency with affected family members

    NARCIS (Netherlands)

    Quee, P.J.; Alizadeh, BZ; Aleman, A.; van den Heuvel, E.R.; Bruggeman, R.; Cahn, W.; de Haan, L.; Kahn, R.; Krabbendam, L.; Linzen, D.; Myin-Germeys, I.; van Os, J; Wiersma, D.

    2013-01-01

    Background. Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive

  8. Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

    NARCIS (Netherlands)

    Filézac de L'Etang, Audrey; Maharjan, Niran; Cordeiro Braña, Marisa; Ruegsegger, Céline; Rehmann, Ruth; Goswami, Anand; Roos, Andreas; Troost, Dirk; Schneider, Bernard L.; Weis, Joachim; Saxena, Smita

    2015-01-01

    Mechanisms underlying motor neuron subtype-selective endoplasmic reticulum (ER) stress and associated axonal pathology in amyotrophic lateral sclerosis (ALS) remain unclear. Here we show that the molecular environment of the ER between motor neuron subtypes is distinct, with characteristic

  9. Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI in humans from General Belgrano Island, Formosa, Argentina

    Directory of Open Access Journals (Sweden)

    Cámara Alicia

    2003-01-01

    Full Text Available This work presents the results of the detection of antibodies (immunoglobulin G for subtypes I and VI of VEE viruses complex (Togaviridae family in people from the General Belgrano island, Formosa province (Argentina. The prevalence of neutralizing (NT antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

  10. The Limits of Exercise Physiology

    DEFF Research Database (Denmark)

    Gabriel, Brendan M; Zierath, Juleen R

    2017-01-01

    Many of the established positive health benefits of exercise have been documented by historical discoveries in the field of exercise physiology. These investigations often assess limits: the limits of performance, or the limits of exercise-induced health benefits. Indeed, several key findings have...... been informed by studying highly trained athletes, in addition to healthy or unhealthy people. Recent progress has been made in regard to skeletal muscle metabolism and personalized exercise regimes. In this perspective, we review some of the historical milestones of exercise physiology, discuss how...

  11. Hepatitis C virus sequences from different patients confirm the existence and transmissibility of subtype 2q, a rare subtype circulating in the metropolitan area of Barcelona, Spain.

    Science.gov (United States)

    Martró, Elisa; Valero, Ana; Jordana-Lluch, Elena; Saludes, Verónica; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Bracho, Maria Alma

    2011-05-01

    The hepatitis C virus (HCV) has been classified into six genotypes and more than 70 subtypes with distinct geographical and epidemiological distributions. While 18 genotype 2 subtypes have been proposed, only 5 have had their complete sequence determined. The aim of this study was to characterize HCV isolates from three patients from the Barcelona metropolitan area of Spain for whom commercial genotyping methods provided discordant results. Full-length genome sequencing was carried out for 2 of the 3 patients; for the third patient only partial NS5B sequences could be obtained. The generated sequences were subjected to phylogenetic, recombination, and identity analyses. Sequences covering most of the HCV genome (9398 and 9566  nt in length) were obtained and showed a 90.3% identity to each other at the nucleotide level, while both sequences differed by 17.5-22.6% from the other fully sequenced genotype 2 subtypes. No evidence of recombination was found. The NS5B phylogenetic tree showed that sequences from the three patients cluster together with the only representative sequence of the provisionally designed 2q subtype, which also corresponds to a patient from Barcelona. Phylogenetic analysis of the full coding sequence showed that subtype 2q was more closely related to subtype 2k. The results obtained in this study suggest that subtype 2q now meets the requirements for confirmed designation status according to consensus criteria for HCV classification and nomenclature, and its epidemiological value is ensured as it has spread among several patients in the Barcelona metropolitan area. Copyright © 2011 Wiley-Liss, Inc.

  12. Oppositional defiant disorder dimensions and subtypes among detained male adolescent offenders.

    Science.gov (United States)

    Aebi, Marcel; Barra, Steffen; Bessler, Cornelia; Steinhausen, Hans-Christoph; Walitza, Susanne; Plattner, Belinda

    2016-06-01

    In adolescent offenders, oppositional defiant disorder (ODD) and its dimensions/subtypes have been frequently ignored due to the stronger focus on criminal behaviours. The revised criteria of the DSM-5 now allow diagnosing ODD in older youths independent of conduct disorder (CD). This study aimed at analysing ODD dimensions/subtypes and their relation to suicidality, comorbid psychiatric disorders, and criminal behaviours after release from detention in a sample of detained male adolescents. Suicidality and psychiatric disorders (including ODD symptoms) were assessed in a consecutive sample of 158 male adolescents (Mage  = 16.89 years) from the Zurich Juvenile Detention Centre. Based on previous research findings, an irritable ODD dimension and a defiant/vindictive ODD dimension based on ODD symptoms were defined. Latent Class Analysis (LCA) was used to identify distinct subtypes of adolescent offenders according to their ODD symptom profiles. Logistic regression and Cox regression were used to analyse the relations of ODD dimensions/ODD subtypes to comorbid psychopathology and criminal reoffenses from official data. The ODD-irritable dimension, but not the ODD defiant/vindictive dimension predicted comorbid anxiety, suicidality and violent reoffending. LCA identified four subtypes, namely, a no-ODD subtype, a severe ODD subtype and two moderate ODD subtypes with either defiant or irritable symptoms. The irritable ODD subtype and the severe ODD subtype were related to suicidality and comorbid affective/anxiety disorders. The irritable ODD subtype was the strongest predictor of criminal (violent) reoffending even when controlling for CD. The present findings confirm the presence of ODD dimensions/subtypes in a highly disturbed adolescent offender sample. Irritable youths were at risk of suicide and persistent criminal behaviours. Due to the severe consequences of irritability, a standardized assessment approach and a specific treatment is needed in prison to

  13. Nigerian Journal of Physiological Sciences: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. Nigerian Journal of Physiological Sciences (Niger. J. Physiol. Sci.) is a biannual publication of the Physiological Society of Nigeria. It covers diverse areas of research in physiological sciences, publishing reviews in current research areas and original laboratory and clinical research in physiological ...

  14. Immunohistochemical visualization of mouse interneuron subtypes [v1; ref status: indexed, http://f1000r.es/4em

    Directory of Open Access Journals (Sweden)

    Simon Molgaard

    2014-10-01

    Full Text Available The activity of excitatory neurons is controlled by a small, but highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the

  15. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

    Directory of Open Access Journals (Sweden)

    Kenichi Konda

    Full Text Available Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs.We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance.S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41.We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

  16. Avian metapneumovirus subtype C in Wild Waterfowl in Ontario, Canada.

    Science.gov (United States)

    Jardine, C M; Parmley, E J; Buchanan, T; Nituch, L; Ojkic, D

    2018-02-18

    Avian metapneumovirus (aMPV) is an emerging poultry pathogen that has a significant economic impact on poultry production worldwide. The geographic range of the virus continues to expand, and wild birds have been implicated as reservoirs of aMPV that have the potential to spread the virus over long distances. Our objective was to determine the apparent prevalence of aMPV subtype C in wild waterfowl in Ontario, Canada. Wild waterfowl were captured in August and September, 2016 as part of routine migratory waterfowl population monitoring by the Ontario Ministry of Natural Resources and Forestry. Oropharyngeal and cloacal swabs were collected from each bird and placed together for aMPV testing using real-time RT-PCR. A total of 374 live wild birds from 23 lakes were sampled and tested for aMPV. Among all ducks tested, 84 (22%) were positive for aMPV. The proportion of samples that tested positive ranged from 0% in ring-necked ducks (Aythya collaris) and green-winged teal (Anas carolinensis) to 44% (8 of 18) in American black ducks (A. rubripes). Waterfowl positive for aMPV were found at 14 of 23 lakes in the study area and the percent positive at these 14 lakes ranged between 5% and 84%. Although subtype C aMPV has been detected in a variety of wild birds in North America, this is the first report of aMPV in wild ducks in Ontario, Canada. The high apparent prevalence, particularly in mallards and American black ducks (37 and 44%, respectively), suggests that these species may be important reservoirs of aMPV. Given the potential impact of aMPV on domestic poultry and the potential role of wild birds as reservoirs of the virus, further investigation of the geographic distribution, risk factors associated with aMPV carriage in wild waterfowl and potential role of other birds in the epidemiology of aMPV in Canada is warranted. © 2018 Blackwell Verlag GmbH.

  17. HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer.

    Science.gov (United States)

    Lopes de Campos, Walter R; Chirwa, Nthato; London, Grace; Rotherham, Lia S; Morris, Lynn; Mayosi, Bongani M; Khati, Makobetsa

    2014-01-01

    HIV-associated cardiomyopathy (HIVCM) is of clinical concern in developing countries because of a high HIV-1 prevalence, especially subtype C, and limited access to highly active antiretroviral therapy (HAART). For these reasons, we investigated the direct and indirect effects of HIV-1 subtype C infection of cultured human cardiomyocytes and the mechanisms leading to cardiomyocytes damage; as well as a way to mitigate the damage. We evaluated a novel approach to mitigate HIVCM using a previously reported gp120 binding and HIV-1 neutralizing aptamer called UCLA1. We established a cell-based model of HIVCM by infecting human cardiomyocytes with cell-free HIV-1 or co-culturing human cardiomyocytes with HIV-infected monocyte derived macrophages (MDM). We discovered that HIV-1 subtype C unproductively (i.e. its life cycle is arrested after reverse transcription) infects cardiomyocytes. Furthermore, we found that HIV-1 initiates apoptosis of cardiomyocytes through caspase-9 activation, preferentially via the intrinsic or mitochondrial initiated pathway. CXCR4 receptor-using viruses were stronger inducers of apoptosis than CCR5 utilizing variants. Importantly, we discovered that HIV-1 induced apoptosis of cardiomyocytes was mitigated by UCLA1. However, UCLA1 had no protective effective on cardiomyocytes when apoptosis was triggered by HIV-infected MDM. When HIV-1 was treated with UCLA1 prior to infection of MDM, it failed to induce apoptosis of cardiomyocytes. These data suggest that HIV-1 causes a mitochondrial initiated apoptotic cascade, which signal through caspase-9, whereas HIV-1 infected MDM causes apoptosis predominantly via the death-receptor pathway, mediated by caspase-8. Furthermore the data suggest that UCLA1 protects cardiomyocytes from caspase-mediated apoptosis, directly by binding to HIV-1 and indirectly by preventing infection of MDM.

  18. FROM PHYSIOLOGICAL TO PATHOLOGICAL METEOSENSITIVITY

    Directory of Open Access Journals (Sweden)

    M. I. Yabluchanskiy

    2013-12-01

    Full Text Available This paper is dedicated to the problem of physiological and pathological meteosensitivity (meteodependency or meteopathy.We introduce and discuss the definition for individual meteodependency, define factors, mechanisms, clinical signs, diagnosis, and approaches to prophylaxy and treatment of individual pathological meteosensitivity.

  19. Physiological adaptation in desert birds

    NARCIS (Netherlands)

    Williams, JB; Tieleman, BI; Williams, Joseph B.

    We call into question the idea that birds have not evolved unique physiological adaptations to desert environments. The rate at which desert larks metabolize energy is lower than in mesic species within the same family, and this lower rate of living translates into a lower overall energy requirement

  20. Physiology Of Prolonged Bed Rest

    Science.gov (United States)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  1. Electronic Textbook in Human Physiology.

    Science.gov (United States)

    Broering, Naomi C.; Lilienfield, Lawrence S.

    1994-01-01

    Describes the development of an electronic textbook in human physiology at the Georgetown University Medical Center Library that was designed to enhance learning and visualization through a prototype knowledge base of core instructional materials stored in digital format on Macintosh computers. The use of computers in the medical curriculum is…

  2. Exercise Effects on Sleep Physiology

    Directory of Open Access Journals (Sweden)

    Sunao eUchida

    2012-04-01

    Full Text Available This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. Thus, research on the effects of exercise on sleep began, in the 1960’s, with a focus primarily on sleep EEG (CNS sleep changes. Those early studies found only small effects of exercise on sleep. More recent sleep research has explored not only CNS functioning, but somatic physiology as well. As physical exercise mostly affects somatic functions, endocrine and autonomic nervous system (ANS changes that occur during sleep should be affected by daytime exercise. Since endocrinological, metabolic and autonomic changes can be measured during sleep, it should be possible to assess exercise effects on somatic physiology in addition to CNS sleep quality, building from standard polysomnographic (PSG techniques. Incorporating measures of somatic physiology in the quantitative assessment of sleep could further our understanding of sleep's function as an auto-regulatory, global phenomenon.

  3. Physiological Monitoring in Diving Mammals

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Physiological Monitoring in Diving Mammals Andreas...825-2025 email: andreas.fahlman@tamucc.edu Peter L. Tyack School of Biology Sea Mammal Research Unit Scottish Oceans Institute...OBJECTIVES This project is separated into three aims: Aim 1: Develop a new generation of tags/data logger for marine mammals that will

  4. Does Subtype Matter? Assessing the Effects of Maltreatment on Functioning in Preadolescent Youth in Out-of-Home Care

    Science.gov (United States)

    Petrenko, Christie L. M.; Friend, Angela; Garrido, Edward F.; Taussig, Heather N.; Culhane, Sara E.

    2012-01-01

    Objectives: Attempts to understand the effects of maltreatment subtypes on childhood functioning are complicated by the fact that children often experience multiple subtypes. This study assessed the effects of maltreatment subtypes on the cognitive, academic, and mental health functioning of preadolescent youth in out-of-home care using both…

  5. Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

    DEFF Research Database (Denmark)

    Aure, Miriam Ragle; Vitelli, Valeria; Jernström, Sandra

    2017-01-01

    subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between...

  6. 75 FR 69046 - Notice of Determination of the High Pathogenic Avian Influenza Subtype H5N1 Status of Czech...

    Science.gov (United States)

    2010-11-10

    ... Avian Influenza Subtype H5N1 Status of Czech Republic and Sweden AGENCY: Animal and Plant Health... the highly pathogenic avian influenza (HPAI) subtype H5N1 status of the Czech Republic and Sweden... status of the Czech Republic and Sweden relative to highly pathogenic avian influenza (HPAI) subtype H5N1...

  7. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls.

    NARCIS (Netherlands)

    R.A.M. Fouchier (Ron); V.J. Munster (Vincent); A. Wallensten (Anders); T.M. Bestebroer (Theo); S. Herfst (Sander); D.J. Smith (Derek James); G.F. Rimmelzwaan (Guus); B. Olsen (Björn); A.D.M.E. Osterhaus (Albert)

    2005-01-01

    textabstractIn wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses

  8. Peculiarities of diagnostics and clinical course of different immunohistochemical subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    El Khazhzh M.Kh.

    2014-09-01

    Full Text Available Modern global guidelines in oncology consider treatment of various forms of breast cancer according to molecular tumor subtype. Steroid receptors, epidermal growth factor receptors, p53, Ki67 proliferative activity index and others are the key indicators of aggressiveness of malignant breast tumors. The material for this study was the retrospective study of the standard set of breast cancer immuno¬histochemical markers (estrogen receptors, progesterone, epidermal growth factor type 2 in 8171 patients. 4 groups of patients - luminal A, luminal B, triple negative and HER2-neu positive subtypes of tumors were identified according to immunohistochemical status. We analyzed overall survival without relapse in 491 patients with breast cancer, clinical data and data of immunohistochemical studies were matched. Based on the investigation it was determined that in the early stages of the disease (1-2 luminal A subtype of cancer is often diagnosed. In the late stages the most common subtype is HER2-neu positive breast cancer. Herewith, patients with luminal A subtype of cancer have the best performance of the overall survival (OS (32,91±2,33 months, and the worst results were found in patients with HER2 - neu positive breast cancer (22,58±1,28 months. The data obtained determine HER2 - neu positive subtype as the most aggressive type of breast cancer, and the luminal A subtype – as the least aggressive one.

  9. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

    Directory of Open Access Journals (Sweden)

    Park Hyung Seok

    2012-01-01

    Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

  10. Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Naka, H.; Ohshita, T.; Murata, Y.; Imon, Y.; Mimori, Y.; Nakamura, S. [Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima (Japan)

    2002-03-01

    We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation. (orig.)

  11. Geographic distribution of hepatitis C virus genotype 6 subtypes in Thailand.

    Science.gov (United States)

    Akkarathamrongsin, Srunthron; Praianantathavorn, Kesmanee; Hacharoen, Nisachol; Theamboonlers, Apiradee; Tangkijvanich, Pisit; Tanaka, Yasuhito; Mizokami, Masashi; Poovorawan, Yong

    2010-02-01

    The nucleotide sequence of hepatitis C virus (HCV) genotype 6 found mostly in south China and south-east Asia, displays profound genetic diversity. The aim of this study to determine the genetic variability of HCV genotype 6 (HCV-6) in Thailand and locate the subtype distribution of genotype 6 in various geographic areas. Four hundred nineteen anti-HCV positive serum samples were collected from patients residing in - the central part of the country. HCV RNA positive samples based on reverse transcriptase- polymerase chain reaction (RT-PCR) of the 5'UTR were amplified with primers specific for the core and NS5B regions. Nucleotide sequences of both regions were analyzed for the genotype by phylogenetic analysis. To determine geographic distribution of HCV-6 subtypes, a search of the international database on subtype distribution in the respective countries was conducted. Among 375 HCV RNA positive samples, 71 had HCV-6 based on phylogenetic analysis of partial core and NS5B regions. The subtype distribution in order of predominance was 6f (56%), 6n (22%), 6i (11%), 6j (10%), and 6e (1%). Among the 13 countries with different subtypes of HCV-6, most sequences have been reported from Vietnam. Subtype 6f was found exclusively in Thailand where five distinct HCV-6 subtypes are circulating. HCV-6, which is endemic in south China and south-east Asia, displays profound genetic diversity and may have evolved over a considerable period of time. (c) 2009 Wiley-Liss, Inc.

  12. The Dissociative Subtype of Post-traumatic Stress Disorder: Research Update on Clinical and Neurobiological Features.

    Science.gov (United States)

    van Huijstee, Jytte; Vermetten, Eric

    2017-10-21

    Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in the DSM-5. This review focuses on the clinical and neurobiological features that distinguish the dissociative subtype of PTSD from non-dissociative PTSD. Clinically, the dissociative subtype of PTSD is associated with high PTSD severity, predominance of derealization and depersonalization symptoms, a more significant history of early life trauma, and higher levels of comorbid psychiatric disorders. Furthermore, PTSD patients with dissociative symptoms exhibit different psychophysiological and neural responses to the recall of traumatic memories. While individuals with non-dissociative PTSD exhibit an increased heart rate, decreased activation of prefrontal regions, and increased activation of the amygdala in response to traumatic reminders, individuals with the dissociative subtype of PTSD show an opposite pattern. It has been proposed that dissociation is a regulatory strategy to restrain extreme arousal in PTSD through hyperinhibition of limbic regions. In this research update, promises and pitfalls in current research studies on the dissociative subtype of PTSD are listed. Inclusion of the dissociative subtype of PTSD in the DSM-5 stimulates research on the prevalence, symptomatology, and neurobiology of the dissociative subtype of PTSD and poses a challenge to improve treatment outcome in PTSD patients with dissociative symptoms.

  13. Comparison of two motor subtype classifications in de novo Parkinson's disease.

    Science.gov (United States)

    Choi, Seong-Min; Kim, Byeong C; Cho, Bang-Hoon; Kang, Kyung Wook; Choi, Kang-Ho; Kim, Joon-Tae; Lee, Seung-Han; Park, Man-Seok; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2018-04-18

    Clinical subtypes of Parkinson's disease (PD) have been empirically defined based on the prominent motor symptoms. The aim of this study was to compare the prevalence of non-motor symptoms across PD motor subtypes in patients with PD. A total of 192 patients with de novo PD were included. The patients were classified into the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR) and tremor-dominant/mixed/postural instability and gait disturbance (TD/mixed/PIGD) subtypes, according to previous reports. In the TD/mixed/AR classification, scores for scales related to motor symptoms and activities of daily living (ADL) were significantly different among the groups, and patients with the AR subtype demonstrated more severe scores than patients with the TD subtype. In the TD/mixed/PIGD classification, age, age at symptom onset, scores on motor-related scales, ADL, and non-motor symptoms were significantly different among the groups. Scores including the modified Hoehn and Yahr stages, the motor and ADL subscores of the Unified Parkinson's Disease Rating Scale, the Beck Depression Inventory, and the Non-Motor Symptom Assessment Scale were significantly different after adjustments for age and age at symptom onset, and patients with the PIGD subtype obtained more severe scores than patients with the TD subtype. The TD/mixed/PIGD classification seems to be more suitable for identifying non-motor abnormalities than the TD/mixed/AR classification. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. High prevalence of luminal B breast cancer intrinsic subtype in Colombian women.

    Science.gov (United States)

    Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

    2016-07-01

    Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. HIV-1 epidemiology and circulating subtypes in the countryside of Sout