Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of HD

  • maintenance hd
  • patient undergoing hd
  • star hd
  • undergoing hd

  • Terms modified by HD

  • hd gene
  • hd group
  • hd mouse
  • hd patient
  • hd population
  • hd session

  • Selected Abstracts

    Nearby stars of the Galactic disk and halo.


    Abstract High-resolution spectroscopic observations of about 150 nearby stars or star systems are presented and discussed. The study of these and another 100 objects of the previous papers of this series implies that the Galaxy became reality 13 or 14 Gyr ago with the implementation of a massive, rotationally-supported population of thick-disk stars. The very high star formation rate in that phase gave rise to a rapid metal enrichment and an expulsion of gas in supernovae-driven Galactic winds, but was followed by a star formation gap for no less than three billion years at the Sun's galactocentric distance. In a second phase, then, the thin disk , our "familiar Milky Way" , came on stage. Nowadays it traces the bright side of the Galaxy, but it is also embedded in a huge coffin of dead thick-disk stars that account for a large amount of baryonic dark matter. As opposed to this, cold-dark-matter-dominated cosmologies that suggest a more gradual hierarchical buildup through mergers of minor structures, though popular, are a poor description for the Milky Way Galaxy , and by inference many other spirals as well , if, as the sample implies, the fossil records of its long-lived stars do not stick to this paradigm. Apart from this general picture that emerges with reference to the entire sample stars, a good deal of the present work is however also concerned with detailed discussions of many individual objects. Among the most interesting we mention the blue straggler or merger candidates HD 165401 and HD 137763/HD 137778, the likely accretion of a giant planet or brown dwarf on 59 Vir in its recent history, and HD 63433 that proves to be a young solar analog at , , 200 Myr. Likewise, the secondary to HR 4867, formerly suspected non-single from the Hipparcos astrometry, is directly detectable in the highresolution spectroscopic tracings, whereas the visual binary , Cet is instead at least triple, and presumably even quadruple. With respect to the nearby young stars a complete account of the UrsaMajor Association is presented, and we provide as well plain evidence for another, the "Hercules-Lyra Association", the likely existence of which was only realized in recent years. On account of its rotation, chemistry, and age we do confirm that the Sun is very typical among its G-type neighbors; as to its kinematics, it appears however not unlikely that the Sun's known low peculiar space velocity could indeed be the cause for the weak paleontological record of mass extinctions and major impact events on our parent planet during the most recent Galactic plane passage of the solar system. Although the significance of this correlation certainly remains a matter of debate for years to come, we point in this context to the principal importance of the thick disk for a complete census with respect to the local surface and volume densities. Other important effects that can be ascribed to this dark stellar population comprise (i) the observed plateau in the shape of the luminosity function of the local FGK stars, (ii) a small though systematic effect on the basic solar motion, (iii) a reassessment of the term "asymmetrical drift velocity" for the remainder (i.e. the thin disk) of the stellar objects, (iv) its ability to account for the bulk of the recently discovered high-velocity blue white dwarfs, (v) its major contribution to the Sun's ,220 km s,1 rotational velocity around the Galactic center, and (vi) the significant flattening that it imposes on the Milky Way's rotation curve. Finally we note a high multiplicity fraction in the small but volume-complete local sample of stars of this ancient population. This in turn is highly suggestive for a star formation scenario wherein the few existing single stellar objects might only arise from either late mergers or the dynamical ejection of former triple or higher level star systems. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

    Comorbidity between obesity and attention deficit/hyperactivity disorder: Population study with 13,15-year-olds

    Luis Rojo MD
    Abstract Objective: This study analyzes whether obese children have a higher risk of attention deficit/hyperactivity "characteristics" (AD/HD) than do children with other nutritional states. Method: This study included 35,403 participants from 486 community schools. They completed the AD/HD scale of the Strengths and Difficulties Questionnaire (SDQ) and were weighed and measured. 2879 of the participants were obese and 78 were morbidly obese (BMI >40). Results: A discrete, nonsignificant, increment was found in the AD/HD characteristics of male participants with morbid obesity, as compared with the other nutritional states. Among morbidly obese females, the prevalence of AD/HD characteristics was slightly superior, although not significantly, to that found in participants with normal weight, overweight or obese (BMI <40). Conclusion: Among nonclinical populations with a communitarian origin, previous findings reporting high rates of AD/HD in obese children are not replicated. This increment in the prevalence of AD/HD among hospitalized obese children could be the result of selection bias. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006 [source]

    Social outcomes of children with AD/HD: Contributing factors and implications for practice

    Melissa Stormont
    The purposes of this article are to provide a review of the literature in the area of social characteristics of children with AD/HD, and to outline interventions for working with specific social problems. Research has consistently documented that children with AD/HD are more rejected and less accepted by their peers. Possible reasons for this peer rejection will be presented in this article and include inappropriate social behavior, social knowledge deficits and biases, and negative interactions with peers and teachers. Because children with AD/HD are at risk for negative social outcomes, multiple intervention options are necessary. © 2001 John Wiley & Sons, Inc. [source]

    On the Intersection Between AD/HD and DCD: The DAMP Hypothesis

    Edmund J. S. Sonuga-Barke
    The paper by Gillberg, ,ADHD and DAMP', provides an analysis of the scientific status of the concept of Deficits in Attention Motor Control and Perception (DAMP) in the light of the overlap between Attention Deficit/Hyperactivity Disorder (AD/HD) and Developmental Co-ordination Disorder (DCD), and the current uncertainty surrounding the significance of AD/HD , DCD co-morbidity. [source]

    Emerging Evidence that AD/HD and DCD Interact Multiplicatively

    Christopher Gillberg
    No abstract is available for this article. [source]

    Utility and outcomes of fine-needle aspiration biopsy in Hodgkin's disease

    Wendy S. Moreland M.D.
    Abstract We present our 10-year experience, including clinical utilization and outcomes, with fine-needle aspiration biopsy (FNAB) in Hodgkin's disease (HD). Eighty-six cases from 68 patients with HD that were evaluated by FNAB were identified over a 10-year period. Medical records of these 68 patients were reviewed. Thirty-seven patients with primary HD underwent 41 aspirates. A diagnosis of HD was yielded in 12 and suggested in 13 cases (sensitivity 86.2%, false-positive 0%). Nine were diagnosed as atypical lymphoid cells, four as hyperplasia/other, and three as unsatisfactory. With these diagnoses, six patients began treatment without tissue exam. Thirty-five patients with suspected recurrent HD underwent 45 FNABs. Recurrent HD was confirmed in 15 and suggested in 12 aspirates (sensitivity 81.3%, false-suspicious 14.3%). With these diagnoses, 22 patients began treatment for recurrence without tissue exam. FNAB is useful both for establishing a primary diagnosis and confirming recurrence in HD and thus has a high utilization at our institution. In many instances, patients can begin therapy, negating the need for formal tissue exam. Diagn. Cytopathol. 2002;26:278,282. © 2002 Wiley-Liss, Inc. [source]

    The Effect of Hemodialysis on Left Ventricular Outflow Tract Gradient

    ECHOCARDIOGRAPHY, Issue 6 2010
    Pawel Petkow Dimitrow M.D.
    Background: The aim of the study was to assess the effect of hemodialysis (HD) on left ventricular outflow tract gradient (LVOTG) measured both in supine and upright position (provocative maneuver to unload LV cavity by rapid preload reduction). Supine/standing echocardiography was performed immediately before and immediately after HD. For additional verification of the hypothesis about preload-dependence of LVOTG, the echocardiograms after long (2-day delay HD due to weekend) versus short (usual 1-day) pause between HDs were compared. Methods: Forty-one patients on chronic HD (mean age 44 ± 11 years) were examined using a portable hand-carried echocardiograph. In accordance with the prestudy assumption the ultrafiltration volume was significantly greater during HD after a long pause in comparison to HD after a short pause (3707 ± 2826 mL vs. 2665 ± 1152 mL P < 0.05). Results: After a long pause, the mean value of LVOTG at the pre-HD was mildly increased in the supine position and remained at a similar level in the upright position (13.1 ± 6.1 vs. 13.6 ± 9.1 mmHg). Mean LVOTG at the post-HD in the supine position was similar to pre-HD, however the orthostatic stress test induced a significant increase of LVOTG (13.9 ± 15.2 vs. 18.2 ± 19.9 mmHg P < 0.05). After a short pause at the pre-HD the LVOTG in the supine position and after the orthostatic provocation was very similar to measurements after long pause (13.3 ± 9.1 vs. 13.3 ± 10.8 mmHg). At the post-HD the mean value of LVOTG increased during upright posture but the differences were of borderline significance (13.2 ± 6.6 vs. 17.9 ± 18.6 mmHg P = 0.052). Conclusions: HD predisposed to standing-provoked LVOTG especially when a long pause (2 days) between HDs induced a greater weight gain and subsequently a larger volume of ultrafiltration was needed to reduce hypervolemia. (Echocardiography 2010;27:603-607) [source]

    Effect of Preload on Left Ventricular Longitudinal Strain by 2D Speckle Tracking

    ECHOCARDIOGRAPHY, Issue 8 2008
    Jin-Oh Choi M.D.
    Background: Peak systolic longitudinal strain (PSLS) obtained using the 2D speckle tracking method is a novel indicator of the long-axis function of the left ventricle (LV). We used the 2D strain profile to examine the effect of preload reduction by hemodialysis (HD) on LV PSLS in patients with end-stage renal disease (ESRD). Method and results: Twenty-nine pairs of echocardiographic evaluations were obtained before and after dialysis. Global LV PSLS was ,18.4 ± 2.9%, at baseline and decreased to ,16.9 ± 3.2% after HD (P < 0.001). Segmental analysis showed that the decrease in PSLS after dialysis was most prominent in mid-LV segments (,17.1 ± 3.5% vs. ,15.4 ± 3.4%, P < 0.001). Conclusion: PSLS obtained from the 2D strain profile is a reliable parameter that may be useful for evaluating LV systolic long-axis function. However, PSLS should be applied cautiously in ESRD patients because it could be affected by dialysis. [source]

    Surveillance of Infectious Disease Occurrences in the Community: An Analysis of Symptom Presentation in the Emergency Department

    Joe Suyama MD
    Objectives: To determine the effectiveness of a simulated emergency department (ED)-based surveillance system to detect infectious disease (ID) occurrences in the community. Methods: Medical records of patients presenting to an urban ED between January 1, 1999, and December 31, 2000, were retrospectively reviewed for ICD-9 codes related to ID symptomatology. ICD-9 codes, categorized into viral, gastrointestinal, skin, fever, central nervous system (CNS), or pulmonary symptom clusters, were correlated with reportable infectious diseases identified by the local health department (HD). These reportable infectious diseases are designated class A diseases (CADs) by the Ohio Department of Health. Cross-correlation functions (CCFs) tested the temporal relationship between ED symptom presentation and HD identification of CADs. The 95% confidence interval for lack of trend correlation was 0.0 ± 0.074; thus CCFs > 0.074 were considered significant for trend correlation. Further cross-correlation analysis was performed after chronic and non-community-acquirable infectious diseases were removed from the HD database as a model for bioterrorism surveillance. Results: Fifteen thousand five hundred sixty-nine ED patients and 6,489 HD patients were identified. Six thousand two hundred eight occurrences of true CADs were identified. Only 87 (1.33%) HD cases were processed on weekends. During the study period, increased ED symptom presentation preceded increased HD identification of respective CADs by 24 hours for all symptom clusters combined (CCF = 0.112), gastrointestinal symptoms (CCF = 0.084), pulmonary symptoms (CCF = 0.110), and CNS symptoms (CCF = 0.125). The bioterrorism surveillance model revealed increased ED symptom presentation continued to precede increased HD identification of the respective CADs by 24 hours for all symptom clusters combined (CCF = 0.080), pulmonary symptoms (CCF = 0.100), and CNS symptoms (CCF = 0.120). Conclusions: Surveillance of ED symptom presentation has the potential to identify clinically important ID occurrences in the community 24 hours prior to HD identification. Lack of weekend HD data collection suggests that the ED is a more appropriate setting for real-time ID surveillance. [source]

    Effects of oral electrolyte supplementation on endurance horses competing in 80 km rides

    Summary Reasons for performing study: There is no evidence that use of oral electrolyte pastes enhances performance in competing endurance horses. Objective: To ascertain whether oral administration of a high dose (HD) of sodium chloride (NaCl) and potassium chloride (KCl) to endurance horses would differentially increase water intake, attenuate bodyweight (bwt) loss and improve performance when compared to a low dose (LD). Methods: A randomised, blinded, crossover study was conducted on 8 horses participating in two 80 km rides (same course, 28 days apart). Thirty minutes before and at 40 km of the first ride 4, horses received orally 0.2 g NaCl/kg bwt and 0.07 g KCl/kg bwt. The other 4 received 0.07 g NaCl/kg bwt and 0.02 g KCl/kg bwt. Horses received the alternate treatment in the second ride. Data were analysed with 2-way ANOVA for repeated measures (P<0.05). Results: Estimated water intake was significantly greater with HD both at the 40 km mark and as total water intake; however, differences in bwt loss and speed between HD and LD were not found. Treatment significantly affected serum Na+, Cl,, HCO3, pH and water intake, but not serum K+ or bwt. Serum Na+ and Cl, were significantly higher at 80 km when horses received HD, but no differences were found in early recovery. Venous HCO3 and pH were significantly lower throughout the ride and in early recovery when horses received HD. Conclusions and potential relevance: Other than enhancing water intake, supplementing endurance horses with high doses of NaCl and KCl did not provide any detectable competitive advantage in 80 km rides. Further, the elevated serum electrolyte concentrations induced with HD might not be appropriate for endurance horses. [source]

    Haemodialysis induces mitochondrial dysfunction and apoptosis

    D. S. C. Raj
    Abstract Background Mitochondria play a crucial role in the regulation of the endogenous pathways of apoptosis activated by oxidant stress. Nuclear factor-,B (NF-,B) is a central integration site for pro-inflammatory signals and oxidative stress. Materials and methods Peripheral blood mononuclear cells (PBMC) were isolated from eight end-stage renal disease (ESRD) patients before haemodialysis (Pre-HD) and during the last 10 min of HD (End-HD). A new polysulfone membrane (F70, Fresenius) was used for dialysis. Intracellular generation of reactive oxygen species (ROS), mitochondrial redox potential (,,m) and PBMC apoptosis were determined by flow-cytometry. Results Plasma levels of interleukin-6 (IL-6) (24·9 ± 7·0 vs. 17·4 ± 5·5 pg dL,1, P < 0·05), IL-6 soluble receptor (52·2 ± 4·9 vs. 37·6 ± 3·2 ng dL,1, P < 0·02) and IL-6 gp130 (405·7 ± 41·0 vs. 235·1 ± 38·4 ng dL,1, P < 0·02) were higher end-HD compared to pre-HD. IL-6 secretion by the isolated PBMC (24·0 ± 2·3 vs. 19·3 ± 3·5 pg dL,1, P < 0·02) increased end-HD. Percentage of lymphocytes exhibiting collapse of mitochondrial membrane potential (43·4 ± 4·6% vs. 32·6 ± 2·9%, P < 0·01), apoptosis (33·4 ± 7·1% vs. 23·7 ± 7·7%, P < 0·01), and generation of superoxide (20·7 ± 5·2% vs. 12·5 ± 2·9%, P < 0·02) and hydrogen peroxide (51·1 ± 7·8% vs.38·2 ± 5·9%, P < 0·04) were higher at end-HD than pre-HD. NF-,B activation (3144·1 ± 208·1 vs. 2033·4 ± 454·6 pg well,1, P < 0·02), expression of B-cell lymphoma protein-2 (6494·6 ± 1461 vs. 3501·5 ± 796·5 ng mL,1, P < 0·03) and heat shock protein-70 (9·81 ± 1·47 vs. 6·38 ± 1·0 ng mL,1, P < 0·05) increased during HD. Conclusions Intra-dialytic activation of cytokines, together with impaired mitochondrial function, promotes generation of ROS culminating in augmented PBMC apoptosis. There is concomitant activation of pathways aimed at attenuation of cell stress and apoptosis during HD. [source]

    Autologous transplantation in relapsed and refractory Hodgkin's disease

    Andreas Josting
    Abstract:, The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD. [source]

    Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4+ T-cell proliferation and IFN-, production in response to myelin basic protein and myelin oligodendrocyte glycoprotein

    Christopher T. Harp
    Abstract Recent evidence suggests that B- and T-cell interactions may be paramount in relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin-, secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4+ T-cell proliferation and IFN-, secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4+ T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells. [source]

    Autonomic symptoms in patients and pre-manifest mutation carriers of Huntington's disease

    N. A. Aziz
    Background and purpose:, Although autonomic function tests have revealed abnormalities of the autonomic nervous system in Huntington's disease (HD), autonomic symptoms and their association with other symptoms and signs of HD have not yet been assessed in large groups of patients or pre-manifest mutation carriers. Therefore, we aimed at delineating the characteristics and correlates of autonomic symptoms in HD. Methods:, Using the scales for outcomes in Parkinson's disease-autonomic symptoms (SCOPA-AUT) and Beck Depression Inventory questionnaires, autonomic symptoms and depressed mood were assessed in 63 patients with HD, 21 pre-manifest mutation carriers, and 85 controls. The Unified Huntington's Disease Rating Scale was used to assess other HD symptoms and signs. Results:, Relative to controls, patients with HD experienced significantly more gastrointestinal, urinary, cardiovascular and, in men, sexual problems. The most prevalent symptoms were swallowing difficulties, erection and ejaculation problems, dysphagia, sialorrhea, early abdominal fullness, straining for defecation, fecal and urinary incontinence, urgency, incomplete bladder emptying, and light-headedness whilst standing. Pre-manifest mutation carriers experienced significantly more swallowing difficulties and light-headedness on standing up compared with controls. In patients with HD, autonomic symptoms were associated with a greater degree of functional disability, more severe depression, and antidepressant drugs use. However, depression was the only independent predictor of autonomic dysfunction. Conclusions:, Autonomic symptoms are highly prevalent in patients with HD and may even precede the onset of motor signs. Moreover, autonomic dysfunction is related to functional disability and depression in HD. [source]

    Chronic daily headache with medication overuse: predictors of outcome 1 year after withdrawal therapy

    M. G. Bøe
    Background and purpose:, We examined prospectively the results of withdrawal therapy in 80 patients with probable medication overuse headache. The aim was to identify baseline patient characteristics that might predict outcome after 1 year (end of study). Methods:, We classified patients according to results of withdrawal therapy measured as the improvement of headache days (HD) from baseline to end of study. Results:, Thirty-six per cent (29/80) had at least 50% improvement. Sixty-four per cent (51/80) had <50% improvement, and among these, 30% (24/80) had <10% improvement. The following baseline characteristics were associated with poor outcome of withdrawal therapy: use of codeine-containing drugs, low self-reported sleep quality, and high self-reported bodily pain as measured by the quality of life tool SF-36. Conclusion:, Before suggesting withdrawal therapy, one should probably pay more close attention to sleep problems. [source]

    BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtin

    Rebecca Leon
    Abstract Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the N-terminus of the huntingtin protein. It is characterized by a selective loss of medium spiny neurons in the striatum. It has been suggested that impaired proteasome function and endoplasmic reticulum (ER) stress play important roles in mutant huntingtin (mHtt)-induced cell death. However, the molecular link involved is poorly understood. In the present study, we identified the essential role of the extra long form of Bim (Bcl-2 interacting mediator of cell death), BimEL, in mHtt-induced cell death. BimEL protein expression level was significantly increased in cell lines expressing the N-terminus of mHtt and in a mouse model of HD. Although quantitative RT-PCR analysis indicated that BimEL mRNA was increased in cells expressing mHtt, we provided evidence showing that, at the post-translational level, phosphorylation of BimEL played a more important role in regulating BimEL expression. Up-regulation of BimEL facilitated the translocation of Bax to the mitochondrial membrane, which further led to cytochrome c release and cell death. On the other hand, knocking down BimEL expression prevented mHtt-induced cell death. Taken together, these findings suggest that BimEL is a key element in regulating mHtt-induced cell death. A model depicting the role of BimEL in linking mHtt-induced ER stress and proteasome dysfunction to cell death is proposed. [source]

    Mechanisms of neurodegeneration in Huntington's disease

    Joana M. Gil
    Abstract Huntington's disease (HD) is caused by an expansion of cytosine,adenine,guanine (CAG) repeats in the huntingtin gene, which leads to neuronal loss in the striatum and cortex and to the appearance of neuronal intranuclear inclusions of mutant huntingtin. Huntingtin plays a role in protein trafficking, vesicle transport, postsynaptic signaling, transcriptional regulation, and apoptosis. Thus, a loss of function of the normal protein and a toxic gain of function of the mutant huntingtin contribute to the disruption of multiple intracellular pathways. Furthermore, excitotoxicity, dopamine toxicity, metabolic impairment, mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy have been implicated in the progressive degeneration observed in HD. Nevertheless, despite the efforts of a multidisciplinary scientific community, there is no cure for this devastating neurodegenerative disorder. This review presents an overview of the mechanisms that may contribute for HD pathogenesis. Ultimately, a better understanding of these mechanisms will lead to the development of more effective therapeutic targets. [source]

    Hypothalamic,endocrine aspects in Huntington's disease

    Åsa Petersén
    Abstract Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic,pituitary,adrenal axis occurs as well as pancreatic ,-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions. [source]

    Striatal modulation of cAMP-response-element-binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

    Carmela Giampà
    Abstract Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763,6768; Gines et al. (2003)Hum. Mol. Genet., 12, 497,508; Rouaux et al. (2004) Biochem. Pharmacol., 68, 1157,1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988,4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al. (2003)Hum. Mol. Genet., 12, 497,508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron, 35, 605,623; Lonze et al. (2002)Neuron, 34, 371,385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual-label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease. [source]

    Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

    Helen E. Grote
    Abstract Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice. [source]

    Increased glucose metabolism and ATP level in brain tissue of Huntington's disease transgenic mice

    FEBS JOURNAL, Issue 19 2008
    Judit Oláh
    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, the formation of inclusions caused by the mutation of huntingtin protein and its relationship with changes in energy metabolism and with pathological alterations were investigated both in transgenic and 3-nitropropionic acid-treated mouse models for HD. The HD and normal mice were characterized clinically; the affected brain regions were identified by immunohistochemistry and used for biochemical analysis of the ATP-producing systems in the cytosolic and the mitochondrial compartments. In both HD models, the activities of some glycolytic enzymes were somewhat higher. By contrast, the activity of glyceraldehyde-3-phosphate dehydrogenase was much lower in the affected region of the brain compared to that of the control. Paradoxically, at the system level, glucose conversion into lactate was enhanced in cytosolic extracts from the HD brain tissue, and the level of ATP was higher in the tissue itself. The paradox could be resolved by taking all the observed changes in glycolytic enzymes into account, ensuing an experiment-based detailed mathematical model of the glycolytic pathway. The mathematical modelling using the experimentally determined kinetic parameters of the individual enzymes and the well-established rate equations predicted the measured flux and concentrations in the case of the control. The same mathematical model with the experimentally determined altered Vmax values of the enzymes did account for an increase of glycolytic flux in the HD sample, although the extent of the increase was not predicted quantitatively. This suggested a somewhat altered regulation of this major metabolic pathway in HD tissue. We then used the mathematical model to develop a hypothesis for a new regulatory interaction that might account for the observed changes; in HD, glyceraldehyde-3-phosphate dehydrogenase may be in closer proximity (perhaps because of the binding of glyceraldehyde-3-phosphate dehydrogenase to huntingtin) with aldolase and engage in channelling for glyceraldehyde-3-phosphate. By contrast to most of the speculation in the literature, our results suggest that the neuronal damage in HD tissue may be associated with increased energy metabolism at the tissue level leading to modified levels of various intermediary metabolites with pathological consequences. [source]

    Supercritical carbon dioxide extraction of volatiles from Satureja fruticosa Béguinot

    J. A. Coelho
    Abstract Dried flowers and leaves of Satureja fruticosa Béguinot were submitted to supercritical CO2 extraction (SFE), followed by a two-stage fractional separation. The extraction was carried out at 40 °C in a flow apparatus, provided with a 1 l extraction vessel and two separators of 0.27 l each. Conditions of extraction, such as pressure, particle size of plant material and CO2 flow rate, were studied in order to assess their influence on the yield and composition of the volatiles. The best conditions of extraction were 90 bar pressure at 1.32 kg/h CO2 flow rate and a plant material particle size of 0.5 mm. The SFE volatiles obtained and the essential oil isolated by hydrodistillation (HD) were analysed and compared by GC and GC,MS. The oxygen-containing monoterpenes, pulegone (33,36% for SFE and 40,41% for HD), isomenthone (14,18% for SFE and 21% for HD), piperitenone (11,12% for SFE and 9,11% for HD) and piperitenone oxide (11,13% for SFE and 7,9% for HD) were the dominant components in all samples. Copyright © 2007 John Wiley & Sons, Ltd. [source]

    Histo-cytochemistry and scanning electron microscopy of lavender glandular trichomes following conventional and microwave-assisted hydrodistillation of essential oils: a comparative study

    Marcello Iriti
    Abstract The conventional hydrodistillation method (HD) has been compared with three different variants of the microwave-assisted hydrodistillation technique (MADH), on Lavandula angustifolia flowers, both in terms of oil yield and effects on the glandular trichome morpho-structure. The amount and composition of essential oil extracted in 4 h by HD was similar to that obtained in only 20 min by MADH and even lower than that extracted with a steam variant (MASD) of MADH itself. Histo-cytochemical investigations and scanning electron microscopy showed that glandular trichome, after 4 h of HD, appeared swollen, with a deeply wrinkled surface and empty of essential oil, however maintaining the integrity of their cuticle. Many oil droplets were stuck to the outside of the trichome cuticle, sometimes arranged in large aggregates. After 20 min of MADH or MASD, trichomes appeared empty as well, but also particularly disrupted, or at least with holes in their head cuticle. Oil droplets were present outside the glands and in the inter-rib regions of the flower calyx, except in the case of MASD. After this extraction method, neither oil droplets nor other lipid staining were present in the samples, confirming the effectiveness of this particular MADH technique. These investigations suggest that the rapidity of MADH and MASD in extracting essential oil is mainly due to the collapse of trichome structure and the consequent direct release of its content, without which it has to slowly permeate through membranes and cuticle, as in the case of HD. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor

    Junjiro Ohshima
    A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2 and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors; L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations or SOSTDC1 mutation (P = 0.056). There were no significant differences in clinical characteristics between nine patients with 7p alterations and 88 patients with no 7p alterations; however, there was a difference in the status of IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may be prime candidates for 7p tumor suppressor genes, which may have a role in the progression of Wilms tumorigenesis. © 2009 Wiley-Liss, Inc. [source]

    Huntington's disease with onset ages greater than 60 years

    Kunihiro Yoshida
    We examined five patients with late-onset Huntington's disease (HD), who developed chorea as an initial symptom at age 60 or later. The mean disease duration from the onset of chorea was approximately 8 years (range, 2,16 years). All carried expanded HD alleles with 39 or 40 CAG repeats. Cognitive or psychiatric decline was observed in four patients, the mean duration of the disease being approximately 10 years. One of them had been institutionalized in a nursing home undiagnosed for a long time. Late-onset HD patients with shorter repeat expansions may be overlooked in Japan. Non-disabling chorea, mild cognitive or psychiatric decline in such patients are sometimes unrecognized or misunderstood as aging-related phenomena, and do not come to medical attention. Considering the potential genetic risk to younger generations, however, genetic testing on such late-onset HD patients should be conducted with careful genetic counseling and psychological support for their family members. [source]

    Cytochrome c oxidase isoform IV-2 is involved in 3-nitropropionic acid-induced toxicity in striatal astrocytes

    GLIA, Issue 14 2009
    Shilpee Singh
    Abstract Astrocyte mitochondria play an important role for energy supply and neuronal survival in the brain. Toxic and degenerative processes are largely associated with mitochondrial dysfunction. We, therefore, investigated the effect of 3-nitropropionic acid (NPA), a mitochondrial toxin and in vitro model of Huntington's disease (HD), on mitochondrial function and viability of primary striatal astrocytes. Although NPA is known as an irreversible inhibitor of succinate dehydrogenase, we observed an increase of astrocyte ATP levels after NPA treatment. This effect could be explained by NPA-mediated alterations of cytochrome c oxidase subunit IV isoform (COX IV) expression. The up-regulation of COX isoform IV-2 caused an increased enzyme activity at the expense of elevated mitochondrial peroxide production causing increased cell death. The application of a small interfering RNA against COX IV-2 revealed the causal implication of COX isoform IV-2 in NPA-mediated elevation of oxidative stress and necrotic cell death. Thus, we propose a novel, additional mechanism of NPA-induced cell stress and death which is based on structural and functional changes of astrocyte COX and which could indirectly impair neuronal survival. © 2009 Wiley-Liss, Inc. [source]

    Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: Relevance for Huntington's disease

    GLIA, Issue 11 2009
    Onintza Sagredo
    Abstract Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions, but they are markedly upregulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labeled with the marker of reactive microglia OX-42, and also in cells labeled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-, (TNF-,) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-,. Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. © 2008 Wiley-Liss, Inc. [source]

    The influence of strain of Holstein-Friesian dairy cow and pasture-based feeding system on grazing behaviour, intake and milk production

    GRASS & FORAGE SCIENCE, Issue 1 2007
    S. McCarthy
    Abstract A comparative study of grazing behaviour, herbage intake and milk production of three strains of Holstein-Friesian dairy cow was conducted using three grass-based feeding systems over two years. The three strains of Holstein-Friesian cows were: high production North American (HP), high durability North American (HD) and New Zealand (NZ). The three grass-based feeding systems were: high grass allowance (MP), high concentrate (HC) and high stocking rate (HS). In each year seventy-two pluriparous cows, divided equally between strains of Holstein-Friesian and feeding systems were used. Strain of Holstein-Friesian cow and feeding system had significant effects on grazing behaviour, dry matter (DM) intake and milk production. The NZ strain had the longest grazing time while the HD strain had the shortest. The grazing time of cows in the HC system was shorter than those in both the HS and MP systems. There was a significant strain of Holstein-Friesian cow by feeding system interaction for DM intake of grass herbage and milk production. The NZ strain had the highest substitution rate with the HP strain having the lowest. Hence, response in milk production to concentrate was much greater with the HP than the NZ strain. Reduction in milk yield as a consequence of a higher stocking rate (MP vs. HS system) was, however, greater for the HP and HD strains compared with the NZ strain. The results suggest that differences in grazing behaviour are important in influencing DM intake and milk production. [source]

    Hematological malignancies in the island of Sardinia, 1974,1993: age and sex distributions and temporal changes in incidence

    G. Broccia
    Abstract We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974,1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984,1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    Epidemiology Of Hodgkin's disease: a review

    R. A. Cartwright
    Abstract The descriptive and aetiological epidemiology of Hodgkin's Disease (HD) are reviewed. Key issues which are highlighted include the evidence suggesting that HD is a complex of related conditions that are part mediated by infectious diseases, immune deficits and genetic susceptibilities. There is little convincing evidence to suggest any other environmental factors are involved in the aetiology. The apparent changing pattern of disease by time and from country to country, needs careful future study. Copyright © 2004 John Wiley & Sons, Ltd. [source]