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Sample records for pick disease of the brain

  1. Pick disease

    Science.gov (United States)

    Semantic dementia; Dementia - semantic; Frontotemporal dementia; FTD; Arnold Pick disease; 3R tauopathy ... doctors tell Pick disease apart from Alzheimer disease. (Memory loss is often the main, and earliest, symptom ...

  2. Niemann-Pick disease

    Science.gov (United States)

    NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage disease - Niemann-Pick ... lipofuscinoses or Batten disease (Wolman disease, cholesteryl ... metabolism of lipids. In: Kliegman RM, Stanton BF, St. Geme JW, ...

  3. Cataplexy leading to the diagnosis of Niemann-Pick disease type C.

    Science.gov (United States)

    Smit, Liesbeth S; Lammers, Gert Jan; Catsman-Berrevoets, Coriene E

    2006-07-01

    Cataplexy in childhood is a rare and often misdiagnosed symptom. It is described as a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions and in particular with unexpected laughter. This report presents a 9-year old male with progressive cerebellar and pyramidal symptoms and a cognitive decline since the age of 4. His recently developed "drop attacks" on laughter were recognized as cataplexy and led to the diagnosis of Niemann-Pick type C disease. With biochemical studies this diagnosis, a lysosomal storage disease, was confirmed. With cataplexy narcolepsy, Niemann-Pick type C disease, Norrie disease, Prader-Willi syndrome, and Coffin-Lowry syndrome are associated disorders. Recognition of cataplexy in children with concomitant neurologic symptoms may lead to an early and straight diagnosis of one of these disorders.

  4. Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability.

    Science.gov (United States)

    Pontikis, Charles C; Davidson, Cristin D; Walkley, Steven U; Platt, Frances M; Begley, David J

    2013-05-01

    Niemann-Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments. It has been observed that the administration of hydroxypropyl-β-cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal/lysosomal compartment. Here, we present evidence that refutes this hypothesis. We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain. The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi-time-point regression analysis. Neither study demonstrates significant, time-dependent uptake of HPBCD in either adult or neonatal mice. However, the volume of distribution available to HPBCD (0.113 ± 0.010 ml/g) exceeds the accepted values for plasma and vascular volume of the brain. In fact, it is nearly three times larger than that for sucrose (0.039 ± 0.006 ml/g). We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.

  5. Exploring the role of picker personality in predicting picking performance with pick by voice, pick to light and RF-terminal picking

    NARCIS (Netherlands)

    de Vries, J.; de Koster, R.; Stam, D.

    2016-01-01

    Order pickers and individual differences between them could have a substantial impact on picking performance, but are largely ignored in studies on order picking. This paper explores the role of individual differences in picking performance with various picking tools (pick by voice, RF-terminal

  6. Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    Héron Bénédicte

    2012-06-01

    Full Text Available Abstract Background Niemann-Pick disease type C (NP-C is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Published data on the use of miglustat in paediatric patients in clinical practice settings are limited. We report findings from a prospective open-label study in the French paediatric NP-C cohort. Methods Data on all paediatric NP-C patients treated with miglustat in France between October 2006 and December 2010 were compiled. All patients had a confirmed diagnosis of NP-C, and received miglustat therapy according to manufacturer’s recommendations. Pre-treatment and follow-up assessments were conducted according to a standardized protocol. Results Twenty children were enrolled; 19 had NPC1 gene mutations and 1 had NPC2 gene mutations. The median age at diagnosis was 1.5 years, and the median age at miglustat initiation was 6.0 years. Eight NPC1 patients had the early-infantile, eight had the late-infantile, and three had the juvenile-onset forms of NP-C. A history of hepatosplenomegaly and/or other cholestatic symptoms was recorded in all 8 early-infantile onset patients, 3/8 late-infantile patients, and 1/3 juvenile onset patients. Brain imaging indicated white matter abnormalities in most patients. The median (range duration of miglustat therapy was 1.3 (0.6–2.3 years in early-infantile, 1.0 (0.8–5.0 year in late-infantile, and 1.0 (0.6–2.5 year in juvenile onset patients. NP-C disability scale scores indicated either stabilization or improvement of neurological manifestations in 1/8, 6/8, and 1/3 NPC1 patients in these subgroups, respectively. There were no correlations between brain imaging findings and disease course. Mild-to-moderate gastrointestinal disturbances were frequent during the first 3 months of miglustat therapy, but were easily managed with dietary modifications and/or anti-propulsive medication. Conclusions Miglustat can improve or stabilize neurological

  7. Treatment of cataplexy in Niemann-Pick disease type C with the use of miglustat.

    Science.gov (United States)

    Zarowski, Marcin; Steinborn, Barbara; Gurda, Barbara; Dvorakova, Lenka; Vlaskova, Hana; Kothare, Sanjeev V

    2011-01-01

    Cataplexy is the sudden muscle weakness brought on by strong emotions, particularly joking, laughter, or anger. Cataplexy may involve only certain group of muscles or the entire voluntary musculature. In rare cases, symptoms of cataplexy can be seen during the course of some inherited diseases (Niemann-Pick type C (NPC), Prader-Willi syndrome, myotonic dystrophy, Norrie disease). We report the successful use of miglustat, a reversible inhibitor of the enzyme glucosylceramide synthase, approved for use in Gaucher's disease, and which catalyses the first step in the biosynthesis of most glycosphingolipid, in a boy with NPC with cataplexy. A 9-year-old boy was admitted for assessments of frequent "drop attacks" while laughing. The filipin fluorescence tests of cultured skin fibroblasts revealed massive accumulation of unesterified cholesterol, confirming the diagnosis of NPC disease. Molecular studies confirmed the diagnosis of NPC too. After approval from the bioethics committee, miglustat was initiated on the child at 100mg three times a day. Cataplectic attacks disappeared completely after 6 months on treatment, and patient continues to be in remission from the cataplectic attacks at 16 months follow-up. There was no further progression of neurological signs or symptoms or splenomegaly, with some improvement in cognitive function as well as social, affective and attention problems, up-gaze, and gait. Miglustat was well tolerated with no side effects observed. In summary, this is the first report of miglustat treatment of cataplexy in NPC. Long-term follow-up for continuing efficacy and tolerability in a larger cohort with NPC is needed to substantiate our observation. © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  8. Type a niemann-pick disease. Description of three cases with delayed myelination.

    Science.gov (United States)

    D'Amico, A; Sibilio, M; Caranci, F; Bartiromo, F; Taurisano, R; Balivo, F; Melis, D; Parenti, G; Cirillo, S; Elefante, R; Brunetti, A

    2008-06-03

    We describe three patients with type A Niemann-Pick disease (NPD-A). NPD-A is an autosomal recessive neuronal storage disease classified among the sphingolipidoses, characterized by accumulation of sphingomyelin in various tissues and in the brain. Magnetic Resonance imaging (MRI) of our three patients showed a marked delay of myelination with frontal atrophy. Few descriptions of this MRI pattern of delayed myelination have been published to date.

  9. Prion diseases of the brain

    International Nuclear Information System (INIS)

    Lutz, Kira; Urbach, Horst

    2015-01-01

    The prion diseases of the brain, especially Creutzfeldt-Jakob disease, are rare fatal neurodegenerative disorders. A definitive CJD diagnosis is currently only possible by a brain biopsy or post mortem autopsy. The diagnosis of Creutzfeldt-Jakob disease is based on clinical signs, pathognomonic EEG, on typical MRI findings and the examination of the cerebrospinal fluid. Using the MRI the diagnosis Creutzfeldt-Jakob disease can be confirmed or excluded with high certainty. The MRI examination should contain diffusion-weighted and FLAIR imaging sequences. This review article provides an overview of the prion diseases of the brain with the corresponding imaging findings.

  10. Neuroimaging Findings in a Brain With Niemann–Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Jei-Yie Huang

    2011-08-01

    Full Text Available Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI, magnetic resonance spectrography (MRS and 18-fluoro-2-deoxyglucose positron emission tomography (PET imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

  11. Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1

    Directory of Open Access Journals (Sweden)

    Anja Meyer

    2017-04-01

    Full Text Available Niemann–Pick disease type C1 (NPC1 is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1−/− mutant mice compared with healthy controls (NPC1+/+. Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1−/− mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1−/− mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1+/+ controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1.

  12. The cost of brain diseases

    DEFF Research Database (Denmark)

    DiLuca, Monica; Olesen, Jes

    2014-01-01

    Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists.......Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists....

  13. Inflammatory diseases of the brain

    International Nuclear Information System (INIS)

    Haehnel, Stefan

    2009-01-01

    This book provides a comprehensive overview of inflammatory brain diseases from a neuroradiological point of view. Such diseases may be either infectious (e.g., viral encephalitis and pyogenic brain abscess) or non-infectious (e.g., multiple sclerosis), and many of these entities are becoming increasingly important for differential diagnosis, particularly in immunocompromised persons. Neuroimaging contributes greatly to the differentiation of infectious and noninfectious brain diseases and to the distinction between brain inflammation and other, for instance neoplastic, diseases. In order to ensure a standardized approach throughout the book, each chapter is subdivided into three principal sections: epidemiology, clinical presentation and therapy; imaging; and differential diagnosis. A separate chapter addresses technical and methodological issues and imaging protocols. All of the authors are recognized experts in their fields, and numerous high-quality and informative illustrations are included. This book will be of great value not only to neuroradiologists but also to neurologists, neuropediatricians, and general radiologists. (orig.)

  14. Inflammatory diseases of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Haehnel, Stefan (ed.) [University of Heidelberg Medical Center (Germany). Div. of Neuroradiology

    2009-07-01

    This book provides a comprehensive overview of inflammatory brain diseases from a neuroradiological point of view. Such diseases may be either infectious (e.g., viral encephalitis and pyogenic brain abscess) or non-infectious (e.g., multiple sclerosis), and many of these entities are becoming increasingly important for differential diagnosis, particularly in immunocompromised persons. Neuroimaging contributes greatly to the differentiation of infectious and noninfectious brain diseases and to the distinction between brain inflammation and other, for instance neoplastic, diseases. In order to ensure a standardized approach throughout the book, each chapter is subdivided into three principal sections: epidemiology, clinical presentation and therapy; imaging; and differential diagnosis. A separate chapter addresses technical and methodological issues and imaging protocols. All of the authors are recognized experts in their fields, and numerous high-quality and informative illustrations are included. This book will be of great value not only to neuroradiologists but also to neurologists, neuropediatricians, and general radiologists. (orig.)

  15. In Vivo Assessment of Neurodegeneration in Type C Niemann-Pick Disease by IDEAL-IQ.

    Science.gov (United States)

    Guo, Ruo-Mi; Li, Qing-Ling; Luo, Zhong-Xing; Tang, Wen; Jiao, Ju; Wang, Jin; Kang, Zhuang; Chen, Shao-Qiong; Zhang, Yong

    2018-01-01

    To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). Routine brain MRI, IDEAL-IQ and 1 H-proton magnetic resonance spectroscopy ( 1 H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15-61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20-65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1 H-MRS. Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7-4.9%, p IQ instead of 1 H-MRS. The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.

  16. 'Limits and current knowledge of Pick's disease: its differential diagnosis'. A translation of the 1957 Delay, Brion, Escourolle article.

    Science.gov (United States)

    Thibodeau, Marie-Pierre; Miller, Bruce L

    2013-01-01

    This article is a translation of a French article by Delay, Brion, and Escourolle. In a seminal article published in French in 1957 these authors summarized the work of previous researchers and reviewed a wide sample of frontotemporal dementia (FTD) cases formerly referred to as Pick's disease. The authors were among the first to define the critical clinical and anatomical differences between Alzheimer's disease (AD) and FTD and they even delineated distinctive FTD subtypes making possible the advances that now constitute the base of our studies. Reviewing their work allows us to appreciate the progress research has made.

  17. Application of closed queueing network in the performance of a pick-and-pass order picking system

    NARCIS (Netherlands)

    Gaast, van der J.P.; Koster, de M.B.M.; Adan, I.J.B.F.; Resing, J.A.C.

    2011-01-01

    This paper presents a method for obtaining approximate solutions for pick-and-pass order picking systems with multiple classes of orders. The pick-and-pass system is decomposed into an entrance station, conveyor nodes and pick stations. A customer order needs to visit multiple pick stations, but the

  18. National Niemann-Pick Disease Foundation

    Science.gov (United States)

    ... nor does it host or receive funding from advertising or from the display of commercial content. This site complies to the HONcode standard for trustworthy health information: verify here . The National Niemann-Pick Disease Foundation ...

  19. Collaborative Development of 2-Hydroxypropyl-β-Cyclodextrin for the Treatment of Niemann-Pick Type C1 Disease

    Science.gov (United States)

    Ottinger, Elizabeth A.; Kao, Mark L.; Carrillo-Carrasco, Nuria; Yanjanin, Nicole; Shankar, Roopa Kanakatti; Janssen, Marjo; Brewster, Marcus; Scott, Ilona; Xu, Xin; Cradock, Jim; Terse, Pramod; Dehdashti, Seameen; Marugan, Juan; Zheng, Wei; Portilla, Lili; Hubbs, Alan; Pavan, William J.; Heiss, John; Vite, Charles H.; Walkley, Steven U.; Ory, Daniel S.; Silber, Steven A.; Porter, Forbes D.; Austin, Christopher P.; McKew, John C.

    2014-01-01

    In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Science (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collaborative model between the NIH, academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies. This paper describes one of the first TRND programs, the development of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of Niemann-Pick disease type C1 (NPC1). NPC is a neurodegenerative, autosomal recessive rare disease caused by a mutation in either the NPC1 (about 95% of cases) or the NPC2 gene (about 5% of cases). These mutations affect the intracellular trafficking of cholesterol and other lipids, which leads to a progressive accumulation of unesterified cholesterol and glycosphingolipids in the CNS and visceral organs. Affected individuals typically exhibit ataxia, swallowing problems, seizures, and progressive impairment of motor and intellectual function in early childhood, and usually die in adolescence. There is no disease modifying therapy currently approved for NPC1 in the US. A collaborative drug development program has been established between TRND, public and private partners that has completed the pre-clinical development of HP-β-CD through IND filing for the current Phase I clinical trial that is underway. Here we discuss how this collaborative effort helped to overcome scientific, clinical and financial challenges facing the development of new drug treatments for rare and neglected diseases, and how it will incentivize the commercialization of HP-β-CD for the benefit of the NPC patient community. PMID:24283970

  20. Normalization of Hepatic Homeostasis in the Npc1nmf164 Mouse Model of Niemann-Pick Type C Disease Treated with the Histone Deacetylase Inhibitor Vorinostat.

    Science.gov (United States)

    Munkacsi, Andrew B; Hammond, Natalie; Schneider, Remy T; Senanayake, Dinindu S; Higaki, Katsumi; Lagutin, Kirill; Bloor, Stephen J; Ory, Daniel S; Maue, Robert A; Chen, Fannie W; Hernandez-Ono, Antonio; Dahlson, Nicole; Repa, Joyce J; Ginsberg, Henry N; Ioannou, Yiannis A; Sturley, Stephen L

    2017-03-17

    Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no Food and Drug Administration (FDA)-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1 nmf164 mice, which express a missense mutation in the Npc1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of vorinostat (150 mg/kg, 5 days/week). Disease progression was measured via gene expression, liver function and pathology, serum and tissue lipid levels, body weight, and life span. Transcriptome analyses of treated livers indicated multiple changes consistent with reversal of liver dysfunction that typifies NP-C disease. Significant improvements in liver pathology and function were achieved by this treatment regimen; however, NPC1 protein maturation and levels, disease progression, weight loss, and animal morbidity were not detectably altered. Vorinostat concentrations were >200 μm in the plasma compartment of treated animals but were almost 100-fold lower in brain tissue. Apolipoprotein B metabolism and the expression of key components of lipid homeostasis in primary hepatocytes from null ( Npc1 -/- ) and missense ( Npc1 nmf164 ) mutant mice were altered by vorinostat treatment, consistent with a response by these cells independent of the status of the Npc1 locus. These results suggest that HDAC inhibitors have utility to treat visceral NP-C disease. However, it is clear that improved blood-brain barrier penetration will be required to alleviate the neurological symptoms of human NP-C disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Normalization of Hepatic Homeostasis in the Npc1nmf164 Mouse Model of Niemann-Pick Type C Disease Treated with the Histone Deacetylase Inhibitor Vorinostat*

    Science.gov (United States)

    Munkacsi, Andrew B.; Hammond, Natalie; Schneider, Remy T.; Senanayake, Dinindu S.; Higaki, Katsumi; Lagutin, Kirill; Bloor, Stephen J.; Ory, Daniel S.; Maue, Robert A.; Chen, Fannie W.; Hernandez-Ono, Antonio; Dahlson, Nicole; Repa, Joyce J.; Ginsberg, Henry N.; Ioannou, Yiannis A.; Sturley, Stephen L.

    2017-01-01

    Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no Food and Drug Administration (FDA)-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the Npc1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of vorinostat (150 mg/kg, 5 days/week). Disease progression was measured via gene expression, liver function and pathology, serum and tissue lipid levels, body weight, and life span. Transcriptome analyses of treated livers indicated multiple changes consistent with reversal of liver dysfunction that typifies NP-C disease. Significant improvements in liver pathology and function were achieved by this treatment regimen; however, NPC1 protein maturation and levels, disease progression, weight loss, and animal morbidity were not detectably altered. Vorinostat concentrations were >200 μm in the plasma compartment of treated animals but were almost 100-fold lower in brain tissue. Apolipoprotein B metabolism and the expression of key components of lipid homeostasis in primary hepatocytes from null (Npc1−/−) and missense (Npc1nmf164) mutant mice were altered by vorinostat treatment, consistent with a response by these cells independent of the status of the Npc1 locus. These results suggest that HDAC inhibitors have utility to treat visceral NP-C disease. However, it is clear that improved blood-brain barrier penetration will be required to alleviate the neurological symptoms of human NP-C disease. PMID:28031458

  2. A comparative study of Alzheimer's disease and Pick's disease by CT

    International Nuclear Information System (INIS)

    Ichimiya, Yosuke; Kobayashi, Kazunari; Arai, Heii; Ikeda, Kenji; Kosaka, Kenji

    1984-01-01

    17 patients with clinically diagnosed Alzheimer's disease, 11 patients with clinically diagnosed Pick's disease and 13 healthy age-matched subjects as the control were studied by computed tomography (CT). In order to study cerebral atrophy, volumetric measurement was performed. Subarachnoid Space Volume Index (SVI). Frontal, Temporal, and Parieto-Occipital Subarachnoid Space Volume Indices (SfVI, StVI, and SpoVI, respectively) as well as Ventricle Volume Index (VVI), The volume indices of anterior horn, inferior horn, and posterior horn of the lateral ventricles (VaVI, ViVI, and VpVI, respectively) were calculated as the indices for the atrophy of the cerebral cortex and white matter. Furthermore, to evaluate lobar atrophy, SfVI+VaVI (FA), StVI+ViVI (TA), and SpoVI+VpVI (POA) were defined as the indices of frontal lobe atrophy, temporal lobe atrophy, and parieto-occipital lobe atrophy respectively. In Alzheimer's patients, FA and POA were significantly large (p<0.001) in stage I group and TA was significantly enlarged (p<0.001) in stage II group. In Pick's patients, FA and TA were significantly large (FA : p<0.001, TA : p<0.01) in stage I group and POA became significantly prominent (p<0.001) in stage III group. Pick's patients showed significantly larger SfVI (p<0.2 in stage I group and p<0.001 in stage II group) and FA (p<0.01 in stage II group) than Alzheimer's patients. The results in this study give us the following suggestions; 1) Alzheimer's patients show a diffuse cerebral atrophy in the early stage. 2) Pick's patients have a localized atrophy of frontal and temporal lobes already in the early stage. 3) Compared with Alzheimer's patients, Pick's patients show significantly more severe atrophy in frontal lobe at the early stage. (J.P.N.)

  3. PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner

    Directory of Open Access Journals (Sweden)

    Jin Wenying

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channel 1a (ASIC1a is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1, an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown. Results Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1. Conclusions Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.

  4. The hidden Niemann-Pick type C patient : Clinical niches for a rare inherited metabolic disease

    NARCIS (Netherlands)

    Hendriksz, Christian J.; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J.; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Kluenemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Bergh, Florian Then; Topcu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A.

    2017-01-01

    Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to

  5. Tau-mediated nuclear depletion and cytoplasmic accumulation of SFPQ in Alzheimer's and Pick's disease.

    Directory of Open Access Journals (Sweden)

    Yazi D Ke

    Full Text Available Tau dysfunction characterizes neurodegenerative diseases such as Alzheimer's disease (AD and frontotemporal lobar degeneration (FTLD. Here, we performed an unbiased SAGE (serial analysis of gene expression of differentially expressed mRNAs in the amygdala of transgenic pR5 mice that express human tau carrying the P301L mutation previously identified in familial cases of FTLD. SAGE identified 29 deregulated transcripts including Sfpq that encodes a nuclear factor implicated in the splicing and regulation of gene expression. To assess the relevance for human disease we analyzed brains from AD, Pick's disease (PiD, a form of FTLD, and control cases. Strikingly, in AD and PiD, both dementias with a tau pathology, affected brain areas showed a virtually complete nuclear depletion of SFPQ in both neurons and astrocytes, along with cytoplasmic accumulation. Accordingly, neurons harboring either AD tangles or Pick bodies were also depleted of SFPQ. Immunoblot analysis of human entorhinal cortex samples revealed reduced SFPQ levels with advanced Braak stages suggesting that the SFPQ pathology may progress together with the tau pathology in AD. To determine a causal role for tau, we stably expressed both wild-type and P301L human tau in human SH-SY5Y neuroblastoma cells, an established cell culture model of tau pathology. The cells were differentiated by two independent methods, mitomycin C-mediated cell cycle arrest or neuronal differentiation with retinoic acid. Confocal microscopy revealed that SFPQ was confined to nuclei in non-transfected wild-type cells, whereas in wild-type and P301L tau over-expressing cells, irrespective of the differentiation method, it formed aggregates in the cytoplasm, suggesting that pathogenic tau drives SFPQ pathology in post-mitotic cells. Our findings add SFPQ to a growing list of transcription factors with an altered nucleo-cytoplasmic distribution under neurodegenerative conditions.

  6. Impact of miglustat on evolution of atypical presentation of late-infantile-onset Niemann?Pick disease type C with early cognitive impairment, behavioral dysfunction, epilepsy, ophthalmoplegia, and cerebellar involvement: a case report

    OpenAIRE

    Cuisset, Jean-Marie; Sukno, S.; Trauffler, A.; Latour, P.; Dobbelaere, D.; Michaud, L.; Vall?e, L.

    2016-01-01

    Background Niemann?Pick disease type C is a rare inherited neurodegenerative disease involving impaired intracellular lipid trafficking and accumulation of glycolipids in various tissues, including the brain. Miglustat, a reversible inhibitor of glucosylceramide synthase, has been shown to be effective in the treatment of progressive neurological manifestations in pediatric and adult patients with Niemann?Pick disease type C, and has been used in that indication in Europe since 2010. Case pre...

  7. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    OpenAIRE

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H.M.; Cassady, John P.; Cohen, Malkiel A.; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I.; Jaenisch, Rudolf

    2013-01-01

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal prot...

  8. Clinical evaluation of chitotriosidase enzyme activity in Gaucher and Niemann Pick A/B diseases: A retrospective study from India.

    Science.gov (United States)

    Kadali, Srilatha; Kolusu, Anusha; Sunkara, Satish; Gummadi, Maheshwar Reddy; Undamatla, Jayanthi

    2016-06-01

    Plasma chitotriosidase originates from activated macrophages and is reported to be elevated in many Lysosomal Storage Disorders. Measurement of this enzyme activity has been an available tool for monitoring therapy of Gaucher disease. The degree of elevation of chitotriosidase is useful for differential diagnosis of Gaucher disease and Niemann Pick A/B. However the potential utility of this chitotriosidase assay depends on the frequency of deficient chitotriosidase activity in a particular population. We therefore aim to study the clinical utility of this assay Gaucher and Niemann Pick A/B diseases in the backdrop of chitotriosidase deficiency in our population. The study comprises 173 patients with clinical suspicion of either Gaucher disease (n=108) or Niemann Pick A/B (n=65) and 92 healthy controls. The plasma samples of controls, Gaucher disease, and Niemann Pick A/B showed chitotriosidase deficiency of 12%, 25% and 27% respectively. The degree of elevation of chitotriosidase in Gaucher disease and Niemann Pick A/B patients is 40-326 (11,325.7±6395.4nmol/h/ml) and 7-22 folds (1192.5±463.0nmol/h/ml) respectively. In view of these findings of distinguishable fold elevation of chitotriosidase in Gaucher disease or Niemann Pick A/B, it can be a potential surrogate differential diagnostic marker for these groups of diseases, except in the patients in whom this enzyme is deficient. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Niemann-Pick disease type C

    OpenAIRE

    Vanier, Marie T

    2010-01-01

    Abstract Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in...

  10. Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann-Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease.

    Science.gov (United States)

    Tanaka, Yuta; Yamada, Yusei; Ishitsuka, Yoichi; Matsuo, Muneaki; Shiraishi, Koki; Wada, Koki; Uchio, Yushiro; Kondo, Yuki; Takeo, Toru; Nakagata, Naomi; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Mochinaga, Sakiko; Higaki, Katsumi; Ohno, Kousaku; Irie, Tetsumi

    2015-01-01

    Niemann-Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1(-/-)) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000-4000 mg/kg HPBCD improved the lifespan of Npc1(-/-) mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1(-/-) mice. Serum HPBCD concentrations, when treated at the effective dosages (1000-4000 mg/kg), were approximately 1200-2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1(-/-) mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1(-/-) mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.

  11. Methodology of Evaluation of the Impact of Picking Area Location on the Total Costs of Warehouse

    Directory of Open Access Journals (Sweden)

    Apsalons Raitis

    2017-12-01

    Full Text Available The picking system and the layout of the picking area are the key drivers for the evaluation of a warehouse picking cost. There are five variants for organizing the picking process of orders in a warehouse. The choice of a specific variant depends on the total cost of picking. The picking cost is evaluated within an uninterrupted picking process. It means that no stock out occurs in the time period of the picking process. The storing area and the picking area are created as two separate zones for picking quantities of the customer’s orders; the principle of division of orders is observed strictly. Referring to the locations of stock keeping units (SKU, two approaches of the layout of SKU in the picking area can be estimated. The first one is the single picking location for each single SKU, where replenishment is realized in the picking process. The second one - various picking locations for each single SKU, and the replenishment here is realized just only prior to a picking process or after it. The main benefits of the economy of the picking cost as far as these two approaches are concerned are the shortest picking route in the first case and one common replenishment option in the second case.

  12. The relationship of psychological trauma with trichotillomania and skin picking.

    Science.gov (United States)

    Özten, Eylem; Sayar, Gökben Hızlı; Eryılmaz, Gül; Kağan, Gaye; Işık, Sibel; Karamustafalıoğlu, Oğuz

    2015-01-01

    Interactions between psychological, biological and environmental factors are important in development of trichotillomania and skin picking. The aim of this study is to determine the relationship of traumatic life events, symptoms of post-traumatic stress disorder and dissociation in patients with diagnoses of trichotillomania and skin picking disorder. The study included patients who was diagnosed with trichotillomania (n=23) or skin picking disorder (n=44), and healthy controls (n=37). Beck Depression Inventory, Traumatic Stress Symptoms Scale and Dissociative Experiences Scale were administered. All groups checked a list of traumatic life events to determine the exposed traumatic events. There was no statistical significance between three groups in terms of Dissociative Experiences Scale scores (P=0.07). But Beck Depression Inventory and Traumatic Stress Symptoms Scale scores of trichotillomania and skin picking groups were significantly higher than the control group. Subjects with a diagnosis of trichotillomania and skin picking reported statistically significantly higher numbers of traumatic and negative events in childhood compared to healthy subjects. We can conclude that trauma may play a role in development of both trichotillomania and skin picking. Increased duration of trichotillomania or skin picking was correlated with decreased presence of post-traumatic stress symptoms. The reason for the negatively correlation of severity of post-traumatic stress symptoms and self-harming behavior may be speculated as developing trichotillomania or skin picking symptoms helps the patient to cope with intrusive thoughts related to trauma. Future longitudinal research must focus on whether trauma and post-traumatic stress or trichotillomania and skin picking precede the development of mental disorder.

  13. Genetics Home Reference: Niemann-Pick disease

    Science.gov (United States)

    ... are compartments within cells that break down and recycle different types of molecules. Acid sphingomyelinase is responsible ... A, Brodie SE, Desnick RJ, Wasserstein MP. Natural history of Type A Niemann-Pick disease: possible endpoints ...

  14. The relationship of psychological trauma with trichotillomania and skin picking

    Directory of Open Access Journals (Sweden)

    Özten E

    2015-05-01

    Full Text Available Eylem Özten,1 Gökben Hızlı Sayar,1 Gül Eryilmaz,1 Gaye Kağan,2 Sibel Işik,3 Oğuz Karamustafalioğlu4 1Neuropsychiatry Health, Practice, and Research Center, Üsküdar University, 2Istanbul Neuropsychiatry Hospital, Üsküdar University, 3Turkish Red Crescent Altintepe Medical Center, 4Department of Psychology, Faculty of Human and Social Sciences, Üsküdar University, Istanbul, Turkey Objective: Interactions between psychological, biological and environmental factors are important in development of trichotillomania and skin picking. The aim of this study is to determine the relationship of traumatic life events, symptoms of post-traumatic stress disorder and dissociation in patients with diagnoses of trichotillomania and skin picking disorder.Methods: The study included patients who was diagnosed with trichotillomania (n=23 or skin picking disorder (n=44, and healthy controls (n=37. Beck Depression Inventory, Traumatic Stress Symptoms Scale and Dissociative Experiences Scale were administered. All groups checked a list of traumatic life events to determine the exposed traumatic events.Results: There was no statistical significance between three groups in terms of Dissociative Experiences Scale scores (P=0.07. But Beck Depression Inventory and Traumatic Stress Symptoms Scale scores of trichotillomania and skin picking groups were significantly higher than the control group. Subjects with a diagnosis of trichotillomania and skin picking reported statistically significantly higher numbers of traumatic and negative events in childhood compared to healthy subjects.Conclusion: We can conclude that trauma may play a role in development of both trichotillomania and skin picking. Increased duration of trichotillomania or skin picking was correlated with decreased presence of post-traumatic stress symptoms. The reason for the negatively correlation of severity of post-traumatic stress symptoms and self-harming behavior may be speculated as

  15. Frontotemporal Dementia (Pick's Disease)

    Science.gov (United States)

    ... changes in food preferences; agitation or, conversely, blunted emotions; neglect of personal hygiene; repetitive or compulsive behavior, and decreased energy and motivation. The second type primarily features symptoms of language ...

  16. Recent Advances in the Diagnosis and Treatment of Niemann-Pick Disease Type C in Children: A Guide to Early Diagnosis for the General Pediatrician

    Directory of Open Access Journals (Sweden)

    Hanna Alobaidy

    2015-01-01

    Full Text Available Niemann-Pick disease (NP-C is a lysosomal storage disease in which impaired intracellular lipid transport leads to accumulation of cholesterol and glycosphingolipids in various neurovisceral tissues. It is an autosomal recessive disorder, caused by mutations in the NPC1 or NPC2 genes. The clinical spectrum is grouped by the age of onset and onset of neurological manifestation: pre/perinatal; early infantile; late infantile; and juvenile periods. The NP-C Suspicion Index (SI screening tool was developed to identify suspected patients with this disease. It is especially good at recognizing the disease in patients older than four years of age. Biochemical tests involving genetic markers and Filipin staining of skin fibroblast are being employed to assist diagnosis. Therapy is mostly supportive and since 2009, the first specific therapy approved for use was Miglustat (Zavesca aimed at stabilizing the rate of progression of neurological manifestation. The prognosis correlates with age at onset of neurological signs; patients with early onset form progress faster. The NP-C disease has heterogeneous neurovisceral manifestations. A SI is a screening tool that helps in diagnostic process. Filipin staining test is a specific biomarker diagnostic test. Miglustat is the first disease-specific therapy.

  17. Defining natural history: assessment of the ability of college students to aid in characterizing clinical progression of Niemann-Pick disease, type C.

    Directory of Open Access Journals (Sweden)

    Jenny Shin

    Full Text Available Niemann-Pick Disease, type C (NPC is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.

  18. Pathological skin picking: case presentation and review of the literature

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2015-04-01

    Full Text Available Pathological skin picking is a condition in which patients induce skin lesions through repetitive, compulsive excoriations of normal skin or skin with minor surface irregularities and they admit their role in the production of the lesions, but are unable to stop their behavior. Psychiatric comorbidities most often associated with skin picking include obsessive-compulsive disorder (OCD, anxiety disorders, mood disorders, body dysmorphic disorders, trichotillomania and compulsive-buying disorder. We report the case of a 17 year old female patient who addressed the dermatology department of our hospital with an eruption consisting of erythematous papules and plaques. The local examination revealed several clues of paramount importance in drawing the final conclusion and the psychiatric examination helped establish the diagnosis of pathological skin picking in a patient with obsessive-compulsive disorder.

  19. Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Elena-Raluca Nicoli

    2018-04-01

    Full Text Available Niemann-Pick disease type C (NPC disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and also in post-mortem liver from NPC patients. We demonstrated the ability of the hydrophobic bile acid ursodeoxycholic acid (UDCA (3α, 7β-dihydroxy-5β-cholanic acid to correct the P450 system suppression. UDCA is used to treat several cholestatic disorders and was tested in NPC due to the P450 system being regulated by bile acids. Here, we compare the effect of UDCA and cholic acid (CA, another bile acid, in the NPC mouse model. We observed unexpected hepatotoxicity in response to CA treatment of NPC mice. No such hepatotoxicity was associated with UDCA treatment. These results suggest that CA treatment is contraindicated in NPC patients, whilst supporting the use of UDCA as an adjunctive therapy in NPC patients.

  20. Editor’s Pick: Non-Alcoholic Fatty Liver Disease – Changing the Prevalence of Liver Cancer?

    Directory of Open Access Journals (Sweden)

    Benedetta Campana

    2015-01-01

    Full Text Available Due to its increasing prevalence, exceeding 25% of the Western population, non-alcoholic fatty liver disease (NAFLD merits recognition as one of the most frequent chronic liver diseases (CLD and requires consideration of the associated disease-related complications and their consequences for the surveillance and treatment of patients and the socio-economy worldwide. Along with the increasing incidence of NAFLD-related cirrhosis and end-stage liver disease, the frequency of NAFLD-related hepatocellular carcinoma (HCC is rising and expected to surpass HCC related to chronic hepatitis C in the upcoming future. These epidemiologic changes will impact on the overall mortality of CLD and the requirement of organs for transplantation. Although the risk of HCC in NAFLD, similar to other CLD, is related to fibrosis (advanced fibrosis increases the risk of HCC 25-fold, there are reports suggesting a considerable rate of HCC also developing in simple hepatic steatosis. Moreover, HCC is nowadays the leading cause of obesity-related cancer mortality; cancers of other origin such as colorectal cancer are more prevalent in patients with NAFLD and obesity. The pathophysiology of HCC has mainly been studied in models of viral hepatitis. Given the expected raise in NAFLD-related HCC, a better understanding of the pathophysiology of carcinogenesis in NAFLD and obesity is desired in order to better define chemopreventive strategies. Here we review the epidemiology, aetiology, and pathogenesis of HCC on the background of NAFLD and deduce potential consequences for the management of patients in respect to the NAFLD epidemic.

  1. Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    Vanier Marie T

    2010-06-01

    Full Text Available Abstract Niemann-Pick C disease (NP-C is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood. The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period, gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period, and ataxia not unfrequently following initial psychiatric disturbances (adult form. The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype. Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential

  2. Quantitative Analysis of the Proteome Response to the Histone Deacetylase Inhibitor (HDACi) Vorinostat in Niemann-Pick Type C1 disease.

    Science.gov (United States)

    Subramanian, Kanagaraj; Rauniyar, Navin; Lavalleé-Adam, Mathieu; Yates, John R; Balch, William E

    2017-11-01

    Niemann-Pick type C (NPC) disease is an inherited, progressive neurodegenerative disorder principally caused by mutations in the NPC1 gene. NPC disease is characterized by the accumulation of unesterified cholesterol in the late endosomes (LE) and lysosomes (Ly) (LE/Ly). Vorinostat, a histone deacetylase inhibitor (HDACi), restores cholesterol homeostasis in fibroblasts derived from NPC patients; however, the exact mechanism by which Vorinostat restores cholesterol level is not known yet. In this study, we performed comparative proteomic profiling of the response of NPC1 I1061T fibroblasts to Vorinostat. After stringent statistical criteria to filter identified proteins, we observed 202 proteins that are differentially expressed in Vorinostat-treated fibroblasts. These proteins are members of diverse cellular pathways including the endomembrane dependent protein folding-stability-degradation-trafficking axis, energy metabolism, and lipid metabolism. Our study shows that treatment of NPC1 I1061T fibroblasts with Vorinostat not only enhances pathways promoting the folding, stabilization and trafficking of NPC1 (I1061T) mutant to the LE/Ly, but alters the expression of lysosomal proteins, specifically the lysosomal acid lipase (LIPA) involved in the LIPA->NPC2->NPC1 based flow of cholesterol from the LE/Ly lumen to the LE/Ly membrane. We posit that the Vorinostat may modulate numerous pathways that operate in an integrated fashion through epigenetic and post-translational modifications reflecting acetylation/deacetylation balance to help manage the defective NPC1 fold, the function of the LE/Ly system and/or additional cholesterol metabolism/distribution pathways, that could globally contribute to improved mitigation of NPC1 disease in the clinic based on as yet uncharacterized principles of cellular metabolism dictating cholesterol homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H M; Cassady, John P; Cohen, Malkiel A; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I; Jaenisch, Rudolf

    2013-12-12

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

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    Sovan Sarkar

    2013-12-01

    Full Text Available Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1 disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease.

  5. Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

    Science.gov (United States)

    Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

    2016-12-01

    : Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of

  6. A Preliminary Analysis of the Phenomenology of Skin-Picking in Prader-Willi Syndrome

    Science.gov (United States)

    Morgan, Jessica R.; Storch, Eric A.; Woods, Douglas W.; Bodzin, Danielle; Lewin, Adam B.; Murphy, Tanya K.

    2010-01-01

    To examine the nature and psychosocial correlates of skin-picking behavior in youth with Prader-Willi Syndrome (PWS). Parents of 67 youth (aged 5-19 years) with PWS were recruited to complete an internet-based survey that included measures of: skin-picking behaviors, the automatic and/or focused nature of skin-picking, severity of skin-picking…

  7. Close up of the pick and place tool carrying a dummy silicon sensor.

    CERN Multimedia

    Bernd Surrow

    1999-01-01

    The gantry positioning head contains a vacuum pick-up system thatallows several different pick-up tools to be used. This one isdesigned to pick up the silicon sensors. The pick-up tool containsa pressure sensitive contact which can stop the motion of the machine when the tool touches a fixed object. The shiny cylinderis the end of the microscope optics of the CCD camera.

  8. Evaluation of an anti-tumor necrosis factor therapeutic in a mouse model of Niemann-Pick C liver disease.

    Directory of Open Access Journals (Sweden)

    Melanie Vincent

    2010-09-01

    Full Text Available Niemann-Pick type C (NPC disease is a lysosomal storage disease characterized by the accumulation of cholesterol and glycosphingolipids. The majority of NPC patients die in their teen years due to progressive neurodegeneration; however, half of NPC patients also suffer from cholestasis, prolonged jaundice, and hepatosplenomegaly. We previously showed that a key mediator of NPC liver disease is tumor necrosis factor (TNF α, which is involved in both proinflammatory and apoptotic signaling cascades. In this study, we tested the hypothesis that blocking TNF action with an anti-TNF monoclonal antibody (CNTO5048 will slow the progression of NPC liver disease.Treatment of wild-type C57BL/6 mice with NPC1-specific antisense oligonucleotides led to knockdown of NPC1 protein expression in the liver. This caused classical symptoms of NPC liver disease, including hepatic cholesterol accumulation, hepatomegaly, elevated serum liver enzymes, and lipid laden macrophage accumulation. In addition, there was a significant increase in the number of apoptotic cells and a proliferation of stellate cells. Concurrent treatment of NPC1 knockdown mice with anti-TNF had no effect on the primary lipid storage or accumulation of lipid-laden macrophages. However, anti-TNF treatment slightly blunted the increase in hepatic apoptosis and stellate cell activation that was seen with NPC1 knockdown.Current therapeutic options for NPC disease are limited. Our results provide proof of principle that pharmacologically blocking the TNF-α inflammatory cascade can slightly reduce certain markers of NPC disease. Small molecule inhibitors of TNF that penetrate tissues and cross the blood-brain barrier may prove even more beneficial.

  9. Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease.

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    André R A Marques

    Full Text Available Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC disease. In addition, glycosphingolipids (GSLs accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation.

  10. The assessment of skin picking in adolescence: psychometric properties of the Skin Picking Scale-Revised (German version).

    Science.gov (United States)

    Gallinat, Christina; Keuthen, Nancy J; Stefini, Annette; Backenstrass, Matthias

    2017-02-01

    Skin picking disorder has received growing attention since the release of DSM-5, yet there are no evidence-based assessment instruments for adolescent samples. The present study examines the psychometric properties of the Skin Picking Scale-Revised (SPS-R, German version) in adolescents. A total of 76 adolescents (96% female) completed the SPS-R, the Clinical Psychological Diagnostic System (KPD-38), and a questionnaire assessing demographics and clinical characteristics online. The SPS-R had high internal consistency (α = 0.89) and significant small-to-medium correlations with reduced competence skills, psychological impairment, general life satisfaction, social support, and social problems on the KPD-38. Similar to prior findings for adults, an exploratory factor analysis suggested a two-factor model for the SPS-R in adolescents. Group comparisons failed to show significant differences on SPS-R scores between participants with and without dermatological conditions. The current results suggest that the SPS-R can be useful in adolescent samples as a reliable and valid instrument for the assessment of skin picking severity. Future research investigating scale validity and factor structure in a clinical sample of adolescent skin pickers is warranted.

  11. Complex lipid trafficking in Niemann-Pick disease type C.

    Science.gov (United States)

    Vanier, Marie T

    2015-01-01

    Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".

  12. A case of variant biochemical phenotype of Niemann-Pick disease type C accompanying savant syndrome.

    Science.gov (United States)

    Hamatani, Mio; Jingami, Naoto; Uemura, Kengo; Nakasone, Naoe; Kinoshita, Hisanori; Yamakado, Hodaka; Ninomiya, Haruaki; Takahashi, Ryosuke

    2016-06-22

    A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis of schizophrenia in his teenage. He also developed a savant skill of calendar calculating. (123)I-IMP-SPECT showed decreased cerebral blood flow in the left frontotemporal lobe as often seen in savant syndrome. Although genetic analysis of NPC1 and NPC2 revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance.

  13. Prion diseases of the brain; Prionenerkrankung des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, Kira; Urbach, Horst [Universitaetsklinik Freiburg (Germany). Klinik fuer Neuroradiologie

    2015-09-15

    The prion diseases of the brain, especially Creutzfeldt-Jakob disease, are rare fatal neurodegenerative disorders. A definitive CJD diagnosis is currently only possible by a brain biopsy or post mortem autopsy. The diagnosis of Creutzfeldt-Jakob disease is based on clinical signs, pathognomonic EEG, on typical MRI findings and the examination of the cerebrospinal fluid. Using the MRI the diagnosis Creutzfeldt-Jakob disease can be confirmed or excluded with high certainty. The MRI examination should contain diffusion-weighted and FLAIR imaging sequences. This review article provides an overview of the prion diseases of the brain with the corresponding imaging findings.

  14. Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis

    Directory of Open Access Journals (Sweden)

    R. Saxena

    2009-09-01

    Full Text Available We present 2 cases of Niemann Pick disease, type B with secondary sea-blue histiocytosis. Strikingly, in both cases the Pick cells were positive for tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher cells. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

  15. Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease

    Directory of Open Access Journals (Sweden)

    Muneaki Matsuo

    2014-01-01

    Full Text Available Niemann–Pick Type C disease (NPC is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration. Previously, we reported that intravenous administration of 2-hydroxypropyl-β-cyclodextrin (HPB-CD in two patients with NPC had only partial and transient beneficial effects on neurological function. The most likely reason for HPB-CD not significantly improving the neurological deficits of NPC is its inability to cross the blood–brain barrier. Herein, we describe the effects of intrathecal HPB-CD in an eight-year-old patient with a perinatal onset of NPC, administered initially at a dose of 10 mg/kg every other week and increased up to 10 mg/kg twice a week. Clinically, the patient maintained residual neurological functions for two years, at which time nuclear magnetic resonance spectroscopy showed a decreased choline to creatine ratio and increased N-acetylaspartate to creatine ratio, and positron emission tomography revealed increased standardized uptake values. Total-tau in the cerebrospinal fluid (CSF was also decreased after two years. No adverse effects were observed over the course of treatment. The CSF concentrations of HPB-CD during the distribution phase after the injections were comparable with those at which HPB-CD could normalize cellular cholesterol abnormality in vitro. Further studies are necessary to elucidate the mechanisms of action of HPB-CD in NPC, and to determine the optimal dose and intervals of HPB-CD injection.

  16. Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease.

    Directory of Open Access Journals (Sweden)

    Gitte Krogh Nielsen

    Full Text Available Niemann-Pick type C2 (NPC2 disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6-phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background. NPC2 was purified from bovine milk and its functional competence assured in NPC2-deficient fibroblasts using the specific cholesterol fluorescent probe filipin. For evaluation of phenotype correction in vivo, three-week-old NPC2(-/- mice received two weekly intravenous injections of 5 mg/kg NPC2 until trial termination 66 days later. Whereas the saline treated NPC2(-/- mice exhibited massive visceral cholesterol storage as compared to their wild-type littermates, administration of NPC2 caused a marked reduction in cholesterol build up. The histological findings, indicating an amelioration of the disease pathology in liver, spleen, and lungs, corroborated the biochemical results. Little or no difference in the overall cholesterol levels was observed in the kidneys, blood, cerebral cortex and hippocampus when comparing NPC2(-/- and wild type mice. However, cerebellum cholesterol was increased about two fold in NPC2(-/- mice compared with wild-type littermates. Weight gain performance was slightly improved as a result of the NPC2 treatment but significant motor coordination deficits were still observed. Accordingly, ultrastructural cerebellar abnormalities were detected in both saline treated and NPC2 treated NPC2(-/- animals 87 days post partum. Our data indicate that protein replacement may be a beneficial therapeutic approach in the

  17. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

    Science.gov (United States)

    Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

    2017-05-01

    Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

  18. Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy.

    Science.gov (United States)

    Irwin, David J; Byrne, Matthew D; McMillan, Corey T; Cooper, Felicia; Arnold, Steven E; Lee, Edward B; Van Deerlin, Vivianna M; Xie, Sharon X; Lee, Virginia M-Y; Grossman, Murray; Trojanowski, John Q

    2016-01-01

    Digital image analysis of histology sections provides reliable, high-throughput methods for neuropathological studies but data is scant in frontotemporal lobar degeneration (FTLD), which has an added challenge of study due to morphologically diverse pathologies. Here, we describe a novel method of semi-automated digital image analysis in FTLD subtypes including: Pick's disease (PiD, n=11) with tau-positive intracellular inclusions and neuropil threads, and TDP-43 pathology type C (FTLD-TDPC, n=10), defined by TDP-43-positive aggregates predominantly in large dystrophic neurites. To do this, we examined three FTLD-associated cortical regions: mid-frontal gyrus (MFG), superior temporal gyrus (STG) and anterior cingulate gyrus (ACG) by immunohistochemistry. We used a color deconvolution process to isolate signal from the chromogen and applied both object detection and intensity thresholding algorithms to quantify pathological burden. We found object-detection algorithms had good agreement with gold-standard manual quantification of tau- and TDP-43-positive inclusions. Our sampling method was reliable across three separate investigators and we obtained similar results in a pilot analysis using open-source software. Regional comparisons using these algorithms finds differences in regional anatomic disease burden between PiD and FTLD-TDP not detected using traditional ordinal scale data, suggesting digital image analysis is a powerful tool for clinicopathological studies in morphologically diverse FTLD syndromes. © The Author(s) 2015.

  19. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway.

    Science.gov (United States)

    Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A; Platt, Nick; Davis, Lianne C; Morgan, Anthony J; Höglinger, Doris; Tatituri, Raju Venkata V; Clark, Simon; Williams, Ian M; Tynan, Patricia; Al Eisa, Nada; Nazarova, Evgeniya; Williams, Ann; Galione, Antony; Ory, Daniel S; Besra, Gurdyal S; Russell, David G; Brenner, Michael B; Sim, Edith; Platt, Frances M

    2016-11-18

    Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis , achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria

  20. Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R. (Sanofi Aventis); (UMASS, Amherst)

    2016-10-26

    Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.

  1. A REVIEW OF ORDER PICKING IMPROVEMENT METHODS

    Directory of Open Access Journals (Sweden)

    Johan Oscar Ong

    2014-09-01

    Full Text Available As a crucial and one of the most important parts of warehousing, order picking often raises discussion between warehousing professionals, resulting in various studies aiming to analyze how order picking activity can be improved from various perspective. This paper reviews various past researches on order picking improvement, and the various methods those studies analyzed or developed. This literature review is based on twenty research articles on order picking improvement viewed from four different perspectives: Automation (specifically, stock-to-picker system, storage assignment policy, order batching, and order picking sequencing. By reviewing these studies, we try to identify the most prevalent order picking improvement approach to order picking improvement. Keywords: warehousing; stock-to-picker; storage assignment; order batching; order picking sequencing; improvement

  2. Blood-brain barrier transport of drugs for the treatment of brain diseases.

    Science.gov (United States)

    Gabathuler, Reinhard

    2009-06-01

    The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

  3. Immune dysfunction in Niemann?Pick disease type C

    OpenAIRE

    Platt, Nick; Speak, Annelise O.; Colaco, Alexandria; Gray, James; Smith, David A.; Williams, Ian M.; Wallom, Kerri?Lee; Platt, Frances M.

    2015-01-01

    Abstract Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann?Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative ...

  4. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C

    NARCIS (Netherlands)

    Wijburg, F. A.; Sedel, F.; Pineda, M.; Hendriksz, C. J.; Fahey, M.; Walterfang, M.; Patterson, M. C.; Wraith, J. E.; Kolb, S. A.

    2012-01-01

    Objectives: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive lysosomal lipid storage disorder that is invariably fatal. NP-C diagnosis can be delayed for years due to heterogeneous presentation; adult-onset NP-C can be particularly difficult to diagnose. We developed a Suspicion

  5. Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches

    OpenAIRE

    Rosenbaum, Anton I.; Maxfield, Frederick R.

    2011-01-01

    Cholesterol is an important lipid of mammalian cells. Its unique physicochemical properties modulate membrane behavior and it serves as the precursor for steroid hormones, oxysterols and vitamin D. Cholesterol is effluxed from the late endosomes/lysosomes via the concerted action of at least two distinct proteins: Niemann-Pick C1 and Niemann-Pick C2. Mutations in these two proteins manifest as Niemann-Pick type C disease – a very rare, usually fatal, autosomal, recessive, neurovisceral, lysos...

  6. Pre-symptomatic activation of antioxidant responses and alterations in glucose and pyruvate metabolism in Niemann-Pick Type C1-deficient murine brain.

    Directory of Open Access Journals (Sweden)

    Barry E Kennedy

    Full Text Available Niemann-Pick Type C (NPC disease is an autosomal recessive neurodegenerative disorder caused in most cases by mutations in the NPC1 gene. NPC1-deficiency is characterized by late endosomal accumulation of cholesterol, impaired cholesterol homeostasis, and a broad range of other cellular abnormalities. Although neuronal abnormalities and glial activation are observed in nearly all areas of the brain, the most severe consequence of NPC1-deficiency is a near complete loss of Purkinje neurons in the cerebellum. The link between cholesterol trafficking and NPC pathogenesis is not yet clear; however, increased oxidative stress in symptomatic NPC disease, increases in mitochondrial cholesterol, and alterations in autophagy/mitophagy suggest that mitochondria play a role in NPC disease pathology. Alterations in mitochondrial function affect energy and neurotransmitter metabolism, and are particularly harmful to the central nervous system. To investigate early metabolic alterations that could affect NPC disease progression, we performed metabolomics analyses of different brain regions from age-matched wildtype and Npc1 (-/- mice at pre-symptomatic, early symptomatic and late stage disease by (1H-NMR spectroscopy. Metabolic profiling revealed markedly increased lactate and decreased acetate/acetyl-CoA levels in Npc1 (-/- cerebellum and cerebral cortex at all ages. Protein and gene expression analyses indicated a pre-symptomatic deficiency in the oxidative decarboxylation of pyruvate to acetyl-CoA, and an upregulation of glycolytic gene expression at the early symptomatic stage. We also observed a pre-symptomatic increase in several indicators of oxidative stress and antioxidant response systems in Npc1 (-/- cerebellum. Our findings suggest that energy metabolism and oxidative stress may present additional therapeutic targets in NPC disease, especially if intervention can be started at an early stage of the disease.

  7. Seven novel mutations of the SMPD1 gene in four Chinese patients with Niemann-Pick disease type A and prenatal diagnosis for four fetuses.

    Science.gov (United States)

    Ding, Yuan; Li, Xiyuan; Liu, Yupeng; Hua, Ying; Song, Jinqing; Wang, Liwen; Li, Mengqiu; Qin, Yaping; Yang, Yanling

    2016-04-01

    Niemann-Pick disease type A (NPD-A) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency. Only a few cases have been documented in mainland China, and prenatal diagnosis has not been performed to date. In this study, the clinical and laboratory features of four Chinese patients with early-onset NPD-A were summarized. Four patients with NPD-A were the firstborns of non-consanguineous parents from four unrelated Chinese families. Bone marrow analysis, acid sphingomyelinase assay and genetic studies were performed. SMPD1 gene studies on amniocytes were performed for the prenatal diagnosis of four fetuses from three families. Four patients were admitted at the age of 1-10 months due to jaundice, hepatosplenomegaly and psychomotor retardation. Liver histopathological analysis revealed glucolipid accumulation. Massive foamy histiocytes were found in the bone marrow. Acid sphingomyelinase activities of peripheral blood leukocytes were significantly decreased (4.05-21.9 nmol/h/mg protein, normal range 216.1-950.9 nmol/h/mg protein). Seven novel mutations (c.518-519insT, c.562_563insC, c.792Gdel, c.949G>A, c.1487_1499delACCGTGTGTACCA, c.1495T>C and c.1670T>C) of the SMPD1 gene were identified in four patients. Only one fetus had two mutations of the SMPD1 gene of amniocytes. The results suggested that the fetus was affected by NPD-A. The mother chose artificial abortion. The other three fetuses were not affected by NPD-A. No mutation of the SMPD1 gene was detected in the cultured amniocytes from the mothers. Postnatal genetic analysis and normal development of the three infants confirmed the prenatal diagnosis. Seven novel mutations associated with NPD-A were identified in the Chinese population. Prenatal diagnosis for four fetuses of three families was successfully performed by amniocyte gene analysis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  9. Restarting stalled autophagy a potential therapeutic approach for the lipid storage disorder, Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Maetzel, Dorothea; Korolchuk, Viktor I; Jaenisch, Rudolf

    2014-06-01

    Autophagy is essential for cellular homeostasis and its dysfunction in human diseases has been implicated in the accumulation of misfolded protein and in cellular toxicity. We have recently shown impairment in autophagic flux in the lipid storage disorder, Niemann-Pick type C1 (NPC1) disease associated with abnormal cholesterol sequestration, where maturation of autophagosomes is impaired due to defective amphisome formation caused by failure in SNARE machinery. Abrogation of autophagy also causes cholesterol accumulation, suggesting that defective autophagic flux in NPC1 disease may act as a primary causative factor not only by imparting its deleterious effects, but also by increasing cholesterol load. However, cholesterol depletion treatment with HP-β-cyclodextrin impedes autophagy, whereas pharmacologically stimulating autophagy restores its function independent of amphisome formation. Of potential therapeutic relevance is that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may rescue both the cholesterol and autophagy defects in NPC1 disease.

  10. Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease

    Directory of Open Access Journals (Sweden)

    Sandra Torres

    2017-11-01

    Full Text Available Lysosomal storage disorders (LSD are characterized by the accumulation of diverse lipid species in lysosomes. Niemann-Pick type A/B (NPA/B and type C diseases Niemann-Pick type C (NPC are progressive LSD caused by loss of function of distinct lysosomal-residing proteins, acid sphingomyelinase and NPC1, respectively. While the primary cause of these diseases differs, both share common biochemical features, including the accumulation of sphingolipids and cholesterol, predominantly in endolysosomes. Besides these alterations in lysosomal homeostasis and function due to accumulation of specific lipid species, the lysosomal functional defects can have far-reaching consequences, disrupting intracellular trafficking of sterols, lipids and calcium through membrane contact sites (MCS of apposed compartments. Although MCS between endoplasmic reticulum and mitochondria have been well studied and characterized in different contexts, emerging evidence indicates that lysosomes also exhibit close proximity with mitochondria, which translates in their mutual functional regulation. Indeed, as best illustrated in NPC disease, alterations in the lysosomal-mitochondrial liaisons underlie the secondary accumulation of specific lipids, such as cholesterol in mitochondria, resulting in mitochondrial dysfunction and defective antioxidant defense, which contribute to disease progression. Thus, a better understanding of the lysosomal and mitochondrial interactions and trafficking may identify novel targets for the treatment of Niemann-Pick disease.

  11. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    OpenAIRE

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s dis...

  12. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression.

    Directory of Open Access Journals (Sweden)

    Cristin D Davidson

    2009-09-01

    Full Text Available Niemann-Pick type C (NPC disease is a fatal neurodegenerative disorder caused most commonly by a defect in the NPC1 protein and characterized by widespread intracellular accumulation of unesterified cholesterol and glycosphingolipids (GSLs. While current treatment therapies are limited, a few drugs tested in Npc1(-/- mice have shown partial benefit. During a combination treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ and allopregnanolone, we noted increased lifespan for Npc1(-/- mice receiving only 2-hydroxypropyl-beta-cyclodextrin (CD, the vehicle for allopregnanolone. This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit.Administration of CD to Npc1(-/- mice beginning at either P7 or P21 and continuing every other day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as well as free sphingosine accumulation, reduced markers of neurodegeneration, and led to longer survival than any previous treatment regime. We reasoned that other lysosomal diseases characterized by cholesterol and GSL accumulation, including NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis (MPS type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/- mice showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or MPS IIIA failed to show reduction in storage.Treatment with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1(-/- and Npc2(-/- mice. In contrast, CD failed to ameliorate cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA disease. Understanding the mechanism(s by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis.

  13. White matter disease of the brain

    International Nuclear Information System (INIS)

    Melville, G.E.; Fernandez, R.E.; Kishore, P.R.S.; Lee, S.H.

    1987-01-01

    The white matter disorders that are discussed in this chapter are subdivided into those disorders within which there is breakdown of normal myelin, termed myelinoclastic, and those diseases involving either formation or maintenance of abnormal myeline, termed dysmyelinating. CT is a well-established technique for studying white matter disease. Magnetic resonance imaging (MRI) is a new noninvasive technique which has shown greater sensitivity to white matter abnormalities. However, because of the rarity of may white matter diseases coupled with limited availability of MR facilities, the MRI experience in evaluating these patients is not extensive yet. Some patients may not be suitable for MRI because of the longer period of patient immobility that is required to avoid motion artifacts

  14. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1

    DEFF Research Database (Denmark)

    Madsen, Kenneth L; Beuming, Thijs; Niv, Masha Y

    2005-01-01

    PICK1 (protein interacting with C kinase 1) contains a single PDZ domain known to mediate interaction with the C termini of several receptors, transporters, ion channels, and kinases. In contrast to most PDZ domains, the PICK1 PDZ domain interacts with binding sequences classifiable as type I (te...

  15. Radiotherapy of brain inflammatory diseases

    International Nuclear Information System (INIS)

    Pil', B.N.

    1982-01-01

    An experience of radiation treatment of brain inflammatory diseases is described. Radiation treatment goes with antiinflammatory, anticonvulsive agents, with resorbing and dehydrating measures and some times with surgical treatment. The methods of radiation treatment of convexital and optochiasmic arachnoiditis

  16. Efficacy of thepick and roll” offense in top level European basketball teams

    Science.gov (United States)

    Marmarinos, Christos; Kostopoulos, Nikolaos; Apostolidis, Alexandros

    2016-01-01

    Abstract Team offense in basketball games consists of a set of offensive actions carried out with the cooperation of two or more players. Of these actions, the most commonly used in the last decade is the on-ball screen called thepick and roll.” The aim of this study was to analyze all of the pick and rolls conducted in the Euroleague championship from all of the 24 participating teams and to investigate the possible relationships between success in the pick and roll and overall success of the teams. For this purpose, 12,376 pick and rolls from 502 matches were analyzed and classified in categories according to the end result of the offensive possession. The results showed that the most effective type of pick and roll offense was when a shot was attempted after 2 passes from the pick and roll occurrence, followed by the screener’s shot when he rolled to the basket. Additionally, linear regression analysis confirmed that pick and roll effectiveness could predict the final classification of the teams. Conclusively, coaches of the high level European clubs should focus on training the players to the most efficient phases of the pick and roll offense, so that the chances of winning the championship to be maximized. PMID:28149375

  17. Efficacy of thepick and roll” offense in top level European basketball teams

    Directory of Open Access Journals (Sweden)

    Marmarinos Christos

    2016-06-01

    Full Text Available Team offense in basketball games consists of a set of offensive actions carried out with the cooperation of two or more players. Of these actions, the most commonly used in the last decade is the on-ball screen called thepick and roll.” The aim of this study was to analyze all of the pick and rolls conducted in the Euroleague championship from all of the 24 participating teams and to investigate the possible relationships between success in the pick and roll and overall success of the teams. For this purpose, 12,376 pick and rolls from 502 matches were analyzed and classified in categories according to the end result of the offensive possession. The results showed that the most effective type of pick and roll offense was when a shot was attempted after 2 passes from the pick and roll occurrence, followed by the screener’s shot when he rolled to the basket. Additionally, linear regression analysis confirmed that pick and roll effectiveness could predict the final classification of the teams. Conclusively, coaches of the high level European clubs should focus on training the players to the most efficient phases of the pick and roll offense, so that the chances of winning the championship to be maximized.

  18. Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening

    Directory of Open Access Journals (Sweden)

    Janine Reunert

    2016-02-01

    Full Text Available Niemann Pick type C (NP-C is a rare neurodegenerative disorder caused by an impairment of intracellular lipid transport. Due to the heterogeneous clinical phenotype and the lack of a reliable blood test, diagnosis and therapy are often delayed for years. In the cell, accumulating cholesterol leads to increased formation of oxysterols that can be used as a powerful screening parameter for NP-C. In a large scale study, we evaluated the oxysterol cholestane-3β,5α,6β-triol (c-triol as potential biomarker for a rapid diagnosis of NP-C. Using GC/MS, c-triol has been analyzed in 1902 plasma samples of patients with the suspicion for NP-C. Diagnosis in patients with elevated oxysterols was confirmed by genetic analysis. 71 new NP-C patients (69 NP-C1 and two NP-C2 and 12 Niemann Pick type A/B patients were identified. 24 new mutations in NPC1, one new mutation in NPC2 and three new mutations in the SMPD1 gene were found. Cholestane-3β,5α,6β-triol was elevated in Niemann Pick type C1, type C2, type A/B and in CESD disease. No other study has ever identified so many NP-C patients, proving that c-triol is a rapid and reliable biomarker to detect patients with NP-C disease and related cholesterol transport disorders. It should replace the filipin test as the first-line diagnostic assay.

  19. The impact of COI-based storage on order-picking times

    Directory of Open Access Journals (Sweden)

    Grzegorz Tarczyński

    2017-09-01

    Full Text Available Background: The increasing competitiveness on the global markets enforces the need for a fast and reliable delivery. This task is possible to perform by improving the order-picking systems. The implementation of automated storage and retrieval systems (AS/RS is not always profitable. In the warehouses where the order-picking is performed in accordance with the principle of picker-to-part rule, the picking efficiency optimization includes among others: the warehouse layout, the storage policy, the routing heuristic, the way of zoning, the order-batching method, and the sequencing of pick-lists. In the paper the impact of the storage policy on the order-picking times is checked. Methods: The influence of storage based on Heskett’s cube-per-order index (COI on the average order-picking times is analyzed. The items based on increasing values of COI index are divided on classes. To determine the demand for items the analytical function proposed by Caron is used. Results: In the paper the benefits of storage based on COI index are compared with random storage and storage based only on picking frequency. It is assumed that the bin, to which the picker collects items has limited capacity – some orders has to be divided on smaller pick-lists. The analysis was performed using simulation tools. Additionally, the algorithm (taking into account different sizes of picker’s bin for order-batching is presented. Conclusions: The analysis shows that the COI-based storage is particularly effective when the size of items increases. The COI-based curve is less skewed than the curve based only on picking frequency. The choice of storage policy should be carried out together with routing heuristic. The use of batching algorithm significantly increases the effectiveness of the order-picking process, but the optimal size of picker’s bin (and batch should be optimized with consideration the sorting process.

  20. MRI of the brain and craniocervical junction in Morquio's disease

    International Nuclear Information System (INIS)

    Hughes, D.G.; Chadderton, R.D.; Cowie, R.A.; Wraith, J.E.; Jenkins, J.P.R.

    1997-01-01

    We reviewed MRI of the brain and cervical spine in 11 patients with Morquio's disease. No abnormality was seen in the brain. The odontoid peg was abnormal in all patients, with varying degrees of cord compression due to an anterior soft tissue mass and indentation by the posterior arch of the atlas. The degree of cord compression was more marked than suggested by the symptoms and signs. We recommend MRI of the cervical spine in children with Morquio's disease before the development of neurological symptoms, to optimise the timing and type of surgical intervention. (orig.). With 5 figs., 2 tabs

  1. Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

    Science.gov (United States)

    Ranganath, Prajnya; Matta, Divya; Bhavani, Gandham SriLakshmi; Wangnekar, Savita; Jain, Jamal Mohammed Nurul; Verma, Ishwar C; Kabra, Madhulika; Puri, Ratna Dua; Danda, Sumita; Gupta, Neerja; Girisha, Katta M; Sankar, Vaikom H; Patil, Siddaramappa J; Ramadevi, Akella Radha; Bhat, Meenakshi; Gowrishankar, Kalpana; Mandal, Kausik; Aggarwal, Shagun; Tamhankar, Parag Mohan; Tilak, Preetha; Phadke, Shubha R; Dalal, Ashwin

    2016-10-01

    Acid sphingomyelinase (ASM)-deficient Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann-Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

    Directory of Open Access Journals (Sweden)

    Edward Rockenstein

    Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

  3. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    Science.gov (United States)

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

  4. Using the Min/Max Method for Replenishment of Picking Locations

    Directory of Open Access Journals (Sweden)

    Apsalons Raitis

    2017-03-01

    Full Text Available The irregularity of removing quantities from a definite picking location in a warehouse very often results in the stock out in the particular picking address. In practice, the Red Card principle is used to determine a critical level for each picking location when it is necessary to start the replenishment of stock in the picking address. The question is how to calculate an adequate critical level. The guidelines in this paper explain in detail the solution of the problem using the Min/Max stock control method and mathematical algorithms adjusted by authors. In order to check the validity of these mathematical algorithms of the Min/Max method, the simulation modelling has been also done and presented.

  5. A multi-objective approach to the assignment of stock keeping units to unidirectional picking lines

    Directory of Open Access Journals (Sweden)

    Le Roux, G. J.

    2017-05-01

    Full Text Available An order picking system in a distribution centre consisting of parallel unidirectional picking lines is considered. The objectives are to minimise the walking distance of the pickers, the largest volume of stock on a picking line over all picking lines, the number of small packages, and the total penalty incurred for late distributions. The problem is formulated as a multi-objective multiple knapsack problem that is not solvable in a realistic time. Population-based algorithms, including the artificial bee colony algorithm and the genetic algorithm, are also implemented. The results obtained from all algorithms indicate a substantial improvement on all objectives relative to historical assignments. The genetic algorithm delivers the best performance.

  6. Brain metastasis from extramammary Paget's disease of the scrotum.

    Science.gov (United States)

    Kim, In-Young; Yun, Suk-Jung; Lee, Ji-Shin; Jung, Shin; Jung, Tae-Young; Moon, Kyung-Sub; Jang, Woo-Youl

    2014-04-01

    We present to our knowledge the first patient with histopathologically proven brain metastasis from extramammary Paget's disease (EMPD) and discuss the effect of brain radiation therapy for this condition. A 68-year-old man presented to our hospital with headache and gait disturbance. Brain MRI showed multiple enhancing mass lesions, and two large cystic lesions in the left cerebellum. The patient had been diagnosed with scrotal Paget's disease 3 months previously but no further management had been performed due to his refusal. The patient underwent stereotactic aspiration and biopsy of the two large cystic lesions. A histopathological examination revealed that the tumor was a metastatic adenocarcinoma. Immunohistochemical staining revealed that the tumor cells were strongly positive for cytokeratin 7 and moderately positive for carcinoembryonic antigen and gross cystic disease fluid protein 15. These findings were similar to those of his scrotal skin lesions and were consistent with metastatic EMPD. The patient underwent brain radiation therapy with a total radiation dose of 30 Gy in 10 fractions. The patient improved neurologically so as to be self-ambulatory, and a mild improvement in the metastatic tumors was found on follow-up MRI. We had planned systemic chemotherapy, but the patient died of acute respiratory failure 2 months after radiation therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. In vivo calcium imaging of the aging and diseased brain

    International Nuclear Information System (INIS)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga

    2008-01-01

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  8. Heat Shock Protein Beta-1 Modifies Anterior to Posterior Purkinje Cell Vulnerability in a Mouse Model of Niemann-Pick Type C Disease.

    Directory of Open Access Journals (Sweden)

    Chan Chung

    2016-05-01

    Full Text Available Selective neuronal vulnerability is characteristic of most degenerative disorders of the CNS, yet mechanisms underlying this phenomenon remain poorly characterized. Many forms of cerebellar degeneration exhibit an anterior-to-posterior gradient of Purkinje cell loss including Niemann-Pick type C1 (NPC disease, a lysosomal storage disorder characterized by progressive neurological deficits that often begin in childhood. Here, we sought to identify candidate genes underlying vulnerability of Purkinje cells in anterior cerebellar lobules using data freely available in the Allen Brain Atlas. This approach led to the identification of 16 candidate neuroprotective or susceptibility genes. We demonstrate that one candidate gene, heat shock protein beta-1 (HSPB1, promoted neuronal survival in cellular models of NPC disease through a mechanism that involved inhibition of apoptosis. Additionally, we show that over-expression of wild type HSPB1 or a phosphomimetic mutant in NPC mice slowed the progression of motor impairment and diminished cerebellar Purkinje cell loss. We confirmed the modulatory effect of Hspb1 on Purkinje cell degeneration in vivo, as knockdown by Hspb1 shRNA significantly enhanced neuron loss. These results suggest that strategies to promote HSPB1 activity may slow the rate of cerebellar degeneration in NPC disease and highlight the use of bioinformatics tools to uncover pathways leading to neuronal protection in neurodegenerative disorders.

  9. Imaging of demyelinating and degenerative diseases of the brain

    International Nuclear Information System (INIS)

    Drayer, B.P.

    1987-01-01

    The emergence of cross-sectional brain imaging in the past decade has greatly expanded the role of imaging as a primary diagnostic modality for demyelinating and degenerative brain disorders. To remain an effective neurologic consultant, the radiologist must better understand the neuropathology and functional significance of these disorders. MR imaging has become the dominant imaging modality for multiple sclerosis and all demyelinating and dysmyelinating disorders. Detection is most sensitive with intermediate and T2-weighted spin-echo pulse sequences. Although increased signal intensity in the white matter is a sensitive but nonspecific finding, a knowledge of the patient's history and disease pathoanatomy greatly improves diagnostic specificity. Since an increasing proportion of the population is over 65 years of age, the distinction of normal versus pathologic aging becomes critical. The role of imaging in dementing illness is to distinguish primary degenerative dementia from normal aging changes, vascular medullary artery distribution disease, microangiopathic leukoencephalopathy, communicating hydrocephalus, and mass lesions. The role of MR imaging, including brain iron mapping, is analyzed in bradykinetic, choreiform, and dystonic disorders. The complications of chronic ethanol abuse, including vermian atrophy, central pontine myelinolysis, and Wernicke encephalopathy, are also reviewed

  10. Sleep disorders of Whipple's disease of the brain.

    Science.gov (United States)

    Panegyres, P K; Goh, J

    2015-02-01

    To understand the effects of Whipple's disease (WD) of the brain on sleep function. Clinical and polysomnographic studies of two patients with severe disruption of sleep due to WD: a 48-year-old female with primary WD of the brain and a 41-year-old male with secondary WD of the brain. The patient with primary WD had hypersomnolence with severe obstructive sleep apnoea, reduced sleep efficiency, frequent waking and sleep fragmentation. The patient with secondary WD was also hypersomnolent with oculomastictory myorhythmia. He was shown to have severe sleep initiation insomnia with poor sleep efficiency, severe obstructive sleep apnoea/hypopnoea and oculomasticatory myorhythmia at sleep-wake transitions. WD of the brain may affect sleep biology in its primary and secondary forms leading to hypersomnolence from obstructive sleep apnoea, sleep fragmentation, reduced sleep efficiency, sleep initiation insomnia and intrusive oculomasticatory myorhythmia. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Experimental Investigation of the Influence of Confining Stress on Hard Rock Fragmentation Using a Conical Pick

    Science.gov (United States)

    Li, Xibing; Wang, Shaofeng; Wang, Shanyong

    2018-01-01

    High geostress is a prominent condition in deep excavations and affects the cuttability of deep hard rock. This study aims to determine the influence of confining stress on hard rock fragmentation as applied by a conical pick. Using a true triaxial test apparatus, static and coupled static and dynamic loadings from pick forces were applied to end faces of cubic rock specimens to break them under biaxial, uniaxial and stress-free confining stress conditions. The cuttability indices (peak pick force, insertion depth and disturbance duration), failure patterns and fragment sizes were measured and compared to estimate the effects of confining stress. The results show that the rock cuttabilities decreased in order from rock breakages under stress-free conditions to uniaxial confining stress and then to biaxial confining stress. Under biaxial confining stress, only flake-shaped fragments were stripped from the rock surfaces under the requirements of large pick forces or disturbance durations. As the level of uniaxial confining stress increased, the peak pick force and the insertion depth initially increased and then decreased, and the failure patterns varied from splitting to partial splitting and then to rock bursts with decreasing average fragment sizes. Rock bursts will occur under elastic compression via ultra-high uniaxial confining stresses. There are two critical uniaxial confining stress levels, namely stress values at which peak pick forces begin to decrease and improve rock cuttability, and those at which rock bursts initially occur and cutting safety decreases. In particular, hard rock is easiest to split safely and efficiently under stress-free conditions. Moreover, coupled static preloading and dynamic disturbance can increase the efficiency of rock fragmentation with increasing preloading levels and disturbance amplitudes. The concluding remarks confirm hard rock cuttability using conical pick, which can improve the applicability of mechanical excavation in

  12. Revisiting the theory of the evolution of pick-up ion distributions: magnetic or adiabatic cooling?

    Directory of Open Access Journals (Sweden)

    H. J. Fahr

    2007-01-01

    Full Text Available We study the phasespace behaviour of heliospheric pick-up ions after the time of their injection as newly created ions into the solar wind bulk flow from either charge exchange or photoionization of interplanetary neutral atoms. As interaction with the ambient MHD wave fields we allow for rapid pitch angle diffusion, but for the beginning of this paper we shall neglect the effect of quasilinear or nonlinear energy diffusion (Fermi-2 acceleration induced by counterflowing ambient waves. In the up-to-now literature connected with the convection of pick-up ions by the solar wind only adiabatic cooling of these ions is considered which in the solar wind frame takes care of filling the gap between the injection energy and energies of the thermal bulk of solar wind ions. Here we reinvestigate the basics of the theory behind this assumption of adiabatic pick-up ion reactions and correlated predictions derived from it. We then compare it with the new assumption of a pure magnetic cooling of pick-up ions simply resulting from their being convected in an interplanetary magnetic field which decreases in magnitude with increase of solar distance. We compare the results for pick-up ion distribution functions derived along both ways and can point out essential differences of observational and diagnostic relevance. Furthermore we then include stochastic acceleration processes by wave-particle interactions. As we can show, magnetic cooling in conjunction with diffusive acceleration by wave-particle interaction allows for an unbroken power law with the unique power index γ=−5 beginning from lowest velocities up to highest energy particles of about 100 KeV which just marginally can be in resonance with magnetoacoustic turbulences. Consequences for the resulting pick-up ion pressures are also analysed.

  13. Revisiting the theory of the evolution of pick-up ion distributions: magnetic or adiabatic cooling?

    Directory of Open Access Journals (Sweden)

    H. J. Fahr

    2008-01-01

    Full Text Available We study the phasespace behaviour of heliospheric pick-up ions after the time of their injection as newly created ions into the solar wind bulk flow from either charge exchange or photoionization of interplanetary neutral atoms. As interaction with the ambient MHD wave fields we allow for rapid pitch angle diffusion, but for the beginning of this paper we shall neglect the effect of quasilinear or nonlinear energy diffusion (Fermi-2 acceleration induced by counterflowing ambient waves. In the up-to-now literature connected with the convection of pick-up ions by the solar wind only adiabatic cooling of these ions is considered which in the solar wind frame takes care of filling the gap between the injection energy and energies of the thermal bulk of solar wind ions. Here we reinvestigate the basics of the theory behind this assumption of adiabatic pick-up ion reactions and correlated predictions derived from it. We then compare it with the new assumption of a pure magnetic cooling of pick-up ions simply resulting from their being convected in an interplanetary magnetic field which decreases in magnitude with increase of solar distance. We compare the results for pick-up ion distribution functions derived along both ways and can point out essential differences of observational and diagnostic relevance. Furthermore we then include stochastic acceleration processes by wave-particle interactions. As we can show, magnetic cooling in conjunction with diffusive acceleration by wave-particle interaction allows for an unbroken power law with the unique power index γ=−5 beginning from lowest velocities up to highest energy particles of about 100 KeV which just marginally can be in resonance with magnetoacoustic turbulences. Consequences for the resulting pick-up ion pressures are also analysed.

  14. Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease.

    Science.gov (United States)

    Domon, Magdalena; Nasir, Mehmet Nail; Matar, Gladys; Pikula, Slawomir; Besson, Françoise; Bandorowicz-Pikula, Joanna

    2012-06-01

    Growing evidence suggests that membrane microdomains enriched in cholesterol and sphingomyelin are sites for numerous cellular processes, including signaling, vesicular transport, interaction with pathogens, and viral infection, etc. Recently some members of the annexin family of conserved calcium and membrane-binding proteins have been recognized as cholesterol-interacting molecules and suggested to play a role in the formation, stabilization, and dynamics of membrane microdomains to affect membrane lateral organization and to attract other proteins and signaling molecules onto their territory. Furthermore, annexins were implicated in the interactions between cytosolic and membrane molecules, in the turnover and storage of cholesterol and in various signaling pathways. In this review, we focus on the mechanisms of interaction of annexins with lipid microdomains and the role of annexins in membrane microdomains dynamics including possible participation of the domain-associated forms of annexins in the etiology of human lysosomal storage disease called Niemann-Pick type C disease, related to the abnormal storage of cholesterol in the lysosome-like intracellular compartment. The involvement of annexins and cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes mellitus, and cancer is likely, but is not supported by substantial experimental observations, and therefore awaits further clarification.

  15. Membrane Localization is Critical for Activation of the PICK1 BAR Domain

    Science.gov (United States)

    Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

    2013-01-01

    The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative α-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain’s membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment. PMID:18466293

  16. Sphingomyelin lipidosis (Niemann-Pick disease) in a juvenile raccoon (Procyon lotor).

    Science.gov (United States)

    Vapniarsky, N; Wenger, D A; Scheenstra, D; Mete, A

    2013-01-01

    A wild caught juvenile male raccoon with neurological disease was humanely destroyed due to poor prognosis. Necropsy examination revealed hepatomegaly, splenomegaly and multicentric lymphadenomegaly with diffuse hepatic pallor and pulmonary consolidation with pinpoint pale subpleural foci. Microscopically, there was marked pale cytoplasmic swelling of the central and peripheral neurons as well as the glial cells in the brain, accompanied by multiorgan infiltration by abundant foamy macrophages. Ultrastructural investigation revealed accumulation of concentrically arranged lamellar material within lysosomes of the affected neurons, macrophages and endothelial cells. Biochemical enzymatic analysis detected sphingomyelinase deficiency and lysosomal storage disease consistent with sphingomyelin lipidosis (Niemann-Pick disease [NPD]) was diagnosed. This is the first report of NPD in a raccoon. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Public participation: Picking the players

    International Nuclear Information System (INIS)

    McNeill, L.; Jernigan, G.

    1995-01-01

    When citizens become involved in the public policy decision-making process, who picks the players? Are there any criteria for determining which members of the public should sit at the table? These are questions frequently asked by new participants and observers of the public involvement process. In the interest of trust and credibility, the process must be one of self-selection. Any exclusion on the part of the sponsoring organization would probably be interpreted by the public and the press as manipulative self-interest. Clearly, at times there are irrational people attending public meetings or submitting written comments. But if an organization begins excluding participants, the risk increases that the process will be perceived as a travesty

  18. Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing.

    Science.gov (United States)

    Zeiger, William A; Jamal, Nasheed I; Scheuner, Maren T; Pittman, Patricia; Raymond, Kimiyo M; Morra, Massimo; Mishra, Shri K

    2018-02-17

    Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4, c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical testing was consistent with a diagnosis of probable Niemann-Pick disease Type C (NP-C). This case illustrates the potential of whole exome sequencing for diagnosing rare complex neurologic diseases. It also identifies several potential common pitfalls that must be navigated by clinicians when interpreting commercial whole exome sequencing results.

  19. The Impact of Visual Guided Order Picking on Ocular Comfort, Ocular Surface and Tear Function.

    Directory of Open Access Journals (Sweden)

    Angelika Klein-Theyer

    Full Text Available We investigated the effects of a visual picking system on ocular comfort, the ocular surface and tear function compared to those of a voice guided picking solution.Prospective, observational, cohort study.Institutional.A total of 25 young asymptomatic volunteers performed commissioning over 10 hours on two consecutive days.The operators were guided in the picking process by two different picking solutions, either visually or by voice while their subjective symptoms and ocular surface and tear function parameters were recorded.The visual analogue scale (VAS values, according to subjective dry eye symptoms, in the visual condition were significantly higher at the end of the commissioning than the baseline measurements. In the voice condition, the VAS values remained stable during the commissioning. The tear break-up time (BUT values declined significantly in the visual condition (pre-task: 16.6 sec and post-task: 9.6 sec in the right eyes, that were exposed to the displays, the left eyes in the visual condition showed only a minor decline, whereas the BUT values in the voice condition remained constant (right eyes or even increased (left eyes over the time. No significant differences in the tear meniscus height values before and after the commissioning were observed in either condition.In our study, the use of visually guided picking solutions was correlated with post-task subjective symptoms and tear film instability.

  20. Changes in Caries Risk and Activity of a 9-Year-Old Patient with Niemann-Pick Disease Type C

    Directory of Open Access Journals (Sweden)

    Késsia Suênia Fidelis Mesquita-Guimarães

    2015-01-01

    Full Text Available Objective. This case report describes the changes in caries risk and activity and dental treatment of a 9-year-old patient who presented with signs and symptoms of Niemann-Pick disease type C (NPC. Treatment. The preventive dental treatment included instructions to caregivers for oral hygiene and diet. A calcium hydroxide pulpotomy and restorative dental treatments were performed in a dental office with desensitization techniques and behavioral management. The patient was attended every 3 months for the control of dental plaque biofilm, for topical fluoride application, and for observing the pulpotomized tooth. Results. The bacterial plaque biofilm was being adequately controlled by the caregiver. After 2 years, the clinical and radiographic examination of the pulpotomized tooth showed the absence of internal root resorption and bone rarefaction, and clinical examination showed tooth sensitivity, dental pain, and gingival swelling. Conclusion. The pulpotomy prevented clinical and radiographic success. Dentists must be aware of and be able to identify systemic and local aspects associated with caries risk of children with NPC disease. Furthermore, dentists must employ stringent preventive measures and provide instructions to caregivers to reduce caries risk.

  1. Automatic first-break picking using the instantaneous traveltime attribute

    KAUST Repository

    Saragiotis, Christos; Alkhalifah, Tariq Ali

    2012-01-01

    Picking the first breaks is an important step in seismic processing. The large volume of the seismic data calls for automatic and objective picking. We introduce a new automatic first-break picker, which uses specifically designed time windows

  2. Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1

    Directory of Open Access Journals (Sweden)

    Meghann W. Lau

    2016-09-01

    Full Text Available Niemann-Pick Disease, type C1 (NPC1 is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA and mean diffusivity (MD negatively correlate with NIH NPC neurological severity score (NNSS and motor severity subscores. Magnetic resonance imaging (MRI was obtained for thirty-nine NPC1 subjects, ages 1–21.9 years (mean = 11.1, SD = 6.1. Using an atlas-based automated approach, the cerebellum of each patient was measured for FA, MD and volume. Additionally, each patient was given an NNSS. Decreased cerebellar FA and volume, and elevated MD correlate with higher NNSS. The cognition subscore and motor subscores for eye movement, ambulation, speech, swallowing, and fine motor skills were also statistically significant. Microstructural disorganization negatively correlated with motor severity in subjects. Additionally, Miglustat therapy correlated with lower severity scores across ranges of FA, MD and volume in all regions except the inferior peduncle, where a paradoxical effect was observed at high FA values. These findings suggest that DTI is a promising prognostication tool.

  3. Final version of the pick-up wheels in the Pelletron tandem accelerator at Lund

    International Nuclear Information System (INIS)

    Hakansson, K.; Hellborg, R.

    1993-01-01

    A new type of pick-up wheel has been designed and constructed for the charge transport system of the Lund 3UDH Pelletron tandem accelerator. The major improvements compared with older types are a slender design with only one ball bearing and more robust contact pins with a rubber ring between the pinhead and the wheel nave. (orig.)

  4. Detection of interstellar pick-up hydrogen in the solar system

    Science.gov (United States)

    Gloeckler, G.; Geiss, J.; Balsiger, H.; Fisk, L. A.; Galvin, A. B.; Ipavich, F. M.; Ogilvie, K. W.; Von Steiger, R.; Wilken, B.

    1993-01-01

    Interstellar hydrogen ionized primarily by the solar wind has been detected by the Solar Wind Ion Composition Spectrometer instrument on the Ulysses spacecraft at a distance of 4.8 AUs from the sun. This 'pick-up' hydrogen is identified by its distinct velocity distribution function, which drops abruptly at twice the local solar wind speed. From the measured fluxes of pick-up protons and singly charged helium, the number densities of neutral hydrogen and helium in the distant regions of the solar system are estimated to be 0.077 +/- 0.015 and 0.013 +/- 0.003 per cu cm, respectively.

  5. Membrane Localization is Critical for Activation of the PICK1 BAR Domain

    OpenAIRE

    Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

    2008-01-01

    The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redis...

  6. Evaluation by statistical brain perfusion SPECT analysis on MRI findings, kana pick-out test and Mini-Mental State Examination results in patients with forgetfulness

    International Nuclear Information System (INIS)

    Nakatsuka, Hiroki; Matsubara, Ichirou; Ohtani, Haruhiko

    2003-01-01

    The aim of this single photon emission computed tomography (SPECT) study was to determine the abnormality of the regional cerebral blood flow (rCBF) using a three-dimensional stereotactic surface projection (3D-SSP) in 18 patients who were referred to the hospital because of forgetfulness. Two intergroup comparison by 3D-SSP analysis was conducted based on MRI, kana pick-out test and Mini-Mental State Examination (MMSE) results. Of the MRI findings, in the brain atrophy group, rCBF was decreased in the posterior cingulate gyrus, medial temporal structure and parieto-temporal association cortex; these rCBF-decreased areas are similar to the Alzheimer disease pattern. In the group where the MMSE was normal but the kana pick-out test was abnormal, rCBF was decreased in the posterior cingulate gyrus and cinguloparietal transitional area. In the group where both the MMSE and kana pick-out test were abnormal, rCBF was decreased in the parieto-temporal association cortex, temporal cortex and medial temporal structure. These results suggest that 3D-SSP analysis of the SPECT with MMSE and the kana pick-out test provides the possibility of early diagnosis of initial stage of Alzheimer's disease. (author)

  7. "They just come, pick and go." The Acceptability of Integrated Medication Adherence Clubs for HIV and Non Communicable Disease (NCD) Patients in Kibera, Kenya.

    Science.gov (United States)

    Venables, Emilie; Edwards, Jeffrey K; Baert, Saar; Etienne, William; Khabala, Kelly; Bygrave, Helen

    2016-01-01

    The number of people on antiretroviral therapy (ART) for the long-term management of HIV in low- and middle-income countries (LMICs) is continuing to increase, along with the prevalence of Non-Communicable Diseases (NCDs). The need to provide large volumes of HIV patients with ART has led to significant adaptations in how medication is delivered, but access to NCD care remains limited in many contexts. Medication Adherence Clubs (MACs) were established in Kibera, Kenya to address the large numbers of patients requiring chronic HIV and/or NCD care. Stable NCD and HIV patients can now collect their chronic medication every three months through a club, rather than through individual clinic appointments. We conducted a qualitative research study to assess patient and health-care worker perceptions and experiences of MACs in the urban informal settlement of Kibera, Kenya. A total of 106 patients (with HIV and/or other NCDs) and health-care workers were purposively sampled and included in the study. Ten focus groups and 19 in-depth interviews were conducted and 15 sessions of participant observation were carried out at the clinic where the MACs took place. Thematic data analysis was conducted using NVivo software, and coding focussed on people's experiences of MACs, the challenges they faced and their perceptions about models of care for chronic conditions. MACs were considered acceptable to patients and health-care workers because they saved time, prevented unnecessary queues in the clinic and provided people with health education and group support whilst they collected their medication. Some patients and health-care workers felt that MACs reduced stigma for HIV positive patients by treating HIV as any other chronic condition. Staff and patients reported challenges recruiting patients into MACs, including patients not fully understanding the eligibility criteria for the clubs. There were also some practical challenges during the implementation of the clubs, but MACs

  8. Comparison of magnetic and electrostatic Schottky pick-up in the CERN AD

    CERN Document Server

    Federmann, S

    2013-01-01

    The present note is intended to exploit the possibility of using a dedicated electrostatic beam pick-up for Schottky diagnostics in the future ELENA ring. A test setup is described allowing the evaluation of its performance compared to the extra low-noise beam current transformer used successfully in the AD. The results of this experiment are summarized and discussed.

  9. Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers.

    Science.gov (United States)

    Garnacho, Carmen; Dhami, Rajwinder; Simone, Eric; Dziubla, Thomas; Leferovich, John; Schuchman, Edward H; Muzykantov, Vladimir; Muro, Silvia

    2008-05-01

    Type B Niemann-Pick disease (NPD) is a multiorgan system disorder caused by a genetic deficiency of acid sphingomyelinase (ASM), for which lung is an important and challenging therapeutic target. In this study, we designed and evaluated new delivery vehicles for enzyme replacement therapy of type B NPD, consisting of polystyrene and poly(lactic-coglycolic) acid polymer nanocarriers targeted to intercellular adhesion molecule (ICAM)-1, an endothelial surface protein up-regulated in many pathologies, including type B NPD. Real-time vascular imaging using intravital microscopy and postmortem imaging of mouse organs showed rapid, uniform, and efficient binding of fluorescently labeled ICAM-1-targeted ASM nanocarriers (anti-ICAM/ASM nanocarriers) to endothelium after i.v. injection in mice. Fluorescence microscopy of lung alveoli actin, tissue histology, and 125I-albumin blood-to-lung transport showed that anti-ICAM nanocarriers cause neither detectable lung injury, nor abnormal vascular permeability in animals. Radioisotope tracing showed rapid disappearance from the circulation and enhanced accumulation of anti-ICAM/125I-ASM nanocarriers over the nontargeted naked enzyme in kidney, heart, liver, spleen, and primarily lung, both in wild-type and ASM knockout mice. These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders.

  10. The number of pickers and stock-keeping unit arrangement on a uni-directional picking line

    Directory of Open Access Journals (Sweden)

    Hagspihl, Robert

    2014-10-01

    Full Text Available The order picking process is often the single largest expense in a distribution centre (DC. The DC considered in this paper uses a picking line configuration to perform order picking. The number of pickers in a picking line, and the initial arrangement of stock-keeping units (SKUs, are two important factors that affect the total completion time of the picking lines. In this paper, the picking line configuration is simulated with an agent-based approach to describe the behaviour of an individual picker. The simulation is then used to analyse the effect of the number of pickers and the SKU arrangement. Verification and validation of this model shows that the model represents the real-world picking line to a satisfactory degree. Marginal analysis (MA was chosen to determine a ‘good’ number of pickers by means of the simulation model. A look-up table is presented to provide decision support for the choice of a ‘good’ number of pickers to improve completion times of the picking line, for the properties of a specific picking line. The initial SKU arrangement on a picking line is shown to be a factor that can affect the level of picker congestion and the total completion time. The greedy ranking and partitioning (GRP and organ pipe arrangement (OPA techniques from the literature, as well as the historical SKU arrangements used by the retailer under consideration, were compared with the proposed classroom discipline heuristic (CDH for SKU arrangement. It was found that the CDH provides an more even spread of SKUs that are picked most frequently, thus decreasing congestion and total completion time.

  11. Case Report: Genetic analysis and anesthetic management of a child with Niemann-Pick disease Type A [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Priti G. Dalal

    2015-12-01

    Full Text Available A 14-month-old child, recently diagnosed with Niemann-Pick disease type A, presented for a laparoscopic placement of a gastrostomy tube under general anesthesia. The disease was confirmed and further characterized by genetic testing, which revealed evidence of the presence of two known pathogenic mutations in the SMPD1 gene, and enzyme studies showed a corresponding very low level of enzymatic activity of acidic sphingomyelinase. The anesthetic management involved strategies to manage an anticipated difficult intubation and avoid post-operative ventilation.

  12. The class characteristic mark of the H&M Mul-T-Lock picking tool in toolmarks examination.

    Science.gov (United States)

    Volkov, Nikolai; Finkelstein, Nir; Novoselsky, Yehuda; Tsach, Tsadok

    2014-07-01

    Mul-T-Lock is a high security lock cylinder distinguished by the use of a telescoping "pin-in-pin"-tumbler design. Picking the Mul-T-Lock cylinder with a traditional picking tool is highly complicated because it can get stuck between the inner and outer pins. The H&M Mul-T-Lock picking tool was designed to overcome this problem and facilitate the picking of the "pin-in-pin" cylinder. The purpose of this research is to determine whether H&M Mul-T-Lock picking tool leaves class characteristic mark and whether it can be distinguished from traditional picking tools marks and from regular key marks. It also describes and determines the class characteristic mark left on telescopic pins, its origin, recurrence, and its benefit to the toolmarks examiner. When receiving a Mul-T-Lock from a crime scene, a toolmarks examiner can quickly determine whether or not it was picked by an H&M Mul-T-Lock picking tool by noticing the class characteristic mark which this typical tool leaves. © 2014 American Academy of Forensic Sciences.

  13. The Effect of Slot-Code Optimization in Warehouse Order Picking

    Directory of Open Access Journals (Sweden)

    Andrea Fumi

    2013-07-01

    most appropriate material handling resource configuration. Building on previous work on the effect of slot-code optimization on travel times in single/dual command cycles, the authors broaden the scope to include the most general picking case, thus widening the range of applicability and realising former suggestions for future research.

  14. Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD

    DEFF Research Database (Denmark)

    Thorsen, Thor S; Madsen, Kenneth L; Rebola, Nelson

    2010-01-01

    interacting protein 1 (GRIP1). Pretreatment of cultured hippocampal neurons with FSC231 inhibited coimmunopreciptation of the AMPA receptor GluR2 subunit with PICK1. In agreement with inhibiting the role of PICK1 in GluR2 trafficking, FSC231 accelerated recycling of pHluorin-tagged GluR2 in hippocampal...

  15. Design and Control of Warehouse Order Picking: a literature review

    NARCIS (Netherlands)

    M.B.M. de Koster (René); T. Le-Duc (Tho); K.J. Roodbergen (Kees-Jan)

    2006-01-01

    textabstractOrder picking has long been identified as the most labour-intensive and costly activity for almost every warehouse; the cost of order picking is estimated to be as much as 55% of the total warehouse operating expense. Any underperformance in order picking can lead to unsatisfactory

  16. Membrane localization is critical for activation of the PICK1 BAR domain

    DEFF Research Database (Denmark)

    Madsen, Kenneth L; Eriksen, Jacob; Milan-Lobo, Laura

    2008-01-01

    The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood....

  17. Sodium Pick-Up Ion Observations in the Solar Wind Upstream of Mercury

    Science.gov (United States)

    Jasinski, J. M.; Raines, J. M.; Slavin, J. A.; Regoli, L. R.; Murphy, N.

    2018-05-01

    We present the first observations of sodium pick-up ions upstream of Mercury’s magnetosphere. From these observations we infer properties of Mercury’s sodium exosphere and implications for the solar wind interaction with Mercury’s magnetosphere.

  18. The assessment of muscle strain with surface electromyograms during simulated mushroom picking

    DEFF Research Database (Denmark)

    Ohashi, Jun-Ya; Blangsted, Anne Katrine; Kofoed Nielsen, Pernille B.

    2008-01-01

    Muscle strain was assessed with surface EMG during simulated mushroom picking. Nine female subjects performed five periods of work (W1-W5). The duration of each period was about 20 min. W1, W2 and W3 were separated by a short break of several minutes. W3, W4 and W5 were separated by a rest period...

  19. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Borre, Lars; Braunstein, Thomas H

    2013-01-01

    The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulato...

  20. Making the Right Pick: Aligning Order Picking Methods, Incentive Systems and Regulatory Focus to Increase Picking Performance

    NARCIS (Netherlands)

    J. de Vries (Jelle); M.B.M. de Koster (René); D.A. Stam (Daan)

    2015-01-01

    textabstractA unique controlled field experiment investigates order picking performance (in terms of productivity, quality, and job satisfaction). We examined three manual picker-to-parts order picking methods (parallel, zone, and dynamic zone picking) under two different incentive systems

  1. Dietary cholesterol induces trafficking of intestinal Niemann-Pick Type C1 Like 1 from the brush border to endosomes

    DEFF Research Database (Denmark)

    Skov, Marianne; Tønnesen, Carina K; Hansen, Gert H

    2011-01-01

    The transmembrane protein Niemann-Pick C1 Like 1 (NPC1L1) belongs to the Niemann-Pick C1 (NPC1) family of cholesterol transporters and is mainly expressed in the liver and the small intestine. NPC1L1 is believed to be the main transporter responsible for the absorption of dietary cholesterol. Lik...

  2. Ac-loss measurement of coated conductors: The influence of the pick-up coil position

    International Nuclear Information System (INIS)

    Schmidt, Curt

    2008-01-01

    The ac-loss measurement by the magnetization method requires calibration for obtaining absolute values. A convenient way of calibration is the calorimetric measurement which yields, within the measuring accuracy, absolute loss values. In the magnetization measurement the hysteresis loop of sample magnetization which determines the losses is measured via the integration of magnetic flux penetrating a pick-up coil. The ratio of flux integral to magnetization integral and hence the calibration factor is however, for a given pick-up coil geometry, not exactly a constant, but depends on the magnetization current pattern within the sample. Especially for thin tapes in perpendicular external field this effect has to be taken into consideration in order to avoid miss measurements. The relation between measured flux and sample magnetization was calculated for special cases of magnetization current distribution in the sample as a function of the pick-up coil position. Furthermore calibration factors were measured as a function of the ac-field amplitude and the result compared with available theoretical models. A good agreement was found between experiment and theory

  3. A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease.

    Science.gov (United States)

    Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Martinelli, Diego; Verrigni, Daniela; Carrozzo, Rosalba; Bertini, Enrico; Pastore, Anna; Dionisi-Vici, Carlo; Johnson, David W

    2014-11-01

    Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200ng/mL for C-triol and 1.0-200ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV%) were <15% for both metabolites. Receiver operating characteristic analysis estimates that the area under curve was 0.998 for C-triol, and 0.972 for 7-KC, implying a significant discriminatory power for the method in this patient population of both oxysterols. In summary, our method provides a simple, rapid and non-invasive diagnostic tool for the biochemical diagnosis of NP-C disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The Diagnostic Value of Brain Scanning in the Diseases of the Central Nervous System

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kwang Won; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho; Chang, Kee Hyun; Han, Man Chung; Choi, Kil Su; Son, Hyo Chung; Cho, Byung Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-03-15

    The purpose of this study is to evaluate the diagnostic value of the brain scanning and compare the diagnostic accuracy between the scan and carotid angiography. 109 cases which are proved by specific method to each disease, are analyzed to evaluate the diagnostic value of the brain scanning. The 70 cases among the proven 109 case are performed both the scanning and the arteriography and analyzed to compare the accuracy between the scanning and the arteriography. The results are as follows; 1) The diagnostic accuracy of the brain scanning in the diseases of the central nervous system is 64.2%. 2) The diagnostic accuracy of the brain scanning in the brain tumor is 88%, especially brain abscess, glioma, glioblastoma multiforme, meningioma and metastic tumor show high positive rate. 3) The diagnostic accuracy in the disease of the brain vessels is 54%. The comparison of the diagnostic value between the scanning and the arteriography is as follows;1) The diagnostic value in all diseases of the central nervous system is nearly equal. 2) The diagnostic accuracy in the intracranial tumor is slightly higher in the brain scanning (90. 9%) than in the arteriography (81.8%). 3) The diagnostic accuracy in the disease of the brain vessel is higher in the arteriography (77.3%) than in the scanning (54.5%). 5) The diagnostic value when combining the scanning and the arteriography, is 83% in the all central nervous system-lesions, 97% in the cranial tumor and 81.8% in the disease of the central nervous system-vessel. The brain scanning is simple and safe procedure, and moreover has excellent diagnostic value in the diagnosis of the central nervous system lesion.

  5. The Diagnostic Value of Brain Scanning in the Diseases of the Central Nervous System

    International Nuclear Information System (INIS)

    Kim, Kwang Won; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho; Chang, Kee Hyun; Han, Man Chung; Choi, Kil Su; Son, Hyo Chung; Cho, Byung Kyu

    1974-01-01

    The purpose of this study is to evaluate the diagnostic value of the brain scanning and compare the diagnostic accuracy between the scan and carotid angiography. 109 cases which are proved by specific method to each disease, are analyzed to evaluate the diagnostic value of the brain scanning. The 70 cases among the proven 109 case are performed both the scanning and the arteriography and analyzed to compare the accuracy between the scanning and the arteriography. The results are as follows; 1) The diagnostic accuracy of the brain scanning in the diseases of the central nervous system is 64.2%. 2) The diagnostic accuracy of the brain scanning in the brain tumor is 88%, especially brain abscess, glioma, glioblastoma multiforme, meningioma and metastic tumor show high positive rate. 3) The diagnostic accuracy in the disease of the brain vessels is 54%. The comparison of the diagnostic value between the scanning and the arteriography is as follows;1) The diagnostic value in all diseases of the central nervous system is nearly equal. 2) The diagnostic accuracy in the intracranial tumor is slightly higher in the brain scanning (90. 9%) than in the arteriography (81.8%). 3) The diagnostic accuracy in the disease of the brain vessel is higher in the arteriography (77.3%) than in the scanning (54.5%). 5) The diagnostic value when combining the scanning and the arteriography, is 83% in the all central nervous system-lesions, 97% in the cranial tumor and 81.8% in the disease of the central nervous system-vessel. The brain scanning is simple and safe procedure, and moreover has excellent diagnostic value in the diagnosis of the central nervous system lesion.

  6. FLAIR images of brain diseases

    International Nuclear Information System (INIS)

    Segawa, Fuminori; Kinoshita, Masao; Kishibayashi, Jun; Kamada, Kazuhiko; Sunohara, Nobuhiko.

    1994-01-01

    The present study was designed to assess the usefulness of fluid-attenuated inversion recovery (FLAIR) images in diagnosing brain diseases. The subjects were 20 patients with multiple cerebral infarction, multiple sclerosis, temporal epilepsy, or brain trauma, and 20 other healthy adults. FLAIR images, with a long repetitive time of 6000 msec and a long inversion time of 1400-1600 msec, showed low signal intensity in the cerebrospinal fluid in the lateral ventricles and the cerebral sulci, and high signal intensity in brain tissues. Signal intensity on FLAIR images correlated well with T2 relaxation times under 100 msec. For multiple sclerosis and cerebral infarction, cystic lesions, which were shown on T2-weighted images with long relaxation times over 100 msec, appeared as low-signal areas; and the lesions surrounding the cystic lesions appeared as high-signal areas. For temporal lobe epilepsy, the hippocampus was visualized as a high-signal area. Hippocampal lesions were demonstrated better with FLAIR images than with conventional T2-weighted and proton-density images. In a patient with cerebral trauma, FLAIR images revealed the lobulated structure with the residual cortex shown as a high signal area. The lesions surrounding the cystic change were imaged as high signal areas. These structural changes were demonstrated better with FLAIR images than with conventional T2-weighted sequences. FLAIR images were useful in detecting white matter lesions surrounding the lateral ventricles and cortical and subcortical lesions near the brain surface, which were unclear on conventional T2-weighted and proton-density images. (N.K.)

  7. Clinicoelectrophysiologic and magnetoresonance and tomographic investigation of hereditary and congenital diseases of the brain

    International Nuclear Information System (INIS)

    Kamalov, I.I.; Pikuza, O.I.; Idrisova, L.G.; Uryvskij, V.I.

    1996-01-01

    The combined investigation of hereditary and congenital diseases of the brain using magnetoresonance tomography is performed. The hereditary and congenital diseases of the brain accompanied by disorders of liquoroconductive tracts with medullary substance lesion are revealed. The investigation results provide timely development of the treatment tactics and rehabilitation of sick children. Refs. 3

  8. Plasma chitotriosidase and CCL18: Early biochemical surrogate markers in type B Niemann-Pick disease

    NARCIS (Netherlands)

    Brinkman, J.; Wijburg, F. A.; Hollak, C. E.; Groener, J. E.; Verhoek, M.; Scheij, S.; Aten, J.; Boot, R. G.; Aerts, J. M.

    2005-01-01

    Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the

  9. MRI/MRA evaluation of sickle cell disease of the brain

    International Nuclear Information System (INIS)

    Zimmerman, Robert A.

    2005-01-01

    Sickle cell disease is a major cause of pediatric stroke. Understanding the disease that affects the brain as infarctions, both clinically apparent and silent, requires an understanding of how the blood vessels are affected, the way in which both the brain and the blood vessels are imaged by MRI and MRA and the mechanism of injury. (orig.)

  10. Interaction of intersteller pick-up ions with the solar wind

    International Nuclear Information System (INIS)

    Mobius, E.; Klecker, B.; Hovestadt, D.; Scholer, M.

    1988-01-01

    The interaction of interstellar pick-up ions with the solar wind is studied by comparing a model for the velocity distribution function of pick-up ions with actual measurements of He + ions in the solar wind. The model includes the effects of pitch-angle diffusion due to interplanetary Alfven waves, adiabatic deceleration in the expanding solar wind and the radial variation of the source function. It is demonstrated that the scattering mean free path is in the range ≤0.1 AU and that energy diffusion can be neglected as compared with adiabatic deceleration. The effects of adiabatic focusing, of the radial variation of the neutral density and of an variation of the solar wind velocity with distance from the Sun are investigated. With the correct choice of these parameters the authors can model the measured energy spectra of the pick-up ions does not vary with the solar wind velocity and the direction of the interplanetary magnetic field for a given local neutral gas density and ionization rate. Therefore, the comparison of the model distributions with the measurements leads to a quantitative determination of the local interstellar gas density

  11. Evaluation of strip-line pick-up system for the SPS wideband transverse feedback system

    CERN Document Server

    Kotzian, G; Steinhagen, R J; Valuch, D; Wehrle, U

    2017-01-01

    The proposed SPS Wideband Transverse Feedback sys- tem requires a wide-band pick-up system to be able to de- tect intra-bunch motion within the SPS proton bunches, captured and accelerated in a 200 MHz bucket. We present the electro-magnetic design of transverse beam position pick-up options optimised for installation in the SPS and evaluate their performance reach with respect to direct time domain sampling of the intra-bunch motion. The analy- sis also discusses the achieved subsystem responses of the associated cabling with new low dispersion smooth wall coaxial cables, wide-band generation of intensity and posi- tion signals by means of 180 degree RF hybrids as well as passive techniques to electronically suppress the beam off- set signal, needed to optimise the dynamic range and posi- tion resolution of the planned digital intra-bunch feedback system.

  12. Design and manufacture of mechanical forceps to pick up objects at the bottom of the pool reactor TRIGA MK II

    International Nuclear Information System (INIS)

    Kankunku, K.P.; Lukanda, M.V.

    2011-01-01

    This design helps us to pick up any objects felt in bottom of swimming pool, which is a radioactive area, due to the presence of spent nuclear fuel. Its great advantage is its sample designing and made with local material.

  13. Stirring, charging, and picking: hunting tactics of potamotrygonid rays in the upper Paraná River

    Directory of Open Access Journals (Sweden)

    Domingos Garrone-Neto

    Full Text Available Hunting tactics of potamotrygonid freshwater rays remain unreported under natural conditions. Three main foraging tactics of Potamotrygon falkneri and P. motoro are described here based on underwater observations in the upper Paraná River. Both species displayed similar behaviors. The most common tactic was to undulate the disc margins close to, or on, the bottom and thus stirring the substrate and uncovering hidden preys. Another tactic was to charge upon prey concentrated in the shallows. The least common tactic was to pick out prey adhered to the substrate. The first tactic is widespread in several species of marine rays in the Dasyatidae, whereas the remainder (especially picking up prey on substrata above water surface may be restricted to the Potamotrygonidae.

  14. Picking up the pieces of Super-Kamiokande

    CERN Multimedia

    Lee, T

    2002-01-01

    On Nov 12th as the tank of the SuperK detector was being refilled after routine maintenance, a shock wave calculated at 100 times greater than atmospheric pressure was triggered by the implosion of one weakened photomultiplier tube. In only five seconds the resulting chain reaction destroyed 6,665 PMTs, wrecking the detector and seriously delaying neutrino research.

  15. Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation.

    Science.gov (United States)

    Shamburek, R D; Pentchev, P G; Zech, L A; Blanchette-Mackie, J; Carstea, E D; VandenBroek, J M; Cooper, P S; Neufeld, E B; Phair, R D; Brewer, H B; Brady, R O; Schwartz, C C

    1997-12-01

    Niemann-Pick C disease (NP-C) is a rare inborn error of metabolism with hepatic involvement and neurological sequelae that usually manifest in childhood. Although in vitro studies have shown that the lysosomal distribution of LDL-derived cholesterol is defective in cultured cells of NP-C subjects, no unusual characteristics mark the plasma lipoprotein profiles. We set out to determine whether anomalies exist in vivo in the cellular distribution of newly synthesized, HDL-derived or LDL-derived cholesterol under physiologic conditions in NP-C subjects. Three affected and three normal male subjects were administered [14C]mevalonate as a tracer of newly synthesized cholesterol and [3H]cholesteryl linoleate in either HDL or LDL to trace the distribution of lipoprotein-derived free cholesterol. The rate of appearance of free [14C]- and free [3H]cholesterol in the plasma membrane was detected indirectly by monitoring their appearance in plasma and bile. The plasma disappearance of [3H]cholesteryl linoleate was slightly faster in NP-C subjects regardless of its lipoprotein origin. Appearance of free [14C] cholesterol ill the plasma (and in bile) was essentially identical in normal and affected individuals as was the initial appearance of free [3H]cholesterol derived from HDL, observed before extensive exchange occurred of the [3H]cholesteryl linoleate among lipoproteins. In contrast, the rate of appearance of LDL-derived free [3H]cholesterol in the plasma membrane of NP-C subjects, as detected in plasma and bile, was retarded to a similar extent that LDL cholesterol metabolism was defective in cultured fibroblasts of these affected subjects. These findings show that intracellular distribution of both newly synthesized and HDL-derived cholesterol are essentially unperturbed by the NP-C mutation, and therefore occur by lysosomal-independent paths. In contrast, in NP-C there is defective trafficking of LDL-derived cholesterol to the plasma membrane in vivo as well as in vitro

  16. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    Science.gov (United States)

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system:

  17. Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Mary Carmen Vázquez

    2012-01-01

    Full Text Available Niemann-Pick type C (NPC disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serumof NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.

  18. Abnormal brain activation in excoriation (skin-picking) disorder

    DEFF Research Database (Denmark)

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

    2016-01-01

    Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...... encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions: Abnormalities of neural regions...... involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders....

  19. Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease

    Directory of Open Access Journals (Sweden)

    Sandra Torres

    2017-04-01

    Full Text Available Niemann Pick type C (NPC disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH depletion, we investigated the impact of mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE, but not N-acetylcysteine (NAC, restored the mGSH pool in liver and brain of Npc1-/- mice and in fibroblasts from NPC patients, while both GSH-EE and NAC increased total GSH levels. GSH-EE but not NAC increased the median survival and maximal life span of Npc1-/- mice. Moreover, intraperitoneal therapy with GSH-EE protected against oxidative stress and oxidant-induced cell death, restored calbindin levels in cerebellar Purkinje cells and reversed locomotor impairment in Npc1-/- mice. High-resolution respirometry analyses revealed that GSH-EE improved oxidative phosphorylation, coupled respiration and maximal electron transfer in cerebellum of Npc1-/- mice. Lipidomic analyses showed that GSH-EE treatment had not effect in the profile of most sphingolipids in liver and brain, except for some particular species in brain of Npc1-/- mice. These findings indicate that the specific replenishment of mGSH may be a potential promising therapy for NPC disease, worth exploring alone or in combination with other options.

  20. Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    Yumoto, S.; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

    1996-01-01

    To investigate the cause of Alzheimer's disease (senile dementia of Alzheimer's disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer's disease using heavy ion (5 MeV Si 3+ ) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si 2+ ) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer's disease using 5 MeV Si 3+ microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer's disease is caused by accumulation of Al in the nuclei of brain cells. (author)

  1. Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    Manuel E. Lopez

    2013-09-01

    Full Text Available Understanding neurodegenerative disease progression and its treatment requires the systematic characterization and manipulation of relevant cell types and molecular pathways. The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC is highly amenable to genetic approaches that allow exploration of the disease biology at the organismal, cellular and molecular level. Although NPC is a rare disease, genetic analysis of the associated neuropathology promises to provide insight into the logic of disease neural circuitry, selective neuron vulnerability and neural-glial interactions. The ability to control the disorder cell-autonomously and in naturally occurring spontaneous animal models that recapitulate many aspects of the human disease allows for an unparalleled dissection of the disease neurobiology in vivo. Here, we review progress in mouse-model-based studies of NPC disease, specifically focusing on the subtype that is caused by a deficiency in NPC1, a sterol-binding late endosomal membrane protein involved in lipid trafficking. We also discuss recent findings and future directions in NPC disease research that are pertinent to understanding the cellular and molecular mechanisms underlying neurodegeneration in general.

  2. Infectious diseases of the brain: imaging and differential diagnosis; Infektioese Hirnerkrankungen: Bildgebung und differenzialdiagnostische Aspekte

    Energy Technology Data Exchange (ETDEWEB)

    Haehnel, S.; Seitz, A. [Abt. Neuroradiologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany); Storch-Hagenlocher, B. [Abt. Neurologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany)

    2006-09-15

    Infectious diseases of the central nervous system have to be considered in differential diagnosis particularly in immunocompromised persons. Neuro-imaging, specifically advanced techniques such as diffusion weighted MRI and perfusion MRI contribute much to the differentiation of brain infections and for differentiating brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria of the most important brains infections in adults and in pediatric patients and discuss differential diagnostic aspects in detail. (orig.)

  3. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    Science.gov (United States)

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    OpenAIRE

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial...

  5. Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

    Science.gov (United States)

    Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

    2018-02-01

    Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

  6. The Brain in Congenital Heart Disease across the Lifespan: The Cumulative Burden of Injury

    Science.gov (United States)

    Marelli, Ariane; Miller, Steven P.; Marino, Bradley Scott; Jefferson, Angela L.; Newburger, Jane W.

    2017-01-01

    The number of patients surviving with congenital heart disease (CHD) has soared over the last three decades. Adults constitute the fastest growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has largely been focused on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. In summary, against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID:27185022

  7. Specific diagnosis of brain disease with double isotope brain scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J; Lotritsch, K H; Hilbrand, E; Meixner, M; Barolin, G; Scholz, H [Landesunfallkrankenhaus, Feldkirch (Austria). Dept. of Nuclear Medicine; Landesnervenkrankenhaus, Feldkirch (Austria). Dept. of Neurology)

    1976-02-01

    25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double siotope imaging technique using sup(99m)TcO/sub 4/- and sup(99m)Tc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. sup(99m)Tc-EHDP is shown to be the tracer of choice for the imaging of CVA's and sup(99m)TcO/sub 4/- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.

  8. Prenatal-Onset Niemann–Pick Type C Disease with Nonimmune Hydrops Fetalis

    Directory of Open Access Journals (Sweden)

    Ozge Surmeli-Onay

    2013-10-01

    Full Text Available Niemann–Pick type C (NPC; OMIM 257219 disease is a neurodegenerative lysosomal storage disorder characterized by accumulation of unesterified cholesterol in the lysosomal/late endosomal system. This autosomal recessive disorder occurs in approximately 1/150,000 births. The broad clinical spectrum ranges from a prenatal severe presentation to an adult-onset chronic neurodegenerative disease. Data about prenatal presentation of NPC are limited. A female newborn was born at 342 weeks' gestation with a birth weight of 3070 g, and transferred to the Neonatal Intensive Care Unit because of nonimmune hydrops fetalis (NIHF and respiratory distress. On admission, a physical examination revealed skin edema, mild respiratory distress, and abdominal distention due to massive ascites. Hepatosplenomegaly and cholestasis increased progressively and bleeding diathesis occurred. Results of an abdominal ultrasonography showed hepatosplenomegaly and segmental multicystic dysplastic left kidney. Foamy cells with a lysosomal phospholipid storage pattern compatible with NPC were found in the bone marrow smear. Cultured fibroblasts showed a strongly elevated filipin staining (classical NPC cellular phenotype, establishing the diagnosis of NPC. The infant died on the 52nd day of life because of respiratory distress due to lung involvement of NPC, massive ascites, and progressive liver failure. Results of an autopsy showed multiorgan storage disease involving the liver, spleen, lymph nodes, thymus, lungs, and brain. Here, we present a preterm infant with NIHF as a sign of severe prenatal-onset NPC and review the literature.

  9. The value of brain scanning in cerebro-vascular disease by CT

    International Nuclear Information System (INIS)

    Huber, G.; Emde, H.

    1980-01-01

    Brain scanning by scintigraphy and CT studies of the brain are complementary methods. The precise demonstration of the anatomy and the pathology of the brain by CT is supplemented by brain scintigraphy due to the latter's value to assess the hemodynamic properties of a lesion and thus provide important clues to its site and sometimes even its histology. This is especially true in vascular brain disease thus either dispensing the need for an invasive procedure such as angiography or providing information for a specific approach. (orig.) 891 MG/orig. 892 MKO [de

  10. Estimates of the Hyperbolic Radius Gradient and Schwarz–Pick Inequalities for the Eccentric Annulus

    Directory of Open Access Journals (Sweden)

    D.Kh. Giniyatova

    2016-06-01

    Full Text Available Let Ω and Π be hyperbolic domains in the complex plane C. By A(Ω, Π we shall designate the class of functions f which are holomorphic or meromorphic in Ω and such that f(Ω ϲ Π. Estimates of the higher derivatives |f(n(z| of the analytic functions from the class A(Ω, Π with the punishing factor Cn(Ω, Π is one of the main problems of geometric theory of functions. These estimates are commonly referred to as Schwarz–Pick inequalities. Many results concerning this problem have been obtained for simply connected domains. Therefore, the research interest in such problems for finitely connected domains is natural. As known, the constant C2(Ω, Π for any pairs of hyperbolic domains depends only on the hyperbolic radius gradient of the corresponding domains. The main result of this paper is estimates of the hyperbolic radius gradient and the punishing factor in the Schwarz–Pick inequality for the eccentric annulus. We also consider the extreme case – the randomly punctured circle.

  11. An assessment of the waterside corrosion and hydrogen pick-up in the zircaloy-2 pressure tubes of PHWR

    International Nuclear Information System (INIS)

    Sah, D.N.

    1992-01-01

    In view of the deleterious effect of hydriding on the operating life of zircaloy-2 pressure tubes in PHWRs there is an urgent need for the assessment of the status of the pressure tubes with respect to corrosion and hydrogen pick-up in the operating PHWRs. A model has been developed for analysing the waterside corrosion and hydrogen pick-up in the zircaloy-2 pressure tubes under reactor operating conditions. This model predicts the axial profiles of oxide layer thickness and hydrogen pick-up in the pressure tubes as a function of the operating time of the reactor. The prediction of hydrogen pick-up by the model in the F-10 pressure tube of RAPS-I have been found to be in good agreement with the measured value of hydrogen content. This report gives a brief description of the model and its predictions on the present status of hydrogen pick-up in the pressure tubes of lead reactor RAPS-II. (author). 6 refs., 5 figs., 2 tabs

  12. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  13. Performance of diamond and point attack coal cutter picks

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y. [CSIRO, Brisbane, Qld. (Australia). Division of Exploration and Mining

    1996-12-31

    This paper presents results of laboratory experiments and field trials of PDC (Polycrystalline Diamond Compact) and PA (Point Attack) coal cutter picks. Laboratory cutting tests included linear rock and coal cutting and turning rock cutting. The following parameters were measured to assess performance of PDC and PA cutter picks: cutting force, normal force, specific energy consumption, yield, dust generation and ignitional characteristics (temperature rise). Field trials were conducted on a longwall shearer. Performance of both types of pick interims of pick life and dust generation were assessed. 3 refs., 18 figs., 3 tabs.

  14. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  15. Factor Structure, Validity and Reliability of the Revised Version of Skin Picking Scale

    Directory of Open Access Journals (Sweden)

    Mehdi Rabiei

    2014-09-01

    Full Text Available Background: The purpose of this study was to examine the factor structure, validity and reliability of the Skin Picking Scale-Revised Version. Materials and Methods: In this descriptive and validation study, participants were 550 (250 male and 300 female of the University of Isfahan were selected randomly from 15000 students. In order to examine the factor structure of the SPS-R we conducted both exploratory and confirmatory factor analyses and Cronbach's alpha. Results: Convergent validity of SPS-R with YBOCS-BDD, OCI-R and DASS 21-item were r=0.45, r=0.51 and r=0.70 (p<0.001. Exploratory and confirmatory factor analyses revealed two factors, one assessing impairment and the other symptom severity (4 items each. These factors could determine 58.1% of the variance. The Cronbach's alpha for the two factors were above 0.88. Also, results were shown to possess good psychometric properties, as well as discriminant validity and classification accuracy, in both clinical and community populations. Conclusion: It can be concluded that this instrument is a useful measure for assess skin-picking disorder symptoms in clinical assessment.

  16. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

    Science.gov (United States)

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

    2017-04-01

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

  17. CT evaluation of cystic brain disease

    International Nuclear Information System (INIS)

    Kim, Joon Woo; Lee, Jin Woo; Joo, Yang Goo; Kim, Hong; Zeon, Seok Kil; Suh, Soo Jhi

    1987-01-01

    We retrospectively analysed CT findings of 47 cystic brain lesions of 44 patients, in which operation, biopsy or follow-up study was needed for their final diagnosis. The results were as follows: 1. The etiologic diseases of cystic brain lesions were 15 cases of brain abscess, 9 cases of astrocytoma, 5 cases of glioblastoma multiforme, 3 cases of meningioma, 5 cases of craniopharyngioma, 1 case of hemangioblastoma, 2 cases of dermoid cyst and 4 cases of metastasis. 2. We analyses the cystic lesions in view of their number, location, shape, perifocal edema, mass effect, wall and its thickness, evenness and characteristics of their inner and outer surfaces, mural nodule, calcification and contrast enhancement. a. 13.3% of brain abscess and 75% of metastases were multiple in number, but the remainder showed single lesion. b. The shape of cystic lesions were round or ovoid in 68%, lobulated in 8.5% and irregular in 23.5%, and no demonstrable difference of shape were noticed in different disease. c. In brain abscess, the wall of cystic lesions tend to be thin, even and smooth in inner surface, but the outer surfaces were equally smooth or irregular. d. Mural nodules were found in nearly half of the cases of astrocytoma, glioblastoma multiforme, metastasis and hemangioblastoma, but the brain abscess and dermoid cyst contained no mural nodule. e. Meningiomas were found to be attached to dura mater and showed thickening of the inner table of adjacent skull or of the falx. f. The presence of preceding infectious disease may be helpful in the diagnosis of brain abscess, but in 20% there were no demonstrable preceding infection. g. Lung cancer was confirmed as primary site in two of the cystic metastatic disease, but other 2 cases showed no demonstrable primary malignancy

  18. CT evaluation of cystic brain disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joon Woo; Lee, Jin Woo; Joo, Yang Goo; Kim, Hong; Zeon, Seok Kil; Suh, Soo Jhi [Keimyung University, School of Medicine, Daegu (Korea, Republic of)

    1987-10-15

    We retrospectively analysed CT findings of 47 cystic brain lesions of 44 patients, in which operation, biopsy or follow-up study was needed for their final diagnosis. The results were as follows: 1. The etiologic diseases of cystic brain lesions were 15 cases of brain abscess, 9 cases of astrocytoma, 5 cases of glioblastoma multiforme, 3 cases of meningioma, 5 cases of craniopharyngioma, 1 case of hemangioblastoma, 2 cases of dermoid cyst and 4 cases of metastasis. 2. We analyses the cystic lesions in view of their number, location, shape, perifocal edema, mass effect, wall and its thickness, evenness and characteristics of their inner and outer surfaces, mural nodule, calcification and contrast enhancement. a. 13.3% of brain abscess and 75% of metastases were multiple in number, but the remainder showed single lesion. b. The shape of cystic lesions were round or ovoid in 68%, lobulated in 8.5% and irregular in 23.5%, and no demonstrable difference of shape were noticed in different disease. c. In brain abscess, the wall of cystic lesions tend to be thin, even and smooth in inner surface, but the outer surfaces were equally smooth or irregular. d. Mural nodules were found in nearly half of the cases of astrocytoma, glioblastoma multiforme, metastasis and hemangioblastoma, but the brain abscess and dermoid cyst contained no mural nodule. e. Meningiomas were found to be attached to dura mater and showed thickening of the inner table of adjacent skull or of the falx. f. The presence of preceding infectious disease may be helpful in the diagnosis of brain abscess, but in 20% there were no demonstrable preceding infection. g. Lung cancer was confirmed as primary site in two of the cystic metastatic disease, but other 2 cases showed no demonstrable primary malignancy.

  19. A theoretical model for predicting the Peak Cutting Force of conical picks

    Directory of Open Access Journals (Sweden)

    Gao Kuidong

    2014-01-01

    Full Text Available In order to predict the PCF (Peak Cutting Force of conical pick in rock cutting process, a theoretical model is established based on elastic fracture mechanics theory. The vertical fracture model of rock cutting fragment is also established based on the maximum tensile criterion. The relation between vertical fracture angle and associated parameters (cutting parameter  and ratio B of rock compressive strength to tensile strength is obtained by numerical analysis method and polynomial regression method, and the correctness of rock vertical fracture model is verified through experiments. Linear regression coefficient between the PCF of prediction and experiments is 0.81, and significance level less than 0.05 shows that the model for predicting the PCF is correct and reliable. A comparative analysis between the PCF obtained from this model and Evans model reveals that the result of this prediction model is more reliable and accurate. The results of this work could provide some guidance for studying the rock cutting theory of conical pick and designing the cutting mechanism.

  20. Spotting Fruit versus Picking Fruit as the Selective Advantage of Human Colour Vision

    Directory of Open Access Journals (Sweden)

    Aline Bompas

    2013-04-01

    Full Text Available The spatiochromatic properties of the red–green dimension of human colour vision appear to be optimized for picking fruit in leaves at about arms' reach. However, other evidence suggests that the task of spotting fruit from a distance might be more important. This discrepancy may arise because the task a system (e.g. human trichromacy is best at is not necessarily the same task where the largest advantage occurs over the evolutionary alternatives (dichromacy or anomalous trichromacy. We tested human dichromats, anomalous trichromats and “normal” trichromats in a naturalistic visual search task in which they had to find fruit pieces in a bush at 1, 4, 8 or 12 m viewing distance. We found that the largest advantage (in terms of either performance ratio or performance difference of normal trichromacy over both types of colour deficiency was for the largest viewing distance. We infer that in the evolution of human colour vision, spotting fruit from a distance was a more important selective advantage than picking fruit at arms' reach.

  1. Fifteen Minutes of Fame? The Market Impact of Internet Stock Picks

    OpenAIRE

    Peter Antunovich; Asani Sarkar

    2006-01-01

    We examine 120 Nasdaq and Over-the-Counter "buy" recommendations made by Internet sites from April 1999 to June 2001. The stock picks show substantial short- and long-run price and liquidity gains, although no new information is revealed about them. For example, liquidity one year after the pick day remains higher for these stocks than for a sample matched according to size, book-to-market value, and liquidity in the preceding year. In addition, after controlling for fundamental and microstru...

  2. Performance approximation of pick-to-belt orderpicking systems

    NARCIS (Netherlands)

    M.B.M. de Koster (René)

    1994-01-01

    textabstractIn this paper, an approximation method is discussed for the analysis of pick-to-belt orderpicking systems. The aim of the approximation method is to provide an instrument for obtaining rapid insight in the performance of designs of pick-to-belt orderpicking systems. It can be used to

  3. Analysis of Pick-Up Development in Punching

    DEFF Research Database (Denmark)

    Olsson, David Dam; Bay, Niels; Andreasen, Jan Lasson

    2002-01-01

    The development of pick-up of work piece material on the punch surface with increasing number of strokes during punching of stainless steel sheet is investigated applying Scanning Electron Microscopy (SEM), 3D roughness mapping and measurements of the backstroke force. It is found that pick...

  4. On the Stability of Pick-up Ion Ring Distributions in the Outer Heliosheath

    Science.gov (United States)

    Summerlin, Errol J.; Viñas, Adolfo F.; Moore, Thomas E.; Christian, Eric R.; Cooper, John F.

    2014-10-01

    The "secondary energetic neutral atom (ENA)" hypothesis for the ribbon feature observed by the Interstellar Boundary Explorer (IBEX) posits that the neutral component of the solar wind continues beyond the heliopause and charge exchanges with interstellar ions in the Outer Heliosheath (OHS). This creates pick-up ions that gyrate about the draped interstellar magnetic field (ISMF) lines at pitch angles near 90° on the locus where the ISMF lies tangential to the heliopause and perpendicular to the heliocentric radial direction. This location closely coincides with the location of the ribbon feature according to the prevailing inferences of the ISMF orientation and draping. The locally gyrating ions undergo additional charge exchange and escape as free-flying neutral atoms, many of which travel back toward the inner solar system and are imaged by IBEX as a ribbon tracing out the locus described above. For this mechanism to succeed, the pick-up ions must diffuse in pitch angle slowly enough to permit secondary charge exchange before their pitch angle distribution substantially broadens away from 90°. Previous work using linear Vlasov dispersion analysis of parallel propagating waves has suggested that the ring distribution in the OHS is highly unstable, which, if true, would make the secondary ENA hypothesis incapable of rendering the observed ribbon. In this paper, we extend this earlier work to more realistic ring distribution functions. We find that, at the low densities necessary to produce the observed IBEX ribbon via the secondary ENA hypothesis, growth rates are highly sensitive to the temperature of the beam and that even very modest temperatures of the ring beam corresponding to beam widths of distributions necessary to produce the observed IBEX ENA flux via the secondary ENA hypothesis will be unstable to their own self-generated turbulence.

  5. The gift in interaction: a study of 'picking-up the bill'.

    Science.gov (United States)

    Llewellyn, Nick

    2011-12-01

    This paper analyses the phenomenon of 'picking up the bill', thereby contributing to a resurgence of sociological interest in gift exchange. Drawing on ethnomethodology, it describes and locates a distinctive theoretical approach. Utilizing video recordings, the analysis considers the interactional constitution of gifts and how gift exchange is locally invoked via the norm of reciprocity. Recurrent practices are described, through which gifts are brought into being, with reciprocity invoked, by benefactor and beneficiary alike, to manage social problems of acceptance, rather than to sanction insufficient contributions. The study describes the social character of what are perhaps the preeminent gifts exchanged in modern societies; where one person pays for another's consumption. © London School of Economics and Political Science 2011.

  6. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    Science.gov (United States)

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

  7. Determining stress fields of shearer-loader picks

    Energy Technology Data Exchange (ETDEWEB)

    Luszczkiewicz, J; Sikora, W

    1987-06-01

    Analyzes factors which influence stress distribution in the NK-4 shearer-loader picks during coal cutting. The AFT optically active cover, 0.0015 mm thick, was used. The pick with the AFT cover was loaded using a force of 33 kN. Isoclinic lines showing stress distribution were photographed. Effects of pick design and its holder type on stress distribution were investigated. Investigations showed that distribution of normal stresses in a pick shaft has a non-linear character. The hole in a pick shaft increased stress concentration in that shaft section. Eliminating the hole reduced stress concentration. Reducing shaft length by about 20 mm did not increase stresses in that shaft zone. 15 refs.

  8. Possible improvements in the bubble model description of positronium pick-off annihilation in liquids

    International Nuclear Information System (INIS)

    Beling, C.D.; Smith, F.A.

    1980-01-01

    The universal applicability of the bubble model is examined and attention is drawn to a number of situations in which it is inadequate. Some possible areas of improvements are considered. The effects of van der Waals forces on the bubble radius are estimated to be insignificant, but the problem of the potential well depth and shape is more intractable. We find that when a linear combination of finite potential components is used, the Ps pressure can become independent of well depth when the infinite component becomes large, as may be the case in certain liquids. We have developed the idea of Tao on the description of the wavefunction overlap occurring in a thin skin in the inside of the bubble surface. By considering the contribution from the protrusion of hydrogen atoms from a hard core bubble surface, we calculate that the pick-off rate can be significantly altered. (orig.)

  9. Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry.

    Science.gov (United States)

    Bonnot, Olivier; Gama, Clarissa S; Mengel, Eugen; Pineda, Mercè; Vanier, Marie T; Watson, Louise; Watissée, Marie; Schwierin, Barbara; Patterson, Marc C

    2017-10-09

    Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease that should be recognised by psychiatrists as a possible underlying cause of psychiatric abnormalities. This study describes NP-C patients who had psychiatric manifestations at enrolment in the international NPC Registry, a unique multicentre, prospective, observational disease registry. Treating physicians' data entries describing psychiatric manifestations in NPC patients were coded and grouped by expert psychiatrists. Out of 386 NP-C patients included in the registry as of October 2015, psychiatric abnormalities were reported to be present in 34% (94/280) of those with available data. Forty-four patients were confirmed to have identifiable psychiatric manifestations, with text describing these psychiatric manifestations. In these 44 patients, the median (range) age at onset of psychiatric manifestations was 17.9 years (2.5-67.9; n = 15), while the median (range) age at NP-C diagnosis was 23.7 years (0.2-69.8; n = 34). Almost all patients (43/44; 98%) had an occurrence of ≥1 neurological manifestation at enrolment. These data show that substantial delays in diagnosis of NP-C are long among patients with psychiatric symptoms and, moreover, patients presenting with psychiatric features and at least one of cognitive impairment, neurological manifestations, and/or visceral symptoms should be screened for NP-C.

  10. Heliospheric pick-up ions influencing thermodynamics and dynamics of the distant solar wind

    Directory of Open Access Journals (Sweden)

    H. J. Fahr

    2002-01-01

    Full Text Available Neutral interstellar H-atoms penetrate into the inner heliosphere and upon the event of ionization are converted into pick-up ions (PUIs. The magnetized solar wind flow incorporates these ions into the plasma bulk and enforces their co-motion. By nonlinear interactions with wind-entrained Alfvén waves, these ions are then processed in the comoving velocity space. The complete pick-up process is connected with forces acting back to the original solar wind ion flow, thereby decelerating and heating the solar wind plasma. As we show here, the resulting deceleration cannot be treated as a pure loading effect, but requires adequate consideration of the action of the pressure of PUI-scattered waves operating by the PUI pressure gradient. Hereby, it is important to take into proper account the stochastic acceleration which PUIs suffer from at their convection out of the inner heliosphere by quasi-linear interactions with MHD turbulences. Only then can the presently reported VOYAGER observations of solar wind decelerations and heatings in the outer heliosphere be understood in view of the most likely values of interstellar gas parameters, such as an H-atom density of 0.12 cm-3 . Solar wind protons (SWPs appear to be globally heated in their motion to larger solar distances. Ascribing the needed heat transfer to the action of suprathermal PUIs, which drive MHD waves that are partly absorbed by SWPs, in order to establish the observed SWP polytropy, we can obtain a quantitative expression for the solar wind proton pressure as a function of solar distance. This expression clearly shows the change from an adiabatic to a quasi-polytropic SWP behaviour with a decreasing polytropic index at increasing distances. This also allows one to calculate the average percentage of initial pick-up energy fed into the thermal proton energy. In a first order evaluation of this expression, we can estimate that about 10% of the initial PUI injection energy is eventually

  11. The Quality of Rambak Cracker from Rabbit Skin (Water Content and Swelling Power using The Different Technique of Fur Picking

    Directory of Open Access Journals (Sweden)

    Dedes Amertaningtyas

    2014-11-01

    Full Text Available This objective of this researchwas to compare the different technique of fur picking (liming and boiling inthe quality rambak cracker from rabbit skin on water content and swelling power.Materials of this research were 20 drying rabbit skin 5 – 6 months old. The tTest was using to compare the different technique of fur picking. Theindependent variables of this research were water content and swelling power onrambak cracker from rabbit skin. The result showed that the different techniqueof fur picking had highly significant effect (P<0.01 on water content and  expanding rate. The best result was limingtechnique of fur picking. It had the following properties: Water content of 1.5922% and expending rate of 855.3798 %. The conclusion showed that the use limingof 4% produced high quality of rambak cracker from rabbit skin or anotheranimal skin (cow, buffalo, chicken or fish. Keywords: rambak cracker, rabbit skin, water content,expanding rate

  12. Proposal of an efficient operation method about order processing sequence and allocating goods to racks in the automatic picking system; Jido picking system ni okeru shohin no tanawaritsuke to chumon shori junjo no koritsuka un`yo hoshiki no teian

    Energy Technology Data Exchange (ETDEWEB)

    Ono, T.; Kagami, A.; Kosaka, M. [Hitachi Ltd., Tokyo (Japan)

    1997-07-05

    The material distribution center is a facility to store the goods from a factory and to prepare to ship the goods in response to order from retail store. Recently, with multiplication of consumption market, multi-variety and less-amount of the goods, multi-frequency of delivery and time saving form order to delivery are required. As picking work to prepare the stored goods for each customer requires specially many man-hours out of the works in this center, time saving of working becomes an important problem. In this paper, for an object of the automatic picking system constructed by plural equipments and to execute picking of small goods for each order, the following two operation methods were proposed: (1) To define shelf sharing of the goods so that the picking requirement numbers for each picking hand may be uniform as well as possible in response to order distribution for each goods, and (2) to define treating sequence of order so as not to generate large difference in order treating times among each treating hand on operation in parallel. These operation methods were confirmed their total treating time saving by some experiments using actual ordered data. 7 refs., 8 figs., 6 tabs.

  13. Niemann-Pick disease Type C - Sea-blue histiocytosis: Phenotypic and imaging observations and mini review

    Directory of Open Access Journals (Sweden)

    Praveen K

    2007-01-01

    Full Text Available We present a report on an 18-year-old boy with Niemann-Pick disease Type C (NP-C who presented with progressive decline in scholastic performance since 9 years of age. At 12 years, he developed abnormal behavior and after 2 years had insidious onset, progressive gait ataxia and dysarthria followed by dystonia of the right upper extremity, excessive drooling, dysphagia and nasal regurgitation. He had coarse facies, depressed nasal bridge, high arched palate, crowded teeth, splenomegaly and peculiar facial grin. In addition, impaired vertical saccadic and pursuit eye movements, brisk muscle stretch reflexes and limb and gait ataxia were observed. He had a low IQ of 47 on Binet-Kamat test. The ultrasound examination of the abdomen confirmed the presence of moderate splenomegaly. Magnetic resonance imaging brain showed symmetrical leucoencephalopathy and mild cerebellar atrophy. Bone marrow aspiration showed numerous foamy macrophages and sea-blue histiocytes suggesting the diagnosis of NP-C.

  14. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    Science.gov (United States)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  15. Analysis of the Impact of Storage Parameters and the Size of Orders on the Choice of the Method for Routing Order Picking

    Directory of Open Access Journals (Sweden)

    Grzegorz Tarczyński

    2012-01-01

    Full Text Available The paper presents an analysis of the impact of the number of picking aisles, slots in a rack, the size of pick lists, and the routing method on the performance of the order picking process. In the analysis, the forklift truck's maneuvers such as turns back and turns aside, omitted by some scientists, are considered. Although only random storage assignment is examined in this paper, the possible congestion effect is considered. Experiments were performed by the use of simulations. (original abstract

  16. On the stability of pick-up ion ring distributions in the outer heliosheath

    International Nuclear Information System (INIS)

    Summerlin, Errol J.; Viñas, Adolfo F.; Moore, Thomas E.; Christian, Eric R.; Cooper, John F.

    2014-01-01

    The 'secondary energetic neutral atom (ENA)' hypothesis for the ribbon feature observed by the Interstellar Boundary Explorer (IBEX) posits that the neutral component of the solar wind continues beyond the heliopause and charge exchanges with interstellar ions in the Outer Heliosheath (OHS). This creates pick-up ions that gyrate about the draped interstellar magnetic field (ISMF) lines at pitch angles near 90° on the locus where the ISMF lies tangential to the heliopause and perpendicular to the heliocentric radial direction. This location closely coincides with the location of the ribbon feature according to the prevailing inferences of the ISMF orientation and draping. The locally gyrating ions undergo additional charge exchange and escape as free-flying neutral atoms, many of which travel back toward the inner solar system and are imaged by IBEX as a ribbon tracing out the locus described above. For this mechanism to succeed, the pick-up ions must diffuse in pitch angle slowly enough to permit secondary charge exchange before their pitch angle distribution substantially broadens away from 90°. Previous work using linear Vlasov dispersion analysis of parallel propagating waves has suggested that the ring distribution in the OHS is highly unstable, which, if true, would make the secondary ENA hypothesis incapable of rendering the observed ribbon. In this paper, we extend this earlier work to more realistic ring distribution functions. We find that, at the low densities necessary to produce the observed IBEX ribbon via the secondary ENA hypothesis, growth rates are highly sensitive to the temperature of the beam and that even very modest temperatures of the ring beam corresponding to beam widths of <1° are sufficient to damp the self-generated waves associated with the ring beam. Thus, at least from the perspective of linear Vlasov dispersion analysis of parallel propagating waves, there is no reason to expect that the ring distributions necessary to

  17. Adult Niemann-Pick disease type B with myositis ossificans: a case report

    Directory of Open Access Journals (Sweden)

    Russka Shumnalieva

    2016-07-01

    Full Text Available Niemann-Pick Disease (NPD is a rare autosomal recessive lysosomal lipid storage disorder. The disease is caused by gene mutations that affect the metabolism of sphingolipids. The dysfunctions cause sphingomyelin to accumulate in different organs. NPD includes forms with low and high levels of sphingomyelin. We report a case of a 34 year-old man with a family history of NPD type B who presented with hepatosplenomegaly, neurological deficiency, bone abnormalities, and myositis ossificans. The clinical, biochemical, and imaging data confirmed the combined diagnosis of NPD type B with myositis ossificans.

  18. Nanoparticle technology for treatment of Parkinson's disease: the role of surface phenomena in reaching the brain.

    Science.gov (United States)

    Leyva-Gómez, Gerardo; Cortés, Hernán; Magaña, Jonathan J; Leyva-García, Norberto; Quintanar-Guerrero, David; Florán, Benjamín

    2015-07-01

    The absence of a definitive treatment for Parkinson's disease has driven the emerging investigation in the search for novel therapeutic alternatives. At present, the formulation of different drugs on nanoparticles has represented several advantages over conventional treatments. This type of multifunctional carrier, owing to its size and composition, has different interactions in biological systems that can lead to a decrease in ability to cross the blood-brain barrier. Therefore, this review focuses on the latest advances in obtaining nanoparticles for Parkinson's disease and provides an overview of technical aspects in the design of brain drug delivery of nanoparticles and an analysis of surface phenomena, a key aspect in the development of functional nanoparticles for Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Features of brain atrophy in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, I; Melamed, E; Gomori, J M

    1985-03-01

    Multiple parameters for brain volume and mass were studied in 85 parkinsonian patients and in 149 normal controls aged 24 to 89 using CT scanning. In controls there was reduction in brain substance with advancing age. Increased brain atrophy in patients with Parkinson's disease (PD) was mainly observed in the younger age group of 24 to 49. This included parameters evaluating the size of the lateral and third ventricles and the size of the subarachnoid space in the frontal interhemispheric and Sylvian fissures. With computed canonical correlation analysis a formula was obtained which expressed the tendency of the atrophic process in PD to involve the areas surrounding the third ventricle and the mesial aspect of the frontal lobes more than during normal aging.

  20. Brain metastasis from melanoma: the prognostic value of varying sites of extracranial disease.

    Science.gov (United States)

    Bates, James E; Youn, Paul; Usuki, Kenneth Y; Walter, Kevin A; Huggins, Christine F; Okunieff, Paul; Milano, Michael T

    2015-11-01

    Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis-generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis.

  1. Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, S. [Tokyo Univ. (Japan). Faculty of Medicine; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

    1996-12-31

    To investigate the cause of Alzheimer`s disease (senile dementia of Alzheimer`s disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer`s disease using heavy ion (5 MeV Si{sup 3+}) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si{sup 2+}) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer`s disease using 5 MeV Si{sup 3+} microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer`s disease is caused by accumulation of Al in the nuclei of brain cells. (author)

  2. The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats

    OpenAIRE

    Chen, Yuan; Lian, Yajun; Ma, Yunqing; Wu, Chuanjie; Zheng, Yake; Xie, Nanchang

    2017-01-01

    The expression and significance of tyrosine hydroxylase (TH) in brain tissue of rats with Parkinson's disease (PD) were explored and analyzed. A total of 120 clean-grade and healthy adult Wistar rats weighing 180–240 g were randomly divided equally into four groups according to the random number table method. Rats were sacrificed before and after the model establishment for 3, 6 or 8 weeks. The number of revolutions in rats was observed and the relative expression of TH mRNA in brain tissue w...

  3. An improved contour symmetry axes extraction algorithm and its application in the location of picking points of apples

    Energy Technology Data Exchange (ETDEWEB)

    Wang, D.; Song, H.; Yu, X.; Zhang, W.; Qu, W.; Xu, Y.

    2015-07-01

    The key problem for picking robots is to locate the picking points of fruit. A method based on the moment of inertia and symmetry of apples is proposed in this paper to locate the picking points of apples. Image pre-processing procedures, which are crucial to improving the accuracy of the location, were carried out to remove noise and smooth the edges of apples. The moment of inertia method has the disadvantage of high computational complexity, which should be solved, so convex hull was used to improve this problem. To verify the validity of this algorithm, a test was conducted using four types of apple images containing 107 apple targets. These images were single and unblocked apple images, single and blocked apple images, images containing adjacent apples, and apples in panoramas. The root mean square error values of these four types of apple images were 6.3, 15.0, 21.6 and 18.4, respectively, and the average location errors were 4.9°, 10.2°, 16.3° and 13.8°, respectively. Furthermore, the improved algorithm was effective in terms of average runtime, with 3.7 ms and 9.2 ms for single and unblocked and single and blocked apple images, respectively. For the other two types of apple images, the runtime was determined by the number of apples and blocked apples contained in the images. The results showed that the improved algorithm could extract symmetry axes and locate the picking points of apples more efficiently. In conclusion, the improved algorithm is feasible for extracting symmetry axes and locating the picking points of apples. (Author)

  4. Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study.

    Science.gov (United States)

    Battisti, Carla; Tarugi, Patrizla; Dotti, Maria Teresa; De Stefano, Nicola; Vattimo, Angelo; Chierichetti, Francesea; Calandra, Sebastiano; Federico, Antonio

    2003-11-01

    We report on a patient with adult-onset Niemann-Pick type C (NPC) disease, carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked psychiatric changes followed by dystonia and cognitive impairment. Filipin staining, single photon emission computed tomography perfusional, positron emission tomography metabolic, conventional magnetic resonance imaging, and magnetic resonance spectroscopy findings suggested a pathophysiological correlation with phenotype expression. This case expands the clinical and genetic spectrum of the rare adult-onset NPC disease phenotype.

  5. Automatic first-break picking using the instantaneous traveltime attribute

    KAUST Repository

    Saragiotis, Christos

    2012-01-01

    Picking the first breaks is an important step in seismic processing. The large volume of the seismic data calls for automatic and objective picking. We introduce a new automatic first-break picker, which uses specifically designed time windows and an iterative procedure based on the instantaneous traveltime attribute. The method is fast as it only uses a few FFT\\'s per trace. We demonstrate the effectiveness of this automatic method by applying it on real test data.

  6. Multimodal neuroimaging of male and female brain structure in health and disease across the life span.

    Science.gov (United States)

    Jahanshad, Neda; Thompson, Paul M

    2017-01-02

    Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large-scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex-related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  7. Factors affecting the outcome of in vitro bovine embryo production using ovum pick-up-derived cumulus oocyte complexes

    NARCIS (Netherlands)

    Merton, J.S.

    2013-01-01

    Optimization of bovine ovum pick up (OPU) followed by in vitro embryo production (IVP) has been driven by the desire of both beef and dairy cattle breeders to enhance genetic improvement. The work presented in this thesis focuses on optimizing the efficiency and efficacy of the OPU-IVP program.

  8. Assignment of stock keeping units to parallel undirectional picking

    Directory of Open Access Journals (Sweden)

    Matthews, Jason

    2015-05-01

    Full Text Available An order picking system consisting of a number of parallel unidirectional picking lines is investigated. Stock keeping units (SKUs that are grouped by product type into distributions (DBNs are assigned daily to available picking lines. A mathematical programming formulation and its relaxations is presented. A greedy insertion and a greedy phased insertion are further introduced to obtain feasible results within usable computation times for all test cases. The walking distance of the pickers was shown to decrease by about 22 per cent compared with the current assignment approach. However, product handling and operational risk increases.

  9. Automatic picking of the first arrival event using the unwrapped-phase of the Fourier transformed wavefield

    KAUST Repository

    Choi, Yun Seok

    2011-01-01

    First-arrival picking has long suffered from cycle skipping, especially when the first arrival is contaminated with noise or have experienced complex near surface phenomena. We propose a new algorithm for automatic picking of first arrivals using an approach based on unwrapping the phase. We unwrap the phase by taking the derivative of the Fourier-transformed wavefield with respect to the angular frequency and isolate its amplitude component. To do so, we first apply a damping function to the seismic trace, calculate the derivative of the wavefield with respect to the angular frequency, divide the derivative of wavefield by the wavefield itself, and finally take its imaginary part. We compare our derivative approach to the logarithmic one and show that the derivative approach does not suffer from the phase wrapping or cycle-skipping effects. Numerical examples show that our automatic picking algorithm gives convergent and reliable results for the noise-free synthetic data and noisy field data. © 2011 Society of Exploration Geophysicists.

  10. An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

    Science.gov (United States)

    Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

    2018-05-15

    BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. A study of 99mTc-HM-PAO brain SPECT in the senile parkinson's disease

    International Nuclear Information System (INIS)

    Chen Wenxin; Lin Xiangtong; Song Wenzhong; Liu Yongchang

    1996-01-01

    Thirty-three cases of senile Parkinson's disease (PD) imaged by 99m Tc-HM-PAO brain SPECT were reported. 66.7% of the patients had cortical hypoperfusion and 18.2% showed asymmetrical hypoperfusion in the basal ganglia. Such a finding was not related with the Hoehn-Yahr stage and the laterality of motor symptoms. If complicated with dementia, the SPECT brain imaging showed similar pattern in Alzheimer's disease with diffuse hypoperfusion in cortical area reflecting widespread pathological changes in tremor paralysis

  12. Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy.

    Science.gov (United States)

    Manix, Marc; Kalakoti, Piyush; Henry, Miriam; Thakur, Jai; Menger, Richard; Guthikonda, Bharat; Nanda, Anil

    2015-11-01

    Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis-the gold standard for definitive diagnosis is considered to be histopathological confirmation-but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Imaging studies, electroencephalography, and biomarkers are used in conjunction with the clinical picture to try to make the diagnosis of CJD without brain tissue samples, and all of these are reviewed in this article. The current diagnostic criteria are limited; test sensitivity and specificity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. The authors review CJD, discuss the role of brain biopsy in this patient population, provide a diagnostic pathway for the patient presenting with rapidly progressive dementia, and propose newer diagnostic criteria.

  13. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  14. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway [version 2; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Paul Fineran

    2017-06-01

    Full Text Available Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC, a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC.  Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed.  Results. Macrophages infected with intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in

  15. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Paul Fineran

    2016-11-01

    Full Text Available Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC, a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Results. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were

  16. 3.3 Å structure of Niemann–Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaochun; Lu, Feiran; Trinh, Michael N.; Schmiege, Philip; Seemann, Joachim; Wang, Jiawei; Blobel, Günter

    2017-08-07

    Niemann–Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann–Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its C-terminal luminal domain (CTD) remains poorly understood even though 45% of NPC disease-causing mutations are in this domain. Here, we report a crystal structure at 3.3 Å resolution of NPC1* (residues 314–1,278), which—in contrast to previous lower resolution structures—features the entire CTD well resolved. Notably, all eight cysteines of the CTD form four disulfide bonds, one of which (C909–C914) enforces a specific loop that in turn mediates an interaction with a loop of the N-terminal domain (NTD). Importantly, this loop and its interaction with the NTD were not observed in any previous structures due to the lower resolution. Our mutagenesis experiments highlight the physiological relevance of the CTD–NTD interaction, which might function to keep the NTD in the proper orientation for receiving cholesterol from NPC2. Additionally, this structure allows us to more precisely map all of the disease-causing mutations, allowing future molecular insights into the pathogenesis of NPC disease.

  17. [The brain and cytokines - the mutual origin of depression, obesity and cardiovascular diseases?].

    Science.gov (United States)

    Ufnal, Marcin; Wolynczyk-Gmaj, Dorota

    2011-04-19

    Accumulating evidence points to a pivotal role of the brain in the regulation of the circulatory system and energy balance. It has also been found that common civilization diseases such as depression, obesity, hypertension, myocardial infarction or heart failure are accompanied by an increase in concentration of inflammatory mediators in the blood, cerebrospinal fluid and various tissues. Recent studies have revealed that inflammatory mediators that are synthesized peripherally or in the brain may affect the nervous regulation of animal body systems. For example, it has been found that non-specific pro-inflammatory stimuli as well as treatment with several cytokines may cause depressive behavior, disturbances in energy balance and alterations in the circulatory system. On the other hand, knockout of genes for pro-inflammatory cytokines or administration of anti-inflammatory mediators may normalize the pathological changes. In the present manuscript we will review studies that imply the common neuroinflammatory pathogenesis of cardiovascular diseases, depression and energy balance disorders.

  18. Normative values and the effects of age, gender, and handedness on the Moberg Pick-Up Test.

    Science.gov (United States)

    Amirjani, Nasim; Ashworth, Nigel L; Gordon, Tessa; Edwards, David C; Chan, K Ming

    2007-06-01

    The Moberg Pick-Up Test is a standardized test for assessing hand dexterity. Although reduction of sensation in the hand occurs with aging, the effect of age on a subject's performance of the Moberg Pick-Up Test has not been examined. The primary goal of this study was to examine the impact of aging and, secondarily, the impact of gender and handedness, on performance of the Moberg Pick-Up Test in 116 healthy subjects. The average time to complete each of the four subsets of the test was analyzed using the Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. The results show that hand dexterity of the subjects was significantly affected by age, with young subjects being the fastest and elderly subjects the slowest. Women accomplished the test faster than men, and task performance with the dominant hand was faster than with the non-dominant hand. Use of normative values established based on age and gender is a valuable objective tool to gauge hand function in patients with different neurologic disorders.

  19. Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

    Science.gov (United States)

    Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

    2018-01-01

    Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

  20. Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain

    NARCIS (Netherlands)

    Ishunina, Tatjana A.; Swaab, Dick F.

    2012-01-01

    In this study we identified 62 estrogen receptor alpha (ERα) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively

  1. The role of melatonin on brain iron homeostasis and its relation to Parkinson’s Disease

    OpenAIRE

    Lai, Hien Tet

    2017-01-01

    Parkinson’s Disease (PD) is the second most common neurological disorder after Alzheimer’s Disease. The disease will manifest with the loss of up to 70% of the dopaminergic neurons in the Substantia Nigra (SN) region and it mainly affects the elderly. One of the common pathological hallmarks for PD is the excessive iron accumulation within the SN region of the brain. However, the pathogenesis for of the excessive iron levels accumulation in the SN is unclear. The increase in intracellular oxi...

  2. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease

    NARCIS (Netherlands)

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling; Brown, Peter

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been

  3. Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Feldt-Rasmussen, Ulla; Granqvist, Henrik

    2015-01-01

    tomography (PET) and magnetic resonance imaging (MRI). PATIENTS: Forty patients with Fabry disease (14 males, 26 females, age at inclusion: 10-66 years, median: 39 years) underwent a brain F-18-FDG-PET-scan at inclusion, and 31 patients were followed with FDG-PET biannually for up to seven years. All...... patients (except one) had a brain MRI-scan at inclusion, and 34 patients were followed with MRI biannually for up to nine years. IMAGE ANALYSIS: The FDG-PET-images were inspected visually and analysed using a quantitative 3-dimensional stereotactic surface projection analysis (Neurostat). MRI images were...... also inspected visually and severity of white matter lesions (WMLs) was graded using a visual rating scale. RESULTS: In 28 patients brain-FDG-PET was normal; in 23 of these 28 patients brain MRI was normal--of the remaining five patients in this group, four patients had WMLs and one patient never had...

  4. Picking the right transition strategy.

    Science.gov (United States)

    Watkins, Michael D

    2009-01-01

    Leaders in transition reflexively rely on the skills and strategies that worked for them in the past. That's a mistake, says Watkins, whose research shows that executives moving into new roles must gain a deep understanding of the situation at hand and adapt to it. To help them accurately assess their organizations and tailor their strategies and styles accordingly, he developed the STARS framework. "STARS" is an acronym for the five common situations leaders move into: start-up, turnaround, accelerated growth, realignment, and sustaining success. Thus, the model outlines the challenges of launching a venture or project; saving a business or initiative that's in serious trouble; dealing with rapid expansion; reenergizing a once-leading company that's now facing problems; and following in the footsteps of a highly regarded leader with a strong legacy of success. Executives can accelerate their immersion in new roles by following certain fundamental principles: Organize to learn about the business, establish A-item priorities, define strategic intent, quickly build the leadership team, secure early wins, and create supportive alliances across the company. But the way those principles should be applied depends very much on the business situation, which the STARS framework can help leaders analyze. Turnarounds and realignments present especially distinct leadership challenges that call for particular transition strategies. Regardless of the business situation, leaders must figure out which things need to happen--perhaps a jump in market share or an expansion into different markets--for their business to achieve its goals. And they must determine which leadership style best fits the new culture they're joining. Armed with such clarity, executives can design effective plans to manage their organizations and themselves.

  5. Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

    Science.gov (United States)

    Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2017-12-06

    Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise

    Directory of Open Access Journals (Sweden)

    Takashi eTarumi

    2014-01-01

    Full Text Available Alzheimer disease (AD and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

  7. Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

    Directory of Open Access Journals (Sweden)

    Keiichi Motoyama

    2015-11-01

    Full Text Available The Niemann–Pick type C disease (NPC is one of inherited lysosomal storage disorders, emerges the accumulation of unesterified cholesterol in endolysosomes. Currently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD has been applied for the treatment of NPC. HP-β-CyD improved hepatosplenomegaly in NPC patients, however, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by actively targeted-β-CyD to hepatocytes is expected. In the present study, to deliver β-CyD selectively to hepatocytes, we newly fabricated mono-lactose-appended β-CyD (Lac-β-CyD and evaluated its cholesterol lowering effects in NPC-like HepG2 cells, cholesterol accumulated HepG2 cells induced by treatment with U18666A. Lac-β-CyD (degree of substitution of lactose (DSL 1 significantly decreased the intracellular cholesterol content in a concentration-dependent manner. TRITC-Lac-β-CyD was associated with NPC-like HepG2 cells higher than TRITC-β-CyD. In addition, TRITC-Lac-β-CyD was partially localized with endolysosomes after endocytosis. Thus, Lac-β-CyD entered NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR-mediated endocytosis and decreased the accumulation of intracellular cholesterol in NPC-like HepG2 cells. These results suggest that Lac-β-CyD may have the potential as a drug for the treatment of hepatosplenomegaly in NPC disease.

  8. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

    Science.gov (United States)

    Snowdon, D A; Greiner, L H; Mortimer, J A; Riley, K P; Greiner, P A; Markesbery, W R

    1997-03-12

    To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.

  9. Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

    Science.gov (United States)

    Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

    2016-06-01

    Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

  10. Quantitative comparison of the efficacy of various compounds in lowering intracellular cholesterol levels in Niemann-Pick type C fibroblasts.

    Directory of Open Access Journals (Sweden)

    Zachary T Wehrmann

    Full Text Available Niemann-Pick Type C disease (NPC is a lethal, autosomal recessive disorder caused by mutations in the NPC1 and NPC2 cholesterol transport proteins. NPC's hallmark symptoms include an accumulation of unesterified cholesterol and other lipids in the late endosomal and lysosomal cellular compartments, causing progressive neurodegeneration and death. Although the age of onset may vary in those affected, NPC most often manifests in juveniles, and is usually fatal before adolescence. In this study, we investigated the effects of various drugs, many of which modify the epigenetic control of NPC1/NPC2 gene expression, in lowering the otherwise harmful elevated intracellular cholesterol levels in NPC cells. Our studies utilized a previously described image analysis technique, which allowed us to make quantitative comparisons of the efficacy of these drugs in lowering cholesterol levels in a common NPC1 mutant model. Of the drugs analyzed, several that have been previously studied (vorinostat, panobinostat, and β-cyclodextrin significantly lowered the relative amount of unesterified cellular cholesterol, consistent with earlier observations. In addition, a novel potential treatment, rapamycin, likewise alleviated the NPC phenotype. We also studied combinations of effective compounds with β-cyclodextrin; the addition of β-cyclodextrin significantly enhanced the cholesterol-lowering activity of vorinostat and panobinostat, but had mixed effects with rapamycin. Collectively, these results may provide a basis for the eventual development of improved NPC therapies.

  11. The influence of general anesthesia on the brain in aged patients with previous ischemic cerebrovascular disease

    International Nuclear Information System (INIS)

    Kokubo, Yasuaki; Kayama, Takamasa; Kondo, Rei; Oki, Masato; Takaoka, Seiji

    2008-01-01

    Whenever we discuss the overall results of surgical treatment for unruptured cerebral aneurysms, especially in aged patients, we tend to consider advanced age or general anesthesia as causes for unfavorable results. There are no reports concerning ischemic stroke events following general anesthesia in aged patients with a prior history of cerebrovascular disease. The purpose of this study is to clarify the influence of general anesthesia on the brats in aged patients with a previous history of ischemic cerebrovascular disease. The subjects were 30 consecutive patients over 70 years of age with previous ischemic cerebrovascular disease who underwent various surgeries except brain and cardiac surgery under general anesthesia. The patients were 70 to 85 years old, with a mean age of 76. Twenty-three were men and 7 were women. Surgical procedures were 12 gastrointestinal, 6 orthopedic and 4 urogenital and others. The type of cerebrovascular disease evaluated by neuroradiologist and anesthesiologist based on MR imaging was devided as follows: 16 patients had minor stroke, 7 had transient ischemic attack/reversible ischemic neurological deficit (TIA/RIND) and 7 had asymptomatic cerebral infarction. MR angiography was also assessed to evaluate the main artery in the brain. Blood pressure and arterial blood gas (PaCO 2 ) during general anesthesia were analyzed, and the rate of systemic and neurological complications following general anesthesia were evaluated. MR angiography revealed no occlusion or severe stenosis of the main artery in the brain of any of the patients. The minimum systolic blood pressure showed less than 100 mmHg transiently for 5-20 minutes in 28 of 30 patients during general anesthesia. The minimum value was 65 mmHg maintained for 5 minutes. The minimum PaCO 2 during general anesthesia was as follows: 1 case 36 mmHg. There were no neurological complications following general anesthesia in this study. One of 30 patients (3.3%) had suffered from pneumonia

  12. Fine-mapping the effects of Alzheimer's disease risk loci on brain morphology.

    Science.gov (United States)

    Roshchupkin, Gennady V; Adams, Hieab H; van der Lee, Sven J; Vernooij, Meike W; van Duijn, Cornelia M; Uitterlinden, Andre G; van der Lugt, Aad; Hofman, Albert; Niessen, Wiro J; Ikram, Mohammad A

    2016-12-01

    The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions. Brain regions most significantly associated with AD risk variants were the left postcentral gyrus with ABCA7 (rs4147929, p = 4.45 × 10 -6 ), right superior frontal gyrus by ZCWPW1 (rs1476679, p = 5.12 × 10 -6 ), and right postcentral gyrus by APOE (p = 6.91 × 10 -6 ). Although no individual voxel passed multiple-testing correction, we found significant spatial overlap between the effects of AD risk loci on VBM and the expression of genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas. Results are available online on www.imagene.nl/ADSNPs/. In this single largest imaging genetics data set worldwide, we found that AD risk loci affect cortical gray matter in several brain regions known to be involved in AD, as well as regions that have not been implicated before. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The Implication of the Brain Insulin Receptor in Late Onset Alzheimer’s Disease Dementia

    Directory of Open Access Journals (Sweden)

    Jaume Folch

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ, which form senile plaques, neurofibrillary tangles (NFT and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the “peripheral” symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors.

  14. Lysosomal storage diseases and the blood-brain barrier.

    Science.gov (United States)

    Begley, David J; Pontikis, Charles C; Scarpa, Maurizio

    2008-01-01

    The blood-brain barrier becomes a crucial issue in neuronopathic lysosomal storage diseases for three reasons. Firstly, the function of the blood-brain barrier may be compromised in many of the lysosomal storage diseases and this barrier dysfunction may contribute to the neuropathology seen in the diseases and accelerate cell death. Secondly, the substrate reduction therapies, which successfully reduce peripheral lysosomal storage, because of the blood-brain barrier may not have as free an access to brain cells as they do to peripheral cells. And thirdly, enzyme replacement therapy appears to have little access to the central nervous system as the mannose and mannose-6-phosphate receptors involved in their cellular uptake and transport to the lysosome do not appear to be expressed at the adult blood-brain barrier. This review will discuss in detail these issues and their context in the development of new therapeutic strategies.

  15. Drug Delivery to the Brain in Alzheimer’s Disease: Consideration of the Blood-brain Barrier

    Science.gov (United States)

    Banks, William A.

    2012-01-01

    The successful treatment of Alzheimer’s disease (AD) will require drugs that can negotiate the blood-brain barrier (BBB). However, the BBB is not simply a physical barrier, but a complex interface that is in intimate communication with the rest of the central nervous system (CNS) and influenced by peripheral tissues. This review examines three aspects of the BBB in AD. First, it considers how the BBB may be contributing to the onset and progression of AD. In this regard, the BBB itself is a therapeutic target in the treatment of AD. Second, it examines how the BBB restricts drugs that might otherwise be useful in the treatment of AD and examines strategies being developed to deliver drugs to the CNS for the treatment of AD. Third, it considers how drug penetration across the AD BBB may differ from the BBB of normal aging. In this case, those differences can complicate the treatment of CNS diseases such as depression, delirium, psychoses, and pain control in the AD population. PMID:22202501

  16. Mechanisms of action of brain insulin against neurodegenerative diseases.

    Science.gov (United States)

    Ramalingam, Mahesh; Kim, Sung-Jin

    2014-06-01

    Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.

  17. Diagnostic usefulness of 3 tesla MRI of the brain for cushing disease in a child.

    Science.gov (United States)

    Ono, Erina; Ozawa, Ayako; Matoba, Kaori; Motoki, Takanori; Tajima, Asako; Miyata, Ichiro; Ito, Junko; Inoshita, Naoko; Yamada, Syozo; Ida, Hiroyuki

    2011-10-01

    It is sometimes difficult to confirm the location of a microadenoma in Cushing disease. Recently, we experienced an 11-yr-old female case of Cushing disease with hyperprolactinemia. She was referred to our hospital because of decrease of height velocity with body weight gain. On admission, she had typical symptoms of Cushing syndrome. Although no pituitary microadenomas were detected on 1.5 Tesla MRI of the brain, endocrinological examinations including IPS and CS sampling were consistent with Cushing disease with hyperprolactinemia. Oral administration of methyrapone instead of neurosurgery was started after discharge, but subsequent 3 Tesla MRI of the brain clearly demonstrated a 3-mm less-enhanced lesion in the left side of the pituitary gland. Finally, transsphenoidal surgery was performed, and a 3.5-mm left-sided microadenoma was resected. Compared with 1.5 Tesla MRI, 3 Tesla MRI offers the advantage of a higher signal to noise ratio (SNR), which provides higher resolution and proper image quality. Therefore, 3 Tesla MRI is a very useful tool to localize microadenomas in Cushing disease in children as well as in adults. It will be the first choice of radiological examinations in suspected cases of Cushing disease.

  18. Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain

    Directory of Open Access Journals (Sweden)

    Yuhai Zhao

    2017-09-01

    Full Text Available Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer’s disease (AD brain. Despite many years of intense study, the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here, we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS, part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI tract, are abundant in AD-affected brain neocortex and hippocampus. For the first time, we provide evidence that LPS immunohistochemical signals appear to aggregate in clumps in the parenchyma in control brains, and in AD, about 75% of anti-LPS signals were clustered around the periphery of DAPI-stained nuclei. As LPS is an abundant secretory product of Gram-negative bacilli resident in the human GI-tract, these observations suggest (i that a major source of pro-inflammatory signals in AD brain may originate from internally derived noxious exudates of the GI-tract microbiome; (ii that due to aging, vascular deficits or degenerative disease these neurotoxic molecules may “leak” into the systemic circulation, cerebral vasculature, and on into the brain; and (iii that this internal source of microbiome-derived neurotoxins may play a particularly strong role in shaping the human immune system and contributing to neural degeneration, particularly in the aging CNS. This “Perspectives” paper will further highlight some very recent developments that implicate GI-tract microbiome-derived LPS as an important contributor to inflammatory-neurodegeneration in the AD brain.

  19. Dictionary of cotton: Picking & ginning

    Science.gov (United States)

    Cotton is an essential commodity for textiles and has long been an important item of trade in the world’s economy. Cotton is currently grown in over 100 countries by an estimated 100 producers. The basic unit of the cotton trade is the cotton bale which consists of approximately 500 pounds of raw c...

  20. MR imaging of the brain: metabolic and toxic white matter diseases

    International Nuclear Information System (INIS)

    Forsting, M.

    1999-01-01

    Metabolic disorders of the brain are rare, complex and confusing. The diagnostic modality of choice nowadays is MRI. The high diagnostic sensitivity, however, is coupled with a lack of specificity and usually results in the depiction of similar appearing but clinically diverse white matter processes. For this reason it is essential to perform the MRI as early as possible during the course of the disease and to keep in close contact to the referring clinician to optimize image interpretation. Another precondition is to know the natural course of brain myelination and to know how this appears on the individual MR machine with different parameters. In some diseases like phenylketonuria MRI seems to be an excellent tool to monitor dietary treatment and patient compliance. In patients after radio- and / or chemotherapy MRI reveals the radiation induced leucencephalopathy and can usually differentiate between a recurrent malignancy. (orig.)

  1. MR imaging of the brain: metabolic and toxic white matter diseases

    Energy Technology Data Exchange (ETDEWEB)

    Forsting, M. [Univ. of Essen (Germany). Dept. of Neuroradiology

    1999-08-01

    Metabolic disorders of the brain are rare, complex and confusing. The diagnostic modality of choice nowadays is MRI. The high diagnostic sensitivity, however, is coupled with a lack of specificity and usually results in the depiction of similar appearing but clinically diverse white matter processes. For this reason it is essential to perform the MRI as early as possible during the course of the disease and to keep in close contact to the referring clinician to optimize image interpretation. Another precondition is to know the natural course of brain myelination and to know how this appears on the individual MR machine with different parameters. In some diseases like phenylketonuria MRI seems to be an excellent tool to monitor dietary treatment and patient compliance. In patients after radio- and / or chemotherapy MRI reveals the radiation induced leucencephalopathy and can usually differentiate between a recurrent malignancy. (orig.) With 3 figs., 1 tab., 23 refs.

  2. The treatment of Parkinson's disease with deep brain stimulation: current issues.

    Science.gov (United States)

    Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

    2015-07-01

    Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

  3. The treatment of Parkinson′s disease with deep brain stimulation: current issues

    Directory of Open Access Journals (Sweden)

    Alexia-Sabine Moldovan

    2015-01-01

    Full Text Available Deep brain stimulation has become a well-established symptomatic treatment for Parkinson′s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients′ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

  4. Lycopene reduces cholesterol absorption through the downregulation of Niemann-Pick C1-like 1 in Caco-2 cells.

    Science.gov (United States)

    Zou, Jun; Feng, Dan

    2015-11-01

    Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect was considered to be related to inhibition of cholesterol synthesis. However, since plasma cholesterol levels are also influenced by the absorption of cholesterol in the gut, the present study is to investigate whether lycopene affects cholesterol absorption in the intestinal Caco-2 cells. The Caco-2 cells were pretreated with lycopene at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and liver X receptor α (LXRα) was analyzed by Western blot and qPCR. We found that lycopene dose dependently inhibited cholesterol absorption and the expression of NPC1L1 protein and NPC1L1 mRNA. The inhibitory effects of lycopene on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the LXRα pathway. This study provides the first evidence that lycopene inhibits cholesterol absorption in the intestinal cells and this inhibitory effect of lycopene is mediated, at least in part, by LXRα-NPC1L1 signaling pathway. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. AFM picking-up manipulation of the metaphase chromosome fragment by using the tweezers-type probe

    International Nuclear Information System (INIS)

    Yamanaka, Keiichiro; Saito, Masato; Shichiri, Motoharu; Sugiyama, Sigeru; Takamura, Yuzuru; Hashiguchi, Gen; Tamiya, Eiichi

    2008-01-01

    We have studied the development of a new procedure based on atomic force microscopy (AFM) for the analysis of metaphase chromosome. The aim of this study was to obtain detailed information about the specific locations of genes on the metaphase chromosome. In this research, we performed the manipulation of the metaphase chromosome by using novel AFM probes to obtain chromosome fragments of a smaller size than the ones obtained using the conventional methods, such as glass microneedles. We could pick up the fragment of the metaphase chromosome dissected by the knife-edged probe by using our tweezers-type probe

  6. Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders.

    Science.gov (United States)

    Theoharides, T C; Tsilioni, I; Patel, A B; Doyle, R

    2016-06-28

    Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood-brain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1β), IL-6, 1 L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGFβ induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that

  7. An interactive tool for CT volume rendering and sagittal plane-picking of the prostate for radiotherapy treatment planning

    International Nuclear Information System (INIS)

    Jani, Ashesh B.; Pelizzari, Charles A.; Chen, George T.Y.; Grzezcszuk, Robert P.; Vijayakumar, Srinivasan

    1997-01-01

    Objective: Accurate and precise target volume and critical structure definition is a basic necessity in radiotherapy. The prostate, particularly the apex (an important potential site of recurrence in prostate cancer patients), is a challenging structure to define using any modality, including conventional axial CT. Invasive or expensive techniques, such as retrograde urethrography or MRI, could be avoided if localization of the prostate were possible using information already available on the planning CT. Our primary objective was to build a software tool to determine whether volume rendering and sagittal plane-picking, which are CT-based, noninvasive visualization techniques, were of utility in radiotherapy treatment planning for the prostate. Methods: Using AVS (Application Visualization System) on a Silicon Graphics Indigo 2 High Impact workstation, we have developed a tool that enables the clinician to efficiently navigate a CT volume and to use volume rendering and sagittal plane-picking to better define structures at any anatomic site. We applied the tool to the specific example of the prostate to compare the two visualization techniques with the current standard of axial CT. The prostate was defined on 80-slice CT scans (scanning thickness 4mm, pixel size 2mm x 2mm) of prostate cancer patients using axial CT images, volume-rendered CT images, and sagittal plane-picked images. Results: The navigation of the prostate using the different visualization techniques qualitatively demonstrated that the sagittal plane-picked images, and even more so the volume-rendered images, revealed the prostate (particularly the lower border) better in relationship to the surrounding regional anatomy (bladder, rectum, pelvis, and penile structures) than did the axial images. A quantitative comparison of the target volumes obtained by navigating using the different visualization techniques demonstrated that, when compared to the prostate volume defined on axial CT, a larger volume

  8. Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease.

    Science.gov (United States)

    Aliev, Gjumrakch; Palacios, Hector H; Walrafen, Brianna; Lipsitt, Amanda E; Obrenovich, Mark E; Morales, Ludis

    2009-10-01

    Alzheimer's disease (AD) and cerebrovascular accidents are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. In this regard, hypoperfusion appears to induce oxidative stress (OS), which is largely due to reactive oxygen species (ROS), and over time initiates mitochondrial failure which is known as an initiating factor of AD. Recent evidence indicates that chronic injury stimulus induces hypoperfusion seen in vulnerable brain regions. This reduced regional cerebral blood flow (CBF) then leads to energy failure within the vascular endothelium and associated brain parenchyma, manifested by damaged mitochondrial ultrastructure (the formation of large number of immature, electron-dense "hypoxic" mitochondria) and by overproduction of mitochondrial DNA (mtDNA) deletions. Additionally, these mitochondrial abnormalities co-exist with increased redox metal activity, lipid peroxidation, and RNA oxidation. Interestingly, vulnerable neurons and glial cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels, and, moreover, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We summarize the large body of evidence which indicates that sporadic, late-onset AD results from a vascular etiology by briefly reviewing mitochondrial damage and vascular risk factors associated with the disease and then we discuss the cerebral microvascular changes reason for the energy failure that occurs in normal aging and, to a much greater extent, AD.

  9. Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1.

    Science.gov (United States)

    Park, Walter D; O'Brien, John F; Lundquist, Patrick A; Kraft, Daniel L; Vockley, Cate Walsh; Karnes, Pamela S; Patterson, Marc C; Snow, Karen

    2003-10-01

    The two known complementation groups of Niemann-Pick Type C disease, NPC1 and NPC2, result from non-allelic protein defects. Both the NPC1 and NPC2 (HE1) gene products are intimately involved in cholesterol and glycolipid trafficking and/or transport. We describe mutation analysis on samples from 143 unrelated affected NPC patients using conformation sensitive gel electrophoresis and DNA sequencing as the primary mutation screening methods for NPC1 and NPC2, respectively. These methods are robust, sensitive, and do not require any specialized laboratory equipment. Analyses identified two NPC1 mutations for 115 (80.4%) patients, one NPC1 mutation for 10 (7.0%) patients, two NPC2 mutations for five (3.5%) patients, one NPC2 mutation for one (0.7%) patient, and no mutations for 12 (8.4%) patients. Thus, mutations were identified on 251 of 286 (88%) disease alleles, including 121 different mutations (114 in NPC1 and seven in NPC2), 58 of which are previously unreported. The most common NPC1 mutation, I1061T, was detected on 18% of NPC alleles. Other NPC1 mutations were mostly private, missense mutations located throughout the gene with clustering in the cysteine-rich luminal domain. Correlation with biochemical data suggests classification of several mutations as severe and others as moderate or variable. The region between amino acids 1038 and 1253, which shares 35% identity with Patched 1, appears to be a hot spot for mutations. Additionally, a high percentage of mutations were located at amino acids identical to the NPC1 homolog, NPC1L1. Biochemical complementation analysis of cases negative for mutations revealed a high percentage of equivocal results where the complementation group appeared to be non-NPC1 and non-NPC2. This raises the possibilities of an additional NPC complementation group(s) or non-specificity of the biochemical testing for NPC. These caveats must be considered when offering mutation testing as a clinical service. Copyright 2003 Wiley-Liss, Inc.

  10. Deregulation of brain insulin signaling in Alzheimer's disease.

    Science.gov (United States)

    Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

    2014-04-01

    Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

  11. Magnetic resonance imaging of functional connectivity in Parkinson disease in the resting brain

    International Nuclear Information System (INIS)

    Liu Xian; Liu Bo; Luo Xiaodong; Li Ningna; Chen Zhiguang; Chen Jun

    2009-01-01

    Objective: To investigate functional connectivity changes in Parkinson disease in the resting brain using functional magnetic resonance imaging. Methods: Nine patients with Parkinson disease and eight age-matched healthy volunteers were entered into the study. The bilateral globus pallidus were chosen as seed points, the functional MR data acquired in the resting state were processed to investigate functional connectivity in PD patients and the results were compared with those of the controls. Results: In age-matched healthy controls, there are regions which had functional connectivity with bilateral globus pallidus, including bilateral temporal poles, bilateral hippocampus, bilateral thalami, posterior cingulate cortex, right middle occipital gyms and right superior parietal gyms. In PD patients, brain regions including bilateral cerebellum, left hippocampus, bilateral superior temporal gyri, left inferior frontal gyrus, left middle frontal gyrus, left precentral gyrus, left inferior parietal gyrus and left superior parietal gyrus, had functional connectivity with bilateral globus pallidus. Compared to healthy controls, increased functional connectivity in bilateral cerebellum, bilateral temporal lobes, left frontal lobe and left parietal lobe, and decreased functional connectivity in bilateral thalami were observed in PD patients. Conclusion: Abnormal changes of brain functional connectivity exists in Parkinson's disease in the resting state. (authors)

  12. Order picking in carousel systems under the nearest item heuristic

    NARCIS (Netherlands)

    Litvak, Nelli; Zijm, Willem H.M.; Adan, I.J.B.F.; Wessels, J.

    2001-01-01

    A carousel is a computer-controlled warehousing system, which is widely used to store small- and medium-sized goods. One of the most important performance characteristics of such systems is the pick time of an order, which mostly depends on the travel time of the carousel. In this article, we

  13. Order picking in carousel systems under the nearest item heuristic

    NARCIS (Netherlands)

    Litvak, Nelli; Adan, I.J.B.F.; Wessels, J.; Zijm, Willem H.M.

    2000-01-01

    A carousel is a computer controlled warehousing system, which is widely used to store small and medium sized goods. One of the most important performance characteristics of such systems is the pick time of an order, which mostly depends on the travel time of the carousel. In this paper we consider

  14. Order picking in carousel systems under the nearest item heuristic

    NARCIS (Netherlands)

    Litvak, Nelli; Adan, I.J.B.F.; Wessels, J.B.; Zijm, Willem H.M.

    2001-01-01

    A carousel is a computer-controlled warehousing system, which is widely used to store small- and medium-sized goods+ One of the most important performance character- istics of such systems is the pick time of an order, which mostly depends on the travel time of the carousel+ In this article, we

  15. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  16. Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

    International Nuclear Information System (INIS)

    Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi; Murru, Alessandra; Demelia, Luigi; Sias, Alessandro; Marrosu, Francesco

    2008-01-01

    To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and 99m Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in 99m Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating better the

  17. Deep brain stimulation for the treatment of Alzheimer disease and dementias.

    Science.gov (United States)

    Laxton, Adrian W; Lozano, Andres M

    2013-01-01

    To review the use of deep brain stimulation (DBS) for treatment of dementia. A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia. Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    Science.gov (United States)

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  19. Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

    Science.gov (United States)

    Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

    2014-06-01

    In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Hyper-connectivity of functional networks for brain disease diagnosis.

    Science.gov (United States)

    Jie, Biao; Wee, Chong-Yaw; Shen, Dinggang; Zhang, Daoqiang

    2016-08-01

    Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer's disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help

  1. The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer's Disease: A Randomised Controlled Study

    NARCIS (Netherlands)

    de Waal, H.; Stam, C.J.; Lansbergen, M.M.; Wieggers, R.L.; Kamphuis, P.J.G.H.; Scheltens, P.; Maestu, F.; van Straaten, E.C.W.

    2014-01-01

    Background: Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn

  2. SysML Model of the Pick and Place Unit for Papyrus UML: Scenario Sc4b

    OpenAIRE

    Vogel-Heuser, Birgit; Folmer, Jens; Legat, Christoph

    2014-01-01

    The Pick and Place Unit (PPU) is a bench-scale lab demonstrator which is open to the research community to investigate a variety of different topics. To conduct research on the evolution of production automation systems, a variety of different manifestations of the PPU (referred to as scenarios) were developed. A documentation of the PPU and its scenarios is publicly available at www.ppu-demonstrator.org. In this zipped file, a SysML model consisting of state charts and block definition diagr...

  3. Solar cycle variation of interstellar neutral He, Ne, O density and pick-up ions along the Earth's orbit

    OpenAIRE

    Sokół, Justyna M.; Bzowski, Maciej; Kubiak, Marzena A.; Möbius, Eberhard

    2016-01-01

    We simulated the modulation of the interstellar neutral (ISN) He, Ne, and O density and pick-up ion (PUI) production rate and count rate along the Earth's orbit over the solar cycle from 2002 to 2013 to verify if solar cycle-related effects may modify the inferred ecliptic longitude of the ISN inflow direction. We adopted the classical PUI model with isotropic distribution function and adiabatic cooling, modified by time- and heliolatitude-dependent ionization rates and non-zero injection spe...

  4. Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease.

    Science.gov (United States)

    Schneider, Frank; Habel, Ute; Volkmann, Jens; Regel, Sabine; Kornischka, Jürgen; Sturm, Volker; Freund, Hans-Joachim

    2003-03-01

    High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD). Clinical observations indicate additional influence on emotional behavior. Electrical stimulation of deep brain nuclei with pulse rates above 100 Hz provokes a reversible, lesioning-like effect. Here, the effect of deep brain stimulation of the subthalamic nucleus on emotional, cognitive, and motor performance in patients with PD (n = 12) was examined. The results were compared with the effects of a suprathreshold dose of levodopa intended to transiently restore striatal dopamine deficiency. Patients were tested during medication off/stimulation off (STIM OFF), medication off/stimulation on (STIM ON), and during the best motor state after taking levodopa without deep brain stimulation (MED). More positive self-reported mood and an enhanced mood induction effect as well as improvement in emotional memory during STIM ON were observed, while during STIM OFF, patients revealed reduced emotional performance. Comparable effects were revealed by STIM ON and MED. Cognitive performance was not affected by the different conditions and treatments. Deep brain stimulation of the subthalamic nucleus selectively enhanced affective processing and subjective well-being and seemed to be antidepressive. Levodopa and deep brain stimulation had similar effects on emotion. This finding may provide new clues about the neurobiologic bases of emotion and mood disorders, and it illustrates the important role of the basal ganglia and the dopaminergic system in emotional processing in addition to the well-known motor and cognitive functions.

  5. Olfactory Functioning in Parkinson's Disease: The Effects of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    van Hartevelt, Tim Johannes

    2014-01-01

    The sense of smell is vital for species survival in terms of food selection and detection as well as procreation. Disorders of the sense of smell are not uncommon and can have a significant effect on general health and well-being including quality of life. In Parkinson's disease (PD), the loss...... of sense of smell is one of the most common and earliest symptoms, appearing approximately 5 years prior to any motor symptoms. Deep brain stimulation (DBS) has proven remarkably effective in alleviating the symptoms of PD including olfactory dysfunction. This remains a difficult area to research with many...

  6. Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report

    Directory of Open Access Journals (Sweden)

    Luca Maria

    2012-07-01

    Full Text Available Abstract Introduction Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. Case presentation The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. Conclusions To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

  7. Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

    Science.gov (United States)

    Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

    2017-01-01

    Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine

    OpenAIRE

    Varma, T; Fox, S; Eldridge, P; Littlechild, P; Byrne, P; Forster, A; Marshall, A; Cameron, H; McIver, K; Fletcher, N; Steiger, M

    2003-01-01

    Objectives: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication.

  9. Peripheral neuropathy in type A Niemann-Pick disease. A morphological study.

    Science.gov (United States)

    Landrieu, P; Saïd, G

    1984-01-01

    A black boy had a severe neuropathic form of Niemann-Pick disease (NPD) with a pronounced sphingomyelinase deficiency in the fibroblasts. Nerve conduction velocities were diminished, and a nerve biopsy was performed. Isolated fibers showed segmental demyelination and numerous dense bodies in the Schwann cells (SC). Electron microscopy revealed two categories of inclusions: the first was made up of lysosomal inclusions usually described in NPD. The second comprised myelin inclusions--sometimes still connected to the original myelin sheath--indicating severe myelinopathy. Both myelin debris and NPD inclusions were found in axoplasms and probably came from SC cytoplasm through axolemma lesions. NPD is a unique example of myelinopathy due to sphingomyelinase deficiency.

  10. Vision guided robot bin picking of cylindrical objects

    DEFF Research Database (Denmark)

    Christensen, Georg Kronborg; Dyhr-Nielsen, Carsten

    1997-01-01

    In order to achieve increased flexibility on robotic production lines an investigation of the rovbot bin-picking problem is presented. In the paper, the limitations related to previous attempts to solve the problem are pointed uot and a set of innovative methods are presented. The main elements...

  11. Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

    Science.gov (United States)

    Cole, James H

    2018-07-01

    The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

  12. Pick-and-place process for sensitivity improvement of the capacitive type CMOS MEMS 2-axis tilt sensor

    Science.gov (United States)

    Chang, Chun-I.; Tsai, Ming-Han; Liu, Yu-Chia; Sun, Chih-Ming; Fang, Weileun

    2013-09-01

    This study exploits the foundry available complimentary metal-oxide-semiconductor (CMOS) process and the packaging house available pick-and-place technology to implement a capacitive type micromachined 2-axis tilt sensor. The suspended micro mechanical structures such as the spring, stage and sensing electrodes are fabricated using the CMOS microelectromechanical systems (MEMS) processes. A bulk block is assembled onto the suspended stage by pick-and-place technology to increase the proof-mass of the tilt sensor. The low temperature UV-glue dispensing and curing processes are employed to bond the block onto the stage. Thus, the sensitivity of the CMOS MEMS capacitive type 2-axis tilt sensor is significantly improved. In application, this study successfully demonstrates the bonding of a bulk solder ball of 100 µm in diameter with a 2-axis tilt sensor fabricated using the standard TSMC 0.35 µm 2P4M CMOS process. Measurements show the sensitivities of the 2-axis tilt sensor are increased for 2.06-fold (x-axis) and 1.78-fold (y-axis) after adding the solder ball. Note that the sensitivity can be further improved by reducing the parasitic capacitance and the mismatch of sensing electrodes caused by the solder ball.

  13. Non-invasive brain stimulation for the treatment of brain diseases in childhood and adolescence: state of the art, current limits and future challenges

    Directory of Open Access Journals (Sweden)

    Carmelo Mario Vicario

    2013-11-01

    Full Text Available In the last decades interest in application of non-invasive brain stimulation for enhancing neural functions is growing continuously. However, the use of such techniques in pediatric populations remains rather limited and mainly confined to the treatment of severe neurological and psychiatric diseases. In this article we provide a complete review of non-invasive brain stimulation studies conducted in pediatric populations. We also provide a brief discussion about the current limitations and future directions in a field of research still very young and full of issues to be explored.

  14. Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease

    Directory of Open Access Journals (Sweden)

    Abhilash P. Appu

    2017-06-01

    Full Text Available Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA, a deacetylase that catabolizes N-acetylaspartate (NAA. The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease. We evaluated various serological parameters, oxidative stress, inflammatory and neurodegeneration markers and the results showed that there were no pathological alterations in any measure with increased brain NAA levels. We examined oxidative stress markers, malondialdehyde content (indicator of lipid peroxidation, expression of NADPH oxidase and nuclear translocation of the stress-responsive transcription factor nuclear factor (erythroid-derived 2-like 2 (NRF-2 in brain. We also examined additional pathological markers by immunohistochemistry and the expression of activated caspase-3 and interleukin-6 by Western blot. None of the markers were increased in the brains of M-NAA treated mice, and no vacuoles were observed in any brain region. These results show that ASPA expression prevents the pathologies associated with excessive NAA concentrations in the brain during postnatal myelination. We hypothesize that the pathogenesis of Canavan disease involves not only disrupted NAA metabolism, but also excessive NAA related signaling processes in oligodendrocytes that have not been fully determined and we discuss some of the potential mechanisms.

  15. Relating Education, Brain Structure, and Cognition: The Role of Cardiovascular Disease Risk Factors

    Directory of Open Access Journals (Sweden)

    Moyra E. Mortby

    2014-01-01

    Full Text Available The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD risk factors (i.e., hypertension, smoking, diabetes, and obesity on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study (N=266, we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.

  16. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2013-12-01

    Decline of cognition and increasing risk of neurodegenerative diseases are major problems associated with aging in humans. Of particular importance is how the brain removes potentially toxic biomolecules that accumulate with normal neuronal function. Recently, a biomolecule clearance system using convective flow between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic metabolites in the brain was described. Xie and colleagues now report that in mice the clearance activity of this so-called "glymphatic system" is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation of adrenergic signaling can activate the glymphatic system to clear potentially toxic proteins known to contribute to the pathology of Alzheimer disease (AD) such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold faster than during waking hours. These results support a new hypothesis to answer the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as well as maintenance of cognition. Furthermore, clinical studies suggest that quality and duration of sleep may be predictive of the onset of AD, and that quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE) ɛ4 carriers, who have significantly greater chances of developing AD. Further characterization of the glymphatic system in humans may lead to new therapies and methods of prevention of neurodegenerative diseases. A public health initiative to ensure adequate sleep among middle-aged and older people may prove useful in preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.

  17. Observation of the relationship between regional cerebral blood flow and brain functional changes in the patients with ischemic cerebrovascular diseases

    International Nuclear Information System (INIS)

    Guan Yihui; Lin Xiangtong; Liu Yongchang

    1994-01-01

    The brain perfusion SPECT imaging and functional changes in 27 patients with ischemic cerebrovascular diseases and 20 controls were investigated. Correlated with the clinical findings and MRI study, we discovered the lowered perfusion of Broca and Wernicke area is closely related with the aphasia caused by left basal ganglia infarction. In hemianopia group, as the visual function improved after the light stimulation treatment, the blood perfusion increased in occipital lobe. The lowered perfusion in vestibular center can be observed in vertigo group. From these studies, we concluded that 99m Tc-HMPAO brain SPECT imaging can partly reflect the brain functions

  18. The preliminary study of 18F-FDG brain PET in diagnosis of alzheimer's disease

    International Nuclear Information System (INIS)

    Ma Yunchuan; Zhang Xinqing; Li Depeng; Shang Jianwen; Su Yusheng; Zhang Linying; Peng Cheng; Pan Zhongyun

    2000-01-01

    Objective: To investigate the imaging characteristics and diagnostic criteria of 18 F-FDG brain PET in diagnosis of Alzheimer's disease (AD). Methods: The sutdy included 12 normal subjects, 12 patients with AD and 11 patients with non-AD dementia. 40 min after intravenous administration of 18 F-FDG, brain scan was performed using Siemens ECAT47 scanner. The transaxial, coronal and sagittal images were then reconstructed by computer. At the same time, semiquantitative analysis was also applied to help evaluation using the ratio of mean radioactivity of cerebral lobe to cerebellum (R cl/cb ). Results: In normal subjects PET scan showed clear images of cerebral cortex, basal ganglia, thalamus and cerebellum with symmetrical distribution of radioactivity. PET images from Alzheimer's disease patients were classified into 3 patterns: bilateral parietal hypometabolism in 5 cases, bilateral temporo-parietal hypometabolism in 4 cases and unilateral temporo-parietal hypometabolism in 3 cases. The R cl/cb of AD patients in parietal and temporal lobe was significantly decreased than normal subjects (P cl/cb was also reflecting thedementia degree. Compared with MRI imaging , 12 patients with AD had cerebral hypometabolism but only 10 had hippocampus atrophy. 10 patients with non-AD dementia had local structural foci seen in MRI, including old hemorrhage, infarction and encephalomalacia, but these lesions were not found in AD. Conclusions: Based on excluding cerebral structural lesions which are better detected by MRI, bilateral or unilateral parietal or temporo-parietal hypometabolism found in FDG PET can be considered indicative of Alzheimer's disease. Semiquantitative analysis of the images yielded can help to evaluate the dementia degree

  19. Can Electrical Vestibular Noise Be Used for the Treatment of Brain Diseases?

    Science.gov (United States)

    Yamamoto, Yoshiharu; Soma, Rika; Struzik, Zbigniew R.; Kwak, Shin

    2005-11-01

    The therapy currently available for the treatment of degenerative neurological diseases is far from satisfactory, and a novel therapeutic strategy, especially for pharmacologically unresponsive patients, would be welcomed. The vestibular nerves are known to influence neuronal circuits in the medullary cardiovascular areas and, through the cerebellar vermis, the basal ganglia and the limbic system. By means of noisy galvanic vestibular stimulation (GVS), it may now be possible to ameliorate blunted responsiveness of degenerated neuronal circuits in the brains of multiple system atrophy (MSA) and/or Parkinson's disease (PD) patients, through a mechanism known as stochastic resonance. We evaluate the effect of 24-hour noisy GVS on long-term heart rate dynamics in seven MSA patients, and on daytime locomotor activity dynamics in twelve patients with either PD or levodopa unresponsive parkinsonism. Short-range heart rate variability and long-range anti-correlation of trunk activity are significantly increased by the noisy GVS compared with sham stimulation, suggestive of improved autonomic and motor responsiveness. The noisy GVS is effective in boosting the neuro-degenerative brains of MSA and/or PD patients, including those unresponsive to standard levodopa therapy.

  20. An intelligent identification algorithm for the monoclonal picking instrument

    Science.gov (United States)

    Yan, Hua; Zhang, Rongfu; Yuan, Xujun; Wang, Qun

    2017-11-01

    The traditional colony selection is mainly operated by manual mode, which takes on low efficiency and strong subjectivity. Therefore, it is important to develop an automatic monoclonal-picking instrument. The critical stage of the automatic monoclonal-picking and intelligent optimal selection is intelligent identification algorithm. An auto-screening algorithm based on Support Vector Machine (SVM) is proposed in this paper, which uses the supervised learning method, which combined with the colony morphological characteristics to classify the colony accurately. Furthermore, through the basic morphological features of the colony, system can figure out a series of morphological parameters step by step. Through the establishment of maximal margin classifier, and based on the analysis of the growth trend of the colony, the selection of the monoclonal colony was carried out. The experimental results showed that the auto-screening algorithm could screen out the regular colony from the other, which meets the requirement of various parameters.

  1. Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

    NARCIS (Netherlands)

    Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

    1993-01-01

    The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

  2. An analysis of the first-arrival times picked on the DSS and wide-angle seismic section recorded in Italy since 1968

    Directory of Open Access Journals (Sweden)

    R. Tondi

    2004-06-01

    Full Text Available We performed an analysis of refraction data recorded in Italy since 1968 in the frame of the numerous deep seismic sounding and wide-angle reflection/refraction projects. The aims of this study are to construct a parametric database including the recording geometric information relative to each profile, the phase pickings and the results of some kinematic analyses performed on the data, and to define a reference 1D velocity model for the Italian territory from all the available refraction data. As concerns the first goal, for each seismic section we picked the P-wave first-arrival-times, evaluated the uncertainties of the arrival-times pickings and determined from each travel time-offset curve the 1D velocity model. The study was performed on 419 seismic sections. Picking was carried out manually by an algorithm which includes the computation of three picking functions and the picking- error estimation. For each of the travel time-offset curves a 1D velocity model has been calculated. Actually, the 1D velocity-depth functions were estimated in three different ways which assume: a constant velocitygradient model, a varying velocity-gradient model and a layered model. As regards the second objective of this work, a mean 1D velocity model for the Italian crust was defined and compared with those used for earthquake hypocentre locations and seismic tomographic studies by different institutions operating in the Italian area, to assess the significance of the model obtained. This model can be used in future works as input for a next joint tomographic inversion of active and passive seismic data.

  3. Pick 'n' mix: neuropatholgical detection of peri-tumour taupathy.

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2013-11-01

    Radiotherapy is used to treat recurrent oligodendrogliomas, WHO grade 2 tumours. Potential morbitities include steroid-responsive radiation necrosis and radiation leucoencephalopathy, characterised pathologically by reactive astrogliosis, focal necrosis, demyelination, axonal loss, and clinically by progressive subcortical deficits (ataxia, amnesia, incontinence, cognitive decline), with relative sparing of cortical function. Although subcortical features may overlap with neurodegenerative conditions (eg frontotemporal dementia), focal cortical atrophy of FTD causes loss of language function in addition to memory, and specific histopathological features characterise FTD subtypes (eg Pick disease). Association between mitotic disease and tauopathy has not been reported widely, but co-existence is possible. Diagnostic accuracy may guide management.

  4. Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Hunter

    Full Text Available Key pathological hallmarks of Alzheimer's disease (AD, including amyloid plaques, cerebral amyloid angiopathy (CAA and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1 nonagenarians with AD and a high amyloid plaque load; 2 nonagenarians with no dementia and a high amyloid plaque load; 3 nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND group (average age 71 years with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD.

  5. Brain Connectivity Alterations Are Associated with the Development of Dementia in Parkinson's Disease.

    Science.gov (United States)

    Bertrand, Josie-Anne; McIntosh, Anthony R; Postuma, Ronald B; Kovacevic, Natasha; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Gagnon, Jean-François

    2016-04-01

    Dementia affects a high proportion of Parkinson's disease (PD) patients and poses a burden on caregivers and healthcare services. Electroencephalography (EEG) is a common nonevasive and nonexpensive technique that can easily be used in clinical settings to identify brain functional abnormalities. Only few studies had identified EEG abnormalities that can predict PD patients at higher risk for dementia. Brain connectivity EEG measures, such as multiscale entropy (MSE) and phase-locking value (PLV) analyses, may be more informative and sensitive to brain alterations leading to dementia than previously used methods. This study followed 62 dementia-free PD patients for a mean of 3.4 years to identify cerebral alterations that are associated with dementia. Baseline resting state EEG of patients who developed dementia (N = 18) was compared to those of patients who remained dementia-free (N = 44) and of 37 healthy subjects. MSE and PLV analyses were performed. Partial least squares statistical analysis revealed group differences associated with the development of dementia. Patients who developed dementia showed higher signal complexity and lower PLVs in low frequencies (mainly in delta frequency) than patients who remained dementia-free and controls. Conversely, both patient groups showed lower signal variability and higher PLVs in high frequencies (mainly in gamma frequency) compared to controls, with the strongest effect in patients who developed dementia. These findings suggest that specific disruptions of brain communication can be measured before PD patients develop dementia, providing a new potential marker to identify patients at highest risk of developing dementia and who are the best candidates for neuroprotective trials.

  6. The relationship between adolescents' academic stress, impulsivity, anxiety, and skin picking behavior.

    Science.gov (United States)

    Yeo, Sun Kyung; Lee, Woo Kyeong

    2017-08-01

    Skin picking behavior involves an individual picking or biting their skin repeatedly. Although this behavior commonly occurs at a young age, little research has addressed its harmful effects among the Korean population. Therefore, we examined the characteristics of South Korean adolescents who reported skin picking behavior. South Korean students aged 12-16 years participated (N=410, females=52.2%). They completed questionnaires that addressed skin picking behavior, academic stress, impulsivity, and anxiety. The survey was conducted in Seoul and Gyeonggi-do from February-March 2016. Among participants, 66.8% reported that they had picked their skin and 15.4% did so currently. Skin picking was positively correlated with academic stress, impulsivity, and anxiety. Students who picked their skin more often displayed more anxiety, academic stress, and impulsivity. Future studies should address skin picking adolescents' characteristics, especially regarding anxiety and academic stress. Educational programs should be implemented to help adolescents decrease their anxiety and academic stress and prevent the worsening of skin picking behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases.

    Science.gov (United States)

    Phan, Chia-Wei; David, Pamela; Sabaratnam, Vikineswary

    2017-01-01

    There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their antidementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.

  8. Imaging of Brain Connectivity in Dementia: Clinical Implications for Diagnosis of its Underlying Diseases

    NARCIS (Netherlands)

    R. Meijboom (Rozanna)

    2017-01-01

    markdownabstractIn this thesis we investigated the use of advanced magnetic resonance imaging (MRI) techniques in identifying subtle brain abnormalities, associating brain abnormalities with disease symptomatology, and improving early (differential) diagnosis in several diseases underlying dementia.

  9. MRI of the foetal brain

    International Nuclear Information System (INIS)

    Rich, P.; Jones, R.; Britton, J.; Foote, S.; Thilaganathan, B.

    2007-01-01

    Ultrasound examinations for foetal brain abnormalities have been a part of the routine antenatal screening programme in the UK for many years. In utero brain magnetic resonance imaging (MRI) is now being used increasingly successfully to clarify abnormal ultrasound findings, often resulting in a change of diagnosis or treatment plan. Interpretation requires an understanding of foetal brain development, malformations and acquired diseases. In this paper we will outline the technique of foetal MRI, relevant aspects of brain development and provide illustrated examples of foetal brain pathology

  10. Magnetic resonance tomography and computed tomography of the brain for diagnosing Wilson's disease

    International Nuclear Information System (INIS)

    Uhlenbrock, D.; Straube, A.; Beyer, H.K.; Leopold, H.C.

    1985-01-01

    The authors report on two woman patients with confirmed Wilson's desease (hepatolenticular degeneration) who had neurological deficits and showed typical changes evident from laboratory data. Both computed tomography and magnetic resonance tomography revealed degenerative changes in the basal ganglia, especially of the lenticular nucleus, MR showing these defects more clearly than CT. There was a noticeable symmetrical enhancement of signals in the lenticular nucleus which was particularly evident on the image basing on the T 2 (spin-spin relaxation time constant) values. MR could be superior to CT with regard to showing up pathological changes in the basal ganglia. The future indication of MR could be the establishment of an exact correlation between clinical signs and symptoms on the one hand, and morphological findings on the other. Over and above this, it should be explored to what extent MR can already detect degenerative changes in the brain in primarily hepatic types of the disease even without prior neurological examination. (orig.) [de

  11. Deep brain stimulation and responsiveness of the Persian version of Parkinson's disease questionnaire with 39-items.

    Science.gov (United States)

    Shahidi, Gholam Ali; Ghaempanah, Zeinab; Khalili, Yasaman; Nojomi, Marzieh

    2014-10-06

    Assessment of quality-of-life (QOF) as an outcome measure after deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD) need a valid, reliable and responsive instrument. The aim of the current study was to determine responsiveness of validated Persian version of PD questionnaire with 39-items (PDQ-39) after DBS surgery in patients with PD. Eleven patients with PD, who were candidate for DBS operation between May 2012 and June 2013 were assessed. PDQ-39 and short-form questionnaire with 36-items (SF-36) were used. To assess responsiveness of PDQ-39 standardized response mean (SRM) was used. Mean age was 51.8 (8.8) and all of the patients, but just one were male (10 patients). Mean duration of the disease was 8.7 (2.1) years. Eight patients were categorized as moderate using Hoehn and Yahr (H and Y) classification. All patients had a better H and Y score compared with the baseline evaluation (3.09 vs. 0.79). The amount of SRM was above 0.70 for all domains means a large responsiveness for PDQ-39. Persian version of PDQ-39 has an acceptable responsiveness and could be used to assess as an outcome measure to evaluate the effect of therapies on PD.

  12. The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

    Science.gov (United States)

    Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

    2015-08-01

    Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. [The role of neurologists in deep brain stimulation for Parkinson disease: a neurosurgical perspective].

    Science.gov (United States)

    Umemura, Atsushi

    2012-01-01

    Deep brain stimulation (DBS) has been accepted as an effective treatment for medically refractory Parkinson disease (PD). Appropriate patient selection, safe and precise surgery, and proper postoperative adjustment of stimulation and medication, are essential for the success of DBS. Patient selection is the most important role for the neurologist in DBS treatment. Neurologists treating PD should understand the correct indications and contraindications for DBS, and introduce it in a timely manner to patients who can be expected to benefit substantially from it. For long term treatment of PD, ideally the neurologist in charge of the patient should adjust both the stimulation parameters and medication. Neurologists engaged in this treatment should also have a comprehensive understanding of the probable complications and how to avoid them.

  14. Olfactory deficits in Niemann-Pick type C1 (NPC1 disease.

    Directory of Open Access Journals (Sweden)

    Marina Hovakimyan

    Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disease characterized by progressive neurodegeneration. As only a few studies have been conducted on the impact of NPC on sensory systems, we used a mutant mouse model (NPC1(-/- to examine the effects of this disorder to morphologically distinct regions of the olfactory system, namely the olfactory epithelium (OE and olfactory bulb (OB. METHODOLOGY/PRINCIPAL FINDINGS: For structural and functional analysis immunohistochemistry, electron microscopy, western blotting, and electrophysiology have been applied. For histochemistry and western blotting, we used antibodies against a series of neuronal and glia marker proteins, as well as macrophage markers. NPC1(-/- animals present myelin-like lysosomal deposits in virtually all types of cells of the peripheral and central olfactory system. Especially supporting cells of the OE and central glia cells are affected, resulting in pronounced astrocytosis and microgliosis in the OB and other olfactory cortices. Up-regulation of Galectin-3, Cathepsin D and GFAP in the cortical layers of the OB underlines the critical role and location of the OB as a possible entrance gate for noxious substances. Unmyelinated olfactory afferents of the lamina propria seem less affected than ensheathing cells. Supporting the structural findings, electro-olfactometry of the olfactory mucosa suggests that NPC1(-/- animals exhibit olfactory and trigeminal deficits. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a pronounced neurodegeneration and glia activation in the olfactory system of NPC1(-/-, which is accompanied by sensory deficits.

  15. Picking of foreign television formats by Czech televisions

    OpenAIRE

    Šopovová, Andrea

    2010-01-01

    This paper is concerned with one of the impacts of media globalisation and it is a picking of foreign television formats. It analyzes the structure of television programs offered by Czech television broadcasters and its change from 2005 when TV Nova and TV Prima changed their owners to international ones. After the introduction of media globalisation, the paper describes the television formats and then it includes a list of licensed television programs and a comparison of chosen programs with...

  16. Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease.

    Science.gov (United States)

    Antoniades, Chrystalina A; Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z; Green, Alexander L; FitzGerald, James J

    2015-09-23

    The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows

  17. POLYMORPHISM OF THE SYNDROME OF HYPERACTIVE URINARY BLADDER IN PATIENTS WITH ACUTE AND CHRONIC VASCULAR DISEASES OF THE BRAIN

    Directory of Open Access Journals (Sweden)

    P. G. Shvarts

    2016-01-01

    Full Text Available Abstract. The paper discusses the main etiological, phenomenological and pathogenetic mechanisms of forming the syndrome of overactive bladder (OAB in patients with acute and chronic cerebrovascular diseases. Describes the role of melatonin, arginine vasopressin (AVP and corticotropin-releasing factor hormone (CRFH in maintaining the rhythms of urination, urine formation and retention of urine in norm and abnormalities in these systems in acute and chronic vascular pathology of the brain. Described phenomenology OAB syndrome in vascular diseases of the brain. Shows a differentiated approach to pharmacological correction in patients with different clinical variants of urinary disorders and urine formation in the framework of the OAB syndrome with the use of neurotransmitter therapy and hormonesensitive.

  18. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    Science.gov (United States)

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

  19. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  20. Use of ergonomic principles in manual order picking systems

    Directory of Open Access Journals (Sweden)

    Labus Nina

    2018-02-01

    Full Text Available Successful companies are continually striving to streamline costs and optimize processes, enabling them to grow progress, develop and ensure competitiveness on the market. A large part of the costs arises in warehouses, where up to 55% of total costs are generated by order-picking, which makes it important and interesting in terms of research. The paper explores “picker to part” order-picking concept, which enables flexible work and is the optimal choice for most companies. The concept is associated with a high level of work-related injuries and work-related illnesses. Work requires physical efforts resulting from handling heavy goods, performing repetitive movements and using manipulative means. Human as the main actor of the concept affects the costs caused by picking and the quality of work done, which depends on technological support, physically and psychologically capable and motivated people. Due to the high costs of service, the focus on time planning and productivity increases. Contrary, the lack of attention is paid to the working conditions and the health status of the pickers. To overcome this gab, a review of scientific and professional literature on ergonomic principles in picking concept »picker to part« was carried out, followed by a quantitative survey of ergonomic properties in warehousing activities. Results revealed that more than 60% of the surveyed order-pickers associate problems with health with the characteristics of work, about 24% of them associate health problems with the use of a particular means of transport, and all agree that provided measures to reduce physical effort and greater support of technologies influence on increased speed of work and better health status of order-pickers.

  1. Two-dimensional ultrasonography of the brain: its diagnostic usefullness in herpes simplex encephalitis and cytomegalic inclusion disease.

    Science.gov (United States)

    Matsumoto, N; Yano, S; Miyao, M; Kamoshita, S; Itoh, K

    1983-01-01

    We have used brain ultrasonography in diagnosing and following up two infants, one with herpes simplex encephalitis and the other with cytomegalic inclusion disease. It was found that this technique was very useful to observe the changes of the brain parenchyma such as cystic degeneration and periventricular calcification. Also because it is non-invasive and an easy procedure, ultrasonography can be applied even for infants in critical condition when needed.

  2. Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

    Science.gov (United States)

    Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

    2017-11-01

    Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

  3. Clearance systems in the brain-implications for Alzheimer disease.

    Science.gov (United States)

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

  4. Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    de Oliveira, Diêgo Madureira; Ferreira Lima, Rute Maria; El-Bachá, Ramon Santos

    2012-05-01

    Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.

  5. Theory of feedback controlled brain stimulations for Parkinson's disease

    Science.gov (United States)

    Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

    2016-01-01

    Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

  6. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford; Jagust, William; Trojanowski, John Q; Shaw, Leslie M; Saykin, Andrew J; Green, Robert C; Harvey, Danielle; Toga, Arthur W; Friedl, Karl E; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2014-06-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  7. Vestibular function in patients with Niemann-Pick type C disease.

    Science.gov (United States)

    Bremova, Tatiana; Krafczyk, Siegbert; Bardins, Stanislavs; Reinke, Jörg; Strupp, Michael

    2016-11-01

    We investigated whether vestibular dysfunction may cause or contribute to postural imbalance and falls in patients with Niemann-Pick type C disease (NP-C). Eight patients with NP-C disease and 20 healthy controls were examined using the video-based head impulse test (vHIT) and caloric irrigation to investigate horizontal canal function as well as ocular- and cervical vestibular evoked myogenic potentials (o- and cVEMP), and binocular subjective visual vertical estimation (SVV) for otolith function, and static posturography. There were no significant differences in vestibulo-ocular gain, caloric excitability, o-/cVEMP measures or SVV between the two groups. Posturographic total sway path (tSP) and root mean square (RMS) were significantly higher in NP-C than in controls in 3 out of 4 conditions. The Romberg quotient (RQ) to assess the amount of visual stabilization was significantly lower in the NP-C than in the HC group. In contrast to other inherited metabolic disorders, such as Morbus Gaucher type 3, we did not find any evidence for an impairment of canal or otolith function in patients with NP-C as their cause of postural imbalance. Since RQ was low in NP-C patients, indicating proper sensory input, the observed increased postural sway is most likely due to a cerebellar dysfunction in NP-C, which may therefore, explain postural imbalance.

  8. From miracle to reconciliation: a hermeneutic phenomenological study exploring the experience of living with Parkinson's disease following deep brain stimulation.

    Science.gov (United States)

    Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

    2010-10-01

    Deep Brain Stimulation for Parkinson's disease is a promising treatment for patients who can no longer be treated satisfactorily with L-dopa. Deep Brain Stimulation is known to relieve motor symptoms of Parkinson's disease and improve quality of life. Focusing on how patients experience life when treated with Deep Brain Stimulation can provide essential information on the process patients go through when receiving a treatment that alters the body and changes the illness trajectory. The aim of this study was to explore and describe the experience of living with Parkinson's disease when treated with Deep Brain Stimulation. The study was designed as a longitudinal study and data were gathered through qualitative in-depth interviews three times during the first year of treatment. Nine patients participated in the study. They were included when they had accepted treatment with Deep Brain Stimulation for Parkinson's disease. Data collection and data analysis were inspired by the hermeneutic phenomenological methodology of Van Manen. The treatment had a major impact on the body. Participants experienced great bodily changes and went through a process of adjustment in three phases during the first year of treatment with Deep Brain Stimulation. These stages were; being liberated: a kind of miracle, changes as a challenge: decline or opportunity and reconciliation: re-defining life with Parkinson's disease. The course of the process was unique for each participant, but dominant was that difficulties during the adjustment of stimulation and medication did affect the re-defining process. Patients go through a dramatic process of change following Deep Brain Stimulation. A changing body affects their entire lifeworld. Some adjust smoothly to changes while others are affected by loss of control, uncertainty and loss of everyday life as they knew it. These experiences affect the process of adjusting to life with Deep Brain Stimulation and re-define life with Parkinson's disease

  9. 99mTc-ECD brain SPECT in patients with Moyamoya disease: a reflection of cerebral perfusion status at tissue level in the disease process

    International Nuclear Information System (INIS)

    Kashyap, Raghava; Mittal, Bhagwant Rai; Sunil, Hejjaji Venkataramarao; Bhattacharya, Anish; Singh, Baljinder; Mukherjee, Kanchan Kumar; Gupta, Sunil Kumar

    2011-01-01

    Moyamoya disease is a rare, progressive cerebrovascular disorder caused by intracranial stenosis of the circle of Willis, resulting in successive ischemic events. Computed tomography (CT) and magnetic resonance imaging (MRI) play a major role in diagnosis. The aim of the study was to describe the spectrum of findings on brain SPECT in patients with Moyamoya disease and to compare the findings with other investigations. 99m Tc-ECD SPECT scans of seventeen patients (7 children and 10 adults) were analysed to study the brain perfusion. Features of Moyamoya disease were detected on DSA in 11 patients, CTA in one, MR angiography in one patient. Brain perfusion SPECT analysis showed unilateral perfusion defects in 11 patients, normal perfusion in 2 and bilateral defects in 4 patients. No perfusion defects despite bilateral vascular changes were noted in one patient. Cerebral infarcts were detected on MRI unilaterally in three subjects while multiple infarcts were identified in one. 99m Tc-ECD Brain SPECT showed perfusion defects that were more extensive compared to those detected on MRI. Post acetazolamide studies for assessment of cerebrovascular reserve were done in three patients. Two of them showed good cerebrovascular reserve (>1). Follow-up studies post-surgical procedures (Myo-dura synangiosis) done in two patients showed partial resolution of perfusion defects in the involved areas. Brain perfusion scintigraphy is an important adjunct in evaluation of patients with Moyamoya disease yielding information about the direct end results of the pathology in the vessels and also prognostic information. (author)

  10. Pick-up and impact of flexible bodies

    Science.gov (United States)

    Singh, H.; Hanna, J. A.

    2017-09-01

    Picking up, laying down, colliding, rolling, and peeling are partial-contact interactions involving moving discontinuities. We examine the balances of momentum and energy across a moving discontinuity in a string, with allowance for injection or dissipation by singular supplies. We split the energy dissipation according to its invariance properties, discuss analogies with systems of particles and connections with the literature on shocks and phase transition fronts in various bodies, and derive a compatibility relation between supplies of momentum and translation-invariant energy. For a moving contact discontinuity between a string and a smooth rigid plane in the presence of gravity, we find a surprising asymmetry between the processes of picking up and laying down, such that steady-state kinks in geometry and associated jumps in tension are not admissible during pick-up. This prediction is consistent with experimental observations. We briefly discuss related problems including the falling folded chain, peeling of an adhesive tape, and the "chain fountain". Our approach is applicable to the study of impact and locomotion, and to systems such as moored floating structures and some musical instruments that feature vibrating string and cable elements interacting with a surface.

  11. Material flow enhancement in production assembly lines under application of zoned order picking systems

    Directory of Open Access Journals (Sweden)

    D. Živanić

    2014-10-01

    Full Text Available Introduced research work relates to the possibility of material flow enhancement in production systems, with the apostrophe on material order picking in production assembly lines. The paper presents basic rules and the results related to formed computer models of zoned order picking systems under the application of developed bound cavities method.

  12. siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.

    Science.gov (United States)

    Gomes, Maria João; Martins, Susana; Sarmento, Bruno

    2015-05-01

    As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways.

    Science.gov (United States)

    Zilka, Norbert; Kazmerova, Zuzana; Jadhav, Santosh; Neradil, Peter; Madari, Aladar; Obetkova, Dominika; Bugos, Ondrej; Novak, Michal

    2012-03-07

    Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.

  14. The brain's default network: anatomy, function, and relevance to disease.

    Science.gov (United States)

    Buckner, Randy L; Andrews-Hanna, Jessica R; Schacter, Daniel L

    2008-03-01

    Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.

  15. Influence of age and sex on quantitative parameters in CT of the brain in neurogeriatric diseases. 2

    International Nuclear Information System (INIS)

    Ternovoj, S.K.; Damulin, I.V.

    1991-01-01

    The paper is devoted to a study of age and sex differences of linear, volumetric, volumetric longitudinal and densitometric parameters of CT of the brain in patients with neurogeriatric diseases with chronic cerebrovascular insufficiency. The ventricular system of the brain and subarachnoid space was shown to increase with age; a decrease in the relative density of the white substance at the anterior horns was noted. Sex differences were most noticeable in younger patients. Average sizes of the ventricular system and subarachnoid space were indicated for men and women belonging to different age groups. A conclusion was made that assessment of CT results in neurogeriatric patients must include their age and sex

  16. Order Picking Process in Warehouse: Case Study of Dairy Industry in Croatia

    Directory of Open Access Journals (Sweden)

    Josip Habazin

    2017-02-01

    Full Text Available The proper functioning of warehouse processes is fundamental for operational improvement and overall logistic supply chain improvement. Order picking is considered one of the most important from the group. Throughout picking orders in warehouses, the presence of human work is highly reflected, with the main goal to reduce the process time as much as possible, that is, to the very minimum. There are several different order picking methods, and nowadays, the most common ones are being developed and are significantly dependent on the type of goods, the warehouse equipment, etc., and those that stand out are scanning and picking by voice. This paper will provide information regarding the dairy industry in the Republic of Croatia with the analysis of order picking process in the observed company. Overall research highlighted the problem and resulted in proposals of solutions.

  17. Biomechanics of the brain

    CERN Document Server

    Miller, Karol

    2011-01-01

    With contributions from scientists at major institutions, this book presents an introduction to brain anatomy for engineers and scientists. It provides, for the first time, a comprehensive resource in the field of brain biomechanics.

  18. Treatment of Chronic Skin-Picking in an Adolescent With Asperger Syndrome and Borderline Intellectual Disability

    NARCIS (Netherlands)

    Lang, R.B.; Didden, H.C.M.; Sigafoos, J.; Rispoli, M.; Regester, A.; Lancioni, G.E.

    2009-01-01

    We present the case of a 17-year-old girl with Asperger syndrome and borderline intellectual disability with a 5-year history of chronic skin-picking. Our intervention approach included an initial functional assessment to identify variables maintaining skin-picking, followed by evaluation of a

  19. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

    2017-08-28

    In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

    Science.gov (United States)

    Mascalchi, M; Ginestroni, A; Bessi, V; Toschi, N; Padiglioni, S; Ciulli, S; Tessa, C; Giannelli, M; Bracco, L; Diciotti, S

    2013-01-01

    Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the

  1. Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

    Science.gov (United States)

    Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

    Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease

    DEFF Research Database (Denmark)

    Hoglund, K; Thelen, K M; Syversen, S

    2005-01-01

    During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients...... with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well...... as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta-amyloid (Abeta)(1-42). However, by analysis of APP isoforms, we found...

  3. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson's disease

    NARCIS (Netherlands)

    van Wouwe, N.C.; Ridderinkhof, K.R.; van den Wildenberg, W.P.M.; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD).

  4. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson’s disease

    NARCIS (Netherlands)

    Wouwe, N.C. van; Ridderinkhof, K.R.; Wildenberg, W.P.M. van den; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson’s disease (PD).

  5. The correlation between cherry picking and the distance that consumers travel to do grocery shopping

    Directory of Open Access Journals (Sweden)

    Louise Van Scheers

    2013-04-01

    Full Text Available Retailers often use price promotions to discriminate between consumers who can shift purchases over time and those who cannot. Retailers consistently tend to charge lower prices than necessary, pricing defensively to prevent loyal customers from cherry picking, or shifting to competitors. Knowledge about cherry picking behaviour will enable retailers to obtain a higher share of disposable income from even price-sensitive shoppers, while at the same time charging higher prices. Recent studies indicate that effective cherry picking entails saving costs through price searching over time, price searching across stores, or both. This study examines the relationship between cherry picking and the distance that consumers travel to do grocery shopping. Interviews were conducted at ten different retail outlets over three days, and the results show that there is a highly significant correlation between cherry picking and the distance that consumers travel to do grocery shopping.These results should help retailers to benefit from cherry picking by taking a proactive approach to store switching and store location, two of the main influences on cherry picking behaviour.

  6. A bone to pick? Fish bones of the upper aerodigestive tract: review of the literature.

    Science.gov (United States)

    Sands, Noah B; Richardson, Keith; Mlynarek, Alex

    2012-10-01

    Fish bones are of particular interest to the otolaryngologist as accidental ingestion is one of the most common reasons for otolaryngology-related emergency department referrals. Furthermore, removal of fish bones deeply lodged in the oropharynx or hypopharynx can be both hazardous and technically difficult, and failure to accomplish safe removal could result in considerable morbidity and various critical complications. We present here a literature review on the topic of fish bones in otolaryngology with a focus on selection of patients for intervention and on removal techniques. We emphasize that retained fish bones should be approached with caution as their course can at times be unpredictable, as we describe here.

  7. The pick-up mechanism in composite particle emission processes

    International Nuclear Information System (INIS)

    Zhang Jingshang; Yan Shiwei; Wang Cuilan

    1992-01-01

    The pick-up mechanism has been included in the exciton model for the light composite particle emissions. Based on the cluster phase space integration method the formation probabilities of α,d,t, 3 He are obtained. The calculation results of (n,t) cross sections indicate that this theoretical method can reproduce the experimental data nicely. For triton emissions in pre-equilibrium reaction processes, the semi-direct reactions are the dominant terms which are just omitted in the previous model calculation

  8. Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

    Science.gov (United States)

    Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

    2015-07-01

    Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The social impact of Parkinson's disease in Spain: Report by the Spanish Foundation for the Brain.

    Science.gov (United States)

    García-Ramos, R; López Valdés, E; Ballesteros, L; Jesús, S; Mir, P

    2016-01-01

    Understanding the social and economic impact of Parkinson's disease is essential for resource planning and raising social awareness. Researchers reviewed the data published to date on epidemiology, morbidity and mortality, dependency, and economic impact of Parkinson's disease in Spain. In addition, a study has been carried out in order to define the public and private health care resources of Spanish patients affected by Parkinson's disease by means of an e-mail survey of all neurologists specialising in this disease and belonging to the Spanish Society of Neurology's study group for movement disorders. The incidence and prevalence rates of Parkinson's disease in Spain are similar to those in the rest of Europe. According to current population estimates, there are at least 300.000 patients with Parkinson's disease and one new case per 10.000 habitants per year in Spain. This has a major impact on the patient's quality of life and nearly doubles patient mortality. In addition, the disease generates sizeable costs for the country that may exceed 17.000€ per year per patient; costs will rise due to the ageing of the population and the new therapies employed. Healthcare professionals and administrators dedicate their efforts to providing quality care to patients. Despite the above, we still have a long way to go in order to provide quality, efficient, multidisciplinary, and universal healthcare. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. How to reliably deliver narrow individual-patient error bars for optimization of pacemaker AV or VV delay using a "pick-the-highest" strategy with haemodynamic measurements.

    Science.gov (United States)

    Francis, Darrel P

    2013-03-10

    Intuitive and easily-described, "pick-the-highest" is often recommended for quantitative optimization of AV and especially VV delay settings of biventricular pacemakers (BVP; cardiac resynchronization therapy, CRT). But reliable selection of the optimum setting is challenged by beat-to-beat physiological variation, which "pick-the-highest" combats by averaging multiple heartbeats. Optimization is not optimization unless the optimum is identified confidently. This document shows how to calculate how many heartbeats must be averaged to optimize reliably by pick-the-highest. Any reader, by conducting a few measurements, can calculate for locally-available methods (i) biological scatter between replicate measurements, and (ii) curvature of the biological response. With these, for any clinically-desired precision of optimization, the necessary number of heartbeats can be calculated. To achieve 95% confidence of getting within ±∆x of the true optimum, the number of heartbeats needed is 2(scatter/curvature)(2)/∆x(4) per setting. Applying published scatter/curvature values (which readers should re-evaluate locally) indicates that optimizing AV, even coarsely with a 40ms-wide band of precision, requires many thousand beats. For VV delay, the number approaches a million. Moreover, identifying the optimum twice as precisely requires 30-fold more beats. "Pick the highest" is quick to say but slow to do. We must not expect staff to do the impossible; nor criticise them for not doing so. Nor should we assume recommendations and published protocols are well-designed. Reliable AV or VV optimization, using "pick-the-highest" on commonly-recommended manual measurements, is unrealistic. Improving time-efficiency of the optimization process to become clinically realistic may need a curve-fitting strategy instead, with all acquired data marshalled conjointly. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Examining the Relationship between Heart Rate and Problem Behavior: A Case Study of Severe Skin Picking in Prader-Willi Syndrome

    Science.gov (United States)

    Hall, Scott S.; Hammond, Jennifer L.; Hustyi, Kristin M.

    2013-01-01

    Few studies have examined the relationship between heart rate and self-injurious behavior (SIB) shown by individuals with IDD (intellectual and developmental disabilities). In this single-case study, we simultaneously monitored heart rate and activity levels during a functional analysis of severe skin picking behavior exhibited by a young man with…

  12. Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?

    International Nuclear Information System (INIS)

    Purandare, Nilendu C.

    2011-01-01

    Metastases to the brain can affect about 10-20% cancer patients. Rising incidence of brain metastases in recent years is related to improved survival rates as a result of advances in cancer therapy and development of more sensitive diagnostic imaging techniques. In patients with extracranial malignancies detection of brain metastases is very important in deciding further diagnostic procedures, planning therapeutic strategies and also to ascertain prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are the modalities which have been traditionally used to assess metastatic disease to the central nervous system. It is generally accepted that MRI (contrast enhanced) is superior to CT scan (contrast enhanced) in the diagnosis of brain metastases. An inherently better soft tissue contrast resolution, stronger contrast enhancement, lack of bone artifacts and partial volume effects and direct multiplanar imaging enables MRI to pick up smaller sized as well as more number of metastases than a CT scan

  13. Solar cycle variation of interstellar neutral He, Ne, O density and pick-up ions along the Earth's orbit

    Science.gov (United States)

    Sokół, Justyna M.; Bzowski, Maciej; Kubiak, Marzena A.; Möbius, Eberhard

    2016-06-01

    We simulated the modulation of the interstellar neutral (ISN) He, Ne, and O density and pick-up ion (PUI) production rate and count rate along the Earth's orbit over the solar cycle (SC) from 2002 to 2013 to verify if SC-related effects may modify the inferred ecliptic longitude of the ISN inflow direction. We adopted the classical PUI model with isotropic distribution function and adiabatic cooling, modified by time- and heliolatitude-dependent ionization rates and non-zero injection speed of PUIs. We found that the ionization losses have a noticeable effect on the derivation of the ISN inflow longitude based on the Gaussian fit to the crescent and cone peak locations. We conclude that the non-zero radial velocity of the ISN flow and the energy range of the PUI distribution function that is accumulated are of importance for a precise reproduction of the PUI count rate along the Earth orbit. However, the temporal and latitudinal variations of the ionization in the heliosphere, and particularly their variation on the SC time-scale, may significantly modify the shape of PUI cone and crescent and also their peak positions from year to year and thus bias by a few degrees the derived longitude of the ISN gas inflow direction.

  14. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    Science.gov (United States)

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial and each received a single dose of rhASM and underwent a repeat liver biopsy on Day 14. Biopsies were evaluated for fibrosis, sphingomyelin accumulation and macrophage infiltration by light and electron microscopy. When present, fibrosis was periportal and pericellular, predominantly surrounding affected Kupffer cells. Two baseline biopsies exhibited frank cirrhosis. Sphingomyelin was localized to isolated Kupffer cells in mildly affected biopsies and was present in both Kupffer cells and hepatocytes in more severely affected cases. Morphometric quantification of sphingomyelin storage in liver biopsies ranged from 4–44% of the microscopic field. Skin biopsies were also performed at baseline and Day 14 in order to compare the sphingomyelin distribution in a peripheral tissue to that of liver. Sphingomyelin storage was present at lower levels in multiple cell types of the skin, including dermal fibroblasts, macrophages, vascular endothelial cells, vascular smooth muscle cells and Schwann cells. This Phase 1 trial of rhASM in adults with ASMD provided a unique opportunity for a prospective assessment of hepatic and skin pathology in this rare disease and their potential usage as pharmacodynamic biomarkers. PMID:22613999

  15. Hydrogen pick-up effect on the deformation characteristics of the 20 steel

    International Nuclear Information System (INIS)

    Steklov, O.I.; Perunov, B.Vs.; Krovyakova, V.M.

    1977-01-01

    An experiment aimed at ascertaining the possibility of using plasticity characteristis as a criterion of the resistance of a material to slow failure through hydrogenation is set up in a manner to permit an evaluation of the individual effects of mechanical stresses hydrogenation medium and their combined action upon the plasticity characteristics. It is shown that the variation of the rupturing load for hydrogenated specimens of grade 20 steel, held under load, takes place on the initial holding stage, after which the changes in the plasticity characteritics are immaterial. In consequence, the deformation characteristics allow no judgement to be made on the resistance to slow cracking of grade 20 steel due to hydrogenation

  16. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Science.gov (United States)

    Vonberg, Isabelle; Ehlen, Felicitas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

    2016-01-01

    Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

  17. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Directory of Open Access Journals (Sweden)

    Isabelle Vonberg

    Full Text Available Reduced verbal fluency (VF has been reported in patients with Parkinson's disease (PD, especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS. To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS.Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields. The results were compared to those of eleven healthy control subjects.PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls.Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

  18. [The systemic and differential psychoprophylaxis of vascular brain diseases in the workers of an industrial enterprise].

    Science.gov (United States)

    Andreev, A G

    1994-01-01

    Basing on epidemiological, prospective and clinicopsychological data obtained on 1900 industrial workers of Nizhni Novgorod city, the system of psychoprophylaxis and psychotherapy of cerebrovascular diseases has been developed. The system of psychoprophylaxis was used with consideration of the disease stage and phase, psychic and psychosomatic status in risk groups, in subjects with initial and apparent symptoms of cerebrovascular failure. The psychoprophylactic system proved effective in the conditions of a large industrial enterprise.

  19. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  20. Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

    Directory of Open Access Journals (Sweden)

    Irune Diaz-Aparicio

    2016-01-01

    Full Text Available Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

  1. Multimodal Imaging of Brain Connectivity Using the MIBCA Toolbox: Preliminary Application to Alzheimer's Disease

    Science.gov (United States)

    Ribeiro, André Santos; Lacerda, Luís Miguel; Silva, Nuno André da; Ferreira, Hugo Alexandre

    2015-06-01

    The Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox is a fully automated all-in-one connectivity analysis toolbox that offers both pre-processing, connectivity, and graph theory analysis of multimodal images such as anatomical, diffusion, and functional MRI, and PET. In this work, the MIBCA functionalities were used to study Alzheimer's Disease (AD) in a multimodal MR/PET approach. Materials and Methods: Data from 12 healthy controls, and 36 patients with EMCI, LMCI and AD (12 patients for each group) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu), including T1-weighted (T1-w), Diffusion Tensor Imaging (DTI) data, and 18F-AV-45 (florbetapir) dynamic PET data from 40-60 min post injection (4x5 min). Both MR and PET data were automatically pre-processed for all subjects using MIBCA. T1-w data was parcellated into cortical and subcortical regions-of-interest (ROIs), and the corresponding thicknesses and volumes were calculated. DTI data was used to compute structural connectivity matrices based on fibers connecting pairs of ROIs. Lastly, dynamic PET images were summed, and the relative Standard Uptake Values calculated for each ROI. Results: An overall higher uptake of 18F-AV-45, consistent with an increased deposition of beta-amyloid, was observed for the AD group. Additionally, patients showed significant cortical atrophy (thickness and volume) especially in the entorhinal cortex and temporal areas, and a significant increase in Mean Diffusivity (MD) in the hippocampus, amygdala and temporal areas. Furthermore, patients showed a reduction of fiber connectivity with the progression of the disease, especially for intra-hemispherical connections. Conclusion: This work shows the potential of the MIBCA toolbox for the study of AD, as findings were shown to be in agreement with the literature. Here, only structural changes and beta-amyloid accumulation were considered. Yet, MIBCA is further able to

  2. O-6 Optical Property Degradation of the Hubble Space Telescope's Wide Field Camera-2 Pick Off Mirror

    Science.gov (United States)

    McNamara, Karen M.; Hughes, D. W.; Lauer, H. V.; Burkett, P. J.; Reed, B. B.

    2011-01-01

    Degradation in the performance of optical components can be greatly affected by exposure to the space environment. Many factors can contribute to such degradation including surface contaminants; outgassing; vacuum, UV, and atomic oxygen exposure; temperature cycling; or combinations of parameters. In-situ observations give important clues to degradation processes, but there are relatively few opportunities to correlate those observations with post-flight ground analyses. The return of instruments from the Hubble Space Telescope (HST) after its final servicing mission in May 2009 provided such an opportunity. Among the instruments returned from HST was the Wide-Field Planetary Camera-2 (WFPC-2), which had been exposed to the space environment for 16 years. This work focuses on the identifying the sources of degradation in the performance of the Pick-off mirror (POM) from WFPC-2. Techniques including surface reflectivity measurements, spectroscopic ellipsometry, FTIR (and ATR-FTIR) analyses, SEM/EDS, X-ray photoelectron spectroscopy (XPS) with and without ion milling, and wet and dry physical surface sampling were performed. Destructive and contact analyses took place only after completion of the non-destructive measurements. Spectroscopic ellipsometry was then repeated to determine the extent of contaminant removal by the destructive techniques, providing insight into the nature and extent of polymerization of the contaminant layer.

  3. Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

    Science.gov (United States)

    Parbo, Peter; Ismail, Rola; Hansen, Kim V; Amidi, Ali; Mårup, Frederik H; Gottrup, Hanne; Brændgaard, Hans; Eriksson, Bengt O; Eskildsen, Simon F; Lund, Torben E; Tietze, Anna; Edison, Paul; Pavese, Nicola; Stokholm, Morten G; Borghammer, Per; Hinz, Rainer; Aanerud, Joel; Brooks, David J

    2017-07-01

    See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

    Science.gov (United States)

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

  5. Put order picking system

    Directory of Open Access Journals (Sweden)

    Đurđević Dragan D.

    2014-01-01

    Full Text Available Nowadays the warehouse is very important logistic component of the supply chain, where order-picking systems have important role. Due to the significant impact on logistics performance permanent goals are to increase efficiency and reduce the cost of these systems. To achieve these goals, there are different researches, and their success is determined by the achieved performances. Performances order picking process are dependent on the applied technology concepts of order-picking system, as well as the ways in which it is organized and managed. In addition to the standard conceptions (the man to good and good to the man is one of the newer, so-called. 'put' system - the inverse order-picking. The aim of this paper is to describe this concept, point out its core strengths and weaknesses and provide a basis that may be of importance in the development of warehouse technological solutions and application of this order-picking systems concept.

  6. Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease.

    Science.gov (United States)

    Wu, Dan; Faria, Andreia V; Younes, Laurent; Mori, Susumu; Brown, Timothy; Johnson, Hans; Paulsen, Jane S; Ross, Christopher A; Miller, Michael I

    2017-10-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset ("premanifest" period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, "change-points"), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035-5050, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. The ATLAS beam pick-up based timing system

    International Nuclear Information System (INIS)

    Ohm, C.; Pauly, T.

    2010-01-01

    The ATLAS BPTX stations are composed of electrostatic button pick-up detectors, located 175 m away along the beam pipe on both sides of ATLAS. The pick-ups are installed as a part of the LHC beam instrumentation and used by ATLAS for timing purposes. The usage of the BPTX signals in ATLAS is twofold: they are used both in the trigger system and for LHC beam monitoring. The BPTX signals are discriminated with a constant-fraction discriminator to provide a Level-1 trigger when a bunch passes through ATLAS. Furthermore, the BPTX detectors are used by a stand-alone monitoring system for the LHC bunches and timing signals. The BPTX monitoring system measures the phase between collisions and clock with a precision better than 100 ps in order to guarantee a stable phase relationship for optimal signal sampling in the sub-detector front-end electronics. In addition to monitoring this phase, the properties of the individual bunches are measured and the structure of the beams is determined. On September 10, 2008, the first LHC beams reached the ATLAS experiment. During this period with beam, the ATLAS BPTX system was used extensively to time in the read-out of the sub-detectors. In this paper, we present the performance of the BPTX system and its measurements of the first LHC beams.

  8. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Aliev, Gjumrakch; Gasimov, Eldar; Obrenovich, Mark E; Fischbach, Kathryn; Shenk, Justin C; Smith, Mark A; Perry, George

    2008-01-01

    The pathogenesis that is primarily responsible for Alzheimer's disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD biopsy samples and two transgenic mouse models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which overexpress human amyloid beta precursor protein (AbetaPP). In situ hybridization using probes for normal and 5 kb deleted human and mouse mitochondrial DNA (mtDNA) was performed along with immunocytochemistry using antibodies against the Abeta peptide processed from AbetaPP, 8-hydroxy-2'-guanosine (8OHG), and cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as well as mitochondrial DNA deletions and structural abnormalities were present in the vascular walls of the human AD samples and the AbetaPP-YAC and C57B6/SJL Tg (+) transgenic mice compared to age-matched controls. Ultrastructural damage in perivascular cells highly correlated with endothelial lesions in all samples. Therefore, pharmacological interventions, directed at correcting the chronic hypoperfusion state, may change the natural course of the development of dementing neurodegeneration.

  9. Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.

    Science.gov (United States)

    Ekmekci, Hakan; Kaptan, Hulagu

    2016-01-01

    Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.

  10. Picking up the pieces: a generic porous Si biosensor for probing the proteolytic products of enzymes.

    Science.gov (United States)

    Shtenberg, Giorgi; Massad-Ivanir, Naama; Moscovitz, Oren; Engin, Sinem; Sharon, Michal; Fruk, Ljiljana; Segal, Ester

    2013-02-05

    A multifunctional porous Si biosensor that can both monitor the enzymatic activity of minute samples and allow subsequent retrieval of the entrapped proteolytic products for mass spectrometry analysis is described. The biosensor is constructed by DNA-directed/reversible immobilization of enzymes onto a Fabry-Pérot thin film. We demonstrate high enzymatic activity levels of the immobilized enzymes (more than 80%), while maintaining their specificity. Mild dehybridization conditions allow enzyme recycling and facile surface regeneration for consecutive biosensing analysis. The catalytic activity of the immobilized enzymes is monitored in real time by reflective interferometric Fourier transform spectroscopy. The real-time analysis of minute quantities of enzymes (concentrations at least 1 order of magnitude lower, 0.1 mg mL(-1), in comparison to previous reports, 1 mg mL(-1)), in particular proteases, paves the way for substrate profiling and the identification of cleavage sites. The biosensor configuration is compatible with common proteomic methods and allows for a successful downstream mass spectrometry analysis of the reaction products.

  11. Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain

    International Nuclear Information System (INIS)

    Caviness, V.S. Jr.; Phil, D.; Filipek, P.A.; Kennedy, D.N.

    1992-01-01

    The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging-based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently avaiable MRI-based methods. Opimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level. (author)

  12. Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.

    Science.gov (United States)

    Huang, Xiao-Tian; Qian, Zhong-Ming; He, Xuan; Gong, Qi; Wu, Ka-Chun; Jiang, Li-Rong; Lu, Li-Na; Zhu, Zhou-Jing; Zhang, Hai-Yan; Yung, Wing-Ho; Ke, Ya

    2014-05-01

    Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The BAR Domain Protein PICK1 Controls Vesicle Number and Size in Adrenal Chromaffin Cells

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; Jansen, Anna M; de Wit, Heidi

    2014-01-01

    , a marker for immature granules. In chromaffin cells isolated from a PICK1 knockout (KO) mouse the amount of exocytosis was reduced, while release kinetics and Ca(2+) sensitivity were unaffected. Vesicle-fusion events had a reduced frequency and released lower amounts of transmitter per vesicle (i...... in vesicle number and size, whereas the fusion competence of generated vesicles was unaffected by the absence of PICK1. Viral rescue experiments demonstrated that long-term re-expression of PICK1 is necessary to restore normal vesicular content and secretion, while short-term overexpression is ineffective...

  14. Collision free pick up and movement of large objects

    International Nuclear Information System (INIS)

    Drotning, W.D.; McKee, G.R.

    1998-01-01

    An automated system is described for the sensor-based precision docking and manipulation of large objects. Past work in the remote handling of large nuclear waste containers is extensible to the problems associated with the handling of large objects such as coils of flat steel in industry. Computer vision and ultrasonic proximity sensing as described here are used to control the precision docking of large objects, and swing damped motion control of overhead cranes is used to control the position of the pick up device and suspended payload during movement. Real-time sensor processing and model-based control are used to accurately position payloads

  15. The imaging of HIV-related brain disease | Hoare | Southern African ...

    African Journals Online (AJOL)

    2 In addition, there is growing recognition that many HIV-infected individuals will develop neuropsychiatric disorders relatively early in the course of HIV ... the neurotoxic effects of HIV result in damage to white matter tracts in the brain.6 Once damage is established and related cognitive disorders ensue, the ability of HAART ...

  16. Psychopathology of Time in Brain Disease and Schizophrenia

    Directory of Open Access Journals (Sweden)

    John Cutting

    1990-01-01

    Full Text Available The literature on disturbance of time-sense in brain disease and schizophrenia is reviewed and the subjective experience of altered time-sense reported by 45 out of 350 personally interviewed schizophrenics is analyzed. A review of the literature on the effect of brain damage revealed that some phenomena (déjà vu, reduplication of time, altered tempo to events were linked with right hemisphere dysfunction, one phenomenon (incorrect sequencing of events was linked with left anterior brain damage, and others (disrupted “biological clock”, disturbed serise of rate of flow of current or past events could arise from subcortical as well as focal cortical damage. The sparse literature on disturbed time-sense in schizophrenia suggested that there was a shared psychopathology in this respect with right hemisphere dysfunction. The phenomena encountered in the 45 schizophrenics are described and classified.

  17. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

    Directory of Open Access Journals (Sweden)

    Kristina Leuner

    2010-09-01

    Full Text Available Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g. might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential (MMP, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease (AD. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, these new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

  18. Specific proof of various stages of Osler's disease of the brain via high field magnetic resonance tomography (1. 5 Tesla)

    Energy Technology Data Exchange (ETDEWEB)

    Billet, F; Bluemm, R G; Beyer, H K

    1988-08-01

    MR is a sensitive noninvasive examination method for diagnosing parenchymatous cryptic arteriovenous malformations and sequels of cerebral haemorrhage. In a patient with recurring nosebleed and brain stem syndrome eleven so-called cryptic arteriovenous malformations or their haemorrhage sequels were diagnosed via magnetic resonance tomography. Basing on these specific findings, nosebleeding, and a positive family anamnesis, the findings could be classified as belonging to manifestations of Osler's disease (hereditary haemorrhagic telangiectasia). This rare disease is characterised by a triad of signs: telangiectasias, recurring bleeding, and heredity. In this article the specific MR image is compared with the CT pattern and the results are discussed against the background of literature on Osler's disease which is also known as Rendu-Osler-Weber disease.

  19. Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

    Science.gov (United States)

    Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

  20. Perspectives of a systems biology of the brain: the big data conundrum understanding psychiatric diseases.

    Science.gov (United States)

    Mewes, H W

    2013-05-01

    Psychiatric diseases provoke human tragedies. Asocial behaviour, mood imbalance, uncontrolled affect, and cognitive malfunction are the price for the biological and social complexity of neurobiology. To understand the etiology and to influence the onset and progress of mental diseases remains of upmost importance, but despite the much improved care for the patients, more then 100 years of research have not succeeded to understand the basic disease mechanisms and enabling rationale treatment. With the advent of the genome based technologies, much hope has been created to join the various dimension of -omics data to uncover the secrets of mental illness. Big Data as generated by -omics do not come with explanations. In this essay, I will discuss the inherent, not well understood methodological foundations and problems that seriously obstacle in striving for a quick success and may render lucky strikes impossible. © Georg Thieme Verlag KG Stuttgart · New York.

  1. A PICKED SAMPLE TO THE FOOTPRINT OF PRIMITIVE INDIVIDUALISM OF RECENT DATE ART: BASQUIAT

    Directory of Open Access Journals (Sweden)

    Ozgur TOSUN

    2015-09-01

    Full Text Available Through the culturel history, meaning of art and art object have been queried and these researchs have emerged thesis and antithesis. Fundamentaly, this article aim to comparison interaction and/or conflict with mathematical rationalist art and primitive/heuristical/romantic art. In this context, effects of primitive and experssive art to the nowadays’ art perception are examined to envolve out of Basquiat and neo expressionism. Entailment of expressive art in contemporary art is researched for answers for questions in terms of cultural and genetic heritage of art and instinctive origins of making art object.

  2. Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial diseased-Magnetic Resonance (SMART-MR) study

    NARCIS (Netherlands)

    Kooistra, M.; Geerlings, M.I.; van der Graaf, Y.; Mali, W.P.T.M.; Vincken, K.L.; Kappelle, L.J.; Muller, M.; Biessels, G.J.

    2014-01-01

    We examined the association between brain atrophy and vascular brain lesions (i.e., white matter lesions [WMLs] or brain infarcts), alone or in combination, with decline in memory and executive functioning over 4 years of follow-up in 448 patients (57 ± 9.5 years) with symptomatic atherosclerotic

  3. The role of deep brain stimulation in Parkinson’s disease: an overview and update on new developments

    Directory of Open Access Journals (Sweden)

    Fang JY

    2017-03-01

    Full Text Available John Y Fang, Christopher Tolleson Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Parkinson’s disease (PD is a progressive neurodegenerative disorder characterized by the loss of neuronal dopamine production in the brain. Oral therapies primarily augment the dopaminergic pathway. As the disease progresses, more continuous delivery of therapy is commonly needed. Deep brain stimulation (DBS has become an effective therapy option for several different neurologic and psychiatric conditions, including PD. It currently has US Food and Drug Administration approval for PD and essential tremor, as well as a humanitarian device exception for dystonia and obsessive-compulsive disorder. For PD treatment, it is currently approved specifically for those patients suffering from complications of pharmacotherapy, including motor fluctuations or dyskinesias, and a disease process of at least 4 years of duration. Studies have demonstrated superiority of DBS and medical management compared to medical management alone in selected PD patients. Optimal patient selection criteria, choice of target, and programming methods for PD and the other indications for DBS are important topics that continue to be explored and remain works in progress. In addition, new hardware options, such as different types of leads, and different software options have recently become available, increasing the potential for greater efficacy and/or reduced side effects. This review gives an overview of therapeutic management in PD, specifically highlighting DBS and some of the recent changes with surgical therapy. Keywords: Parkinson’s disease, deep brain stimulation, functional neurosurgery 

  4. Excoriation (skin-picking disorder: a systematic review of treatment options

    Directory of Open Access Journals (Sweden)

    Lochner C

    2017-07-01

    Full Text Available Christine Lochner,1 Annerine Roos,1 Dan J Stein2 1SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, South Africa; 2SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, South Africa Abstract: Although pathological skin-picking has been documented in the medical literature since the 19th century, it has only recently been included as a distinct entity in psychiatric classification systems. In the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposed International Classification of Diseases, Eleventh Revision, excoriation (skin-picking disorder (ED, also known as neurotic excoriation, psychogenic excoriation, or dermatillomania, is described as recurrent picking of skin, leading to skin lesions and significant distress or functional impairment. ED is listed as one of the obsessive–compulsive and related disorders, given its overlap with conditions such as trichotillomania (hair-pulling disorder. Arguably, its inclusion and delineation in the diagnostic nomenclature will lead to increased awareness of the condition, more research, and ultimately in treatment advances. This systematic review aims to provide readers with an up-to-date view of current treatment options for ED. A MEDLINE search of the ED treatment literature was conducted to collate relevant articles published between 1996 and 2017. The findings indicate that a number of randomized controlled trails on ED have now been published, and that current management options include behavioral therapy (habit reversal or acceptance-enhanced behavior therapy, and medication (selective serotonin reuptake inhibitors or N-acetyl cysteine. Keywords: excoriation, skin-picking, treatment, habit reversal therapy, behavioral therapy, pharmacotherapy, systematic review

  5. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease.

    Science.gov (United States)

    Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

    2013-01-01

    Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  6. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

    DEFF Research Database (Denmark)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

    2009-01-01

    in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

  7. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

    Science.gov (United States)

    Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

    1992-01-01

    This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

  9. Significance of cranial computerized tomography for diagnosis and therapy of inflammatory diseases of the brain and meninges in children

    Energy Technology Data Exchange (ETDEWEB)

    Kotlarek, F; Hauke, P; Zeumer, H [Technische Hochschule Aachen (Germany, F.R.). Abt. Kinderheilkunde; Technische Hochschule Aachen (Germany, F.R.). Abt. Neurologie)

    1979-01-01

    The significance of cranial computerized tomography (CCT) for the diagnosis and therapy of inflammatory diseases of the central nervous system in children is discussed in connection with five characteristic case studies. CCT is shown to be superior to classical neuroradiological approaches, and to allow important diagnostic insights: 1. the early recognition of diffuse brain edema and the resulting possibility of an early begin of therapy - 2. the pathological expansions of the cerebral ventricles of various etiology before a pathological enlargement of the head can be detected, and the size of the ventricles after neurosurgical therapy can be measured - 3. the early recognition of space-occupying inflammatory complications.

  10. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1985-01-01

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  11. Hypometabolism in Posterior and Temporal Areas of the Brain is Associated with Cognitive Decline in Parkinson's Disease.

    Science.gov (United States)

    Tard, Céline; Demailly, Franck; Delval, Arnaud; Semah, Franck; Defebvre, Luc; Dujardin, Kathy; Moreau, Caroline

    2015-01-01

    Brain metabolic profiles of patients with Parkinson's disease (PD) and cognitive impairment or dementia are now available. It would be useful if data on brain metabolism were also predictive of the risk of a pejorative cognitive evolution - especially in the multidisciplinary management of advanced PD patients. The primary objective was to determine whether a specific brain metabolic pattern is associated with cognitive decline in PD. Sixteen advanced PD patients were screened for the absence of cognitive impairment (according to the Mattis dementia rating scale, MDRS) and underwent [18F]-fluorodeoxyglucose positron emission tomography brain imaging in the "off drug" state. The MDRS was scored again about two years later, categorizing patients as having significant cognitive decline (decliners) or not (stables). The two groups were then compared in terms of their brain metabolism at inclusion. There were six decliners and ten stables. Significant hypometabolism in the two precunei (Brodmann area (BA) 31), the left middle temporal gyrus (BA21) and the left fusiform gyrus (BA37) was found in the decliner group compared withthe stables. In advanced PD, a particular metabolic pattern may be associated with the onset of significant cognitive decline.

  12. Characteristics of Brain Perfusion in Patients of Parkinson's Disease

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Park, Min Jung; Kim, Jae Woo; Kang, Young Kang

    2008-01-01

    It was well known that cerebral blood perfusion is normal or diffusely decreased in the majority of patients with Parkinson's disease (PD). Actually we interpreted brain perfusion SPECT images of PD patients in the clinical situation, we observed various cerebral perfusion patterns in patients with PD. So we performed brain perfusion SPECT to know the brain perfusion patterns of PD patients and the difference of perfusion patterns according to the sex and the age. Also we classified PD patients into small groups based on the brain perfusion pattern. Two hundred nineteen patients (M: 70, F: 149, mean age: 62.9±6.9 y/o) who were diagnosed as PD without dementia clinically and 55 patients (M: 15, F: 40, mean age: 61.4±9.2 y/o) as normal controls who had no past illness history were performed 99m Tc-HMPAO brain perfusion SPECT and neuropsychological test. At first, we compared all patients with PD and normal controls. Brain perfusion in left inferior frontal gyrus, left insula, left transverse temporal gyrus, left inferior parietal lobule, left superior parietal lobule, right precuneus, right caudate tail were lower in patients with PD than normal controls. Secondly, we compared male and female patients with PD and normal controls, respectively. Brain perfusion SPECT showed more decreased cerebral perfusion in left hemisphere than right side in both male and female patients compared to normal controls. And there was larger hypoperfusion area in female patients compared with male. Thirdly, we classified patients with PD and normal controls into 4 groups according to the age and compared brain perfusion respectively. In patient below fifties, brain perfusion in both occipitoparietal and left temporal lobe were lower in PD group. As the patients with PD grew older, hypoperfusion area were shown in both frontal, temporal and limbic lobes. Fourthly, We were able to divide patients into small groups based on cerebral perfusion pattern. There was normal cerebral blood

  13. Functional brain SPECT with 99mTc-HMPAO in the diagnosis of Alzheimer disease

    International Nuclear Information System (INIS)

    Urbanek, J.; Kupka, K.; Samal, M.; Jirak, R.; Obenberger, J.

    1998-01-01

    The explanatory power of perfusion diagrams obtained by the title technique was examined. In addition to the standard reconstruction procedure, a special reorientation procedure aimed at a differentiation of the hippocampus structure was applied. The study gave evidence of a high specificity and sensitivity of brain SPECT in the differential diagnosis of dementias. Multifactorial analysis of all available diagnostic techniques has borne out the dominant position of brain SPECT with 99m Tc-HMPAO, particularly when using special projection onto the hippocampus, and has led to the formulation of an examination algorithm where a combination of SPECT and MRI (and CT) enables DAT to be distinguished from dementias of other etiologies with a probability higher than 90%

  14. The hot pick-up technique for batch assembly of van der Waals heterostructures

    DEFF Research Database (Denmark)

    Pizzocchero, Filippo; Gammelgaard, Lene; Jessen, Bjarke Sørensen

    2016-01-01

    The assembly of individual two-dimensional materials into van der Waals heterostructures enables the construction of layered three-dimensional materials with desirable electronic and optical properties. A core problem in the fabrication of these structures is the formation of clean interfaces...... between the individual two-dimensional materials which would affect device performance. We present here a technique for the rapid batch fabrication of van der Waals heterostructures, demonstrated by the controlled production of 22 mono-, bi- and trilayer graphene stacks encapsulated in hexagonal boron...

  15. Travel motives of participants in the Cape Argus Pick n Pay Cycle Tour

    African Journals Online (AJOL)

    participation motives) that cyclists participate. The literature review recorded that little research has been done on travel motives of participants in sport events and this was the first of its kind in South Africa. The research was conducted by means of a ...

  16. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

    Science.gov (United States)

    Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

    2015-10-01

    In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  18. Interpersonal traits change as a function of disease type and severity in degenerative brain diseases.

    Science.gov (United States)

    Sollberger, Marc; Neuhaus, John; Ketelle, Robin; Stanley, Christine M; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Miller, Bruce L; Rankin, Katherine P

    2011-07-01

    Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage; however, little is known about the natural history of these personality changes throughout the course of each disease. To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth and ingenuousness were collected annually for 1 to 4 years on 188 patients (67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimer's disease (AD)) and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild or moderate-to-severe disease stages were compared within and between patient groups. Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits were associated with emotional affiliation (ie, extraversion, warmth and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression.

  19. Lack of evidence for dysfunction of the blood-brain barrier in Alzheimer's disease: an immunohistochemical study

    NARCIS (Netherlands)

    Rozemuller, J. M.; Eikelenboom, P.; Kamphorst, W.; Stam, F. C.

    1988-01-01

    With immunohistoperoxidase techniques the presence of plasma (serum) proteins was investigated in senile plaques, congophilic angiopathy, neurons and glial cells in brains of patients with Alzheimer's dementia. Other investigators have found plasma proteins in brain parenchyma and suggested that

  20. The hour equivalent solar pick, definition and interpretation

    International Nuclear Information System (INIS)

    Pérez Martínez, Maykop; Morales Rodríguez; Clemente; Castro Ingeniero, Elio

    2017-01-01

    Photovoltaic solar energy takes advantage of the light energy of the sun to produce electricity through semiconductor plates that are altered by solar radiation, these systems are called Photovoltaic Solar Panels (PSP). In order to calculate the energy absorbed by these PSPs, it is necessary to use technical terms that are a little difficult to interpret, for those less experienced in the subject, above all because of the ambiguity, the level of abstraction required in their understanding and the variety of ways of expressing very similar ideas without offering a clear and unique definition. The main term to which this article is dedicated is the Hour Solar Pick (HSP), which in the experiences of the authors has generated strong discussions about its interpretation. In order to arrive at the desired term, it is necessary to start with others, so the aim is to propose a definition and physical and mathematical interpretation to clarify the meaning of this term. (author)

  1. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    International Nuclear Information System (INIS)

    Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed; Abdalla, Ahmed; Fathy, Abeer; Azab, Ahmed; Rahman, Ashraf Abdel

    2009-01-01

    The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm 2 was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

  2. Distribution of Arsenic, Manganese, and Selenium in the Human Brain in Chronic Renal Insufficiency, Parkinsons Disease and Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Larsen, N. A.; Pakkenberg, H.; Damsgaard, Else

    1981-01-01

    The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were...... determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis...

  3. Picking Robot Arm Trajectory Planning Method

    Directory of Open Access Journals (Sweden)

    Zhang Zhiyong

    2014-01-01

    Full Text Available The picking robot arm is scheduled to complete picking tasks in the working space, to overcome the shaking vibration to improve the picking stability, its movement should follow specific consistence trajectory points. Usually we should give definite multiple feature picking points, map their inverse kinematics to the joint space, establish motion equation for the corresponding point in the joint space, then follow these equations motion for the interpolation on the joint so that we can meet the movement requirements. Trajectory planning is decisive significance for accuracy and stability of controlling robot arm. The key issue that picking arm complete picking task will be come true by trajectory planning, namely, robot arm track the desired trajectory. which based on kinematics and statics picking analysis in a joint space according to the requirements of picking tasks, and obtain the position and orientation for picking robot arm, study and calculate the theory of trajectory parameters timely.

  4. An assessment of the efficacy and safety of cross technique with 100% TCA in the management of ice pick acne scars

    Directory of Open Access Journals (Sweden)

    Deepali Bhardwaj

    2010-01-01

    Full Text Available Background : Chemical reconstruction of skin scars (CROSS is a technique using high concentrations of trichloroacetic acid (TCA focally on atrophic acne scars to induce inflammation followed by collagenisation. This can lead to reduction in the appearance of scars and cosmetic improvement. Aims : The aim of this pilot study is to investigate the safety of the CROSS technique, using 100% TCA, for atrophic ice pick acne scars. Settings and Design : Open prospective study. Materials and Methods : Twelve patients with predominant atrophic ice pick post acne scars were treated with the CROSS technique, using 100% TCA, applied with a wooden toothpick, at two weekly intervals for four sittings. Efficacy was assessed on the basis of the physician′s clinical assessment, photographic evaluation at each sitting and patient′s feedback after the fourth treatment, and at the three-month and six-month follow-up period, after the last treatment. Results : More than 70% improvement was seen in eight out of ten patients evaluated and good results (50 - 70% improvement were observed in the remaining two patients. No significant side effects were noted. Transient hypopigmentation and hyperpigmentation was observed in one patient each. Physician′s findings were in conformity with the patient′s assessment. Three months after the last treatment, one patient noted a decrease in improvement with no further improvement even at the six-month follow-up period. Conclusion : The CROSS technique with 100% TCA is a safe, efficacious, cost-effective and minimally invasive technique for the management of ice pick acne scars that are otherwise generally difficult to treat. In few patients the improvement may not be sustained, probably due to inadequate or delayed collagenisation.

  5. The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

    Directory of Open Access Journals (Sweden)

    Hanneke de Waal

    Full Text Available Synaptic loss is a major hallmark of Alzheimer's disease (AD. Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.179 drug-naïve mild AD patients who participated in the Souvenir II study.Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.In a secondary analysis of the Souvenir II study, electroencephalography (EEG brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma and global network integration (normalised characteristic path length lambda were compared between study groups, and related to memory performance.THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and

  6. The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

    Science.gov (United States)

    de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

    2014-01-01

    Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for

  7. Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature

    International Nuclear Information System (INIS)

    Cakmakci, Handan; Pekcevik, Yeliz; Yis, Uluc; Unalp, Aycan; Kurul, Semra

    2010-01-01

    The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p < 0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.

  8. Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Cakmakci, Handan, E-mail: handan.cakmakci@deu.edu.t [Dokuz Eylul University Faculty of Medicine, Department of Radiology, Izmir (Turkey); Pekcevik, Yeliz [Dokuz Eylul University Faculty of Medicine, Department of Radiology, Izmir (Turkey); Yis, Uluc [Dokuz Eylul University Faculty of Medicine, Department of Pediatric Neurology, Izmir (Turkey); Unalp, Aycan [Behcet Uz Hospital, Department of Pediatric Neurology, Izmir (Turkey); Kurul, Semra [Dokuz Eylul University Faculty of Medicine, Department of Pediatric Neurology, Izmir (Turkey)

    2010-06-15

    The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p < 0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.

  9. Clinical significance of I-123 IMP brain SPECT in children with brain diseases

    International Nuclear Information System (INIS)

    Takishima, Teruo; Machida, Kikuo; Honda, Norinari; Mamiya, Toshio; Takahashi, Taku; Kamano, Tsuyoshi; Hasegawa, Noriko

    1990-01-01

    Single photon emission computed tomography (SPECT) of the brain using N-isopropyl p-I-123-iodoamphetamine (I-123 IMP) was performed in 43 children with suspected brain diseases. Forty-three children (25 males and 18 females), with an age range of 24 days-15 years (mean: 6.6 years), were included in the study. Six patients were subsequently diagnosed as normal. Early SPECT of the brain was performed 30 minutes after intravenous administration of 74-111 MBq (2-3 mCi) I-123 IMP using a rotating gamma camera equipped with a 30-degree slant hole and medium energy collimator. Transverse images were reconstructed by Shepp-Logan filtered back projection method with attenuation correction after spatial filtering using an 8th order Butterworth-Wiener filter. Findings of I-123 IMP SPECT were compared with those of X-ray computed tomography (CT) and electroencephalography (EEG). The results showed that in I-123 IMP SPECT, abnormality was found in 30 out of 37 children with brain diseases. The incidence of abnormal findings in the 37 patients was 81% in I-123 IMP SPECT, 61% in X-ray CT, and 78% in EEG; in both cryptogenic and secondary epilepsy, the incidence of abnormality was higher in I-123 IMP SPECT than in X-ray CT. (70% and 94% vs 50% and 81% respectively), and epileptic foci detected by EEG did not correspond with defects found using I-123 IMP SPECT in 27% of the patients; and in asphyxiated infants, a high incidence of abnormality was observed on both I-123 IMP SPECT (86%) and X-ray CT (86%). In conclusion, I-123 IMP SPECT is a clinically useful examination in children with brain disease. (author)

  10. Metabolism of glucose in brain of patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki.

    1984-01-01

    We examined 11 C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11 C-glucose (per os). 11 C-glucose was prepared from 11 CO 2 by photosynthesis. 1) No significant difference was observed in the 11 C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11 C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

  11. A Comparative Analysis of Structural Brain MRI in the Diagnosis of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Jason Appel

    2009-01-01

    Full Text Available Dementia is a debilitating and life-altering disease which leads to both memory impairment and decline of normal executive functioning. While causes of dementia are numerous and varied, the leading cause among patients 60 years and older is Alzheimer’s disease. The gold standard for Alzheimer’s diagnosis remains histological identification of amyloid plaques and neurofibrillary tangles within the medial temporal lobe, more specifically the entorhinal cortex and hippocampus. Although no definitive cure for Alzheimer's disease currently exists, there are treatments targeted at preserving cognition and memory while delaying continued loss of function. Alzheimer's disease exists along a spectrum of cognitive decline and is often preceded by Mild Cognitive Impairment (MCI. Patients with MCI demonstrate memory loss and cognitive impairment while still continuing normal activities of daily living, and are considered to be at increased risk for developing Alzheimer's Dementia. Identifying patients with prodromal states of Alzheimer's dementia such as MCI may allow initiation of appropriate treatment planning and delay of cognitive decline. Therefore, the need for a non-invasive early biomarker for the detection of Alzheimer's disease has never been greater. Multiple neuroimaging methods utilizing visual rating scales, volumetric measurements, and automated methods have been developed to identify, quantify, and track anatomic sequelae of Alzheimer’s Disease.

  12. Cholesterol-dependent energy transfer between fluorescent proteins-insights into protein proximity of APP and BACE1 in different membranes in Niemann-Pick type C disease cells.

    Science.gov (United States)

    von Einem, Bjoern; Weber, Petra; Wagner, Michael; Malnar, Martina; Kosicek, Marko; Hecimovic, Silva; Arnim, Christine A F von; Schneckenburger, Herbert

    2012-11-26

    Förster resonance energy transfer (FRET) -based techniques have recently been applied to study the interactions between β-site APP-cleaving enzyme-GFP (BACE1-GFP) and amyloid precursor protein-mRFP (APP-mRFP) in U373 glioblastoma cells. In this context, the role of APP-BACE1 proximity in Alzheimer's disease (AD) pathogenesis has been discussed. FRET was found to depend on intracellular cholesterol levels and associated alterations in membrane stiffness. Here, NPC1 null cells (CHO-NPC1-/-), exhibiting increased cholesterol levels and disturbed cholesterol transport similar to that observed in Niemann-Pick type C disease (NPC), were used to analyze the influence of altered cholesterol levels on APP-BACE1 proximity. Fluorescence lifetime measurements of whole CHO-wild type (WT) and CHO-NPC1-/- cells (EPI-illumination microscopy), as well as their plasma membranes (total internal reflection fluorescence microscopy, TIRFM), were performed. Additionally, generalized polarization (GP) measurements of CHO-WT and CHO-NPC1-/- cells incubated with the fluorescence marker laurdan were performed to determine membrane stiffness of plasma- and intracellular-membranes. CHO-NPC1-/- cells showed higher membrane stiffness at intracellular- but not plasma-membranes, equivalent to cholesterol accumulation in late endosomes/lysosomes. Along with higher membrane stiffness, the FRET efficiency between BACE1-GFP and APP-mRFP was reduced at intracellular membranes, but not within the plasma membrane of CHO-NPC1-/-. Our data show that FRET combined with TIRF is a powerful technique to determine protein proximity and membrane fluidity in cellular models of neurodegenerative diseases.

  13. The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

    OpenAIRE

    Dong-Kug Choi; In Su Kim; Sushruta Koppula; Byung-Wook Kim; Sandeep Vasant More; Hyung-Woo Lim; Hemant Kumar

    2012-01-01

    Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson’s disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5–10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at...

  14. Skin Picking Disorder

    Directory of Open Access Journals (Sweden)

    Pinar Cetinay Aydin

    2014-08-01

    Full Text Available Skin picking disorder is not a dermatological disorder and it is a table characterized with picking skin excessively and repetitively, leading to damage in skin tissue. Unlike normal picking behaviour, psychogenic skin picking is repetitive and it can lead to severe damage in the skin and even complications which constitute vital danger. While some patients define frequent but short lasting picking attacks, others define rarer attacks which last a few hours. Skin picking disorder, which is not included in the classification systems up to DSM-5 as a separate diagnosis category, is included as an independent diagnosis in Obsessive Compulsive Disorder and Associated Disorders category in DSM-5. In case reports, open label studies and double blind studies selective serotonin reuptake inhibitors are shown to be effective in the treatment of skin picking disorder. Mostly, cognitive-behaviourial techniques are used and have been proven to be useful in psychotherapy. Habit reversal is one of the behaviourial techniques which are frequently applied, give positive results in which well-being state can be maintained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 401-428

  15. Analysis of abnormal findings observed on brain MRI T2 weighted image in a system for the detection of asymptomatic brain disease in 1,200 cases

    International Nuclear Information System (INIS)

    Horiguchi, Takashi; Yoshida, Kazunari; Sato, Syuzo; Kawase, Takeshi; Toya, Shigeo; Mizukami, Masahiro

    1998-01-01

    In this study we described the significance of asymptomatic cerebral infarction (ACI) and periventricular hyperintensity (PVH) observed on brain MRI in a system for detection of asymptomatic brain disease with 1,200 cases. The risk factors (RF), population in each age bracket of ACI and PVH, among groups with hypertension (HTG) and without RF (no-RFG), were investigated. The RF of ACI were hypertension (HT), diabetes mellitus (DM), and aging. Without DM, those are common RF of PVH. The population of PVH and ACI with PVH increased with aging in no-RFG. On the other hand, only the population of ACI with PVH increased with aging in HTG. The rate of these abnormal findings in HTG was significantly higher than that in no-RFG. In addition, HT accelerated the occurrence of these findings by 10-20 years. When patients were over 60 years old, ACI increased rapidly. Accordingly, we concluded that PVH and ACI had a common background. Long term follow up concerning the incidence of ACI in the group with only PVH was necessary. It was desirable that treatment for RF should be effected before the age of sixty. (author)

  16. Loss of brain function - liver disease

    Science.gov (United States)

    Hepatic coma; Encephalopathy - hepatic; Hepatic encephalopathy; Portasystemic encephalopathy ... 2017:417-421. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal ... of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

  17. Using Robot Skills for Flexible Reprogramming of Pick Operations in Industrial Scenarios

    DEFF Research Database (Denmark)

    Andersen, Rasmus S.; Nalpantidis, Lazaros; Krüger, Volker

    2014-01-01

    objects on tabletops and pick them up in a user-specified manner. The programming itself is primarily done through kinesthetic teaching. We show that the skill has robustness towards the location and shape of the object to pick, and that objects from a real industrial production line can be handled. Also......, preliminary tests indicate that non-expert users can learn to use the skill after only a short introduction....

  18. Development of a doorframe-typed swinging seedling pick-up device for automatic field transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Han, H.; Mao, H.; Hu, J.; Tian, K.

    2015-07-01

    A doorframe-typed swing seedling pick-up device for automatic field transplanters was developed and evaluated in a laboratory. The device, consisting of a path manipulator and two grippers, can move the pins slowly to extract seedlings from the tray cells and return quickly to the pick-up point for the next extraction. The path manipulator was constructed with the creative design of type-Ⅱ mechanism combination in series. It consists of an oscillating guide linkage mechanism and a grooved globoidal cam mechanism. The gripper is a pincette-type mechanism using the pick-up pins to penetrate into the root mass for seedling extraction. The dynamic analysis of the designed seedling pick-up device was simulated with ADAMS software. Being the first prototype, various performance tests under local production conditions were conducted to find out the optimal machine operation parameters and transplant production conditions. As the gripper with multiple fine pins was moved by the swing pick-up device, it can effectively complete the transplanting work cycle of extracting, transferring, and discharging a seedling. The laboratory evaluation showed that the pick-up device equipped with two grippers can extract 80 seedlings/min with a 90% success and a 3% failure in discharging seedlings, using 42-day-old tomato plantlets. The quality of extracting seedlings was satisfactory. (Author)

  19. Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease

    DEFF Research Database (Denmark)

    Christiansen, P; Schlosser, A; Henriksen, O

    1995-01-01

    The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetylaspartate (NAA), creatine + phosphocreatine [Cr + PCr], and choline-containing metabolites (Cho) in the frontal part of the brain in 12 patients...... with probable Alzheimer's disease. Eight age-matched healthy volunteers served as controls. Furthermore, T1 and T2 relaxation times of the metabolites and signal ratios: NAA/Cho, NAA/[Cr + PCr], and [Cr + PCr]/Cho at four different echo times (TE) and two different repetition times (TR) were calculated....... The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. The concentration of NAA was significantly lower in the patients with probable Alzheimer's disease than in the healthy volunteers. No significant difference was found for any other metabolite concentration...

  20. Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Bravenboer, B.

    2004-01-01

    The brain has long been viewed as an insulin-insensitive organ. Following the demonstration of insulin receptors in the brain, this assumption has been challenged, and a whole new field of research has emerged. Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin

  1. Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi [Policlinico Universitario, University of Cagliari, Nuclear Medicine, Department of Medical Science, Monserrato, Cagliari (Italy); Murru, Alessandra; Demelia, Luigi [Policlinico Universitario, University of Cagliari, Gastroenterology, Department of Medical Science, Monserrato, Cagliari (Italy); Sias, Alessandro [Policlinico Universitario, University of Cagliari, Radiology, Department of Medical Science, Monserrato, Cagliari (Italy); Marrosu, Francesco [Policlinico Universitario, University of Cagliari, Neurology, Department of Medical Science, Monserrato, Cagliari (Italy)

    2008-04-15

    To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and {sup 99m}Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in {sup 99m}Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating

  2. Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor

    Science.gov (United States)

    Sainz, Bruno; Barretto, Naina; Martin, Danyelle N.; Hiraga, Nobuhiko; Imamura, Michio; Hussain, Snawar; Marsh, Katherine A.; Yu, Xuemei; Chayama, Kazuaki; Alrefai, Waddah A.; Uprichard, Susan L.

    2011-01-01

    Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ~170 million individuals infected and current interferon-based treatment having toxic side-effects and marginal efficacy, more effective antivirals are critically needed1. Although HCV protease inhibitors were just FDA approved, analogous to HIV therapy, optimal HCV therapy likely will require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a promising multi-faceted target for antiviral intervention; however, to date FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1-Like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection as silencing or antibody-mediated blocking of NPC1L1 impairs cell-cultured-derived HCV (HCVcc) infection initiation. In addition, the clinically-available FDA-approved NPC1L1 antagonist ezetimibe2,3 potently blocks HCV uptake in vitro via a virion cholesterol-dependent step prior to virion-cell membrane fusion. Importantly, ezetimibe inhibits infection of all major HCV genotypes in vitro, and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor, but also discovered a new antiviral target and potential therapeutic agent. PMID:22231557

  3. Serine 77 in the PDZ domain of PICK1 is a protein kinase Cα phosphorylation site regulated by lipid membrane binding

    DEFF Research Database (Denmark)

    Ammendrup-Johnsen, Ina; Thorsen, Thor Seneca; Gether, Ulrik

    2012-01-01

    PICK1 (protein interacting with C kinase 1) contains an N-terminal protein binding PDZ domain and a C-terminal lipid binding BAR domain. PICK1 plays a key role in several physiological processes, including synaptic plasticity. However, little is known about the cellular mechanisms governing the a...... lipid binding and/or polymerization capacity. We propose that PICK1 is phosphorylated at Ser77 by PKCα preferentially when bound to membrane vesicles and that this phosphorylation in turn modulates its cellular distribution....

  4. Lysosomal pH-inducible supramolecular dissociation of polyrotaxanes possessing acid-labile N-triphenylmethyl end groups and their therapeutic potential for Niemann-Pick type C disease

    Science.gov (United States)

    Tamura, Atsushi; Nishida, Kei; Yui, Nobuhiko

    2016-01-01

    Niemann-Pick type C (NPC) disease is characterized by the accumulation of cholesterol in lysosomes. We have previously reported that biocleavable polyrotaxanes (PRXs) composed of β-cyclodextrins (β-CDs) threaded onto a linear polymer capped with bulky stopper molecules via intracellularly cleavable linkers show remarkable cholesterol reducing effects in NPC disease patient-derived fibroblasts owing to the stimuli-responsive intracellular dissociation of PRXs and subsequent β-CD release from the PRXs. Herein, we describe a series of novel acid-labile 2-(2-hydroxyethoxy)ethyl group-modified PRXs (HEE-PRXs) bearing terminal N-triphenylmethyl (N-Trt) groups as a cleavable component for the treatment of NPC disease. The N-Trt end groups of the HEE-PRXs underwent acidic pH-induced cleavage and led to the dissociation of their supramolecular structure. A kinetic study revealed that the number of HEE groups on the PRX did not affect the cleavage kinetics of the N-Trt end groups of the HEE-PRXs. The effect of the number of HEE groups of the HEE-PRXs, which was modified to impart water solubility to the PRXs, on cellular internalization efficiency, lysosomal localization efficiency, and cholesterol reduction ability in NPC disease-derived fibroblasts (NPC1 fibroblasts) was also investigated. The cellular uptake and lysosomal localization efficiency were almost equivalent for HEE-PRXs with different numbers of HEE groups. However, the cholesterol reducing ability of the HEE-PRXs in NPC1 fibroblasts was affected by the number of HEE groups, and HEE-PRXs with a high number of HEE groups were unable to reduce lysosomal cholesterol accumulation. This deficiency is most likely due to the cholesterol-solubilizing ability of HEE-modified β-CDs released from the HEE-PRXs. We conclude that the N-Trt group acts as a cleavable component to induce the lysosomal dissociation of HEE-PRXs, and acid-labile HEE-PRXs with an optimal number of HEE groups (4.1 to 5.4 HEE groups per single

  5. Brain-Reactive Antibodies and Disease

    OpenAIRE

    Diamond, B.; Honig, G.; Mader, S.; Brimberg, L.; Volpe, B.T.

    2013-01-01

    Autoimmune diseases currently affect 5–7% of the world's population; in most diseases there are circulating autoantibodies. Brain-reactive antibodies are present in approximately 2–3% of the general population but do not usually contribute to brain pathology. These antibodies penetrate brain tissue only early in development or under pathologic conditions. This restriction on their pathogenicity and the lack of correlation between serum titers and brain pathology have, no doubt, contributed to...

  6. Picking up Clues from the Discard Pile

    Science.gov (United States)

    2008-01-01

    As NASA's Phoenix Mars Lander excavates trenches, it also builds piles with most of the material scooped from the holes. The piles, like this one called 'Caterpillar,' provide researchers some information about the soil. On Aug. 24, 2008, during the late afternoon of the 88th Martian day after landing, Phoenix's Surface Stereo Imager took separate exposures through red, green and blue filters that have been combined into this approximately true-color image. This conical pile of soil is about 10 centimeters (4 inches) tall. The sources of material that the robotic arm has dropped onto the Caterpillar pile have included the 'Dodo' and ''Upper Cupboard' trenches and, more recently, the deeper 'Stone Soup' trench. Observations of the pile provide information, such as the slope of the cone and the textures of the soil, that helps scientists understand properties of material excavated from the trenches. For the Stone Soup trench in particular, which is about 18 centimeters (7 inches) deep, the bottom of the trench is in shadow and more difficult to observe than other trenches that Phoenix has dug. The Phoenix team obtained spectral clues about the composition of material from the bottom of Stone Soup by photographing Caterpillar through 15 different filters of the Surface Stereo Imager when the pile was covered in freshly excavated material from the trench. The spectral observation did not produce any sign of water-ice, just typical soil for the site. However, the bigger clumps do show a platy texture that could be consistent with elevated concentration of salts in the soil from deep in Stone Soup. The team chose that location as the source for a soil sample to be analyzed in the lander's wet chemistry laboratory, which can identify soluble salts in the soil. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed

  7. Picking flowers in the breast cancer field

    African Journals Online (AJOL)

    degree, the subject of which was clothing-related problems patients may experience .... mammary chain through the second intercostal space, and one from the apex of the ..... the skin. On the other hand, when we looked at the two losers with.

  8. The Use of N-Terminal Pro-Brain Natriuretic Peptide to Evaluate Vascular Disease in Elderly Patients with Mental Illness

    OpenAIRE

    Nilsson, Karin; Gustafson, Lars; Hultberg, Björn

    2012-01-01

    Background: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment. Method: In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease. Results and Conclusion: Patients with vascular disease and elevated...

  9. The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease

    Science.gov (United States)

    Kokiko-Cochran, Olga N.; Godbout, Jonathan P.

    2018-01-01

    The post-injury inflammatory response is a key mediator in long-term recovery from traumatic brain injury (TBI). Moreover, the immune response to TBI, mediated by microglia and macrophages, is influenced by existing brain pathology and by secondary immune challenges. For example, recent evidence shows that the presence of beta-amyloid and phosphorylated tau protein, two hallmark features of AD that increase during normal aging, substantially alter the macrophage response to TBI. Additional data demonstrate that post-injury microglia are “primed” and become hyper-reactive following a subsequent acute immune challenge thereby worsening recovery. These alterations may increase the incidence of neuropsychiatric complications after TBI and may also increase the frequency of neurodegenerative pathology. Therefore, the purpose of this review is to summarize experimental studies examining the relationship between TBI and development of AD-like pathology with an emphasis on the acute and chronic microglial and macrophage response following injury. Furthermore, studies will be highlighted that examine the degree to which beta-amyloid and tau accumulation as well as pre- and post-injury immune stressors influence outcome after TBI. Collectively, the studies described in this review suggest that the brain’s immune response to injury is a key mediator in recovery, and if compromised by previous, coincident, or subsequent immune stressors, post-injury pathology and behavioral recovery will be altered. PMID:29686672

  10. Genetic engineering: picking up the pieces.

    Science.gov (United States)

    Budiansky, S

    Proposals from two private companies for the field testing of recombinant organisms are still slated to be considered by the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH), despite a federal district court ruling that temporarily halted a University of California field test and barred RAC from approving any other experiments involving NIH funds that would deliberately release recombinant DNA into the environment. The ruling, which was prompted by a lawsuit filed by Jeremy Rifkin, specifically exempted private companies because they are not legally bound by RAC decisions, but have been complying voluntarily. The temporary injunction is being appealed by the university.

  11. Meta-Analysis of the Relationship between Deep Brain Stimulation in Patients with Parkinson’s Disease and Performance in Evaluation Tests for Executive Brain Functions

    Directory of Open Access Journals (Sweden)

    A. M. Martínez-Martínez

    2017-01-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative condition, which compromises the motor functions and causes the alteration of some executive brain functions. The presence of changes in cognitive symptoms in PD could be due to the procedure of deep brain stimulation (DBS. We searched in several databases for studies that compared performance in executive function tests before and after the DBS procedure in PE and then performed a meta-analysis. After the initial search, there were 15 articles that specifically evaluated the functions of verbal fluency, working memory, cognitive flexibility, abstract thinking, and inhibition. It was found that there were differences in the evaluation of the cognitive functions in terms of the protocols, which generated heterogeneity in the results of the meta-analysis. Likewise, a tendency to diminish functions like verbal fluency and inhibition was found, being this consistent with similar studies. In the other functions evaluated, no difference was found between pre- and postsurgery scores. Monitoring of this type of function is recommended after the procedure.

  12. SAVING LIVES: WHO PICKS UP THE TAB?

    African Journals Online (AJOL)

    Nicky

    state. All are used to some extent on fixed or ad hoc contract by 6 of the 9 .... capacity but the political will for .... Red Cross Air Mercy Service volunteer, German national Dr Florian Funk, at the AMS .... she was secretary of the Black Sports.

  13. CARS microscopy of Alzheimer's diseased brain tissue

    Science.gov (United States)

    Enejder, Annika; Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia-Yi

    2014-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.

  14. Analysis of the brain tissues from a patient with Alzheimer's disease and effects of chelating treatment

    International Nuclear Information System (INIS)

    Ektessabi, A.M.; Fujisawa, S.; Takada, K.; Yoshida, K.; Murayama, H.; Shin, R.W.

    1999-01-01

    Alzheimer's, Parkinson's disease and ALS are among major neurodegenerative diseases. The cause of neurodegeneration is unknown, but there are indications that excessive accumulation of essential elements, and sometimes, incorporation of toxic foreign elements in neurons aggravate neurodegeneration. During the past decade, many researchers investigated the causative factors in degenerative diseases to specify genetic or environmental factor. PIXE analysis has been used for these studies because of the sample preparation is easy and detection limit is very low. However, the concentration of matrix elements and foreign elements are extremely low and difficult to detect and to quantify. In this study, specimens from patients with Alzheimer's disease with no chemical treatment, and those with chelating were analyzed. In all analyzed specimens, Na, Al, Si, P, S, Cl, Ca, Ti, Vi, Cr, Fe and Cu were detected. Each specimen in this study consisted of cerebral cortex and substantia alba. From these experiments we can observe a clear tendency that the accumulation of the metal elements use different depending on the constituent tissues, and the method of sample preparation has a dominant role in the measurement results. (author)

  15. The role of chemotherapy in brain metastases

    International Nuclear Information System (INIS)

    Ohori, Hisatsugu; Takahashi, Shin; Ishioka, Chikashi

    2007-01-01

    Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases have a very poor prognosis with a median survival of 1-2 months. Despite the use of surgery and radiotherapy including whole-brain radiation and stereotactic radiosurgery to locally control brain metastases, survival times for those patients has not improved. Although chemotherapy plays a limited role in the treatment of brain metastases, metastases from lung or breast cancer are often well-controlled by chemotherapy. Accumulating evidence suggest that brain metastases are equally sensitive to chemotherapy as are metastases elsewhere in the body in particular chemotherapy-naive cases. Finally, since nearly a half of patients with brain metastases die from progression of systemic disease, control of systemic disease as well as intracranial disease are both important. (author)

  16. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Atalar, Banu [Department of Radiation Oncology, Acibadem University School of Medicine, Istanbul (Turkey); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Choi, Clara Y.H.; Adler, John R. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Gibbs, Iris C. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Nagpal, Seema [Department of Neurology, Stanford University Medical Center, Stanford, California (United States); Hanlon, Alexandra [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States)

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  17. Metastatic disease of the brain: extra-axial metastases (skull, dura, leptomeningeal) and tumour spread

    Energy Technology Data Exchange (ETDEWEB)

    Maroldi, Roberto; Ambrosi, Claudia; Farina, Davide [University of Brescia, Department of Radiology, Brescia, BS (Italy)

    2005-03-01

    Extra-axial intracranial metastases may arise through several situations. Hematogenous spread to the meninges is the most frequent cause. Direct extension from contiguous extra-cranial neoplasms, secondary invasion of the meninges by calvarium and skull base metastases, and migration along perineural or perivascular structures are less common. Leptomeningeal invasion gives rise to tumour cell dissemination by the cerebrospinal fluid (CSF), eventually leading to neoplastic coating of brain surfaces. Contrast-enhanced magnetic resonance (MR) imaging is complementary to CSF examinations and can be invaluable, detecting up to 50% of false-negative lumbar punctures. MR findings range from diffuse linear leptomeningeal enhancement to multiple enhancing extra-axial nodules, obstructive communicating and non-communicating hydrocephalus. Both calvarial and epidural metastases infrequently transgress the dura, which acts as a barrier against tumour spread. Radionuclide bone studies are still a valuable screening test to detect bone metastases. With computed tomography (CT) and MR, bone metastases extending intracranially and primary dural metastases show the characteristic biconvex shape, usually associated with brain displacement away from the inner table. Although CT is better in detecting skull base erosion, MR is more sensitive and provides more detailed information about dural involvement. Perineural and perivascular spread from head and neck neoplasms require thin-section contrast-enhanced MR. (orig.)

  18. Development of the Young Brain

    Medline Plus

    Full Text Available ... Training (1 item) Other Treatments (15 items) Alzheimer’s Disease (2 items) Coping with Traumatic Events (3 items) Institute Announcements (24 items) Development of the Young Brain May 2, 2011 For more than twenty years, National Institute of Mental Health neuroscientist Dr. Jay Giedd has studied the ...

  19. Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome

    Science.gov (United States)

    Ong, Timothy Yu Yee; Siddiqui, Ruqaiyyah

    2017-01-01

    ABSTRACT Acanthamoeba spp. and Balamuthia mandrillaris are causative agents of granulomatous amoebic encephalitis (GAE), while Naegleria fowleri causes primary amoebic meningoencephalitis (PAM). PAM is an acute infection that lasts a few days, while GAE is a chronic to subacute infection that can last up to several months. Here, we present a literature review of 86 case reports from 1968 to 2016, in order to explore the affinity of these amoebae for particular sites of the brain, diagnostic modalities, treatment options, and disease outcomes in a comparative manner. PMID:28404683

  20. Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson's disease.

    Science.gov (United States)

    Su, Xin-Ling; Luo, Xiao-Guang; Lv, Hong; Wang, Jun; Ren, Yan; He, Zhi-Yi

    2017-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies, however there were different conclusions about that through long- and short-term follow-ups. We aimed to investigate the factors which influence the predictive value of levodopa responsiveness, and discover more predictive factors of surgical outcomes. Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up. Clinical evaluations were performed 1 week before and 3 months after surgery. STN-DBS significantly improved motor function of PD patients after 3 months; preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function; gender, disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement; the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement. The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients, patients with shorter disease duration or shorter motor fluctuations; PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms, especially in their later disease stage.

  1. Effects of rhythmic stimulus presentation on oscillatory brain activity: the physiology of cueing in Parkinson's disease

    NARCIS (Netherlands)

    Woerd, E.S. te; Oostenveld, R.; Bloem, B.R.; Lange, F.P. de; Praamstra, P.

    2015-01-01

    The basal ganglia play an important role in beat perception and patients with Parkinson's disease (PD) are impaired in perception of beat-based rhythms. Rhythmic cues are nonetheless beneficial in gait rehabilitation, raising the question how rhythm improves movement in PD. We addressed this

  2. Infectious diseases of brain parenchyma in adults: imaging and differential diagnosis

    International Nuclear Information System (INIS)

    Haehnel, S.; Kress, B.; Stippich, C.; Sartor, K.; Seitz, A.; Storch-Hagenlocher, B.; Forsting, M.; Jansen, O.

    2005-01-01

    Infectious diseases of the central nervous system have often to be considered in differential diagnosis, particularly in immunocompromised persons. Neuroimaging, specifically advanced techniques such as diffusion-weighted MRI and perfusion MRI contribute much to the differentiation of various brain infections and to delineation of brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria for the most important brain infections in adults and discuss in detail differential diagnostic aspects. (orig.)

  3. Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

    Science.gov (United States)

    Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

    2018-04-01

    Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease: Methodology and Baseline Sample Characteristics.

    Science.gov (United States)

    Byun, Min Soo; Yi, Dahyun; Lee, Jun Ho; Choe, Young Min; Sohn, Bo Kyung; Lee, Jun-Young; Choi, Hyo Jung; Baek, Hyewon; Kim, Yu Kyeong; Lee, Yun-Sang; Sohn, Chul-Ho; Mook-Jung, Inhee; Choi, Murim; Lee, Yu Jin; Lee, Dong Woo; Ryu, Seung-Ho; Kim, Shin Gyeom; Kim, Jee Wook; Woo, Jong Inn; Lee, Dong Young

    2017-11-01

    The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimer's disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. All participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [ 11 C]Pittsburgh compound B-positron emission tomography (PET), and [ 18 F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitoring and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannually with the full KBASE assessment, including neuroimaging and laboratory tests. As of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants-291 cognitively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)-were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. The KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.

  5. Incidence of Traumatic Brain Injury Across the Full Disease Spectrum: A Population-Based Medical Record Review Study

    Science.gov (United States)

    Leibson, Cynthia L.; Brown, Allen W.; Ransom, Jeanine E.; Diehl, Nancy N.; Perkins, Patricia K.; Mandrekar, Jay; Malec, James F.

    2012-01-01

    Background Extremely few objective estimates of traumatic brain injury incidence include all ages, both sexes, all injury mechanisms, and the full spectrum from very mild to fatal events. Methods We used unique Rochester Epidemiology Project medical records-linkage resources, including highly sensitive and specific diagnostic coding, to identify all Olmsted County, MN, residents with diagnoses suggestive of traumatic brain injury regardless of age, setting, insurance, or injury mechanism. Provider-linked medical records for a 16% random sample were reviewed for confirmation as definite, probable, possible (symptomatic), or no traumatic brain injury. We estimated incidence per 100,000 person-years for 1987–2000 and compared these record-review rates with rates obtained using Centers for Disease Control and Prevention (CDC) data-systems approach. For the latter, we identified all Olmsted County residents with any CDC-specified diagnosis codes recorded on hospital/emergency department administrative claims or death certificates 1987–2000. Results Of sampled individuals, 1257 met record-review criteria for incident traumatic brain injury; 56% were ages 16–64 years, 56% were male, 53% were symptomatic. Mechanism, sex, and diagnostic certainty differed by age. The incidence rate per 100,000 person-years was 558 (95% confidence interval = 528–590) versus 341 (331–350) using the CDC data system approach. The CDC approach captured only 40% of record-review cases. Seventy-four percent of missing cases presented to hospital/emergency department; none had CDC-specified codes assigned on hospital/emergency department administrative claims or death certificates; 66% were symptomatic. Conclusions Capture of symptomatic traumatic brain injuries requires a wider range of diagnosis codes, plus sampling strategies to avoid high rates of false-positive events. PMID:21968774

  6. Voxel-based analysis of diffusion tensor indices in the brain in patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Zhang Kaiyuan; Yu Chunshui; Zhang Yujin; Wu Xiaoli; Zhu Chaozhe; Chan Piu; Li Kuncheng

    2011-01-01

    Purpose: To investigate the abnormal diffusion in cerebral white matter and its relationship with the olfactory dysfunction in patients with Parkinson's disease (PD) through diffusion tensor imaging (DTI). Materials and methods: Diffusion tensor imaging of the cerebrum was performed in 25 patients with Parkinson's disease and 25 control subjects matched for age and sex. Differences in fractional anisotropy (FA) and mean diffusivity (MD) between these two groups were studied by voxel-based analysis of the DTI data. Correlations between diffusion indices and the olfactory function in PD patients were evaluated using the multiple regression model after controlling for the duration of the disease, Unified Parkinson's Disease Rating Sale (UPDRS), and age. Results: The damaged white and gray matter showed decreased FA or increased MD, localized bilaterally in the cerebellar and orbitofrontal cortex. In addition, in PD patients there was a positive correlation between FA values in the white matter of the left cerebellum and the thresholds of olfactory identification (TOI) and a negative correlation between MD values in the white matter of right cerebellum and the TOI. Conclusion: In patients with PD, there was disruption in the cerebellar white matter which may play an important role in the olfactory dysfunction in patients with Parkinson's disease.

  7. Gas Bubble Disease in the Brain of a Living California Sea Lion (Zalophus californianus).

    Science.gov (United States)

    Van Bonn, William; Dennison, Sophie; Cook, Peter; Fahlman, Andreas

    2013-01-01

    A yearling California sea lion (Zalophus californianus) was admitted into rehabilitation with signs of cerebellar pathology. Diagnostic imaging that included radiography and magnetic resonance imaging (MRI) demonstrated space-occupying lesions predominantly in the cerebellum that were filled partially by CSF-like fluid and partially by gas, and cerebral lesions that were fluid filled. Over a maximum period of 4 months, the brain lesions reduced in size and the gas resorbed and was replaced by CSF-like fluid. In humans, the cerebellum is known to be essential for automating practiced movement patterns (e.g., learning to touch-type), also known as procedural learning or the consolidation of "motor memory." To test