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Chitotriosidase

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https://www.readbyqxmd.com/read/29747453/chitinase-mrna-levels-determined-by-qpcr-in-crab-eating-monkey-macaca-fascicularis-tissues-species-specific-expression-of-acidic-mammalian-chitinase-and-chitotriosidase
#1
Maiko Uehara, Eri Tabata, Kazuhiro Ishii, Akira Sawa, Misa Ohno, Masayoshi Sakaguchi, Vaclav Matoska, Peter O Bauer, Fumitaka Oyama
Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey ( Macaca fascicularis ) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule...
May 9, 2018: Genes
https://www.readbyqxmd.com/read/29596541/association-of-cerebrospinal-fluid-biomarkers-of-central-nervous-system-injury-with-neurocognitive-and-brain-imaging-outcomes-in-children-receiving-chemotherapy-for-acute-lymphoblastic-leukemia
#2
Yin Ting Cheung, Raja B Khan, Wei Liu, Tara M Brinkman, Michelle N Edelmann, Wilburn E Reddick, Deqing Pei, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Cheng Cheng, Leslie L Robison, Melissa M Hudson, Ching-Hon Pui, Kevin R Krull
Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. Design, Setting, and Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol...
March 29, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29572197/nod-2-expression-dna-damage-and-oxido-inflammatory-status-in-egyptian-patients-with-atopic-bronchial-asthma-exploring-their-nexus-to-disease-severity
#3
Hanaa H Gaballah, Rasha A Gaber, Ragia S Sharshar, Samah A Elshweikh
BACKGROUND: Allergic asthma is a chronically relapsing inflammatory airway disease with a complex pathophysiology. AIM: This study was undertaken to investigate the potential contribution of NOD2 signaling, proinflammatory cytokines, chitotriosidase (CHIT1) activity, oxidative stress and DNA damage to atopic asthma pathogenesis, as well as to explore their possible role as surrogate noninvasive biomarkers for monitoring asthma severity. METHODS: Sixty patients with atopic bronchial asthma who were divided according to asthma severity into 40 mild-moderate, 20 severe atopic asthmatics, in addition to thirty age-matched healthy controls were enrolled in this study...
March 20, 2018: Gene
https://www.readbyqxmd.com/read/29530534/plasma-chitotriosidase-activity-versus-plasma-glucosylsphingosine-in-wide-spectrum-of-gaucher-disease-phenotypes-a-statistical-insight
#4
Anna Tylki-Szymańska, Paulina Szymańska-Rożek, Piotr Hasiński, Agnieszka Ługowska
Deficiency of beta-glucocerebrosidase (GBA) leads to Gaucher disease (GD), an inherited disorder characterised by storage of glucosylceramide (GlcCer) in lysosomes of tissue macrophages. Macrophages activated by accumulated GlcCer secrete chitotriosidase. Plasma chitotriosidase activity is significantly elevated in patients with active GD and has been suggested to indicate total body Gaucher cell load. There are two biomarkers used to assess the severity of GD - chitotriosidase has been measured for over 20 years, and deacylated GlcCer, known as glucosylsphingosine (GlcSph) is thought to be even more adequate, as it is almost a direct storage substrate...
April 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29420850/chitotriosidase-inhibits-allergic-asthmatic-airways-via-regulation-of-tgf-%C3%AE-expression-and-foxp3-treg-cells
#5
J Y Hong, M Kim, I S Sol, K W Kim, C-M Lee, J A Elias, M H Sohn, C G Lee
BACKGROUND: Chitotriosidase (chitinase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. However, the role and the mechanisms that underlie these contributions to the diseases have not been defined. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. METHODS: Wild-type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation...
February 8, 2018: Allergy
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#6
Alexander G Thompson, Elizabeth Gray, Marie-Laëtitia Thézénas, Philip D Charles, Samuel Evetts, Michele T Hu, Kevin Talbot, Roman Fischer, Benedikt M Kessler, Martin R Turner
OBJECTIVE: The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid (CSF) samples. METHODS: Liquid chromatography/tandem mass spectrometry with label-free quantification was used to identify CSF proteins using samples from a well-characterized longitudinal cohort comprising patients with ALS (n = 43), the upper motor neuron variant, primary lateral sclerosis (PLS; n = 6), and cross-sectional healthy (n = 20) and disease controls (Parkinsons' disease, n = 20; ALS mimic disorders, n = 12)...
February 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29305734/olipudase-alfa-for-treatment-of-acid-sphingomyelinase-deficiency-asmd-safety-and-efficacy-in-adults-treated-for-30-months
#7
Melissa P Wasserstein, George A Diaz, Robin H Lachmann, Marie-Hélène Jouvin, Indrani Nandy, Allena J Ji, Ana Cristina Puga
Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain...
January 5, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29290526/rapid-screening-for-lipid-storage-disorders-using-biochemical-markers-expert-center-data-and-review-of-the-literature
#8
M Voorink-Moret, S M I Goorden, A B P van Kuilenburg, F A Wijburg, J M M Ghauharali-van der Vlugt, F S Beers-Stet, A Zoetekouw, W Kulik, C E M Hollak, F M Vaz
BACKGROUND: In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. MATERIAL AND METHODS: A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74)...
February 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29283260/targeting-acidic-mammalian-chitinase-is-effective-in-animal-model-of-asthma
#9
Marzena Mazur, Jacek Olczak, Sylwia Olejniczak, Robert Koralewski, Wojciech Czestkowski, Anna Jedrzejczak, Jakub Golab, Karolina Dzwonek, Barbara Dymek, Piotr L Sklepkiewicz, Agnieszka Zagozdzon, Tom Noonan, Keyvan Mahboubi, Bruce Conway, Ryan Sheeler, Paul Beckett, William M Hungerford, Alberto Podjarny, Andre Mitschler, Alexandra Cousido-Siah, Firas Fadel, Adam Golebiowski
This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150× against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity...
February 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29247734/human-chitotriosidase-does-not-catabolize-hyaluronan
#10
Ben Danielson, Che-Hong Chen, Gernot Kaber, Daria Mochly-Rosen, Kevin Grimes, Robert Stern, Paul L Bollyky
Humans express an enzyme that degrades chitin, called chitotriosidase, despite the fact that we do not produce chitin. One possible explanation for this is that chitinase also degrades hyaluronan, a polysaccharide that is abundant in human tissues and shares structural attributes in common with chitinase. The objective of this study was to determine whether human chitotriosidase is capable of hydrolyzing hyaluronan. Hyaluronan of various sizes under a range of pH conditions displayed no degradation when incubated with various chitinases over a period of 5 days, while commercial hyaluronidase readily digested the hyaluronan...
April 1, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29246232/etiogenic-factors-present-in-the-cerebrospinal-fluid-from-amyotrophic-lateral-sclerosis-patients-induce-predominantly-pro-inflammatory-responses-in-microglia
#11
Pooja-Shree Mishra, K Vijayalakshmi, A Nalini, T N Sathyaprabha, B W Kramer, Phalguni Anand Alladi, T R Raju
BACKGROUND: Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated. METHODS: We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis...
December 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29197565/molecular-and-biochemical-biomarkers-for-diagnosis-and-therapy-monitorization-of-niemann-pick-type-c-patients
#12
Tatiane Grazieli Hammerschmidt, Graziela de Oliveira Schmitt Ribas, Maria Luiza Saraiva-Pereira, Márcia Polese Bonatto, Rejane Gus Kessler, Fernanda Timm Seabra Souza, Franciele Trapp, Kristiane Michelin-Tirelli, Maira Graeff Burin, Roberto Giugliani, Carmen Regla Vargas
BACKGROUND: Niemann-Pick type C (NP-C), one of 50 inherited lysosomal storage disorders, is caused by NPC protein impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. The clinical manifestations of NP-C include hepatosplenomegaly, neurological and psychiatric symptoms. Current diagnosis for NP-C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining...
November 29, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29180539/chitotriosidase-shucking-the-role-of-microglia-in-amyotrophic-lateral-sclerosis
#13
EDITORIAL
Henrik Zetterberg
No abstract text is available yet for this article.
March 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29142138/chitotriosidase-chit1-is-increased-in-microglia-and-macrophages-in-spinal-cord-of-amyotrophic-lateral-sclerosis-and-cerebrospinal-fluid-levels-correlate-with-disease-severity-and-progression
#14
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
March 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29090525/hematopoietic-stem-cell-transplantation-in-niemann-pick-disease-type-b-monitored-by-chitotriosidase-activity
#15
Paola Quarello, Marco Spada, Francesco Porta, Elena Vassallo, Fabio Timeus, Franca Fagioli
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.
February 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29021549/protease-resistance-of-porcine-acidic-mammalian-chitinase-under-gastrointestinal-conditions-implies-that-chitin-containing-organisms-can-be-sustainable-dietary-resources
#16
Eri Tabata, Akinori Kashimura, Satoshi Wakita, Misa Ohno, Masayoshi Sakaguchi, Yasusato Sugahara, Yasutada Imamura, Shiro Seki, Hitoshi Ueda, Vaclav Matoska, Peter O Bauer, Fumitaka Oyama
Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), is a major structural component in chitin-containing organism including crustaceans, insects and fungi. Mammals express two chitinases, chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase). Here, we report that pig AMCase is stable in the presence of other digestive proteases and functions as chitinolytic enzyme under the gastrointestinal conditions. Quantification of chitinases expression in pig tissues using quantitative real-time PCR showed that Chit1 mRNA was highly expressed in eyes, whereas the AMCase mRNA was predominantly expressed in stomach at even higher levels than the housekeeping genes...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890071/serum-lipid-alterations-in-gba-associated-parkinson-s-disease
#17
Leonor Correia Guedes, Robin Barry Chan, Marcos António Gomes, Vasco A Conceição, Raquel Bouça Machado, Tiago Soares, Yimeng Xu, Paulo Gaspar, Joao André Carriço, Roy N Alcalay, Joaquim J Ferreira, Tiago Fleming Outeiro, Gabriel Miltenberger-Miltenyi
INTRODUCTION: Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. METHODS: We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2...
November 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28793282/increased-risk-of-atherosclerosis-in-patients-with-sarcoidosis
#18
Elena Bargagli, Elisabetta Rosi, Massimo Pistolesi, Federico Lavorini, Luca Voltolini, Paola Rottoli
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Recent studies demonstrated that its pathogenesis is related with enhanced oxidative stress (protein carbonylation and lipid peroxidation) and alterations in the circulating lipid profile. Alterations of lipid metabolism (including the reduction in high-density lipoprotein cholesterol levels and apolipoprotein A1 concentrations) induce plasma membrane, bronchial and lung capillary endothelial cell damage in sarcoidosis patients. Dyslipidemia is associated with increased oxidative stress, diminished overall antioxidative protection and increased risk for atherosclerosis...
2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28736246/in-vitro-osteoclastogenesis-from-gaucher-patients-cells-correlates-with-bone-mineral-density-but-not-with-chitotriosidase
#19
C Bondar, J Mucci, A Crivaro, M Ormazabal, R Ceci, B Oliveri, D González, P Rozenfeld
Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase. Type I GD (GD1) patients present anemia, hepatosplenomegaly and bone alterations. In spite of treatment, bone alterations in GD patients persist, including poor bone mineral density (BMD). Mechanisms leading to bone damage are not completely understood, but previous reports suggest that osteoclasts are involved. Chitotriosidase (CHIT) is the most reliable biomarker used in the follow up of patients, although its correlation with bone status is unknown...
July 20, 2017: Bone
https://www.readbyqxmd.com/read/28677113/plasma-chitotriosidase-and-carotid-intima-media-thickness-in-children-with-sickle-cell-disease
#20
Normeen A Kaddah, Dalia A Saied, Hanan A Alwakeel, Rania H Hashem, Sara M Rowizak, Mohamed A Elmonem
The relationship between chronic hemolysis with subsequent iron overload, inflammation, and premature atherosclerosis has been documented in hemolytic anemias, particularly β-thalassemia. However, no such relationship has been established in sickle cell disease (SCD). We sought to evaluate SCD as a risk factor for early vascular insult by measuring carotid intima-media thickness (CIMT) and plasma chitotriosidase and to assess the role of the latter as a potential quantitative indicator of vascular inflammation and atherogenesis...
November 2017: International Journal of Hematology
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