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https://www.readbyqxmd.com/read/28395882/should-studies-on-glanzmann-thrombasthenia-not-be-telling-us-more-about-cardiovascular-disease-and-other-major-illnesses
#1
REVIEW
Alan T Nurden
Glanzmann thrombasthenia (GT) is a rare inherited bleeding disorder caused by loss of αIIbβ3 integrin function in platelets. Most genetic variants of β3 also affect the widely expressed αvβ3 integrin. With brief mention of mouse models, I now look at the consequences of disease-causing ITGA2B and ITGB3 mutations on the non-hemostatic functions of platelets and other cells. Reports of arterial thrombosis in GT patients are rare, but other aspects of cardiovascular disease do occur including deep vein thrombosis and congenital heart defects...
April 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28370162/simultaneous-human-platelet-antigen-genotyping-and-detection-of-novel-single-nucleotide-polymorphisms-by-targeted-next-generation-sequencing
#2
Sue Davey, Cristina Navarrete, Colin Brown
BACKGROUND: Twenty-nine human platelet antigen systems have been described to date, but the majority of current genotyping methods are restricted to the identification of those most commonly associated with alloantibody production in a clinical context. This can result in a protracted investigation if causative human platelet antigens are rare or novel. A targeted next-generation sequencing approach was designed to detect all known human platelet antigens with the additional capability of identifying novel mutations in the encoding genes...
March 28, 2017: Transfusion
https://www.readbyqxmd.com/read/28370062/simultaneous-genotyping-of-human-platelet-alloantigen-1-to-28bw-systems-by-multiplex-polymerase-chain-reaction-sequence-based-typing
#3
X Hong, S Chen, Y Ying, Y Liu, X Xu, J He, F Zhu
BACKGROUND AND OBJECTIVES: Human platelet alloantigen (HPA) genotyping is important for the diagnosis and prevention the alloimmune platelet disorders. In this study, a simultaneous genotyping method for HPA-1 to -28bw systems was established using multiplex PCR-SBT and the frequencies of genotypes and alleles of HPA-1 to -28bw systems in the Zhejiang Han population were analysed. MATERIALS AND METHODS: The specific primers were designed according to the nucleotide sequences of HPA-1 to 28bw systems which are located in ITGB3, GP1BA, ITGA2B, ITGA2, GP1BB and CD109, respectively...
March 31, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28358707/polymorphisms-of-platelet-glycoprotein-receptors-and-cell-adhesion-molecules-in-fetuses-with-fetal-growth-restriction-and-their-mothers-as-detected-with-pyrosequencing
#4
Maria Simou, Evaggelia Kouskouni, Nikolaos Vitoratos, Emmanuel Economou, George Creatsas
BACKGROUND: Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR. MATERIALS AND METHODS: We compared the maternal and fetal genotypic frequencies of single nucleotide polymorphisms (SNPs) in four genes coding for platelet receptors and cell adhesion molecules [integrin alpha subunit 2 (ITGA2)C807T, integrin subunit beta 3(ITGB3) T1565C, platelet cell adhesion protein 1 (PECAM1) CTG-GTG and selectin P(SELP)A/C]...
March 2017: In Vivo
https://www.readbyqxmd.com/read/28318110/on-the-association-analysis-of-genome-sequencing-data-a-spatial-clustering-approach-for-partitioning-the-entire-genome-into-nonoverlapping-windows
#5
Heide Loehlein Fier, Dmitry Prokopenko, Julian Hecker, Michael H Cho, Edwin K Silverman, Scott T Weiss, Rudolph E Tanzi, Christoph Lange
For the association analysis of whole-genome sequencing (WGS) studies, we propose an efficient and fast spatial-clustering algorithm. Compared to existing analysis approaches for WGS data, that define the tested regions either by sliding or consecutive windows of fixed sizes along variants, a meaningful grouping of nearby variants into consecutive regions has the advantage that, compared to sliding window approaches, the number of tested regions is likely to be smaller. In comparison to consecutive, fixed-window approaches, our approach is likely to group nearby variants together...
March 20, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28273461/integrin-beta-3-regulates-cellular-senescence-by-activating-the-tgf-%C3%AE-pathway
#6
Valentina Rapisarda, Michela Borghesan, Veronica Miguela, Vesela Encheva, Ambrosius P Snijders, Amaia Lujambio, Ana O'Loghlen
Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3) is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β) pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS) through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS), independently of its ligand-binding activity...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28250242/itgav-alpha-v-integrins-bind-spp1-osteopontin-to-support-trophoblast-cell-adhesion
#7
James W Frank, Heewon Seo, Robert C Burghardt, Kayla J Bayless, Gregory A Johnson
Attachment of the conceptus trophoblast (Tr) to the uterine luminal epithelium (LE) is critical for successful implantation. This study determined whether alpha v (av) integrins (ITGAV) directly mediate porcine trophoblast cell adhesion to secreted phosphoprotein 1 [SPP1, also known as osteopontin (OPN)], and examined the temporal/spatial expression of ITGAV, beta 3 (b3, ITGB3) and beta 6 (b6, ITGB6) integrin subunits, and SPP1, at the uterine-placental interface of pigs. Knockdown of ITGAV in a porcine Tr (pTr2) cells by siRNA reduced pTr2 attachment to SPP1...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28186591/-application-of-recombinant-gp%C3%A2-a-combined-luminex-beads-for-the-detection-of-hpa-1a-antibody
#8
Sudan Tao, Ying Liu, Yanming He, Yanling Ying, Ji He, Faming Zhu
OBJECTIVE: To generate recombinant GPⅢa as an alternative source for HPA-1a antigen and combine it with Luminex xMAP beads for the detection of HPA-1a-specific alloantibody. METHODS: The full coding region of ITGB3 gene was amplified and ligated with pcDNA3.1. The recombinant plasmid was transfected into CHO cells, and those with stable expression were screened with G418. Expressed protein was identified and coupled with Luminex xMAP beads, which were then reacted with sera samples...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28135763/the-cyp2c19-2-and-cyp2c19-17-polymorphisms-play-a-vital-role-in-clopidogrel-responsiveness-after-percutaneous-coronary-intervention-a-pharmacogenomics-study
#9
Faruk Saydam, İrfan Değirmenci, Alparslan Birdane, Mahmut Özdemir, Taner Ulus, Cansu Özbayer, Ertuğrul Çolak, Necmi Ata, Hasan Veysi Güneş
Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y12 receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study...
January 30, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28096474/junb-regulates-angiogenesis-and-neurovascular-parallel-alignment-in-mouse-embryonic-skin
#10
Yasuo Yoshitomi, Takayuki Ikeda, Hidehito Saito, Yoshino Yoshitake, Yasuhito Ishigaki, Toshihisa Hatta, Nobuo Kato, Hideto Yonekura
Blood vessels and nerve fibers are often closely arranged in parallel throughout the body. Therefore, neurovascular interactions have been suggested to be important for the development of vascular networks. However, the molecular mechanisms and genes regulating this process remain unclear. In the present study, we investigated the genes that are activated in endothelial cells (ECs) following interactions with neurons during vascular development. Microarray analyses of human primary microvascular ECs co-cultured with mouse primary dorsal root ganglion cells showed that JunB is strongly upregulated in ECs by neurovascular interactions...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/27965976/identification-of-itga2b-and-itgb3-single-nucleotide-polymorphisms-and-their-influences-on-the-platelet-function
#11
Qian Xiang, Shun-Dong Ji, Zhuo Zhang, Xia Zhao, Yi-Min Cui
The aim of the study was to investigate ITGA2B and ITGB3 genetic polymorphisms and to evaluate the variability in the platelet function in healthy Chinese subjects. The genetic sequence of the entire coding region of the ITGA2B and ITGB3 genes was investigated. Adenosine diphosphate-induced platelet aggregation, glycoprotein IIb/IIIa content, bleeding time, and coagulation indexes were detected. Thirteen variants in the ITGA2B locus and 29 variants in the ITGB3 locus were identified in the Chinese population...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27940296/induction-of-type-1-iodothyronine-deiodinase-expression-inhibits-proliferation-and-migration-of-renal-cancer-cells
#12
Piotr Poplawski, Beata Rybicka, Joanna Boguslawska, Katarzyna Rodzik, Theo J Visser, Alicja Nauman, Agnieszka Piekielko-Witkowska
Type 1 iodothyronine deiodinase (DIO1) regulates peripheral metabolism of thyroid hormones that control cellular proliferation, differentiation and metabolism. The significance of DIO1 in cancer is unknown. In this study we hypothesized that diminished expression of DIO1, observed in renal cancer, contributes to the carcinogenic process in the kidney. Here, we demonstrate that ectopic expression of DIO1 in renal cancer cells changes the expression of genes controlling cell cycle, including cyclin E1 and E2F5, and results in inhibition of proliferation...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27932211/a-novel-class-of-somatic-mutations-in-blood-detected-preferentially-in-cd8-cells
#13
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
February 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27901069/molecular-profiling-of-circulating-tumour-cells-identifies-notch1-as-a-principal-regulator-in-advanced-non-small-cell-lung-cancer
#14
Javier Mariscal, Marta Alonso-Nocelo, Laura Muinelo-Romay, Jorge Barbazan, Maria Vieito, Alicia Abalo, Antonio Gomez-Tato, Casares de Cal Maria de Los Angeles, Tomas Garcia-Caballero, Carmela Rodriguez, Elena Brozos, Francisco Baron, Rafael Lopez-Lopez, Miguel Abal
Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27833078/dapper-homolog-1-alpha-suppresses-metastasis-ability-of-gastric-cancer-through-inhibiting-planar-cell-polarity-pathway
#15
Yuegeng Liu, Jingwan Zhang, Weifang Yu, Xiaoming Zhang, Guiqi Wang, Zengren Zhao
Dapper homolog 1 alpha (DACT1α) is a member of DACT family and an important regulator in the planar cell polarity pathway. We aim to clarify its functional role in metastasis ability of gastric cancer. DACT1α was silenced in all gastric cancer cell lines (8/8), but expressed in normal gastric tissue. Ectopic expression of DACT1α in silenced gastric cancer cell lines (AGS, BGC823 and MGC803) by stable transfection significantly suppressed cancer cell spreading (P < 0.05), migration (P < 0.01) and invasion (P < 0...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27792840/maternal-genetic-polymorphisms-and-unexplained-recurrent-miscarriage-a-systematic-review-and-meta-analysis
#16
REVIEW
X Shi, X Xie, Y Jia, S Li
The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. However, the results of these studies were inconsistent, especially when conducted in different populations. Therefore, we performed the current study to systematically review the broad spectrum of genetic polymorphisms that were suspected to be involved in RM, and discussed potential genetic biomarkers of RM. Eligible articles were identified in PubMed, Medline, Embase and CNKI. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association, and a probability value (p value) of 0...
February 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27759448/toward-optimal-set-of-single-nucleotide-polymorphism-investigation-before-ivf
#17
A V Ivanov, A G Dedul, Y N Fedotov, E V Komlichenko
BACKGROUND: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP...
October 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/27753953/os-08-03-pharmacogenetic-markers-of-survival
#18
Vera Erdman, Ilsia Tuktarova, Timur Nasibullin, Ianina Timasheva, Olga Mustafina
OBJECTIVE: Physiological and biochemical changes during aging alter drug metabolism. Drug intake is increased with age because of cumulative morbidity, in particular, high prevalence of cardiovascular diseases. Antihypertensive medications are the most commonly used drugs. Individual drug sensitivity or resistance may be influenced by the variance of the "pharmacological response" genes.Our purpose was to search for the polymorphic variants of "pharmacological response" genes associated with survival in different age periods...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27746115/generation-and-analysis-of-gata2-w-egfp-human-escs-reveal-itgb3-cd61-as-a-reliable-marker-for-defining-hemogenic-endothelial-cells-during-hematopoiesis
#19
Ke Huang, Jiao Gao, Juan Du, Ning Ma, Yanling Zhu, Pengfei Wu, Tian Zhang, Wenqian Wang, Yuhang Li, Qianyu Chen, Andrew Paul Hutchins, Zhongzhou Yang, Yi Zheng, Jian Zhang, Yongli Shan, Xuejia Li, Baojian Liao, Jiajun Liu, Jinyong Wang, Bing Liu, Guangjin Pan
The transition from hemogenic endothelial cells (HECs) to hematopoietic stem/progenitor cells (HS/PCs), or endothelial to hematopoietic transition (EHT), is a critical step during hematopoiesis. However, little is known about the molecular determinants of HECs due to the challenge in defining HECs. We report here the generation of GATA2(w/eGFP) reporter in human embryonic stem cells (hESCs) to mark cells expressing GATA2, a critical gene for EHT. We show that during differentiation, functional HECs are almost exclusively GATA2/eGFP(+)...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27743928/distortion-of-the-normal-function-of-synaptic-cell-adhesion-molecules-by-genetic-variants-as-a-risk-for-autism-spectrum-disorders
#20
REVIEW
Deeba Noreen Baig, Toru Yanagawa, Katsuhiko Tabuchi
Synaptic cell adhesion molecules (SCAMs) are a functional category of cell adhesion molecules that connect pre- and postsynapses by the protein-protein interaction via their extracellular cell adhesion domains. Countless numbers of common genetic variants and rare mutations in SCAMs have been identified in the patients with autism spectrum disorders (ASDs). Among these, NRXN and NLGN family proteins cooperatively function at synaptic terminals both of which genes are strongly implicated as risk genes for ASDs...
October 12, 2016: Brain Research Bulletin
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