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https://www.readbyqxmd.com/read/28230974/femtogram-resolution-of-iron-content-on-a-per-cell-basis-ex-vivo-storage-of-human-red-blood-cells-leads-to-loss-of-hemoglobin
#1
Jeffrey J Chalmers, Xiaoxia Jin, Andre Francis Palmer, Peter Amaya, Mark H Yazer, Lee R Moore, Kyoung-Joo Park, X Jeff Pan, Maciej Zborowski
The magnetic characteristics of hemoglobin (Hb) changes with the binding of dioxygen (O2) to the heme prosthetic groups of the globin chains: from paramagnetic ferrous Hb to diamagnetic ferrous oxyhemoglobin (oxyHb) with reversibly bound O2, or paramagnetic ferric methemoglobin (metHb). When multiplied over the number of Hb molecules in a red blood cell (RBC), the effect is detectable through motion analysis of RBCs in a high magnetic field and gradient. This motion is referred to as magnetophoretic mobility which can be conveniently expressed as a fraction of the cell sedimentation coefficient...
February 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28220744/burden-genotype-and-phenotype-profiles-of-adult-patients-with-sickle-cell-disease-in-cape-town-south-africa
#2
G D Pule, K Mnica, M Joubert, S Mowla, N Novitsky, A Wonkam
BACKGROUND: An exponential increase in the number of sickle cell disease (SCD) patients in paediatric services in Cape Town, South Africa, has been reported. The trend in adult/adolescent services has not been investigated. OBJECTIVES: To evaluate epidemiological trends of SCD and the profile of patients affected by SCD attending the Haematology Clinic at Groote Schuur Hospital (GSH), Cape Town. METHODS: (i) A retrospective review of the number of SCD patients over the past 20 years; (ii) a cross-sectional analysis of clinical and haematological characteristics of SCD patients; and (iii) molecular analysis of the haemoglobin S mutation, the haplotype in the β-globin-like genes cluster, the 3...
January 30, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28220719/protector-effect-of-%C3%AE-thalassaemia-on-cholecystitis-and-cholecystectomy-in-sickle-cell-disease
#3
Robéria M Pontes, Elaine S Costa, Patrícia F R Siqueira, Jussara F F Medeiros, Andréa Soares, Fabiana V de Mello, Maria C Maioli, Isaac L S Filho, Liliane R Alves, Marcelo G P Land, Marcos K Fleury
OBJECTIVES: Cholecystitis is one of the complications of symptomatic cholelithiasis responsible for high levels of morbidity of sickle cell disease (SCD) patients. Here, we investigated the possible protective role of single gene deletions of α-thalassaemia in the occurrence of cholelithiasis and cholecystitis in SCD patients, as well as the cholecystectomy requirements. METHODS: The α-globin genotype was determined in 83 SCD patients using the multiplex-polymerase chain reaction and compared with clinical events...
February 21, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28216629/matrix-attachment-region-combinations-increase-transgene-expression-in-transfected-chinese-hamster-ovary-cells
#4
Chun-Peng Zhao, Xiao Guo, Si-Jia Chen, Chang-Zheng Li, Yun Yang, Jun-He Zhang, Shao-Nan Chen, Yan-Long Jia, Tian-Yun Wang
Matrix attachment regions (MARs) are cis-acting DNA elements that can increase transgene expression levels in a CHO cell expression system. To investigate the effects of MAR combinations on transgene expression and the underlying regulatory mechanisms, we generated constructs in which the enhanced green fluorescent protein (eGFP) gene flanked by different combinations of human β-interferon and β-globin MAR (iMAR and gMAR, respectively), which was driven by the cytomegalovirus (CMV) or simian virus (SV) 40 promoter...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216155/forced-fog1-expression-in-erythroleukemia-cells-induction-of-erythroid-genes-and-repression-of-myelo-lymphoid-transcription-factor-pu-1
#5
Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#6
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205625/%C3%AE-globin-gene-cluster-haplotypes-in-ethnic-minority-populations-of-southwest-china
#7
Hao Sun, Hongxian Liu, Kai Huang, Keqin Lin, Xiaoqin Huang, Jiayou Chu, Shaohui Ma, Zhaoqing Yang
The genetic diversity and relationships among ethnic minority populations of southwest China were investigated using seven polymorphic restriction enzyme sites in the β-globin gene cluster. The haplotypes of 1392 chromosomes from ten ethnic populations living in southwest China were determined. Linkage equilibrium and recombination hotspot were found between the 5' sites and 3' sites of the β-globin gene cluster. 5' haplotypes 2 (+---), 6 (-++-+), 9 (-++++) and 3' haplotype FW3 (-+) were the predominant haplotypes...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199413/low-prevalence-of-human-papillomavirus-in-head-and-neck-squamous-cell-carcinoma-in-the-northwest-region-of-the-philippines
#8
Pia Marie Albano, Dana Holzinger, Christianne Salvador, Jose Orosa, Sheryl Racelis, Modesty Leaño, Danilo Sanchez, Lara Mae Angeles, Gordana Halec, Markus Schmitt, John Donnie Ramos, Michael Pawlita
BACKGROUND: Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines. METHODS: Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28195097/phenotypic-expression-of-hbo-indonesia-in-two-indian-families-and-its-interaction-with-sickle-hemoglobin
#9
Amar Das Gupta, Anita Nadkarni, Pallavi Mehta, Manju Goriwale, Manisha Ramani, Pradnya Chaudhary, Vishal Mehrotra, Roshan Colah
BACKGROUND: Alpha globin chain variants are clinically significant since they directly influence the structure and function of the hemoglobin (Hb) molecules they constitute, either in combination with normal beta globin chains or with variant beta chains, thereby altering the morbidity and mortality associated with the resultant hemoglobinopathies. We describe here two unrelated families from Madhya Pradesh who had a nondeletional alpha-chain variant, HbO Indonesia (CD116 G → A). Members of one of the two families also had coinheritance of sickle hemoglobin (HbS)...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28193153/molecular-evolution-of-globin-genes-in-gymnotiform-electric-fishes-relation-to-hypoxia-tolerance
#10
Ran Tian, Mauricio Losilla, Ying Lu, Guang Yang, Harold Zakon
BACKGROUND: Nocturnally active gymnotiform weakly electric fish generate electric signals for communication and navigation, which can be energetically taxing. These fish mainly inhabit the Amazon basin, where some species prefer well-oxygenated waters and others live in oxygen-poor, stagnant habitats. The latter species show morphological, physiological, and behavioral adaptations for hypoxia-tolerance. However, there have been no studies of hypoxia tolerance on the molecular level. Globins are classic respiratory proteins...
February 13, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28190779/lentiviral-transfer-of-%C3%AE-globin-with-fusion-gene-nup98-hoxa10hd-expands-hematopoietic-stem-cells-and-ameliorates-murine-%C3%AE-thalassemia
#11
Hui Fen Zhao, Allistair Abraham, Yoon-Sang Kim, Yong-Dong Wang, Tamara Pestina, Jun Zhan, Keith Humphries, Arthur W Nienhuis, Derek A Persons
Recently, an engineered Homeobox-nucleoporin fusion gene, NUP98-HOXA10HD or NA10HD, was reported to expand and maintain murine hematopoietic stem cells (HSCs). We postulated that NA10HD would increase the number of human γ-globin-expressing cells to therapeutic levels. We developed a double gene lentiviral vector encoding both human γ-globin and NA10HD, which was used to transduce human peripheral blood CD34(+) cells and increased engraftment 2- to 2.5-fold at 15 weeks post-transplantation in immunodeficient mice...
February 9, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28186586/-analysis-of-clinical-phenotype-and-genotype-of-unstable-hemoglobin-rush
#12
Shijun Ge, Biqing Yang, Wei Yi, Kai Huang, Hongxian Liu, Xiaoqin Huang, Jiayou Chu, Zhaoqing Yang
OBJECTIVE: To analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia. METHODS: Peripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site of (G)γ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing...
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/28185829/a-systematic-review-of-the-literature-for-severity-predictors-in-children-with-sickle-cell-anemia
#13
Emily Riehm Meier, Ross M Fasano, Paul R Levett
All patients with HbSS (SCA) share the same genetic mutation but the clinical phenotype is variable and difficult to predict early in life. A reliable severity predictor would be invaluable toward directing therapeutic decisions in those patients at highest risk of SCA complications. A search of PubMed, Cochrane Clinical Trials Register, and Scopus was performed to determine which SCA severity predictors have been validated in pediatric patients. The full text of 94 of the 590 references identified was reviewed based on the title/abstract...
February 2, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28181495/expression-of-%C3%AE-globin-by-cancer-cells-promotes-cell-survival-during-blood-borne-dissemination
#14
Yu Zheng, David T Miyamoto, Ben S Wittner, James P Sullivan, Nicola Aceto, Nicole Vincent Jordan, Min Yu, Nezihi Murat Karabacak, Valentine Comaills, Robert Morris, Rushil Desai, Niyati Desai, Erin Emmons, John D Milner, Richard J Lee, Chin-Lee Wu, Lecia V Sequist, Wilhelm Haas, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Shyamala Maheswaran, Daniel A Haber
Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179501/drug-discovery-for-diamond-blackfan-anemia-using-reprogrammed-hematopoietic-progenitors
#15
Sergei Doulatov, Linda T Vo, Elizabeth R Macari, Lara Wahlster, Melissa A Kinney, Alison M Taylor, Jessica Barragan, Manav Gupta, Katherine McGrath, Hsiang-Ying Lee, Jessica M Humphries, Alex DeVine, Anupama Narla, Blanche P Alter, Alan H Beggs, Suneet Agarwal, Benjamin L Ebert, Hanna T Gazda, Harvey F Lodish, Colin A Sieff, Thorsten M Schlaeger, Leonard I Zon, George Q Daley
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28179282/the-gata-factor-revolution-in-hematology
#16
Koichi R Katsumura, Emery H Bresnick, GATA Factor Mechanisms Group
The discovery of the GATA transcription factor family revolutionized hematology. Studies of GATA proteins have yielded vital contributions to our understanding of how hematopoietic stem and progenitor cells (HSPCs) develop from precursors, how progenitors generate red blood cells, how hemoglobin synthesis is regulated, and the molecular underpinnings of non-malignant and malignant hematologic disorders. This thrilling journey began with mechanistic studies on a β-globin enhancer- and promoter-binding factor, GATA-1, the founding member of the GATA family...
8, 2017: Blood
https://www.readbyqxmd.com/read/28178945/comparative-genomics-of-canine-hemoglobin-genes-reveals-primacy-of-beta-subunit-delta-in-adult-carnivores
#17
Sara Zaldívar-López, Jennie L Rowell, Elise M Fiala, Isain Zapata, C Guillermo Couto, Carlos E Alvarez
BACKGROUND: The main function of hemoglobin (Hb) is to transport oxygen in the circulation. It is among the most highly studied proteins due to its roles in physiology and disease, and most of our understanding derives from comparative research. There is great diversity in Hb gene evolution in placental mammals, mostly in the repertoire and regulation of the β-globin subunits. Dogs are an ideal model in which to study Hb genes because: 1) they are members of Laurasiatheria, our closest relatives outside of Euarchontoglires (including primates, rodents and rabbits), 2) dog breeds are isolated populations with their own Hb-associated genetics and diseases, and 3) their high level of health care allows for development of biomedical investigation and translation...
February 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28173090/evolution-and-expression-of-tissue-globins-in-ray-finned-fishes
#18
Michael D Gallagher, Daniel J Macqueen
No abstract text is available yet for this article.
January 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28168416/the-first-validated-criteria-for-effective-screening-and-a-new-simplified-method-for-%C3%AE-globin-gene-sequencing-for-diagnosis-of-uncommon-%C3%AE-globin-mutations
#19
Noppacharn Uaprasert, Rung Settapiboon, Supaporn Amornsiriwat, Pranee Sutcharitchan, Ponlapat Rojnuckarin
No well-defined phenotypes that distinguish between unknown α- and β-globin mutations have been reported to date. Direct DNA sequencing of α-globin genes can be technically challenging, as α1- and α2-globin genes are nearly indistinguishable. To detect hemoglobin variants (HbXs) on Hb analysis, the entire β- and α-globin genes were directly sequenced using a newly developed sequencing protocol for α-globin genes. An algorithm to distinguish between α- and β-HbXs was constructed and subsequently validated in the independent validation group...
February 6, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28165867/hypermethylated-ltr-retrotransposon-exhibits-enhancer-activity
#20
Tianxiang Hu, Xingguo Zhu, Wenhu Pi, Miao Yu, Huidong Shi, Dorothy Tuan
LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. They are silenced by hypermethylation of cytosines in CpG dinucleotides and are considered parasitic DNA serving no useful function for the host genome. However, hypermethylated LTRs contain enhancer and promoter sequences and can promote tissue-specific transcription of cis-linked genes. To resolve the apparent paradox of hypermethylated LTRs possessing transcriptional activities, we studied the ERV-9 LTR retrotransposon located at the 5' border of the transcriptionally active β-globin gene locus in human erythroid progenitor and erythroleukemia K562 cells...
February 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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