27 results on '"Yilmaz, Omer"'
Search Results
2. Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation
- Author
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Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mana, Miyeko, Yilmaz, Omer, Sabatini, David, Dominguez-Brauer, Carmen, Hao, Zhenyue, Elia, Andrew J., Fortin, Jérôme M., Nechanitzky, Robert, Brauer, Patrick M., Sheng, Yi, Chio, Iok In Christine, Haight, Jillian, Pollett, Aaron, Cairns, Robert, Tworzyanski, Leanne, Inoue, Satoshi, Reardon, Colin, Marques, Ana, Silvester, Jennifer, Cox, Maureen A., Wakeham, Andrew, van Es, Johan H., Clevers, Hans, Sato, Toshiro, Mak, Tak W., Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mana, Miyeko, Yilmaz, Omer, Sabatini, David, Dominguez-Brauer, Carmen, Hao, Zhenyue, Elia, Andrew J., Fortin, Jérôme M., Nechanitzky, Robert, Brauer, Patrick M., Sheng, Yi, Chio, Iok In Christine, Haight, Jillian, Pollett, Aaron, Cairns, Robert, Tworzyanski, Leanne, Inoue, Satoshi, Reardon, Colin, Marques, Ana, Silvester, Jennifer, Cox, Maureen A., Wakeham, Andrew, van Es, Johan H., Clevers, Hans, Sato, Toshiro, and Mak, Tak W.
- Abstract
The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown. Here, we show in vivo that Mule controls murine intestinal stem and progenitor cell proliferation by modulating Wnt signaling via c-Myc. Mule also regulates protein levels of the receptor tyrosine kinase EphB3 by targeting it for proteasomal and lysosomal degradation. In the intestine, EphB/ephrinB interactions position cells along the crypt-villus axis and compartmentalize incipient colorectal tumors. Our study thus unveils an important new avenue by which Mule acts as an intestinal tumor suppressor by regulation of the intestinal stem cell niche.
- Published
- 2018
3. Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer
- Author
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Koch Institute for Integrative Cancer Research at MIT, Yilmaz, Omer, Roper, Jatin, Sinnamon, Mark J., Coffee, Erin M., Belmont, Peter, Keung, Lily, Georgeon-Richard, Larissa, Wang, Wei Vivian, Faber, Anthony C., Yun, Jihye, Bronson, Roderick T., Martin, Eric S., Tsichlis, Philip N., Hung, Kenneth E., Koch Institute for Integrative Cancer Research at MIT, Yilmaz, Omer, Roper, Jatin, Sinnamon, Mark J., Coffee, Erin M., Belmont, Peter, Keung, Lily, Georgeon-Richard, Larissa, Wang, Wei Vivian, Faber, Anthony C., Yun, Jihye, Bronson, Roderick T., Martin, Eric S., Tsichlis, Philip N., and Hung, Kenneth E.
- Abstract
PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. Keywords: PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cancer
- Published
- 2018
4. Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
- Author
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Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mana, Miyeko, Yilmaz, Omer, Barriga, Francisco M., Montagni, Elisa, Mendez-Lago, Maria, Hernando-Momblona, Xavier, Sevillano, Marta, Guillaumet-Adkins, Amy, Rodriguez-Esteban, Gustavo, Buczacki, Simon J.A., Gut, Marta, Heyn, Holger, Winton, Douglas J., Attolini, Camille Stephan-Otto, Gut, Ivo, Batlle, Eduard, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mana, Miyeko, Yilmaz, Omer, Barriga, Francisco M., Montagni, Elisa, Mendez-Lago, Maria, Hernando-Momblona, Xavier, Sevillano, Marta, Guillaumet-Adkins, Amy, Rodriguez-Esteban, Gustavo, Buczacki, Simon J.A., Gut, Marta, Heyn, Holger, Winton, Douglas J., Attolini, Camille Stephan-Otto, Gut, Ivo, and Batlle, Eduard
- Abstract
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment. Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration. Keywords: Lgr5+ ISC heterogeneity; quiescent stem cell; chemotherapy resistance
- Published
- 2018
5. IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic Enteropathy
- Author
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Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Yilmaz, O, Cheng, Chia-Wei, Yilmaz, Omer, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Yilmaz, O, Cheng, Chia-Wei, and Yilmaz, Omer
- Abstract
Patients with type 1 diabetes (T1D) often experience gastrointestinal enteropathy (DE) of unclear etiology. Now in Cell Stem Cell, D’Addio et al. (2015) utilize organoid culture models to study the roles of stem cells in DE and show that circulating IGF/IGFBP3 controls colonic stem cell function during homeostasis and in T1D patients.
- Published
- 2017
6. Dietary and Metabolic Control of Stem Cell Function in Physiology and Cancer
- Author
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Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research at MIT, Mihaylova, Maria M., Sabatini, David M., Yilmaz, Omer, Sabatini, David, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research at MIT, Mihaylova, Maria M., Sabatini, David M., Yilmaz, Omer, and Sabatini, David
- Abstract
Organismal diet has a profound impact on tissue homeostasis and health in mammals. Adult stem cells are a keystone of tissue homeostasis that alters tissue composition by balancing self-renewal and differentiation divisions. Because somatic stem cells may respond to shifts in organismal physiology to orchestrate tissue remodeling and some cancers are understood to arise from transformed stem cells, there is a likely possibility that organismal diet, stem cell function, and cancer initiation are interconnected. Here we will explore the emerging effects of diet on nutrient-sensing pathways active in mammalian tissue stem cells and their relevance to normal and cancerous growth., Damon Runyon Cancer Research Foundation (DRG-2146-13), Howard Hughes Medical Institute (Investigator), National Institutes of Health (U.S.) (NIH CA129105), National Institutes of Health (U.S.) (NIH CA103866 award), National Institutes of Health (U.S.) (NIH AI047389), David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute Frontier Research Program), Lawrence Ellison Foundation, National Institutes of Health (U.S.) (NIH/NIA AG045144, K99/ R00 Pathway to Independence Award), National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (CSIBD grant from the NIDDK/NIH (DK043351))
- Published
- 2016
7. ZFHX4 Interacts with the NuRD Core Member CHD4 and Regulates the Glioblastoma Tumor-Initiating Cell State
- Author
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Kevin D. Woolard, Warren A. Whyte, Richard A. Young, Siyuan Zheng, Dohoon Kim, Keith L. Ligon, Roel G.W. Verhaak, Jeongwu Lee, Anne E. Carpenter, Steve Bilodeau, Maya Mitalipova, Ömer H. Yilmaz, Mark-Anthony Bray, David M. Sabatini, Shuba Gopal, Ingo K. Mellinghoff, Andrea Califano, Riko Nishimura, Mukesh Bansal, Yakov Chudnovsky, William C. Hahn, David E. Root, Julien Muffat, Nobuo Sakata, Matthew A. Theisen, Milan G. Chheda, Prathapan Thiru, Howard A. Fine, Serena J. Silver, Koch Institute for Integrative Cancer Research at MIT, Chudnovsky, Yakov, Kim, Dohoon, Whyte, Warren A., Thiru, Prathapan, Muffat, Julien, Yilmaz, Omer, Mitalipova, Maya, Young, Richard A., and Sabatini, David M.
- Subjects
Transcription, Genetic ,Carcinogenesis ,Medical Physiology ,Biology ,Autoantigens ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Mice ,Rare Diseases ,Genetic ,Mice, Inbred NOD ,Cell Line, Tumor ,Precursor cell ,Gene expression ,Genetics ,Animals ,Humans ,Nucleosome ,Gene ,Transcription factor ,lcsh:QH301-705.5 ,Cancer ,Homeodomain Proteins ,Neoplastic ,Tumor ,Neurosciences ,Molecular biology ,Mi-2/NuRD complex ,Phenotype ,Brain Disorders ,3. Good health ,Cell biology ,nervous system diseases ,Brain Cancer ,Gene Expression Regulation, Neoplastic ,Gene Expression Regulation ,lcsh:Biology (General) ,Inbred NOD ,Biochemistry and Cell Biology ,CHD4 ,Glioblastoma ,Transcription ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Protein Binding ,Transcription Factors - Abstract
Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state., American Cancer Society (Postdoctoral Fellowship), American Brain Tumor Association (Discovery Grant), National Institutes of Health (U.S.) (Grant P30CA016672), National Institutes of Health (U.S.) (Grant U24CA143883), European Leukodystrophy Association, Japan. Ministry of Education, Culture, Sports, Science and Technology (MEXT/JSPS (KAKENHI 256701), Broad Institute of MIT and Harvard, National Institutes of Health (U.S.) (NIH (R01GM089652), National Institutes of Health (U.S.) (NIH (U01CA168426), National Institutes of Health (U.S.) (NIH U54CA121852), National Institutes of Health (U.S.) (NIH (R01HG002668), National Institutes of Health (U.S.) (NIH R01CA146455), National Institutes of Health (U.S.) (NIH (R01CA170592), National Institutes of Health (U.S.) (NIH P01CA095616), Sontag Foundation, Goldhirsh Foundation, National Institutes of Health (U.S.) (NIH R01NS080944), Starr Foundation, National Institutes of Health (U.S.) (NIH (R01CA129105), David H. Koch Institute for Integrative Cancer Research at MIT, National Institutes of Health (U.S.) (NIH P01CA142536), National Institutes of Health (U.S.) (NIH U01CA176058), National Institutes of Health (U.S.) (NIH K08NS062907), National Institutes of Health (U.S.) (NIH K12CA090354), American Association for Cancer Research, National Brain Tumor Society (fellowship), Dana-Farber Cancer Institute (Pediatric Low Grade Astrocytoma Program grant), Broad Institute of MIT and Harvard (SPARC grant), Howard Hughes Medical Institute (Investigator)
- Published
- 2014
8. Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells
- Author
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Ömer H. Yilmaz, Francisco M. Barriga, Elisa Montagni, Ivo Gut, Xavier Hernando-Momblona, Marta Sevillano, Amy Guillaumet-Adkins, Miyeko D. Mana, Eduard Batlle, Simon J.A. Buczacki, Maria Mendez-Lago, Camille Stephan-Otto Attolini, Holger Heyn, Douglas J. Winton, Marta Gut, Gustavo Rodriguez-Esteban, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mana, Miyeko, and Yilmaz, Omer
- Subjects
0301 basic medicine ,education.field_of_study ,Regeneration (biology) ,Population ,LGR5 ,Cell Biology ,Stem cells ,Biology ,Intestinal epithelium ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Mucosa intestinal ,Intestinal mucosa ,Immunology ,Genetics ,Molecular Medicine ,Compartment (development) ,RNA ,Stem cell ,education ,Cèl·lules mare ,Proteïnes ,Homeostasis ,Cèl·lules -- Proliferació - Abstract
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment. Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration. Keywords: Lgr5+ ISC heterogeneity; quiescent stem cell; chemotherapy resistance
- Published
- 2017
9. IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic Enteropathy
- Author
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Ömer H. Yilmaz, Chia-Wei Cheng, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Yilmaz, O, Cheng, Chia-Wei, and Yilmaz, Omer
- Subjects
Type 1 diabetes ,IGFBP3 ,Cell Biology ,Biology ,medicine.disease ,Diabetes mellitus ,Immunology ,medicine ,Organoid ,Genetics ,Experimental pathology ,Molecular Medicine ,Enteropathy ,Stem cell ,Homeostasis - Abstract
Patients with type 1 diabetes (T1D) often experience gastrointestinal enteropathy (DE) of unclear etiology. Now in Cell Stem Cell, D'Addio et al. (2015) utilize organoid culture models to study the roles of stem cells in DE and show that circulating IGF/IGFBP3 controls colonic stem cell function during homeostasis and in T1D patients.
- Published
- 2015
10. Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer
- Author
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Peter J. Belmont, Erin M. Coffee, Lily Keung, Anthony C. Faber, Ömer H. Yilmaz, Roderick T. Bronson, Eric S. Martin, Philip N. Tsichlis, Kenneth E. Hung, Jihye Yun, Larissa Georgeon-Richard, Wei Vivian Wang, Jatin Roper, Mark J. Sinnamon, Koch Institute for Integrative Cancer Research at MIT, and Yilmaz, Omer
- Subjects
MAPK/ERK pathway ,Cancer Research ,Class I Phosphatidylinositol 3-Kinases ,Colorectal cancer ,Mutant ,Apoptosis ,mTORC1 ,medicine.disease_cause ,Article ,Mice ,Phosphatidylinositol 3-Kinases ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,neoplasms ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,Chemistry ,Wild type ,Cancer ,MAP Kinase Kinase Kinases ,medicine.disease ,Molecular biology ,digestive system diseases ,Mice, Inbred C57BL ,Genes, ras ,Oncology ,Mutation ,Cancer research ,KRAS ,Colorectal Neoplasms - Abstract
PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. Keywords: PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cancer
- Published
- 2014
11. Bacterial contamination of multi-use tear drops, gels, and ointments.
- Author
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Faruk Yilmaz O, Sarmis A, Ali Mutlu M, Büsra Sahin Z, Pelin Kaya S, and Oguz H
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- Humans, Ointments, Bacteria, Gels, Lubricants, Methicillin-Resistant Staphylococcus aureus
- Abstract
Purpose: This study aimed to investigate the bacterial contamination of multi-use tear drops, gels, and ointments that patients use at home., Method: A total of 271 multi-use containers used by 168 patients were examined. Conjunctival culture samples were obtained from patients who used tear drops, gels, and ointments that were found to be contaminated., Results: Bacterial contamination was detected in 33 (12.2 %) out of the 271 containers. The contamination rate was 7.9 % in tear drops, 11.7 % in gels, and 32 % in ointments. A statistically significant difference was found between the drops, gels, and ointment groups (P = 0.04). Bacterial contamination was detected in 25 (18.9 %) out of 132 collapsible tubes and 8 (5.8 %) out of 139 plastic bottles (P = 0.01). Important bacteria, including Pseudomonas stutzeri, Pseudomonas aeruginosa, Bacillus licheniformis, Paenibacillus pabuli, Proteus mirabilis, Pantoea agglomerans, Morganella morganii, Serratia marcescens, and Serratia liquefaciens, were detected. Mucorales spp. fungus was seen in a gel. Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and M. morganii were found in the conjunctival microbiota of three patients., Conclusion: The overall contamination rate of ocular lubricants was low (12.2%); however, a significant difference was found between the drops, gels, and ointments. The contamination rate was higher in gels and ointments than that in drops. The contamination rate was found to be increased in the collapsible tube. The use of ocular lubricants is safe; however, patients must be cautious when using multi-use tear drops, gels, and ointments to avoid contamination. Whenever possible, bottles should be preferred instead of collapsible tubes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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12. The ureteral diameter ratio as a predictive factor in renal scarring associated with primary vesicoureteral reflux.
- Author
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Akyol Onder EN, Ensari E, Ozkol M, Yilmaz O, Taneli C, and Ertan P
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- Humans, Infant, Cicatrix etiology, Retrospective Studies, Ureteroscopy methods, Vesico-Ureteral Reflux diagnosis, Ureter pathology, Urinary Tract Infections diagnosis
- Abstract
Introduction: The ureteral diameter ratio (UDR) is reported to be effective in predicting the outcomes of vesicoureteral reflux (VUR) in several studies., Objective: The objective of the current study was to compare the risk of scarring in patients with VUR relative to UDR and the VUR grade. We also aimed to demonstrate other associated risk factors in scarring and investigate the long-term complications of VUR and their relationship with UDR., Study Design: Patients diagnosed with primary VUR were retrospectively enrolled in the study. UDR was calculated by dividing the largest ureteral diameter (UD) by the distance between L1-L3 vertebral bodies. Demographic and clinical data, laterality, VUR grade, UDR, delayed upper tract drainage on voiding cystourethrogram, recurrent urinary tract infections (UTI), and long-term complications of VUR were compared between the patients with and without renal scars., Results: A total of 127 patients and 177 renal units were included in the study. There was a significant difference between the patients with and without renal scars according to age at diagnosis, bilaterality, reflux grade, UDR, recurrent UTI, bladder bowel dysfunction, hypertension, decreased estimated glomerular filtration rate, and proteinuria. The logistic regression analysis revealed that UDR had the highest odds ratio among the factors affecting scarring in VUR., Discussion: VUR grading based on the evaluation of the upper urinary tract is one of the most important predictors for treatment options and prognosis. However, it is more likely to reflect ureterovesical junctional anatomy and function, which play a crucial role in the pathogenesis of VUR., Conclusion: UDR measurement seems to be an objective method that can help clinicians predict renal scarring in patients with primary VUR., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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13. Pain, wound healing and refractive comparison of mechanical and transepithelial debridement in photorefractive keratectomy for myopia: results of 1 year follow-up.
- Author
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Celik U, Bozkurt E, Celik B, Demirok A, and Yilmaz OF
- Subjects
- Adult, Debridement methods, Eye Pain diagnosis, Eye Pain prevention & control, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Myopia physiopathology, Recovery of Function, Refraction, Ocular, Treatment Outcome, Eye Pain etiology, Keratectomy, Subepithelial, Laser-Assisted methods, Myopia diagnosis, Myopia surgery, Photorefractive Keratectomy methods, Wound Healing
- Abstract
Purpose: To compare the efficacy, safety and postoperative pain of mechanical versus transepithelial photorefractive keratectomy (PRK) techniques., Setting: Cornea and refractive surgery subspecialty., Design: Prospective clinical trial., Methods: This prospective comparative study included 84 eyes of 42 patients with myopia who received mechanical PRK (m-PRK) in 1 eye and transepithelial PRK (t-PRK) in the contralateral eye. The mean patient age was 28.5±6.3 years (range 20-46 years). Postoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refractions, postoperative epithelial healing time, surgical time, postoperative pain rating and corneal haze were recorded., Results: At week 1, statistically the UDVA was significantly better in the t-PRK eyes; however, at 3 months, similar refractive stability was achieved in both groups. The mean spherical equivalent (SE) decreased from -2.44±1.00D (m-PRK eyes) and -2.88±1.24D (t-PRK eyes) at baseline to -0.19±0.38D and -0.30±0.40D, respectively, after 1 year. Surgical time was 98.6±9.8s in m-PRK eyes and 58.0±6.4s in t-PRK eyes. On postoperative days 1 and 3, using the global assessment rating, 81% of mPRK eyes that had pain, reported more pain than that reported for the tPRK eyes. In addition, m-PRK treated eyes demonstrated higher mean pain scores based on the 11-point numerical rating scale and Visual Analogue Scale (VAS). The mean time to complete epithelial healing was 2.19±0.39 days (t-PRK) and 3.76±0.43 days (m-PRK)., Conclusion: t-PRK for mild-to-moderate myopia was more comfortable than conventional m-PRK; patients had less pain, and faster healing time., (Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2014
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14. Comparison of visual acuity and higher-order aberrations after femtosecond lenticule extraction and small-incision lenticule extraction.
- Author
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Ağca A, Demirok A, Cankaya Kİ, Yaşa D, Demircan A, Yildirim Y, Ozkaya A, and Yilmaz OF
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- Adult, Corneal Surgery, Laser instrumentation, Female, Humans, Male, Myopia complications, Myopia diagnosis, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Treatment Outcome, Vision Disorders etiology, Visual Acuity, Corneal Surgery, Laser adverse effects, Corneal Surgery, Laser methods, Myopia surgery, Refractive Errors etiology, Refractive Errors prevention & control, Vision Disorders diagnosis, Vision Disorders prevention & control
- Abstract
Purpose: To compare postoperative visual acuity and higher-order aberrations (HOAs) after femtosecond lenticule extraction (FLEX) and after small-incision lenticule extraction (SMILE)., Methods: Medical records of refractive lenticule extraction patients were retrospectively reviewed. Twenty patients were treated with FLEX. A comparable group of 20 SMILE patients were retrospectively identified. Only one eye of each patient was randomly chosen for the study. Visual acuity, subjective manifest refraction and corneal topography before and 6 months after the surgery were analyzed for both groups. Total HOAs, spherical aberrations, coma and trefoil were calculated from topography data over the 4- and 6-mm-diameter central corneal zone., Results: The mean preoperative SE was -4.03 ± 1.61 in the SMILE group and -4.46 ± 1.61 in the FLEX group. One year after surgery, the mean SE was -0.33 ± 0.25 in the SMILE group and -0.31 ± 0.41 in the FLEX group (p=0.86). In the SMILE group a greater number of eyes were within ±0.50D of the target refraction (95% versus 75%); however, the difference was not statistically significant (p=0.18). Furthermore, 80% of FLEX eyes and 95% of SMILE eyes had an uncorrected distance visual acuity of 20/25 or better (p=0.34). Total HOAs, spherical aberration, coma and trefoil increased postoperatively in both groups. However, there was no statistically significant difference between the groups preoperatively and postoperatively., Conclusion: FLEX and SMILE result in comparable refractive results. In addition, corneal aberrations induced by different techniques of lenticule extraction seemed similar to each other., (Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)
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- 2014
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15. Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease.
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Demircelik MB, Yilmaz OC, Gurel OM, Selcoki Y, Atar IA, Bozkurt A, Akin K, and Eryonucu B
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- Adult, Female, Humans, Male, Multidetector Computed Tomography, ROC Curve, Risk Factors, Severity of Illness Index, Adipose Tissue diagnostic imaging, Atherosclerosis diagnostic imaging, Coronary Artery Disease diagnostic imaging, Pericardium diagnostic imaging
- Abstract
Objective: The aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease., Methods: The study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing <50% in diameter), Group 2; and obstructive atherosclerosis (luminal narrowing ≥ 50%) in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium). Epicardial adipose tissue thickness (mm) was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses., Results: The average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm., Conclusion: We showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases.
- Published
- 2014
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16. Comparison of corneal hysteresis and corneal resistance factor after small incision lenticule extraction and femtosecond laser-assisted LASIK: a prospective fellow eye study.
- Author
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Agca A, Ozgurhan EB, Demirok A, Bozkurt E, Celik U, Ozkaya A, Cankaya I, and Yilmaz OF
- Subjects
- Adult, Corneal Topography, Elasticity, Female, Hardness, Humans, Male, Myopia diagnosis, Prospective Studies, Treatment Outcome, Viscosity, Cornea physiopathology, Cornea surgery, Keratomileusis, Laser In Situ methods, Minimally Invasive Surgical Procedures methods, Myopia physiopathology, Myopia surgery, Refractive Surgical Procedures methods
- Abstract
Purpose: To compare corneal hysteresis (CH) and corneal resistance factor (CRF) between eyes treated with small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (femto-LASIK)., Setting: Beyoğlu Eye Training and Research Hospital., Design: Prospective comparative case series., Methods: Sixty eyes from 30 patients with bilateral myopia or myopic astigmatism were studied. Inclusion criteria were spherical equivalent of subjective manifest refraction (SE) <10diopters (D) and a difference ≤0.50D between the SEs of both eyes. One eye of each patient was treated with SMILE, and the fellow eye underwent femto-LASIK. Randomization was performed using a sealed envelope system. The main outcome measures were CH and CRF measured preoperatively and postoperatively (1 and 6 months)., Results: Preoperative SE was similar in both groups (p=0.852). CH and CRF values were reduced postoperatively in both groups compared to their corresponding preoperative values (p<0.001). At the 6-month follow-up visit, the mean CH values in the SMILE and femto-LASIK groups were 8.95±1.47 and 9.02±1.27, respectively (p=0.852), and the mean CRF values were 7.77±1.37 and 8.07±1.26, respectively (p=0.380)., Conclusion: CH and CRF decreased after SMILE. There were no differences between SMILE and femto-LASIK treatments in postoperative CH or CRF values., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2014
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17. Association between gamma-glutamyltransferase and coronary artery calcification.
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Atar AI, Yilmaz OC, Akin K, Selcoki Y, Er O, and Eryonucu B
- Subjects
- Adult, Aged, Biomarkers blood, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography methods, Coronary Artery Disease blood, Coronary Artery Disease diagnostic imaging, Vascular Calcification blood, Vascular Calcification diagnostic imaging, gamma-Glutamyltransferase blood
- Abstract
Background: The exact mechanisms behind the association between atherosclerosis and gamma-glutamyltransferase (GGT) are unclear. Coronary artery calcification (CAC) detected by computerized tomography is an important marker of atherosclerosis and its severity correlates with coronary plaque burden. The aim of this study was to investigate if serum GGT levels are associated with CAC in patients without known coronary heart disease (CHD) who had low-intermediate risk for CHD., Methods: Two hundred and seventy two patients who had low-intermediate risk for coronary artery disease were included in the study. Serum GGT levels were measured spectrophotometrically. CACS (Agatston method) were performed using a 64-slice computerized tomography scanner. The patients were grouped according to their GGT values in four quartiles., Results: Patients in higher GGT quartiles had elevated CAC score (P<0.001). Patients in higher GGT quartiles were predominantly males (P<0.001) and were more likely to be smoking (P=0.004), and have elevated uric acid (P<0.001), fasting blood glucose (P<0.001), CRP levels (P=0.003) and 10-year total cardiovascular risk (P=0.007) and low HDL levels (P<0.001). Positive correlations were found between log GGT and CAC (r=0.233, P<0.001). In the multivariate analysis GGT, age, smoking and serum uric acid levels appeared as independent factors predictive of presence of CAC., Conclusions: We demonstrated a significant correlation between serum GGT levels and CAC and CHD risk factors. Serum GGT level was an independent marker of CAC., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
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18. Response letter to 'Uric acid: a crucial marker of coronary artery calcium score?'.
- Author
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Atar AI, Yilmaz OC, Akin K, Selcoki Y, Er O, and Eryonucu B
- Subjects
- Humans, Cardiovascular Diseases blood, Cardiovascular Diseases diagnosis, Uric Acid blood
- Published
- 2013
- Full Text
- View/download PDF
19. Pathology and Genetics of Pancreatic Neoplasms.
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Yilmaz OH and Deshpande V
- Abstract
This is a state-of-the-art review of the molecular genetics of pancreatic neoplasms. Although understanding of the molecular features underlying pancreatic neoplasms is still in its infancy, a strong emphasis on the relevance of these findings for the practicing surgical pathologist is provided. The application of molecular techniques has yielded a wealth of information that may soon enhance diagnostics, and will also lead to the development of safer, more effective targeted therapies. The pathologist will play a key role in integrating the current pathologic classification system with newly validated molecular markers., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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20. Double right coronary artery: a report of two cases.
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Selcoki Y, Yilmaz OC, Er O, and Eryonucu B
- Subjects
- Adult, Aged, Coronary Angiography, Female, Humans, Risk Factors, Coronary Vessel Anomalies diagnosis
- Published
- 2010
- Full Text
- View/download PDF
21. Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems.
- Author
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Levi BP, Yilmaz OH, Duester G, and Morrison SJ
- Subjects
- Aging physiology, Aldehyde Dehydrogenase genetics, Aldehyde Dehydrogenase 1 Family, Animals, Cells, Cultured, Cyclophosphamide pharmacology, Fluorescent Dyes, Gene Expression Regulation, Enzymologic, Hematopoiesis physiology, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells drug effects, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Myeloablative Agonists pharmacology, Retinal Dehydrogenase, Stem Cells cytology, Aldehyde Dehydrogenase metabolism, Central Nervous System cytology, Hematopoietic Stem Cells enzymology, Peripheral Nervous System cytology, Stem Cells enzymology
- Abstract
High levels of aldehyde dehydrogenase (ALDH) activity have been proposed to be a common feature of stem cells. Adult hematopoietic, neural, and cancer stem cells have all been reported to have high ALDH activity, detected using Aldefluor, a fluorogenic substrate for ALDH. This activity has been attributed to Aldh1a1, an enzyme that is expressed at high levels in stem cells and that has been suggested to regulate stem cell function. Nonetheless, Aldh1a1 function in stem cells has never been tested genetically. We observed that Aldh1a1 was preferentially expressed in mouse hematopoietic stem cells (HSCs) and expression increased with age. Hematopoietic cells from Aldh1a1-deficient mice exhibited increased sensitivity to cyclophosphamide in a non-cell-autonomous manner, consistent with its role in cyclophosphamide metabolism in the liver. However, Aldh1a1 deficiency did not affect hematopoiesis, HSC function, or the capacity to reconstitute irradiated recipients in young or old adult mice. Aldh1a1 deficiency also did not affect Aldefluor staining of hematopoietic cells. Finally, Aldh1a1 deficiency did not affect the function of stem cells from the adult central or peripheral nervous systems. Aldh1a1 is not a critical regulator of adult stem cell function or Aldefluor staining in mice.
- Published
- 2009
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22. CD150- cells are transiently reconstituting multipotent progenitors with little or no stem cell activity.
- Author
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Kiel MJ, Yilmaz OH, and Morrison SJ
- Subjects
- Animals, Ataxin-1, Ataxins, Bone Marrow Cells cytology, Cell Lineage, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells cytology, Mice, Nerve Tissue Proteins metabolism, Nuclear Proteins metabolism, Proto-Oncogene Proteins c-kit metabolism, Signaling Lymphocytic Activation Molecule Family Member 1, Antigens, CD metabolism, Multipotent Stem Cells cytology, Receptors, Cell Surface metabolism
- Published
- 2008
- Full Text
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23. Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors.
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Kim I, He S, Yilmaz OH, Kiel MJ, and Morrison SJ
- Subjects
- Animals, CD48 Antigen, Fetus cytology, Glycoproteins analysis, Graft Survival, Hematopoietic Stem Cell Transplantation, Immunoglobulins analysis, Immunophenotyping, Liver cytology, Membrane Glycoproteins analysis, Mice, Mice, Inbred C57BL, Receptors, Cell Surface, Signaling Lymphocytic Activation Molecule Family, Signaling Lymphocytic Activation Molecule Family Member 1, Antigens, CD analysis, Cell Separation methods, Hematopoietic Stem Cells cytology, Receptors, Immunologic analysis
- Abstract
Although adult mouse hematopoietic stem cells (HSCs) have been purified to near homogeneity, it remains impossible to achieve this with fetal HSCs. Adult HSC purity recently has been enhanced using the SLAM family receptors CD150, CD244, and CD48. These markers are expressed at different stages of the hematopoiesis hierarchy, making it possible to highly purify adult HSCs as CD150(+)CD48(-)CD244(-) cells. We found that SLAM family receptors exhibited a similar expression pattern in fetal liver. Fetal liver HSCs were CD150(+)CD48(-)CD244(-), and the vast majority of colony-forming progenitors were CD48(+)CD244(-)CD150(-) or CD48(+)CD244(+)CD150(-), just as in adult bone marrow. SLAM family markers enhanced the purification of fetal liver HSCs. Whereas 1 (11%) of every 8.9 Thy(low)Sca-1(+)lineage(-)Mac-1(+) fetal liver cells gave long-term multilineage reconstitution in irradiated mice, 1 (18%) of every 5.7 CD150(+)CD48(-)CD41(-) cells and 1 (37%) of every 2.7 CD150(+)CD48(-)Sca-1(+)lineage(-)Mac-1(+) fetal liver cells gave long-term multilineage reconstitution. These data emphasize the robustness with which SLAM family markers distinguish progenitors at different stages of the hematopoiesis hierarchy and enhance the purification of definitive HSCs from diverse contexts. Nonetheless, CD150, CD244, and CD48 are not pan-stem cell markers, as they were not detectably expressed by stem cells in the fetal or adult nervous system.
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- 2006
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24. SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.
- Author
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Yilmaz OH, Kiel MJ, and Morrison SJ
- Subjects
- Animals, Antigens, Ly, Antineoplastic Agents, Alkylating administration & dosage, CD48 Antigen, Cell Separation, Cyclophosphamide administration & dosage, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoietic Stem Cell Mobilization methods, Membrane Proteins, Mice, Proto-Oncogene Proteins c-kit, Receptors, Cell Surface, Signaling Lymphocytic Activation Molecule Family Member 1, Thy-1 Antigens, Whole-Body Irradiation, Aging metabolism, Antigens, CD metabolism, Glycoproteins metabolism, Graft Survival radiation effects, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells metabolism, Immunoglobulins metabolism
- Abstract
Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1 low Sca-1+ Lineage- c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+ CD48-, just as in normal young bone marrow. Thy-1 low Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+ CD48- Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.
- Published
- 2006
- Full Text
- View/download PDF
25. CD144 (VE-cadherin) is transiently expressed by fetal liver hematopoietic stem cells.
- Author
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Kim I, Yilmaz OH, and Morrison SJ
- Subjects
- Animals, Antigens, CD, Biomarkers analysis, Cadherins genetics, Endothelial Cells chemistry, Fetus cytology, Hematopoietic Stem Cells metabolism, Liver cytology, Mice, Mice, Inbred C57BL, Cadherins analysis, Gene Expression Regulation, Developmental, Hematopoietic Stem Cells chemistry, Liver embryology
- Abstract
Hematopoietic stem cells (HSCs) and endothelial progenitors arise from a common embryonic precursor. However, these populations diverge prior to the onset of definitive hematopoiesis, as HSCs become CD45+ and are thought to lose the expression of endothelial markers. After the onset of definitive hematopoiesis, CD144 (vascular endothelial [VE]-cadherin) has been considered a specific marker of endothelial cells. In contrast, we found that virtually all HSC activity from embryonic day 13.5 (E13.5) fetal liver was CD144+. CD144 expression declined on E16.5 fetal liver HSCs and was absent from adult bone marrow HSCs. This identified a new marker that is differentially expressed between fetal and adult HSCs, and enhanced the purification of HSCs from the E13.5 fetal liver. These results emphasize the close developmental relationship between hematopoietic and endothelial cells, while indicating that CD144 is not a specific marker of endothelial cells during fetal development.
- Published
- 2005
- Full Text
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26. Spatial differences in hematopoiesis but not in stem cells indicate a lack of regional patterning in definitive hematopoietic stem cells.
- Author
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Kiel MJ, Iwashita T, Yilmaz OH, and Morrison SJ
- Subjects
- Animals, Cells, Cultured, Colony-Forming Units Assay, Embryonic Development, Female, Fetus physiology, Gene Expression Profiling, Gene Expression Regulation, Developmental, Leukocyte Common Antigens genetics, Liver embryology, Mice, Mice, Inbred C57BL, Pregnancy, Reverse Transcriptase Polymerase Chain Reaction, Spleen embryology, Stem Cells cytology, Body Patterning, Hematopoiesis physiology, Stem Cells physiology
- Abstract
Most tissues are patterned so that progenitors in different locations are programmed to have different properties. Stem cells from different regions of the nervous system acquire intrinsic differences in their properties as they migrate through distinct environments. Hematopoietic stem cells (HSCs) also migrate through diverse environments throughout life, raising the question of whether HSCs also acquire at least transient changes in their properties as they are exposed to diverse environments. Although we observed significant differences in hematopoiesis between the fetal liver and fetal spleen, we were not able to detect phenotypic, functional, or gene expression differences between the HSCs in these organs. Regional differences in definitive hematopoiesis are therefore not determined by regional differences between HSCs. We were also not able to detect phenotypic, functional, or gene expression differences between HSCs in different adult bone marrow compartments. Our failure to detect differences among stem cells from different regions of the hematopoietic system at the same time during development suggests that the hematopoietic system has evolved mechanisms to prevent the spatial reprogramming of HSC properties as they migrate between distinct environments.
- Published
- 2005
- Full Text
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27. Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia.
- Author
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Bakan N, Taysi S, Yilmaz O, Bakan E, Kuşkay S, Uzun N, and Gündoğdu M
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Glutathione blood, Glutathione Peroxidase blood, Glutathione Reductase blood, Leukemia, Lymphocytic, Chronic, B-Cell blood, Malondialdehyde blood, Nitric Oxide blood, Superoxide Dismutase blood
- Abstract
Background: Chronic lymphocytic leukemia (CLL) is a rare neoplasm that comprises a substantial proportion of all leukemias in middle-aged persons and is the most common type among elderly persons. The major causes are not known nor is there a detailed understanding about how the elusive origin(s) may relate to clinical expression, basic biological mechanisms, or pathogenesis., Methods: Glutathione peroxidase (GSH-Px), glutathione reductase (GRD), Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, glutathione (GSH), nitric oxide (NO(*), and malondialdehyde (MDA) concentrations were measured in serum of patients with CLL and a healthy control group., Results: Serum GSH-Px, Cu-Zn SOD activities, GSH concentration were lower in patients with CLL while serum NO(*) and MDA concentrations were higher in these patients compared with the control group. Serum GRD activity was not statistically significant in patients with CLL compared with the control. However, there was no statistically significant difference in the parameters on the basis of stages in these patients. Serum GSH concentration negatively correlated with serum MDA (r=30.63, p<0.05) and NO(*) concentrations (r=0.72, p<0.05) in patients with advanced stage (III+IV). However, no other correlation could be found among the parameters in healthy controls and patients with CLL CONCLUSIONS: There is significant changes in antioxidant defense system in CLL cases, which may lead to enhanced action of oxygen radical, resulting in lipid peroxidation.
- Published
- 2003
- Full Text
- View/download PDF
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