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Öğe Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors(Spandidos Publ Ltd, 2015) Kodaz, Hilmi; Hacibekiroglu, Ilhan; Erdogan, Bulent; Turkmen, Esma; Tozkir, Hilmi; Albayrak, Dogan; Uzunoglu, SernazThe aim of this study was to investigate the clinicopathological characteristics and distribution by tumor localization of KRAS point mutations in metastatic colorectal cancer. A total of 189 patients diagnosed with colorectal cancer between 2007 and 2014, who were either metastatic at the time of diagnosis or developed metastasis subsequently, were included in this study. KRAS mutation analysis was performed in the primary tumor tissues and KRAS mutations were identified in 47.6% of the patients. There was a high frequency of the p.G13D point mutation in left-colon tumors (P=0.011), while the p.G12D point mutation was more frequent in right-colon tumors (P=0.004). KRAS wild-type frequency (P=0.02) was higher among patients aged <40 years. A comparison of codon 12 and 13 mutations revealed that codon 12 mutations were more common in the >50-year-old group (P=0.03) and codon 13 mutations were more common in the <70-year-old group (P=0.04). KRAS wild-type tumors were localized in the right colon (P=0.005) and tumors with the p.G13D point mutation (P=0.018) were diagnosed at non-metastatic stages. In conclusion, KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization. In addition, the p.G13D point mutation was found to differ from other mutations in several aspects.Öğe BETA-GLOBIN GENE MUTATIONS AND MICRO-HAPLOTYPE POLYMOPHISMS OF BETA-THALASSEMIA PATIENTS IN TRAKYA POPULATION(John Wiley & Sons Inc, 2009) Gurkan, Hakan; Turgut, Burhan; Tozkir, Hilmi; Bozkurt, Gokay; Tekgunduz, Emre[Abstract Not Available]Öğe BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares(Springer London Ltd, 2017) Pamuk, Omer Nuri; Gurkan, Hakan; Pamuk, Gulsum Emel; Tozkir, Hilmi; Duymaz, Julide; Yazar, MetinWe aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values < 0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.Öğe BLK Pathway-Associated rs13277113 GA Genotype Is More Frequent in Systemic Lupus Erythematosus Patients and Associated with Low Gene Expression and Increased Flares(Wiley, 2015) Pamuk, Omer Nuri; Gurkan, Hakan; Balci, Mehmet Ali; Tozkir, Hilmi; Duymaz, Julide; Sari, Gulce; Yazar, Metin[Abstract Not Available]Öğe CASP10, LEF1, BCL2 genes are hypomethylated and CDKN2B is hypermethylated in chronic lymphocytic leukemia(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Tozkir, Hilmi; Pamuk, Omer Nuri[Abstract Not Available]Öğe CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it associated with poor outcome?(Wolters Kluwer Medknow Publications, 2018) Pamuk, Gulsum Emel; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Pamuk, Omer NuriObjective: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL. Methods: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction. Results: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score. Discussion: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes. Conclusions: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome.Öğe Effect Mechanism Of Immunosupressive Drugs(Pera Yayincilik Hizmetleri, 2009) Ayna, Tulay Kilicaslan; Ciftci, Hayriye Senturk; Tozkir, Hilmi; Gurtekin, Mehmet; Carin, MahmutEffective immunosuppression is a key to successful organ transplantation. This study will provide an overview of different immunosuppressive agents used in solid organ transplantation. An increasing number of immunosuppressive agents are available and these agents target different steps of the immunological response to an allograft. These immunosuppressive agents are steroids, anti- proliferative agents (azathioprine and mycophenolate), calcineurin inhibitors (cyclosporine and tacrolimus), TOR inhibitors (sirolimus and everolimus), polyclonal and monoclonal antibody preparations.Öğe Effect of Leptin and Apelin Preconditioning on Hepatic Ischemia Reperfusion Injury in Rats(Springer India, 2014) Sagiroglu, Tamer; Aksoy, Mustafa Burak; Sagiroglu, Gonul; Tozkir, Hilmi; Oguz, Serhat; Yalta, Tulin; Yagci, Mehmet A.Leptin and apelin are important adipocytokines involved in a variety of endocrine and paracrine functions. The aim of this study was to evaluate the effect of exogenous leptin and apelin preconditioning on hepatic ischemia reperfusion (I/R) injury in rats. Forty mice were assigned to four groups (n = 10): sham-operated control (sham), I/R injury, I/R + leptin (I/R + L), and I/R + apelin (I/R + A). Leptin 100 mu g/kg/day and apelin 2 mu g/kg/day were delivered intraperitoneally starting 3 days prior to surgical procedure in I/R + L and I/R + A groups, respectively. All I/R groups underwent 45 min of warm ischemia, followed by 30 min of reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver malondialdehyde (MDA) and glutathione (GSH), and liver histopathology were compared between groups. MDA was elevated in I/R, but stayed similar in I/R + L and I/R + A compared to sham. I/R + A had significantly lower MDA compared to I/R. GSH levels did not differ significantly between the groups. ALT and AST were elevated in all I/R groups, but significant reduction was observed in I/R + L and I/R + A compared to I/R. Liver histopathology was mostly mild in I/R + L and I/R + A, in contrast to severe injury observed in the I/R group. Leptin and apelin preconditioning significantly reduced hepatic I/R injury in rats.Öğe Genetic screening results of individuals with high risk BRCA-related breast/ovarian cancer in Trakya region of Turkey(Imprimatur Publications, 2020) Demir, Selma; Tozkir, Hilmi; Gurkan, Hakan; Atli, E. Ikbal; Yalcintepe, Sinem; Atli, Engin; Sezer, Y. AtakanPurpose: Pathogenic/likely pathogenic (P/LP) germline variations in BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. This study presents the BRCA1/BRCA2 sequencing and deletion duplication analyses results of of 493 participants (485 women, 8 men) selected based on the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Next generation sequencing (NGS) and multiplex ligation-dependent probe amplification methods (MLPA) were used to define germline BRCA1/BRCA2 positivity. Results: Overall, the P/LP frequency of the participants was 17.8%. Five of the likely pathogenic variants were novel. The 5266dupC pathogenic variation, which is a founder mutation in the Ashkenazi Jewish population, was the most common variation among the patients, with a frequency of 5.47%. The pathogenic/likely pathogenic variation frequency was significantly higher (p=0.01) among clinically diagnosed familial cancer patisents than those participants without personal history of cancer but enrolled for BRCA1 testing due to familial risk. BRCA1/BRCA mutation positivity was significantly higher (p=0.000) among those who had at least one first- or second-degree relative with breast/ovarian cancer from patients who had no family history. BRCA1/BRCA2 mutation positivity was 69.23% between the patients who had personal history of both breast and ovarian cancer. Conclusion: Based on our findings, we suggest that sequencing all of the coding regions of the BRCA1/BRCA2 genes using NGS is a feasible approach for individuals who are at risk of developing BRCA-related cancer according to NCCN guidelines. The 5266dupC pathogenic variation, as the most common pathogenic variation in the Trakya region of Turkey, should be included if a targeted mutatin screening is planned.Öğe Identification of a novel homozygous TBC1D24 mutation in a Turkish family with DOORS syndrome(Lippincott Williams & Wilkins, 2018) Atli, Engin; Gurkan, Hakan; Ulusal, Selma; Karal, Yasemin; Atli, Emine I.; Tozkir, Hilmi[Abstract Not Available]Öğe Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2016) Erdogan, Bulent; Kodaz, Hilmi; Karabulut, Senem; Cinkaya, Ahmet; Tozkir, Hilmi; Tanriverdi, Ozgur; Cabuk, DevrimLung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01). The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.Öğe Increased frequency of class I and II anti-human leukocyte antigen antibodies in systemic lupus erythematosus and scleroderma and associated factors: a comparative study(Wiley, 2016) Tozkir, Hilmi; Pamuk, Omer Nuri; Duymaz, Julide; Gurkan, Hakan; Yazar, Metin; Sari, Gulce; Tanrikulu, HazelAim: There is significant autoantibody production in systemic lupus erythematosus (SLE) and scleroderma (SSc); microchimerism is also thought to play a role in pathogenesis. We determined the frequency of anti-HLA antibodies in SLE and SSc patients and evaluated associated clinical factors. Methods: We included 77 SLE patients, 46 SSc patients and 53 healthy controls into the study. Clinical data about the patients were obtained from hospital records. Anti-human leukocyte (anti-HLA) antigen antibody analysis of sera was performed by applying Lifecodes anti-HLA Class I and Class II Screening kits based on xMAP technology. Results: The frequencies of class I and II anti-HLA antibodies were significantly higher in SLE (27.3% and 41.6%) and SSc (26.1% and 41.3%) groups than in healthy controls (1.9% and 5.7%) (all P < 0.001). Frequencies of thrombocytopenia (P = 0.021), anti-ribonucleoprotein (P = 0.037) and anti-Ro (P = 0.027) were significantly higher in the class I antibody-positive SLE group; however, pericarditis was less frequent (P = 0.05). On the other hand, the class II antibody-positive SLE group had more frequent anti-ribosomal P antibody (P = 0.038), but less frequent active disease (P = 0.038). In the SSc group, class I antibody-positive patients had more frequent digital ulcers (P = 0.048) and anti-centromere antibodies (P = 0.01). There was no association of anti-HLA antibodies with pulmonary hypertension and interstitial fibrosis in SSc patients. Conclusions: Both class I and class II antibodies were found to be significantly increased in SLE and SSc. Rather than major organ involvement, anti-HLA antibodies were associated with the presence of other antibodies in both diseases.Öğe Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2018) Gorker, Isik; Gurkan, Hakan; Ulusal, Selma; Atli, Engin; Ayaz, Guclu; Ceylan, Cansin; Tozkir, HilmiAim: The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduptication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization. Methods: Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood. Results According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). Conclusion: The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD.Öğe Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population(Aves, 2016) Can, Guray; Tezel, Ahmet; Gurkan, Hakan; Tozkir, Hilmi; Unsal, Gulbin; Soylu, Ali Riza; Umit, Hasan CelalettinBackground/Aims: Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population. Materials and Methods: Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohn's disease patients, 157 ulcerative colitis patients, and 89 healthy controls. Results: The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohn's disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohn's disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohn's disease. The presence of rs10758669 (AC) was protective against perianal Crohn's disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohn's disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohn's disease and rs11209026 in ulcerative colitis were associated with disease-related operation. Conclusion: This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.Öğe The investigation of killer cell immunoglobulin-like receptor genotyping in patients with systemic lupus erytematosus and systemic sclerosis(Springer London Ltd, 2016) Tozkir, Julide Duymaz; Tozkir, Hilmi; Gurkan, Hakan; Donmez, Salim; Eker, Damla; Pamuk, Gulsum Emel; Pamuk, Omer NuriSystemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls (p values < 0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p = 0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined (p values < 0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients (p values < 0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE.Öğe Investigation the Relationship of Autism Spectrum Disorder and FOXP2, GRIN2B, KATNAL2, GABRA4 Genes(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2021) Yalcintepe, Sinem; Gorker, Isik; Demir, Selma; Atli, Emine Ikbal; Atli, Engin; Tozkir, Hilmi; Sut, NecdetIntroduction: Autism spectrum disorder is a genetically and phenotypically heterogeneous group. Genetic studies carried out to date have suggested that both common and rare genetic variants play a role in the etiology of this disorder. In our study, we aimed to investigate the effect of FOXP2, GRIN2B, KATNAL2 and GABRA4 gene variants in the pathogenesis of autism spectrum disorder. Method: In our prospectively planned study, all exons and exon-intron junctions of FOXP2, GRIN2B, KATNAL2 and GABRA4 genes were screened by next generation sequencing analysis in 96 patients who diagnosed with autism spectrum disorder. Results: In our study, the average age was 10.1 and the male/female ratio was 75/21. Pathogenic or likely pathogenic variants were not detected in FOXP2, GRIN2B, KATNAL2 and GABRA4 genes, however, 69 intronic variants of unknown clinical significance were detected in 50 cases (52%). Among those, 26 were in the GABRA4 gene, 22 in the FOXP2 gene, 13 in the KATNAL2 gene, and 8 in the GRIN2B gene. Twenty three of these 69 variants were novel that were not previously reported in the literature. Conclusion: In our study, we could not identify a relationship between the autism spectrum disorder and FOXP2, GRIN28, KATNAL2 and GABRA4 genes. Identifying genetic risk factors that play a role in the etiopathogenesis of autism spectrum disorder will contribute significantly to understanding the molecular mechanisms of the disease and the development of new treatment strategies. In this context, comprehensive molecular genetic studies such as whole exome or whole genome sequencing are required with higher number of cases in different populations.Öğe Mediterranean Fever Gene Mutations and Messenger Ribonucleic Acid Expressions in Pediatric Patients With Familial Mediterranean Fever in the Trakya Region of Turkey(Turkish League Against Rheumatism, 2014) Tozkir, Hilmi; Gusrkan, Hakan; Ozkayin, Nese; Sut, NecdetObjectives: This study aims to investigate the possible relationship between Mediterranean fever (MEFV) gene mutations and messenger ribonucleic acid (mRNA) expressions and to identify the link between phenotype and genotype of pediatric patients with Familial Mediterranean fever (FMF). Patients and methods: Seventy-one pediatric FMF patients who were identified with FMF symptoms and diagnosed with FMF according to Tel Hashomer criteria were included at Trakya University, Faculty of Medicine, Department of Paediatric Nephrology. The control group consisted of 73 healthy pediatric participants. Genomic deoxyribonucleic acid was isolated from whole blood samples and the following mutations of MFEV gene were analyzed: E148Q, P369S, H478Y, H479L, S675N, G678E, M680L, M680I (G>A and G>C), T681I, I692del, M694V, M694L, M694I, M695R, M695M, R717S, I720M, V722M, V726A, A744S and R761H. Total RNA isolation from leukocytes was performed and MEFV mRNA expression levels of the patients were compared by using real-time quantitative polymerase chain reaction method. beta 2 microglobulin was selected as the control gene. The comparison of mRNA expression levels among the patients was performed using the Delta CT method. Results: The most common clinical findings were abdominal pain, fever and vomiting. The mutation detection rate in the patient group was OR=4.1 (95% CI: 1.8-9.0) times higher than that of the control group. The MEFV mRNA expression level of the patients with MEFV gene mutations was lower compared to the control group, indicating statistical significance. Conclusion: Our study results support the findings of previous studies indicating that the MEFV mRNA expression levels of pediatric FMF patients with MEFV gene mutation are lower than the MEFV mRNA expression levels of healthy controls.Öğe Natural killer cell killer immunoglobulin-like gene receptor polymorphisms in non-Hodgkin lymphoma: possible association with clinical course(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Pamuk, Omer NuriNatural killer (NK) cell killer immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of many diseases. We determined the association between polymorphisms of KIR and their ligands and susceptibility to non-Hodgkin lymphoma (NHL), clinical features and prognosis. We included 90 patients with NHL and 94 controls. In the NHL group, KIR2DS1, HLA-Bw4 (Thr80) and HLA-Bw4 (Thr80)+/Bw4 (Iso80)- ligands were significantly more frequent. Patients with early-stage NHL had more frequent KIR2DL5 and KIR2DL5B than patients with advanced-stage NHL. During a median follow-up of 27 months, 26 patients with NHL died. Poor prognostic factors in univariate analysis were KIR2DL5A, KIR2DS1 and KIR3DS1 genotypes. In multivariate Cox regression analysis, advanced age and early relapse were poor prognostic factors. KIR genes and ligands had no significant effect on survival. The activating KIR2DS1 gene might activate NK cells, contributing to the production of more lymphoma cells. In addition, KIR2DS1, KIR2DL5A and KIR3DS1 might also be associated with a poor prognosis in NHL.Öğe Nonoccupational Exposure of Agricultural Area Residents to Pesticides: Pesticide Accumulation and Evaluation of Genotoxicity(Springer, 2018) Doganlar, Zeynep Banu; Doganlar, Oguzhan; Tozkir, Hilmi; Gokalp, Fulya Dilek; Dogan, Ayten; Yamac, Ferah; Askin, Orhan Onur; Aktas, Ummuhan ErsinAlthough many studies related the toxic effects of pesticides on agricultural workers, little research has been done about agricultural area residents. The purpose of this work was to monitor the presence of pesticides, as well as their genotoxic and cytotoxic potential, in humans with blood samples collected from control and intensive agricultural areas in the Thrace region. Pesticide accumulations were determined by LC-MS/MS. Cytotoxicity and genotoxicity were analyzed by comet assay, and the effect of pesticide accumulation on oxidative stress, DNA repair, and molecular chaperone response were analyzed by qRT-PCR assays in the human blood samples. The agricultural area residents had a significantly higher concentration of pesticides than those in the control area at all three sampling times, and the total pesticide amounts were 4.3 and 10 times significantly higher in blood sampled in the pesticide use period (August 2015 and 2016, respectively) than in the nonuse period (November 2015). The results showed that the pesticide level in blood during the use period led to oxidative stress, DNA damage (mean comet length and % tail DNA), and unfolded/misfolded protein response. Particularly, in pesticide use season, difference between these parameters was found statistically significant with comparison to control. Our results indicate that individuals residing around a monoculture rice farming area comprise an at-risk group as a result of increased genotoxicity evidenced in human blood. We suggest that biological monitoring efforts should be used to control nonoccupational exposures to pesticides and thus safeguard the health of agricultural area residents.Öğe A novel mutation in the ABCA12 gene in a Turkish case of Harlequin ichthyosis(Lippincott Williams & Wilkins, 2015) Gurkan, Hakan; Fischer, Judith; Ulusal, Selma; Vatansever, Ulfet; Hartmann, Britta; Tozkir, Hilmi; Schlipf, Nina[Abstract Not Available]
