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Öğe Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in PCOS(Elsevier Sci Ltd, 2010) Celik, Onder; Yesilada, Elif; Hascalik, Seyma; Celik, Nilufer; Sahin, Ibrahim; Keskin, Lezzan; Ozerol, ElifThe aim of this study was to establish the frequency of angiotensin-converting enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with polycystic ovary syndrome (PCOS) and to examine the association of this polymorphism with insulin resistance. A total of 32 women with PCOS and 31 healthy, age- and body mass index-matched controls were studied. Serum lipids, fasting glucose, insulin and other hormones concentrations were measured. Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR). DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D polymorphism was carried out by polymerase chain reaction. ACE genotypes were distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in four (12.9%) of healthy subjects. The frequency of D and I alleles were found in 69% and 31% of the PCOS group and 55% and 45% in the control group, respectively. There were no significant differences regarding the genotypic distribution and allelic frequency between the groups. However the ACE DD genotype was significantly associated with serum insulin concentrations and HOMA-IR measurement (both P = 0.005). ACE DD genotype is associated with an increased insulin resistance in women with PCOS. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.Öğe Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome(Hindawi Ltd, 2016) Seckin, Yuksel; Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Cagin, Yasir Furkan; Gozukara, Harika; Bilgic, YilmazBackground. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS.Öğe Calreticulin Mutations in Philadelphia Chromosome Negative Myeloproliferative Neoplasms(Akad Doktorlar Yayinevi, 2022) Gulbay, Gonca; Bar, Harika Gozukara; Yesilada, Elif; Erkurt, Mehmet AliCalreticulin (CALR) is a multifunctional protein. CALR gene mutations are one of the driver mutations in cases with essential thrombocythemia (ET) and primary myelofibrosis (PMF). The aim of this study is to comprehend the functional relationship of CALR type1 and type2 mutations in the pathogenesis of Phi-ladelphia Chromosome Negative Myeloproliferative Neop-lasms (MPNs) by emphasizing the incidence, biological and clinical features of CALR mutations in Janus Kinase2 (JAK2) V617F mutation negative and thrombopoietin receptor gene (MPL) mutation negative ET and PMF cases, and to determine their effect on the disease phenotype. The laboratory results of cases analyzed with essential throm-bocythemia and primary myelofibrosis were analyzed retros-pectively. In our study of the ET cases, 18.4% CALR exon9 mutation car-ried, 5.1% a thrombopoietin receptor gene (MPL) mutation, and 57.1% JAK2 V617F mutation. 19.4% of our cases do not carry any of these three mutations. Our ET patients with CALR muta-tion positive, 61.1% have type1, 27.8% have type2 and 11.1% have mutations other than type1 and type2. In our study of the PMF cases, 27.7% CALR exon9 mutation carried, 3.6% a MPL mutation, and 47% JAK2 V617F muta-tion. 21.7% cases are triple negative. Our PMF patients with CALR mutation positive, 69.6% have type1, 30.4% have type2 mutations. CALR mutations are a new and important molecular marker for Philadelphia chromosome negative myeloproliferative neoplasm cases. Longer follow-up and larger case populations are required to investigate the effects of clinical and laboratory pa-rameters of diseases.Öğe Chronic liver fibrosis induction in aging causes significant ultra-structural deterioration in liver and alteration on immune response gene expressions in liver-spleen axis(Taylor & Francis Inc, 2024) Karaca, Zeynal Mete; Karaca, Gamze; Kayhan, Basak; Gul, Mehmet; Ersan, Veysel; Bag, Harika Gozukara; Yesilada, ElifThe relationship between damage to the liver and spleen by aging and the immune response status in these two organs, which are anatomically and immunologically interconnected, is unknown. The authors investigated the histopathological, ultrastructural, and immunological effects of aging in young and aged fibrotic mice by using an experimental model. Four groups were planned, with 10 mice in each experimental group. The levels of fibrosis and ultrastructural destruction in the liver were determined by alpha-SMA staining and TEM analysis. Expression levels of immunity genes (Il2, Il4, Il6, Il10, Il12, Il17, Tnf, Ifng, Tgfb1, Gata3, Rorc, Tbx21, Foxp3, Ccl2, Ccr2, Cxcr3, Pf4, Cxcl10) were carried out by qRT-PCR. While structural disorders were detected in the mitochondria of aged healthy group, cellular destruction in the fibrosis-induced elderly group was at a dramatic level. Fibrosis induction in aged mice caused an elevation in the expression of chemokines (CCl2, CXCL10, CCR2) and cytokine (IL-17a) genes that induce autoinflammatory response in the liver. Unlike the cellular pathology and genes activated in fibrosis in youth and the natural occurrence of fibrosis with aging, induction of fibrosis during aging causes deterioration in the liver and expression of genes responsible for autoimmunity in both the liver and spleen.Öğe Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes(Int Press Editing Centre Inc, 2009) Emre, Sinan; Gul, Mehmet; Ates, Burhan; Esrefoglu, Mukaddes; Koc, Bekir; Erdogan, Ali; Yesilada, ElifThis study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrified. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGA-treated groups and the NaCl-treated group (P<0.05). Similarly, apoptotic cell counts in different retinal layers showed that PGA-treated groups had fewer apoptotic cells in all retinal layers than the NaCl-treated ischemic group (P<0.05). PGA may have high protective potential for different retinal layers and cells. Biochemical analysis of vitreous showed that all PGAs decreased vitreous XO activity significantly compared to the NaCl-treated group (P<0.05). However we could not find any statistically significant differences among the analogues. PGAs may reduce the injury induced by I/R, through the inhibition of XO activity, and it seems that their effects are elicited through numerous pathways.Öğe The Evaluation of Common Chromosomal Rearrangements and Their Frequencies in Adult Acute Myeloid Leukemia Cases in Malatya Province of Turkey(2020) Gülbay, Gonca; Yesilada, Elif; Erkurt, Mehmet Ali; Gözükara Bağ, HarikaAbstract: Recurrent balanced translocations are generally considered as the main parameter for prognosis in acute myeloid leukemia (AML). In recent years, genetic studies have focused on the ascertaintment of molecular aspects of various oncofusion proteins associated with AML, such as t(15;17) PML-RARA, t(8;21) RUNX1-RUNX1T1, t(9;22) BCR-ABL1 and inv (16) CBFB-MYH11. Therefore, we evaluated AML cases with RT-PCR for known specific genetic abnormalities that could lead to more accurate prognosis. In our study, we retrospectively reviewed the records of 211 cases (59.2% males and 40.8% females). RT-PCR technique was performed to identify t(15;17) PML-RARA, t(8;21) RUNX1-RUNX1T1, t(9;22) BCR-ABL1 and inv (16) CBFBMYH11. The most common rearrangement was found to be t (15; 17) (%12.8) followed by t (8; 21) (7.11%), t (9; 22) (7.6%) and inv (16) (1.42%). Also, in two other cases (0.95%) t(15;17) and t(8;21) were seen together. In addition, none of these rearrangement were found in 148 cases (70.14%) with AML. The presence of chromosomal rearrangements are very important in the diagnosis of AML. Therefore, rapid identification of specific rearrangements during diagnosis is important for prognostic purposes and can help identifying the cause of leukemogenesis and provide new strategies for the treatment of cases. This study is useful for both in Turkey oncologists and transplant centers in other regions will be a reference for the future analyzes and epidemiological data.Öğe Evaluation of the JAK2 V617F gene mutation in myeloproliferative neoplasms cases: a one-center study from Eastern Anatolia(Walter De Gruyter Gmbh, 2019) Gulbay, Gonca; Yesilada, Elif; Erkurt, Mehmet Ali; Bag, Harika Gozukara; Kuku, Irfan; Kaya, EminObjective: Detection of JAK2 V617F in myeloproliferative neoplasms (MPNs) is very important in both diagnosis and disease progression. In our study, we investigated the frequency of JAK2 V617F mutation in patients with myeloproliferative disorders. Methods: We retrospectively reviewed the records of 720 patients (174 females and 546 males) who were tested for JAK2 V617F mutation from January 2007 to December 2017. Results: In our patients were determined 22.6% JAK2 V617F mutation. 33.3% in women, 19.2% in men have been positive for JAK2 V617F mutation. In our study JAK2 V617F present in 48.6% of essential thrombocythemia, 80.5% of polycythemia rubra vera (PV), 47.5% of primary myelofibrosis, 10% of MPNs, unclassifiable, 0.8% of others. We also investigated the difference in hematological parameters [white blood cell, hemoglobin (Hb), hematocrit (HCT), red blood cell distribution widths (RDW) and platelets count (PLT)] between JAK2 V617F positive and JAK2 V617F negative patients. Conclusions: Investigation of the JAK2 V617F mutation is very important in cases of MPNs. In our study JAK2 V617F mutation was higher in PV, essential thrombocythemia, and primary myelofibrosis patients. However, there were significant differences in Hb, HCT, RDW and PLT levels in mutation-positive patients.Öğe GENOTOXICITY TESTING OF TRIBUTYLTIN AND METHIDATHION IN DROSOPHILA MELANOGASTER USING THE WING SOMATIC MUTATION AND RECOMBINATION TEST(Parlar Scientific Publications (P S P), 2014) Karabulut, Aygul Kilic; Yesilada, ElifIn this study, genotoxic effects of tributyltin (TBT) and methidathion (MD) were investigated using Drosophila wing somatic mutation and recombination test (SMART). This test is based on the principle that the loss of heterozygosity of suitable recessive marker hairs such as multiple wing (mwh) and flare-3 (flr(3)), can lead to the formation of mutant clones of larval cells, which are then expressed as spots on the wings of the adult flies. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr(3) were treated at different doses (0,1 mg/L, 1 mg/L, 10 mg/L, 30 mg/L, and 50 mg/L of TBT and 0.01 mg/L, 0.025 mg/L, 0.05 mg/L, 0.06 mg/L, and 0.075 mg/L of MD) of the test compounds. Mitomycin C (MMC), a commonly known mutagen, was used as positive control. The results indicated that highest experimental dose of TBT showed toxic and genotoxic effects, including recombinogenic activity in the marker-heterozygous flies. However, based on our results, MD showed no genotoxicity in the SMART assay, an in vivo model.Öğe LRRK2 G2019S, I2020T, R1441C GENE mutation analysis in patients with idiopathic Parkinson’s in Turkey(2020) Adıguzel, Ahmet; Altınayar, Sibel; Gülbay, Gonca; Yesilada, ElifAbstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The number of genetic studies on the etiopathogenesis of the disease has increased in the recent years. Leucine-rich repeat kinase 2 (LRRK2) gene mutation is the most common in autosomal dominant and sporadic PD. In this study, we aim to investigate the LRRK2 mutation frequency in patients diagnosed with idiopathic PD in and around Malatya province in eastern Turkey and to determine certain parameters in positive cases such as phenotype characteristics and treatment efficacy. A total of 170 patients (106 male and 64 female) were included. The most common loci of the LRRK2 gene (G2019S, I2020T and R1441C) were examined. To identify mutations, genotyping studies were performed by targeting related gene regions in isolated DNA using real-time polymerase chain reaction. No mutation was detected in any patient. Therefore, the probability of G2019S, I2020T and R1441C point mutations in the LRRK2 gene was very low in PD patients in Malatya region, which is a region of Turkey closer to the Middle East. Future studies investigating mutations involved in other loci of the LRRK2 gene with larger sample size in a wider geography in Turkey will provide more information about the genotype–phenotype relationship, incidence and carrier characteristics.Öğe Preliminary Results on Antigenotoxic Effects of Dried Mycelia of Two Medicinal Mushrooms in Drosophila melanogaster Somatic Mutation and Recombination Test(Begell House Inc, 2013) Kylyc, Aygul; Yesilada, ElifIn this study, the antigenotoxic effects of dried mycelia from Trametes versicolor and Pleurotus ostreatus were investigated using a Drosophila melanogaster somatic mutation and recombination test (SMART), which is based on the principle that the loss of heterozygosity of suitable recessive marker hairs, such as multiple wing (mwh) and flare-3 (flr(3)), can lead to the formation of mutant clones of larval cells, which then are expressed as spots on the wings of the adult flies. In this study, dried mycelia from T versicolor and P. ostreatus alone (7.5, 15, and 30 mg) were examined for genotoxicity and combined with mitomycin C (MMC; 0.05 mM) for antigenotoxicity. Commonly known mutagen which is mitomycin C (MMC) was used as positive control. The results showed that the dried mycelia of mushrooms were not genotoxic themselves. Nevertheless, the mushrooms have antigenotoxic activity by reducing the frequency of MMC-induced spots in varying proportions. Thus, powders of these 2 fungi were able to suppress somatic cell mutation induced by MMC. These results suggest that T versicolor and P ostreatus have antigenotoxic activity, including antirecombinogenic activity.Öğe Prevalence of Familial Mediterranean Fever in Children with Cryptogenic Cirrhosis(Oxford Univ Press, 2021) Varol, Fatma Ilknur; Tabel, Yilmaz; Yologlu, Saim; Yesilada, ElifBackground: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by abdominal and chest pain and recurrent fever due to inflammation in the serosal membranes such as peritoneum, pleura and synovia. In FMF, recurrent inflammatory cytokine production may lead to cirrhosis. The aim of this study was to determine the prevalence of FMF in children with cryptogenic cirrhosis and it was found to be high, to add FMF among the etiological causes of cirrhosis. Materials and methods: This prospective cohort study conducted at the Hospital of Inonu University, Malatya, Turkey. In this study, 44 patients diagnosed with cryptogenic cirrhosis by biopsy, in the Pediatric Gastroenterology, Hepatology and Nutrition Clinic, were included, after the other reasons that may cause chronic liver disease were excluded. MEVF gene analysis was performed for all patients with cryptogenic cirrhosis. Results: FMF genetic mutation was detected in 9 (20%) of 44 patients. M694V mutation was detected in one patient (2.27%) and E148Q homozygous mutation was detected in one patient (2.27%). Various other heterozygous mutations were detected in seven other patients. Homozygous and heterozygous R202Q mutations were detected in one patient. Conclusion: We suggest that FMF plays a role in the etiologic differential diagnosis of cryptogenic cirrhosis.Öğe Prevalence of known mutations and a novel missense mutation (M694K) in the MEFV gene in a population from the Eastern Anatolia Region of Turkey(Elsevier Science Bv, 2012) Yesilada, Elif; Taskapan, Hulya; Gulbay, GoncaFamilial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis. Mutations in the Mediterranean fever gene (MEFV) localized on the short arm of chromosome 16 cause FMF. Over 90 MEFV missense/nonsense mutations have been identified so far in FMF patients, mostly in the 10th exon of the gene. In this study, the molecular test results of 891 patients identified as having FMF clinical symptoms referred to Molecular Genetics Laboratory of the Department of Medical Biology and Genetics, Faculty of Medicine, Inonu University, Malatya/Turkey were retrospectively evaluated. Patients were referred by their physicians for MEFV mutation detection. The DNA fragments including hot spots within the coding sequences of the MEFV gene were amplified by PCR using genomic DNA and analyzed by pyrosequencing technique. Of the 891 patients investigated, 420 (47.13%) had at least one mutation. The most frequent mutation was E148Q, followed by M694V, M680I (G/C), P369S, V726A, R761H, A744S, M694I, K695R and F479L mutations. In addition, a novel missense mutation (M694K) was reported in seven members of a family in the course of mutation screening of patients. (C) 2012 Elsevier B.V. All rights reserved.Öğe Prevalence of Pericentric Inversion of Chromosome 9 in Eastern Anatolia Region and Relationship to Reproductive Efficiency(Kare Publ, 2018) Yuksel, Sengul; Savaci, Serap; Ekici, Cemal; Kurtoglu, Elcin Latife; Korkmaz, Selcen; Yesilada, ElifObjectives: One of the most common, structurally balanced chromosome rearrangements is the pericentric inversion of chromosome (inv[9]). It is considered to be a variant of the normal karyotype, and has been found in both normal populations and patients with various abnormal phenotypes. The aim of this study was to determine the frequency of chromosome 9 rearrangement in the Malatya Province and check whether it is correlated with certain diseases. Methods: In this study, we investigated the karyotype analysis of 4168 patients admitted in the Turgut Ozal Medical Center and Research Hospital, Genetic Disease Diagnosis Center Laboratory, between 2014 and 2016 and retrospectively reviewed their clinical data. Chromosomes from cultured peripheral blood lymphocytes were analyzed using Giemsa Trypsin-Giemsa (GTG) banding. Results: Pericentric inversion was detected in 71 (1.7 %) of 4168 cases, including 32 (45.1%) cases with inv(9) causing infertilty, 21 (29.6%) causing growth retardation, four (5.6%) causing multiple spontaneous abortion, and 14 (19.7%) causing other abnormalities, all of which were referred to our laboratory. Conclusion: In this study, the distribution of inv (9) in the Malatya Province was shown, and it is believed that these results would contribute to the knowledge regarding the incidence of inv (9) in the Eastern Anatolia Region and Turkey.Öğe PROTECTIVE EFFECT OF MYRICETIN AGAINST E2-INDUCED GENOTOXIC DAMAGE IN HUMAN LYMPHOCYTES(Parlar Scientific Publications (P S P), 2012) Yuksel, Sengul; Yesilada, Elif; Gulbay, Gonca; Kurtoglu, Elcin; Savaci, S. SerapProtective effect of myricetin (MRY) against the cytotoxic and genotoxic effects of a hormonal steroid, 17 beta-estradiol (E-2), was assessed in peripheral blood human lymphocyte culture. Sister chromatid exchanges (SCE), mitotic index (MI) and replication index (RI) were scored as genetic endpoints. Firstly, the genotoxic effect of different amounts (5, 10 and 20 mu M final concentration) of E2 was tested, and 10 and 20 mu M E-2 levels were detected as genotoxic. In the second set, E-2 groups were treated with 10 mu M MRY. MRY reduced the SCE but increased MI as well as RI, suggesting its protective action on human lymphocytes in vitro against E-2-induced genotoxic damage.
