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Öğe 9 Years Follow-up of a Patient with Pituitary Form of Resistance to Thyroid Hormones (PRTH): Comparison of Two Treatment Periods of D-Thyroxine and Triiodothyroacetic Acid (TRIAC)(Walter De Gruyter Gmbh, 2009) Güran, Tülay; Turan, Serap; Bircan, Rifat; Bereket, AbdullahPatients with pituitary resistance to thyroid hormones (PRTH) exhibit features of hyperthyroidism due to normal sensitivity to thyroid hormones in some of the peripheral tissues. There is a lack of information in the literature on the long-term follow-up and treatment of patients with PRTH. Here, we present long-term (9 years) clinical and biochemical follow-up of a patient with PRTH under the treatment of D-T4 initially (for 1.5 years) followed by TRIAC for 5.5 years. An 11.5 year-old girl was evaluated for goiter, palpitations, heat intolerance, sleep disorders, nervousness and frequent stools for 3 years. Her thyroid function tests were consistent with PRTH. Molecular analysis revealed a heterozygous missense mutation of the TR beta gene at codon 243 in exon 7 (R243Q) and a silent mutation at codon 245 in the index patient and the mother who was later also diagnosed to have PRTH. The patient was started on D-T4 treatment since she exhibited clinical symptoms of hyperthyroidism. After 1.5 years, D-T4 treatment was switched to TRIAC which lasted 5.5 years. During the long course of both treatments, thyroid hormones, TSH, heart rate, thyroid size, and markers of peripheral thyroid status (SHBG and alkaline phosphatase) were monitored. It was concluded that compared to D-T4, TRIAC treatment is more effective in suppressing TSH and lowering thyroid hormone levels in PRTH. However, both treatments were unable to reduce thyroid size. The effects of treatment on symptomatology were also modest. Spontaneous improvement in symptoms was observed with age.Öğe A new approach to DNA isolation from dileptid ciliates (Ciliophora: Litostomatea: Rhynchostomatia)(Bulgarska Akademiya na Naukite, 2020) Ural, Hilal; Bircan, Rifat; Aral, Cenk; Yıldız, İsmail; Şenler, Naciye GülkızMolecular diagnostic methods have been used to supplement morphological methods in taxonomy. In this study, we used molecular methods to diagnose populations of dileptid ciliates, which commonly occur in terrestrial and semi-terrestrial habitats. Molecular investigations based on the comparison of DNA sequences have been carried out with a limited number of ciliate species due to insufficient genomic DNA for PCR because of their small population size and difficulties to maintain monocultures. The present study shows that there is a loss of DNA with conventional methods and proposes a novel approach: cells (stored at –20°C or fresh) are directly subjected to PCR, without being processed by any chemical treatment. The small subunit ribosomal DNA (SSU rDNA) (18S rRNA gene) of dileptid ciliates was successfully amplified by direct PCR, without DNA extraction, for single-cell and multi-cell samples. This method has been found to be simpler and especially useful for species that are rare and have small population sizes. © 2020 Bulgarian Academy of Sciences. All rights reserved.Öğe A New Approach to DNA Isolation from Dileptid Ciliates (Ciliophora: Litostomatea: Rhynchostomatia)(Inst Zoology, Bas, 2020) Ural, Hilal; Bircan, Rifat; Aral, Cenk; Yıldız, İsmail; Şenler, Naciye GülkızMolecular diagnostic methods have been used to supplement morphological methods in taxonomy. In this study, we used molecular methods to diagnose populations of dileptid ciliates, which commonly occur in terrestrial and semi-terrestrial habitats. Molecular investigations based on the comparison of DNA sequences have been carried out with a limited number of ciliate species due to insufficient genomic DNA for PCR because of their small population size and difficulties to maintain monocultures. The present study shows that there is a loss of DNA with conventional methods and proposes a novel approach: cells (stored at -20 degrees C or fresh) are directly subjected to PCR, without being processed by any chemical treatment. The small subunit ribosomal DNA (SSU rDNA) (18S rRNA gene) of dileptid ciliates was successfully amplified by direct PCR, without DNA extraction, for single-cell and multi-cell samples. This method has been found to be simpler and especially useful for species that are rare and have small population sizes.Öğe Alopecia: Association with Resistance to Thyroid Hormones(Freund Publishing House Ltd, 2009) Güran, Tülay; Bircan, Rifat; Turan, Serap; Bereket, AbdullahResistance to thyroid hormone (RTH) syndrome is caused by thyroid hormone beta receptor (TR beta) mutations. Goiter, learning disabilities, psychological abnormalities, sinus tachycardia, hearing deficits, short stature, and growth delay are among the most common symptoms in patients with RTH. Alopecia areata (AA) is an autoimmune disease of the hair follicle, frequently associated with other autoimmune disorders. In some cases local alopecia of different genetic backgrounds could be misdiagnosed as AA. We describe here clinical, biochemical and genetic features of a family having RTH syndrome, caused by a novel TR beta mutation, coexistent with alopecia. Mutational analyses of the TR beta gene and the hairless gene (HR) in genomic DNA were performed. The index patient is a 9-(4)/(12) year-old boy with RTH due to a novel heterozygous missense mutation of the TR beta gene (I353V), and diffuse, patchy alopecia without autoimmune thyroid disease. This mutation was also detected in his father and elder brother, who also have local alopecia. One of his paternal aunts and paternal grandmother have local alopecia and they have previously been operated for goiter. Although they refused any genetic analysis, the pre-operative medical report of the paternal aunt was compatible with RTH. A second paternal aunt has alopecia totalis universalis but has no RTH mutation in genomic DNA. Genomic DNA sequence of the HR gene of the family (index patient, two brothers, father, mother and second paternal aunt) was normal as well. Conclusion: We speculate that RTH due to a novel I353V TR beta 1 mutation could be causally related to different phenotypic expressions of alopecia in this family, either by a direct effect of unresponsiveness to T3 of the hair follicle or by the modulated action of the HR gene.Öğe Angiotensin Converting Enzyme Gene Polymorphism in Turkish Asthmatic Patients(Taylor & Francis Inc, 2009) Eryuksel, Emel; Ceyhan, Berrin Bagci; Bircan, Rifat; Avşar, Melike; Çirakoğlu, BeyazıtAsthma is a chronic inflammatory disease of the airways. Several candidate genes have been identified with a potential role in the pathogenesis of asthma, including the angiotensin converting enzyme (ACE) gene. We aimed to investigate the frequency of an ACE gene polymorphism in Turkish asthmatic patients and to determine its impact on clinical parameters and disease severity. Ninety-seven asthmatic patients (M/F 25/72, mean age 39 13 years) and 96 healthy subjects (M/F 26/70, mean age 38 12 years) were included. At baseline, all participants completed a questionnaire on demographics, symptoms, triggering factors, severity of asthma, and the presence of atopism. Blood samples were obtained from all patients and genomic DNA was isolated. The frequency of the ACE genotypes (I = insertion and D = deletion) among asthmatics and controls were compared: asthmatics showed a 40.2% prevalence of the DD genotype (n = 39), ID was 45.4% (n = 44), and II was 14.4% (n = 14.4). In the control subjects, the frequency of DD was18.8% (n = 18), ID was 50% (n = 48) and II was 31.3% (n = 30). The DD ACEgenotype was significantly more frequent in asthmatics compared with controls (p 0.001). Asthmatics with the ID ACE genotype showed a higher frequency of drug allergies, although this was not statistically significant (p = 0.08). Asthmatics with the DD genotype appeared to have a higher incidence of asthmatic episode exacerbations due to viral infections, but again this was not statistically significant (p = 0.08). Patients with mild or moderate-severe asthma had similar frequencies of these mutations. We found a higher frequency of the ACE DD gene mutation in Turkish asthmatic patients compared with non-asthmatics, suggesting that this ACE gene polymorphism may be a risk factor for asthma but does not increase the severity of the disease.Öğe BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure(Via Medica, 2019) Özçelik, Serhat; Bircan, Rifat; Sarıkaya, Şükran; Gül, Aylin E.; Aydın, Büşra; Özçelik, Melike; Ilıksu Gözü, HülyaIntroduction: BRAF(V600E) activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAF(V600E )mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure. Material and methods: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAF(V600E) mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised that BRAF(V600E) mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012). Results: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed between BRAF(V600E) mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p= 0.002), vascular invasion (p= 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related with BRAF(V600E) mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%). Conclusion: We revealed that BRAF(V600E) mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAF(V600E).Öğe Çapraz bağlayıcı ve büyüme faktörü emdirilen hidrojel sistemlerinden kontrollü ilaç salımı: Sistematik inceleme(2012) Gökçe, Alper; Yılmaz, İbrahim; Tonbul, Murat; Gökay, Nevzat Selim; Bircan, Rifat; Gökçe, ÇiğdemAmaç: Bu çalışmada, dünya genelinde son 31 yılda yapılan çalışmalar içerisinde, kontrollü ilaç taşıma sistemi olan ve çapraz bağlayıcı ilavesi ile biodegradasyona uğratılmış büyüme faktörü emdirilen hidrojelin, kıkırdak dejenerasyonunun tedavisindeki yeri sistematik olarak incelenerek konu hakkında daha büyük bir fotoğrafı görebilmek amaçlandı. Gereç ve Yöntem: Bu çalışmada, elektronik veritabanlarında dil kısıtlaması olmadan, The Cochrane Collaboration The Cochrane, The Cochrane Library (Issue 2 of 12, Feb. 2011), Ovid MEDLINE (1950 to 5th March Week 1 2011), ProQuest, US National Library of Medicine National Institutes of Health (NLM) ve PubMed, Elektronik ortamda veritabanlarında literatür taraması yapılarak, Mayıs 1970 ile 5 Mart 2011 tarihleri arasında kıkırdak , kontrollü salım , çapraz bağlayıcı , büyüme faktörü ve hidrojel üzerine yapılmış ve basılı olan deneysel çalışmalar VE , VEYA şeklinde tarandı. Elde edilen makaleler arasından, inceleme kriterlerini karşılayan dört adet makale çalışmaya dahil edildi. P değeri <0.05 heterojenite açısından istatistiksel olarak anlamlı kabul edildi. Sonuç: İlk tarama sonrasında ortaya konan 957.829 adet makaleden 88 adet makale tam olarak incelendi. Kontrollü ilaç taşıma sistemi olan hidrojelin çapraz bağlayıcı ile biyodegradasyon süresi uzatıldığında ve içerisine büyüme faktörleri emdirildiğinde, kıkırdak dejenerasyonuna etkilerinin yeri üzerine literatür içerisinden dört tanesi kriterlerimizi karşıladı. İstatistiksel değerlendirme amacıyla yapılan heterojenite testi sonucu, null hipotezi reddedildi (p=.75). Bulgular: Çapraz bağlayıcı ilavesi ile biyodegradasyon süresi uzatılan ve içerisine büyüme faktörü emdirilmiş kontrollü ilaç taşıma sistemi olan hidrojelin, kıkırdak hasarı tedavisindeki yeri hakkında yeterli bir kanıt bulunamamıştır. Klinik kullanımına ilişkin yorum yapabilmek amacıyla in-vivo, daha uzun dönem fonksiyonel sonuçlar veren, randomize kontrollü çalışmalara gereksinim duyulmaktadır.Öğe Cases of Borderline in Vitro Constitutive Thyrotropin Receptor Activity: How to Decide Whether a Thyrotropin Receptor Mutation Is Constitutively Active or Not?(Mary Ann Liebert, Inc, 2009) Mueller, Sandra; Gözü, Hülya İliksu; Bircan, Rifat; Jaeschke, Holger; Eszlinger, Markus; Lueblinghoff, Julia; Paschke, RalfBackground: Previous in vitro data for several constitutively activating thyrotropin receptor (TSHR) mutations reported divergent results for the constitutive activity of the same mutations. Moreover, several case reports have highlighted the difficulties in determining whether a TSHR mutation is constitutively active or not. Retrospectively, this has repeatedly been the case for mutants with only a slight increase of basal cAMP activity. We re-examined 10 previously described TSHR germline mutations with minor increases of basal cAMP activity and analyzed the influences of the cell line and vector system on the basal receptor activity. Methods: TSHR mutations were characterized by determination of cell surface expression, cAMP accumulation, and linear regression analysis of constitutive activity. Results: Re-examination of the previously described constitutively active TSHR germline mutations did not show constitutive activity for R310C and N670S as tested in COS-7 cells and confirmed constitutive activity for the other eight mutations. However, mutant N670S showed a slight but significant increase of basal activity measured by linear regression analysis when analyzed in HEKGT cells transiently transfected with pcDNA but not with the pSVL vector. This was not the case for R310C. Conclusions: Our findings indicate that current methods to precisely classify mutants with only a slight increase of the basal activity as constitutively active are limited. The results concerning the level of the basal activity can be influenced by the vector and/or the cell system. A comprehensive clinical characterization of the respective patients appears as a necessary and promising adjunct for the activity classification of these borderline mutations.Öğe Crimean-Congo hemorrhagic fever virus in tortoises and Hyalomma aegyptium ticks in East Thrace, Turkey: Potential of a cryptic transmission cycle(BioMed Central Ltd., 2020) Kar, Sırrı; Rodriguez, S.E.; Akyıldız, Gürkan; Cajimat, M.N.B.; Bircan, Rifat; Mears, M.C.; Keleş, A.G.Background: Recent reports have demonstrated the presence of Crimean-Congo hemorrhagic fever virus (CCHFV) genomic material in Hyalomma aegyptium ticks feeding primarily on tortoises belonging to the genus Testudo. This raises the question if these ticks and their hosts play a role in the natural transmission dynamics of CCHFV. However, the studies are limited, and assessing the relevance of H. aegyptium in perpetuating the virus in nature, and a potential spillover to humans remains unknown. This study aimed to detect CCHFV in H. aegyptium ticks and their tortoise hosts in the East Thrace region of Turkey, where H. aegyptium is the most common human-biting tick and where a high density of tortoises of the genus Testudo can be found. Methods: During the study period, 21 blood samples from different tortoises (2 T. hermanni and 19 T. graeca), 106 tick pools (containing 448 males, 152 females, 93 nymphs and 60 larvae) collected from 65 tortoises (5 T. hermanni and 60 T. graeca), 38 adult unfed questing ticks (25 males and 13 females, screened individually) and 14 pools (containing 8 nymphs and 266 larvae) of immature unfed questing ticks collected from the ground were screened for CCHFV genome by nested PCR and partial genomes sequenced. Results: As a result of the screening of these 179 samples, 17 (9.5%) were detected as positive as follows: 2 of 21 blood samples (9.52%), 13 (containing 18 nymphs in 3 pools, and 52 males and 8 females in 10 pools) of 106 tick pools from tortoises (12.26%), and 2 of 38 adult questing ticks (5.26%). No positive result was determined in 14 pools of immature questing ticks. Conclusions: Previous studies have shown that reptiles can participate in the transmission of arthropod-borne viruses, but they may contribute to different aspects of the disease ecology and evolution of tick-borne viral pathogens. Our results indicate the presence of CCHFV in questing and feeding H. aegyptium ticks as well as tortoise hosts. This may indicate that CCHFV circulates in a cryptic transmission cycle in addition to the primary transmission cycle that could play a role in the natural dynamic of the virus and the transmission to humans.[Figure not available: see fulltext.] © 2020 The Author(s).Öğe Does the mitochondrial genome much more stabile in the aggressive papillary thyroid cancers ('PTCs)? - the preliminary findings(Wiley, 2018) Aral, Cenk; Gözü, Hülya İliksu; Sarıkaya, S.; Gül, A. Ege; Özçelik, S.; Bircan, Rifat[No Abstract Available]Öğe Effects of confluency, roscovitine and serum starvation on the cell-cycle synchronization and viability of sheep and goat adult fibroblasts(Elsevier Science Bv, 2014) Eren, Aysel; Arat, Sezen; Tuna, Metin; Bircan, Rifat[No Abstract Available]Öğe Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism(Elsevier Ireland Ltd, 2010) Gözü, Hülya İliksu; Lueblinghoff, Julia; Bircan, Rifat; Paschke, RalfTSH receptor (TSHR) germline mutations occur as activating mutations in familial non-autoimmune hyperthyroidism (FNAH) or sporadic non-autoimmune hyperthyroidism (SNAH). Up to date 17 constitutively activating TSHR mutations have been reported in 24 families with FNAH. The diagnosis of FNAH should be considered in cases with a positive family history, early onset of hyperthyroidism, goiter, absence of clinical stigmata of autoimmunity and recurrent hyperthyroidism. Moreover, 14 subjects with sporadic non-autoimmune hyperthyroidism and 10 different TSH receptor germline mutations have been reported. The main characteristic of SNAH is a negative family history. Additional consequences of prolonged neonatal hyperthyroidism (mental retardation, speech disturbances and craniosynostosis) have often been reported in SNAH. No genotype-phenotype relationship has been reported in patients with germline TSHR mutations. There is no association of in vitro activities determined by linear regression analysis (LRA) and several clinical indicators of hyperthyroidism activity for SNAH. However, the comparison of the LRA values of sporadic TSHR mutations with LRA values of familial TSHR mutations does show a significantly higher median LRA value for sporadic as compared to familial autosomal dominant hyperthyroidism. This finding is in line with the clinical impression of a more active clinical course in patients with SNAH. However, additional genetic, constitutional or environmental factors are most likely responsible for the phenotypic variations of the disease and the lack of correlation between in vitro activities of the TSHR mutations and the severity of hyperthyroidism. (C) 2010 Elsevier Ireland Ltd. All rights reserved.Öğe How Different Methodologies of Harvesting and Analysing the Samples Affect the Test Results in Determining Joint Mediators(Hindawi Ltd, 2013) Yılmaz, İbrahim; Gökay, Nevzat Selim; Bircan, Rifat; Saraçoğlu Varol, Gamze; Dervişoğlu, Sergülen; Gökçe, AlperPurpose. This study has researched the affect of different methodologies of harvesting and analysing the samples in determining the mediators emerging after the rat articular cartilage injury. Materials and Methods. One hundred and forty-four male wistar rats were divided into 2 groups. Synovial fluid samples were taken from all of the rats. We entered into the right knees of the rats in group I (n = 36) under anaesthesia and took cartilage tissue samples from their distal femur. Samples were taken as reference values for enzyme linked immunosorbent assay (ELISA) and histopathological evaluations. We entered into the right knees of the rats in group II (n = 108) and formed complete layer of cartilage injury in their medial femoral condyles. At the end of the 15th day, the rats were sacrificed after taking synovial fluid samples from their right knees creating defect in the rats in group II. The molecular markers in the synovial fluid and cartilage tissue samples which were taken from the experimental and control groups (MMP-9, MMP-13, TIMP-1, TNF-alpha', and NO) were analysed by direct or indirect methodologies. SPSS 18.0 Package program was used in the statistical evaluation. Students t-test where the measurement variables between the experimental and control groups were compared was applied. Receiver Operating Characteristics (ROC) curves were used in the determination of the diagnostic sufficiency from the tissue. Results. No difference was found between TIMP-1 (P = 0.67) and MMP-9 (P = 0.28) levels in synovial fluid and cartilage tissue. From the molecular markers, when MMP-9, MMP-13, NO, TIMP-1, TNF-alpha', the area under ROC curve, and P values were examined, MMP-13 (P < 0.0001, 95% CI: 0.70-0.85), NO (P < 0.0001, 95% CI: 0.72-0.86), and TNF-alpha. (P < 0.0001, 95% CI: 0.91-0.98) results were found to be statistically significant. Inferences. The indirect ELISA protocol which we apply for the cartilage tissue as an alternative to synovial lavage fluid is a reliable method which can be used in the determination of articular cartilage injury markers.Öğe Identification and Assemblage Types of Giardia duodenalis from Patients in Thrace, Turkey(Doc Design Informatics Co Ltd, 2019) Kucuk, Sadiye Kaplan; Akyildiz, Gurkan; Bircan, Rifat; Yilmazer, Nadim; Gargili, Aysen; Kar, SirriObjective: Giardiasis is a common disease, and clinical forms can vary based on the assemblage types of the parasite. Detailed information on the subgenotypes may indicate the transmission routes and enlighten the gaps in the epidemiology of the disease. This study aims to reveal the occurrence of giardiasis in Thrace, Turkey, and assemblage types of Giardia duodenalis. Materials and Methods: In total, 573 stool samples taken from the individuals applied to Tekirdag Central State Hospital in 2009, were examined by wet-mount and zinc sulfate floatation methods. Giardia-positive 26 samples and 64 samples taken from the individuals with gastrointestinal complaints were analyzed by nested PCR-RFLP to differentiate the assemblage types. Sequence analysis was employed for confirmation of assemblage types and subgenotypes. Results: Giardia spp. cysts were detected in 3.66% and 4.54% of the samples with wet-mount and zinc sulphate floatation techniques respectively. A total of 27 samples were found positive by nested PCR-RFLP out of 90 samples. Fifteen samples were determined as assemblage A, 2 and 10 samples as B and B/E mix respectively. Sequence analysis showed that the latter assemblage (B/E mix) as A3-B3 mix. Conclusion: Fast identification techniques, namely zinc sulphate flotation can be used for screening stool samples in order to determine Giardia cysts with considerably high sensitivity and specificity. Based on this method, the occurrence rate of giardiasis was found as 4.54% in the studied group. DNA sequencing is necessary to distinguish assemblages and confirm the results of PCR-RFLP.Öğe Is the TSHR D727E polymorphism a genetic predisposition for multinodular goiter in the Turkish population?(Funpec-Editora, 2016) Gözü, Hülya İliksu; Özçelik, S.; Aloglu, M.; Şahin, A.; Temiz, S.; Dayan, A.; Bircan, RifatThe D727E germline polymorphism in the thyroid-stimulating hormone receptor gene (TSHR) may cause genetic susceptibility to the development of goiter. Therefore, in this study we investigated allele frequencies and genotype distributions of the TSHR D727E polymorphism, their association with clinical parameters, and the development of goiter in the Turkish population. We investigated the TSHR D727E polymorphism in 123 patients and 97 healthy subjects using the polymerase chain reaction-restriction fragment length polymorphism technique. Peripheral blood was used for DNA extraction. Although no significant difference was found in TSHR D727E polymorphism frequencies between the patients with nodular goiters (26/123 patients, 21.1%) and the controls (12/97 patients, 12.4%) (P = 0.107), the frequency of the TSHR D727E polymorphism in the hyperthyroid+ subclinical hyperthyroid patient groups (23%) was significantly higher than in the control subjects (12.4%) (P = 0.024). In this study, nodular goiter presented significantly earlier in GC genotype patients (mean age 35 years) than in CC genotype patients (mean age 42 years) in the hyperthyroid group (P = 0.009). More importantly, TSH levels in the GC variant controls were closely significant lower (1.26 +/- 0.49) than in the CC variant controls (1.74 +/- 0.84) (P = 0.053). The TSHR D727E polymorphism might be involved in the pathogenesis of toxic multinodular goiter (TMNG). Moreover, this polymorphism might be an indication of early-onset TMNG. However, development of MNG is multifactorial. Therefore, further case-control studies with larger populations are required to verify these observations.Öğe Melatonin reverses the oxidative stress and mitochondrial dysfunction caused by LETM1 silencing(Wiley, 2020) Aral, Cenk; Demirkesen, Seyma; Bircan, Rifat; Yasar Şirin, DuyguLETM1 is a mitochondrial inner-membrane protein, which is encoded by a gene present in a locus of 4p, which, in turn, is deleted in the Wolf-Hirschhorn Syndrome, and is assumed to be related to its pathogenesis. The cellular damage caused by the deletion is presumably related to oxidative stress. Melatonin has many beneficial roles in protecting mitochondria by scavenging reactive oxygen species, maintaining membrane potential, and improving functions. The aim of this study was to investigate the effects of melatonin administration to LETM1-silenced mouse embryonic fibroblast cells as a cellular model for LETM1 deficiency. We transfected mouse embryonic fibroblast cells with a pair of siRNA against LETM1 and monitored the oxidative stress and mitochondrial functions with or without melatonin addition. MnSOD expression and aconitase activity decreased and oxidized protein levels increased in LETM1-silenced cells. LETM1 suppression did not alter the expression of OXPHOS complexes, but the oxygen consumption rates decreased significantly; however, this change was not related to complex I but instead involved complex IV and complex II. Melatonin supplementation effectively normalized the parameters studied, including the oxygen consumption rate. Our findings identified a novel effect of LETM1 deficiency on cellular respiration via complex II as well as a potential beneficial role of melatonin treatment. On the other hand, these effects may be specific to the cell line used and need to be verified in other cell lines.Öğe MTHFR, prothrombin and Factor V gene variants in Turkish patients with coronary artery stenosis(Soc Brasil Genetica, 2008) Caner, Müge; Bircan, Rifat; Sevinc, Deniz; Benli, Fehime; Guney, A. Ilter; Kurtoglu, NuriMany epidemiological studies have reported an association between hemostatic factors and risk of both coronary and peripheral artery diseases. Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated the association between coronary artery disease and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), prothrombin (G20210A), and factor V (A4070G) genes. We screened these gene variants in 174 subjects who had undergone coronary angiography - 115 patients with patent coronary artery disease (grade 3 vessel disease, i.e., significant coronary stenosis), and 59 healthy controls with grade 0 vessel disease. The analysis of our data did not show any statistically significant association between coronary artery disease (CAD) and the investigated polymorphisms.Öğe Phylogenetic and phylogeographic analysis of Myrmeleotettix maculatus (Orthoptera: Acrididae: Gomphocerinae) species group in Anatolia(Magnolia Press, 2021) Şirin, Deniz; Taylan, Mehmet Sait; Bircan, Rifat; Akyıldız, Gürkan; Can, LeventSix Anatolian and one European populations of the Myrmeleotettix maculatus species group, which contains M. maculatus and M. ethicus species, have been studied by using molecular genetics methods with mitochondrial COI gene. Myrmeleotettix ethicus is an Anatolian endemic species with local distribution whereas M. maculatus is distributed in western Palearctic. The phylogenetic analysis (ML and BI analyses) of the M. maculatus species group in Anatolia reveals that it consistently recovered two well-supported main clades and four different lineages. Molecular time estimates suggest that the diversification of the M. maculatus species group took place between the Late Tortonian (around 8-9 My) and the Middle of Pliocene-Pleistocene (around 4.3 My-present) periods and the current distribution of the genetic diversity has been affected by the uplifting of the Central Anatolian plateau, the termination of the Messinian salinity crisis, and the Quaternary climatic changes. Copyright © 2021 Magnolia Press.Öğe Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas(Amer Soc Clinical Investigation Inc, 2016) Calebiro, Davide; Grassi, Elisa S.; Eszlinger, Markus; Ronchi, Cristina L.; Godbole, Amod; Bathon, Kerstin; Paschke, Ralf; Bircan, RifatAutonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism. Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein alpha subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other genes and the pathogenesis of the remaining cases are presently unknown. Here, we performed whole-exome sequencing in 19 ATAs that were paired with normal DNA samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit of the polycomb complex. Targeted screening in an independent cohort confirmed that this mutation occurs with high frequency (27%) in ATAs. EZH1 mutations were strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9 [ADCY9]) alterations in cAMP pathway genes. Furthermore, functional studies revealed that the p.Gln571Arg EZH1 mutation caused increased histone H3 trimethylation and increased proliferation of thyroid cells. In summary, this study revealed that a hot-spot mutation in EZH1 is the second most frequent genetic alteration in ATAs. The association between EZH1 and TSHR mutations suggests a 2-hit model for the pathogenesis of these tumors, whereby constitutive activation of the cAMP pathway and EZH1 mutations cooperate to induce the hyperproliferation of thyroid cells.Öğe Screening of the BRAF V600E mutation prevalance at papillary thyroid carcinomas (PTCs) in Turkish population(Nature Publishing Group, 2018) Bircan, Rifat; Özçelik, S.; Sarıkaya, S.; Aydın, B.; Dayan, A.; Karadayı, N.; Gözü, Hülya İliksu[No Abstract Available]
