Neurology Psychiatry and Brain Research, Aug 1, 2013
Abstract Introduction Schizophrenia is a complex neuropsychiatric disorder with deficits of multi... more Abstract Introduction Schizophrenia is a complex neuropsychiatric disorder with deficits of multiple domains of cognitive functions, volition and emotions. Family and twin studies have provided cumulative evidence for the genetic basis of schizophrenia. The aetiolgy of this disease involves the interplay of multifactiorial inheritance operating on brain maturational processes and polygenic inheritance with some genes showing susceptibility at many genomic locations such as 22q and 11q. The catechol-O-methyltransferase (COMT-22q11) is an extensively studied candidate gene for schizophrenia. COMT acts as an enzymatic detoxicating barrier between the blood and other tissues regulating the amounts of active dopamine and norepinephrine in various parts of the brain and therefore to be associated with schizophrenia. The presence of a common functional single nucleotide polymorphism (SNP) in exon 4 [Guanine (G) Adenine (A); Val108/158Met], alters the enzymatic activity with a trimodal distribution of high-HH, intermediate-HL and low-LL activity alleles which appear to have association with schizophrenia. Brain-derived neurotrophic factor (BDNF-11q13) is a member of the nerve growth factor family working as a molecular regulator of neuronal development and plasticity. Molecules that are critical in the development and survival of neurons such as BDNF play a significant role in the neuropathology of schizophrenia. While upregulation of BDNF increases the neuronal cell size and synaptic plasticity, a functional polymorphism at codon 66 [G→A; Val66Met] down regulates this process and induces schizophrenia. Objective In the present study, our aim was to investigate the differences in allele frequencies between schizophrenic patients [n = 97 (51 men, 46 women)] and control group [n = 376 (228 men, 148 women)] subjects. Results When the control and schizophrenia groups were compared for BDNFVal66Met polymorphism, we did not find a significant difference between the study groups either for genotype (χ2 = 3.370447, p > 0.05) or Val/Met haplotype analysis (χ2 = 2.840264, p > 0.05). When a comparison was revealed for COMT-Val108/158Met polymorphism, no significant difference was detected among schizophrenia and control groups for genotype (χ2 = 0.373330, p > 0.05) and Val/Met haplotype analysis (χ2 = 0.339073, p > 0.05). When the control and study groups were compared for BDNFVal66Met–COMTVal108/158Met polymorphisms compound genotype and haplotype analyses, there was no significant difference between the two groups (χ2 = 11.015; p > 0.05 and χ2 = 3.191; p > 0.05), respectively. Conclusion Our results indicate that there is no association between schizophrenia and BDNF–COMT polymorphisms and haplotypes analysis. We also did not find an association between schizophrenia and BDNF–COMT compound genotype and haplotype analyses. Although our study is unique in Turkey as combining BDNF and COMT compound genotype–haplotype analyses, for a generalization of Turkish schizophrenia patient's susceptibility to schizophrenia; we need further studies with an enlarged cohort.
Objective: The neurotrophine 'brain derived neurotrophic factor' (BDNF) which is expressed in the... more Objective: The neurotrophine 'brain derived neurotrophic factor' (BDNF) which is expressed in the brain is responsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to define the frequency of the functional Val66Met [G196A; (rs6265)] polymorphism of BDNF gene for Turkish male and female alcohol dependent cases and also to identify whether this polymorphism had any effect upon tendency to alcoholism. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase
Chemotherapy resistance is a major limiting factor for the extensive use of chemotherapeutic drug... more Chemotherapy resistance is a major limiting factor for the extensive use of chemotherapeutic drugs in cancer treatment. Despite the large number of newly discovered medications, treatment success rates are still unsatisfactory. Programmed cell death, called apoptosis, is one of the main tissue homeostasis mechanisms that balances cell survival and death. Apoptosis can be induced through extrinsic and intrinsic pathways or repressed by inhibitor proteins. During tumor progression, homeostasis between the anti-apoptotic and pro-apoptotic regulators is disturbed and shifted towards survival through various escape mechanisms. Dysregulation of apoptosis-regulatory mediators, particularly high levels of anti-apoptotic proteins, is one of the main mechanisms by which tumor cells acquire resistance to chemo-and radiotherapy. Therefore, it is important to restore apoptosis in the chemo-and radiotherapy-resistant tumor cells. In this chapter, we summarize general chemotherapy resistance mechanisms, discuss the role of extrinsic and intrinsic pathways in chemoresistance, and review the current experimental strategies to overcome chemotherapy resistance targeting the apoptotic pathways.
Amaç: Bu çalışmada, tedavi amaçlı uygulanan endotelin reseptör antagonist-A'nın (ERA-A) streptozo... more Amaç: Bu çalışmada, tedavi amaçlı uygulanan endotelin reseptör antagonist-A'nın (ERA-A) streptozotozin (STZ) ile indüklenmiş diyabetik sıçanların aortlarındaki hücresel bağlantı ve hücre adezyon moleküllerinin gen ekspresyonları üzerine etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Toplamda 80 sıçan 4 eşit gruba bölünerek incelenmiştir: Grup1: Kontrol, Grup2: ERA-A uygulanan, Grup3: Diyabet ve Grup4: Diyabet sonrası ERA-A uygulanan grup. Kırk sıçanda tek doz STZ enjeksiyonu ile diyabet indüklenmiştir ve hayvanlar 2 ay takip edilmiştir. Ayrıca, 20 diyabetik ve 20 sağlıklı sıçana 7. ve 15. günlerde ERA-A uygulanmıştır. Sıçan aort doku örneklerindeki hücreler arası bağlantı birimlerinin bileşenlerini ve hücre adezyon moleküllerini kodlayan genlerin ekspresyonları kantitatif gerçek-zamanlı ters transkripsiyon-polimer zincir reaksiyonu ile analiz edilmiştir. Bulgular: Konneksin-30 (Cx30), Cx33, Cx37, Cx40 ve Cx45 ekspresyonları diyabet grubunda azalmıştır. ERA-A uygulanan diyabetik sıçanlarda ise Cx33 ve Cx36 ekspresyonları istatistiksel olarak anlamlı artış göstermiştir. Diyabet grubu kontrol grubu ile karşılaştırıldığında α-1-katenin ekspresyonunun anlamlı olarak arttığı, ve β-1-katenin ekspresyonunun da anlamlı olarak azaldığı görülmüştür. Sonuç: Çalışmamızda, endotel hücrelerin hücreler arası iletişimini sağlayan oluklu bağlantılarında diyabet ile indüklenen hasar saptanmıştır. ERA-A uygulaması bazı konneksin alt tiplerinin ekspresyonlarını arttırdığı için, bu durumun sağaltımı için gelecekteki rutin kullanımı düşünülebilir.
Objective: In the present study, we have aimed to determine the frequency of common inherited thr... more Objective: In the present study, we have aimed to determine the frequency of common inherited thrombophilias among women with preeclampsia, intrauterine growth retardation, placental abruption, recurrent pregnancy loss, and stillbirth. Materials and Methods: Sixty women with complicated pregnancies and as a control group 53 normal pregnant women were included in the study. Women with complicated pregnancies consist of preeclampsia (n=21), intrauterine growth restriction (n=12), intrauterine fetal death (n=12), placental abruption (n=5) and recurrent pregnancy loss (n=10). Genotype analysis for factor V Leiden mutation, prothrombin mutation (PT 20210G/A), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were performed by real-time online polymerase chain reaction. Results: The frequency of Factor V Leiden mutation was found statistically higher in the complicated pregnancy group, compared to normal group (23.3% vs 7.5%) (p=0.04). On the other hand, no difference was detected on the heterozygous MTHFR frequencies between the two groups. However, 9% of the women with complicated pregnancies had homozygous mutation and no woman was homozygous for MTHFR in the control group. PT gene mutation was found in only one patient from the control group. Discussion: Factor V Leiden mutation and homozygousity for the MTHFR polymorphism, rather than its heterozygousity, might be involved in the pathogenesis of adverse pregnancy outcome associated with placental vasculopathy.
A 68-year-old woman presented with acute chest pain and a greatly increased platelet count. Cardi... more A 68-year-old woman presented with acute chest pain and a greatly increased platelet count. Cardiac catheterization revealed subtotal occlusion and a thrombus-like filling defect in the right coronary artery. The patient was successfully treated with intravenous tirofiban. Essential thrombocythemia was diagnosed based on bone marrow findings, clinical presentation and laboratory analysis. The relationship between intracoronary thrombus and essential thrombocythemia is discussed.
Düzenli aralıklarla bölünmüş kısa palindromik tekrar kümeleri [clustered regularly interspaced pa... more Düzenli aralıklarla bölünmüş kısa palindromik tekrar kümeleri [clustered regularly interspaced palindromic repeats (CRISPR)] ve CRISPR-ilişkili (CRISPR-associated) Cas endonükleazlar prokaryotik canlıların virüs ve diğer mobil genetik elementlere karşı bağışıklık kazanmalarını sağlayan savunma mekanizması bileşenleridir. 1 Adaptasyon, ekspresyon ve interferans aşamalarından oluşan bu süreçte istilacı geno
Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G2... more Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs). Materials and Methods: The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers. Results: The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15%) of the patients, and there wasn't an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation. Conclusion: We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation.
Introduction: Fat graft survival has been studied numerously but has not gone beyond hypothetical... more Introduction: Fat graft survival has been studied numerously but has not gone beyond hypothetical solutions. The molecular changes in survival of standard fat grafts and enhanced survival by platelet-rich plasma (PRP) are compared in this study to reveal the etiology that causes the loss of fat grafts after transplantation. Materials and methods: A New Zealand rabbit's inguinal fat pads were excised and divided into three groups: Sham, Control (C), and PRP. Each weighing 1 g, C and PRP fat were placed into the bilateral parascapular area of the rabbit. After 30 days, the remaining fat grafts were harvested and weighed (C = 0.7 g, PRP = 0.9 g). All three specimens were put into transcriptome analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analysis were done to compare the genetic pathways between the specimens. Results: Transcriptome analysis showed similar differential expressions in Sham vs. PRP and Sham vs. C comparisons, indicating the dominance of the cellular immune response in both C and PRP specimens. C and PRP comparison resulted in inhibited migration and inflammation pathways in PRP. Conclusion: Fat graft survival is more related to immune responses than any other physiological process. PRP enhances survival by attenuating cellular immune reactions.
Amaç: Kistik fibroz genellikle çocukluk yaşlarında ortaya çıkan ve tüm ekzokrin bezlerin fonksiyo... more Amaç: Kistik fibroz genellikle çocukluk yaşlarında ortaya çıkan ve tüm ekzokrin bezlerin fonksiyon bozukluğu ile seyreden kalıtsal bir hastalıktır. Avrupa' da yaygın olarak görülen bu hastalık kişilerin yaşam kalitesini etkilemekte ve tekrarlayan ağır solunum yolu enfeksiyonlarının açtıkları komplikasyonlar nedeniyle, erken yaşta ölüme yol açmaktadır. Kistik fibroz' daki en yaygın mutasyon ?F508' dir. Bununla birlikte, binden fazla kistik fibroz gen (CFTR) mutasyonu tanımlanmıştır; ?I507 ve F508C gibi. F508C ve ?F508 mutasyonları ayrıca konjenital vas deferens agenezin gelişiminde de rol oynarlar. Çalışmadaki amacımız, aynı CFTR gen bölgesine düşen bu üç mutasyonu gerçek-zamanlı multipleks PCR yöntemi ile hızlı analizlerini gerçekleştirmekti. Gereç ve Yöntem: Ege Bölgesinde yaşayan kistik fibrozlu veya konjenital unilateral vas deferens agenezisi bulunan toplam 116 olgunun DNA örnekleri, tek bir çalışmada üç CFTR mutasyonun ayırıcı tanılarına gidilecek şekilde tasarlanmı...
Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF... more Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF4 geninin 11q23 kromozomal bandına yerleşim gösteren MLL genine füzyonu sonucu gelişen kromozomal bir anomalidir. Bu çalışmada, retrospektif olarak 2009-2013 yılları arasındaki akut lenfoblastik lösemi (ALL) hastalarındaki t(4;11) MLL- AF4 translokasyonunun analiz sonuçlarının incelenmesi amaçlandı. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut lösemi ön tanısıyla 176 çocuk (70 kız, 106 erkek) ve 144 yetişkin (60 kadın, 84 erkek) olgunun kan veya kemik iliği örnekleri incelendi. Bu olgulara ait 71 kan ve 473 kemik iliği örneğinin t(4;11) translokasyon RNA sonuçları, gerçek zamanlı RT-PCR yöntemi ile kantitatif olarak değerlendirildi. İlk aşamada, kan ve kemik iliği örneklerinden izole edilen total RNA veya mRNA’dan konvansiyonel bir PCR cihazı ile komplementer DNA sentezlendi. İkinci aşamada, gerçek zamanlı PCR cihazı ile t(4;11) kantitasyonu gerçekleştirildi. Olguların kantitatif olarak değerlendirilmesi, pozitif kontrol ve negatif kontrolün karşılaştırılması ile örneklerin negatif yada pozitif (pozitif olgu kopya sayısının referans kopya sayısına oranı) olması şeklinde yapıldı. Bulgular: Çalışmamızda 98’i takip hastası olmak üzere toplam 320 hasta t(4;11) MLL-AF4 translokasyonu için değerlendirildi. Çalışmaların sonucunda toplam 34 olgu (24 çocuk, 10 yetişkin) pozitif ve diğer örnekler negatif olarak bulundu. Sonuç: Bu değerlendirmenin sonuçları, RT-PCR yöntemi ile ALL hastalarında yeni tanı döneminde ve tedavi sürecinde t(4;11) MLL-AF4 translokasyonunun kantitatif tayini, hem tanının kesinleştirilmesinde hem de moleküler remisyon sağlanmasına yönelik tedaviyi yönlendirmesinde değerli bir yöntem olduğunu desteklemektedir.Aim: t(4,11) is a chromosomal abnormality formed by the translocation MLL-AF4, which is the result of the fusion of the AF4 gene, localized on 4q21 chromosomal band, to the MLL gene, localized on 11q23 chromosomal band. The aim of this study is to examine the results of the analysis of t (4;11) MLL-AF4 translocation in acute lymphoblastic leukemia (ALL) patients retrospectively. Materials and Methods: Peripheral blood or bone marrow samples of 176 children (70 girls, 106 boys) and 144 adults (60 women, 84 men) with a preliminary diagnosis of acute leukemia between 2009-2013 were analyzed in the Medical Biology Department of Ege University Faculty of Medicine. The translocation RNA results of 71 peripheral blood and 473 bone marrow samples of these patients were evaluated quantitatively for t(4;11) with real-time RT- PCR. t(4;11) quantitation was performed by real-time qRT-PCR instrument after the synthesis of complementary DNA with conventional PCR from total RNA or mRNA isolated from blood and bone marrow. Quantitative analysis of the patients was performed by comparing positive and negative controls and samples classified as positive or negative (the ratio of the number of positive copies to the number of reference copies). Results: A total of 320 patients, with 98 having also follow-ups, were evaluated for t(4;11) translocation. Totally 34 patients (24 children and 10 adults) were found positive and the other samples were negative. Conclusion: The assessment of these results supports that, quantitative determination of t(4;11) with RT-PCR method among newly diagnosed ALL patients and ALL patients undergoing treatment, is a valuable method for both confirming the diagnosis and guiding the treatment intended to achieve molecular remission
Objective: The neurotrophine ‘brain derived neurotrophic factor’ (BDNF) which is expressed in the... more Objective: The neurotrophine ‘brain derived neurotrophic factor’ (BDNF) which is expressed in the brain is responsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to define the frequency of the functional Val66Met [G196A; (rs6265)] polymorphism of BDNF gene for Turkish male and female alcohol dependent cases and also to identify whether this polymorphism had any effect upon tendency to alcoholism. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase
Introduction Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the pres... more Introduction Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the presence of a reciprocal chromosomal translocation of the Abelson (ABL1) oncogene on the 9th chromosome and a breakpoint cluster region (BCR) on the 22nd chromosome, resulting in t(9,22). This results in chimeric fusion, producing oncoprotein BCR-ABL with tyrosine kinase activity (Groffen et al., 1984). The subsequent uncontrolled tyrosine kinase activity results in excess activation of multiple signaling pathways such as RAS/RAF/MAPK, PI3K/Akt, JUN, MYC, and Janus kinase/signal transducers and activators of transcription (JAK/STAT), leading to persistent cell proliferation, reduced apoptosis, and malignant expansion of pluripotent stem cells in bone marrow (Steelman et al., 2004). Since CML is due to a well-recognized translocation, it is possible to inhibit the aberrant BCR-ABL tyrosine kinase (TK) activity using molecularly targeted therapies. Imatinib was the first BCR-ABL TK inhibitor (TKI) introduced for the treatment of CML (Kantarjian et al, 2002). Although imatinib and other second-generation (including dasatinib and nilotinib) and third-generation TKIs are generally well tolerated, ensuing resistance remains a major clinical challenge (Apperley, 2007). Cytokines and growth factors can activate the JAK/ STAT signaling pathway, which has been well investigated in CML. Thus, the cascade transmits information from extracellular chemical signals to the nucleus, resulting in DNA transcription and expression of genes involved in immunity, proliferation, cellular migration, angiogenesis, differentiation, apoptosis, and oncogenesis (Rawlings et al., 2004). Therefore, overexpression of STATs, especially STAT5, is associated with leukemogenesis and carcinogenesis (Bowman et al., 2000; Rawlings et al., 2004). BCR/ABL chimeric protein constitutively activates the JAK/STAT cascade and causes antiapoptotic activity and uncontrolled proliferation of the malignant clone
Neurology Psychiatry and Brain Research, Aug 1, 2013
Abstract Introduction Schizophrenia is a complex neuropsychiatric disorder with deficits of multi... more Abstract Introduction Schizophrenia is a complex neuropsychiatric disorder with deficits of multiple domains of cognitive functions, volition and emotions. Family and twin studies have provided cumulative evidence for the genetic basis of schizophrenia. The aetiolgy of this disease involves the interplay of multifactiorial inheritance operating on brain maturational processes and polygenic inheritance with some genes showing susceptibility at many genomic locations such as 22q and 11q. The catechol-O-methyltransferase (COMT-22q11) is an extensively studied candidate gene for schizophrenia. COMT acts as an enzymatic detoxicating barrier between the blood and other tissues regulating the amounts of active dopamine and norepinephrine in various parts of the brain and therefore to be associated with schizophrenia. The presence of a common functional single nucleotide polymorphism (SNP) in exon 4 [Guanine (G) Adenine (A); Val108/158Met], alters the enzymatic activity with a trimodal distribution of high-HH, intermediate-HL and low-LL activity alleles which appear to have association with schizophrenia. Brain-derived neurotrophic factor (BDNF-11q13) is a member of the nerve growth factor family working as a molecular regulator of neuronal development and plasticity. Molecules that are critical in the development and survival of neurons such as BDNF play a significant role in the neuropathology of schizophrenia. While upregulation of BDNF increases the neuronal cell size and synaptic plasticity, a functional polymorphism at codon 66 [G→A; Val66Met] down regulates this process and induces schizophrenia. Objective In the present study, our aim was to investigate the differences in allele frequencies between schizophrenic patients [n = 97 (51 men, 46 women)] and control group [n = 376 (228 men, 148 women)] subjects. Results When the control and schizophrenia groups were compared for BDNFVal66Met polymorphism, we did not find a significant difference between the study groups either for genotype (χ2 = 3.370447, p > 0.05) or Val/Met haplotype analysis (χ2 = 2.840264, p > 0.05). When a comparison was revealed for COMT-Val108/158Met polymorphism, no significant difference was detected among schizophrenia and control groups for genotype (χ2 = 0.373330, p > 0.05) and Val/Met haplotype analysis (χ2 = 0.339073, p > 0.05). When the control and study groups were compared for BDNFVal66Met–COMTVal108/158Met polymorphisms compound genotype and haplotype analyses, there was no significant difference between the two groups (χ2 = 11.015; p > 0.05 and χ2 = 3.191; p > 0.05), respectively. Conclusion Our results indicate that there is no association between schizophrenia and BDNF–COMT polymorphisms and haplotypes analysis. We also did not find an association between schizophrenia and BDNF–COMT compound genotype and haplotype analyses. Although our study is unique in Turkey as combining BDNF and COMT compound genotype–haplotype analyses, for a generalization of Turkish schizophrenia patient's susceptibility to schizophrenia; we need further studies with an enlarged cohort.
Objective: The neurotrophine 'brain derived neurotrophic factor' (BDNF) which is expressed in the... more Objective: The neurotrophine 'brain derived neurotrophic factor' (BDNF) which is expressed in the brain is responsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to define the frequency of the functional Val66Met [G196A; (rs6265)] polymorphism of BDNF gene for Turkish male and female alcohol dependent cases and also to identify whether this polymorphism had any effect upon tendency to alcoholism. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase
Chemotherapy resistance is a major limiting factor for the extensive use of chemotherapeutic drug... more Chemotherapy resistance is a major limiting factor for the extensive use of chemotherapeutic drugs in cancer treatment. Despite the large number of newly discovered medications, treatment success rates are still unsatisfactory. Programmed cell death, called apoptosis, is one of the main tissue homeostasis mechanisms that balances cell survival and death. Apoptosis can be induced through extrinsic and intrinsic pathways or repressed by inhibitor proteins. During tumor progression, homeostasis between the anti-apoptotic and pro-apoptotic regulators is disturbed and shifted towards survival through various escape mechanisms. Dysregulation of apoptosis-regulatory mediators, particularly high levels of anti-apoptotic proteins, is one of the main mechanisms by which tumor cells acquire resistance to chemo-and radiotherapy. Therefore, it is important to restore apoptosis in the chemo-and radiotherapy-resistant tumor cells. In this chapter, we summarize general chemotherapy resistance mechanisms, discuss the role of extrinsic and intrinsic pathways in chemoresistance, and review the current experimental strategies to overcome chemotherapy resistance targeting the apoptotic pathways.
Amaç: Bu çalışmada, tedavi amaçlı uygulanan endotelin reseptör antagonist-A'nın (ERA-A) streptozo... more Amaç: Bu çalışmada, tedavi amaçlı uygulanan endotelin reseptör antagonist-A'nın (ERA-A) streptozotozin (STZ) ile indüklenmiş diyabetik sıçanların aortlarındaki hücresel bağlantı ve hücre adezyon moleküllerinin gen ekspresyonları üzerine etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Toplamda 80 sıçan 4 eşit gruba bölünerek incelenmiştir: Grup1: Kontrol, Grup2: ERA-A uygulanan, Grup3: Diyabet ve Grup4: Diyabet sonrası ERA-A uygulanan grup. Kırk sıçanda tek doz STZ enjeksiyonu ile diyabet indüklenmiştir ve hayvanlar 2 ay takip edilmiştir. Ayrıca, 20 diyabetik ve 20 sağlıklı sıçana 7. ve 15. günlerde ERA-A uygulanmıştır. Sıçan aort doku örneklerindeki hücreler arası bağlantı birimlerinin bileşenlerini ve hücre adezyon moleküllerini kodlayan genlerin ekspresyonları kantitatif gerçek-zamanlı ters transkripsiyon-polimer zincir reaksiyonu ile analiz edilmiştir. Bulgular: Konneksin-30 (Cx30), Cx33, Cx37, Cx40 ve Cx45 ekspresyonları diyabet grubunda azalmıştır. ERA-A uygulanan diyabetik sıçanlarda ise Cx33 ve Cx36 ekspresyonları istatistiksel olarak anlamlı artış göstermiştir. Diyabet grubu kontrol grubu ile karşılaştırıldığında α-1-katenin ekspresyonunun anlamlı olarak arttığı, ve β-1-katenin ekspresyonunun da anlamlı olarak azaldığı görülmüştür. Sonuç: Çalışmamızda, endotel hücrelerin hücreler arası iletişimini sağlayan oluklu bağlantılarında diyabet ile indüklenen hasar saptanmıştır. ERA-A uygulaması bazı konneksin alt tiplerinin ekspresyonlarını arttırdığı için, bu durumun sağaltımı için gelecekteki rutin kullanımı düşünülebilir.
Objective: In the present study, we have aimed to determine the frequency of common inherited thr... more Objective: In the present study, we have aimed to determine the frequency of common inherited thrombophilias among women with preeclampsia, intrauterine growth retardation, placental abruption, recurrent pregnancy loss, and stillbirth. Materials and Methods: Sixty women with complicated pregnancies and as a control group 53 normal pregnant women were included in the study. Women with complicated pregnancies consist of preeclampsia (n=21), intrauterine growth restriction (n=12), intrauterine fetal death (n=12), placental abruption (n=5) and recurrent pregnancy loss (n=10). Genotype analysis for factor V Leiden mutation, prothrombin mutation (PT 20210G/A), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were performed by real-time online polymerase chain reaction. Results: The frequency of Factor V Leiden mutation was found statistically higher in the complicated pregnancy group, compared to normal group (23.3% vs 7.5%) (p=0.04). On the other hand, no difference was detected on the heterozygous MTHFR frequencies between the two groups. However, 9% of the women with complicated pregnancies had homozygous mutation and no woman was homozygous for MTHFR in the control group. PT gene mutation was found in only one patient from the control group. Discussion: Factor V Leiden mutation and homozygousity for the MTHFR polymorphism, rather than its heterozygousity, might be involved in the pathogenesis of adverse pregnancy outcome associated with placental vasculopathy.
A 68-year-old woman presented with acute chest pain and a greatly increased platelet count. Cardi... more A 68-year-old woman presented with acute chest pain and a greatly increased platelet count. Cardiac catheterization revealed subtotal occlusion and a thrombus-like filling defect in the right coronary artery. The patient was successfully treated with intravenous tirofiban. Essential thrombocythemia was diagnosed based on bone marrow findings, clinical presentation and laboratory analysis. The relationship between intracoronary thrombus and essential thrombocythemia is discussed.
Düzenli aralıklarla bölünmüş kısa palindromik tekrar kümeleri [clustered regularly interspaced pa... more Düzenli aralıklarla bölünmüş kısa palindromik tekrar kümeleri [clustered regularly interspaced palindromic repeats (CRISPR)] ve CRISPR-ilişkili (CRISPR-associated) Cas endonükleazlar prokaryotik canlıların virüs ve diğer mobil genetik elementlere karşı bağışıklık kazanmalarını sağlayan savunma mekanizması bileşenleridir. 1 Adaptasyon, ekspresyon ve interferans aşamalarından oluşan bu süreçte istilacı geno
Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G2... more Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs). Materials and Methods: The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers. Results: The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15%) of the patients, and there wasn't an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation. Conclusion: We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation.
Introduction: Fat graft survival has been studied numerously but has not gone beyond hypothetical... more Introduction: Fat graft survival has been studied numerously but has not gone beyond hypothetical solutions. The molecular changes in survival of standard fat grafts and enhanced survival by platelet-rich plasma (PRP) are compared in this study to reveal the etiology that causes the loss of fat grafts after transplantation. Materials and methods: A New Zealand rabbit's inguinal fat pads were excised and divided into three groups: Sham, Control (C), and PRP. Each weighing 1 g, C and PRP fat were placed into the bilateral parascapular area of the rabbit. After 30 days, the remaining fat grafts were harvested and weighed (C = 0.7 g, PRP = 0.9 g). All three specimens were put into transcriptome analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analysis were done to compare the genetic pathways between the specimens. Results: Transcriptome analysis showed similar differential expressions in Sham vs. PRP and Sham vs. C comparisons, indicating the dominance of the cellular immune response in both C and PRP specimens. C and PRP comparison resulted in inhibited migration and inflammation pathways in PRP. Conclusion: Fat graft survival is more related to immune responses than any other physiological process. PRP enhances survival by attenuating cellular immune reactions.
Amaç: Kistik fibroz genellikle çocukluk yaşlarında ortaya çıkan ve tüm ekzokrin bezlerin fonksiyo... more Amaç: Kistik fibroz genellikle çocukluk yaşlarında ortaya çıkan ve tüm ekzokrin bezlerin fonksiyon bozukluğu ile seyreden kalıtsal bir hastalıktır. Avrupa' da yaygın olarak görülen bu hastalık kişilerin yaşam kalitesini etkilemekte ve tekrarlayan ağır solunum yolu enfeksiyonlarının açtıkları komplikasyonlar nedeniyle, erken yaşta ölüme yol açmaktadır. Kistik fibroz' daki en yaygın mutasyon ?F508' dir. Bununla birlikte, binden fazla kistik fibroz gen (CFTR) mutasyonu tanımlanmıştır; ?I507 ve F508C gibi. F508C ve ?F508 mutasyonları ayrıca konjenital vas deferens agenezin gelişiminde de rol oynarlar. Çalışmadaki amacımız, aynı CFTR gen bölgesine düşen bu üç mutasyonu gerçek-zamanlı multipleks PCR yöntemi ile hızlı analizlerini gerçekleştirmekti. Gereç ve Yöntem: Ege Bölgesinde yaşayan kistik fibrozlu veya konjenital unilateral vas deferens agenezisi bulunan toplam 116 olgunun DNA örnekleri, tek bir çalışmada üç CFTR mutasyonun ayırıcı tanılarına gidilecek şekilde tasarlanmı...
Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF... more Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF4 geninin 11q23 kromozomal bandına yerleşim gösteren MLL genine füzyonu sonucu gelişen kromozomal bir anomalidir. Bu çalışmada, retrospektif olarak 2009-2013 yılları arasındaki akut lenfoblastik lösemi (ALL) hastalarındaki t(4;11) MLL- AF4 translokasyonunun analiz sonuçlarının incelenmesi amaçlandı. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut lösemi ön tanısıyla 176 çocuk (70 kız, 106 erkek) ve 144 yetişkin (60 kadın, 84 erkek) olgunun kan veya kemik iliği örnekleri incelendi. Bu olgulara ait 71 kan ve 473 kemik iliği örneğinin t(4;11) translokasyon RNA sonuçları, gerçek zamanlı RT-PCR yöntemi ile kantitatif olarak değerlendirildi. İlk aşamada, kan ve kemik iliği örneklerinden izole edilen total RNA veya mRNA’dan konvansiyonel bir PCR cihazı ile komplementer DNA sentezlendi. İkinci aşamada, gerçek zamanlı PCR cihazı ile t(4;11) kantitasyonu gerçekleştirildi. Olguların kantitatif olarak değerlendirilmesi, pozitif kontrol ve negatif kontrolün karşılaştırılması ile örneklerin negatif yada pozitif (pozitif olgu kopya sayısının referans kopya sayısına oranı) olması şeklinde yapıldı. Bulgular: Çalışmamızda 98’i takip hastası olmak üzere toplam 320 hasta t(4;11) MLL-AF4 translokasyonu için değerlendirildi. Çalışmaların sonucunda toplam 34 olgu (24 çocuk, 10 yetişkin) pozitif ve diğer örnekler negatif olarak bulundu. Sonuç: Bu değerlendirmenin sonuçları, RT-PCR yöntemi ile ALL hastalarında yeni tanı döneminde ve tedavi sürecinde t(4;11) MLL-AF4 translokasyonunun kantitatif tayini, hem tanının kesinleştirilmesinde hem de moleküler remisyon sağlanmasına yönelik tedaviyi yönlendirmesinde değerli bir yöntem olduğunu desteklemektedir.Aim: t(4,11) is a chromosomal abnormality formed by the translocation MLL-AF4, which is the result of the fusion of the AF4 gene, localized on 4q21 chromosomal band, to the MLL gene, localized on 11q23 chromosomal band. The aim of this study is to examine the results of the analysis of t (4;11) MLL-AF4 translocation in acute lymphoblastic leukemia (ALL) patients retrospectively. Materials and Methods: Peripheral blood or bone marrow samples of 176 children (70 girls, 106 boys) and 144 adults (60 women, 84 men) with a preliminary diagnosis of acute leukemia between 2009-2013 were analyzed in the Medical Biology Department of Ege University Faculty of Medicine. The translocation RNA results of 71 peripheral blood and 473 bone marrow samples of these patients were evaluated quantitatively for t(4;11) with real-time RT- PCR. t(4;11) quantitation was performed by real-time qRT-PCR instrument after the synthesis of complementary DNA with conventional PCR from total RNA or mRNA isolated from blood and bone marrow. Quantitative analysis of the patients was performed by comparing positive and negative controls and samples classified as positive or negative (the ratio of the number of positive copies to the number of reference copies). Results: A total of 320 patients, with 98 having also follow-ups, were evaluated for t(4;11) translocation. Totally 34 patients (24 children and 10 adults) were found positive and the other samples were negative. Conclusion: The assessment of these results supports that, quantitative determination of t(4;11) with RT-PCR method among newly diagnosed ALL patients and ALL patients undergoing treatment, is a valuable method for both confirming the diagnosis and guiding the treatment intended to achieve molecular remission
Objective: The neurotrophine ‘brain derived neurotrophic factor’ (BDNF) which is expressed in the... more Objective: The neurotrophine ‘brain derived neurotrophic factor’ (BDNF) which is expressed in the brain is responsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to define the frequency of the functional Val66Met [G196A; (rs6265)] polymorphism of BDNF gene for Turkish male and female alcohol dependent cases and also to identify whether this polymorphism had any effect upon tendency to alcoholism. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase
Introduction Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the pres... more Introduction Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the presence of a reciprocal chromosomal translocation of the Abelson (ABL1) oncogene on the 9th chromosome and a breakpoint cluster region (BCR) on the 22nd chromosome, resulting in t(9,22). This results in chimeric fusion, producing oncoprotein BCR-ABL with tyrosine kinase activity (Groffen et al., 1984). The subsequent uncontrolled tyrosine kinase activity results in excess activation of multiple signaling pathways such as RAS/RAF/MAPK, PI3K/Akt, JUN, MYC, and Janus kinase/signal transducers and activators of transcription (JAK/STAT), leading to persistent cell proliferation, reduced apoptosis, and malignant expansion of pluripotent stem cells in bone marrow (Steelman et al., 2004). Since CML is due to a well-recognized translocation, it is possible to inhibit the aberrant BCR-ABL tyrosine kinase (TK) activity using molecularly targeted therapies. Imatinib was the first BCR-ABL TK inhibitor (TKI) introduced for the treatment of CML (Kantarjian et al, 2002). Although imatinib and other second-generation (including dasatinib and nilotinib) and third-generation TKIs are generally well tolerated, ensuing resistance remains a major clinical challenge (Apperley, 2007). Cytokines and growth factors can activate the JAK/ STAT signaling pathway, which has been well investigated in CML. Thus, the cascade transmits information from extracellular chemical signals to the nucleus, resulting in DNA transcription and expression of genes involved in immunity, proliferation, cellular migration, angiogenesis, differentiation, apoptosis, and oncogenesis (Rawlings et al., 2004). Therefore, overexpression of STATs, especially STAT5, is associated with leukemogenesis and carcinogenesis (Bowman et al., 2000; Rawlings et al., 2004). BCR/ABL chimeric protein constitutively activates the JAK/STAT cascade and causes antiapoptotic activity and uncontrolled proliferation of the malignant clone
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