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Background and Aims The transient receptor potential ion channels (TRPC) are non-selective Ca+ 2 permeable cation channels and are widely expressed in the tissues of vertebrates. They become active in response to signal transduction pathways associated with phospholipase C stimulation. TRPC6 is expressed in podocytes and is a component of the slit diaphragm. In genetic and acquired glomerular kidney diseases, TRPC6 overactivation causes podocyte damage by pathological Ca+ 2 entry. TRPC1, TRPC2, TRPC4, and TRPC5 interact with a protein called stromal-interacting molecule 1 (STIM 1), which is susceptible to intracellular calcium storage content. As a result of binding with this protein, TRPC channels bind to calcium-releasing zone in endosomes. The aim of the study was to investigate different expression profiles of TRPC family members in renal biopsy specimens in patients with clinically considered glomerulonephritis. Method This study was conducted with 108 patients admitted to Ege University Faculty of Medicine Nephrology Clinic who underwent a kidney biopsy with a preliminary diagnosis of glomerulonephritis and 37 patients who underwent a nephrectomy in urology clinic with a diagnosis of primary kidney tumour as a control case. PKD2, NPHS2, TRPC1, TRPC3, TRPC6, STIM-1 and Orai-1 mRNA levels were studied in the biopsy samples. Results When we compared the patient and the control group, the gender distribution of both groups was similar. The frequency of diabetes and hypertension was similar. The control group was statistically significantly older and glomerular filtration rates were higher than the patient group. In pathological examination, glomerulonephritis (57.5%) was diagnosed in the majority of patients. The most common etiologic factors were membranous nephropathy 23.1%, IgA nephropathy 13%, Amyloidosis 11.2%, focal segmental glomerulosclerosis 7.1%, proliferative glomerulonephritis 4.6%, minimal change disease 2.8% and membranoproliferative glomerulonephritis was 1.9%. 7.4% of the patients were diagnosed with diabetic nephropathy by renal biopsy. When we compared the TRPC expression profiles of the patient and the control group, the TRPC1, TRPC6, PKD2, NPHS2, STIM-1 and ORAi-1 mRNA levels of the patient group were statistically significantly higher than those of the control group (Figure). In contrast, TRPC3 mRNA levels were significantly lower in the patient group compared to the control group. When we performed subgroup analysis, the TRPC1, TRPC6 and STIM1 levels of the diabetic group were statistically significantly higher compared to the non-diabetic group of patients. We could not find any difference between TRPC expression profiles between the patients according to pathological diagnosis. Similarly, there was no difference between the amount of proteinuria (nephrotic level versus nephritic level). In correlation analysis, there was a negative correlation with TRPC6 and STIM1 levels with positive C4d staining of glomeruli in renal biopsy. Positive correlation was found between ORAI and glomerular sclerosis rate. Conclusion As a result, we found that other than TRPC3 mRNA level, other TRPC and related protein channels mRNA levels were statistically significantly increased in proteinuric kidney patients compared to healthy kidney tissue. We did not find a positive relationship between proteinuria severity and TRPC expression profiles. We found that TRPC6 and STIM1 expression levels were increased in diabetic patients, which supports the knowledge that intracellular calcium pathways were activated in podocyte damage. In our study, there were significantly increased STIM1 and ORAi-1 expression levels in proteinuric patients compared to the control group and their increase was closely related to TRPC6. From this we can conclude that these proteins play an important role in proteinuric kidney damage.

/0000-0003-3636-6082; Kantar, Mehmet/0000-0002-1669-4321, WOS: 000497443600019, PubMed: 31586226, Purpose We aimed to investigate the cisplatin-related hearing toxicity and its possible relationship with polymorphic variants in DNA repair genes, ERCC1, ERCC2, and XRCC1. Methods Fifty patients treated with cisplatin in the past were included in the study. There were 29 females and 21 males; mean age 13.4 +/- 6.0 years). the polymorphism in DNA repair genes was studied using primer and probes in Light Cycler device after DNA isolation was carried out with PCR technique. the polymorphisms and clinical risk factors were evaluated using Chi square test and logistic regression modelling. Results the patients had hearing loss in 44%. For ERCC1 gene, the patients with hearing loss had 50% of GG (wild type), 40.9% of AG and 9.1% of AA genotypes, while the patients without hearing loss had 28.6% of GG, 53.5% of AG, and 17.9% of AA genotypes. For ERCC2 gene, the patients with hearing loss had 18.2% of GG (wild type), 40.9% of TG, and 40.9% of TT genotypes, while the patients without hearing loss had 10.7% of GG 39.3% of TG, and 50% of TT genotypes. For XRCC1 gene, the patients with hearing loss had 18.2% of CC (wild type), 59.1% of CT, and 22.7% of TT genotypes, while the patients without hearing loss had 35.7% of CC, 50% of CT, and 14.3% of TT genotypes. There was no statistically significant association among the groups (p = 0.24). Conclusion We did not find a relationship between DNA repair gene polymorphisms and hearing toxicity of cisplatin.

Purpose Previously, we observed reciprocal changes in TRPC1 and TRPC6 expression levels in aging rat aorta and A7r5, rat embryonic vascular smooth muscle cells. Furthermore, downregulation of TRPC1 significantly elevated store-operated Ca 2+ entry suggesting the regulatory role of TRPC1 in A7r5 cells. Since TRPC6 upregulation shown to be associated with cell proliferation, the purpose of our study was to investigate the functional consequences of TRPC1 ion channel downregulation by RNA interference in Huh7 human hepatocellular carcinoma cell line. Methods Huh7 cells used in quantitative gene and protein expression as well as in functional analyses. To determine mRNA and protein levels, quantitative real-time RT-PCR and western blot analyses were performed, respectively. In functional analyses, real-time changes in proliferation, migration and intracellular Ca 2+ levels were monitored. Results In shTRPC1 -transfected Huh7 cells, TRPC1 mRNA and protein levels significantly decreased whereas store-operated Ca 2+ entry significantly elevated. TRPC1 -silencing suppressed cell proliferation without affecting cell migration in real-time cellular analyses. Conclusion These results suggest that TRPC1 may take part both in regulation of store-operated Ca 2+ entry and proliferation of hepatocellular carcinoma cells.

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.

WOS: 000403951100008, PubMed ID: 28218607, We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs) in myeloproliferative neoplasms (MPNs). TET2 (rs763480), ASXL1 (rs2208131), and IDH1 (rs11554137) variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET) and 1.7% in ET and 5% in primary myelofibrosis (PMF), respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV) group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies.

WOS: 000318652100001, PubMed ID: 23671879, The aim of this study was to investigate the effects of experimentally induced diabetes on (a) germ cells, (b) in vitro fertilization (IVF) success rate, and (c) gap junction and cell adhesion molecule gene and protein expressions during the early blastocyst period. Germ cells were obtained from healthy and diabetic rats, analyzed for number, motility, and morphology, and used for IVF. After reaching the early blastocyst stage, the expressions of genes encoding gap junction proteins and cell adhesion molecules were analyzed by quantitative RT-PCR. Histomorphologically and immunohistochemically analyses were also performed. Diabetes significantly affected sperm number and motility and the development of oocytes. Gene expressions of beta-catenin and connexin family members and protein expressions of E-cadherin and connexin-43 significantly decreased in groups including germ cells isolated from diabetic rats. Connective tissue growth factor expression increased in groups that included sperm cells isolated from diabetic male rats, whereas mucin-1 expression increased in the group that included oocytes isolated from diabetic female rats paired with sperm cells isolated from healthy male rats. In summary, experimentally induced diabetes was found to influence gap junctions, cell adhesion molecules, and associated proteins which all have important roles in germ cell maturation, fertilization, and development., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK 109S457], This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK 109S457 to H. Aktug).

Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18)(q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based onthe detection of mbr or mcr in paraffin-embedded tissue samples. Material and Methods: The study included 32 paraffin-embedded tissue samples collected from 32 consecutive FL patients that were diagnosed and followed-up at our hospital between 1999 and 2006. The MBR breakpoint wasidentified based on real-time PCR using a LightCycler v.2.0 t(14;18) Quantification Kit (MBR), multiplex PCR, and seminestedPCR. To identify the mcr breakpoint, real-time PCR was performed using specific primers and the FastStart DNAMaster SYBR Green I Kit. To detect t(14;18) via fluorescence in situ hybridization (FISH) nuclei from paraffin-embeddedtissue sections were extracted and used together with LSI IgH (immunoglobulin heavy chain) (spectrum green)/bcl-2(B-cell leukemia-lymphoma 2) (spectrum orange) probes. Results: The DNA and nuclei isolation success rate for B5 formalin-fixed, paraffin-embedded tissue sections (n = 12)was 42% and 33%, respectively, versus 95% and 60%, respectively, for 20 tissue sections fixed in formalin only. In all,24 paraffin-embedded tissue sections were analyzed and mbr positivity was observed in the DNA of 82.14% via seminested PCR, in 53.57% via multiplex PCR, and in 28.57% via real-time PCR. We did not detect mcr rearrangementin any of the samples. In all, 15 of 16 patients (93.75%) whose nuclei were successfully isolated were observed to bet(14;18) positive via the FISH method. Conclusion: Semi-nested PCR and FISH facilitated the genetic characterization of FL tumors. As such, FISH and PCR complement each other and are both essential for detecting t(14;18) translocation.

WOS: 000297962900009, PubMed ID: 27264588, 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. (Turk J Hematol 2011; 28: 306-11)

Objective: Apolipoprotein E (ApoE) genetic variation which is a major constituent of plasma lipoproteins causes diabetic nephropathy progress. Chronic kidney disease is associated with increased E2 allele and the decreased E4 allele risk. The aim of this study was to investigate the association between ApoE gene polymorphism in the development of diabetic nephropathy in Type 2 diabetes Turkish patients. Research design and methods: The objective of the study is to investigate the influence of ApoE gene polymorphism in the development of diabetic nephropathy in Turkish Type 2 diabetes. The ApoE genotypes were determined retrospectively in 46 patients with nephropathy and 56 without nephropathy and a control group of 35 healthy individuals. Genomic DNA was extracted from peripheral leukocytes of the subjects using the High Pure PCR Template Preparation Kit. For the detection of the presence of the three ApoE E alleles e2, e3, and e4 (codon 112 and 158) were analyzed by the commercial LightCycler ApoE Mutation Detection Kit. Results: No differences in ApoE genotype or the allelic frequencies of e2, e3 or e4 were found between the Type 2 diabetic patient group (with and without nephropathy) and a control group. Conclusions: We conclude that the ApoE gene polymorphism is not associated with the development of diabetic nephropathy in Turkish Type 2 diabetic patients. Lack of association between ApoE gene polymorphism and Type 2 diabetic nephropathy might be due to ethnic differences.

This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.

Objective Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. Research Design and Methods We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature ( T m ) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. Results The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively ( P =.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively ( P =.758). Conclusions There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

Recent findings suggest that hypertension, dyslipidemia, diabetes mellitus, coronary heart disease are more common in adults who born with intrauterine growth restriction (IUGR). Several studies have shown that polymorphisms in angiotensin-converting enzyme (ACE) and apolipoprotein-E (Apo-E) are effective in developing the insulin resistance and also in increasing the risk of coronary heart disease. In present study, the frequencies of ACE, Apo-E gene polymorphisms, apolipoprotein-B (Apo-B) mutation and lipid compositions were determined in full-term newborn infants with IUGR. Forty-four newborn infants who had completed 36 weeks of gestational age, 24 healthy infants and 20 with IUGR, were taken into the scope of the study. While total cholesterol (TC) and Apo-B concentrations in infants with IUGR was found to be significantly higher than that of the control group (p0.05), triglyceride (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL) and Apo-A1 levels were similar (p0.05). An insertion/deletion (I/D) polymorphism with a significantly increased frequency was observed in the IUGR group (65%) as compared with the control group (33%) (p0.05). When the distribution of the Apo-E gene polymorphism (E2, E3 and E4) was studied, no difference was found between the IUGR and control groups with respect to frequency. No Apo-B gene mutation was identified in the study groups. In conclusion, we may suggest that I/D polymorphism is responsible, though in part, for the etiology of intrauterine growth restriction. Levels of total cholesterol and Apo-B are elevated in IUGR infants, suggesting a linkage between low birth weight and atherosclerosis.

To determine if the functional Val108/158Met polymorphism causes a tendency toward alcohol addiction in Turkish cases. This polymorphism of the catechol-O-methyltransferase (COMT) gene has been associated with many psychiatric disorders, as well as with alcoholism. Materials and methods: The allele and genotype associations of the Val108/158Met polymorphism in 110 Turkish alcoholics and 330 healthy subjects were investigated, constituting our study and control groups, by polymerase chain reaction-restriction fragment length polymorphism. Results: Distribution of the Met/Met genotype was 16.4% to 20.6% and frequency of the Met allele was 36.8% to 39.5% in the study group compared to the control group. The results did not show any significant differences in the genotype distribution and allele frequencies of the polymorphism, neither between the study and the control groups (c2 = 0.985, P = 0.611 and c2 = 0.517, P = 0.472) nor between female (c2 = 0.247, P = 0.884 and c2 = 0.115, P = 0.735, respectively) and male (c2 = 0.728, P = 0.695 and c2 = 0.485, P = 0.486, respectively) alcoholics. The power of the study for genotype analysis was set at 79.1%. Conclusion: The present study shows that the polymorphic Met allele of the COMT polymorphism is not associated with alcoholism in Turkish cases; however, due to the lack of statistical power, this research should be evaluated again with an enlarged study group to confirm the possible association between the polymorphism and alcoholism.

Kronik Lenfositik Lösemi (KLL), eriskinlerde en sık görülen lösemidir. KLL hastalarında, son zamanlarda CD38 ZAP70 ve hTERT etkinliğinin değerlendirilmesi ve prognozun yanında evreleme ve lenfosit ikileme zamanı ile iliskisinin belirlenebilmesi için çalısmalar yapılmaktadır. KLL hastalarında prognozun değerlendirilmesi için yapılan çalısmalarda tutarsız sonuçların olduğu görülmektedir. Bu çalısmada KLL hastalarında CD38 ZAP70 ve hTERT değerleri birbirleriyle ve bilinen prognostik faktörler arasında karsılastırma yapılarak değerlendirildi. Çalısmaya dâhil edilen 30 KLL hastası ilk tanıdan sonra 5 yıl boyunca takip edildi. KLL hastaları ve kontrol olguları ortalama hTERT değeri sırasıyla 1.00±1.31 ve 3.89±3.58 idi (p< 0.05). Ortalama CD38 ve ZAP70 değerleri sırasıyla 6.20±7.60 ve 5.51±5.67 olarak saptandı. CD38 ZAP70 ve hTERT aktiviteleri arasında anlamlı bir iliski saptanmadı. Bu parametrelerle, Rai evrelemesi, periferik lenfosit değerleri, yas, cinsiyet, beta-2 mikroglobulin (B2M) ve tedaviye cevap gibi bilinen prognostik faktörler arasında istatiksel olarak anlamlı bir fark saptanmadı. KLL hastalarında 5 yıllık ortalama sağ kalım süresi %96.7 olarak saptandı. Daha büyük, takip süreleri daha uzun hasta grupları ile ileri çalısmaların yapılmasının uygun olacağı düsünülmüstür., Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults. Recently CD38, ZAP70 and hTERT activity have been studied for the evaluation of the prognosis of CLL besides clinical staging and lymphocyte doubling time. There are inconsistent results regarding these markers for the evaluation of the prognosis in CLL patients. In this study CD38, ZAP70 and hTERT values in CLL patients were measured to make comparisons between each other and known prognostic factors. Thirty CLL patients who were included in the study were followed up for 5 years after the initial diagnosis. The mean hTERT value in CLL and control cases were 1.00±1.31 and 3.89±3.58, respectively (p< 0.05). The mean CD38 and ZAP70 were 6.20±7.60 and 5.51±5.67, respectively. No significant association was detected between CD38, ZAP70 and hTERT activity. There was no correlation between those parameters and known prognostic parameters such as Rai staging, peripheral lymphocyte levels, age, and sex of the patients, beta-2 microglobulin and reply to treatment in CLL. The overall five-year survival rate in CLL patients is 96.7%. The overall five-year survival rate in CLL patients is 96.7%. In conclusion, further studies including larger series of patients with longer follow-up periods are recommended.

Latest statistics based on GLOBOCAN 2008, the standard set of worldwide estimates of can‐ cer incidence and mortality produced by the International Agency for Research on Cancer (IARC), revealed that prostate cancer (PC) is the most commonly diagnosed malignancy and the second leading cause of cancer-related mortality in male in developed countries [1]. The options in the treatment of PC are surgical tumor resection, hormonal therapy, radiothera‐ py, and adjuvant chemotherapy. These therapies, alone or in combination, show beneficial effects and a significant curative rate in treating patients with localized PC in the early stages. However, the development of locally advanced and/or metastatic hormone-refracto‐ ry prostate cancers (HRPCs) eventually results in disease recurrence. Most patients who un‐ dergo potentially curative resection for advanced and/or metastatic HRPCs subsequently relapse due to the persistence of foci and micro-metastases. Therefore systemic chemothera‐ py may represent another option to eradicate the PC cells, including the highly tumorigenic stem/ progenitor cells that can drive tumor growth at primary neoplasms and distant meta‐ static sites.

WOS: 000313165500093, PubMed ID: 23076533, The aim of this work was to report two cases of hypereosinophilic syndrome (HES). FIP1L1-PDGFRA fusion was assessed with two protocols at RNA level. The fusion transcript was found positive at the RNA level with both PCR methods in two cases. In this study, the efficiency of imatinib treatment and a dramatic response in two HES cases with multisystemic involvement showing the characteristics of a chronic myeloproliferative disease were presented. Both cases showed complete responses confirming that imatinib mesylate treatment could be successful even in patients with advanced HES having myeloproliferative disease.

Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly. A total of 102 unrelated acromegaly subjects were prospectively included into this case–control association study and constituted our study group. The study group was comparable by age and gender with 200 unrelated healthy subjects constituting our control group. Genomic DNA was isolated from the peripheral blood leukocytes of all subjects and Apo E genotype (codon 112/158) was assessed by melting temperature analyses after using a real-time PCR protocol. The Apolipoprotein E4 allele was found at a significantly higher frequency in the study group when compared with the control group (P = 0.032). Subjects with the E2 allele, on the other hand, had significantly increased values in body mass index (P = 0.004), waist circumference (P = 0.001), C-reactive protein (CRP) (P < 0.001), and left-side carotid intima media thickness (P = 0.025). The Apolipoprotein E2 genotype might contribute to increased risk of cardiovascular complications in subjects with acromegaly since it is concurrently present with other cardiovascular risk factors such as the left-side carotid intima media thickness and CRP.

Object: Multidrug resistance 1 gene is respon- sible for the resistance of a large variety of drugs in human cells. We tried to evaluate this in the present study in thyroid stimulant hormone receptor antibody positive subjects. Method: In study enrolled 23 female and 10 male subjects. Hyperthyroid subjects were treated with PTU and remission was assured between 6-12 months. Blood samples were col- lected before the start of this treatment. Permis- sion for this study was taken from the patients and the local ethical committee. Results: Serum F-T3, F-T4 levels in Graves sub- jects were markedly high, whereas TSH levels were markedly low than normal range. We also found that with increased age of the Graves ' sub- jects, MDR-1 gene expression decreased. There was also a direct correlation between blood MDR-1 gene expression and TSH-R Ab levels in patients with Graves ' s disease. We observed that the duration of being euthyroid was length- ened with the elevation of MDR-1 gene expres- sion. There was a direct correlation between blood MDR-1 gene expression levels and ultra- sonografi c size of thyroid gland. Conclusion: As a result, raised blood MDR-1 gene expression levels in patients with Graves- Basedow disease may be associated with the activity of the disease and the resistance to its treatment. The more blood MDR-1 expression increases the more the duration of being euthy- roid increases.

Objectives To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)–induced diabetic rats. Methods Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, diabetic rats treated with ERA-A, and healthy rats treated with ERA-A. Diabetes was induced in 40 rats by a single intraperitoneal injection of STZ and followed for 2 months. A total of 20 diabetic and 20 healthy rats were also intravenously treated with ERA-A at days 7 and 15. The remaining untreated healthy rats served as controls. Blood glucose levels of ≥ 250 mg/dL were considered to indicate diabetes and were measured at the end of the second month. Formalin-fixed paraffin-embedded testis tissue sections were analyzed after staining with hematoxylin and eosin or specific antibodies for apoptotic markers. mRNA expressions of genes involved in the apoptotic pathway or spermatogenesis were evaluated by real-time reverse transcription–polymerase chain reaction. Results Major therapeutic effects of ERA-A could be achieved for damages caused by oxidative stress. Although a decrease in apoptotic cell death could be detected, no statistically meaningful results could be obtained for the duration of spermatogenesis. Conclusions ERA-A could prevent germ cell death by apoptosis and testicular damage in diabetic rats.

WOS: 000277198300009, PubMed ID: 20431989, We previously showed that the expression of transient receptor potential canonical (TRPC)6 ion channel elevated when TRPC1 was knocked down in A7r5 cultured vascular smooth muscle cells. Therefore, the purpose of this study was to explore whether TRPC6 is also upregulated in aging rat aorta comparable to that of TRPC1 in longitudinal in vivo aging model. We further investigated a possible causal relationship between altered phenylephrine-induced contractions and the expression levels of TRPC6, a purported essential component of alpha-adrenergic receptor signaling in aging aorta. Immunoblot analysis showed that TRPC1 protein levels significantly decreased whereas TRPC6 increased drastically in aorta from 16- to 20-month-old rats compared to that from 2 to 4 months. Immunohistochemical data demonstrated spatial changes in TRPC6 expression within the smooth muscle layers along with increased detection in the adventitia of the aged rat aorta. The phenylephrine-induced contractions were potentiated in aging aorta. In conclusion, based on this aging model, TRPC6 overexpression could be related with TRPC1 downregulation and might be responsible for the increased adrenoceptor sensitivity which contributes to the development of age-related vasospastic disorders., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG-2735, BIDEB-2211]; Ege UniversityEge University [BAP04ECZ011, 05BIL016]; Bilkent UniversityIhsan Dogramaci Bilkent University, This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, SBAG-2735 to M. T. and graduate scholarship, BIDEB-2211 to C.S.). A partial support was also provided by the Ege University (BAP04ECZ011 and 05BIL016 to M.T.) and Bilkent University Research Grants. Authors thank Dr. R.M. Rapoport (University of Cincinnati, College of Medicine) for his critical comments on the study and I.T. Aydin (Bilkent University, Faculty of Science) for technical assistance.

WOS: 000263834000001, PubMed ID: 19057990, Dyslipidemia, cardiovascular disease and hypertension are more frequently seen in patients with PCOS than in normal patients. We aimed at evaluating the distribution of Apo E alleles that can influence cardiovascular risk of the PCOS patients and control subjects. In this study, 129 young women with PCOS and 91 healthy women were included. In all subjects we performed hormonal, biochemical and Apo E genetic analysis. The Apo E3 allele was found at a significantly higher frequency in the PCOS patient group compared with the control group. The Apo E2 allele was found at a significantly higher frequency in the control group compared with the patient group with PCOS. Although there were genotype and allele differences between control and patient groups in this study, no statistically significant change was determined in lipid and other cardiovascular risk factors in connection with allele and genotype.

Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed to evaluate telomerase activity in a group of Turkish patients with various connective tissue diseases. In this cross sectional study, 19 patients with systemic sclerosis (SSc), 15 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA) and 14 with primary Sjogren's syndrome (pSjS) were studied. As the control group, 29 healthy subjects were also included. Human telomerase-specific reverse transcriptase (hTERT) was measured in peripheral blood lymphocytes, using online real-time reverse-transcriptase polymerase chain reaction (PCR). We also investigated if hTERT values in each patient group were correlated with clinical parameters and disease activity. Highest hTERT values were observed in RA group (21.24 +/- 28.54), followed by SLE (13.38 +/- 26.05) and pSjS (11.73 +/- 10.59) groups. Only hTERT values in RA group was significantly higher than the healthy control group (7.62 +/- 4.21) (p < 0.05). Interestingly, hTERT values in SSc were very low (2.09 +/- 3.18), even less than the healthy control group. In consistent with previous studies, telomerase activity was increased in SLE and RA. Very low telomerase activity in SSc group was rather surprising. Since existing telomerase data in SSc was limited and telomere shortening was previously reported in SSc, our finding of low telomerase activity in SSc group deserves relevant discussion and further studies.

PubMed ID: 18293058, The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reverse- transcriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival. © 2008 The Japanese Society of Hematology., Acknowledgments This study was supported by Ege University Science and Technology Center.

Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677CT) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.DNA was extracted from peripheral leukocytes of the subjects. Genotyping of the MTHFR C677T polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR.This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 6.8% were TT, 43.7% were CT and 49.5% were CC (chi2 = 0.201, p0.05). The frequency of the mutant T allele was 23.4% in diabetic patients with nephropathy versus 33.0% in those without nephropathy. The genotype frequencies were TT, 2.1%; CT, 46.6%; CC, 55.3% in diabetic patients with nephropathy versus TT, 10.7%; CT, 44.6%; CC, 44.6% in those without nephropathy.The MTHFR genotype and allele frequencies were not different between diabetic patients with and without nephropathy (chi2 = 3, 386, p0.005; chi2 = 2.320, p0.005, respectively). Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients.

WOS: 000245418600012, PubMed ID: 16988555, Acute myocardial infarction (AMI) due to arthropod envenomation has rarely been reported in the literature. In the present report, we describe two cases who developed AMI following an arthropod bite. Coronary angiograms revealed normal coronary arteries in both patients. Both events were probably secondary to coronary artery thrombosis and/or coronary artery vasospasm. Both patients were subsequently found to be heterozygous for prothrombin mutation (G20210A). As a result, we recommend ruling out the possibility of hereditary thrombophilias in young patients with AMI developing after an arthropod bite.

UNLABELLED Abstract Background and Aim: The presence of apolipoprotein E epsilon4 allele is being considered as a risk factor for cognitive decline after cardiac surgery. We sought the effect of apolipoprotein E epsilon4 allele on neurobehavioral status after on-pump coronary artery bypass grafting. METHODS Prior to the operation, neurologic examination and neurobehavioral cognitive status test (COGNISTAT) were performed. Both procedures were repeated on the day of discharge and 3 months after surgery. Apolipoprotein E epsilon4 allele positive and apolipoprotein E epsilon4 allele negative patients' performance on COGNISTAT were compared. RESULTS There was no statistically significant demographic and operative data difference between two groups. No neurological impairment was observed on examinations. There was no statistically significant neurocognitive decline difference between two groups' postoperative performances. CONCLUSIONS It seems that apolipoprotein E epsilon4 allele may not affect neurobehavioral status in the intermediate period after on-pump coronary artery bypass grafting.

Although factor V Leiden mutation, is the most common established genetic risk factor for venous thrombosis, its effect on the development of myocardial infarction remains unclear. We describe a family case of homozygous factor V Leiden mutation in two siblings presenting with acute myocardial infarction as a rare cause of myocardial infarction in the young.

PubMed ID: 15621763, Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children. © 2004 Taylor & Francis Ltd.

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 identify whether the functional Val66Met [G196A; (rs6265)] polymorphism in BDNF gene has effect upon tendency to alcoholism in Turkish male and female alcohol dependent cases. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method in 110 alcoholic cases (10 female, 100 male) and 376 healthy subjects (148 female, 228 male) constituting our study and control groups, statistical analyses were revealed by chi-square and ANOVA tests. Results: The distribution of the mutant AA genotype was 3.6% to 1.6% and frequency of the A allele was 16.0% to 15.0% in the study group when compared to control group. Our results didn’t show any significant differences in genotype distribution and allele frequencies of polymorphism neither between the study and control groups nor between female case and female controls and male alcoholics and male controls. The power of the study for genotype analysis was set at 80.2%. Conclusion: These results indicate that the polymorphic A allele of BDNF gene is not related with alcoholism in Turkish subjects. But since AA genotyped male subjects’ starting ages of alcohol usage and pathological drinking were detected to be earlier among other genotypes, this gave rise to a conclusion that BDNF polymorphism might be important in the alcoholism phenotype.

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. © 2009 Alioglu et al; licensee BioMed Central Ltd.