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Öğe Two New Dysdera Species From Turkey (Araneae: Dysderidae)(Amer Entomol Soc, 2015) Varol, İsmailTwo new species of the genus Dysdera, D. turcica sp. n. and D. akpinarae sp. n. (male) from Turkey were discovered in the Aegean region and are described and illustrated. Detailed morphological descriptions and diagnoses are presented together with figures of the copulatory organs and an accompanying distribution map. The two new species are compared with similar species in the genus.Öğe DNA methyltransferase expression differs with proliferation in childhood acute lymphoblastic leukemia(Springer, 2010) Sayın, Derya Beyza; Kürekçi, Emin; Karabulut, Halil Gürhan; Ezer, Üstün; Bökesoy, Işık…Öğe Molecular and functional analysis of a novel recombinant clone of rat (Rattus norvegicus) CD40 ligand (CD40L) gene(Springer, 2009) Esendağlı, Güneş; Günel-Özcan, Ayşen; Canpınar, Hande; Güç, DicleGenetic material obtained from various individuals may contain certain polymorphisms which may conflict with the predetermined DNA sequence and consequently, may modulate the function of gene products. In this study, coding sequence of rat CD40 ligand (CD40L, CD154) was obtained from activated splenocytes, amplified, and cloned into a eukaryotic expression vector by using directional cloning method. Sequence of the recombinant rat CD40L DNA, pCD40L-IRES2-EGFP (pCD40L), was compared with the previously reported rat CD40L cDNA sequences and a 99% identity was found. Differing nucleotides were on the positions; 122-T/C, 341-G/A, 476G/A, 762-T/A. Further alignment analysis showed that pCD40L was collectively carrying the nucleotides each previously reported by different groups. The sequence was submitted to NCBI GenBank and nucleotide database accession number EF066490 was obtained. Following transfection of the construct into NIH/3T3 cell line, novel CD40L clone was functionally expressed de novo, increasing the expression of CD80 and CD86 costimulatory molecules and augmenting the proliferation rate of effector splenocytes in immune reactions ex vivo. Based on these data, here we report a novel recombinant clone of the rat CD40L gene which may represent a potential polymorphic variant.Öğe Primary tumor cells obtained from MNU-induced mammary carcinomas show immune heterogeneity which can be modulated by low-efficiency transfection of CD40L gene(Taylor & Francis Inc, 2009) Esendağlı, Günşs; Canpınar, Hande; Yılmaz, Güldal; Gunel-Ozcan, Aysen; Güç, M. Oğuz; Kansu, Emin; Güç, DicleThe presence of CD40 on carcinoma cells is an important factor for the generation of tumor-specific responses induced by CD40 ligation. In an N-methyl-N-nitrosourea (MNU)-induced autochthonous mammary tumor model, we analyzed the immune features of primary tumor cells. Here, CD40 was frequently detected on the primary tumor cultures and selectively expressed on the malignant mammary tissue in vivo. On the other hand, every mammary tumor cell culture had a heterogeneous and reduced expression of proinflammatory TNF alpha, IL-1 beta, IL-6 and CXCL1 cytokines compared to normal mammary epithelial cells. Low-efficiency transfection of CD40 ligand (CD40L) gene enhanced the expression of proinflammatory cytokines in the tumor cells, and strengthened allogeneic immune reactions and costimulatory activity which may help overwhelming suppressive features of the tumor.Öğe The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at KÄaut +/- rÄaut +/- kkale University in Turkey(Springer, 2009) Günel-Özcan, Ayşen; Sayin, Derya Beyza; Mısırlıoğlu, Emine Dibek; Guliter, Sefa; Yakaryilmaz, Fahri; Ensari, CüneytFamilial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder characterised by recurrent and self-limited abdominal pain, synovitis and pleuritis. MEFV gene mutations are responsible from the disease and its protein product, pyrin or marenostrin, plays an essential role in the regulation of the inflammatory reactions. MEFV gene contains 10 exons and most of the mutations have been found on the last exon. Up to date, 152 mutations and polymorpisms have been reported inwhere V726A, M694V, M694I, M680I and E148Q are the most common mutations. In this study, MEFV allele frequencies of 136 individuals (60 from Pediatry, 76 from Internal Medicine) have been evaluated, and compared with each other. Asymptomatic individuals with FMF family history (4 from Pediatry, 6 from Internal Medicine) were excluded from the analysis. The prominent mutations indicated in the Pediatry group are V726A, M694V and M680I (G/C) and with the allele frequency of 0.06, 0.05 and 0.04 respectively while they were E148Q, M694V, M680I (G/C) in the Internal Medicine group with the allele frequency of 0.12, 0.08 and 0.04. The E148Q mutation is significantly overrepresented in the adult referrals (P = 0.02). Mutation on both alleles was observed in only 12% of cases. Overall mutation frequency was low, seen in 26.2% (66/252). However, when only diagnosed patients were analyzed it is 72.7% (16/22). It is also interesting that 63% of individuals are female that there may be sex influence on FMF phenotype.Öğe Determination of the Risk Group in Patients with Venous Thrombosis(Ortadogu Ad Pres & Publ Co, 2009) Eren, Pinar Ata; Denizli, Nazim; Sokmen, H. Mehmet; Erdem, Solmaz; Solak, MustafaObjective: We aimed to investigate the frequency of Factor V Leiden mutation among venous thromboembolism patients admitted to our center and we intended to detect the risk of thromboembolism in mutation carrying family members by genetic counseling. Material and Methods: In this study a total of 72 patients with venous thrombosis admitted to Haydarpasa Numune Research and Training Hospital, Genetic Diseases Diagnosis Center between January and August in 2008 were investigated for Factor V Leiden mutation. Patients were informed and their consents were obtained. All of the patients had pedigree analysis and affected family members were investigated. Genomic DNA was isolated from peripheral blood using proteinase K digestion method. Factor V gene, covering 1691. nucleotide region was amplified with appropriate oligonucleotide primers and products were analyzed with RFLP method. Results: Twenty two percent (n= 16) of the our patients had chronic renal disease with fistula problems, 17% (n= 12) had deep venous thrombosis, 32% (n= 23) had cerebrovascular accidents and the remaining 29% (n= 21) had recurrent abortus. In our center, the molecular genetic analysis for Factor V Leiden mutation 59 revealed that had a normal allele. Among the remaining 13 patients, 4 of them were detected as homozygote and 9 of them as heterozygote for the mutation. Mutation carrier status was found 18% among all patients. The risk of having at least one family member with thrombosis was 23% in mutation carrying patients' family. Conclusion; As a result of this study, the importance of molecular genetic analysis and genetic counseling for the patients admitted to our center has been demonstrated. It could be possible to detect the target risk population through investigation of thrombophilia in a larger study group.Öğe Methylation and cancer: Review(Ortadogu Ad Pres & Publ Co, 2008) Sayin, Derya BeyzaDNA methylation is the major epigenetic modification in mammals, and is seen in CpG dinucleotides. In normal cells, the CpG dinucleotides in repetitive DNA are methylated, and CpG islands, which are found in the promotor region in 50% of genes, are demethylated. Epigenetic modifications may be defined as inheritable gene expression changes, without altering the primary sequence of DNA. It is well established that epigenetic modifications are as important as genetic changes in cancer development. Cancer cells show genomic hypomethylation and gene promotor hypermethylation. Both are independent from each other, but are effective in cancerogenesis in different ways. Hypermethylation of the promotor has a supressive effect on the downstream gene, and is important in turnout supressor gene inactivation. hMLH1 and O-6-MGMT gene methylations are the most studied among different cancer types. Knudson's two hit hypothesis is the most common hypotesis for cancer development, and one of these hits may be epigenetic. Genomewide hypomethylation may favor for genomic instability and reactivation of parasitic sequences. Promotor hypermethylation may show different patterns in different cancers, or different types of the same cancer, and methylation patterns may be useful as a cancer biomarker or a prognostic marker. Epigenetic mutations are reversible, and there is sparse promotor hypermethylation in normal cells, which makes demethylating agents highly specific for cancer cells. Increasing our knowledge on the methylation changes in cancer cells will improve our approaches to the treatment, diagnosis and prevention of cancer.
