Ender Altıok - Academia.edu (original) (raw)

Papers by Ender Altıok

Research paper thumbnail of Nörogenetik Hastalıklarda Gen Tedavisi Klinik Araştırmaları

Turkiye Klinikleri Journal of Neurology Special Topics, 2011

Research paper thumbnail of Agarose gel electrophoretic evidence for domains of nuclear DNA linked with bonds cleavable with sulfhydryl molecules

FEBS Letters, 1985

Complexes of intact nuclear DNA with proteins undissociable by 2.0 M NaCl and nonionic detergents... more Complexes of intact nuclear DNA with proteins undissociable by 2.0 M NaCl and nonionic detergents were analyzed by agarose gel electrophoresis following physical or enzymatic fragmentation. Sulfhydryl molecules converted these DNAs (but not the bacteriophage lambda DNA) into smaller-Mr forms. Following limited restriction endonuclease digestion of complexes with PstI most of the nuclear DNA formed a high-molecular-mass band in the 60-110 kbp range. These 60-110 kbp fragments, releasable from the rest of nuclei by sulfhydryl molecules, have similar sizes to nuclear DNA loops detected by other techniques and may derive from supranucleosomal organizational units in the chromatin complex.

Research paper thumbnail of Conjunctival papilloma caused by human papillomavirus type 11 treated with systemic interferon in a five-year-old boy

The Turkish journal of pediatrics

Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma repr... more Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma represents 7-10% of conjunctival tumors. Human papillomavirus (HPV)-6 and HPV-11 are the major HPV types responsible for conjunctival lesions. A five-year-old boy with a two-year history of conjunctival papilloma caused by HPV type 11 treated with systemic interferon alpha is reported and the literature is reviewed.

Research paper thumbnail of Do MEFV mutations play a role in the development of Behçet's disease related amyloidosis?

Clinical and experimental rheumatology

Research paper thumbnail of Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells

Gan to kagaku ryoho. Cancer & chemotherapy, 2000

Three types of virus-host cell interactions have been described in cells latently infected with E... more Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBN...

Research paper thumbnail of Differential c-myc protein expression in Burkitt's lymphomas and EBV-transformed lymphoblastoid lines

European journal of cancer (Oxford, England : 1990), 1991

The levels of c-myc protein expression in three types of Epstein-Barr virus (EBV) transformed hum... more The levels of c-myc protein expression in three types of Epstein-Barr virus (EBV) transformed human B-cell derived lines were examined with an ELISA assay. Six independently maintained sublines of the same EBV-transformed pro-B-cell line (FLEB-14), six B-cell lines (LCL) and six Burkitt's lymphoma lines (BL) were compared. The average amount of c-myc protein, calculated from at least three independent tests on each line, differed between the three groups. Expressed in relative units, the ratio of the means was 1:2:5 for the LCL:FLEB:BL lines. The differences were statistically significant at P less than 0.01.

Research paper thumbnail of Pulmonary Alveolar Microlithiasis with Homozygous c.316g>C (p.G106R) Mutation: A Case Report

Turkish Journal of Pathology, 2012

Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar ... more Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar spaces. Sporadic cases are more common, but the disease also presents in an inherited familial form. The greatest number of reported cases is from Europe and especially Turkey. We present a 43-year-old female with complaints of dyspnea for many years. She had a suspicious familial history of pulmonary alveolar microlithiasis. The surgical lung biopsy specimen appeared gritty and firm. Histological sections showed diffuse involvement of the lung parenchyma by innumerable tiny calcospherites. Genetic studies showed a homozygous c.316G>C (p.G106R) mutation in exon 4 and confirmed the diagnosis of pulmonary alveolar microlithiasis. The present report aims to contribute to the literature with a pathologically and genetically confirmed new case to add insight into the etiology of this rare disease. This case confirms an autosomal recessive inheritance and does not support the role of non-genetic and other factors in the pathogenesis of pulmonary alveolar microlithiasis.

Research paper thumbnail of Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the   chain gene and other chromosomes

Proceedings of the National Academy of Sciences, 1990

Research paper thumbnail of Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6

Proceedings of the National Academy of Sciences, 1992

Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. E... more Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr viruscarrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus-carrying cells with a lymphoblastoid phenotype including group HI Burkitt lymphoma (BL) lines positive for B-cell activation markers. Transcripts are initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid cell lines and group m BL lines. In group I BL lines, nasopharyngeal carcinoma, and the somatic cell hybrids,

Research paper thumbnail of Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes

Proceedings of the National Academy of Sciences, 1989

Research paper thumbnail of Novel Mutation of Aspartoacylase Gene in a Turkish Patient with Canavan Disease

Journal of Tropical Pediatrics, 2007

Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although thi... more Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although this disease is prevalant among Ashkenazi Jewish population, several cases have been reported from all over the world. Canavan disease is caused by a genetic mutation in aspartoacylase gene. We have identified a novel mutation, a homozygous C432+1G>A mutation, in a 10-month-old boy who has a typical Canavan phenotype (without macrocephaly) accompanied by typical brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and diffusion magnetic resonance findings. The patient's mother was found to be heterozygous for this mutation. We believe that future studies of aspartoacylase gene in various ethnic groups could lead to a better understanding of Canavan's pathophysiology and gene therapy.

Research paper thumbnail of Functional interaction of Oct transcription factors with the family of repeats in Epstein-Barr virus oriP

Journal of General Virology, 2005

The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C ... more The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C promoter (Cp) that controls transcription of six different latent nuclear proteins following interaction with the EBV nuclear protein EBNA1. Here, it was shown that Cp could also be activated by octamer-binding factor (Oct) proteins. Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay. Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells. Cp controlled by the FR was also activated by binding of Oct-2 to the FR. This may have direct implications for B cell-specific regulation of Cp.

Research paper thumbnail of B Cell Phenotype-dependent Expression of the Epstein-Barr Virus Nuclear Antigens EBNA-2 to EBNA-6: Studies with Somatic Cell Hybrids

Journal of General Virology, 1991

Research paper thumbnail of Influence of transforming growth factor-beta (TGF-β) on the immunoglobulin production by EBV-infected B cell cultures

Immunology Letters, 1994

TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a variety of activators,... more TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a variety of activators, including EBV. However, EBV-immortalised cells are refractory to TGF-beta. The influence of TGF-beta on B cell maturation varies, apparently depending on the origin of the B lymphocytes and their maturation/activation state, the strength of the stimulus and the presence of cofactors. We investigated the effect of TGF-beta on immunoglobulin production by 5-day-old EBV-infected B cells. TGF-beta added at the initiation of the cultures inhibited IgM, IgG and IgA secretion by decreasing the numbers of secretory cells. The inhibition of IgM secretion was strongest. At the cytoplasmic level, TGF-beta reduced the expression of IgM heavy, lambda and kappa light chains but not IgG and IgA heavy chains. However, the IgM production by an established EBV-transformed B cell line was not affected by TGF-beta. Thus, TGF-beta inhibited EBV-induced maturation of the B cells until they acquired a transformed state. We discuss the relevance of these findings for the potential role of TGF-beta on EBV infection.

Research paper thumbnail of Meiotic recombinations within major histocompatibility complex of human embryos

Immunogenetics, 2012

We studied the rate and pattern of recombinations within the extended major histocompatibility co... more We studied the rate and pattern of recombinations within the extended major histocompatibility complex (MHC) locus of the human embryos obtained during preimplantation genetic diagnosis (PGD) for HLA compatibility. Recombinant allele frequency was on average 5.33 %, and recombination rate was 0.44 cM/Mb in the 12.2 Mb of the extended MHC locus. Recombination rate varied up to 14-fold (0.19-2.73 cM/Mb) between cases, and maternal recombination rate was on average 3.8 times higher than paternal alleles. More than 69 % of the recombination hot spots were clustered within the extended class II region where the recombination rate was 5.4 times more than that in extended class I region. These findings indicate the potential of PGD to study the mechanisms of linkage disequilibrium within MHC locus of human embryos, demonstrate the recombination characteristics within extended MHC loci of human embryos in comparison to sperm and family studies, and point to the significance of design and interpretation of PGD for HLA compatibility to avoid misdiagnosis because of meiotic recombinations.

Research paper thumbnail of Effect of Transforming Growth Factor-Beta 1 and -Beta 2 on the Proliferation of Burkitt Lymphoma and Lymphoblastoid Cell Lines

Growth Factors, 1991

We tested the effect of transforming growth factor (TGF)-beta 1 and TGF-beta 2 on the proliferati... more We tested the effect of transforming growth factor (TGF)-beta 1 and TGF-beta 2 on the proliferation of human B cell lines. The panel was selected to give information whether (1) their origin, (2) their phenotype, (3) their Epstein-Barr virus (EBV) carrier state, influence their responsiveness. The growth of lymphoblastoid cell lines (LCL) was not inhibited by TGF-beta 1. The EBV-carrying Burkitt lymphoma (BL) lines, Daudi, Jijoye, Rael but not Raji were inhibited. Three EBV-negative BL lines and the majority of their converted sublines were sensitive. The cell lines tested expressed TGF-beta receptors and TGF-beta 1 transcripts. The proliferation of EBV-infected B cells was inhibited by TGF-beta, their sensitivity decreased, however, after 3 days. The results suggest that the activation state of the B cells is decisive for TGF-beta sensitivity and EBV influences it indirectly by changing the cell phenotype.

Research paper thumbnail of Higher pregnancy rates after PGD of monogenic disease combined with HLA typing: single center experience

Fertility and Sterility, 2008

Research paper thumbnail of P0096 It is Not Always Non-Hfe Hemochromatosis in Turkey

European Journal of Internal Medicine, 2009

procedure to reach the exact diagnose, and endoscopic and pathological findings. We also document... more procedure to reach the exact diagnose, and endoscopic and pathological findings. We also documented the refusal of second endoscopy offers and if available the final diagnose. All patients were performed gastroscopy by same endoscopist. Results: In this period 83 patients with gastric ulcer underwent repeat gastroscopy. Average numbers of endoscopy was 2.15. In nine patients, 3 gastroscopy procedures were needed where as only two patients were in need of fourth gastroscopy and no one needed fifth. Seventy-seven of 83 patients were ulcer free at repeat endoscopies. But in 6 (7.2%) patients were shown to have malignant ulcer. Four of them were diagnosed after second endoscopy but two patients' malignancies could be diagnosed at third procedure. Five of the patients had gastric adenocancer and the other single case had gastric lymphoma. Two of 5 (40%) adenocancer were early gastric cancer. Conclusion: Our study re-enforced the recommendation that all patient with gastric ulcers should undergo repeat endoscopy to exclude malignancy. The malignancy rate was 7.2% in our cases. This high rate must encourage clinicians and endoscopist to insist on repeating endoscopy to assess ulcer healing.

Research paper thumbnail of BRAFV600E mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness

Endocrine, 2012

Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK p... more Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK pathway plays an important role in the development of several cancers. BRAF which is a member of Raf-kinase family activates this way. BRAF gene activating mutations lead to neoplastic transformation in thyroid follicle cells. In PTC, this mutation itself is a poor prognostic sign independent of other clinicopathological characteristics. We evaluated BRAF(V600E) mutation and clinical-pathological characteristics in Turkish population with PTC. We assessed 109 patients with PTC (88 female, 21 male). The average age was 38.7 ± 9.9 (17-71). BRAF(V600E) mutation was detected using polymerase chain reaction and fluorescent melting curve analysis. The results show that BRAF(V600E) mutation rate was found in 39.45% of our patients. We observed that BRAF(V600E) mutation was significantly higher in men, in tumors larger than 1 cm in size, and in patients with classical PTC. Moreover, statistically significant correlations of BRAF(V600E) with indicators of tumor aggressiveness such as thyroid capsular invasion, multifocality, lymph node metastasis, and extrathyroidal spread were found. Patient groups below and over the age of 45 did not differ in mutation frequency. Patients with micro-PTC were evaluated separately, it was found that BRAF(V600E) mutation was more frequent in the classic type and that lymph node metastasis rate significantly increased when the mutation was present. We concluded that BRAF(V600E) was correlated with indicators of tumor aggressiveness in our study population. This fact is taken into consideration in treatment and follow-up of our patients with PTC and positive BRAF(V600E) mutation.

Research paper thumbnail of Mutations in Influenza A Virus (H5N1) and Possible Limited Spread, Turkey, 2006

Emerging Infectious Diseases, 2008

We report mutations in infl uenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. F... more We report mutations in infl uenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. Four novel amino acid changes (Q447L, N556K, and R46K in RNA polymerase and S133A in hemagglutinin) were detected in virus isolates from 2 siblings who died.

Research paper thumbnail of Nörogenetik Hastalıklarda Gen Tedavisi Klinik Araştırmaları

Turkiye Klinikleri Journal of Neurology Special Topics, 2011

Research paper thumbnail of Agarose gel electrophoretic evidence for domains of nuclear DNA linked with bonds cleavable with sulfhydryl molecules

FEBS Letters, 1985

Complexes of intact nuclear DNA with proteins undissociable by 2.0 M NaCl and nonionic detergents... more Complexes of intact nuclear DNA with proteins undissociable by 2.0 M NaCl and nonionic detergents were analyzed by agarose gel electrophoresis following physical or enzymatic fragmentation. Sulfhydryl molecules converted these DNAs (but not the bacteriophage lambda DNA) into smaller-Mr forms. Following limited restriction endonuclease digestion of complexes with PstI most of the nuclear DNA formed a high-molecular-mass band in the 60-110 kbp range. These 60-110 kbp fragments, releasable from the rest of nuclei by sulfhydryl molecules, have similar sizes to nuclear DNA loops detected by other techniques and may derive from supranucleosomal organizational units in the chromatin complex.

Research paper thumbnail of Conjunctival papilloma caused by human papillomavirus type 11 treated with systemic interferon in a five-year-old boy

The Turkish journal of pediatrics

Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma repr... more Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma represents 7-10% of conjunctival tumors. Human papillomavirus (HPV)-6 and HPV-11 are the major HPV types responsible for conjunctival lesions. A five-year-old boy with a two-year history of conjunctival papilloma caused by HPV type 11 treated with systemic interferon alpha is reported and the literature is reviewed.

Research paper thumbnail of Do MEFV mutations play a role in the development of Behçet's disease related amyloidosis?

Clinical and experimental rheumatology

Research paper thumbnail of Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells

Gan to kagaku ryoho. Cancer & chemotherapy, 2000

Three types of virus-host cell interactions have been described in cells latently infected with E... more Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBN...

Research paper thumbnail of Differential c-myc protein expression in Burkitt's lymphomas and EBV-transformed lymphoblastoid lines

European journal of cancer (Oxford, England : 1990), 1991

The levels of c-myc protein expression in three types of Epstein-Barr virus (EBV) transformed hum... more The levels of c-myc protein expression in three types of Epstein-Barr virus (EBV) transformed human B-cell derived lines were examined with an ELISA assay. Six independently maintained sublines of the same EBV-transformed pro-B-cell line (FLEB-14), six B-cell lines (LCL) and six Burkitt's lymphoma lines (BL) were compared. The average amount of c-myc protein, calculated from at least three independent tests on each line, differed between the three groups. Expressed in relative units, the ratio of the means was 1:2:5 for the LCL:FLEB:BL lines. The differences were statistically significant at P less than 0.01.

Research paper thumbnail of Pulmonary Alveolar Microlithiasis with Homozygous c.316g>C (p.G106R) Mutation: A Case Report

Turkish Journal of Pathology, 2012

Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar ... more Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar spaces. Sporadic cases are more common, but the disease also presents in an inherited familial form. The greatest number of reported cases is from Europe and especially Turkey. We present a 43-year-old female with complaints of dyspnea for many years. She had a suspicious familial history of pulmonary alveolar microlithiasis. The surgical lung biopsy specimen appeared gritty and firm. Histological sections showed diffuse involvement of the lung parenchyma by innumerable tiny calcospherites. Genetic studies showed a homozygous c.316G>C (p.G106R) mutation in exon 4 and confirmed the diagnosis of pulmonary alveolar microlithiasis. The present report aims to contribute to the literature with a pathologically and genetically confirmed new case to add insight into the etiology of this rare disease. This case confirms an autosomal recessive inheritance and does not support the role of non-genetic and other factors in the pathogenesis of pulmonary alveolar microlithiasis.

Research paper thumbnail of Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the   chain gene and other chromosomes

Proceedings of the National Academy of Sciences, 1990

Research paper thumbnail of Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6

Proceedings of the National Academy of Sciences, 1992

Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. E... more Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr viruscarrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus-carrying cells with a lymphoblastoid phenotype including group HI Burkitt lymphoma (BL) lines positive for B-cell activation markers. Transcripts are initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid cell lines and group m BL lines. In group I BL lines, nasopharyngeal carcinoma, and the somatic cell hybrids,

Research paper thumbnail of Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes

Proceedings of the National Academy of Sciences, 1989

Research paper thumbnail of Novel Mutation of Aspartoacylase Gene in a Turkish Patient with Canavan Disease

Journal of Tropical Pediatrics, 2007

Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although thi... more Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although this disease is prevalant among Ashkenazi Jewish population, several cases have been reported from all over the world. Canavan disease is caused by a genetic mutation in aspartoacylase gene. We have identified a novel mutation, a homozygous C432+1G>A mutation, in a 10-month-old boy who has a typical Canavan phenotype (without macrocephaly) accompanied by typical brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and diffusion magnetic resonance findings. The patient's mother was found to be heterozygous for this mutation. We believe that future studies of aspartoacylase gene in various ethnic groups could lead to a better understanding of Canavan's pathophysiology and gene therapy.

Research paper thumbnail of Functional interaction of Oct transcription factors with the family of repeats in Epstein-Barr virus oriP

Journal of General Virology, 2005

The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C ... more The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C promoter (Cp) that controls transcription of six different latent nuclear proteins following interaction with the EBV nuclear protein EBNA1. Here, it was shown that Cp could also be activated by octamer-binding factor (Oct) proteins. Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay. Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells. Cp controlled by the FR was also activated by binding of Oct-2 to the FR. This may have direct implications for B cell-specific regulation of Cp.

Research paper thumbnail of B Cell Phenotype-dependent Expression of the Epstein-Barr Virus Nuclear Antigens EBNA-2 to EBNA-6: Studies with Somatic Cell Hybrids

Journal of General Virology, 1991

Research paper thumbnail of Influence of transforming growth factor-beta (TGF-β) on the immunoglobulin production by EBV-infected B cell cultures

Immunology Letters, 1994

TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a variety of activators,... more TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a variety of activators, including EBV. However, EBV-immortalised cells are refractory to TGF-beta. The influence of TGF-beta on B cell maturation varies, apparently depending on the origin of the B lymphocytes and their maturation/activation state, the strength of the stimulus and the presence of cofactors. We investigated the effect of TGF-beta on immunoglobulin production by 5-day-old EBV-infected B cells. TGF-beta added at the initiation of the cultures inhibited IgM, IgG and IgA secretion by decreasing the numbers of secretory cells. The inhibition of IgM secretion was strongest. At the cytoplasmic level, TGF-beta reduced the expression of IgM heavy, lambda and kappa light chains but not IgG and IgA heavy chains. However, the IgM production by an established EBV-transformed B cell line was not affected by TGF-beta. Thus, TGF-beta inhibited EBV-induced maturation of the B cells until they acquired a transformed state. We discuss the relevance of these findings for the potential role of TGF-beta on EBV infection.

Research paper thumbnail of Meiotic recombinations within major histocompatibility complex of human embryos

Immunogenetics, 2012

We studied the rate and pattern of recombinations within the extended major histocompatibility co... more We studied the rate and pattern of recombinations within the extended major histocompatibility complex (MHC) locus of the human embryos obtained during preimplantation genetic diagnosis (PGD) for HLA compatibility. Recombinant allele frequency was on average 5.33 %, and recombination rate was 0.44 cM/Mb in the 12.2 Mb of the extended MHC locus. Recombination rate varied up to 14-fold (0.19-2.73 cM/Mb) between cases, and maternal recombination rate was on average 3.8 times higher than paternal alleles. More than 69 % of the recombination hot spots were clustered within the extended class II region where the recombination rate was 5.4 times more than that in extended class I region. These findings indicate the potential of PGD to study the mechanisms of linkage disequilibrium within MHC locus of human embryos, demonstrate the recombination characteristics within extended MHC loci of human embryos in comparison to sperm and family studies, and point to the significance of design and interpretation of PGD for HLA compatibility to avoid misdiagnosis because of meiotic recombinations.

Research paper thumbnail of Effect of Transforming Growth Factor-Beta 1 and -Beta 2 on the Proliferation of Burkitt Lymphoma and Lymphoblastoid Cell Lines

Growth Factors, 1991

We tested the effect of transforming growth factor (TGF)-beta 1 and TGF-beta 2 on the proliferati... more We tested the effect of transforming growth factor (TGF)-beta 1 and TGF-beta 2 on the proliferation of human B cell lines. The panel was selected to give information whether (1) their origin, (2) their phenotype, (3) their Epstein-Barr virus (EBV) carrier state, influence their responsiveness. The growth of lymphoblastoid cell lines (LCL) was not inhibited by TGF-beta 1. The EBV-carrying Burkitt lymphoma (BL) lines, Daudi, Jijoye, Rael but not Raji were inhibited. Three EBV-negative BL lines and the majority of their converted sublines were sensitive. The cell lines tested expressed TGF-beta receptors and TGF-beta 1 transcripts. The proliferation of EBV-infected B cells was inhibited by TGF-beta, their sensitivity decreased, however, after 3 days. The results suggest that the activation state of the B cells is decisive for TGF-beta sensitivity and EBV influences it indirectly by changing the cell phenotype.

Research paper thumbnail of Higher pregnancy rates after PGD of monogenic disease combined with HLA typing: single center experience

Fertility and Sterility, 2008

Research paper thumbnail of P0096 It is Not Always Non-Hfe Hemochromatosis in Turkey

European Journal of Internal Medicine, 2009

procedure to reach the exact diagnose, and endoscopic and pathological findings. We also document... more procedure to reach the exact diagnose, and endoscopic and pathological findings. We also documented the refusal of second endoscopy offers and if available the final diagnose. All patients were performed gastroscopy by same endoscopist. Results: In this period 83 patients with gastric ulcer underwent repeat gastroscopy. Average numbers of endoscopy was 2.15. In nine patients, 3 gastroscopy procedures were needed where as only two patients were in need of fourth gastroscopy and no one needed fifth. Seventy-seven of 83 patients were ulcer free at repeat endoscopies. But in 6 (7.2%) patients were shown to have malignant ulcer. Four of them were diagnosed after second endoscopy but two patients' malignancies could be diagnosed at third procedure. Five of the patients had gastric adenocancer and the other single case had gastric lymphoma. Two of 5 (40%) adenocancer were early gastric cancer. Conclusion: Our study re-enforced the recommendation that all patient with gastric ulcers should undergo repeat endoscopy to exclude malignancy. The malignancy rate was 7.2% in our cases. This high rate must encourage clinicians and endoscopist to insist on repeating endoscopy to assess ulcer healing.

Research paper thumbnail of BRAFV600E mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness

Endocrine, 2012

Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK p... more Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK pathway plays an important role in the development of several cancers. BRAF which is a member of Raf-kinase family activates this way. BRAF gene activating mutations lead to neoplastic transformation in thyroid follicle cells. In PTC, this mutation itself is a poor prognostic sign independent of other clinicopathological characteristics. We evaluated BRAF(V600E) mutation and clinical-pathological characteristics in Turkish population with PTC. We assessed 109 patients with PTC (88 female, 21 male). The average age was 38.7 ± 9.9 (17-71). BRAF(V600E) mutation was detected using polymerase chain reaction and fluorescent melting curve analysis. The results show that BRAF(V600E) mutation rate was found in 39.45% of our patients. We observed that BRAF(V600E) mutation was significantly higher in men, in tumors larger than 1 cm in size, and in patients with classical PTC. Moreover, statistically significant correlations of BRAF(V600E) with indicators of tumor aggressiveness such as thyroid capsular invasion, multifocality, lymph node metastasis, and extrathyroidal spread were found. Patient groups below and over the age of 45 did not differ in mutation frequency. Patients with micro-PTC were evaluated separately, it was found that BRAF(V600E) mutation was more frequent in the classic type and that lymph node metastasis rate significantly increased when the mutation was present. We concluded that BRAF(V600E) was correlated with indicators of tumor aggressiveness in our study population. This fact is taken into consideration in treatment and follow-up of our patients with PTC and positive BRAF(V600E) mutation.

Research paper thumbnail of Mutations in Influenza A Virus (H5N1) and Possible Limited Spread, Turkey, 2006

Emerging Infectious Diseases, 2008

We report mutations in infl uenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. F... more We report mutations in infl uenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. Four novel amino acid changes (Q447L, N556K, and R46K in RNA polymerase and S133A in hemagglutinin) were detected in virus isolates from 2 siblings who died.