Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and uns... more Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and unsteady biotinidase activity. Increasing enzyme activity and maturation throughout childhood. This study aims to reveal the course of biotinidase activities in a long-term follow-up period and concordance with their genotypes .Participants/Methods: A total of 1,773 biotinidase enzyme (BT) activity measurements were performed in 711 newborns with variants in the BTD gene over a 4-year follow-up period. Biochemical phenotyping was classified into four groups based on the highest measured enzyme activity level during the follow-up: Profound(≤10%), Partial(10.1-30%), Heterozygous(30.1-66.5%), and Normal(>66.6%). Results: The number of participants with BTD in the biochemical phenotype groups assigned based on the first measurement was 59, 217, 314, and 121 in the profound, partial, heterozygous, and normal groups respectively. Based on the highest measurement value during follow-up, the num...
Although it is known that there is generally a good correlation between genotypes and phenotypes,... more Although it is known that there is generally a good correlation between genotypes and phenotypes, the number of studies reporting discrepancies has recently increased, exclusively between milder genotypes and their phenotypes due to the complex nature of the CYP21A2 gene and methodological pitfalls. This study aimed to assess CYP21A2 genotyping in children with 21-hydroxylase deficiency (21-OHD) and establish their predictive genotype–phenotype correlation features using a large cohort in Southeastern Anatolia’s ethnically diverse population. The patients were classified into three groups: salt-wasting (SW), simple virilizing (SV) and non-classical (NC). The genotypes were categorized into six groups due to residual enzyme activity: null–A–B–C–D–E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes. A total of 118 unrelated children with 21-OHD were included in this study (61% SW, 24.5% SV and 14.5% NC). The pathogenic variants were found in 79.5% of 171 mutated alleles (60.2%, 22.2%, and 17.6% in SW, SV and NC, respectively). Patient distribution based on genotype groups was as follows: null—16.1%, A—41.4%, B—6.0%, C—14.4%, E—22%). In2G was the most common pathogenic variant (33.9% of all alleles) and the most common variant in the three phenotype groups (SW—38.8%, SV—22.2% and NC—23.3%). The total genotype–phenotype correlation was 81.5%. The correlations of the null and A groups were 100% and 76.1%, respectively, while it was lower in group B and poor in group C (71.4% and 23.5%, respectively). This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.
Background/Aim: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and th... more Background/Aim: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and the regulation of innate and adaptive immune system functions. Biotinidase deficiency (BTD) leads to impairment in biotin-dependent immune functions. This study focused on immunophenotypic analysis of lymphocyte subsets in newborns with BTD. Patients and Methods: A total of 181 (95 female and 86 male; 114 with BTD and 67 healthy) newborns underwent biotinidase enzyme activity, molecular, and lymphocyte immunophenotyping analyses. BTD is classified into four biochemical phenotypes: profound, partial, heterozygous, and normal. The following lymphocyte subsets were studied in all participants: total B lymphocyte (CD19), total T lymphocyte (CD3), helper T lymphocyte (CD3/CD4), cytotoxic T lymphocyte Accepted Article This article is protected by copyright. All rights reserved (CTL) (CD3/CD8), natural killer T lymphocyte (CD16/56), and a T lymphocyte activation marker (HLA-DR). Results: The percentages of lymphocyte subsets were similar in newborns with and without BTD. In all newborns with BTD, the mean CD3/CD4 levels were higher in females, while the CD3/CD8 levels were higher in males (p<0.001for each). In female and male newborns, the CD3/CD4 levels were 53.83±9.46 and 16.82±5.19, respectively, and the CD3/CD8 levels were 48.80±8.65 and 21.48±6.02, respectively. A moderate negative correlation was found between CD3/CD4 and CD3/CD8 in female and male newborns (r female =-0.488, r male =-0.574, p <0.001). Conclusion: This study showed that although there were no differences in the lymphocyte subsets in newborns with BTD, the CD3/CD4 levels were higher in females, and the CD3/CD8 levels were higher in males. In addition, there was a negative correlation between the CD3/CD4 and CD3/CD8 levels in both genders. Although these results indicate sexual dimorphism between CD3/CD4 and CD3/CD8 levels, whether this dissociation is unique to BTD in newborns is not fully clear.
Consent to participate Authors declare that informed consent was obtained from all mothers for th... more Consent to participate Authors declare that informed consent was obtained from all mothers for the study. Consent for publication: Parents have signed an consent publication form to use their data. We also declare that these forms were held by the treating institution.
Maturity‐onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes beca... more Maturity‐onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes because it is overlooked due to atypical clinical presentations. This study aims to reveal the clinical and laboratory clues and examine their compatibility with MODY genotypes.
Acute Myeloid Leukemia (AML) is a hematopoietic stem cell disorder. Many of the tumor development... more Acute Myeloid Leukemia (AML) is a hematopoietic stem cell disorder. Many of the tumor development steps are processes regulated by Ca2+ dependent signaling pathways found in tumor growth. Calcium channels, which can be blocked by pharmacological agents such as verapamil, are important in the regulation of intracellular Ca2+ homeostasis. The failure to stop cell cycle and to achieve programmed cell death are the most important factors in AML or other types of cancers and are considered to be the real cause of cancer. Our aim in this study was to investigate the effect of verapamil on apoptosis and cell cycle in AML cell line, HL-60, using flow cytometry. The effective dose of verapamil was determined as 50 mg / ml by MTT method, and was applied to HL-60 cells, subsequently, they were assessed for apoptosis and cell cycle. After 50 mg / ml of verapamil application, apoptotic cell ratio was found to be 77.7% after 24 hours (p< 0.05). In cell cycle analysis, the ratio of diploid cell...
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Shift to night preference in the circadian rhythm was higher and this preference was associated with attention deficit in the children with ADHD. The presence of psychopathology in the family and the mother's psychopathology affected the miR-142-3p and miR378 levels No statisticaly significant difference between the ADHD group and controls in terms of the associated miRNA levels
ABSTRACT Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by ... more ABSTRACT Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment.
Pterygium is a benign fibrovascular proliferation that develops from the conjunctiva and invades ... more Pterygium is a benign fibrovascular proliferation that develops from the conjunctiva and invades the cornea. The etiology of this disorder remains unclear. Current treatment of pterygium is surgical. The postoperative recurrence rate of pterygium is reported be high. To the best of our knowledge, these results are the first to demonstrate the contribution of proteins expressions of the small GTPase Rho proteins in patients with pterygium. Our data showed that leukocyte RhoA, RhoB, RhoD, and RhoE protein expressions were markedly elevated in primary pterygium. However, no significant modifications were noted in pterygial tissues.
Pterygium is one of the most common ocular surface diseases, and characterized by inflammatory in... more Pterygium is one of the most common ocular surface diseases, and characterized by inflammatory infiltrates, proliferation, fibrosis, angiogenesis, and extracellular matrix breakdown. We investigated the association of polymorphisms in the RHO genes RHOA, RHOB, RHOC, RHOD, and RND3 (RHOE). The results of this study demonstrate for the first time the association of RHO genes with the pterygium. We displayed that the RHO gene polymorphisms were significantly associated with pterygium in the Turkish population.
Journal of Clinical and Experimental Investigations, 2016
Introduction: Beta-thalassemia is the most common autosomal recessive disease. More than 200 diff... more Introduction: Beta-thalassemia is the most common autosomal recessive disease. More than 200 different mutations determined in beta-globin gene. Beta thalassemia disease has a severe clinical picture. Treatment of the diseases should be maintained properly otherwise quality of life and life period can be affected. In this study, we tried to reveal inherited beta-thalassemia mutations in surrounding areas of Gaziantep. In this study, we included 208 patients who applied with beta -thalassemia suspicion to the pediatric hematology clinic (age range 4-14). In that study, 138 patients with homozygous mutations and 70 patients' heterozygous mutations were identified. HBB gene was sequenced by Sanger DNA Sequencing method. Results: Most common homozygote mutations are IVS I-110 G>A, IVS I-1 G>A, IVS II-1 G>A, the heterozygote mutations are IVS I-110 G>A, IVS II-1 G>A, codon 8 (AA) del. The incidence of IVS 1.110 (G>A) mutation is 24%, 28 in homozygote patients, 29.7% in heterozygote patients. The 8% homozygote patients and 19.7% heterozygote patients were effected with IVS 1.110 (G>A) mutation. The consanguinity marriages are very abundant particularly in our region due to fact that we are able to see many autosomal recessive diseased in our region. Reducing incidence of autosomal recessive disease by given genetic counseling could help the solution but it is still a major problem.
Arteriyel hipertansiyon, obezite, dislipidemi veya diabetes mellitus gibi kardiyovasküler hastalı... more Arteriyel hipertansiyon, obezite, dislipidemi veya diabetes mellitus gibi kardiyovasküler hastalık (CVD) risk faktöleri ve buna ek olarak, miyokard infarktüsü, koroner arter hastalığı veya inme, tekrarlayan düşüklerin de dahil olduğu CVD’ler en yaygın hastalıklardır ve tüm dünyadaki ana ölüm sebeplerini oluşturmaktadırlar. Bu çalışmaya 2010-2013 yılları arasında Türkiye’nin güneydoğu bölgesinde CVD paneli uygulanmış birbirinden bağımsız 4.709 hasta dahil edilmiştir. Metodolojik olarak, bu hastalardan elde edilen kan örneklerinden DNA izolasyonu gerçekleştirilmiştir. Mutasyon analizi, CVD panelinde bulunan altı yaygın mutasyonu (Faktör VG1691A, Protrombin G20210A, Faktör XIII V34L, MTHFR A1298C, MTHFR C677T ve PAI-1 -675 4G/5G) taramak amacıyla real-time PCR reaksiyonu (RT-PCR) metodu kullanılarak yapılmıştır. Bu mutasyonların sıklığı homozigot formda sırasıyla sırasıyla % 0,57, % 0,25, % 2,61, % 13,78, % 9,34 ve % 24,27 olarak tespit edildi. Benzer şekilde, bu mutasyonların heterozi...
Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia o... more Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010– 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction (RT-PCR) method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 -675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57%, 0.25%, 2.61%, 13.78%, 9.34% and 24.27% in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43%, 3.44%, 24.91%, 44.94%, 41.09% and 45.66%, respectively. No mutation was d...
The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer ... more The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The antiestrogen tamoxifen gains agonistic property by transactivating ERα. PAK1-mediated phosphorylation of serine 305 (S305) of ERα leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ERα-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3′ UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory in our department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer.
Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia o... more Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in southeast part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the realtime polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1-675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66 %, respectively. No mutation was detected in 92 (1.95 %) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in southeast region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.
Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 2491... more Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 249100), particularly common in populations of Mediterranean extraction. MEFV gene, responsible for FMF, encoding pyrin has recently been mapped to chromosome 16p13.3. In the present study, 3,341 unrelated patients with the suspicion of FMF in south-east part of Turkey between the years 2009 and 2013 were enrolled and genomic sequences of exon 2 and exon 10 of the MEFV gene were scanned for mutations by direct sequencing. We identified 43 different type of mutations and 9 of them were novel. DNA was amplified by PCR and subjected to direct sequencing for the detection of MEFV gene mutations. Among the 3,341 patients, 1,598 (47.8 %) were males and 1,743 (52.1 %) were females. The mutations were heterozygous in 806 (62.3 %), compound heterozygous in 188 (14.5 %), homozygous in 281 (21.8 %) and mutations had complex genotype in 17 (1.32 %) patients. No mutation was detected in 2,051 (61.4 %) patients. The most frequent mutations were M694V, E148Q, M680I(G/C) and V726A. We could not find any significant differences between the two common mutations according to the gender. Molecular diagnosis of MEFV is a useful tool in clinical practice, thus a future study relating to genotype/phenotype correlation of FMF in more and larger group in Turkish population involving the whole MEFV gene mutations is necessary.
sinde; tümör baskılayıcı genler ve deoksiribonükleik asit (DNA) tamir mekanizması genlerini hedef... more sinde; tümör baskılayıcı genler ve deoksiribonükleik asit (DNA) tamir mekanizması genlerini hedef alan mutasyonların etkisiyle beraber artan yaş, beslenme alışkanlıkları, sedanter yaşam, obezite, inflamatuvar barsak hastalıkları GİRİŞ Kolorektal kanserler dünya genelinde en yaygın üçüncü kanser olup, kanserden kaynaklanan ölümler arasında dördüncü sıradadır. Kansere bağlı ölümlerin ise yaklaşık %10'unu oluşturur (1). Kolorektal kanser etiyopatoloji
Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and uns... more Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and unsteady biotinidase activity. Increasing enzyme activity and maturation throughout childhood. This study aims to reveal the course of biotinidase activities in a long-term follow-up period and concordance with their genotypes .Participants/Methods: A total of 1,773 biotinidase enzyme (BT) activity measurements were performed in 711 newborns with variants in the BTD gene over a 4-year follow-up period. Biochemical phenotyping was classified into four groups based on the highest measured enzyme activity level during the follow-up: Profound(≤10%), Partial(10.1-30%), Heterozygous(30.1-66.5%), and Normal(>66.6%). Results: The number of participants with BTD in the biochemical phenotype groups assigned based on the first measurement was 59, 217, 314, and 121 in the profound, partial, heterozygous, and normal groups respectively. Based on the highest measurement value during follow-up, the num...
Although it is known that there is generally a good correlation between genotypes and phenotypes,... more Although it is known that there is generally a good correlation between genotypes and phenotypes, the number of studies reporting discrepancies has recently increased, exclusively between milder genotypes and their phenotypes due to the complex nature of the CYP21A2 gene and methodological pitfalls. This study aimed to assess CYP21A2 genotyping in children with 21-hydroxylase deficiency (21-OHD) and establish their predictive genotype–phenotype correlation features using a large cohort in Southeastern Anatolia’s ethnically diverse population. The patients were classified into three groups: salt-wasting (SW), simple virilizing (SV) and non-classical (NC). The genotypes were categorized into six groups due to residual enzyme activity: null–A–B–C–D–E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes. A total of 118 unrelated children with 21-OHD were included in this study (61% SW, 24.5% SV and 14.5% NC). The pathogenic variants were found in 79.5% of 171 mutated alleles (60.2%, 22.2%, and 17.6% in SW, SV and NC, respectively). Patient distribution based on genotype groups was as follows: null—16.1%, A—41.4%, B—6.0%, C—14.4%, E—22%). In2G was the most common pathogenic variant (33.9% of all alleles) and the most common variant in the three phenotype groups (SW—38.8%, SV—22.2% and NC—23.3%). The total genotype–phenotype correlation was 81.5%. The correlations of the null and A groups were 100% and 76.1%, respectively, while it was lower in group B and poor in group C (71.4% and 23.5%, respectively). This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.
Background/Aim: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and th... more Background/Aim: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and the regulation of innate and adaptive immune system functions. Biotinidase deficiency (BTD) leads to impairment in biotin-dependent immune functions. This study focused on immunophenotypic analysis of lymphocyte subsets in newborns with BTD. Patients and Methods: A total of 181 (95 female and 86 male; 114 with BTD and 67 healthy) newborns underwent biotinidase enzyme activity, molecular, and lymphocyte immunophenotyping analyses. BTD is classified into four biochemical phenotypes: profound, partial, heterozygous, and normal. The following lymphocyte subsets were studied in all participants: total B lymphocyte (CD19), total T lymphocyte (CD3), helper T lymphocyte (CD3/CD4), cytotoxic T lymphocyte Accepted Article This article is protected by copyright. All rights reserved (CTL) (CD3/CD8), natural killer T lymphocyte (CD16/56), and a T lymphocyte activation marker (HLA-DR). Results: The percentages of lymphocyte subsets were similar in newborns with and without BTD. In all newborns with BTD, the mean CD3/CD4 levels were higher in females, while the CD3/CD8 levels were higher in males (p<0.001for each). In female and male newborns, the CD3/CD4 levels were 53.83±9.46 and 16.82±5.19, respectively, and the CD3/CD8 levels were 48.80±8.65 and 21.48±6.02, respectively. A moderate negative correlation was found between CD3/CD4 and CD3/CD8 in female and male newborns (r female =-0.488, r male =-0.574, p <0.001). Conclusion: This study showed that although there were no differences in the lymphocyte subsets in newborns with BTD, the CD3/CD4 levels were higher in females, and the CD3/CD8 levels were higher in males. In addition, there was a negative correlation between the CD3/CD4 and CD3/CD8 levels in both genders. Although these results indicate sexual dimorphism between CD3/CD4 and CD3/CD8 levels, whether this dissociation is unique to BTD in newborns is not fully clear.
Consent to participate Authors declare that informed consent was obtained from all mothers for th... more Consent to participate Authors declare that informed consent was obtained from all mothers for the study. Consent for publication: Parents have signed an consent publication form to use their data. We also declare that these forms were held by the treating institution.
Maturity‐onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes beca... more Maturity‐onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes because it is overlooked due to atypical clinical presentations. This study aims to reveal the clinical and laboratory clues and examine their compatibility with MODY genotypes.
Acute Myeloid Leukemia (AML) is a hematopoietic stem cell disorder. Many of the tumor development... more Acute Myeloid Leukemia (AML) is a hematopoietic stem cell disorder. Many of the tumor development steps are processes regulated by Ca2+ dependent signaling pathways found in tumor growth. Calcium channels, which can be blocked by pharmacological agents such as verapamil, are important in the regulation of intracellular Ca2+ homeostasis. The failure to stop cell cycle and to achieve programmed cell death are the most important factors in AML or other types of cancers and are considered to be the real cause of cancer. Our aim in this study was to investigate the effect of verapamil on apoptosis and cell cycle in AML cell line, HL-60, using flow cytometry. The effective dose of verapamil was determined as 50 mg / ml by MTT method, and was applied to HL-60 cells, subsequently, they were assessed for apoptosis and cell cycle. After 50 mg / ml of verapamil application, apoptotic cell ratio was found to be 77.7% after 24 hours (p< 0.05). In cell cycle analysis, the ratio of diploid cell...
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Shift to night preference in the circadian rhythm was higher and this preference was associated with attention deficit in the children with ADHD. The presence of psychopathology in the family and the mother's psychopathology affected the miR-142-3p and miR378 levels No statisticaly significant difference between the ADHD group and controls in terms of the associated miRNA levels
ABSTRACT Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by ... more ABSTRACT Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment.
Pterygium is a benign fibrovascular proliferation that develops from the conjunctiva and invades ... more Pterygium is a benign fibrovascular proliferation that develops from the conjunctiva and invades the cornea. The etiology of this disorder remains unclear. Current treatment of pterygium is surgical. The postoperative recurrence rate of pterygium is reported be high. To the best of our knowledge, these results are the first to demonstrate the contribution of proteins expressions of the small GTPase Rho proteins in patients with pterygium. Our data showed that leukocyte RhoA, RhoB, RhoD, and RhoE protein expressions were markedly elevated in primary pterygium. However, no significant modifications were noted in pterygial tissues.
Pterygium is one of the most common ocular surface diseases, and characterized by inflammatory in... more Pterygium is one of the most common ocular surface diseases, and characterized by inflammatory infiltrates, proliferation, fibrosis, angiogenesis, and extracellular matrix breakdown. We investigated the association of polymorphisms in the RHO genes RHOA, RHOB, RHOC, RHOD, and RND3 (RHOE). The results of this study demonstrate for the first time the association of RHO genes with the pterygium. We displayed that the RHO gene polymorphisms were significantly associated with pterygium in the Turkish population.
Journal of Clinical and Experimental Investigations, 2016
Introduction: Beta-thalassemia is the most common autosomal recessive disease. More than 200 diff... more Introduction: Beta-thalassemia is the most common autosomal recessive disease. More than 200 different mutations determined in beta-globin gene. Beta thalassemia disease has a severe clinical picture. Treatment of the diseases should be maintained properly otherwise quality of life and life period can be affected. In this study, we tried to reveal inherited beta-thalassemia mutations in surrounding areas of Gaziantep. In this study, we included 208 patients who applied with beta -thalassemia suspicion to the pediatric hematology clinic (age range 4-14). In that study, 138 patients with homozygous mutations and 70 patients' heterozygous mutations were identified. HBB gene was sequenced by Sanger DNA Sequencing method. Results: Most common homozygote mutations are IVS I-110 G>A, IVS I-1 G>A, IVS II-1 G>A, the heterozygote mutations are IVS I-110 G>A, IVS II-1 G>A, codon 8 (AA) del. The incidence of IVS 1.110 (G>A) mutation is 24%, 28 in homozygote patients, 29.7% in heterozygote patients. The 8% homozygote patients and 19.7% heterozygote patients were effected with IVS 1.110 (G>A) mutation. The consanguinity marriages are very abundant particularly in our region due to fact that we are able to see many autosomal recessive diseased in our region. Reducing incidence of autosomal recessive disease by given genetic counseling could help the solution but it is still a major problem.
Arteriyel hipertansiyon, obezite, dislipidemi veya diabetes mellitus gibi kardiyovasküler hastalı... more Arteriyel hipertansiyon, obezite, dislipidemi veya diabetes mellitus gibi kardiyovasküler hastalık (CVD) risk faktöleri ve buna ek olarak, miyokard infarktüsü, koroner arter hastalığı veya inme, tekrarlayan düşüklerin de dahil olduğu CVD’ler en yaygın hastalıklardır ve tüm dünyadaki ana ölüm sebeplerini oluşturmaktadırlar. Bu çalışmaya 2010-2013 yılları arasında Türkiye’nin güneydoğu bölgesinde CVD paneli uygulanmış birbirinden bağımsız 4.709 hasta dahil edilmiştir. Metodolojik olarak, bu hastalardan elde edilen kan örneklerinden DNA izolasyonu gerçekleştirilmiştir. Mutasyon analizi, CVD panelinde bulunan altı yaygın mutasyonu (Faktör VG1691A, Protrombin G20210A, Faktör XIII V34L, MTHFR A1298C, MTHFR C677T ve PAI-1 -675 4G/5G) taramak amacıyla real-time PCR reaksiyonu (RT-PCR) metodu kullanılarak yapılmıştır. Bu mutasyonların sıklığı homozigot formda sırasıyla sırasıyla % 0,57, % 0,25, % 2,61, % 13,78, % 9,34 ve % 24,27 olarak tespit edildi. Benzer şekilde, bu mutasyonların heterozi...
Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia o... more Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010– 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction (RT-PCR) method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 -675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57%, 0.25%, 2.61%, 13.78%, 9.34% and 24.27% in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43%, 3.44%, 24.91%, 44.94%, 41.09% and 45.66%, respectively. No mutation was d...
The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer ... more The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The antiestrogen tamoxifen gains agonistic property by transactivating ERα. PAK1-mediated phosphorylation of serine 305 (S305) of ERα leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ERα-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3′ UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory in our department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer.
Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia o... more Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in southeast part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the realtime polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1-675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66 %, respectively. No mutation was detected in 92 (1.95 %) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in southeast region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.
Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 2491... more Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 249100), particularly common in populations of Mediterranean extraction. MEFV gene, responsible for FMF, encoding pyrin has recently been mapped to chromosome 16p13.3. In the present study, 3,341 unrelated patients with the suspicion of FMF in south-east part of Turkey between the years 2009 and 2013 were enrolled and genomic sequences of exon 2 and exon 10 of the MEFV gene were scanned for mutations by direct sequencing. We identified 43 different type of mutations and 9 of them were novel. DNA was amplified by PCR and subjected to direct sequencing for the detection of MEFV gene mutations. Among the 3,341 patients, 1,598 (47.8 %) were males and 1,743 (52.1 %) were females. The mutations were heterozygous in 806 (62.3 %), compound heterozygous in 188 (14.5 %), homozygous in 281 (21.8 %) and mutations had complex genotype in 17 (1.32 %) patients. No mutation was detected in 2,051 (61.4 %) patients. The most frequent mutations were M694V, E148Q, M680I(G/C) and V726A. We could not find any significant differences between the two common mutations according to the gender. Molecular diagnosis of MEFV is a useful tool in clinical practice, thus a future study relating to genotype/phenotype correlation of FMF in more and larger group in Turkish population involving the whole MEFV gene mutations is necessary.
sinde; tümör baskılayıcı genler ve deoksiribonükleik asit (DNA) tamir mekanizması genlerini hedef... more sinde; tümör baskılayıcı genler ve deoksiribonükleik asit (DNA) tamir mekanizması genlerini hedef alan mutasyonların etkisiyle beraber artan yaş, beslenme alışkanlıkları, sedanter yaşam, obezite, inflamatuvar barsak hastalıkları GİRİŞ Kolorektal kanserler dünya genelinde en yaygın üçüncü kanser olup, kanserden kaynaklanan ölümler arasında dördüncü sıradadır. Kansere bağlı ölümlerin ise yaklaşık %10'unu oluşturur (1). Kolorektal kanser etiyopatoloji
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