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O Yegin

Publications and source records attributed to O Yegin.

At least 19 recordsLinked to original sources

TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behçet's disease.

BACKGROUND: Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play an important role in development of the disease. The tumour necrosis factor (TNF)-alpha gene, which is closely linked to the HLA-B51 gene, is involved in susceptibility for BD. Recently, a polymorphism at position -1031 within the TNF-alpha promoter region was demonstrated to be responsible for susceptibility to BD in a British population. However, the functional effects of this polymorphism have not yet been determined. OBJECTIVES: To investigate the possible relation of the TNF-alpha-1031 T/C polymorphism with susceptibility to BD in a Turkish population and to determine the functional importance of this polymorphism. METHODS: Ninety-nine unrelated patients (47 women, 52 men; mean +/- SD age, 34.10 +/- 10.53 years) with BD and 103 ethnically matched healthy controls (52 males, 51 females; mean +/- SD age, 40.25 +/- 14.15) were enrolled in the study. For genotyping, polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis was employed. The functional importance of TNF-alpha-1031 T/C polymorphism was determined with an enzyme-linked immunospot (ELISPOT) assay. For this purpose, mononuclear cells obtained from BD patients and controls were analysed for TNF-alpha and interferon (IFN)-gamma production. RESULTS: A significant difference was observed between BD patients and controls with respect to the allele frequency of TNF-alpha-1031C [P = 0.018, OR = 1.83, 95% confidence interval (CI) = 1.07-3.13]. When the allele frequencies were analysed according to the clinical features, the T allele in patients with positive skin pathergy test (SPT) was significantly increased when compared with those of patients without these findings (P = 0.004, OR = 2.75, 95% CI = 1.3-5.86). To demonstrate the frequency of TNF-alpha and IFN-gamma producing cells, mononuclear cells from four representative individuals of each genotype were used and the spontaneous and stimulated TNF-alpha and IFN-gamma values (spot numbers) were analysed. Compared with the control groups, a significant increase was observed in the number of cells producing TNF-alpha obtained from BD patients (P < 0.001). Moreover, the stimulation index for TNF-alpha [bacterial lipopolysaccharide (LPS) stimulated/unstimulated] was higher for the CC genotype (9 +/- 9.5) with respect to the other genotypes (TT; 1.3 +/- 0.3 and TC; 1.2 +/- 0.2). While the difference in the spontaneous IFN-gamma values between groups were not statistically significant, the stimulated IFN-gamma values were found to be significantly increased in the BD group when compared with the healthy control group (P = 0.004). CONCLUSIONS: Our results showed that, in the Turkish population the TNF-alpha-1031C allele is associated with susceptibility to BD. On the other hand, carrying the T allele may render patients more prone to developing a positive skin pathergy test. In addition, ELISPOT assays revealed that BD patients exhibited a significantly higher number of mononuclear cells producing TNF-alpha, and cells obtained from patients with a CC genotype had a stronger response to LPS stimulation. The strong IFN-gamma response upon LPS stimulation in BD patients supports the previous findings that BD is a Th1 driven disease. These findings suggest that the TNF-alpha-1031 polymorphism may have a functional effect and could explain the reason for high levels of TNF-alpha production observed in BD patients.

Adult↗

Toll-like receptor 2 Arg753Gln gene polymorphism in Turkish patients with Behçet's disease.

Having considered the impact of the function of TLR2 in the recognition of several microorganisms that are thought to have an association with Behçet's disease (BD), we aimed to determine a possible association between the TLR2 Arg753Gln polymorphism and susceptibility to BD. We genotyped 83 patients with BD, 95 ethnically matched healthy controls, 12 patients with recurrent aphthous stomatitis (RAS) and 21 patients with rheumatoid arthritis (RA) by restriction fragment length polymorphism after PCR amplification of the genomic region encompassing the polymorphic site. Comparison of the TLR2 Arg753Gln A allele and A/G genotype frequencies did not show a significant difference between patients with BD and healthy controls (1.2% vs. 0.6%, and 2.1% vs. 1.1%, respectively). None of the patients from the RAS and RA groups had the A allele or A/G genotype. Our results indicate that the TLR2 Arg753Gln polymorphism does not play a role in the aetiopathogenesis of BD.

Adult↗

Simvastatin therapy in lymphocyte cross-match-positive kidney transplantation candidates.

OBJECTIVES: Recent identification of several mechanisms by which statins decrease recruitment of monocytes and T cells into the arterial wall and inhibit both T-cell and B-cell activation and proliferation in vitro prompted us to study the immunomodulatory effects of statins. In this study, we examined the effect of simvastatin therapy on lymphocyte cross-match positivity in kidney transplantation candidates. METHODS: Simvastatin therapy (20 mg/d) was administered to 25 patients (18 men, 7 women of mean age 34 +/- 11.7 years who displayed positive lymphocyte cross-matches between July 2002 and October 2004. The etiologies of end-stage renal disease were vesicoureteral reflux (n = 5), urinary stone disease (n = 4), glomerulonephritis (n = 6), amyloidosis secondary to familial Mediterranean fever (n = 1), and unknown (n = 9). RESULTS: The lymphocyte cross-match became negative in 10 patients 4-9 months, and successful kidney transplantation was performed in 6 of them. The serum creatinine levels of these patients ranged between 0.8 and 1.4 mg/dL. Two patients required higher doses, but none suffered from adverse effects. The remaining 4 patients are still undergoing pretransplantation evaluation. CONCLUSION: Simvastatin therapy seems to be a cost-effective and useful method for lymphocyte cross-match-positive kidney transplantation candidates compared with immunoadsorption or intravenous immunoglobulin use.

Adult↗

CTLA-4 gene 49A/G polymorphism in Turkish patients with Behçet's disease.

Genetic factors predisposing individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. Patients with BD exhibit elevated levels of pro-inflammatory cytokines, and affected organs show a significant neutrophil and lymphocyte infiltration. Current evidence suggests that the activated lymphocytes contribute to neutrophil and endothelial cell activation in these patients. The cytotoxic T lymphocyte-associated antigen (CTLA)-4 molecule plays an important role in immune regulation by downregulating T-cell activation, and the CTLA-4 49A/G polymorphism in the exon 1 has been shown to be associated with a number of autoimmune diseases. In an attempt to demonstrate whether there is an association of the CTLA-4 49A/G polymorphism with BD in the Turkish population, we genotyped 59 Turkish patients and 99 healthy individuals for single-nucleotide polymorphisms. For this purpose, genomic DNA was obtained from the peripheral blood of individuals and the region of interest was amplified using PCR. Genotyping was performed using the BbvI restriction endonuclease. It was shown that the distribution of the CTLA-4 exon 1 49A/G allele and genotype frequencies did not differ between patients with BD and healthy controls. However, allele and genotype frequencies of CTLA-4 49 A and A/A were significantly higher in patients with ocular involvement compared with patients without these symptoms (90.6% vs. 65.1%, odds ratio (OR) = 9.67, P = 0.011; and 81.25% vs. 39.5%, OR = 9.56, P = 0.015, respectively). A statistically significant difference in the A allele frequency was observed in patients with erythema nodosum-like lesions (86.1% vs. 65.8%, OR = 6.24, P = 0.04). There was also an increase in A/A genotype frequency, but the difference was not statistically significant (72.2% vs. 41.5%, OR = 6.5, P = 0.068). Our data suggest that BD patients with ocular involvement and erythema nodosum-like lesions have a higher frequency of both the A allele and the A/A genotype at position 49 of exon 1 of CTLA-4. These results may also indicate that CTLA-4 is a disease-modifying rather than a susceptibility gene for BD.

Adult↗

The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease.

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04- and 1.60-fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.

Adult↗

Peripheral blood stem cell transplantation in children with beta-thalassemia.

Fifteen patients with beta-thalassemia received an allogeneic peripheral blood stem cell transplant. Median age was 3.5 years (1-15 years). Six were class I, four class II and five class III according to the Pesaro criteria. All of the donors were HLA-phenotypically identical (13 siblings and two parents). Nine patients were given BU + CY and six BU + CY plus ATG as conditioning. All patients received MTX (+1, +3, +6) and CsA (9-12 months) post transplant for GVHD prophylaxis. The median neutrophil and platelet engraftment times were day 12 and day 16, respectively. cGVHD was observed in three patients. Two patients died. Thirteen patients are well, and transfusion-independent 2-30 months after PSCT. No recurrences of thalassemia have been seen. Overall and event-free survival were 86.6%. In conclusion, we suggest that PSCT can be considered a safe and effective treatment for children with beta- thalassemia.

Adolescent↗

Interleukin-1beta, interleukin-1 receptor antagonist levels in patients with subacute sclerosing panencephalitis and the effects of different treatment protocols.

Subacute sclerosing panencephalitis is a rare progressive inflammatory disease of the central nervous system caused by a persistent aberrant measles virus infection. Cytokines are polypeptides that regulate immune responses and inflammatory reactions. Interleukin-1beta has been implicated as a central mediator of tissue damage and destruction in a number of central nervous system diseases. Interleukin-1 receptor antagonist could function as an important anti-inflammatory cytokine. We studied interleukin-1beta and interleukin-1 receptor antagonist levels in the cerebrospinal fluids of patients with subacute sclerosing panencephalitis and evaluated the effects of different treatment protocols on these cytokines. Interleukin-1beta and interleukin-1 receptor antagonist levels were measured in 15 patients who had a recent diagnosis of subacute sclerosing panencephalitis (group 1), 6 patients who had been treated with isoprinosine (group 2), 5 patients with intraventricular interferon-alpha (group 3), and 6 patients with interferon-beta (group 4). The results were compared within the groups and also with the results of 10 patients with other neurologic disease (group 5). The interleukin-1beta concentrations in cerebrospinal fluid and sera were all below the detection limits (3.9 pg/mL). Interleukin-1 receptor antagonist levels were not statistically different, except for the group treated with intraventricular interferon-alpha. Interleukin-1 receptor antagonist levels were 170 +/- 52, 175 +/- 58, 1605 +/- 518, 77.5 +/- 24, and 108 +/- 18 pg/mL in groups 1 to 5, respectively. Interleukin-1 receptor antagonist levels and cerebrospinal fluid serum ratios were significantly increased during interferon-alpha treatment. In conclusion, interleukin-1 and interleukin-1 receptor antagonist levels were not elevated in the patients with subacute sclerosing panencephalitis. The only treatment protocol that affects interleukin-1 receptor antagonist levels in cerebrospinal fluid was intraventricular interferon-alpha. Further studies on higher numbers of patients may better document the immunologic status of patients with subacute sclerosing panencephalitis and the effects of different treatment modes.

Administration, Oral↗

Peripheral stem cell transplantation in a child with amegakaryocytic thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an unusual cause of thrombocytopenia without radial or other congenital anomalies in the newborn. Generalized bone marrow dysfunction developing later in life has been reported. We present a 13-month-old girl who was diagnosed as having congenital amegakaryocytic thrombocytopenia and was successfully treated with allogeneic peripheral stem cell transplantation (PSCT) from her fully matched sibling donor. The neutrophil engraftment was on post transplant day 12 and platelet engraftment was on day 14. Her last hemogram revealed platelets of 168 x 10(9)/l 20 months post transplant.

Female↗

Stem cell factor (SCF) levels in newborns.

We studied Stem cell factor (SCF) levels in 15 mother-newborn pairs, 15 healthy adult controls, and 16 newborn with bacterial sepsis. SCF levels were also determined in six newborns with sepsis before and after completion of treatment. SCF levels (pg/mL) were found to be 2141 +/- 529 in cord blood, 1385 +/- 314 in mothers, 1546 +/- 443 in healthy adult controls, and 1742 +/- 655 in septic newborns. Cord blood SCF levels were significantly higher than their mothers' and healthy controls (p < 0.05). There were no differences in SCF levels between mothers and healthy adult controls. No correlation was found between the SCF levels and absolute neutrophil counts. There were no differences in SCF levels between the before and after treatment levels in six newborn with sepsis. In conclusion, our study suggests that SCF levels were increased in cord blood, and this increase is not a reflection of mothers' levels. SCF levels do not show significant changes during sepsis in newborns.

Adult↗

Effect of cefodizime on peritoneal mononuclear- and polymorphonuclear-cell chemotaxis.

In this study, a third-generation cephalosporin with proposed immunomodulatory properties, cefodizime, was investigated to see if it has any effect on the chemotactic activity of human peritoneal monocyte and polymorphonuclear cell populations ex vivo. Ten continuous ambulatory peritoneal dialysis patients with peritonitis were entered in the study. Monocytes and polymorphonuclear cells were isolated from the patients' peritoneal effluent prior to initiation of any antibiotic therapy. Chemotaxis was measured by the Boyden chamber method before and after 2-hour incubation with cefodizime (200 mg/2L). Following 2-hour incubation with 200 mg/2L cefodizime, monocyte chemotaxis was increased from 36.8 +/- 5.6 microns to 50.2 +/- 6.6 microns (P = 0.0005). A similar increase was observed in polymorphonuclear cells from 42.0 +/- 8.8 microns to 48.7 +/- 10.3 microns (P = 0.02). We conclude that cefodizime acts as a priming agent on peritoneal polymorphonuclear cells, particularly on monocytes, and increases their chemotactic movements.

Adult↗

Effect of intraperitoneal immunoglobulin infusion on neutrophil function in CAPD children with and without peritonitis.

The present study was designed to assess the effect of intraperitoneal infusion of immunoglobulin (Ig) on neutrophil functions in uninfected and infected patients treated by continuous ambulatory peritoneal dialysis (CAPD). Fourteen children were included in the study. Healthy laboratory and medical personnel (n = 10) served as controls. Blood and peritoneal dialysate effluent (PDE) samples were obtained before and after Ig infusion. In all patients, chemotactic response of peripheral blood neutrophils (PBN) was significantly lower than in healthy controls. Peripheral blood neutrophils obtained from patients during peritonitis episodes (n = 10) showed significantly higher values compared to the values obtained from patients without peritonitis (n = 12). After the intraperitoneal infusion of Ig (100 mg/kg), chemotaxis of PBNs increased significantly in both patient groups. Chemiluminescence measures of PBN of the uninfected (n = 12) and infected patients (n = 7) were similar. They increased significantly in both groups after the Ig infusion, although they remained within the lower limits of the controls. The peritoneal neutrophils (PNs) showed significantly lower chemotactic activity in uninfected patients (n = 11) than in the infected ones (n = 10). The response of PNs to the Ig infusion was also more prominent in infected patients. Immunoglobulin infusion did not increase the chemiluminescence of PNs in infected patients (n = 7); the chemoluminescence of PNs did increase after Ig infusion in uninfected patients (n = 12). These data suggest the of administration intraperitoneal Ig for prophylaxis and/or treatment of peritonitis in CAPD patients.

Adolescent↗

Is medical therapy effective for regional lymphadenitis following BCG vaccination?

We describe 120 patients with regional lymphadenitis following intradermal BCG vaccination. Seventy-eight of the patients were given medical therapy to prevent drainage and suppuration, and 42 patients were followed up without such treatment. The medical therapy group is divided into three subgroups: 36 were given erythromycin stearate, 21 isoniazid, and 21 isoniazid plus rifampin. No statistical difference in the incidence of spontaneous drainage and suppuration was found between the "no therapy" and the "medical therapy" groups. No significant superiority of any specific therapy was shown. If lymphadenitis develops rapidly (in two months), the incidence of spontaneous drainage and suppuration is significantly higher than in patients with slowly developing lesions. Total surgical excision is recommended to prevent spontaneous drainage and chronic suppuration in these rapidly evolving instances.

BCG Vaccine↗