Browsing by Author "Oral, Haluk Barbaros"
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Item Alterations of serum cytokine levels and their relation with inflammatory markers in candidemia(Oxford University, 2015-04-01) Gürcüoğlu, Emel; Akın, Hicran; Akalın, Halis; Budak, Ferah; Ener, Beyza; Ocakoğlu, Gökhan; Göral, Güher; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; 0000-0001-7625-9148; 0000-0002-4803-8206; 0000-0003-0463-6818; CBT-0656-2022; AAU-8952-2020; F-4657-2014; AAG-8523-2021; AAH-5180-2021; EUR-5589-2022; K-7285-2012; 54782139900; 57207553671; 6701913697; 15053025300; 15832295800; 6603453166; 7004498001The roles of CRP, PCT, serum amyloid A (SAA), and cytokines in the diagnosis of fungal infections have not yet been clearly demonstrated. This study aims to measure the serum levels of interleukin (IL)-23, IL-17, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-10, transforming growth factor (TGF)-beta, C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) in cases of candidemia and to compare them with those observed in cases of bacteremia. For this purpose, the serum cytokine levels from 50 patients with candidemia were compared with those of 14 patients with polymicrobial sepsis, 30 patients with bacteremia, and 27 healthy control subjects. The cytokine levels were studied using sandwich ELISAs according to the manufacturer protocol. The serum levels of TGF-beta, IL-23, and IL-17 were found to be significantly higher in the candidemia group in comparison with the samples from those with bacteremia and healthy controls. The PCT and SAA levels were higher in samples from the group with bacteremia those from individuals with candidemia and the healthy control group. Assuming an IL-17 level threshold of > 38.79 pg/ml, the sensitivity and specificity were 38% and 96.6%, respectively but considering an IL-23 threshold of > 59.97 pg/ml, the sensitivity and specificity valueswere found to be 72% and 60%, respectively. The sensitivity and the specificity of the TGF-beta levels were found to be 85.71% and 53.33%, respectively, when the TGF-beta threshold is > 560 pg/ml. PCT and SAA demonstrated a superior performance for the differentiation of candidemia and bacteremia. Our study demonstrates that IL-17, IL-23, TGF-beta, PCT, and SAA levels could be a diagnostic marker for candidemiaItem Altered expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the formation of chronic Brucellosis(Hindawi, 2016-07-31) Budak, Ferah; Bal, Salih Haldun; Tezcan, Gülçin; Akalın, Halis; Göral, Güher; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0003-0463-6818; 0000-0002-5956-8755; K-7285-2012; AAU-8952-2020; F-4657-2014; F-8554-2017; AAH-3843-2020; 6701913697; 57191480128; 25650627600; 57207553671; 6603453166; 7004498001Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-1393p were decreased (p< 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.Item Association between serum neopterin, obesity and daytime sleepiness in patients with obstructive sleep apnea(W B Saunders, 2008-08) Ursavaş, Ahmet; Karadağ, Mehmet; Oral, Arzu Yılmaztepe; Demirdöǧen, Ezgi Şen; Oral, Haluk Barbaros; Ege, Ercüment; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; 0000-0003-0463-6818; 0000-0003-0463-6818; 0000-0002-7400-9089; 0000-0002-7400-9089; AAI-3169-2021; A-5841-2017; AAG-8744-2021; AAH-9812-2021; K-7285-2012; 8329319900; 6601970351; 23091316500; 14062849300; 7004498001; 6701341320Objective: Obesity and obstructive sleep apnea (OSA) and systemic inflammation may interact through biochemical pathways. Neopterin (NP) is a monocyte/macrophage activation marker produced by macrophages in response to interferon-gamma secreted by activated T lymphocytes. This study examines the association between NP, obesity and OSA. Patients and methods: The study included 22 newly diagnosed OSA (+) patients and 18 OSA patients. Subjects with history of coronary artery disease, transplant patients, history of alcohol and drug abuse, history of HIV and any other significant medical. illnesses such as active infections, autoimmune disease, malignancy, liver disease, pulmonary disease (COPD, asthma, ...), neuromuscular disease, patients on immunomodulating therapy or HMG-CoA reductase inhibitors were excluded. Results: There were no significant differences in age, body mass index (BMI), and smoking habits of the OSA (+) patients and OSA (-) patients. Serum NP levels did not show any significant difference between the OSA (+) patients and OSA (-) patients, however, NP levels were positively correlated with BMI (r = 0.320, p = 0.044). There was no significant correlation between NP and any of the polysomnographic parameters. The result of stepwise regression analyses (r 2 = 0.320, p < 0.001) showed that high serum NP levels (p = 0.004) and apnea-hypopnea index (AHI) were a risk factor for elevated Epworth sleepiness score, independent of BMI. Conclusion: We suggest that serum NP levels correlate with BMI. There was a significant relationship between serum NP levels and excessive daytime sleepiness in OSA patients.Publication Association of cytotoxic T lymphocyte subsets with disease severity in Covid-19(Wiley, 2021-08-01) Kızmaz, Muhammed Ali; Çağan, Eren; Şimşek, Abdurrahman; Dombaz, Fatma; Tezcan, Gülçin; Aşan, Ali; Demir, H. İbrahim; Bal, S. Haldun; Ermiş, Diğdem Yöyen; Coşkun, Necmiye Funda; Akalın, E. Halis; Oral, Haluk Barbaros; Budak, Ferah; Kızmaz, Muhammed Ali; ŞİMŞEK, ABDURRAHMAN; Dombaz, Fatma; TEZCAN, GÜLÇİN; Demir, H. İbrahim; BAL, SALİH HALDUN; YÖYEN ERMİŞ, DİĞDEM; COŞKUN, NECMİYE FUNDA; AKALIN, EMİN HALİS; ORAL, HALUK BARBAROS; BUDAK, FERAH; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Hastalıkları Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; 0000-0001-5334-7911; 0000-0001-8850-0269; 0000-0001-7288-3250; 0000-0002-5956-8755; 0000-0002-8856-7356; 0000-0001-7585-7971; 0000-0003-3604-8826; 0000-0001-7530-1279; 0000-0003-0463-6818; 0000-0001-7625-9148; 0000-0003-3604-8826; HKN-2347-2023; IZP-9398-2023; AAH-3843-2020; F-4657-2014; AAG-7381-2021; K-7285-2012; AAU-8952-2020; DWR-5356-2022; GPN-1473-2022; KBR-5535-2024; GYL-2038-2022; AAD-1271-2019Item Association of tnf-alpha-308 polymorphism with the outcome of hepatitis B virus infection in Turkey(Elsevier, 2008-01) Karasu, Zeki; Baştürk, Bilkay; Kılıç, Murat; Ulukaya, Sezgin; Boyacıoğlu, Ahmet Sedat; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı İmmünoloji Ünitesi.; 0000-0003-0463-6818; K-7285-2012; 7004498001Background and aim: Cytokines play important roles in the regulation of immune response. The aim of the study was to investigate the association of the cytokine gene polymorphisms with persistence of hepatitis B virus (HBV) infection and the development of end-stage liver disease (ESLD) due to HBV infection. Methods: The study involved 27 patients with end-stage liver disease due to HBV infection, 23 HBV carriers and 60 healthy controls. All genotyping (TNF-alpha, TGF-beta, IL-10, IFN-gamma) experiments were performed using sequence specific primers (PCR-SSP) by using commercial kit according to manufacturers' instructions. Results: The frequencies of TNF-alpha -308 G/G and TGF-beta 1 codon 10-25 T/C-G/G polymorphisms were significantly higher in HBV-infected individuals (patients + carriers) when compared with those of healthy controls (p: 0.02 and p: 0.004, respectively). The frequency of TNF-alpha -308 G/G polymorphism was significantly higher in the patients than those of the healthy controls (p: 0.02), whereas the frequency of TGF-beta 1 codon 10-25 T/T-G/G polymorphism was lower (p: 0.028). On the other hand, TNF-alpha -308 G/G and TGF-beta codon 10-25 T/C-G/G polymorphisms were significantly more common in HBV carriers than the control group (p: 0.017 andp: 0.018, respectively). In addition, TNF-alpha -308 G allele frequency was significantly more common in HBV-infected individuals (patients + carriers) than those of healthy controls (p: 0.0007). TNF-alpha -308 G allele frequency was also found to be higher in patients or carriers when compared with those of healthy controls (p: 0.01 and p: 0.01, respectively). Statistically significant differences were still kept after Bonferroni correction of the p-values for only TNF-alpha -308 G allele frequency in patients or carriers (Pc). Conclusion: Our study suggests that TNF-alpha gene polymorphism in patients infected with HBV would result in relatively inefficient inhibition of HBV and development of ESLD, and therefore, may be valuable predictor determinants for the development of ESLD in patients with chronic HBV infection.Item Autoimmunity and hepatitis a vaccine in children(Esmon Publicidad, 2011) Karalı, Zuhal; Tanır, Sevgen Başaranoğlu; Karalı, Yasin; Oral, Haluk Barbaros; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilimdalı.; 0000-0003-0463-6818; 0000-0003-0710-5422; 0000-0002-9416-1512; 0000-0001-8571-2581; AAH-1658-2021; K-7285-2012; C-7392-2019; U-2921-2017; 35791967200; 53868381900; 49863694000; 7004498001; 34975059200Background: Universal vaccination remains the most effective way of preventing the spread of many infectious diseases. Although most adverse effects attributed to vaccines are mild, rare reactions such as autoimmunity do occur. Objectives: We aimed to evaluate the possible role played by hepatitis A vaccine (HAV) in inducing the synthesis of autoantibodies. The study included 40 healthy children vaccinated with 2 doses of HAV at a 6-month interval. The children were investigated for autoantibodies including anti-nuclear antibodies (ANAs), anti smooth muscle antibodies, anti-nDNA, anti-microsomal antibodies, anti-cardiolipin (aCL) immunoglobulin (Ig) M/IgG, anti-ds DNA, ANA profile, and anti neutrophil cytoplasmic antibody profile. Results: One month after the first dose, ANAs at a titer of 1:100 and aCL IgG at 23.7 IgM phospholipid units were detected in 4 children and 1 child, respectively. Of the ANA-positive children, 1 also had ASMA positivity, and another had perinuclear and cytoplasmic ANCA positivity. After the second dose, 3 of the children had aCL IgM. In addition, 2 distinct children had positive anti-thyroid microsomal antibodies and ANA after the second dose. The presence of these autoantibodies following vaccination was statistically significant (P=.002). At month 12 of the study, only 2 children continued to be ANA-positive at the same titer as after the first vaccine dose. Conclusions: Although HAV can induce the production of autoantibodies, none of the children developed autoimmune disorders. Longterm follow up is necessary to check whether autoimmune disorders develop in children who still have ANA. Genetic, immunological, environmental, and hormonal factors are also important in the development of vaccine-induced autoimmunity.Item Back to the future: Antibody-based strategies for the treatment of infectious diseases(Humana Press, 2002-07) Akdiş, Cezmi; Oral, Haluk Barbaros; Özakın, C.; Uludağ Üniversitesi/Tıp Fakültesi/İmmunoloji Anabilim Dalı/Mikrobiyoloji Bölümü.; 7004498001; 57200678942Before antibiotics, sera from immune animals and humans were used to treat a variety of infectious diseases, often with successful results. After the discovery of antimicrobial agents, serum therapy for bacterial infections was rapidly forsaken. In the last two decades, problems with treatment of newly emerged, re-emerged, or persistent infectious diseases necessitated researchers to develop new and/or improved antibody-based therapeutic approaches. This article reviews some information on the use of antibodies for the treatment of infectious diseases, with special reference to the most seminal discoveries and current advances as well as available treatment approaches in this field.Item Brucella abortus L7/L12 recombinant protein induces strong Th1 response in acute brucellosis patients(Shiraz Institute of Cancer Research, 2010-09) Oliveira, Sergio; Kazak, Esra; Göral, Güher; Akalın, Halis; Yılmaz, Emel; Heper, Yasemin; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/ Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0003-0463-6818; K-7285-2012; AAG-8459-2021; AAH-6506-2021; AAU-8952-2020; 24921238200; 6603453166; 57207553671; 22037135100; 56191003300; 7004498001Background: Because of high morbidity of the brucellosis in humans and the potential use of the microorganism as an agent of biologic warfare, protection of effective vaccines and specific diagnostic reagents become necessary to eradicate brucellosis. Objective: In this study we aimed to investigate the cytokine responses and changes in peripheral blood lymphocyte subgroups of acute brucellosis patients in response to L7/L12 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) recombinant proteins derived from Brucella abortus. Methods: levels of IFN-gamma, IL-4 and IL-10 secreted from PBMCs of 25 acute brucellosis patients and 15 healthy controls, stimulated with Phytohemagglutinin (PHA), L7/L12 or GAPDH were measured by ELISA. Furthermore alterations in lymphocyte subgroups in response to these Brucella antigens were determined by flow cytometry. Results: Extracellular IFN-gamma levels were found to be elevated after stimulation with L7/L12 in patients with acute brucellosis, whereas no significant changes were found in IL-4 and IL-10 levels. Similar data was also obtained with GAPDH, but the stimulation of IFN-gamma production was not observed in all patients and was not as strong as that observed for L7/L12. Moreover, when the distribution of lymphocytes subgroups (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD4(+)CD25(+), CD3(+)CD69(+) and CD3(+)CD152(+)) was evaluated, it was found that the stimulation with L7/L12 and GAPDH only led to an increase in the percentage of CD3(+)CD69(+) lymphocytes. Conclusion: These data indicate that Brucella abortus L7/L12 or GAPDH induce a Th1 type immune response in acute brucellosis patients. Additionally, these recombinant proteins, especially L7/L12, may be used in new vaccine preparations and diagnostic tests.Item Brucellar spondylitis - Review of 25 cases(Lippincott Williams and Wilkins, 2004-12) Yılmaz, Emel; Parlak, Müfit; Akalın, Halis; Heper, Yasemin; Özakın, Cüneyt; Mıstık, Reşit; Oral, Haluk Barbaros; Helvacı, Safiye; Töre, Okan; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Radyoloji Anabilim Dalı.; 0000-0001-5428-3630; 0000-0003-0463-6818; AAU-8952-2020; AAH-6506-2021; AAG-8392-2021; K-7285-2012; 22037135100; 7003589220; 57207553671; 56191003300; 57200678942; 6602564624; 7004498001; 6602103491; 6505909596Objective: Brucellar spondylitis is one of the most serious complications of brucellosis. It should be considered in patients who have back pain and neurologic disorders as well as systemic symptoms and findings in or from endemic areas such as Turkey. This report describes important features of the disease. Methods: Twenty-five patients with brucellar spordylitis were retrospectively evaluated in terms of their clinical, laboratory, and radiologic features and their response to different treatment regimens. Results: The most common symptoms of brucellar spondylitis were back pain, fever, and sweating. Rose Bengal tests were positive in all of these patients. Brucella species was isolated from blood cultures of 8 (32%) patients. Magnetic resonance imaging (MRI) showed that the lumbar segment was the most frequently involved region. Different combination regimens including 2 or 3 antibiotics were used. Combination of tetracycline (especially doxycycline) and streptomycin was the most widely used therapy regimen. Trimethoprim-sulfamethoxazole, ciprofloxacin, ofloxacin, and rifampin were also included in some combination therapies. In this series, the mean duration of antimicrobial therapy was 130 +/- 45.6 days (range, 77-281 days), and 92% of patients received therapy for greater than or equal to 90 days. There were no mortalities in this study. Conclusions: Brucellar spondylitis should be considered in patients with back pain and neurologic disorders as well as systemic symptoms and findings in endemic areas. MR imaging is recommended in suspected cases. The patients can be treated effectively treated with appropriate antibiotic combinations. Follow up is important because relapses can occur.Item Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome(Karger, 2007) Ursavaş, Ahmet; Karadağ, Mehmet; Rodoplu, Erkan; Yılmaztepe, Arzu; Oral, Haluk Barbaros; Gozo, R. Oktay; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Hastalıkları Anabilim Dalı.; 0000-0003-0463-6818; 0000-0003-0463-6818; 0000-0002-9027-1132; A-5841-2017; K-7285-2012; AAI-3169-2021; AAG-8744-2021; 8329319900; 6601970351; 15838170200; 8606136100; 7004498001; 15836640800Background: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. Objectives: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. Methods: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. Results: Circulating levels of both ICAM-1 (480.1 +/- 216.7 vs. 303.4 +/- 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 +/- 79.8 vs. 878.8 +/- 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4-83.0%) and 82.4% ( 95% CI: 65.5-93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9-86.9%) and 64.7% ( 95% CI: 46.5-80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. Conclusion: We conclude that OSAS can independently increase circulating levels of adhesion molecules.Item Combination of esomeprazole with chemotherapeutics results in more pronounced cytotoxic effect via apoptosis on A549 nonsmall-cell lung cancer cell line(TÜBİTAK, 2016-09-22) Yılmaztepe, Oral Arzu; Oral, Haluk Barbaros; Sarımahmut, Mehmet; Cevatemre, Buse; Özkaya, Güven; Korkmaz, Şeniz; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; 0000-0003-0463-6818; 0000-0003-2647-5875; 0000-0003-0297-846X; K-7285-2012; AAG-8288-2021; A-4421-2016; K-5792-2018; 26425326300; 7004498001; 44661687400; 55693788600; 16316866500; 36666461900; 6602927353The vacuolar (H+)-ATPases that pump H+ from the cytoplasm to extracellular compartments can alter the pH of the tumor microenvironment. Esomeprazole can effectively inhibit vacuolar (H+)-ATPases and may increase the effectiveness of chemotherapeutics. Therefore, we used esomeprazole in combination with cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine on the A549 nonsmall-cell lung cancer cell line. Cisplatin and carboplatin combinations with esomeprazole exhibited superior cytotoxicity compared to the other selected chemotherapeutics. Low-dose combinations of esomeprazole with either cisplatin or carboplatin resulted in synergistic interaction. We examined cytotoxic activity of these combinations with the xCELLigence real-time cytotoxicity assay and detected that esomeprazole combinations with both 100% test drug concentrations of cisplatin and carboplatin shifted the antiproliferative effects of these agents towards a cytotoxic effect in a dose-dependent manner. Cell death mode was investigated by M30 assay, Annexin-V-FITC fluorescence imaging, and determination of PARP cleavage in western blotting. The cells treated with the cisplatin and esomeprazole combination displayed characteristic features of apoptosis such as elevated M30 levels, Annexin-V staining, and PARP cleavage. In conclusion, these novel combinations resulted in higher sensitivity of tumors to chemotherapeutics, thereby warranting further in vivo experiments for proof of the concept.Item COVID-19 pozitif hastalarda G-MDSC benzeri alt gruplardaki fenotipik ve fonksiyonel farklılıkların araştırılması(Bursa Uludağ Üniversitesi, 2022-02-24) Dombaz, Fatma; Oral, Haluk Barbaros; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıp Fakültesi İmmünoloji Anabilim Dalı.; 0000-0001-7288-3250Miyeloid hücreler, doğuştan gelen immün sistemin hücreleri olup, virüslere karşı verilen immün yanıtların başlamasında ve sonlanmasında görev alırlar. Özellikle, enfeksiyon sonrası immün regülasyonun sağlanmasında oldukça kritik rolleri olup, hemoastazın sağlanmasında görev alırlar. Efektif immün yanıtın oluşmasıyla beraber viral replikasyon kontrol edilerek, yüksek doku hasarı ve sitokin fırtınası önlenebilmektedir. Böylelikle, immünopatoloji sınırlandırılmakta ve iyi bir klinik tablo ile sonuçlanmaktadır. İlgili tez kapsamında, miyeloid kökenli baskılayıcı hücre ve alt grupları ile nötrofillerin hastalık prognozunu hangi yönde etkilediği araştırılmıştır. Çalışma Ocak 2021-Kasım 2021 tarihleri arasında COVID-19 ön tanısı almış ve PCR testi ile pozitifliği doğrulanan hem çocuk hem de erişkin bireylerin periferik kan örnekleri ile gerçekleştirilmiştir. Bu hastaların MDSC’leri ve nötrofilleri fenotipik ve fonsiyonel açıdan değerlendirilmiş olup klinik tablo ile ilişkilendirilmiştir. Sağlıklı çocuklarda özellikle erken yaş döneminde (0-13 yaş) hali hazırda G-MDSC ve E-MDSC hücre grubunun yüksek bulunması ve hastalığın akut döneminde GMDSC hücrelerinin azalarak, E-MDSC hücrelerinin artış göstermesi ve M-MDSC düzeyinde artışın görülmemesi miyeloid hücrelerin inflamasyonu uyarıcı ve durdurucu iki yönlü çalıştığı görülmüştür. Özellikle akut dönem anti-viral yanıtlarda baskılayıcı hücre grubunun var olmasına karşın yüksek düzeylerde bulunmasının kontrollü yanıtta kritik olacağını düşündürmüştür. Erişkin bireylerde literatür ile uyumlu olarak M-MDSC artışının kötü prognoz ile ilişkili olduğu ve ağır klinik tabloya sahip bireylerde yükseldiği belirlenmiştir. MMDSC/G-MDSC oranının ≥1 olması ve E-MDSC oranının düşük düzeylerde bulunmasının kötü prognoz için bir belirteç olabileceği saptanmıştır.Item Cytokine gene polymorphisms in Behçet's disease and their association with clinical and laboratory findings(Clinical & Exper Rheumatology, 2009) Özçimen, Ahmet Ata; Dilek, Kamil; Sancaoğlu, Hayriye; Saba, Davit; Yücel, Ali; Yurtkuran, Mustafa Abbas; Yurtkuran, Merih; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Nefroloji ve Romatoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Dermatoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Kalp Damar Cerrahisi Anabilim Dalı.; 0000-0003-0463-6818; K-7285-2012; 56005080200; 35485529800; 55987378200; 57225839918; 55408539300; 7003389525; 7004498001The association of the cytokine gene polymorphisms with the development of Behcet's Disease (BD) was investigated in this study. DNA samples were obtained from a Turkish population of 97 unrelated patients with BD, and 12 7 unrelated health), control subjects. All genotyping (IL-6, IL10, IFN-gamma, TGF-beta 1 and TNF-alpha) experiments were performed using sequence-specific primers PCR. The frequency of TGF-beta 1 codon 25 GG genotype was found significantly lower in BD patients compared to healthy control subjects. The IL-10 -1082 GA genotype was more frequent whereas the AA genotype was less common in the BD group compared to the control group. The association between clinial findings and cytokine gene polymorphisms was further investigated in the patients with BD. The frequency of IFN-gamma AA genotype was lower in the patients with genital ulcer. Additionally, it was found that the frequency of IL-6 -174 GG genotype was lower in the patients with Pathergy positivity. These results suggest that TGF-beta 1 and IL-10 gene polymorphisms may affect host susceptibility to BD. Also, to confirm the biological significance of our results, further studies should be performed on other population groups and in large number of cases.Item Diagnostic value of serum concentrations of high-mobility group-box protein 1 and soluble hemoglobin scavenger receptor in brucellosis(Wiley, 2013-02) Ayarcı, Ayşe Oǧuz; Yılmaz, Emel; Sığırlı, Deniz; Budak, Ferah Ah; Göral, Güher; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Bölümü.; 0000-0003-0463-6818; 0000-0002-3894-1231; F-4657-2014; K-7285-2012; AAA-7472-2021; 55589179100; 22037135100; 24482063400; 6701913697; 6603453166; 7004498001Both cluster of differentiation (CD)4+ and CD8+ T lymphocytes play key roles in immunity to Brucella, in part because they secrete interferon (IFN)- and activate bactericidal functions in macrophages. Therefore, use of markers of macrophage activation may have diagnostic and prognostic significance. High-mobility group-box 1 protein (HMGB1), a late-onset pro-inflammatory cytokine, is secreted by activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of anti-inflammatory macrophages. The aim of this study was to investigate the diagnostic value of HMGB1 and sCD163 concentrations in brucellosis and its various clinical forms. Serum HMGB1 and sCD163 concentrations in 49 brucellosis patients were compared with those in 52 healthy control subjects. Both serum HMGB1 and sCD163 concentrations were significantly higher in brucellosis patients than in healthy controls (P<0.001). There were no statistically significant differences in serum concentrations of HMGB1 and sCD163 between cases of acute, subacute and chronic brucellosis. Additionally, serum HMGB1 concentrations were positively correlated with sCD163 concentrations, whereas neither HMGB1 nor sCD163 concentrations were correlated with C-reactive protein concentrations, white cell counts or erythrocyte sedimentation rates. Therefore, serum concentrations of HMGB1 and sCD163 may be diagnostic markers for brucellosis, but neither can be used to differentiate the three different forms of this disease (acute, subacute and chronic).Item Diagnostic value of serum high mobility group box protein 1 (HMGB1) and soluble CD163 (sCD163) levels in brucellosis(Wiley, 2012-09) Ayarcı, Ayşe Oǧuz; Yılmaz, Emel; Sığırlı, Deniz; Budak, Ferah; Göral, Güher; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0003-0463-6818; F-4657-2014; AAA-7472-2021; K-7285-2012Both CD4+ and CD8+ T lymphocytes play critical roles in immunity to Brucella, in part because they secrete IFN-c and activate the bactericidal functions in macrophages. Therefore, use of markers which can evaluate macrophage activation may have diagnostic and prognostic importance. High mobility group-box 1 protein (HMGB1) is a late-onset proinflammatory cytokine secreted from activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of antiinflammatory macrophages. The aim of this study was to test potential associations of serum levels of HMGB1 and sCD163 with Brucellosis and its acute, subacute and chronic formsItem Effect of amlodipine on insulin resistance & tumor necrosis factor-alpha levels in hypertensive obese type 2 diabetic patients(Wolters Kluwer Medknow Publications, 2004-11) Ersoy, Canan; İmamoğlu, Şazi; Budak, Ferah; Tuncel, Ercan; Ertürk, Erdinç; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; 0000-0003-0463-6818; AAH-8861-2021; F-4657-2014; K-7285-2012; 6701485882; 6602297533; 6701913697; 7006929833; 7005488796; 7004498001Background & objectives: Tumour necrosis factor-alpha (TNF-α) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-α, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients. Methods: Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amiodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group. Results: Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-α and HOMA-IR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin Alc and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-α values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-α and HOMA-IR. Interpretation & conclusion: Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-α levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.Item The effect of metformin treatment on VEGF and PAI-1 Levels in obese type 2 diabetic patients(Elsevier, 2008-07) Ersoy, Canan; Kıyıcı, Sinem Kucuksaraç; Budak, Ferah Ah; Oral, Haluk Barbaros; Güçlü, Metin; Duran, Cevdet; Selimoǧlu, Hadi; Ertürk, Erdinç; Tuncel, Ercan; İmamoğlu, Şazi; Uludağ Üniversitesi/Tıp Fakültesi/Endokrinoloji ve Metabolizma Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Anabilim Dalı Anabilim Dalı.; 0000-0003-0463-6818; K-7285-2012; ABI-4847-2020; F-4657-2014; AAH-8861-2021; AAJ-6536-2021; 6701485882; 12753880400; 6701913697; 7004498001; 15073842600; 12754039000; 15074185600; 7005488796; 7006929833; 6602297533The aim of the study was to evaluate the effect of metformin on markers of endothelial function, vascular inflammation and factors of thrombosis in obese type 2 diabetic patients. Twenty-four type 2 diabetic patients (15 female, 9 male) previously under medical nutrition treatment (MNT) + regular exercise programme (REP) without chronic micro or macrovascular complications with the mean age of 50.5 +/- 1.5 years, diabetes duration of 17.9 +/- 6.3 months and body mass index (BMI) of 31.7 +/- 0.8 kg/m(2) were enrolled in the study. In the first 4 weeks, all the patients continued MNT + REP. In the following 12 weeks, metformin (mean daily dosage of 1381 +/- 85 mg) was added. After the first period with MNT + REP, BMI, waist circumference, fat percentage, blood pressure and HDL cholesterol decreased significantly. After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial. plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in P cell reserve values of the patients. Our results indicated that, metformin addition had beneficial effect on VEGF and PAI-1 levels in obese type 2 diabetic patients under MNT + REP, independent from its' favourable effects on BMI and glycemic control.Publication Effect of storage period of erythrocyte suspensions on the CD4 & CD8 T cells(Wiley, 2021-08-01) Bal, Salih Haldun; Kumaş, Levent Tufan; Cevhertaş, Laçin; Yılmaz, İzel; Ellergezen, Pınar Hız; Budak, Ferah; Heper, Yasemin; Göral, Güher; Oral, Haluk Barbaros; BAL, SALİH HALDUN; Kumaş, Levent Tufan; Cevhertaş, Laçin; Yılmaz, İzel; ELLERGEZEN, PINAR; BUDAK, FERAH; HEPER, YASEMİN; Göral, Güher; ORAL, HALUK BARBAROS; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dr. Rasit Durusoy Kan Bankası.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Mikrobiyoloji-İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji Anabilim Dalı.; 0000-0003-2287-3569; 0000-0001-7625-9148; 0000-0003-0463-6818; F-4657-2014; IZP-9398-2023; K-7285-2012; JSK-9450-2023; KBR-5535-2024; FHB-1791-2022; FYD-1431-2022; CPH-1647-2022; CTY-9474-2022; JGX-8396-2023Item Effect of storage period of red blood cell suspensions on helper T-cell subpopulations(Simtipro Srl, 2018) Güvenç, Furkan; Bal, Salih Haldun; Kumaş, Levent Tufan; Budak, Ferah; Göral, Güher; Oral, Haluk Barbaros; Heper, Yasemin; Uludağ Üniversitesi/Tıp Fakültesi/Dr. Raşit Durusoy Kan Bankası.; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Mikrobiyoloji/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0001-7625-9148; 0000-0003-0463-6818; HJY-9001-2023; F-4657-2014; AAH-6506-2021; K-7285-2012; 56191003300; 26665534000; 6701913697; 6603453166; 7004498001; 57191480128Background. The aim of this study was to investigate the immunological alterations that occur during the storage of erythrocyte suspensions which may lead to transfusion-related immunomodulation following allogeneic blood transfusion. Materials and methods. One part of the erythrocyte suspensions obtained from donors was leucoreduced while the other part was not. The leucoreduced (LR) and non-leucoreduced (NL) erythrocyte suspensions were then further divided into three equal amounts which were stored for 0, 21 or 42 days prior to measurements, by enzyme-linked immunosorbent assays, of cytokine levels in their supernatants. T-helper (Th) lymphocyte subgroups and gene expression were analysed in the NL erythrocyte suspensions by flow cytometry and real-time polymerase chain reaction, respectively. Results were compared to those of storage day 0. Results. By day 21, the number of Th2 cells had increased significantly and the numbers of Th1, Th22 and Treg cells had decreased significantly in the NL erythrocyte suspensions. On day 42 the numbers of Th2 and Treg cells in the NL suspensions were significantly increased while the number of Th1 cells was significantly decreased. The levels of transcription factors (TBX21, GATA3, and SPI.1) were significantly decreased on days 21 and 42, and AHR, FOXP3 and RORC2 levels were significantly increased on day 42 in NL erythrocyte suspensions. The decrease in interleukin-22 and increase in transforming growth factor-beta levels found in NL erythrocyte suspensions on day 21 were statistically significant. Elevated levels of interleukin-17A were found in both LR and NL erythrocyte suspensions on day 42. Discussion. Our results suggest that allogeneic leucocytes and cytokines may play significant roles in the development of transfusion-related immunomodulation.Item Effects of Malassezia yeasts on serum Th1 and Th2 cytokines in patients with guttate psoriasis(Wiley, 2013-01) Aydoğan, Kenan; Töre, Okan; Akçağlar, Sevim; Oral, Haluk Barbaros; Ener, Beyza; Tunalı, Şükran; Sarıcaoğlu, Hayriye; Uludağ Üniversitesi/Tıp Fakültesi/Dermotoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0002-4803-8206; 0000-0003-0463-6818; 0000-0002-0193-1128; 0000-0002-4759-9634; AAG-8523-2021; AAH-6216-2021; K-7285-2012; 9739755800; 6505909596; 6506194958; 7004498001; 15053025300; 7004191748; 6603722836Background Systemic and focal infections caused by microorganisms have been known to induce or exacerbate psoriasis. Although the role of yeast species of the genus Malassezia in the pathogenesis of psoriasis is not fully understood, it is thought that these lipophilic yeasts may represent a triggering factor in the exacerbation of psoriatic lesions. Objectives This study investigated the effects of Malassezia yeasts on serum Th1 and Th2 cytokines in patients with guttate psoriasis (GP) in order to define their role in the pathogenesis of psoriasis. Methods Fifty patients with GP and 29 clinically healthy individuals were included in the study. All samples consisted of scales and scrapings taken from the scalps, trunks, and upper limbs of both psoriasis patients and healthy subjects. Psoriasis patients and healthy subjects were grouped according to their positivity or negativity for Malassezia yeasts as ascertained by direct microscopy and/or culture. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of Th1 and Th2 cytokines in these groups. Results No significant differences in positivity for Malassezia yeasts were found between psoriatic skin and healthy skin in samples taken from different body sites. Serum interleukin-13 (IL-13) levels were significantly lower in the psoriasis group compared with the control group (P = 0.04). Levels of other cytokines did not differ significantly between the psoriasis and control groups. Mean levels of Th2 cytokines (IL-4, IL-10, IL-13), but not of Th1 cytokines (IL-2 and IFN-?), were significantly lower in psoriasis patients positive for Malassezia yeasts compared with those negative for Malassezia yeasts and control subjects (P = 0.04, P < 0.001 and P = 0.01, respectively). Conclusions The isolation of Malassezia yeasts from GP lesions does not necessarily mean that these species are pathogenic, but their downregulating effects on anti-inflammatory Th2 cytokines may contribute to the occurrence of GP.