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Objectives The data of the monocyte subgroups and expressed toll like receptors (TLR) in the innate immune system response, which develop against chronic inflammation in patients with predialysis chronic kidney disease (CKD) and in patients who undergo dialysis treatment, are limited. We aimed to investigate the effect of the dialysis procedure on the current chronic inflammatory condition and which role of monocyte subgroups ratios, the expressions of TLR2/4 and serum Tumor necrosis factor alpha (TNF-α) levels involved in the innate immune response process. Methods We investigated monocyte subgroups, TLR2/TLR4 expressions and serum TNF-α levels in 30 predialysis CKD patients, 90 CKD patients undergoing dialysis and 30 healthy control subjects. Monocyte subgroup percentages and TLR2/TLR4 expressions were determined using the flow cytometry, serum TNF-α levels were investigated using the enzyme-linked immunosorbent assay (ELISA). Results In the dialysis patients, the percentages of classical (p=0.0001) and non-classical (p=0.078) monocytes were found to be higher when compared with the predialysis CKD patients. The percentages of TLR4 expression on non-classical monocytes was higher in dialysis and predialysis patients compared with the healthy controls (p Conclusions Increased percentages of non-classical monocytes, TLR4 expressions and serum TNF-α levels observed in the predialysis CKD patients and dialysis patients might be related to inflammation.

The impact of core 1,3-galactosyltransferase-specific molecular chaperon (COSMC) gene expression and methylation profile on clinical progression of IgA nephropathy (IgAN) is unclear. The aim of this study was to determine the clinical significance and the relation of the COSMC gene expression and methylation pattern with the progression of IgAN.Thirty-nine biopsy-confirmed IgAN patients, 11 healthy relatives and 20 healthy controls were recruited. The COSMC mRNA levels and methylation profile of COSMC gene promoter were measured using the quantitative real-time PCR. The galactose-deficient IgA1 (Gd-IgA1) levels were measured using ELISA in serum and cell culture supernatant. The effect of IL-4 and AZA on COSMC expression and methylation and the correlation of COSMC gene expression and methylation levels with baseline kidney function tests, histology and long-term outcomes were examined.The mean COSMC mRNA level was significantly lower, and serum Gd-IgA1 level was higher in IgAN patients compared with the control groups (p 0.001, and p = 0.001, respectively). The COSMC mRNA levels were correlated with intensity of hematuria (r = - 0.41, p = 0.009), serum creatinine level (r = - 0.37, p = 0.002) and eGFR (r = 0.36, p = 0.002). The COSMC methylation levels were correlated with age (r = 0.25, p = 0.04) and baseline eGFR (r = - 0.326, p = 0.006). Twenty IgAN patients (51.3%) reached to complete (5, 12.8%) or partial remission (15, 38.5%) after a median of 34.5 months (IQR, 13.75-71). In multivariable Cox regression analysis, COSMC mRNA expression (adjusted HR (aHR) 1.871, 95% CI 1.287-2.722, p = 0.001) and Oxford T score (aHR 0.355, 95% CI 0.146-0.859, p = 0.022) predicted the remission.COSMC mRNA level is a novel biomarker candidate to predict the remission in IgAN patients.

Objectives Graft-versus-host disease (GvHD) is a complex clinical syndrome with organ dysfunction as a consequence of a severe immunological reaction mediated by mainly T cells after hematopoietic stem cell transplantation. Our aim is to evaluate the association of HLA-DRB1 alleles, IFN-γ and TGF-β gene variations, with childhood ALL (c-ALL) patients and with GvHD after transplantation. Methods This study included 30 high-risk c-ALL patients and 100 controls. HLA-DRB1 alleles were studied by the NGS method, and TGF-β and IFN-γ variations were studied by the PCR-RFLP method. Results The rates of HLA-DRB1*15 alleles and IFN-gamma CC genotype were significantly higher in c-ALL patients (p=0.004, p=0.036 respectively). Association of the HLA-DRB1*15 alleles with the TGF-β TC genotype was found with a higher rate in the patient group (p=0.031). Association of the DRB1*04 allele with the IFN-γ CC genotype was found with a higher rate in the patient group (p=0.028). Acute GvHD developed in eight of 19 patients who underwent transplantation. IFN-γ CT was found to have a protective role in occurrence of aGvHD (p=0.044). Association of the DRB1*15 allele with IFN-γ TT was found with a higher rate in a GvHD (p=0.050). Conclusions It is thought that polymorphism of HLA-DR15 and IFN-γ CC may contribute to the development of c-ALL, while IFN-γ CT might be protective for aGvHD.

Objectives The antibodies interact with the “Human Leukocyte Antigen (HLA) antigens” at specific epitopes. “Epitopes” are present on a single HLA or shared by multiple antigens. In this study, we aim to determine the frequency of prevalent epitopes common in the Turkish population. Methods Non-related 644 healthy volunteers were recruited, and The “HLA-A, -B, -C, -DR -DQ’s” were typed using the “Next Generation Sequencing”. The provisional and confirmed epitopes were identified using the “HLA Epitope Registry databases, HLA Epitopia Maps and Immucor Epitope databases” dated 07.02.2018. Epitope frequencies were calculated by counting the shared epitopes in the total number of shared HLA Class epitopes in our sample database. Results Class I HLA’s had 298 epitopes that repeated a total of 158,117 times with frequencies ranging between 0.0006 and 2.03%, and the most frequent epitope was 170RY found on 119 different alleles. Class II HLA’s had 193 epitopes that repeated a total of 93,082 times with frequencies ranging between 0.002 and 1.36%, and the most frequent epitope was 108P found on 42 different alleles. Conclusions Our findings summarize both the provisional, and confirmed epitope frequencies in the Turkish population and may help clinicians and immunogeneticists develop a better understanding of HLA epitope mismatches.

We managed to provide one-step facile electrochromic device (ECD) preparation to incorporate two cathodic coloring components into lithium ion (Li+)-doped UV-curable electrolyte. The hybrid-based flexible ECDs were fabricated by using tungsten trioxide (WO3) and poly(3,4-ethylenedioxythiophene) (PEDOT) as electrochromic components without the need for deposition procedures. The influences of lithium salts (lithium perchlorate (LiClO4) and lithium trifluoromethanesulfonate (LiTRIF)) on the electrochromic performance of flexible ECDs were evaluated. The electrochromic and the intrinsic kinetic features of all ECDs were investigated via transmittance and electrochemical impedance measurements. The ECD fabricated from LiClO4 electrolyte exhibited the highest optical transmittance modulation of 38.7% under an applied potential of +/- 2 V. To evaluate the mechanical robustness of the flexible ECDs, a bending cycle test was also conducted. After performing repetitive bending cycle tests, the optical modulation of ECD fabricated from LiTRIF electrolyte was remained stable for applied potentials of +/- 2 V. Especially, the flexible ECDs prepared from LiTRIF showed high mechanical bendability.

Türkiye Cumhuriyeti’nde, devlet politikaları ve sosyo-ekonomik koşullar, konut sunumunda ve yapılı çevrenin oluşmasında kemikleşmiş bir “habitus” yaratacak kadar etkili olmuştur. 1965’te “Kat Mülkiyeti Kanunu” ile ortaya çıkan ve 80’lerde gelişen “yap-sat konut sunumu”, 1999 Marmara Depremi sonrası 2012’de yürürlüğe giren “Afet Riski Altındaki Alanların Dönüştürülmesi Hakkında Kanun” ile yeni bir ivme kazanmıştır. Bu çalışmanın amacı; Türkiye Cumhuriyeti (konut) politikalarının, konutun ve kentsel dokunun oluşmasındaki etkisini göstermek ve kentsel dönüşüm kapsamında kaliteli konut yerleşimleri yaratmaya yönelik yeni ve bütüncül yaklaşımların gerekliliğini ortaya koymaktır. Araştırmada cumhuriyet döneminde etkili olan konut politikalarına göre, özellikle son 70 yılda parsel ölçeğindeki konut binasının fiziksel değişimi örnekler üzerinden incelenmiştir. Bu değişimin mahalle ve kent dokusuna fiziksel olarak nasıl yansıdığı da haritalar ve resimler yardımıyla değerlendirilmiştir. Araştırma alanı olarak İstanbul’da “kentsel dönüşüm”ün en yoğun şekilde yaşandığı ilçe olan Kadıköy seçilmiştir. Kadıköy Belediyesi’nden temin edilen kentsel dönüşüm öncesi ve sonrası mimari ruhsat projeleri yardımıyla konut binasındaki fiziksel değişim açıkça ortaya konmuştur.Araştırma sonucunda; İstanbul’da kentsel dönüşümle birlikte en yaygın halini alan yap-sat konut sunum kültürünün, kentsel donatı alanlarının yetersiz kalmasında ve kentsel dokunun obezleşmesindeki etkisi; yıllara göre “katlar alanı katsayısı” değişimi ve “konut stoku” verileriyle desteklenerek gösterilmiştir. Mevcut konut sunum biçiminin bizi taşıyacağı bir sonraki durak, karşılaşılması muhtemel sorunlar ve çözüm önerileri Kadıköy örneğinden yola çıkarak tartışılmıştır., The Republic of Turkey, government policies and socio-economic conditions, is effective in forming the housing supply and built environment. This effect is enough to create an ossified "habitus". The "build-and-sell housing supply", which emerged in 1965 with the "Property Ownership Law" and developed in the 80s, gained a new momentum with the "Law on the Transformation of Areas Under Disaster Risk" that entered into force in 2012 after the 1999 Marmara Earthquake.The aim of this study is to show the effect of the policy of the Republic of Turkey on housing and urban tissue. And to reveal the necessity of new and holistic approaches for creating quality housing settlements within the scope of urban transformation. In the research, the physical change of the residential building on the scale of the parcel in the last 70 years, according to the Republican era housing policies, was examined through examples. How this change was reflected physically on the neighborhood and urban fabric was evaluated with the help of maps and pictures.Kadıköy, which is the district where "urban regeneration" is experienced most intensively, was chosen as the research area. The physical change in the residence building has been clearly demonstrated with the help of “building permit projects” before and after regeneration provided by Kadıköy Municipality.A result of the research; The effect of build-and-sell housing presentation culture, which has become the most common with urban transformation in Istanbul, on the inadequacy of urban reinforcement areas and obesity of urban tissue; It is defined by supporting the "floor area ratio" change by years and the "housing stock" data. The next stage where the current housing supply model will carry us, possible problems to be encountered and solution suggestions have been discussed based on the example of Kadıköy.

Background RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system’s 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D. Materials and methods We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants. Results Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively. Conclusions The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise.

Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation.A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively.The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P .05). However, no differences were found according to genotype distribution in all groups (P.05).Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates.Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex).Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042).In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Spondyloarthropathy (SpA) is a group of multi-systemic diseases, whose pathogenesis is not known, characterized by spinal inflammation, peripheral arthritis, and with a lower frequency by extra-articular involvement. Brevverton and Schlosstein introduced the relationship between HLA-B27 and the disease. Along with HLA-B27, the relationship of the disease with other HLA molecules was also shown in studies. Taking this information as a starting point and knowing that the disease is related to ethnic differences, we aimed to investigate the role of the HLA-A and –B alleles in Turkish patients with SpA. Typing of the patients (n=784) was performed by the complement-dependent lymphotoxicity method. The HLA-A and –B tissue groups of the control group (n: 1060) were determined by using serological or molecular methods. The frequency of HLA-B27 in patients was determined as 27%. When B27-negative patients were compared with B27-negative controls, HLA-A29 was found significantly higher in the patients (p: 0.0003, pc: 0.004). Although HLA-B60 was found significantly higher in the patients (p: 0.02), a statistical significance could not be obtained after performing the Bonferroni correction method (pc>0.05). When B27positive patients and controls were compared, HLA-A3 (p:0.0005, pc:0.008), HLA-B35 (P, Spondiloartropati (SpA), spinal inflamasyon ve periferal artrit ile daha az oranda da eklem dışı tutulumla karakterize, patogenezi henüz tam olarak bilinmeyen multisistemik bir grup hastalıktır. Genetik faktörlerin hastalığın gelişiminde önemli rolü vardır. 1973 yılında Brevverton ve Schlosstein, HLA-B27 ile hastalık ilişkisini ortaya çıkarmıştır. HLA-B27 ile birlikte diğer HLA moleküllerinin (DR1, DR4, DR8, DR15, A24, B39 ve B60)hastalıkla ilişkisi yapılan çalışmalarda gösterilmiştir. Bu bilgilerden yola çıkarak ve etnik farklılığın da hastalıkla ilişkili olduğunu düşünerek SpA’lı Türk hastalarda HLA-A ve –B allellerinin rolünü araştırmayı amaçladık. Hastalardan (n=784) heparinli kan örneği alındı. Lenfosit izolasyonunu takiben komplemana bağımlı lenfositotoksisite yöntemi ile ticari kitler (Biotest- HLA-ABC tipleme plağı, 144X2, USA) kullanılarak tipleme yapıldı. Kontrol grubunun (n:1060) HLA-A ve –B doku grupları, serolojik veya moleküler yöntemler kullanılarak tespit edildi. Hastalarda HLA-B27 sıklığı %27 olarak saptandı. B27 negatif hastalar ile B27 negatif kontroller karşılaştırıldığında, hastalarda HLA-A29 anlamlı olarak yüksek bulundu (p:0.0003, pc:0.004, OR:2.6, CI:1.5-4.4). HLA-B60 hastalarda anlamlı olarak yüksek (p:0.02, OR:0.5, CI:0.2-0.9) bulunmasına rağmen Bonferroni doğrulama testi sonrası istatistiksel anlamlılık elde edilemedi (pc>0.05). B27 pozitif hastalarla kontrolleri karşılaştırdığımızda HLA-A3 (p:0.0005, pc:0.008, OR:0.4, CI:0.3-0.7), HLA-B35 (p

Bu tez çalışmasında, Geliştirilmiş Hummers metodu kullanılarak grafen türevleri elde edilmesi hedeflenmektedir. Geliştirilmiş Hummers yöntemi; işlem basamakları açısından daha basit ve düşük maliyetlidir. Ayrıca Hummers yöntemine göre daha tehlikesiz ve daha çevre dostu bir yöntemdir. Bu malzeme sahip olduğu üstün özellikler nedeniyle bir çok uygulama alanı bulmaktadır. Bunların başlıcaları transparan elektrotlar, alan etkili transistörler, sensörler, temiz enerji cihazları, nanokompozitler ve organik fotovoltaik cihazlar olarak sayılabilir. Bu çalışmada üstün özellikleri ile ön plana çıkan grafen nano metaryalinin zehirli toksik gazlar kullanılmadan üretildiği gösterilmiştir. SEM görüntülerinde katmanlı ve çok ince GO yapıları gözlenmiştir. EDX/SEM Elementel analizde oksijen oranının yaklaşık % 24,03 olması oksidasyon işleminin gerçekleştiğini göstermektedir. XRD analizinde 2θ piki, 10,55° de elde edilmiştir. Ayrıca, FT-IR spektroskopisi ve Raman spektroskopisinde ise GO' ya ait karakteristik pikler görülmüştür. Elde edilen sonuçlardan Geliştirilmiş Hummers Yöntemi ile grafit flakeden başarılı bir şekilde rGO sentezlendiği gözlenmiştir. In this thesis, it is aimed to obtain graphene derivativesbyusingthedeveloped Hummers method. Improved Hummers method; it is simplerandlesscostly in terms of processsteps. In addition, it is more safe and environmentally friendly than the Hummers method. This material has many applications because of its süperi or properties. These include transparent electrodes, field effect transistors, sensors, clean energy devices, nanocomposites and organic photo voltaic devices. In this study, it has been shown that graphene nanomaterial, which stands out with its süperi or properties, is produced without theuse of toxictoxicgases. Layered and very thin graphene oxide structures were observed in SEM images. EDX / SEM In the elemental analysis, the oxygen ratio is approximately % 24,03, indicating that oxidation process has taken place. In XRD analysis, 2θ peak was obtained at 10.55 °. In addition, characteristic peaks of GO were observed in FT-IR spectroscopy and Raman spectroscopy. From the results obtained, it was under stood that rGO was successfully synthesized from graphite flake by the developed Hummers method. 78

Background Recently molecular chimerism analysis after allogeneic hematopoietic stem cell transplantation (AHSCT) has become more important. The use of quantitative chimerism methods aims to assess the kinetics of engraftment to determine graft rejection and failure or relapse of the underlying disease after AHSCT. An accurate and sensitive determination of chimerism status is mandatory after AHSCT. This study aimed to compare two chimerism methods: Multiplex Short Tandem Repeat-Polymerase Chain Reaction (STR-PCR) and quantitative Real Time-PCR (qRT-PCR). Methods Thirty-nine blood samples at +28 day were used to extract DNA. Most patients had been diagnosed with acute leukemia (74.3 %) and other hematological diseases. For Multiplex STR-PCR method, PCR products were separated on an ABI 3130 Genetic Analyzer (Applied Biosystem, USA) and for qRT-PCR, an ABI 7500 (Applied Biosystem, USA) Plate System Real Time Analyzer was used to determine the quantification of chimerism per-centage. Results Of the 39 analyzed samples, 82% concordant chimerism results were detected for both STR-PCR and qRT-PCR methods. Ten mixed chimerisms (MC) were found by qRT-PCR whereas of only 3 MC cases were detected by STR-PCR. In the discordant group of 7 by qRT-PCR, we observed Acute Graft versus Host Disease (aGVHD). Three MC cases that were detected by both STR- and qRT-PCR methods died because of relapse. Conclusions The quantitative chimerism method along with multiplex STR-PCR method is important for early detection of MC. qRT-PCR methods can be valuable options in the prevention of graft failure and assisting with fast and early treatment strategies for patients undergoing AHSCT.

Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations.Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit.Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study.Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively.Amaç: Alfa talasemi sendromları, bir ya da daha fazla a-globin genindeki mutasyonlardan kaynaklanır. Mutasyonlar genelikle delesyonel olmakla birlikte non-delesyonel de olabilir. Bazı delesyonlar (3.7 ve 4.2) α+-talasemiye neden olurken bazıları da (-20.5, MED, THAI, FIL) α0-talasemiye yol açar. Bu çalışma ile İstanbul ilinde, diğer nedenlerle açıklanamayan hipokrom mikrositer anemili olgularda alfa talasemi mutasyonlarını belirlemeyi ve mutasyon tiplerini değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu çalışmada 206 hasta alfa talasemi için değerlendirmeye alındı. Her hastadan DNA izolasyonu için 2 ml venöz kan örneği alındı. Strip analiz kiti (ViennaLab Diagnostics GmbH, Austria) kullanılarak alfa talasemi mutasyonları araştırıldı. Bulgular: Doksan beş hastada (%46,1) 14 farklı mutasyon tespit edildi. En sık saptanan mutasyon 3.7 tek gen delesyonu idi (n=37 hasta, %39). Diğer mutasyonlar sıklık sırasına göre; 20,5 kb çift gen delesyonu (n=20, %21), MED çift gen delesyonu (n=17, %17,9), α2 IVS1 (n=10, %10,5), α2 poly-A1 (Suudi tip) (n=6, %6,3), Hb Koya Dora (n=6, %6,3), 4.2 tek gen delesyonu (n=4, %4,2), FIL mutasyonu (n=2, %2,1) ve α1 cd 14 (n=2, %2,1) idi. Hb Adana (n=1), Hb Ikaria (n=1), α2 init cd (n=1) ve α2 poly-A2 (Türk tipi) (n=1) hastaların %1’inde saptandı. Yedi hasta alfa talasemi gen triplikasyonu (%7,4) taşıyordu. Çalışmamızda üç mutasyon (Hb Icaria, α1 cd14, α2 init.cd) Türkiye’de ilk kez tespit edildi. Yedi mutasyon ise (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) hastalarımızda hiç saptanmadı. Sonuç: Alfa talasemi, hipokrom mikrositer anemilerin ayırıcı tanısında özellikle de demir eksikliği ve beta-talasemi taşıyıcılığının saptanmadığı durumlarda akla getirilmelidir. Şüpheli olgularda genetik açıdan mutasyon taraması yapılmalıdır. Alfa talasemi taramasını daha uygun maliyetle yapabilmek için Türkiye’de saptanan tüm alfa talasemi mutasyonlarının toplandığı ulusal bir veritabanı oluşturulmasını önermekteyiz.

Introduction High rates of panel-reactive antibody (PRA) may decrease the chance of kidney transplantation and may result in long waiting periods before transplantation. The calculated PRA (cPRA) is performed based on unacceptable HLA antigens. These antigens are identified by a program that was created based on the antibodies that developed against the HLA antigens circulating in serum and on the risk of binding of these antibodies to antigens. The antigen profile of the population and antigen frequencies can be measured, and more realistic cPRA positivity rates may be obtained using this method. Materials and Methods We developed a program based on the HLA antigens of 494 blood donors in 2 European Federation for Immunogenetics–accredited Tissue Typing Laboratories in Turkey. Next-generation sequencing–based tissue typing (HLA-A, -B, -C, -DR, -DQ, 4 digits) of the samples was performed. The PRA screening test was performed on 380 patients who were waiting for organ transplant from a cadaver in Istanbul Faculty of Medicine. The single antigen bead assay testing was performed to identify the antibody profiles on 48 hypersensitized patients. Results The PRA testing results using the current methods were 44.6% ± 18.5%, and the cPRA rate was 86.2% ± 5.1%. The mean PRA positivity of the sensitized patients using the current methods was 44.6%; however, the rate was 86.2% using the cPRA. Discussion cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. Conclusion In principal, implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match, particularly for hypersensitized patients, by the creation of an unacceptable mismatch program using cPRA software.

The role of neurotrophins in allergic rhinitis (AR) has been well studied, but it has not been evaluated in idiopathic rhinitis (IR).We aimed to evaluate the nasal β-nerve growth factor (β-NGF) expressions of mast cells in patients with AR and IR.Seventeen patients with house dust mites-induced persistent moderate/severe allergic rhinitis (mean age: 29.7 ± 11.96), 14 patients with idiopathic rhinitis (mean age, 29.3 ± 10.62), and 16 healthy controls (29.9 ± 11.57) were included in the study. Nasal biopsy specimens were taken from the posterior part of the inferior turbinate from all of the study subjects. Nasal β-nerve growth factor and its receptors, pan-neurotrophin receptor p75, and tyrosine kinase A (trkA) were assessed with an immunofluorescence assay. Mast cells were determined by both an immunofluorescence assay and immunohistochemistry as tryptase-positive cells.The β-NGF, trkA, and p75 receptor counts were significantly higher in AR and IR patients than in the control group (P.001, for each), but they were not different between AR and IR patients. Similarly, the ratio of β-NGF+ mast cells/total mast cells and the ratio of β-NGF+ mast cells/total β-NGF+ cells in AR and IR patients was found to be elevated when compared with the control group (P.001, P.001, P.001, and P = .046, respectively); furthermore, the 2 ratios were not statistically different between the 2 patient groups.The increase in β-NGF-expressing mast cells does not differ between idiopathic and allergic rhinitis. Therefore, we propose that mast cells do play a role in the pathogenesis of IR as important as in that of AR.

We aimed to investigate (1) the probable correlation between clinical and ultrasonographic findings in chronic painful primary knee OA patients referred with acute flare-ups and (2) the impact of diagnostic ultrasonography (US) to determine the real source of pain in these patients. We included 100 patients consecutively who were admitted to our outpatient unit with a pain complaint on a single knee with the diagnosis of primary knee OA according to the ACR criteria. The control group consisted of the patients with pain-free knees at least during the last month, who were already included in the study group. The sonographic evaluation of the knee was performed by a physician who was blinded to the clinical evaluation and/or the physical and radiological evaluations. In the present study, sonographic findings were significantly more observed on the painful knees (p < 0.001). The most commonly encountered findings on the symptomatic knees were the suprapatellar effusion (55 %), the baker cyst (25 %), and the pes anserine bursitis. The distribution of the findings on the asymptomatic knees was as follows: 22 %, the suprapatellar effusion and 5 %, the Baker cyst. Effusion was detected in 55 % of the painful knees of our patients with knee OA. This finding was statistically significant compared to the painless knees of the subjects included. The results of our study also showed that there was a significant relation between the Kellgren-Lawrence grading and the frequency of suprapatellar effusion on US examination (p = 0.026). It was concluded that in chronic, primary, painful knee osteoarthritis, US is a valuable diagnostic method in the confirmation of synovitis and/or the inflammatory episode in spite of the absence of obvious clinical parameters. In advanced osteoarthritis, when we consider that the inflammatory episodes are expected findings, the early confirmation of the inflammation on US may be particularly valuable in the clinical setting.

Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF-β), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-2, and IL-4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA-treated renal transplant patients and 37 tacrolimus-treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence-specific primers with the cytokine CTS-PCR-sequence-specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF-β at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF-β1-codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL-2-330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Patients who had the TC genotype TGF-β codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF-β-codon 10, IL-2-330 and IL-6-174 polymorphisms may help individualized immunosuppressive dosage regiments.

Certain cytokine gene polymorphisms (CGPs) have been shown to be associated with renal transplant rejection or graft outcomes. We sought to evaluate the relationship between gene polymorphisms in patients with acute rejection episodes (rejection group, RG, n = 19) versus those with stable graft function (nonrejection group, NRG, n = 71) in comparison with healthy control subjects (HCG, n = 150). The follow-up time period was 18 months. In the present study, 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes were genotyped by polymerase chain reaction sequence-specific primers (PCR-SSP) using the Heidelberg kit.The interleukin-2 (IL-2) TT/GT haplotype was observed among 36.8% of patients in the RG and 6.7% of those in the HCG but not in any NRG patient (P.0001; .0007). The IL-2 GG/TT haplotype was observed among 13 NRG and 9 HCG patients (P = .007). The IL-2 GG/GG haplotype was noted in 18.7% of HCG and 4.2% of NRG patients (P = .0033) and the IL-2 TT/TT haplotype in 5 and 8 patients of NRG and HCG, respectively, but not in any RG patient (P.05). The transforming growth factor beta1 CG/CC haplotype was noted in 15 NRG (21.1%) and 4 HCG patients but not any RG (P.0001). The IL-2 + 166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG patients (P = .005, .0244). The IL-2 -330 GG genotype was demonstrated in 32 healthy controls and 3 nonrejection transplant patients (P = .0007). Significant differences were found between NRG and HCG for IL-6 565 AG, IL-1 beta -511 TT and +3962 CC/CT/TT genotypes.We observed significant differences among the frequencies of IL-2 gene polymorphisms between the RG and the NRG, which were consistent with previous clinical but not in vitro studies.

The balance between oxidative stress and anti-oxidant defense systems after renal transplantation may explain the development and progression of allograft dysfunction. Glutathione S-transferase (GST) decreases the damage from oxidative stress. In contrast, recipient antibodies against GSTT1 expressed on the graft are believed to cause its dysfunction. The aim of our research was to study the probable relationship to rejection between GST gene polymorphisms and anti-GSTT1 antibodies. We included 122 patients transplantations from living donors and 51 healthy individuals as controls group in our study. The patient groups were comprised of 57 patients who did and 65 who did not experienced rejection episode. Polymerase chain reactions were used to detect GSTM1 and GSTT1 polymorphisms, whereas PCR-RFLP (restriction fragment length polymorphism), for GSTP1 polymorphism. An enzyme-linked immunosorbent assay method was used for anti-GSTT1 antibody scans. There was no significant difference between the groups for allele and genotype frequencies of GSTT1, GSTM1, GSTP1 polymorphisms of the recipients, donors, and controls. Within the rejection group the frequency of patients with the GSTM1 null genotype was higher among subjects prescribed cyclosporine A versus tacrolimus (P = .029). Among the entire patient group, 46 subjects with GSTT1 null genotype were scanned for anti-GSTT1 antibody which was detected in 5 of 8 patients with an acute rejection episode (P = .04). Anti-GSTT1 antibody was observed more frequently albeit not significantly, among the cyclosporine versus tacrolimus patient group (P = .16). This study suggested that GSTM1 genotype may be important for cyclosporine detoxification and for allograft outcomes due to drug nephrotoxicity. After transplantation, antigens distinct from the HLA system such as GSTT1 protein may also be targets for alloimmune responses.

Fusarin C is a Fusarium mycotoxin that rearranges under reversed phase chromatographic conditions. In this study, the rearrangement of fusarin C was examined in detail, and the formation of fusarins under different conditions was optimized. All relevant fusarins including (10Z)-, (8Z)-, and (6Z)-fusarin C were isolated and identified by NMR. To confirm the involvement of the 2-pyrrolidone ring in the rearrangement of fusarin C, 15-methoxy-fusarin C was synthesized. For the first time, the structure of open-chain fusarin C was elucidated, and on the basis of these data, the rearrangement product of fusarin C was identified as epi-fusarin C. The results were confirmed by detailed NMR measurements and density functional theory calculations. Furthermore, a new fusarin C like metabolite, which was named dihydrofusarin C, was detected by analysis of the crude extract of fusarin C with high-performance liquid chromatography coupled to UV and Fourier transform mass spectrometry.

Summary To investigate possible mutations and/or single nucleotide polymorphisms in the synaptonemal complex protein 3 (SYCP3) gene among nonobstructive azoospermic infertile males in a Turkish population, 75 nonobstructive azoospermic infertile male patients were included in the study. These patients were unrelated to each other and had 46,XY chromosome structure without Y microdeletion. In addition, 75 individuals whose fertility was proven by reproduction were enrolled in the study as controls. Nine exon deep intronic primers belonging to the SYCP3 gene were designed and amplified by PCR, and the nucleotide sequences were identified by DNA sequence analysis. DNA sequence analysis was used to detect mutations and/or single nucleotide polymorphisms in the SYCP3 gene. No mutations were detected in the 9 exons of SYCP3. A total of eleven variations, however, were detected: seven have been identified in the NCBI SNP database, whereas four have not. On the basis of the results, we agree with the idea that SYCP3 mutations are not associated with the genetic susceptibility for meiotic arrest in infertile male patients with nonobstructive azoospermia in the Turkish population and that further studies investigating the other components of the synaptonemal complex protein (SYCP1, SYCP2) should be conducted.

The objective of this study is to investigate the quality of life and the rates of depression in spouses/partners of patients with AS compared with spouses/partners of healthy controls”. Twenty-five persons with AS and their 25 spouses (21 women and 4 men) and 25 healthy controls were recruited consecutively. All the subjects completed 36-item Short Form Health Survey (SF-36) questionnaire forms and 17-item Hamilton Depression Rating Scale (HAM-D17). Mean age was 35 ± 6.47 years in spouse group (SG) and 36.26 ± 5.93 in control group (CG). In SG and CG, the SF-36 subscale scores were compared using Mann–Whitney U test. Social functioning, mental health, emotional role, and general health were significantly (P < 0.05) lower in SG compared with CG. The average score of social functioning was found to be 65.41 in spouses of patients compared with healthy controls (90.75). Depression scores were significantly (P < 0.001) higher in SG compared with CG. Among SF-36 subgroups in spouses, general health perception had a negatively significant correlation with depression scores (P < 0.05) and duration of ankylosing spondylitis (P < 0.05). A positively significant correlation has been identified between bodily pain and depression scores in spouses (P < 0.05). Therefore, female partners of male patients were found to be more depressive. Being a spouse of a patient with AS significantly interferes with quality of life and increases the depression frequency.

Unalan H, Majlesi J, Aydin FY, Palamar D. Comparison of high-power pain threshold ultrasound therapy with local injection in the treatment of active myofascial trigger points of the upper trapezius muscle. Objective To compare the effects of high-power pain threshold ultrasound (HPPTUS) therapy and local anesthetic injection on pain and active cervical lateral bending in patients with active myofascial trigger points (MTrPs) of the upper trapezius muscle. Design Randomized single-blinded controlled trial. Setting Physical medicine and rehabilitation department of university hospital. Participants Subjects (N=49) who had active MTrPs of the upper trapezius muscle. Interventions HPPTUS or trigger point injection (TrP). Main Outcome Measures Visual analog scale, range of motion (ROM) of the cervical spine, and total length of treatments. Results All patients in both groups improved significantly in terms of pain and ROM, but there was no statistically significant difference between groups. Mean numbers of therapy sessions were 1 and 1.5 in the local injection and HPPTUS groups, respectively. Conclusions We failed to show differences between the HPPTUS technique and TrP injection in the treatment of active MTrPs of the upper trapezius muscle. The HPPTUS technique can be used as an effective alternative to TrP injection in the treatment of myofascial pain syndrome.

Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells.

A 31-year-old female with refractory extramedullary myeloid leukemia relapse underwent peripheral blood stem-cell transplantation from her HLA-identical brother. Hematopoietic recovery followed disappearance of the lesions. Studies three-months post-transplant showed complete chimerism (CC). Fourteen months after transplantation, the patient presented with an increasing number of extramedullary sites of biopsy-proven disease relapse (as nodular skin lesions). Bone marrow was in remission with maintenance of CC. However, tissue chimerism analysis showed full recipient-cell population. After one course of conventional dose chemotherapy followed by mobilized donor-lymphocyte infusions (DLI), a complete response was achieved. DLI continued monthly but she developed new skin lesions accompanied by multiple cervical masses. Bone marrow and tissue chimerism revealed both recipient and donor cell population. We conclude that tissue chimerism analysis after DLI may not accurately document the cell origin.

Nigella sativa Linn. (Ranunculaceae) is known to have beneficial effects on a wide range of diseases including asthma. However, the mechanism of action in asthma and other allergic diseases is not entirely clear. The present study was planned to evaluate the effects of Nigella sativa on cytokine production of splenic mononuclear cells in ova-sensitized mice. Nineteen two-month-old BALB/c mice were given 0.3 mL of Nigella sativa oil by oro-eosophageal cannula once a day for a month. The control group consisting of 10 mice took 0.3 mL of 0.9% saline solution by the same route for the same period. In the third week of the study, all mice were sensitized by means of intraperitoneal injections of 20 microg of ovalbumin (OVA-Grade VI, Sigma). Ova injections were repeated three times with 7-day intervals. After another week, all mice were sacrificed by means of cervical dislocation. Then the splenic mononuclear cells (MNCs) of mice were cultured with OVA or Concavalin A (Con-A). From the culture supernatants, IL-4, IL-10 and IFN-gamma were assessed by means of ELISA. The cytokine production of splenic MNCs of mice that were given Nigella sativa for 30 days was not significantly different than those who took saline solution instead. In conclusion, Nigella sativa oil seems not to have an immunomodulatory effect on Th1 and Th2 cell responsiveness to allergen stimulation.

Background Familial Mediterranean fever (FMF) is one of the most frequent genetic diseases encountered in the Mediterranean region. We aimed to investigate the correlation between genetic mutations and the clinical findings in 562 patients with FMF. Methods In this retrospective cross-sectional study conducted with patients’ files between 2006, and 2013, reverse hybridization assay for MEFV gene mutations was used and the 12 most frequent mutations were screened. Mutation types and clinical findings were compared with variance analysis. Results The mean age was 6.9 ± 3.4 years (range, 1.8-11.6 years). The most common symptom was fever (97.3 %). Thirty-four of the patients (6.04 %) were admitted with periodic fever only. Of these patients, M694V was the most common mutation type (73.5 %). The percentage of the patients predominantly presenting with recurrent abdominal pain was 77.78 % and the most frequent mutations were M694V and E148Q. The rate of arthritis and arthralgia was significantly higher in patients with M694V and E148Q mutations. Chest pain was reported more often in patients homozygous for M694V (61.4 %). Pericardial effusion was documented in the echocardiography of 10.9 % of the 229 children with chest pain. Some patients had both FMF and Henoch Schönlein purpura (HSP), and were more likely to harbor either homozygote M694V or E148Q mutations. The frequency of episodes was higher in patients with homozygous M694V mutations (number of attacks = 4.4 ± 1.6/month). Proteinuria was detected in 106 patients of cases (29.2 %), at an average of 854 ± 145 mg/L. Most of the patients with proteinuria and elevated serum amyloid-A had homozygous M694V mutation. Conclusion The most common mutation in children in Turkey with FMF is the M694V mutation. Recurrent abdominal pain, arthritis or arthralgia, chest pain, and pericarditis were commonly seen in patients with M694V and E148Q mutations.