Polisitemia Vera’da CXCL9-CXCR3 Sitokin Sinyal Yolağının Etkisi

Amaç: Miyeloproliferatif Neoplaziler (MPN), miyeloproliferatif bozukluklar arasında en sık görülen hastalıklardandır. Tamamen işlevsel olan ve son aşamaya kadar farklılaşmış kan hücrelerinin aşırı üretimi ile karakterize edilirler. Önceki çalışmalarda Granülosit-Makrofaj Koloni Uyarıcı Faktörün (GM-CSF) sağlıklı hematopoietik kök hücreler (HKH)’de proliferasyon kontrolünden sorumlu CXCR3 ekspresyonunu arttırdığı gösterilmiştir. Bu çalışmanın amacı, CXCL9-CXCR3 sinyal yolağının MPN progresyonunda etkisinin araştırılmasıdır.Gereç ve Yöntem: Çalışmada, MPN ve sağlıklı insan perifer kan mononükleer hücrelerinde (MNH) ve kanser HKH de CXCL9 kemokini ve bunun reseptörü olan CXCR3’ün iki izoformunun (CXCR3A ve CXCR3B) gen ifade seviyeleri, MNH yüzeyinde ise CXCR3 reseptör varlığı incelenmiştir. Ekspresyon seviyelerini araştırmak amacıyla kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (PZR), hücre yüzey reseptör durumunun incelenmesi içinse akım ölçer metotları kullanılmıştır. GM-CSF’in MNH ve CD34+ hücrelerinde uygulamasının ardından CXCR3 ekspresyonu değerlendirilmiştir.Bulgular: MNH’de CXCR3A ifadesinin hastalarda sağlıklılara göre istatistiksel olarak anlamlı arttığı bulunmuşur. Hasta ve sağlıklı kontrol grupları arasında CXCR3B ve CXCL9 ifade seviyeleri kıyaslandığında istatistiksel olarak anlamlı bir fark olmadığı tespit edilmiştir. CXCR3 Hücre yüzey reseptör durumuna bakıldığında ise hastalardan elde edilen MNH’deki anlatımda sağlıklı gruptan elde edilenlere göre anlamlı bir azalma olduğu görülmüştür.Sonuç: Bu sonuçlar MPN’de CXCR3A/CXCR3B dengesi ile bu reseptörlere özgün olarak bağlanan kemokinler CXCL9, CXCL10 ve CXCL11’in inflamasyon ve kanser progresyonu ile ilişkili olabileceğini düşündürmektedir

The comparative effects of the feed additives of yeast (Saccharomyces cerevisiae) and enterococcus faecium on the criteria of ıntestinal microflora, egg quality and performance in laying hens

Bu araştırmada yumurta tavuğu rasyonlarında maya (Saccharomyces cerevisiae) ve Enterococcus faecium yem katkımaddelerinin performans ve yumurta kalite kriterleri üzerine etkilerinin karşılaştırmalı olarak belirlenmesi amaçlandı. Bu amaçla, Grup 1’de: Kontrol (K), Grup 2’de: K+ 1 g/kg Entereococcus faecium (EC) (cylactin ME 10 1x1010 cfu/g) ve Grup 3’te:K+ 1g/kg maya (SC) (Saccharomyces cerevisiae) katkıları yeme uygulanarak yumurta tavuklarının performans parametreleri,bağırsak mikroflorası ve ince barsak villus uzunlukları karşılaştırıldı. Araştırmada 45 haftalık yaşta toplam 108 adet Lohmanırkı kahverengi ticari yumurtacı tavuk kullanıldı. Deneme grupları her grupta 36 tavuk olacak şekilde 3 farklı grup olaraktasarlandı. Yem tüketimi, yumurta üretimi, yumurta ağırlığı, yemden yararlanma oranı bakımından gruplar arasındaistatistiksel olarak fark olmadığı bulundu (P>0.05). Benzer şekilde yumurta kalite kriterleri bakımından gruplar arasındaistatistiki bir farklılık tespit edilmedi. Total bakteri sayısı, Enterococcus feacium katkılı gruba göre kontrol ve maya katkılıgrupta azaldı. Mide barsak sistemindeki total maya-mantar sayısı, maya katkılı grupta artmış ancak kontrol ve Enteroccus faecium katkılı grupta azaldı. Serum kırmızı kan hücreleri (SRBC) bakımından gruplar arasında fark olmadı. Sonuç olarak, Enteroccus faecium ve maya katkısının yumurtlama performansı ve yumurta kalite kriteri üzerine etkisinin olmadığı, ancaktotal bakteri sayısının Enterococcus faecium katkılı grupta, total maya-mantar sayısının ise maya katkılı grupta arttığı,Saccharomyces cerevisiae ve enterococcus’un SRBC üzerine istatistiksel olarak bir etki göstermediği tespit edildi.Abstract: This study was conducted to determine the comparative effects of the additives of yeast and Enterococcus faecium on the criteria of intestinal microflora, egg quality and performance in laying hens. Treatment groups employed were as follows: Group 1- Control (C, n=36): the criteria of intestinal microflora, egg quality and performance were 10 compared, Group 2 (n=36): C + 1 g/kg Enterococcus faecium (EF) (Cylactin ME 10 1x10 cfu/g), and Group 3 (n=36): C +1 g/kg yeast (Saccharomyces cerevisiae) (SC). The experiment was carried out on 108 Lohman Brown strains of hens, aged 45 weeks old, allocated into 3 groups of 12 replications, each containing 3 hens. Trial groups contained 36 hens each. The feed intake, egg production, egg weight and feed conversion ratio did not differ statistically between the groups (P>0.05). Similary, the egg quality criteria also did not differ statistically between the groups. The number of total bacteria increased in the Enteroccocus faecium group as compared to those of control and yeast-added groups. The number of yeast-fungus increased in the gastrointestinal tract of the yeast group, but it decreased in the control and Enterococcus faecium-added groups. The Serum Red Blood Cells (SRBC) showed no difference between the groups. As a result, the additions of Enterococcus faecium and yeast had no effect on the laying performance, but the numbers of total bacteria and and total yeast-fungus increased in the Enterococcus faecium- and yeast-added groups, respectively. The SRBC was not affected statistically by Saccharomyces cerevisiae and enterococcus

Effects of mutational combinations on philadelphia-negative myeloproliferative neoplasms

WOS: 000399199200015PubMed ID: 28360451Philadelphia-negative myeloproliferative neoplasms (MPNs) were first described 65 years ago. Yet, the molecular features of the disease have become of interest since 2005 following the identification of the JAK2V617F mutation.1 Between 90% and 98% of patients with polycythemia vera and about 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) harbor the JAK2V617F mutation.2 In recent years, additional genetic factors such as the mutations of IDH1/2, TET2, EZH2, ASXL1, and CALR have been identified in Ph-negative MPNs.3 However, the significance of mutational combinations on Ph-negative MPNs remains unknown

Activation-induced cytidine deaminase mRNA levels in chronic lymphocytic leukemia

WOS: 000286901600015PubMed ID: 21133730The Rai and Binet staging systems, which are used as standard methods for evaluating the prognosis of chronic lymphocytic leukemia (CLL), have some restrictions in identifying patients with early-stage CLL who will progress rapidly. To solve this defect, other prognostic parameters have become important in recent years. Intracellular up-regulation of the AID gene in the leukemic lymphocytes of patients with CLL may be an important parameter for predicting the progression of CLL. In this study, AID mRNA expression levels were evaluated in 50 patients with CLL and 50 healthy controls. AID mRNA expression was significantly higher in patients than in controls. We then evaluated AID mRNA levels according to the stages of CLL. Regarding AID mRNA levels, patients with Rai stages 0, I, and II were compared with patients with stages III and IV, whereas patients with Binet stage A were compared with patients with Binet stages B and C. In patients with higher-risk Rai stages III and IV and Binet stages B and C, activation-induced cytidine deaminase (AID) mRNA levels were also significantly higher. Additionally, we found that the mRNA levels of patients with AID in CLL were eight-fold higher than those in control patients, suggesting that AID overexpression promotes chromosomal abnormalities and is associated with CLL progression and survival. For this reason, and because of the simplicity of quantitative real-time PCR analysis, AID might be a useful clinical parameter after its importance is confirmed in larger and multivariate studies

The clinical significance of IDH mutations in essential thrombocythemia and primary myelofibrosis

Background: Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). Methods: High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. Results: PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. Conclusions: We conclude that IDH mutations indicate a risk for leukemic transformation in PMF