Investigation of cytokine signal supressor (SOCS)-1 1478 CA/DEL gene polymorphism in patients with ulcerative colitis

Ülseratif kolit, kolonun distalinden proksimaline doğru diffüz mukozal tutulum gösteren, remisyon ve aktivasyonlarla seyreden kronik inflamatuvar bir hastalıktır. İnsidansı ülkemizde ve dünyada giderek artma eğilimindedir. Patogenezi tam olarak aydınlatılamamıştır. Etkilenen kişilerde çevresel faktörler, genetik faktörler ve immun sistemin ilişkisinden kaynaklanan kolon mukozasında kronik inflamatuvar bir süreç gelişmektedir. Ülseratif kolitte gelişen inflamasyonun değişik klinik tablolar sergilemesi immun sistemin aşırı cevap vermesinden olabilir. Mukozal immun sistemdeki bozulmalar aşırı sitokin cevabıyla ortaya çıkan kronik kontrol edilemeyen mukozal inflamasyona yol açar. İmmun sistemin regülasyonunu sağlayan ve bu ölçüsüz cevabı engelleyen önemli proteinlerden biri sitokin sinyal supresör (SOCS-1 ) proteinidir. SOCS-1 sitokin sinyal iletiminin doğal inhibitörüdür. SOCS-1 fonksiyonunu değiştirecek mutasyon ya da polimorfizm neticesinde GİS kanalda gelişen aşırı immun cevaba bağlı olarak inflamatuar süreç meydana gelebilir ve mukozal hasar gelişebilir. SOCS-1 proteininde meydana gelebilecek polimorfizm inflamatuar süreç gelişimine katkıda bulunarak hastalık etyopatogenezinde rol oynuyor olabilir.Biz bu çalışmamızda SOCS-1 gen polimorfizmini, etyopatogenezinde tekrarlayan kronik inflamasyona neden olan baskılanamayan aşırı sitokin cevabının önemli rol aldığı Ülseratif Kolit tanılı hastaların kendi içinde ve sağlıklı kontrol grubu ile karşılaştırarak incelemeyi amaçladık.Çalışmada Ülseratif Kolit tanısı almış hastalarda değişik klinik tabloları (Remisyondaki hastalar, aktivasyondaki hastalar, kollektomili hastalar) ile SOCS-1 1478 CA/DEL polimorfizm ve tiplerinin (majör homozigot CA/CA, minör homozigot DEL/DEL, heterozigot CA/DEL) ilişkisi hastaların kendi içinde ve sağlıklı kontrol grubu ile karşılaştırarak araştırıldı.Çalışma prospektif olarak yürütüldü. Çalışmaya, 52 Ülseratif Kolit tanılı hasta ve 52 sağlıklı kontrol grubu dahil edildi. Çalışmaya katılan hastalarda SOCS-1 1478 CA/DEL gen polimorfizmi, polimeraz zincir reaksiyonu ve restriksiyon fragmanı uzunluk polimorfizmi (PZR-RFLP) yöntemi ile tayin edildi.Ülseratif Kolit tanılı hastalarda SOCS-1 1478 CA/DEL gen polimorfizmi genotipleri sıklığı; CA/CA (Majör homozigot) 24 (%46.2), DEL/DEL (Minör homozigot) 12 (%23.1), CA/DEL (Heterozigot) 16 (%30.8) hastada tespit edildi. Kontrol grubundaki bireylerde ise; CA/CA 23 (%44.2) kişide, DEL/DEL 10 (%19.2) kişide, CA/DEL 19 (%36.5) kişide saptandı. Bu sonuca göre hasta grubunun SOCS-1478 CA/DEL gen polimorfizm genotipleri sıklığı, kontrol grubu bireyleri ile karşılaştırıldığında benzer bulunarak istatisel anlamlılık düzeyine ulaşmadı (p= 0.794).Çalışmamızda Ülseratif Kolit seyri ile SOCS-1 1478 CA/DEL polimorfizmi arasında ilişki saptayamamış olmamız, hasta sayısının azlığından kaynaklanabileceği gibi SOCS1 1478 CA/DEL dışında başka bir SOCS (SOCS-2 -SOCS-7) polimorfizmi ile de ilişkili olabilir.Sonuç olarak; çalışmamız Ülseratif Kolit tanılı hastalarda SOCS-1 gen polimorfizmini araştıran ilk çalışma olması nedeniyle önemlidir. Ancak bu konuda daha kesin bir sonuca varmak için Türkiye' den ve dünyadan daha fazla sayıda vaka içeren çalışmalara ihtiyaç vardır.Ulcerative colitis is a chronic inflammatory disease which shows a diffusely mucosal involvement towards proximal from colon distal and proceeds with remissions and activations. Its incidence is in gradually trend in our country and all over the World. The pathogenesis cannot be completely elicited. Due to the relation of environmental, genetic factors and immune system, at the colon mucosa of the affected people there is a chronic inflammatory process in progress. Display of different clinical tables of inflammation developed at ulcerative colitis can be due to the excessive response of the immune system. Deteriorations at mucosal immune system lead to chronic uncontrallable mucosal inflammation emerging by intense cytokine response. One of the important proteins which provides the regulation of the immune system and prevents this excessive response is cytokine signal suppressor (SOCS-1) protein. SOCS -1 is the natural inhibitor of cytokine signal transmission. At the result of polymorphism or mutation which changes SOCS-1 function, depending on the excessive immune response improved at GIS canal inflammatory process can occur and mucosal deterioration can evolve. Polymorphism which can be at SOCS-1 protein, making contribution to the inflammatory process development, may play a part at disease etiopathogenesis.In our study we aimed to examine SOCS-1 gene polymorphism, comparing patients with ulcerative colitis in their own group with healthy control group that unpressured excessive cytokine response which causes recurring chronic inflammation which plays an important role in etiopathogenesis.In the study, the relation of SOCS-1 1478 CA/DEL polymorphism and types (major homozygous CA/CA, minor homozygous DEL/DEL heterozygote CA/DEL) and different clinical tables of ulcerative colitis diagnosed patients ( patients at remission, patients at activation, colectomy patients) was searched comparing their own group with healthy control group.The study was performed prospectively. 52 ulcerative colitis diagnosed patients and 52 healthy control group were included in the study. SOCS-1 1478 CA/DEL gene polymorphism of the patients in the study was specified with polymerase chain reaction and restriction fragment length polymorphism method (PZR-RFLP).Genotype frequency of SOCS-1 1478 CA/DEL gene polymorphism at ulcerative colitis diagnosed patients, CA/CA (major homozygous ) at 24 patients (46.2%), DEL/DEL (minör homozygous) at 12 patients (23.1 %), CA /DEL (heterozygote) at 16 patients (30.8%) were found. At control group, CA/CA (44.2%) at 23 people, DEL/DEL at 10 people (19.2%), CA/DEL at 19 people (36.5%) were detected. According to this outcome, when SOCS-1478 CA/DEL gene polymorphism genotype frequency of the patient group was compared with control group it was found similar and could not be reached to the statistical significance level (p=0.794).As we could not determine a correlation between ulcerative colitis progress and SOCS-1 1478 CA/DEL polymorphism in our study, except SOCS 1 1478 CA /DEL it could be related with an another polymorphism of SOCS (SOCS -2 - SOCS-7 ) such as it could be based on the lack of number of patients.In conclusion, as our study is the first one to ınvestıgate SOCS-1 gene polymorphism at ulcerative colitis diagnosed patients it is considerable. But to get a more accurate result on this subject more and more studies from Turkey and the World which have many cases are necessary

Retrospective analysis of the microbiological spectrum of pneumonia in Turkish patients with lung cancer

Aim of the study: The spectrum of pulmonary infections in patients with lung cancer is wide, and tools for target-oriented infection control measures are necessary. In this retrospective study we report the microbiological spectrum of pneumonia (based on the results of sputum culture) in a case series of Turkish patients with lung malignancies. Material and methods: Between 2010 and 2011 a total of 119 patients (111 males and 8 females, mean age: 59.8 ±9.6 years) with lung cancer and pneumonia were identified at the Department of Medical Oncology of two Turkish Universities (Uludag University, Bursa and Cumhuriyet University, Sivas). Expectorated sputum samples were collected in sterile specimen containers and processed immediately in the hospital bacteriology laboratory. Results: Of the 119 study patients, 92 (77.3%) had positive isolates from sputum cultures. The most frequent isolate from the sputum of lung cancer patients with pneumonia was Aspergillus fumigatus (n = 22), followed by Haemophilus influenzae (n = 13) and Pseudomonas aeruginosa (n = 12). The likelihood of having a positive Aspergillus fumigatus sputum culture was significantly and independently associated with febrile neutropaenia (OR = 1.32, 95% CI: 1.17–3.68, p < 0.05) and the development of pneumonia within the first 10 days of chemotherapy initiation (OR = 1.78, 95% CI: 1.37–4.12, p < 0.01). Conclusions : We conclude that Aspergillus fumigatus was the most frequent isolate, but the high diversity of pathogens clearly challenges the empirical use of antimicrobial drugs