Küçük Hücreli Akciğer Kanseri ve Behçet Hastalığında oluşan otolog antikor yanıtının belirlenmesi ve tanımlanması için yöntem geliştirilemesi

Cataloged from PDF version of article.Thesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2016.Includes bibliographical references (leaves 46-49).Autologous antibodies are known to be elicited in Behçet’s Disease (BD) and Small Cell Lung Cancer (SCLC). SCLC consists 15-20% of all lung cancer cases. It is follows a most aggressive course and generally patients are diagnosed at later stages. The median survival of patients is 9-12 months. Diagnostic methods such as CT and PET are somewhat useful in the diagnosis of lung cancer but not so much for SCLC as the doubling time of this tumor is very rapid. Therefore, new diagnostic tools are needed for early diagnosis and to increase median survival of patients. Behçet’s Disease is autoimmune disease and the prevalence of BD in Turkey is the highest in the world. Also autologous antibodies against various antigens associated with BD have been discovered in BD. BD has vascular, oral, cutaneous and neuronal subtypes and autologous antibodies correlating with each subtype have been reported. However, for BD, there does not exist a diagnostic or prognostic test as none have been developed yet. However autoantibodies can be utilized for the diagnosis and follow-up of SCLC and BD because it is known that autoantibodies are expressed well in advance of disease symptoms. The first aim of this study was to determine a correlation between antigen expression levels in tumor tissues and the presence of autologous antibodies. The second aim of this study was to extend earlier experiments related to the characterization of autologous antibodies against known and novel antigens in SCLC and BD, utilizing high-density protein arrays (PA). The third and major aim of this study was to develop a reliable and sensitive method that could be used to evaluate protein array screening results and lastly, to validate these results by performing optimized ELISA and Western Blot experiments. Previously, PAs were screened with 50 SCLC, 50 BD and 50 healthy serums in our laboratory, and evaluated visually utilizing no automation. Sensitivity and specificity values were calculated using custom-generated antigen panels which included 180 antigens. ELISA experiments were performed to validate antigens thus discovered. However, largely discrepant PA and ELISA results, together with inconsistent ELISA results required us to optimize ELISA conditions, as well as to generate an automated PA evaluation method that would generate numeric data. We modified ELISA by altering various parameters until we were able to obtain consistent results. We also generated a reliable method by which we could produce numeric data corresponding to antibody presence as determined from PA screening results. The method is based on the calculation of pixel intensities of sero-reactive clones on the array which are converted to numeric data, and the subsequent determination of proper cut-offs by which sensitivity and specificity of antibody responses can be generated by comparing values obtained from healthy to those obtained from diseased serum. We call this the “Digital Spot Evaluation” (DSE) tool. DSE was performed utilizing Adobe Photoshop CS6 and parameters of the test were optimized using five replicate screens of a given serum. Pearson’s r correlation values of repeated experiments after optimization were close to 1. Also, when protein arrays are screened using DSE on different days by different researchers, results are highly concordant. We evaluated protein array screening data obtained for SCLC and healthy sera by DSE. In particular, antibody intensities against SOX2, p53 and POLB proteins were calculated and sensitivity/specificity values were determined. With DSE based evaluation of protein arrays, we reached 44%, 6% and 20% sensitivity at 100% specificity for SOX2, p53 and POLB proteins respectively. On the other hand if we evaluate 3 proteins together as a panel, our sensitivity increases to 56% at 100% specificity, and 66% sensitivity at 96% specificity. However, even after optimization, ELISA results showed 32%, 4% and 4% sensitivity at 100% specificity for SOX2, p53 and POLB proteins respectively, demonstrating that DSE is significantly more sensitive than ELISA. We are planning to use DSE to evaluate PA data generated from many other types of tumors in the future and to and possibly to develop a kit based on this method to be utilized for the diagnosis and follow-up of SCLC and BD.by Alper Poyraz.M.S

The impact of cognitive impairment, neurological soft signs and subdepressive symptoms on functional outcome in bipolar disorder

Background: Cognitive impairments and subsyndromal depressive symptoms are present during euthymic periods of bipolar disorder (BD). Most studies have determined that cognitive impairments and residual depressive symptoms have major impacts on psychosocial functioning. The aim of the present study was to identify the major factor responsible for low psychosocial functioning in a subgroup of patients with BD despite clinical recovery

SEVERE TRICUSPID REGURGITATION AND ATRIOVENTICULAR BLOCK CAUSED BY BLUNT THORACIC TRAUMA IN AN ELDERLY WOMAN

Background: Symptomatic cardiac injury after blunt chest trauma is relatively rare, and valvular injury is even more rare. The valves most commonly affected are tricuspid. Automobile accidents are mostly responsible for this type of injury. Objectives: Unlike with the mitral valve, post-traumatic tricuspid heart valve insufficiency is usually well tolerated. Indeed, severe tricuspid regurgitation can resolve spontaneously. Case Report: A 68-year-old woman with no previous cardiac or medical history was brought to our Emergency Department after an automobile accident. She had chest pain and shortness of breath upon admission. Transthoracic echocardiographic examination revealed severe tricuspid regurgitation with rupture of the chordae tendineae and prolapse of the valve cusps into the right atrium during systole. An electrocardiogram was consistent with second-degree Mobitz II atrioventricular block on admission, which subsequently progressed to complete atrioventricular block on day 3. During follow-up with close hemodynamic monitoring, her symptoms disappeared and repeat echocardiography revealed a regression in the severity of tricuspid regurgitation. Operative repair of the tricuspid valve was deemed unnecessary and the patient was discharged with medical therapy on the eighth day after admission. Conclusions: It is important to be aware of traumatic tricuspid regurgitation after non-penetrating chest trauma. Close follow-up may suffice in some patients with stable hemodynamic conditions, and regression of tricuspid regurgitation can be expected during follow-up. (C) 2012 Elsevier Inc

Autologous anti-SOX2 antibody responses reflect intensity but not frequency of antigen expression in small cell lung cancer

Background: Anti-SOX2 antibody responses are observed in about 10 to 20% of small cell lung cancer (SCLC) patients. The aim of this study was to determine whether such responses reflect a particular pattern of SOX2 protein expression in the tumor and whether this pattern associates with clinical outcome

Electrocardiogram patterns in intermedius coronary artery occlusion

Background: Despite the very high knowledge about the electrocardiogram (ECG) changes in other coronary vessel oclussions, there are a few researches demonstrating ECG changes seen during the total/subtotal occlusion of intermedius coronary artery (IM). The aim of this research was the ECG review of 66 patients who had a primary percutaneous coronary intervention (PCI) and a total/subtotal occluded IM with ST segment elevation myocardial infarction (STEMI)

Reliability and Validity of Rowland Universal Dementia Assessment Scale in Turkish Population

Background: The aim is to validate Turkish version Rowland Universal Dementia Assessment Scale (RUDAS). Methods: One hundred forty patients (>65 years) were included. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition -V was used in all patients. Rowland Universal Dementia Assessment Scale was applied for 2 days. Results were compared with Mini-Mental State Examination; reliability, validity, and statistical values were determined. Results: Time validity was verified. Mini-mental state examination was correlated 45.3% in control and 73% in dementia group. Factor weights varied between 0.44 and 0.81; factor construct was verified as 6-item scoring. When 25 was cutoff point, sensitivity was 92.86% and specificity was 92.86%. Content validity index was found to be 100% by 7 specialists. Cronbach alpha (0.692) and test-retest reliability (intraclass correlation = 0.987) were determined. Conclusion: Rowland Universal Dementia Assessment Scale (Turkish) is validated and verified as reliable. Test could be applied for 5 minutes approximately; results are not affected by educational status, immigrant status, and language used; however, age and gender have significant effect on results