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Amac : Bu calismada akut lenfoblastik losemi (ALL) on tanili olgularda t(12;21) translokasyonu gercek zamanli kantitatif revers transkriptaz polimeraz zincir reaksiyonu (qRT-PZR) yontemi kullanilarak kantite edildi. Hastalar ve yontemler : Ocak 2009 - Aralik 2013 tarihleri arasinda Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali’na basvuran 175 pediatrik ve 138 eriskin olmak uzere toplam 313 olguya ait kan ve kemik iligi orneklerinde t(12;22) (p13;q22) translokasyonu RNA sonuclari kantitatif olarak degerlendirildi. Olgulara ait 75 kan ve 484 kemik iligi orneklerinden total RNA veya haberci RNA izole edildi. RNA izolasyonlarinin ardindan tamamlayici DNA sentezi gerceklestirildi. t(12;21) (p13;q22) translokasyon calismasi LightCycler t(12;21) Kit’i ile fuzyon transkripte ozgul bicimde tasarlanmis primer ve problarla (Way2Gene) uygun olacak sekilde gerceklestirildi. Son adim olarak, t(12;21) translokasyon sonuclarinin kantitatif olarak degerlendirilmesi gercek zamanli qRT-PZR yontemi kullanilarak LightCycler2 ile gerceklestirildi. Bulgular : Otuz dort pediatrik olgu orneginde (%19) ve 17 eriskin olgunun orneginde (%12) TEL-AML-1 (ETV6-RUNX1) pozitif bulundu. TEL-AML1 (ETV6-RUNX1) kantitasyon degeri ortalamasi pediatrik olgularda 0.90±3.21, eriskin olgularda ise 0.34±1.20 olarak belirlendi. Sonuc : Elde ettigimiz veriler, gercek zamanli qRT-PZR yontemi ile ALL hastalarinda yeni tani doneminde ve tedavi surecinde t(12;21) translokasyonunun kantitatif tayininin hem taninin kesinlestirilmesinde hem de molekuler remisyon saglanmasina yonelik tedaviyi yonlendirmesinde degerli bir yontem oldugunu desteklemektedir.

WOS: 000369120000006, PubMed ID: 25914025, Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x10(9)/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF4 geninin 11q23 kromozomal bandına yerleşim gösteren MLL genine füzyonu sonucu gelişen kromozomal bir anomalidir. Bu çalışmada, retrospektif olarak 2009-2013 yılları arasındaki akut lenfoblastik lösemi (ALL) hastalarındaki t(4;11) MLL- AF4 translokasyonunun analiz sonuçlarının incelenmesi amaçlandı. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut lösemi ön tanısıyla 176 çocuk (70 kız, 106 erkek) ve 144 yetişkin (60 kadın, 84 erkek) olgunun kan veya kemik iliği örnekleri incelendi. Bu olgulara ait 71 kan ve 473 kemik iliği örneğinin t(4;11) translokasyon RNA sonuçları, gerçek zamanlı RT-PCR yöntemi ile kantitatif olarak değerlendirildi. İlk aşamada, kan ve kemik iliği örneklerinden izole edilen total RNA veya mRNA’dan konvansiyonel bir PCR cihazı ile komplementer DNA sentezlendi. İkinci aşamada, gerçek zamanlı PCR cihazı ile t(4;11) kantitasyonu gerçekleştirildi. Olguların kantitatif olarak değerlendirilmesi, pozitif kontrol ve negatif kontrolün karşılaştırılması ile örneklerin negatif yada pozitif (pozitif olgu kopya sayısının referans kopya sayısına oranı) olması şeklinde yapıldı. Bulgular: Çalışmamızda 98’i takip hastası olmak üzere toplam 320 hasta t(4;11) MLL-AF4 translokasyonu için değerlendirildi. Çalışmaların sonucunda toplam 34 olgu (24 çocuk, 10 yetişkin) pozitif ve diğer örnekler negatif olarak bulundu. Sonuç: Bu değerlendirmenin sonuçları, RT-PCR yöntemi ile ALL hastalarında yeni tanı döneminde ve tedavi sürecinde t(4;11) MLL-AF4 translokasyonunun kantitatif tayini, hem tanının kesinleştirilmesinde hem de moleküler remisyon sağlanmasına yönelik tedaviyi yönlendirmesinde değerli bir yöntem olduğunu desteklemektedir., Aim: t(4,11) is a chromosomal abnormality formed by the translocation MLL-AF4, which is the result of the fusion of the AF4 gene, localized on 4q21 chromosomal band, to the MLL gene, localized on 11q23 chromosomal band. The aim of this study is to examine the results of the analysis of t (4;11) MLL-AF4 translocation in acute lymphoblastic leukemia (ALL) patients retrospectively. Materials and Methods: Peripheral blood or bone marrow samples of 176 children (70 girls, 106 boys) and 144 adults (60 women, 84 men) with a preliminary diagnosis of acute leukemia between 2009-2013 were analyzed in the Medical Biology Department of Ege University Faculty of Medicine. The translocation RNA results of 71 peripheral blood and 473 bone marrow samples of these patients were evaluated quantitatively for t(4;11) with real-time RT- PCR. t(4;11) quantitation was performed by real-time qRT-PCR instrument after the synthesis of complementary DNA with conventional PCR from total RNA or mRNA isolated from blood and bone marrow. Quantitative analysis of the patients was performed by comparing positive and negative controls and samples classified as positive or negative (the ratio of the number of positive copies to the number of reference copies). Results: A total of 320 patients, with 98 having also follow-ups, were evaluated for t(4;11) translocation. Totally 34 patients (24 children and 10 adults) were found positive and the other samples were negative. Conclusion: The assessment of these results supports that, quantitative determination of t(4;11) with RT-PCR method among newly diagnosed ALL patients and ALL patients undergoing treatment, is a valuable method for both confirming the diagnosis and guiding the treatment intended to achieve molecular remission.

Amac: Bu calismada, Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali'na 2009-2013 yillari arasinda akut myeloid losemi (AML) on tanisi ile basvuran 402 olgunun (322 yetiskin, 80 cocuk) kan veya kemik iligi orneklerinin inv16 kantitasyon analizlerinin RT-PCR yontemi ile degerlendirilmesi amaclandi. Gerec ve Yontem: Hastalardan alinan kan ve kemik iligi orneklerinden total RNA/mRNA izolasyonunu takiben cDNA'lari elde edilerek revers-transkriptaz-polimeraz zincir reaksiyonu (RT-PCR) yontemiyle inv16 kantitasyonu LightCycler2 cihazinda gerceklestirildi. Bulgular: Dort yuz iki olgu, inv(16) CBFBETA-MYH11 inversiyonu acisindan degerlendirildi. Yapilan analiz sonucunda 12 (% 4) eriskin ve 7 (% 9) cocuk olmak uzere toplam 19 olguda inv16 pozitifligi saptandi. Sonuc: Inv16 kantitatif analizi, AML hastalarinin klinik degerlendirilmesinde, hastaligin seyri ve remisyon saglanmasina yonelik tedavi protokollerinin uygulanmasinda etkili bir yontem oldugunu desteklemektedir. AML hasta grubunu iceren daha genis kapsamli calismalar yapilarak elde edilen sonuclar desteklenmelidir.

Multipl Myelom (MM) plazma hücre klonunun malign proliferasyonu ile karakterize bir plazma hücre diskrazisidir. Asit oluşumu MM'un nadir bir komplikasyonudur ve genellikle karaciğerin plazma hücreleri ile infiltrasyonu sonucu meydana gelen portal hipertansiyona bağlıdır. Asit nadiren peritonun plazma hücre infiltrasyonu sonucu da görülebilir. Myelom seyrinde asit oluşumu progresif seyreder ve yüksek doz kemoterapiye refrakterdir. Peritoneal infiltrasyona bağlı masif asit ile başvuran ve intraperitoneal deksametazon tedavisine yanıt veren bir refrakter myelom olgusu sunulmaktadır, Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the malignant proliferation of a plasma cell clone. Ascites is a rare complication of MM and generally occurs because of portal hypertension due to the infiltration of liver by plasma cells. Infrequently, ascites is detected as a result of peritoneal infiltration by plasma cells. Ascites in the course of myeloma has a progressive course and is refractory to high dose chemotherapy. A refractory myeloma case with massive ascites due to peritoneal infiltration and responding to intra-peritoneal dexametasone treatment is presented.

WOS: 000218425500008, PubMed ID: 26072949

Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL-60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.

Achromobacter xylosoxidans is a gram-negative bacteria that may cause invasive infections in immunosuppressive patients. In this article the first A. xylosoxidans bacteremia case reported from Turkey, is presented.

Amaç: Akut promyelösitik lösemi (APL), akut myeloid löseminin (AML) iyi tanımlanmış alt tipidir ve spesifik olarak t(15;17)(q22;q12) translokasyonu ile karakterizedir. t(15;17), 15. kromozom üzerinde bulunan promyelösitik lösemi (PML) ve 17. kromozomda lokalize retinoik asit reseptör alfa (RARA) genlerinin füzyonu sonucu oluşur. Translokasyon varlığı, konvansiyonel sitogenetik, floresan in situ hibridizasyon analizi (FISH) ve sıklıkla gerçek zamanlı kantitatif revers transkriptaz polimeraz zincir reaksiyonu (qRT-PCR) yöntemiyle saptanır. Bu çalışmada, anabilim dalımıza başvuran APL ön tanılı olgulara ait kan ya da kemik iliği materyallerinden t(15;17) translokasyonunun gerçek zamanlı qRT-PCR ile kantitasyonu amaçlanmıştır. Gereç ve Yöntem: Çalışmaya 2009-2013 yılları arasında başvuran 79 çocuk (7.28±5.20 yaş; 45 E, 34 K) ve 359 yetişkin (47.71±15.57 yaş; 193 E, 166 K) olgu dahil edilmiştir. Olguların kan ya da kemik iliği materyallerinden total RNA izolasyonunu takiben cDNA sentezi gerçekleştirilmiştir. Sonrasında, qRT-PCR ile t(15;17) translokasyonu çalışılıp, kantite edilmiştir. Bulgular: Çocuk olgulardan 2'si (%3), toplamda 6 test (%5) t(15;17) için pozitif olarak belirlenmiştir. Bu olgulara ait t(15;17) kantitasyon değeri ortalaması, 0.0002±0.0003’tür. Yetişkin olguların 26'sı (%7), toplamda 30 test (%8) t(15;17) için pozitif olarak belirlenmiştir. Bu olgulara ait t(15;17) kantitasyon değeri ortalaması, 0.067±0,144’tür. Sonuç: qRT-PCR’ın konvensiyonel sitogenetik çalışmalara göre üstünlüğü, tüm çalışma basamaklarının test esnasında eş zamanlı olarak izlenebilmesi ve oluşan amplikonların kantitasyonunun yapılabilmesidir. t(15;17) kalitatif tayininin klinikteki önemi, tanının kesinleştirilmesinde, tüm trans-retinoik asit ve trioksid arsenik tedavisine yanıtın öngörülmesi ve tedavinin yararlılığının bilinmesinde, minimal rezidüel hastalığın (MRH) takibi ve relapsın erken evrede belirlenebilmesidir., Aim: Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid leukemia (AML) specifically characterized by the t(15;17)(q22;q12) translocation. t(15;17) results in the fusion of the genes, promyelocytic leukemia (PML) on chromosome 15 and retinoic acid receptor alpha (RARA) located on 17th chromosome. Translocation is detected by conventional cytogenetic, fluorescence in situ hybridization analyses (FISH) and often a real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method. In this study, quantification of t(15; 17) translocation via real time qRT-PCR was aimed in blood or bone marrow materials belonging to APL pre-diagnosed cases that appealed our department. Materials and Methods: Seventy nine children (7.28 ± 5.20 years; 45 M, 34 F) and 359 adults (47.71 ± 15.57 years; 193 M, 166 F) were included in the study between the years 2009-2013. Following total RNA isolation from blood or bone marrow materials of the cases, cDNA synthesis was carried out. Then, t(15; 17) translocation was studied by qRT-PCR and quantitated. Results: Two cases from children (3%), and in total 6 tests (5%) were detected positive for t(15;17). The average t(15;17) quantification value was 0.0002 ± 0.0003. Twenty six cases of the adults (7%), in total 30 tests (8%) were determined as t(15;17) positive. Average t(15;17) quantification value of these cases was 0.067 ± 0.144. Conclusion: The superiority of qRT-PCR compared to conventional cytogenetic studies can be found in the fact that all working steps can be monitored simultaneously during the test and the resulting amplicons can be quantitated. The clinical significance of t(15;17) qualitative determination is, confirmation of the diagnosis, all trans-retinoic acid and trioxide arsenic treatment response prediction and treatment efficacy knowledge in addition to minimal residual disease (MRD) monitoring and ability to identify relapse at early ages.

Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.

WOS: 000173782500007, PubMed ID: 11818672

WOS: 000264042100006, PubMed ID: 19252348, Background Hypothyroid patients have increased risk of cardiovascular diseases, and several mechanisms have been considered responsible in these patients. Although, a few studies demonstrated fibrinolytic system changes in hypothyroid patients, there is no study demonstrating TAFI activity in hypothyroid Hashimoto's thyroiditis patients. The aim of this study was to evaluate TAFI activity status and the effect of L thyroxin hormone replacement treatment on fibrinolytic system in this patient group. Methods Thirty patients with hypothyroid Hashimoto thyroiditis (all were female and the mean age was 44.3 +/- 14.6 years, ranging between 17-68 years) were enrolled to study. Their TSH levels were high (27.2 +/- 5.2 mU/L) and Free T3 and Free T4 hormone levels were below than normal. In this study, euthyroid 20 healthy volunteers (mean age 32.5 +/- 4.9 years, range 26-42 years) were adopted. L-thyroxin treatment before and after TAFI activity levels were measured in patients. Results In the control group, TAFI activity levels were 9.6 +/- 0.4 mu g/mL. In patients with L-thyroxin before and after treatment there were high levels of TAFI activity value of 14.2 +/- 0.9 and 12.9 +/- 0.8 mu g/mL, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels were decreased but they were not statistically significant (p=0.187). When compared to the control group, high levels of TAFI activity were observed in the patient group (p

Background Although the association between mitral stenosis (MS) and increased coagulation activity is well recognized, it is unclear whether enhanced coagulation remains localized in the left atrium or whether this represents a systemic problem. To assess systemic coagulation parameters and changes in platelet aggregation, we measured fibrinogen levels and performed in vitro platelet function tests in plasma obtained from mitral stenotic patients' and from healthy control subjects' peripheral venous blood. Methods Sixteen newly diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N) were enrolled in the study. Platelet-equalized plasma samples were evaluated to determine in vitro platelet function, using adenosine diphosphate (ADP), collagen and epinephrine in an automated aggregometer. In vitro platelet function tests in group N were performed twice, with and without plasma obtained from group P. Results There were no significant differences between the groups with respect to demographic variables. Peripheral venous fibrinogen levels in Group P were not significantly different from those in Group N. Adenosine diphosphate, epinephrine and collagen-induced platelet aggregation ratios were significantly higher in Group P than in Group N. When plasma obtained from Group P was added to Group N subjects' platelets, ADP and collagen-induced, but not epinephrine-induced, aggregation ratios were significantly increased compared to baseline levels in Group N. Conclusion Platelet aggregation is increased in patients with MS, while fibrinogen levels remain similar to controls. We conclude that mitral stenotic patients exhibit increased systemic coagulation activity and that plasma extracted from these patients may contain some transferable factors that activate platelet aggregation.

Spontan pnömotoraks primer olabileceği gibi, kronik obstrüktif akciğer hastalığı, ağır astım krizi, infeksiyonlar, histiyositozis ve malign hastalıklara sekonder olarak da gelişebilmektedir. İnfeksiyonlar arasında tüberküloz, pneumocystis carinii pnömonisi, nekrotizan pnömoniler ve fungal infeksiyonlar ön sıralarda gelmektedir. Bu yazıda, akut lenfoblastik lösemi tedavisi esnasında, fungal infeksiyona sekonder spontan pnömotoraks gelişen bir olgu sunulmaktadı r. Hasta 18 yaşında, akut lenfoblastik lösemi tanısı ile hastaneye yatırılmış Down sendromlu bir olgudur. Nötropenik dönemde çekilen akciğer grafisinde bilateral fungal infiltrasyonu düşündüren görünüm ve sağda hidropnömotoraks ile uyumlu görünüm saptanmıştır. Olguya, kapalı su altı drenajı uygulanmış ve antifungal antibiyotik dozu artırılmıştır. Bu tedaviden fayda gören olgu iki hafta içinde düzelmiş ve drenaja son verilmiştir. Lösemi tedavisi de tamamlanan olgu halen izlenmektedir., Spontaneous pneumothorax may occur primarily or secondary due to chronic obstructive pulmonary disease, severe asthma crisis, infections, histiocytosis or malignant conditions. Tuberculosis, pneumocystis carinii infection, necrotizing pneumonias and fungal infections are well-documented causes of spontaneous pneumothorax. We here present a case with spontaneous pneumothorax due to fungal infection in the treatment period of acute lymphoblastic leukemia. The patient was diagnosed as acute lymphoblastic leukemia accompanying Down syndrome. The chest Xray in the neutropenic period revealed probable bilateral fungal infiltration and hydropneumothorax at the right side. The patient was treated with closed chest tube drainage and appropriate antibiotherapy. Therapy was resulted with cure in two weeks and drainage was ended. After completing the treatment for leukemia, the patient has been under follow-up with remission in the aspect of leukemia and hydropneumothorax.

Tip II diabetes mellitus seyrinde, vasküler komplikasyonlar mortalite ve morbiditenin en büyük nedenidir. Diabetik vaskülopatinin gelişiminde hemodinamik faktörler, nörohumoral faktörler, metabolik faktörler ve sitokinler rol oynamaktadır. Bunların yanısıra dibetik vaskülopatinin patogenezinde trombositlerin önemi üzerine de birçok çalışma yapılmıştır. Biz bu çalışmamızda tip II diabetes mellituslu hastalarda, komplikasyon durumlarına göre trombosit durumlarının değerlendirilmesini amaçladık. Bu amaçla çalışmaya 48 mikrovasküler komplikasyon gelişmemiş diabetik hasta ve 52 komplikasyonlu diabetik hasta alındı. Hastaların hepsinde trombosit ortalama volümü ölçümü yapıldı ve ADP, epinefrin ve kollajen ile in-vitro trombosit agregasyonu değerlendirildi. Sonuç olarak; komplikasyonlu ve komplikasyonsuz gruplar arasında trombosit ortalama volümü ve in-vitro trombosit agregasyon oranları açısından istatistiksel olarak anlamlı bir fark bulunmadı. Trombositlerin diabetik vasküler komplikasyonların etiyopatogenezinde önemli rol oynadığına dair bir çok kanıt olmasına rağmen bizim çalışmamızda buna ait bir sonuç bulmamamızın nedeni, in-vitro testlerin trombositlerin in vivo olaylardaki rolünü ortaya koyamıyor olması veya komplikasyonlu grupta aktive trombositlerin artmış tüketimi olabilir. Diabetik komplikasyonların gelişiminde trombositlerin in-vitro rolünü açıklamak için daha ileri çalışmalara ihtiyaç vardır., Vascular complications in the course of type II diabetes mellitus are the most important causes of mortality and morbidity. Many different factors such as hemodynamic, neurohumoral, metabolic factors and cytokines have attributed to diabetic vasculopathy. Recently, the role of platelets in diabetic vasculopathy has been shown. In this study, we aimed to investigate the platelet function tests in diabetic patients according to their complications and, mean platelet volume and in-vitro platelet aggregations in patients with type II diabetes mellitus. Fifty two diabetic patients with complications and 48 patients without complications were included into this study. Mean platelets volume measurements and in-vitro platelet aggregations with ADP, collagen and epinephrine were obtained in all patients. As a result; there are no statistically differences between the group with complications and the group without any complications in the aspect of mean platelet volumes and in-vitro aggregation tests. Although the role of platelets regarding diabetic complications in diabetic patients is well-known phenomenon , we could not find any differences between the complication and non-complication group. This could be explained by the differences between in-vitro aggregation and in-vivo platelet functions. In-vitro platelet aggregation tests can not exactly reflect the in-vivo platelet functions in different disease and patients. The another mechanism for explanation this phenomenon could be the rapid consumption of activated platelets from blood circulation in diabetic patients with complications. Further studies are needed to explain the in-vivo role of platelets in diabetic complications.

WOS: 000183659100007, PubMed ID: 12801529, Interferon-alpha (IFN-alpha)-2b is known to have antiproliferative effects on hematological malignant cells, especially chronic myelogenous leukaemia (CML). However, it can induce cytogenetical remissions in a very small percentage of the patients. Also during interferon therapy, resistance can emerge in the CML clones. K562 is an in vitro model cell line transformed from a Ph positive CML patient. It can be induced to differentiate to granulocytic and/or monocytic lineages with certain molecules. IFN-alpha-2b generally exerts its effects on CML cells by Janus family kinases (Jak/Stat) pathway, mostly through tyrosine kinase system. However, there is almost no data on the relevance of serine/threonine (Ser/Thr) protein phosphatase (PP) system in the interferon induced signal transduction pathways. In this study, we investigated serine/threonine protein phosphatases in the IFN-alpha-2b induced K562 cytotoxicity. Trypan blue dye exclusion test and MTT assay were utilised for determining cytotoxicity. IC50 of IFN-alpha-2b on K562 cells was found to be 600 IU/ml. However, no differentiation was determined by analysis of cell surface antigen expressions. Serine/threonine protein phosphatase inhibitors calyculin A (Cal A) and okadaic acid (OKA) augmented the IFN-alpha-2b induced cytotoxicity. Apoptosis assay by the mono-oligonucleosome detection and acridine orange/propidium iodide dye revealed marked apoptosis underlying cytotoxicity. Phosphatase enzyme assay revealed a gradual increase in protein phosphatase 2A (PP2A) activity during interferon induced cytotoxicity. Conversely, immunoblots showed no change in the expression of PP2A catalytic and regulatory subunits. In conclusion, PP2A plays a role in IFN-alpha-2b induced apoptosis of K562 cells and should be investigated as a new window furthermore. (C) 2003 Elsevier Science Ltd. All rights reserved.

Sisplatin başta over, mesane, prostat, testis, küçük hücreli dışı akciğer kanserleri, baş boyun kanserleri olmak üzere birçok solid tümörlerin tedavisinde kullanılan antikanser ajanlardandır. Hematolojik maligniteler içerisinde ise en sık non-Hodgkin lenfoma (NHL) tedavisinde diğer kemoterapötik ajanlarla kombine olarak kullanılır. Sisplatinin nörotoksik yan etkileri genellikle doz kısıtlayıcıdır ve periferik sensorial nöropati, ototoksisite, daha nadir olarak otonom nöropati, Lhermitte belirtisi, retrobulber nörit ve retinal toksisite olarak karşımıza çıkar. Geçici körlük ve nekrotizan lökoensefalopati ise çok daha az rastlanan yan etkiler olarak bildirilmiştir. Bu yazımızda Sisplatin içeren bir kombinasyon rejimi ile tedavi ettiğimiz bir non-Hodgkin Lenfoma olgusunu sunmaktayız. Olgunun izlem periyodunda, sisplatine bağlı gelişen ve MRI görüntüleme ile dökümante edilen akut demyelinizan ensefalomyelit saptanmıştır. Olgu, nörolojik yan etkilerin saptanmasından bir ay sonra septik şok tablosuyla exitus olmuştur., Cisplatin is an anticancer agent which is mostly used in the treatment of broad range cancers including ovarian, breast, testicular cancers, non-small cell lung cancer and, head-neck cancers. It is also used in the treatment of hematological malignancies, especially in non-Hodgkin Lymphomas, with combination of other anti-malignant drugs. Neurological side effects of cisplatin is dose-limiting and consist of peripheral sensorial neuropathy, ototoxicity, rarely autonomous neuropathy and, Lhermitte sign, retrobulber neurit and retinal toxicity. Temporary blindness and necrotising leuko-encephalomyopathy are very rare complications in the cisplatin treatment. We here reported the case with non-Hodgkin Lymphoma treated with cisplatin including combination regimen. During the follow-up period, acute demyelinating encephalomyelitis was detected with MRI scanning caused by cisplatin. We interrupted the treatment and the patient died due to septic shock after one month of detection of neurological side effects.

WOS: 000182595500052, PubMed ID: 12727984, Platelet dysfunction and its association with insulin resistance and/or hyperandrogenemia were evaluated in 50 women with polycystic ovary syndrome (PCOS), 50 women with nonclassic congenital adrenal hyperplasia (NC-CAH), and 30 women in the control group. Agonist-induced platelet aggregation was measured. Women with PCOS had significantly higher levels of platelet aggregations induced by ADP (77.4 +/- 3.3 vs. 67.3 +/- 2.8), collagen (79.7 +/- 1.8 vs. 69.1 +/- 3.9), and epinephrine (84.7 +/- 2.6 vs. 67.8 +/- 3.8), compared with controls. However platelet aggregations of women with NC-CAH because of ADP (68.2 +/- 4.22), collagen (69.5 +/- 5.4), or epinephrine (68.6 +/- 4.3) were similar to those in the control group. There were negative correlations between aggregations induced by agonists and the insulin sensitivity in women with PCOS. These correlations also appeared significant after androgen levels with covariance analysis were excluded. These covariance analyses were performed because serum androgen levels might affect platelet function. Any significant correlations were not found between androgen levels and agonist-induced platelet aggregation in women with NC-CAH. We conclude that platelet dysfunction may be an important reason for the possible cardiovascular heart diseases in women with PCOS.

WOS: 000180568700009, PubMed ID: 12479853, Chalcones have been identified as interesting compounds with cytotoxic and tumor reducing properties. In the present study, the biological activity of synthetic chalcones on, myeloid leukemic. cells was, investigated. Human myeloid HL-60 leukemia cells were exposed to 1-20 muM chemicals for 0-96 h. The viability of the cells was measured using trypan blue dye exclusion method. 4,4'-Dihydroxy chalcone (RVC-588) was selected for further experiments to determine characteristics of cytotoxicity among other compounds. The data show that cell viability decreased after treatment and IC50 value was approximately 2 muM for RVC-588. Cell differentiation was analyzed with cytofluorometry by changes in expression of glicoprotein surface markers CD11b/Mac-1, CD11c and CD14 together with morphological analysis. A maximum level of expression changes was determined at 72 h but these changes were not statistically significant to show the differentiation of HL-60 cells to mature myeloid and/or monocytoid cells. Apoptotic DNA degradation was evaluated and quantitated using sensitive enzyme-linked immunoabsorbant (ELISA) method. Using this technique, a maximum level of apoptosis 1.2-fold higher than control was observed in cultures exposed for 48 h to 2 muM RVC-588. The DNA ladder assay was subsequently used to determine DNA breaks. qualitatively. After 24 h, the cells exposed to 2 muM RVC-588 was shown to have cytotoxic-late apoptotic ladder pattern compared to control cells. These data demonstrate that RVC-588 has a high cytotoxic and antitumor activity in HL-60 cells among other chemicals we synthesized. Although the mechanism by which RVC-588 initiated cell death in these cells is presently not known and apoptotic mechanisms are likely to play less role compared to other chalcone analogues reported previously. (C) 2002 Elsevier Science Ltd. All rights reserved.

WOS: 000080219400010, PubMed ID: 10374865, To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Gal-A on the proliferation/ differentiation of HL60 and K562 cells. Okadaic acid and Gal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells. (C) 1999 Elsevier Science Ltd. AU rights reserved.

WOS: 000259504600009, Hemophilia A (HA) is a hereditary, life-threatening and disabling disorder. In this study, we have examined 61 unrelated HA patients in order to identify the incidence of the intron 1 factor VIII (FVIII) gene inversion in the West Anatolian population. According to the results of DNA analyses of the 61 HA patients, no intron 1 inversion of the FVIII gene was found., Ege University Research Fund (EBIL TEM)Ege University, We are grateful to Dr. Cemal Un (Bogazici University, Istanbul, Turkey) for the mutant DNA sample. This study was supported by Ege University Research Fund (EBIL TEM).

In this report, we present a patient with chronic myeloid leukemia (CML) in blastic phase who had two consecutive episodes of spontaneous regression back to chronic phase without chemotherapy. Although, spontaneous remission (SR) is well documented in acute leukemia, SR in CML blastic phase is extremely rare and to the best of our knowledge only one case has been reported in the world literature. The factors possibly related to this phenomenon are discussed.

PubMedID: 9444948 The incidence of aplastic anemia among hospitalized adult patients was prospectively determined in this first study in Turkey. New cases of aplastic anemia among patients 14 years and older who were admitted to the study centers were included in a 3 year survey. Seventy-three patients fulfilled the diagnostic criteria, yielding a mean annual incidence rate of 1.14 cases in 103 admissions. The male-to-female ratio of the cases (1.6:1) differed from the almost equal ratio of the larger population of Turkey. The median age was 30 years and females were younger at diagnosis. The age distribution of the cases was different from that of the population; showing two incidence peaks in both sexes. The majority of the patients (89%) had severe disease. TAG-0755 Materials Research Society Acknowledgements-The authorsa re gratefult o Professor N. Akman,P rofessoYr . Aydm,P rofessoSr . DtindarP, rofessor B. Ferhanoglu,A ssociateP rofessor0 . Gzcebe, Associate Professor0 . Gzdemir,P rofessorK . Gzerkana nd Associate ProfessorT . Soysal for providingp atientst o the studya nd ProfessorH asanY azrci for his valuables uggestionfso r the studya nda lso Mrs GtinseliD um,M S Figen Aydogana ndM S NurcanG edik for their secretariaal ssistanceTs.h e studyw as supportedb y TL&ITAK (The Scientific and Technical Research Council of Turkey), grant no: TAG-0755

PubMed ID: 7897822, The incidence of atherosclerotic and thromboembolic complications is quite high in hypertensive patients. Blood platelets and fibrinolytic activity may play an important role in the development of these complications. We investigated fibrinolytic activity and in vivo platelet release reaction in essential hypertension. Plasma levels of beta thromboglobulin (BTG), platelet factor-4 (PF4), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and plasminogen were determined in 36 essential hypertensive and 20 age and sex-matched control subjects. Plasma BTG levels were significantly higher in the hypertensive subjects than in controls (p < 0.05), whereas PF4 levels were similar for both groups suggesting an increase of in vivo platelet activity. PAI-1 antigen levels were found to be significandy higher in the hypertensive patients as compared to the control subjects (p< 0.01). On the other hand significant variations of t-PA antigen and plasminogen values were not observed in the two groups. These results suggest that essential hypertension is associated with decreased fibrinolytic activity and enhanced platelet activity as evidenced by high plasma levels of PAI-1 and BTG. (Jpn Heart J 35: 757-763, 1994). © 1994, International Heart Journal Association. All rights reserved.