High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n = 23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p < 0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.     

Detection of mink astrovirus in Poland and further phylogenetic comparison with other European and Canadian astroviruses

Virus Genes - Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and...     

Risk of thromboembolic complications in patients with permanent atrial fibrillation undergoing cardioverter-defibrillator implantation

BACKGROUND: Cardioversion of atrial fibrillation (AF) carries the risk of thromboembolic complications and, therefore, anticoagulation therapy is routinely administered before and after this procedure. In patients with permanent AF who undergo implantation of cardioverter-defibrillator (ICD), anticoagulants are usually withdrawn during the perioperative period. However, in some patients sinus rhythm may be restored during defibrillation threshold (DFT) testing which potentially may increase the risk of thromboembolic complications. AIM: To assess the frequency of sinus rhythm restoration during ICD implantation in patients with permanent AF and the rate of both thromboembolic events and local bleeding complications which may occur due to temporary withdrawal of anticoagulation therapy and its re-initiation early after the procedure. METHODS: Permanent AF was present in 23 (12%) of 193 patients selected for ICD implantation. All patients received prolonged oral anticoagulation according to the generally accepted standards. Anticoagulation therapy was stopped few days before the procedure and replaced by low molecular weight heparin which was administered up to 24 hours before ICD implantation and re-initiated 12-24 hours afterwards. RESULTS: During DFT testing sinus rhythm was restored in 5 (21.7%) patients with AF. Clinical and DFT characteristics were similar in those who were converted to sinus rhythm and those who remained in AF. No thromboembolic events were noted in either group. Local haematoma at the site of ICD implantation occurred in two (8%) patients. CONCLUSIONS: Sinus rhythm was restored in 21.7% of patients with permanent AF who underwent ICD implantation. Temporary withdrawal of anticoagulation therapy did not increase the risk of thromboembolic complications, however, its early re-initiation after implantation resulted in an increase in local bleeding complication rate.     

Algorithm for diagnosing stable coronary artery disease

The aim of the study was to develop simple algorithm for non-invasive estimating probability of the presence of CAD to optimize indications for cardiac catheterization. A prospective collection of clinical, electrocardiography (ECG), exercise electrocardiography (EE), dobutamine stress echocardiography (SE) and catheterization data was performed. All patients (n = 551, 65% male) complaining of chest pain, without prior history of myocardial infarction undergone EE (regarded as positive on the basis of > or = 1 mm ST-depression) SE (ischemia was defined as new or worsening wall motion abnormalities using a 16-segment model) and coronary angiography (CA): CAD was defined as > or = 50% narrowing of at least one major vessel. Two algorithms were developed with the use of probability analysis by computer program which employs Bayes' theory. They incorporated pretest variables: (age, gender, chest pain classification according to Diamond), ECG and results of one or two non-invasive test: EE and (or) SE. The studied population was divided into 3 groups on the basis of pretest likelihood of CAD: 1. low (< 10%), 2. intermediate (10-70%, in man divided into intermediate--low.: 10-29% and intermediate--high: 30-70%) and 3. high (> 70%). RESULTS: The prevalence of CAD in studied population was 61%. The sensitivity of the algorithm is 96% and specificity was 44%. Sensitivity and specificity of EE and SE was respectively: 93%, 21% and 85%, 69%). CONCLUSIONS: 1. An algorithm derived in our study is simple and may be useful in decision making that relates to CA. 2. We showed that when the likelihood of CAD is high on the basis of initial evaluation, diagnostic non-invasive testing is not indicated before CA, when the probability is intermediate or low, implementation of first choice test should be different in women (SE) and men (EE).     

Platelets in idiopathic thrombocytopenic purpura are increased in size but are of normal density

To determine whether platelet size and volume are related to one another or to platelet age, subpopulations of platelets from patients with idiopathic thrombocytopenic purpura (ITP) have been produced on the basis of density using Percoll gradients. The density distribution of platelets from patients with ITP and from patients with other forms of thrombocytopenia (thought to be nonimmune in nature) was the same as in normal controls. However, the platelets in each density subpopulation from ITP patients were increased in size. beta-thromboglobulin (beta TG) content of platelets from each patient group and the normals increased with density and tended to be higher in ITP than in normal controls. beta TG concentration per unit platelet volume and its level in plasma were similar in ITP patients and in normal controls. This suggests that the apparently normal density of ITP platelets was not a result of degranulation of large, dense platelets. Thus platelet size and density are independently determined and the increased size of platelets in immune thrombocytopenia may be the result of abnormalities in their production.