Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

Transcatheter bronchial artery embolization in the multimodality management of massive hemoptysis

To illustrate the potential role of transcatheter bronchial artery embolization (TBAE) in the multimodality management of massive hemoptysis, we describe a case in which TBAE was successfully employed as the definitive therapy. In recent years, the technique of TBAE has joined the armamentarium of managing methods for massive hemoptysis. While massive hemoptysis has traditionally been defined in terms of the volume of blood produced within a period of time, with a rate of 600 ml in 24 hours the most commonly used definition, a more functional definition has been proposed: bleeding into the tracheobronchial tree at a rate that poses a threat to life. It is the life-threatening nature of this symptom that often results in the early involvement of thoracic surgeons in the care of these patients.     

Impact of comorbidity on perioperative mortality after radical cystectomy

The TNM classification integrates the currently valid prognostic factors for tumour-specific survival after radical cystectomy due to bladder cancer. But it does not contain the most important criteria for general survival. We assessed the preoperative and operative aspects of our patients between 1992 and 2007 concerning the early mortality within the hospital stay or within 30 days after surgery. 3% of our 404 patients died within these periods, which is equivalent to the results of other contemporary publications. Except for the comorbidity of the patients, none of the included parameters (initial symptoms, histology, indication for cystectomy, AJCC stadium, year of surgery, durance of surgery, surgeon, concomitant interventions, type of urinary diversion, blood loss and number of transfusions) showed a significant correlation to cause or postoperative time of death. For the preoperative assessment of the health of the patient a multidisciplinary cooperation of urology, anaesthesia and general and/or internal medicine is necessary. In the era of evidence-based medicine the personal judgement of the evaluating physician is not sufficient. Instead a validated index should be used to help one to obtain an objective evaluation of the risks. The ACE-27 (Adult Comorbidity Evaluation-27) provides such a validated assistance in the assessment of the comorbidity of patients and therefore possible mortality after radical cystectomy.     

In vivo MRI visualization of mesh shrinkage using surgical implants loaded with superparamagnetic iron oxides

Background  

Prosthetic mesh implants are widely used in hernia surgery. To show long-term mesh-related complications such as shrinkage or adhesions, a precise visualization of meshes and their vicinity in vivo is important. By supplementing mesh fibers with ferro particles, magnetic resonance imaging (MRI) can help to delineate the mesh itself. This study aimed to demonstrate and quantify time-dependent mesh shrinkage in vivo by MRI.     

A capaciflector provides continuous and accurate respiratory rate monitoring for patients at rest and during exercise

Journal of Clinical Monitoring and Computing - Respiratory rate (RR) is a marker of critical illness, but during hospital care, RR is often inaccurately measured. The capaciflector is a novel...     

Association between endothelial NO synthase polymorphism (rs3918226) and arterial properties

BackgroundRecently, rs3918226 polymorphism in the promoter region of endothelial NO synthase (eNOS) was strongly associated with arterial hypertension in a large genome-wide association study. We investigated whether this polymorphism was associated with arterial phenotypes in a Czech general population.MethodsIn a pilot study, we genotyped 101 untreated subjects (mean age, 54.0 years). Arterial properties were measured using SphygmoCor. We used robust multivariate analysis to assess whether rs3918226 was associated with peripheral or central blood pressure, carotid-femoral pulse wave velocity (PWV) and aortic augmentation index (AIx). As independent covariates we considered sex, age, MAP, heart rate and smoking.ResultsFrequencies of rs3918226 genotypes were CC 85.2%, CT 14.8%, and TT 0%. Current smokers carrying mutated T allele had marginally higher PWV (10.0 ± 0.8 vs. 8.7 ± 0.4 m/s; P = 0.051) and significantly higher AIx (172.2 ± 6.8 vs. 153.2 ± 3.8%; P = 0.024) compared to CC homozygotes. In non-smokers we did not find any association between rs3918226 and arterial properties (P ≥ 0.62). Moreover, we did not observe any association between either peripheral or central blood pressure and the polymorphism under study (P ≥ 0.58).ConclusionsThis is the first study to explore the association of rs3918226 polymorphism in eNOS gene with arterial properties. Mutated T allele was associated with higher PWV and AIx in smokers. We hypothesize that genetic modulation of intermediate arterial phenotypes might lead to higher blood pressure. As the prevalence of T allele is low, further study with a sufficient number of subjects is warranted.