Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Formation of branching tubes is a fundamental step in the development of glandular organs. To identify extracellular cues that orchestrate epithelial tubulogenesis, we employed an in vitro assay in which EpH4-J3B1A mammary epithelial cells form spheroidal cysts when grown in collagen gels under serum-free conditions, but form branching tubules in the presence of fetal calf serum (FCS).', 'Initial experiments showed that the tubulogenesis-inducing activity of FCS was markedly increased by heating (70 degrees C) or transient acidification to pH3. We therefore hypothesized that the tubulogenic agent was transforming growth factor-beta (TGF-beta), a cytokine that is present in serum in latent form and can be activated by heat or acid treatment. We found indeed that the tubulogenic activity of acidified FCS is abrogated by addition of either SB-431542, a selective inhibitor of the TGF-beta type I receptor, or a neutralizing antibody to TGF-beta-1. On the other hand, addition of low concentrations (20-100 pg/ml) of exogenous TGF-beta-1 recapitulated the effect of acidified FCS in inducing morphogenesis of hollow tubes. In contrast, higher concentrations of TGF-beta-1 induced the formation of thin cellular cords devoid of a detectable lumen. To gain insight into the mechanisms underlying TGF-beta-1-induced tube formation, we assessed the potential role of matrix metalloproteinases (MMPs). By western blot and gelatin zymography, we observed a dose-dependent increase in MMP-9 upon TGF-beta-1 treatment. Tube formation was suppressed by a synthetic broad-spectrum metalloproteinase inhibitor, by recombinant tissue inhibitor of metalloproteinases-2 (TIMP-2) and by a selective inhibitor of MMP-9, indicating that this morphogenetic process requires the activity of MMP-9.
Do low concentrations of transforming growth factor-beta-1 induce tubulogenesis in cultured mammary epithelial cells?

This study was designed to determine the relevance of a proposed classification for advanced heart failure (HF). Profiles based on clinical assessment of congestion and perfusion at the time of hospitalization were compared with subsequent outcomes.', 'Optimal design of therapy and trials for advanced HF remains limited by the lack of simple clinical profiles to characterize patients.', "Prospective analysis was performed for 452 patients admitted to the cardiomyopathy service at the Brigham and Women's Hospital with a diagnosis of HF. Patients were classified by clinical assessment into four profiles: profile A, patients with no evidence of congestion or hypoperfusion (dry-warm, n = 123); profile B, congestion with adequate perfusion (wet-warm, n = 222); profile C, congestion and hypoperfusion (wet-cold, n = 91); and profile L, hypoperfusion without congestion (dry-cold, n = 16). Other standard predictors of outcome were included and patients were followed for the end points of death (n = 117) and death or urgent transplantation (n = 137) at one year.", 'Survival analysis showed that clinical profiles predict outcomes in HF. Profiles B and C increase the risk of death plus urgent transplantation by univariate (hazard ratio [HR] 1.83, p = 0.02) and multivariate analyses (HR 2.48, p = 0.003). Moreover, clinical profiles add prognostic information even when limited to patients with New York Heart Association (NYHA) class III/IV symptoms (profile B: HR 2.23, p = 0.026; profile C: HR 2.73, p = 0.009).
Does clinical assessment identify hemodynamic profiles that predict outcomes in patients admitted with heart failure?

The relationship between platelet activity and myocardial injury in patients with ST-segment elevated (ST-se) acute myocardial infarction (AMI) remains unclear. This study tested the hypothesis that platelet activity (expressed by CD62p) is enhanced and predictive of both the extent of myocardial damage and 30-day clinical outcome in patients with ST-se AMI undergoing primary coronary stenting.', 'Platelet CD62p expression prior to coronary angiographic was prospectively measured using flow cytometry in 45 consecutive patients with AMI undergoing primary coronary stenting. The CD62p expression was also evaluated in 20 healthy and 20 at-risk control subjects. The CD62p expression was significantly higher in AMI patients than in healthy and at-risk control subjects (all p values <0.0001). Patients with high CD62p expression (>or=8%) had significantly higher creatine kinase-MB (p<0.0001) levels, higher incidence of cardiogenic shock (p=0.009) upon presentation, significantly lower left ventricular ejection fraction (p=0.0003), and significantly higher incidence of 30-day composite major adverse clinical outcomes (MACO) (advanced congestive heart failure >or=class 3 or 30-day mortality) (p<0.0001) than those patients with low CD62p expression (<8%). Multiple stepwise logistic regression analysis demonstrated that only high CD62p expression (>or=8%) was an independent predictor of 30-day MACO (all p<0.0001).

Is platelet activity a biomarker of cardiac necrosis and predictive of untoward clinical outcomes in patients with acute myocardial infarction undergoing primary coronary stenting?

