Cardiac fibroblasts produce leukemia inhibitory factor and endothelin, which combine to induce cardiac myocyte hypertrophy in vitro

Cardiac fibroblasts in culture produce factor(s) that induce hypertrophy of neonatal rat ventricular myocytes in vitro. As in vivo, the myocyte hypertrophy response in culture is characterized by an increase in cell size and contractile protein content, and by the activation of embryonic genes, including the gene for atrial natriuretic peptide. The purpose of this study was to identify the factor(s) produced by fibroblasts that induce myocyte hypertrophy. The fibroblast hypertrophy activity was inhibited using a combination of the endothelin A receptor blocker BQ-123 and an antibody to leukemia inhibitory factor. The individual antagonists each caused a partial inhibition. The mRNAs for both leukemia inhibitory factor and endothelin were detected by RT-PCR analysis and the concentration of both proteins was determined to be approximately 200 pmol/L in the conditioned medium using immunoassays. Purified leukemia inhibitory factor and endothelin each induced distinctive morphological changes in the myocytes. Their combination generated a different morphology similar to that induced by fibroblast conditioned medium. Each factor also induced atrial natriuretic peptide production, but both were required for the myocytes to produce the levels measured after exposure to fibroblast conditioned medium. These results show that hypertrophy activity produced by cardiac fibroblasts in culture is a result of leukemia inhibitory factor and endothelin.     

Levels of Circulating Microparticles in Lung Cancer Patients and Possible Prognostic Value

Background. Endothelial-derived microparticles (EDMPs) and platelet-derived microparticles (PDMPs) have been reported to be increasing in various diseases including malignant diseases. Here, we investigated whether these MPs may be useful biomarkers for predicting lung cancer (LC) disease status, cell type, or metastasis. Methods and Results. One hundred and thirty LC patients were prospectively enrolled into the study between April 2011 and February 2012. Flow cytometric analysis demonstrated that the circulating levels of platelet-derived activated MPs (PDAc-MPs), platelet-derived apoptotic MPs (PDAp-MPs), endothelial-derived activated MPs (EDAc-MPs), and endothelial-derived apoptotic MPs (EDAp-MPs) were significantly higher in LC patients than in 30 age- and gender-matched normal control subjects (all P < 0.05). Additionally, circulating level of PDAc-MPs was significantly lower (P = 0.031), whereas the circulating levels of the other three biomarkers did not differ (all P > 0.1) in early stage versus late stage LC patients. Furthermore, the circulating levels of the four types of MPs did not differ among patients with different disease statuses (i.e., disease controlled, disease progression, and disease without treatment, i.e., fresh case) (all P > 0.2) or between patients with or without LC metastasis (all P > 0.5). Moreover, only the circulating level of EDAp-MPs was significantly associated with the different cell types (i.e., squamous cell carcinoma, adenocarcinoma, and small cell carcinoma) of LC (P = 0.045). Conclusion. Circulating MP levels are significantly increased in LC patients as compared with normal subjects. Among the MPs, only an increased level of EDAp-MPs was significantly associated with different LC cell types.     

How Do Acetabular Version and Femoral Head Coverage Change With Skeletal Maturity?

BackgroundNormal changes in acetabular version over the course of skeletal development have not been well characterized. Knowledge of normal version development is important because acetabular retroversion has been implicated in several pathologic hip processes.Questions/purposesThe purpose of this study was to characterize the orientation of the acetabulum by measuring (1) acetabular version and (2) acetabular sector angles in pediatric patients during development. We also sought to determine whether these parameters vary by sex in the developing child.MethodsWe evaluated CT images of 200 hips in 100 asymptomatic pediatric patients (45 boys, 55 girls; mean age, 13.5 years; range, 9–18 years) stratified by the status of the triradiate physis and sex. We determined the acetabular anteversion angle at various levels in the axial plane as well as acetabular sector angles at five radial planes around the acetabulum.ResultsFor both genders, anteversion angle was greater for the closed physis group throughout all levels (p < 0.001) and both open and closed physis groups were more anteverted as the cut moved caudally away from the acetabular roof (p < 0.001). At the center of the femoral head, the mean anteversion angle (± SD) in girls was 15° ± 3° in the open group and 19° ± 5° in the closed group (p < 0.001). In boys, the mean anteversion angle increased from 14° ± 4° in the open group to 19° ± 4° in the closed group (p = 0.003). In the superior, posterosuperior, and posterior planes, the acetabular sector angles were greater in the closed compared with the open physis group for both boys and girls with the largest increase occurring in the male posterosuperior plane (approximately 20°) (all p < 0.05).ConclusionsThis study demonstrates that acetabular anteversion and acetabular sector angles in both male and female subjects increase with skeletal maturity as a result of growth of the posterior wall. This suggests that radiographic appearance of acetabular retroversion may not be attributable to overgrowth of the anterior wall but rather insufficient growth of the posterior wall, which has clinical treatment implications for pincer-type impingement.

Level of Evidence

Level IV diagnostic study.