ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion

A distinct feature of malignant gliomas is the intrinsic ability of single tumor cells to disperse throughout the brain, contributing to the failure of existing therapies to alter the progression and recurrence of these deadly brain tumors. Regrettably, the mechanisms underlying the inherent invasiveness of glioma cells are poorly understood. Here, we report for the first time that engulfment and cell motility 1 (ELMO1) and dedicator of cytokinesis 1 (Dock180), a bipartite Rac1 guanine nucleotide exchange factor (GEF), are evidently linked to the invasive phenotype of glioma cells. Immunohistochemical analysis of primary human glioma specimens showed high expression levels of ELMO1 and Dock180 in actively invading tumor cells in the invasive areas, but not in the central regions of these tumors. Elevated expression of ELMO1 and Dock180 was also found in various human glioma cell lines compared with normal human astrocytes. Inhibition of endogenous ELMO1 and Dock180 expression significantly impeded glioma cell invasion in vitro and in brain tissue slices with a concomitant reduction in Rac1 activation. Conversely, exogenous expression of ELMO1 and Dock180 in glioma cells with low level endogenous expression increased their migratory and invasive capacity in vitro and in brain tissue. These data suggest that the bipartite GEF, ELMO1 and Dock180, play an important role in promoting cancer cell invasion and could be potential therapeutic targets for the treatment of diffuse malignant gliomas.     

Cough ability measurements and recurrent respiratory symptoms in individuals with Ataxia Telangiectasia

Objectives: Ataxia-Telangiectasia (A-T) individuals often present with respiratory muscle weakness, causing recurrent respiratory system infections, asthma-like symptoms, and chronic cough life-threatening events. The cough flow volume maneuver may reveal powerless airflow needed for efficient cough. The study aims to explore cough ability in relation to the flow/volume maneuver. Methods: Data collected retrospectively from clinical charts of 35 A-T patients (age 12.7?±?4.9 years) included forced expiratory and cough flow/volume maneuvers performed on the same day. Analysis compared among the maneuvers matching indices, numbers of cough-spikes, flow rate decay, and the reference data of similar ages. Adjusted to age, BMI, and number of hospitalizations prior to the tests, values were correlated with the cough indices. Results: Cough peak-flow (C-PF) was propagated within 90?±?20?ms compared with peak expiratory flow (PEF?>?200?ms). C-PF measured values were higher than expiratory peak-flow measured values (3.27?±?1.53?L/s versus 3.02?±?1.52?L/s, respectively, but C-PF (%predicted) values were significantly lower than expiratory peak-flow (%predicted) (46?±?15 versus 68?±?20 %predicted, respectively, p?<?0.002). The number of spikes/maneuver was low when compared with reference (2.0?±?0.8 versus 6–12 spikes) and cough vital-capacity was lower than expiratory vital capacity (0.95?±?0.43 versus 1.03?±?0.47; p?<?0.01). Inefficient C-PF was more prevalent in patients suffering from recurrent respiratory illness. The length of wheelchair confinement duration mostly influenced the C-VC level. Conclusions: The cough flow–volume curve can be applied as a method to follow cough ability in patients with A-T who showed a significantly reduced cough capacity. Further studies are needed to establish if the findings may aid decisions regarding cough assistance.     

Transcatheter aortic valve implantation of a CoreValve device using novel real-time imaging guidance

Thorough imaging of the aortic valve and related structures is highly important before and during transcatheter aortic-valve implantation. However, conventional aortography is limited for guiding precise valve placement and depends on contrast injections. A real-time imaging system capable of guiding the operator during Edwards-SPAIEN valve procedures has been introduced (C-THV, Paieon, Inc.). We describe the first application of the novel C-THV system during CoreValve implantation in a very challenging clinical scenario that required precise high implantation using minimal contrast.     

Central giant cell granuloma associated with central ossifying fibroma of the jaws: a clinicopathologic study.

OBJECTIVE: To investigate the prevalence of clinical, radiographic, and histopathologic characteristics of combined central giant cell granuloma (CGCG) and central ossifying fibroma (COF). STUDY DESIGN: Retrospective clinical and histomorphometric analysis of all cases diagnosed as CGCG or COF between 1994 and 2002. RESULTS: A total of 51 cases were included in the study: CGCG (n = 23), COF (n = 25), and combined COF-CGCG (n = 3). All 3 lesions presented expansile, well-defined unilocular radiolucencies, with radiopacities (66%), root resorption (66%) and tooth displacement (33%). Microscopically, areas of classical CGCG and COF were separated by a transition zone of nonvascularized densely packed spindle cells. Surgical procedure resulted in recurrence within 1 year in 1 of 2 patients, calcitonin nasal spray treatment resulted in growth arrest in 1 case. CONCLUSIONS: Because of the small number of the combined cases, the biologic behavior of the lesions is uncertain. The CGCG component may drive the clinical behavior toward a more aggressive behavior than classical COF; therefore, close follow-up is recommended.     

The Saccharomyces cerevisiae GSK-3 beta homologs

Yeast cells carry four homologs of GSK-3beta, RIM11, MCK1, MRK1 and YGK3. The significant homologs are RIM11 and MCK1 that presumably arose from a recent genome duplication followed by a rapid divergence. Accordingly, these homologs phosphorylate specific substrates. Rim11 is essential for entry into meiosis, whereas Mck1 is essential for growth at elevated and low temperatures. Both kinases transmit nutrient signals, but Mck1 transmits additional signals including stress signals such as, temperature, osmotic shock and Ca(2+). Consequently, Mck1 plays a role in multiple functions, including cell wall integrity, meiosis and centromere function. The other two homologs, MRK1 and YGK3 that belong to the RIM11 and MCK1 phylogenetic trees, respectively, show no distinct phenotype. These paralogs posses redundant roles, though less important, with Rim11 and Mck1 functions. This review summarizes the cellular roles of these kinases, their mode of regulation, and the signals that they transmit.     

Transient decrease in PaCO2 and asymmetric chest wall dynamics in early progressing pneumothorax

Purpose

Diagnosis of pneumothorax (PTX) in newborn infants has been reported as late. To explore diagnostic indices for early detection of progressing PTX, and offer explanations for delayed diagnoses.

Methods

Progressing PTX was created in rabbits (2.3?±?0.5?kg, n?=?7) by injecting 1?ml/min of air into the pleural space. Hemodynamic parameters, tidal volume, EtCO₂, SpO₂, blood gas analyses and chest wall tidal displacements (TDi) on both sides of the chest were recorded.

Results

(Mean?±?SD): A decrease in SpO₂ below 90?% was detected only after 46.6?±?11.3?min in six experiments. In contrary to the expected gradual increase of CO₂, there was a prolonged transient decrease of 14.2?±?4.5?% in EtCO₂ (p?<?0.01), and a similar decrease in PaCO₂ (p?<?0.025). EtCO₂ returned back to baseline only after 55.2?±?24.7?min, and continued to rise thereafter. The decrease in CO₂ was a mirror image of the 14.6?±?5.3?% increase in tidal volume. The analysis of endotracheal flow and pressure dynamics revealed a paradoxical transient increase in the apparent compliance. Significant decrease in mean arterial blood pressure was observed after 46.2?±?40.1?min. TDi provided the most sensitive and earliest sign of PTX, decreasing on the PTX side after 16.1?±?7.2?min. The TDi progressively decreased faster and lower on the PTX side, thus enabling detection of asymmetric ventilation.

Conclusions

The counterintuitive transient prolonged decrease in CO₂ without changes in SpO₂ may explain the delay in diagnosis of PTX encountered in the clinical environment. An earlier indication of asymmetrically decreased ventilation on the affected side was achieved by monitoring the TDi.     

Early detection of deteriorating ventilation by monitoring bilateral chest wall dynamics in the rabbit

Purpose  

Mechanical complications during assisted ventilation can evolve due to worsening lung disease or problems in airway management. These complications affect lung compliance or airway resistance, which in turn affect the chest wall dynamics. The objective of this study was to explore the utility of continuous monitoring of the symmetry and dynamics of chest wall motion in the early detection of complications during mechanical ventilation.