Inhibition of Anaplastic Lymphoma Kinase (ALK) Activity Provides a Therapeutic Approach for CLTC-ALK-Positive Human Diffuse Large B Cell Lymphomas

ALK positive diffuse large B-cell lymphomas (DLBCL) are a distinct lymphoma subtype associated with a poor outcome. Most of them feature a t(2;17) encoding a clathrin (CLTC)-ALK fusion protein. The contribution of deregulated ALK-activity in the pathogenesis and maintenance of these DLBCLs is not yet known. We established and characterized the first CLTC-ALK positive DLBCL cell line (LM1). LM1 formed tumors in NOD-SCID mice. The selective ALK inhibitor NVP-TAE684 inhibited growth of LM1 cells in vitro at nanomolar concentrations. NVP-TAE684 repressed ALK-activated signalling pathways and induced apoptosis of LM1 DLBCL cells. Inhibition of ALK-activity resulted in sustained tumor regression in the xenotransplant tumor model. These data indicate a role of CLTC-ALK in the maintenance of the malignant phenotype thereby providing a rationale therapeutic target for these otherwise refractory tumors

The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Majid Ezzati and colleagues examine US data on risk factor exposures and disease-specific mortality and find that smoking and hypertension, which both have effective interventions, are responsible for the largest number of deaths

Reliable prediction of giant magnetoresistance characteristics

Zhuravlev MY, Schepper W, Heitmann S, et al. Reliable prediction of giant magnetoresistance characteristics. PHYSICAL REVIEW B. 2002;65(14): 144428.We present a combined theoretical approach to the giant magnetoresistance (GMR) effect in magnetic multilayers which is able to provide good agreement with experimentally obtained GMR characteristics. This approach is based on a quantum statistical treatment, using as input the numerically determined orientation of the magnetic moments in the magnetic layers. It may be applied to determine spin-dependent transport properties, and to predict GMR characteristics for specific applications

Plasma ion evolution in the wake of a high-intensity ultrashort laser pulse RID E-5220-2010 RID F-5260-2010 RID E-7060-2010

Experimental investigations of the late-time ion structures formed in the wake of an ultrashort, intense laser pulse propagating in a tenuous plasma have been performed using the proton imaging technique. The pattern found in the wake of the laser pulse shows unexpectedly regular modulations inside a long, finite width channel. On the basis of extensive particle in cell simulations of the plasma evolution in the wake of the pulse, we interpret this pattern as due to ion modulations developed during a two-stream instability excited by the return electric current generated by the wakefield

Autonomic changes in young smokers: acute effects of inspiratory exercise

One of the most important consequences of smoking is the development of cardiovascular diseases. However, little is known about the early consequences of smoking and the acute effects of a single inspiratory muscle exercise session (IME). We evaluated the acute effects of an IME on cardiac parameters of young smokers.Twelve nonsmokers (C) and fifteen smokers [S; 2.08 (1.0-3.2) pack-years] underwent an acute IME. We evaluated blood pressure (BP) and lactate, and we recorded RR interval for posterior analysis of heart rate variability (HRV), before and after IME.At baseline, systolic BP and HRV parameters in time and frequency domains were changed in S group in comparison with the C. Following IME, S group reduced systolic BP (-8 %), low frequency band (LF) (-21.4 %), LF/high frequency (HF) (-57 %), as well as increased RR variance (+105 %) and HF band.Our findings indicate that a single session of inspiratory muscle exercise was able to both reduce systolic BP and improve parasympathetic and sympathetic modulations in young smokers. the results of the current study highlight the importance of furthering research on this area to better elucidate the acute and chronic effects of inspiratory muscle training on early cardiovascular and pulmonary changes of cigarette smoking.Univ Sao Judas Tadeu, Human Movement Lab, BR-03166000 São Paulo, BrazilUniv São Paulo, Sch Med, Heart Inst InCor, Hypertens Unit, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilNove de Julho Univ, Translat Physiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Distinct associations between energy balance and the sleep characteristics slow wave sleep and rapid eye movement sleep.

Context: Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB). Objective: To investigate inter-individual relationships between EB (EB = |energy intake-energy expenditure|, MJ/24 h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48 h stays in the controlled environment of a respiration chamber. Subjects and methods: A total of 16 men (age 23+/-3.7 years, BMI 23.9+/-1.9 kg m(-2)) stayed in the respiration chamber twice for 48 h to assure EB. Electroencephalography was used to monitor sleep (2330-0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum. Results: The subjects slept on average 441.8+/-49 min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r = -0.43, P Conclusion: A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations