Akt signaling is required for glioblastoma maintenance in vivo

Glioblastoma multiforme (GBM) can be induced in mice through the combined expression of activated forms of KRas and Akt in glial progenitor cells. We have previously demonstrated that KRas is required for the maintenance of these tumors in vivo as inhibition of KRas expression resulted in apoptotic tumor regression and significantly increased survival. To determine the reliance of these tumors on Akt signaling in vivo, we generated a viral vector that allows the expression of Akt to be controlled post-delivery. Survival rates were compared between those animals with continued Akt expression and animals in which expression of Akt was suppressed. Although a fifth of the tumors were refractory to treatment, inhibition of Akt significantly increased the survival of tumor-bearing mice and nearly a fourth of the mice remained in remission four months after the treatment period. These data suggest that Akt is required for glioblastoma maintenance in the context of activated Ras and that loss of Akt expression results in increased survival; therefore, the PI3K/AKT signaling pathway is a viable therapeutic target in this context.     

Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus

We describe a powerful system for revealing the direct monosynaptic inputs to specific cell types in Cre-expressing transgenic mice through the use of Cre-dependent helper virus and a modified rabies virus. We generated helper viruses that target gene expression to Cre-expressing cells, allowing us to control initial rabies virus infection and subsequent monosynaptic retrograde spread. Investigators can use this system to elucidate the connections onto a desired cell type in a high-throughput manner, limited only by the availability of Cre mouse lines. This method allows for identification of circuits that would be extremely tedious or impossible to study with other methods and can be used to build subcircuit maps of inputs onto many different types of cells within the same brain region. Furthermore, by expressing various transgenes from the rabies genome, this system also has the potential to allow manipulation of targeted neuronal circuits without perturbing neighboring cells.     

Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis

1. Download high-res image (368KB)
2. Download full-size image

     

A neural theory of visual attention and short-term memory (NTVA)

The neural theory of visual attention and short-term memory (NTVA) proposed by Bundesen, Habekost, and Kyllingsbæk (2005) is reviewed. In NTVA, filtering (selection of objects) changes the number of cortical neurons in which an object is represented so that this number increases with the behavioural importance of the object. Another mechanism of selection, pigeonholing (selection of features), scales the level of activation in neurons coding for a particular feature. By these mechanisms, behaviourally important objects and features are likely to win the competition to become encoded into visual short-term memory (VSTM). The VSTM system is conceived as a feedback mechanism that sustains activity in the neurons that have won the attentional competition. NTVA accounts both for a wide range of attentional effects in human performance (reaction times and error rates) and a wide range of effects observed in firing rates of single cells in the primate visual system.     

Persisting asymmetries of vision after right side lesions

Visual neglect and extinction are well-known effects of lesions in the right hemisphere. This study shows that even with minor or no clinical signs of these deficits, and in the stable phase of recovery, asymmetric visual perception is common after right side lesions. Whole, partial and colour report experiments were used to estimate psychophysical parameters related to visual capacity and attentional weighting in 26 patients with stroke in the right side of the brain. The results were analyzed using Bundesen's Theory of Visual Attention (TVA [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523-547]) including bootstrap estimation of the measurement error related to each test result [Habekost, T., & Bundesen, C. (2003). Patient assessment based on a theory of visual attention (TVA): Subtle deficits after a right frontal-subcortical lesion. Neuropsychologia, 41, 1171-1188]. Lesions were examined by MR scanning and analyzed statistically. Two main types of deficit were found. The first type was related to perception of unilateral displays, where most patients showed left side reductions of visual processing speed. This visual asymmetry correlated with injury to the putamen and surrounding white matter. The second deficit type occurred with bilateral displays, which increased the visual asymmetry (extinction effect) for most patients with large cortico-subcortical lesions, but rarely for patients with focal lesions. However, in a single case with pulvinar damage, visual asymmetry occurred selectively with bilateral stimulation. Overall, the study provided an overview of the cognitive structure and lesion anatomy of subtle visual asymmetries after right side stroke.     

Transvaginal adjustable tape: an adjustable mesh for surgical treatment of female stress urinary incontinence

After transvaginal adjustable tape, approximately 15% of patients still suffer incontinence, and voiding dysfunction is present in a relatively important number of patients. Transvaginal adjustable tape (TVA) permits postoperative readjustment of tension, suggesting that better results could be obtained. Sixty-four incontinent women received TVA. Patients were monitored 1, 6, and 12 months post-surgery and annually thereafter by medical history, cough stress test, flowmetry and post-void residual test (PVR), incontinence quality of life, International Consultation on Incontinence Questionnaire-Short Form, and Patient Global Impressions of Improvement (PGI-I) questionnaires. After adjustment, all patients rendered continent, and none had PVR. On no occasion was vesical catheterization or uretholysis necessary. Mean follow-up was 40+/-12.9 months. Objective and subjective cure rate were 94% and 56%, respectively. Qmax was 22.3+/-9.9 ml/s. The PGI-I questionnaire showed 94% of patients to be better or very much better than before. Our data suggest that with TVA tape, better results can be obtained, furthermore, without increasing surgical complications.     

Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genes implicated in human melanoma

The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms ...     

Tricuspid annulus diameter does not predict the development of tricuspid regurgitation after mitral valve repair for mitral regurgitation due to degenerative diseases

Background

Heart valve surgery guidelines suggest that tricuspid valve annuloplasty may be beneficial in patients with a tricuspid annulus (TA) ≥40 mm even in the absence of functional tricuspid regurgitation (TR) at the time of surgery for left-sided valve lesions (class 2a). Given the broad spectrum of degenerative diseases that affect the atrioventricular valves, we hypothesize that this measurement might not be predictive of TR after mitral valve (MV) repair.