Background Cognitive deficits in aging, NPH and Alzheimer's disease (AD) are exacerbated by compromised neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). We previously found beta-amyloid (Aβ) retention in cortex and hippocampus of aged rats and diseased humans, due to greater RAGE and lesser LRP-1 expression of microvascular transporters for Aβ. Now we focus on the periventricular DG and SVZ that harbor stem cells convertible to new neurons in adults. Working hypothesis: Aβ retention in neurogenic zones harms neural stem cells, leading to reduced cognition.
10090 Background: Treatment planning for gastric cancer is primarily based on clinical staging of disease. Markers predicting likelihood of disease outcome would help guide treatment decisions, especially for early stage disease. The Shc proteins, implicated in many aggressive cancers, and measured in tumor specimens by the immunohistochemical (IHC) Shc Test, have shown strong ability to predict disease outcome in breast cancer. We report here that the Shc Test is a strong prognostic indicator of disease outcome in early stage gastric cancer. Methods: Histopathology was examined in one hundred and seventeen (117) primary gastric cancer patient samples from Rhode Island Hospital in tissue microarray format (21 disease recurrences; 63 disease-specific deaths; average follow-up of 2.7 yrs). IHC staining of the Shc proteins was independently scored on a 0–5 scale by two pathologists, blinded to patient information. Results: Stage I or II gastric cancers (n=62) could be clearly separated at a cutpoint of 1.1 on a 0–5 scale, into good prognosis (16% 4yr relapse risk; demonstrating high PY-Shc) and poor prognosis (46% 4yr relapse risk; showing low PY-Shc) (log-rank, P=0.003). p66 Shc showed similar prognostic abilities. High PY-Shc in patients with early stage disease showed a significant protective effect on overall survival (P=0.003) by univariate log rank analysis. As a continuous variable, PY-Shc had a strong predictive ability (HR = 0.09, P=0.055) that approached significance. By univariate Cox proportional hazards, patients with high PY-Shc had a 5-fold reduction in disease specific death (DSD) compared to patients with low PY-Shc (P=0.002). By multivariate Cox proportional hazards, adjusted for grade, stage, chemotherapy and radiation therapy, only PY-Shc (HR = 0.22, P=0.015) and Intestinal tumor type (HR = 0.38, P=0.046) remained as significant predictors of survival. Conclusions: The Shc Test shows a strong prognostic ability to stratify early stage gastric cancer patients by risk, making it a valuable tool in selecting therapy for these patients. [Table: see text]
The aim of the presented system is simplification of the daily pathological routine of prostatic cancer diagnostics. The system combines telepathology with computer-aided diagnostics algorithms. To the best of our knowledge, this is the first approach proposing such a comprehensive method. Our system is designed to accumulate knowledge in learning process during diagnostics. Our system targets image acquisition and interpretation stages. The image acquisition subsystem solves various problems related to microscopical slide digitization like biomedical image registration, data representation, and processing. The interpretation subsystem bases on Gabor filter texture features as well as on color features. A support vector machine classifier together with feature selection is used for computer-aided diagnostics. The experimental validation of the system bases on a database of more than three thousand samples.During the experimental evaluation, the system exhibited successful interaction with a pathologist.
Aims: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. Methods: In this study, we examine the time course of CD‐68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post‐insult treatment. Results: We show that preoligodendrocyte injury in the post‐natal day 6 begins within 24 h and continues for 48–96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD‐68+ microglial cell numbers. Conclusions: These results suggest that anti‐inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post‐insult treatment strategy.
