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Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy(More)
Altered degradation of alpha-synuclein (alpha-syn) has been implicated in the pathogenesis of Parkinson disease (PD). We have shown that alpha-syn can be degraded via chaperone-mediated autophagy (CMA), a selective lysosomal mechanism for degradation of cytosolic proteins. Pathogenic mutants of alpha-syn block lysosomal translocation, impairing their own(More)
In a multivariate analysis of 154 patients receiving chemotherapy, baseline CA19-9 was an independent prognostic factor for overall survival (OS) (HR 1.8; 95% CI: 1.3-2.5, P = 0.0004). The 1-year OS was 19 and 46%, respectively, for patients with a baseline CA19-9 above or below the median value. A fall of 20% in CA19-9 level from baseline was an(More)
To determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of irinotecan and raltitrexed given as sequential short infusions every 3 weeks, 33 patients with pretreated gastrointestinal adenocarcinoma (31 colorectal, 2 oesophagogastric) entered this open label dose-escalation study. For the first five dose levels patients received(More)
Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find(More)
Urine produced by wild female house mice, living in high- and low-density populations and confined to areas within a highway cloverleaf, was tested for its ability to delay puberty in juvenile female mice. Only urine collected from females in the dense population at its maximum density delayed puberty in test females. Urine collected when the population was(More)
We recorded brainstem auditory evoked potentials (BAEPs) in two patients with Guillain-Barré syndrome (GBS). One patient was acutely deaf with total absence of BAEP waveforms indicative of acoustic nerve conduction block. Hearing improved during early convalescence, and there were prolonged wave I latencies. Normal BAEPs were recorded on recovery. A second(More)
This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging(More)
INTRODUCTION Gallstone disease has been considered an uncommon entity in children and infants, but its incidence is reportedly increasing which may be attributed to widespread use of diagnostic imaging (ultrasonography). PRESENTATION OF CASE An apparently healthy 2 year old male child presented to our Outpatient department with chief complaint of(More)