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Biotech / Medical : Cistron Biotechnology(CIST)$.30 -- Ignore unavailable to you. Want to Upgrade?

To: Steve Harmon who wrote (2065)	4/23/1999 6:57:00 PM
From: Walter Morton	Respond to of 2742

"The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD."

To: Steve Harmon who wrote (2065)	4/23/1999 7:04:00 PM
From: Walter Morton	Respond to of 2742

"Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF-alpha, and of the active form of TGF-beta1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1beta was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1beta (79% inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies)."