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Pays tribute to medical researcher and doctor Henry M. Wisniewski who died on September 5, 1999. Work experiences; His contributions to Alzheimer's disease diagnosis and management; Career in medical practice.

Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC), which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus), APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ∼ 2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 μM). Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T50%) by APAC (95±6.1 min) or SLK (145±7.1 min) was much longer than that by combined APAC+SLK (65±7.6 min) at the final concentration of 0.025 μM (APAC+SLK vs APAC, p<0.05; APAC+SLK vs SLK, p<0.01). Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo. [ABSTRACT FROM AUTHOR]

An important event in the pathogenesis of Alzheimer's disease (AD) is the deposition of the amyloid \beta (A\beta)1--40 and 1--42 peptides in a fibrillar form, with A\beta42 typically having a greater propensity to undergo this conformational change. A major risk factor for late-onset AD is the inheritance of the apolipoprotein E (apoE) 4 allele [3,14,31]. We previously proposed that apoE may function as a ``pathological chaperone'' in the pathogenesis of AD (i.e. modulate the structure of A\beta, promoting or stabilizing a \beta-sheet conformation), prior to the discovery of this linkage [7,40,41,42]. Data from apoE knockout / A\betaPP...{\rm V717F}mice, has shown that the presence of apoE is necessary for cerebral amyloid formation [1,2], consistent with our hypothesis. However, in\betaPP...{\rm V717F} mice expressing human apoE3 or E4 early A\beta deposition at 9 months is suppressed, but by 15 months both human apoE expressing mice had significant fibrillar A\beta deposits with the apoE4 expressing mice having a 10 fold greater amyloid burden [8,9]. This and other data has suggested that apoE, in addition to having a facilitating role in fibril formation, may also influence clearance of A\beta peptides. In order to address if apoE affects the clearance of A\beta peptides across the blood-brain barrier (BBB) and whether there are differences in the clearance of A\beta40 versus A\beta42, we performed stereotactic, intra-ventricular micro-injections of A\beta40, A\beta42 or control peptides in wild-type, apoE knock-out (KO) or human apoE3 or apoE4 expressing transgenic mice... [ABSTRACT FROM AUTHOR]