Pharmacological regulation of adult stem cells: chondrogenesis can be induced using a synthetic inhibitor of the retinoic acid receptor.

Conventional methods for regulating the differentiation of stem cells are largely based on the use of biological agents such as growth factors. We hypothesize that stem cell differentiation could be driven by specific synthetic molecules. If true, this would offer the possibility of screening chemical libraries to develop pharmacological agents with improved efficacy.

Experimental approaches to TSE prevention via inhibition of prion formation.

Transmissible spongiform encepahalopathies (TSEs) are fatal diseases that damage the central nervous system. TSEs are unique in that they may be inherited, infectious or spontaneous. The central pathogenic agent is thought to be a conformationally distinct form (PrP(Sc;)) of the endogenous prion protein(PrP(c)), which is high in beta-sheet content and is resistant to proteases; infectivity is thought to involve formation of PrP(Sc) via imprinting of abnormal conformation on the normal form of the protein (PrP(c)) by seeds of PrP(Sc).

Age-related expression of the cellular prion protein in human peripheral blood leukocytes.

Background And Objective: Creutzfeldt-Jakob disease typically affects older patients, yet victims of new-variant Creutzfeldt-Jakob disease (nvCJD) are unusually young. Because the cellular prion protein PrP(C) is required for disease development, we investigated age-dependent variability in cell surface PrP(C) expression on various subclasses of human peripheral blood leukocytes (PBL) as a possible susceptibility factor.

Design And Methods: Three age groups of healthy individuals (mean ages: 6, 33 and 68) were studied by two-color FACS analysis of PBL with fluorescent monoclonal antibodies to PrP(C) and to the lineage markers CD3, CD19, CD4, and CD8.

Inhibition of experimental allergic encephalomyelitis with an antibody that recognizes a novel antigen expressed on lymphocytes, endothelial cells, and microglia.

Experimental allergic encephalomyelitis (EAE) is a frequently employed animal model of the human disease multiple sclerosis. EAE can be induced by adoptive transfer of CD4+ T cells that are specific for central nervous system (CNS) antigens, typically myelin proteins. Although the pathogenic mechanism or mechanisms responsible for the clinical signs and histological changes in EAE and multiple sclerosis are not fully defined, the entry of T lymphocytes and antigen recognition within the CNS are required.

Regulation of intracellular free calcium levels by the cellular prion protein.

A rat brain synaptosomal model was used to investigate the possible role of the cellular prion protein (PrP) in the regulation of intracellular free calcium levels ([Ca2+i). Treatment of synaptosomes with bacterially derived recombinant human PrP in the range 20-100 micrograms ml-1 resulted in dose-dependent elevations of [Ca2+]i. These increases were dependent on extracellular calcium and were inhibited by gadolinium chloride, a potent blocker of voltage-sensitive calcium channels.