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Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen-specific antibody repertoires and their possible cross-reactivity against environmental(More)
Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent(More)
Unresolved questions in headache research are the roles of drug abuse and psychopathology in headache disorder, especially in chronic daily headache. We investigated the utility of the revised version of the Minnesota Multiphasic Personality Inventory (MMPI-2) for assessing psychopathology in chronic daily headache patients. Chronic headache sufferers gave(More)
Proteinuric renal diseases are often associated with progressive tubulointerstitial fibrosis that usually defines the degree and rate of progression of renal failure. Glomerular filtration of excess albumin, the dominant protein in proteinuria, into proximal tubule could provide the stimulus to induce certain fibrogenic cytokines from proximal tubular cells(More)
Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed(More)
Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single(More)
94 Organophosphorus toxins (OPTs) are the most toxic compounds for humans and animals known to date. This group includes some pesticides, zarin, zoman, and VX gas. The effect of OPTs is based on irreversible binding of toxin with acetylcholinesterase of higher organisms. Modern protectors and therapeutic agents used in poisoning with OPTs are imperfect.(More)
Active Heymann nephritis (AHN), a rat model of autoimmune glomerulonephritis, is induced by immunization with autologous megalin, a 600-kDa cell surface glycoprotein isolated from crude renal extracts. Recombinant proteins containing a 563-residue N-terminal sequence of megalin were obtained from Escherichia coli and baculovirus-insect cell expression(More)
It was shown previously that an N-terminal fragment (nM60) that encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as efficiently as the native protein. For delineation of a minimal structure within this fragment that is sufficient to induce AHN, smaller protein fragments that encompass residues 1 to 236 (L6), 1(More)
Covalent interactions between antibody combining site residues and substrates have been implicated in the catalytic activity of abzymes elicited by design or occurring naturally in autoimmune disease. In this study, the potential for covalent binding by antibodies (Abs) was investigated by the induction of immune responses against molecules presenting(More)