We tested the proliferative responses of peripheral blood mononuclear cells from 61 patients with multiple sclerosis, 56 healthy control subjects and 52 patients with other neurological diseases to seven synthetic peptides of myelin proteolipid protein (PLP) and 19 synthetic peptides of myelin basic protein (MBP). Increased proliferative responses to two overlapping PLP peptides, PLP184-199 and...

An improved method for extracting the lipids from tissues consists of the use of hexane:isopropanol, followed by a wash of the extract with aqueous sodium sulfate to remove nonlipid contaminants. This method has a number of advantages over the common usage of chlorofomnmethanol. The solvents are somewhat less toxic, interference in processing by proteolipid protein contamination is avoided, the...

An electrochemical gradient of protons (PMF) is a universal high-energy intermediate in biological systems. Two related families of proton pumps, denoted F- and V-ATPases, are among the principal generators of a PMF from ATP and can form ATP at the expense of a PMF. The enzymes of these two families share a similar structure and subunit composition; some subunits in the two families evolved fro...

Proteolipid protein (PLP) is the major myelin membrane protein of the central nervous system. We have isolated a copy of an alternatively spliced PLP gene transcript from a mouse brain cDNA library that was screened for PLP-related sequences. The encoded 241-amino acid protein differs from PLP by an internal deletion of 35-amino acid residues (116-150) from the major hydrophilic domain. This PL...

Experimental autoimmune encephalomyelitis (EAE) is an animal model of the demyelinating disease multiple sclerosis. In EAE cytokines play a critical role in defining the Th1 or Th2 nature of the autoantigen directed immune response, and in propagating and regulating inflammation within the central nervous system. In this review we summarize some of the recent developments in the field of cytoki...

Clinical trials that test the efficacy of Phlogenzym (consisting of the hydrolytic enzymes bromelain and trypsin and the anti-oxidant rutosid) as a treatment for T cell-mediated autoimmune diseases including multiple sclerosis (MS), type 1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects of Phlogenzym treatment in the murine model for MS, experimental allergic ence...

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and fac...

The cellular and subcellular distributions of mRNAs encoding three myelin-specific proteins--myelin basic protein (MBP), proteolipid protein (PLP), and Po protein--were studied in tissue sections of developing rat nervous systems by in situ hybridization. The developmental appearance of these mRNAs closely paralleled the appearance of the proteins they encode as determined by immunocytochemistr...

Oligodendrocytes, the myelin-forming cells of the central nervous system, were cultured from newborn rat brain and optic nerve to allow us to analyze whether two transmembranous myelin proteins, myelin-associated glycoprotein (MAG) and proteolipid protein (PLP), were expressed together with myelin basic protein (MBP) in defined medium with low serum and in the absence of neurons. Using double l...

Plp1 gene expression occurs very early in development, well before the onset of myelination, creating a conundrum with regard to the function of myelin proteolipid protein (PLP), one of the major proteins in compact myelin. Using PLP-EGFP mice to investigate Plp1 promoter activity, we found that, at very early time points, PLP-EGFP was expressed in Sox2+ undifferentiated precursors in the spina...