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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current methods of arresting and synchronizing cell division have not been very successful and have had few applications in embryo studies. Our objective was to determine the reliability of a metaphase arrest agent, nocodazole, for halting and synchronizing blastomere division in cleavage-stage bovine embryos, and to verify its reversibility and toxicity in vitro. Eight-cell-stage embryos obtained at 58 hr postinsemination were treated with varying concentrations of nocodazole for 12 hr. Treated embryos were assessed for cleavage arrest, chromatin morphology, DNA synthesis, and histone H1 and myelin basic protein (MBP) kinase activity, and were scored for blastocyst formation and hatching rate. They were subsequently fixed to count the number of nuclei. Complete arrest of cell division was observed at concentrations of 0.4 micrograms ml-1 and above. Removal from nocodazole treatment led to immediate release from cleavage arrest, and was followed by synchronized mitosis, histone H1 kinase deactivation, and reentry into interphase within 3-5 hr. DNA synthesis was reinitiated at 6 hr after release. Although cell numbers and hatching rate decreased, the proportion of embryos reaching blastocyst stage was not significantly affected in nocodazole-treated embryos. It is concluded that nocodazole is a suitable choice for the cell-cycle synchronization of donor embryos for use in studies on the interactions between nucleus and cytoplasm during early embryogenesis.
Mol Reprod Dev 1996 Aug
PMID:Synchronization of cell division in eight-cell bovine embryos produced in vitro: effects of nocodazole. 884 91

Four genetic constructions have been designed, capable of producing in E. coli the hybrid beta-galactosidases containing the encephalitogenic determinant 114-122 of myelin basic protein. The ability of chromatography-purified proteins to cause allergic encephalomyelitis in guinea pigs has been investigated. Only one out of four proteins carrying at least one complete replica of encephalitogenic determinant did induce allergic encephalomyelitis in animals. Effects of the structural context of the encephalitogenic determinant on its functional activity are discussed.
Mol Gen Mikrobiol Virusol
PMID:[Ability of a recombinant protein containing fragment 114-122 of myelin basic protein, to cause allergic encephalomyelitis in guinea pigs]. 892 58

T cell responses to myelin basic protein (MBP) are implicated to play an important role in the pathogenesis of multiple sclerosis (MS). These MBP autoreactive T cells are found to undergo in vivo activation and clonal expansion in patients with MS. They accumulate in the brain compartment and may reside in the brain lesions of patients with MS. As MBP-reactive T cells potentially hold a central position in initiation and perpetuation of the brain inflammation, specific immune therapies designed to deplete them may improve the clinical course of the disease. We review here the recent application of T cell vaccination in patients with MS to deplete circulating MBP-reactive T cells. The results of our phase I clinical trial indicate that T cell vaccination with inactivated MBP autoreactive T cells induces specific regulatory T cell network of the host immune system to deplete circulating MBP-reactive T cells in a clonotype-specific fashion. The immunity induced by T cell vaccination is clonotype specific and long-lasting. Our longitudinal clinical evaluation further suggests a moderately lower rate of clinical exacerbation, disability score, and brain lesions (measured by magnetic resonance imaging) in vaccinated patients than in matched controls. Our study should encourage further investigation on the treatment efficacy of T cell vaccination and further improvement for its clinical administration in other human autoimmune diseases. This review discusses the immune regulation and therapeutic administration of T cell vaccination in human autoimmune diseases, exemplified by our recent T cell vaccination trial in MS.
J Mol Med (Berl) 1996 Nov
PMID:T cell vaccination: clinical application in autoimmune diseases. 895 51

Control of cell proliferation involves a finely interwoven network of positive and negative cell cycle regulators. Signal transduction pathways linking c-fms (CSF-1R) to cellular proliferation and differentiation are being explored. Part of the strategy is to use a series of G1 inhibitors to help pinpoint relevant targets. Several inhibitors-8Br-cAMP, interferon gamma (IFN gamma), INF alpha/beta, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF alpha), and dimethylamiloride-suppress CSF-1-stimulated proliferation in murine bone marrow-derived macrophages (BMM) even when added in the mid- to late-G1 phase of the cell cycle. The down-modulating effects of the inhibitors on the expression of the following cell cycle regulators have been examined: c-myc, cyclin D1 and D2, cdk4, Rb phosphorylation, E2F binding activity, ribonucleotide reductase subunits, and PCNA. Some differences in the negative control of such regulators were found, for example, in the manner in which IFN gamma and cAMP down-regulate c-myc expression. Using blocking antibodies and BMM from type I IFN receptor knockout mice, it appears that one of these inhibitors, IFN alpha/beta, acts as an endogenous inhibitor in CSF-1-treated BMM and is also responsible, at least in part, for the inhibition of cell cycle progression by LPS and TNF alpha. Another strategy has been to attempt to relate early biochemical changes induced by CSF-1 to later changes in the G1 phase, partly by studying cycling versus noncycling macrophages and partly by using cells expressing c-fms with tyrosine mutations in the intracytoplasmic region. CSF-1-mediated effects on the following signal transduction molecules in these systems will be described: PI3-kinase, myelin basic protein kinases, Erks, and STAT transcription factors.
Mol Reprod Dev 1997 Jan
PMID:CSF-1 and cell cycle control in macrophages. 898 59

A mitogen-activated protein (MAP) kinase gene, PfMAP, from Plasmodium falciparum was recently identified. We expressed this gene in Escherichia coli to test whether it encodes a functional MAP kinase. Recombinant PfMAP kinase autophosphorylates on both the tyrosine and threonine residues within the TXY motif, and readily phosphorylates myelin basic protein as exogenous substrate. This identifies the PfMAP gene product as a true member of the growing family of MAP kinases. Wild-type PfMAP kinase expressed in COS-7 (SV40 transformed African green monkey kidney) cells seemed to induce apoptosis in these cells. Western blots and immunoprecipitations indicated that the kinase is expressed during the growth of the parasite in the red blood cell as three major forms: truncated forms with apparent molecular masses of 40 kDa and 80 kDa, and as a protein of approximately 150 kDa. The 40 kDa form is present throughout the intraerythrocytic development, whereas the two larger forms are only detected in mature parasites. The 40 kDa and 80 kDa forms are tyrosine phosphorylated, indicating that they represent the active forms of the PfMAP kinase. The total PfMAP kinase activity constantly increases with the maturation of the parasite.
Mol Microbiol 1997 Jan
PMID:Characterization of a mitogen-activated protein (MAP) kinase from Plasmodium falciparum. 900 28

To understand the function of the myelin oligodendrocyte glycoprotein (MOG), a myelin specific protein of the central nervous system, transgenic mice were produced. The transgene is a fusion gene containing 1.9 kb of murine myelin basic protein promoter, 430 bp of rat MOG cDNA in the reverse orientation and 4.5 kb of human proteolipid protein gene. In spite of high expression of antisense MOG mRNA in the oligodendrocytes, MOG synthesis was not inhibited in transgenic mice. This lack of inhibition of MOG underlines the difficulties encountered with antisense transgenic strategies.
Brain Res Mol Brain Res 1996 Dec 31
PMID:An antisense transgenic strategy to inhibit the myelin oligodendrocyte glycoprotein synthesis. 903 50

Platelet-derived growth factor (PDGF) is a growth-regulatory dimer with A and B subunits. PDGF-AA, acting via PDGF receptors of the alpha-unit subtype (PDGF-alphaR), is implicated in the differentiation of oligodendrocyte precursors and in the survival of newly formed oligodendrocytes, which gradually lose expression of PDGF-alphaR. However, it is unclear whether terminally differentiated oligodendrocytes express PDGF-alphaR in vivo. To address this question, and to help clarify the role of PDGF-AA in late oligodendrocyte differentiation, we have used double in situ hybridization with digoxigenin- and fluorescein-labeled riboprobes to relate PDGF-alphaR mRNA and myelin basic protein (MBP) mRNA expression in the isolated intact anterior medullary velum (AMV) of rats ages Postnatal Day (P) 10-12 and P30-32. In parallel experiments, AMV were immunolabeled with the oligodendrocyte-specific monoclonal antibody Rip to provide information on oligodendrocyte development and the extent of myelination. At P10, the AMV contained tracts in which axons ranged from unmyelinated to fully myelinated, whereas myelination was complete in P30-32 AMV. The first oligodendrocytes to express MBP mRNA or Rip were promyelinating oligodendrocytes, which had a "star-burst" morphology and had not yet begun to form myelin sheaths. As myelination proceeded, MBP mRNA became dispersed throughout oligodendrocyte units, comprising cell somata, processes, and internodal myelin sheaths. By P30-32, MBP mRNA had been redistributed to the myelin sheaths only, reflecting a change in the site of protein synthesis in mature myelinated axon tracts. At no stage of oligodendrocyte differentiation did we observe cellular coexpression of mRNA for PDGFalphaR and MBP. Our results indicated that oligodendrocytes lost the expression of PDGFalphaR prior to gaining that of myelin gene products, and preclude an action of PDGF-AA on Rip+/MBP+ star-burst promyelinating oligodendrocytes. The spatial and temporal expression of PDGF-alphaR mRNA in the AMV was inversely related to the pattern of maturation of both myelin and oligodendrocytes, and is consistent with PDGF-alphaR being expressed by pro-oligodendrocytes. A notable finding was the high level of expression of PDGF-alphaR mRNA in the AMV of juvenile rats, localized to cell bodies within the myelinated axon tracts, strongly suggesting that oligodendrocyte precursors persisted in the mature velum.
Mol Cell Neurosci 1997
PMID:PDGF-alpha receptor and myelin basic protein mRNAs are not coexpressed by oligodendrocytes in vivo: a double in situ hybridization study in the anterior medullary velum of the neonatal rat. 907 94

The box 1 and 2 motif of the myelin basic protein (MBP) promoter is a potential regulatory sequence of the MBP transcription unit. A DNA fragment that contained the sequence of the box 1 and 2 motif from mouse was synthesized, and its protein binding properties were examined by gel-shift assays. The box 1 and 2 probe and nuclear extracts from mouse brain generated a pattern of six major DNA-protein complexes (a, b, c, d, e, and f). The box 1 and 2 probe and nuclear extracts from oligodendrocyte-like glioma cells 1C10 generated a pattern of DNA-protein complexes that exhibited only complexes a, b, e, and f. Complex b generated by extracts from 1C10 cells, however, was very intense compared to any of the other complexes. It was determined that dephosphorylation of the proteins in nuclear extracts from 1C10 cells with acid phosphatase significantly altered their DNA binding properties. Two proteins of minimum M, approximately 32 and approximately 38 kDa (MBP32 and MBP38) that bind to the box 1 and 2 motif were identified in these nuclear extracts by using a UV crosslinking method. MBP32 and MBP38 are found in cell types and tissues known to express the golli transcription unit of the golli-MBP gene complex and may be involved in the modulation of the MBP unit in those cells.
J Mol Neurosci 1997 Jun
PMID:Two proteins bind to a novel motif in the promoter of the myelin basic protein gene from mouse. 929 31

Experimental autoimmune encephalomyelitis (EAE) serves as a rodent model of the autoimmune disease multiple sclerosis. In mice, EAE is induced by immunizing with spinal cord homogenate, components of the myelin sheath, such as myelin basic protein (MBP) or proteolipid protein (PLP), or peptides derived from these components. EAE can be induced in H-2u or (H-2u x H-2s)F1 mice with the N-terminal peptide of MBP, Ac1-11. Coimmunization with Ac1-11 and Ac1-11[4A], an analog in which lysine at position four is substituted with alanine, prevents EAE. The mechanism of inhibition has not been elucidated, but probably does not work through MHC blockade, T cell anergy or clonal elimination of encephalitogenic T cells. We have isolated T cell clones and hybridomas from (PL/J x SJL/J)F1 mice immunized with either Ac1-11 alone or Ac1-11 and Ac1-11[4A] and analysed these cells for differences in their T cell receptor repertoire and in vitro response. Although T cells elicited by coinjection of Ac1-11 and Ac1-11[4A] expressed TCR that used V alpha and Vbeta gene elements similar to those elicited by Ac1-11 alone, they differed in the sequences of the junctional region of the alpha chain. Most of these T cells also responded less well to Ac1-11 in vitro, suggesting that coinjection of Ac1-11 and Ac1-11[4A] preferentially activates T cells bearing TCR of different affinity for Ac1-11 bound to I-A(u), and which may therefore be less encephalitogenic. Furthermore, our results show that a more diverse repertoire of V alpha and Vbeta genes are elicited by Ac1-11 in (PL/J x SJL/J)F1 mice compared to PL/J and B10.PL mice, providing further evidence that a restricted TCR repertoire is not required for the development of autoimmune disease.
Mol Immunol 1997 Aug
PMID:Induction of a heterogeneous TCR repertoire in (PL/JXSJL/J)F1 mice by myelin basic protein peptide Ac1-11 and its analog Ac1-11[4A]. 944 77

The mitogen-activated protein (MAP) kinases (p44mapk and p42mapk), also known as extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), are activated in response to a variety of extracellular signals, including growth factors, hormones and, neurotransmitters. We have investigated MAP kinase signal transduction pathways in normal human osteoblastic cells. Normal human bone marrow stromal (HBMS), osteoblastic (HOB), and human (TE85, MG-63, SaOS-2), rat (ROS 17/2.8, UMR-106) and mouse (MC3T3-E1) osteoblastic cell lines contained immunodetectable p44mapk/ERK1 and p42mapk/ERK2. MAP kinase activity was measured by 'in-gel' assay using myelin basic protein as the substrate. Mainly ERK2 was rapidly activated (within 10 min) by bFGF, IGF-I and PDGF-BB in normal HOB, HBMS and human osteosarcoma cells, whereas both ERK1 and ERK2 were activated by growth factors in rat osteoblast-like cell lines, ROS 17/2.8 and UMR-106. The ERK1 activation was greater than the ERK2 in ROS 17/2.8 cells. Furthermore, ERK2 was also activated by bFGF and PDGF-BB in the mouse osteoblastic cell line, MC3T3-E1. This is the first demonstration of inter-species differences in the activation of MAP kinases in osteoblastic cells. Cyclic AMP derivatives or cAMP generating agents such as PTH and forskolin inhibited ERK2 activation by bFGF and PDGF-BB suggesting a 'cross-talk' between the two different signalling pathways activated by receptor tyrosine kinases and cAMP-dependent protein kinase. The accumulated results also suggest that the MAP kinases may be involved in mediating mitogenic and other biological actions of bFGF, IGF-I and PDGF-BB in normal human osteoblastic and bone marrow stromal cells.
Mol Cell Biochem 1998 Jan
PMID:Identification and activation of mitogen-activated protein (MAP) kinase in normal human osteoblastic and bone marrow stromal cells: attenuation of MAP kinase activation by cAMP, parathyroid hormone and forskolin. 954 82


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