Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been considerable interest recently in a genetic component as a causative factor in multiple sclerosis, but the identity of putative susceptibility genes is unknown. In the past decade, the primary amino acid sequences of the four proteins making up 90% of the protein content of central nervous system myelin (proteolipid protein, myelin basic protein, 2',3'-cyclic nucleotide-3'-phosphohydrolase, and myelin-associated glycoprotein) have been determined in several species. Additionally, the structural genes coding for these proteins have been analysed and their human chromosomal localization determined. We have been analysing these genes for possible variants conferring susceptibility to multiple sclerosis. Recent results have shown that cholera and pertussis toxin substrates and low molecular-weight GTP-binding proteins are also present in central nervous system myelin. This implies the presence of signal transducing systems whose purpose is currently obscure. The emerging picture of central nervous system myelin is of a complex dynamic structure composed of many more proteins than was previously thought.
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PMID:Genes coding for proteins in central nervous system myelin. 145 36

Immunization with peptides is usually done with the aid of Freund's adjuvant. Using peptides derived from myelin basic protein, we show that aqueous solutions can be antigenic (encephalitogenic in this instance) in Lewis rats. The first procedure involved multiple doses of aqueous peptide, increased absorption into the lymphatic system from the peritoneal cavity in the postinflammatory state, and the use of pertussis vaccine. Three different peptides containing the major encephalitogenic site were active in this system, with the activity somewhat proportional to the size of the fragment. The second procedure, the direct delivery of peptide to lymph nodes by percutaneous inoculation, was equally successful and did not require the use of pertussis vaccine.
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PMID:Peptides of myelin basic protein are encephalitogenic in rats without the aid of emulsions. 170 6

The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the V beta 8.5-J beta 2.3 gene combination, with extensive N region additions to both D beta 1 and D beta 2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different V beta 8 subfamily member (V beta 8.5) than the V beta 8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.
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PMID:T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats. 170 3

The induction of experimental allergic encephalomyelitis (EAE) with purified myelin basic protein (MBP) has, heretofore, required its incorporation in a water-in-oil emulsion or adsorption on particulate adjuvants. In the present work, the absorption of a saline solution of MBP from the peritoneal cavity into the mediastinal lymph nodes was increased by giving repeated inoculations or by pretreating rats with a peritoneal irritant. Under these conditions, the only adjuvant needed for production of EAE was aqueous pertussis vaccine which was injected separately a few hours or one day after the MBP. Pertussis vaccine was also necessary for production of EAE with intradermal injection of aqueous MBP. By injecting the aqueous MBP directly into pre-enlarged popliteal lymph nodes, it was possible to produce EAE without the pertussis vaccine. Thus, EAE can be induced in rats using MBP without the addition of Freund's adjuvant or pertussis vaccine.
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PMID:Encephalitogenicity for rats of myelin basic protein without the aid of water-in-oil emulsions. 170 24

Development of experimental allergic encephalomyelitis (EAE) in the SJL (H-2s) mice is associated with a T cell-dependent autoimmune response to the C-terminal part of the myelin basic protein (MBP). In this study the influence of both H-2 and non-H-2 genetic background on EAE induced with the MBP89-101 peptide is described. Analysis of different H-2q haplotype strains, B10G, B10Q, SWR and NFR/N, showed that the B10 background is relatively resistant to disease induction. Both SWR and NFR/N were susceptible to EAE showing that the H-2q haplotype is permissive for EAE development induced with MBP89-101 and that the T cell receptor (TcR) haplotype or complement C5 deficiency exert no significant influence on disease susceptibility. In a series of H-2-congenic strains on the B10 background only B10RIII (H-2r) mice were susceptible to EAE. The B10RIII mice developed a severe EAE with early onset and chronic progressive or relapsing course of disease. In addition, B10RIII mice treated with Freund's complete adjuvant and pertussis toxin alone showed an early monophasic disease. The clinical observations were confirmed by immunohistopathologic analysis of the central nervous system. In these studies, we also applied antibodies to different TcR V beta elements which showed no specific limitation of the used TcR among infiltrating T cells in the target tissue in any of the strains. It is concluded that an MBP peptide-specific disease can be induced in three different haplotypes and it is possible that shared structures between the As, Aq and Ar molecules are of importance for the trigger of encephalitogenic T cells with different TcR V elements. The presently described chronic EAE model induced in the B10RIII mice will be of value as a model for multiple sclerosis.
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PMID:Chronic experimental autoimmune encephalomyelitis induced by the 89-101 myelin basic protein peptide in B10RIII (H-2r) mice. 170 2

Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the injection of spinal cord tissue or myelin basic protein and adjuvants (Freund's or carbonyl iron or pertussis vaccine), or by adoptive immunization. After an interval of five to 12 weeks, the recovered rats were reinoculated by a different route and usually with a different adjuvant. The onset of the second attack was determined by the histologic detection of EAE lesions at intervals during the incubation period. In each of ten experiments, the second attack of EAE occurred one or two days earlier than in naive controls injected at the same time. Residual EAE lesions left over from the first attack could not explain the findings in the reinoculated rats. The accelerated response to the second inoculation may be related to the anamnestic response of classical immunology or to residual damage to the blood-brain barrier. Resistance to a second attack was not encountered in this histopathologic study.
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PMID:Accelerated response to reinoculation in experimental allergic encephalomyelitis: histopathologic study. 170 89

Treatment of BC3H1 myocytes or 3T3-L1 fibroblasts with fluoroaluminate (AlF4-), a direct activator of G proteins, increased the tyrosine phosphorylation of a 42-kDa cytosolic protein. AlF4- induced a parallel increase in protein kinase activity toward myelin basic protein (MBP) in partially purified cell extracts. To test whether AlF4- was activating the 42-kDa MAP (mitogen-activated protein) kinase, extracts from AlF4--treated cells were taken through the chromatographic steps routinely used to purify MAP kinase from growth factor-stimulated cells. Following phenyl-Superose chromatography, a peak of MBP kinase activity eluted at a position characteristic of MAP kinase. Immunoblotting of the active fractions with anti-phosphotyrosine antibodies revealed a single reactive protein band of Mr 42,000. Stimulation of MAP kinase by AlF4- was rapid, peaking within 15 min and persisting for at least 1 h. In contrast, the activation of MAP kinase by insulin was transient, characteristic of its activation by growth factors in other cell types. Although concentrations of sodium fluoride greater than 1 mM also activated MAP kinase, this effect was shown to be dependent upon the simultaneous presence of aluminum ions in the medium. Activation of MAP kinase by AlF4- was not affected by either cellular depletion of protein kinase C or pretreatment of cells with pertussis toxin. Potential sites of action of AlF4- are discussed. These findings suggest that activation of a G protein(s) in intact cells can initiate events that result in tyrosine phosphorylation and activation of MAP kinase.
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PMID:Activation of mitogen-activated protein kinase in BC3H1 myocytes by fluoroaluminate. 170 25

Myelin basic protein from normal human brain was ADP-ribosylated with Cholera toxin, but not with Pertussis toxin. It bound azido-GTP at a single site in the N-terminal tetrapeptide at the Gln residue. The binding was considerably reduced when GppNHp was present during azido-GTP binding and totally inhibited when GTP gamma S was present. The relevance of this specific binding is not understood at this time.
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PMID:Myelin basic protein binds GTP at a single site in the N-terminus. 245 5

The role of cAMP in lymphocyte proliferation was investigated in the response of a monoclonal T-cell population to a specific antigen and compared to the response to interleukin-2 (IL-2) and allogeneic cells. Myelin basic protein (MBP)-reactive and encephalitogenic T-cell clones were established from long-term lines derived from SJL/J (H-2s) mice. The clone 4b.14a recognizes the peptide sequence 89-101 of the MBP molecule in association with 1-As products of the major histocompatibility complex (MHC). Incubation of 4b.14a cells with syngeneic antigen-presenting cells, previously pulsed with the 89-101 synthetic peptide or with 80 U/ml of IL-2, or allogeneic H-2Ik cells, resulted in a significant increase in the accumulation of intracellular cAMP. This increase was preceded by a peak in membranal adenylate cyclase (AC) activity. Parallel time kinetics but significantly higher cAMP production and AC activity were observed when the cells were treated with pertussis toxin. At the same concentrations the toxin inhibits cellular proliferative responses, assayed by [3H]thymidine incorporation. Our results indicate the involvement of cAMP as a positive signal in the activation of the 4b.14a clone.
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PMID:Cyclic adenosine 3',5'-monophosphate metabolism in activated T-cell clones. 247 34

T helper cells reactive to myelin basic protein are clearly implicated in the pathogenesis of murine EAE. We have developed a T cell line, BML-1 that (1) is reactive to the encephalitogenic amino terminal nonapeptide (1-9NAC) of MBP, (2) is I-Au restricted, and (3) induces relapsing EAE in B10.PL (H-2u) mice. Measurement of the lymphokine profile of BML-1 revealed secretion of IL-2, interferon-gamma and lymphotoxin but not IL-4. This profile is consistent with the Th1/DTH subtype. Coculture of BML-1 with MBP-primed B cells shows that BML-1 does not provide significant helper function in vitro. In addition, BML-1 secretion of interferon-gamma was found to inhibit LPS-induced anti-MBP antibody responses. This suggested that anti-MBP antibodies may not be necessary for induction of EAE. Sera from mice, in which severe disease was induced with the 1-9NAC peptide and Bordetella pertussis, showed no development of serum antibodies to MBP. These data show that MBP-reactive Th cells of the Th-1/DTH subtype can induce EAE and do not provide Th function for anti-MBP responses and that serum anti-MBP antibodies are not found in peptide 1-9NAC-induced disease. T cell lines specific for encephalitogenic epitopes and characterized for lymphokine secretion will provide a useful tool for understanding the role of T cells in the induction of EAE.
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PMID:Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. 247


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