Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have sequenced 200 to 240 bases of the matrix (M) glycoprotein gene of 23 strains of infectious bronchitis virus (IBV) representing the A (D207), B (D3896), C (D3128), D (D212), Massachusetts (Mass), UK11 and UK12 serotypes. The bases examined code for the external, hydrophilic region and the first membrane-embedded hydrophobic region of M, both regions comprising approximately 20 amino acids. As predicted from protein Mr studies the A/D and B/C serotypes had two and one potential glycosylation sites respectively. This variation appeared to derive from a combination of base substitutions and deletions/insertions. The glycosylation sequence Asn-Cys-Thr was highly conserved. Overall, the exposed part of M exhibited a fourfold greater extent of amino acid variation than did the membrane-embedded sequence. The transcription-associated homology region sequence (CUUAACAA) in the 5' intergenic region was identical in all strains but there was considerable variation as to its location. The M gene of UK12 appeared to have evolved from a group A-like M gene by a two stage process involving a base substitution in the intergenic region which generated a new AUG translation start codon followed by deletion of the original AUG. Isolate UK11 closely resembled Mass strains in the intergenic region but was dissimilar from all strains in the protein coding region. The M sequences of serotypes B and C were identical and those of the A and D serotypes very similar. These results are discussed in relation to recent sequencing of part of the spike glycoprotein gene of some of these strains and the discovery of in vitro recombination of murine hepatitis coronavirus.
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PMID:Evolution of avian coronavirus IBV: sequence of the matrix glycoprotein gene and intergenic region of several serotypes. 283 26

Localization of neutralizing, serotype specific epitopes of infectious bronchitis virus has been difficult because these epitopes are conformationally dependent. We identified amino acids involved in a serotype specific, conformationally dependent epitope by analysis of the S1 gene of 13 monoclonal antibody-neutralization-resistant mutants. Substitutions in the predicted amino acid sequence of these mutants were located at residues 304 and/or 386. Most of the substitutions at residue 304 were from threonine to isoleucine, whereas the substitutions at residue 386 were from arginine to proline, histidine, cysteine, or tryptophan. Based on this data, it appears that AA residues at 304 and 386 on the S1 glycoprotein are involved in a virus neutralizing serotype specific epitope.
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PMID:Identification of amino acids involved in a serotype and neutralization specific epitope within the s1 subunit of avian infectious bronchitis virus. 967 90

Chlamydia are obligate intracellular eubacteria that are phylogenetically separated from other bacterial divisions. C. trachomatis and C. pneumoniae are both pathogens of humans but differ in their tissue tropism and spectrum of diseases. C. pneumoniae is a newly recognized species of Chlamydia that is a natural pathogen of humans, and causes pneumonia and bronchitis. In the United States, approximately 10% of pneumonia cases and 5% of bronchitis cases are attributed to C. pneumoniae infection. Chronic disease may result following respiratory-acquired infection, such as reactive airway disease, adult-onset asthma and potentially lung cancer. In addition, C. pneumoniae infection has been associated with atherosclerosis. C. trachomatis infection causes trachoma, an ocular infection that leads to blindness, and sexually transmitted diseases such as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and epididymitis. Although relatively little is known about C. trachomatis biology, even less is known concerning C. pneumoniae. Comparison of the C. pneumoniae genome with the C. trachomatis genome will provide an understanding of the common biological processes required for infection and survival in mammalian cells. Genomic differences are implicated in the unique properties that differentiate the two species in disease spectrum. Analysis of the 1,230,230-nt C. pneumoniae genome revealed 214 protein-coding sequences not found in C. trachomatis, most without homologues to other known sequences. Prominent comparative findings include expansion of a novel family of 21 sequence-variant outer-membrane proteins, conservation of a type-III secretion virulence system, three serine/threonine protein kinases and a pair of parologous phospholipase-D-like proteins, additional purine and biotin biosynthetic capability, a homologue for aromatic amino acid (tryptophan) hydroxylase and the loss of tryptophan biosynthesis genes.
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PMID:Comparative genomes of Chlamydia pneumoniae and C. trachomatis. 1019 88

Chlamydophila pneumoniae is an obligate intracellular bacterium that causes bronchitis, pharyngitis, and pneumonia and may be involved in atherogenesis and Alzheimer's disease. Genome sequencing has identified three eukaryote-type serine/threonine protein kinases, Pkn1, Pkn5, and PknD, that may be important signaling molecules in Chlamydia. Full-length PknD was cloned and expressed as a histidine-tagged protein in Escherichia coli. Differential centrifugation followed by sodium carbonate treatment of E. coli membranes demonstrated that His-PknD is an integral membrane protein. Fusions of overlapping PknD fragments to alkaline phosphatase revealed that PknD contains a single transmembrane domain and that the kinase domain is in the cytoplasm. To facilitate solubility, the kinase domain was cloned and expressed as a glutathione S-transferase (GST) fusion protein in E. coli. Purified GST-PknD kinase domain autophosphorylated, and catalytic mutants (K33G, D156G, and K33G-D156G mutants) and activation loop mutants (T185A and T193A) were inactive. PknD phosphorylated recombinant Cpn0712, a type III secretion YscD homolog that has two forkhead-associated domains. Thin-layer chromatography revealed that the PknD kinase domain autophosphorylated on threonine and tyrosine and phosphorylated the FHA-2 domain of Cpn0712 on serine and tyrosine. To our knowledge, this is the first demonstration of a bacterial protein kinase with amino acid specificity for both serine/threonine and tyrosine residues and this is the first study to show phosphorylation of a predicted type III secretion structural protein.
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PMID:Chlamydophila pneumoniae PknD exhibits dual amino acid specificity and phosphorylates Cpn0712, a putative type III secretion YscD homolog. 1776 19

The lungworm, Dictyocaulus viviparus, causes parasitic bronchitis in cattle, and is responsible for substantial economic losses in temperate regions of the world. Here, we undertake the first large-scale exploration of available transcriptomic data for this lungworm, examine differences in transcription between different stages/both genders and identify and prioritize essential molecules linked to fundamental metabolic pathways, which could represent novel drug targets. Approximately 3 million expressed sequence tags (ESTs), generated by 454 sequencing from third-stage larvae (L3s) as well as adult females and males of D. viviparus, were assembled and annotated. The assembly of these sequences yielded ~61,000 contigs, of which relatively large proportions encoded collagens (4.3%), ubiquitins (2.1%) and serine/threonine protein kinases (1.9%). Subtractive analysis in silico identified 6928 nucleotide sequences as being uniquely transcribed in L3, and 5203 and 7889 transcripts as being exclusive to the adult female and male, respectively. Most peptides predicted from the conceptual translations were nucleoplasmins (L3), serine/threonine protein kinases (female) and major sperm proteins (male). Additional analyses allowed the prediction of three drug target candidates, whose Caenorhabditis elegans homologues were linked to a lethal RNA interference phenotype. This detailed exploration, combined with future transcriptomic sequencing of all developmental stages of D. viviparus, will facilitate future investigations of the molecular biology of this parasitic nematode as well as genomic sequencing. These advances will underpin the discovery of new drug and/or vaccine targets, focused on biotechnological outcomes.
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PMID:Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention. 2118 26

Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.
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PMID:Suppression of coronavirus replication by cyclophilin inhibitors. 2369 97

Lung cancer shows the highest incidence rate in the world. Thus, it has become increasingly important to find therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in traditional Chinese medicine to treat pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti-proliferation effects of petroleum extracts of FF (PEFF) on Lewis lung cancer cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related to the anti-proliferation effect of PEFF were identified, which were probably involved in pyruvate metabolism and glycine, serine and threonine metabolism. For the cellular uptake compounds in PEFF, six metabolites derived from two prototype compounds were also tentatively identified by UHPLC-Q-Orbitrap high-resolution MS. Network pharmacology analysis demonstrated that the anti-proliferation mechanism of PEFF was also probably related to the target genes, including, Aurora-A, glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase P 1 (GSTP1), progesterone receptor and heme oxygenase-1 (HO-1), and further associated with the proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method to investigate the anti-proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF.
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PMID:Uncovering the anticancer mechanism of petroleum extracts of Farfarae Flos against Lewis lung cancer by metabolomics and network pharmacology analysis. 3238 57


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