Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.
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PMID:Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides. 754 46

A 6.4-kb DNA fragment containing the DNA gyrase gyrA and gyrB genes was cloned and sequenced from the quinolone-susceptible Staphylococcus aureus type strain ATCC 12600. An expression plasmid was constructed by inserting the cloned genes into the Escherichia coli-S. aureus shuttle vector pAT19, and deletion plasmids carrying only functional gyrA and gyrB genes were derived from this plasmid. An efficient transformation system for S. aureus RN4220 was established by using these plasmids. Quinolone-resistant mutants of S. aureus RN4220 were isolated by three-step selection with quinolones. The first- and second-step mutants were considered to be transport mutants, and the third-step mutants were divided into five groups with respect to their resistance patterns and transformation results with gyrA and gyrB genes. Sequencing analysis of the resulting mutant gyrase genes showed that they had the following point mutations: group 1, Ser-84 (TCA) to Leu (TTA) in GyrA; group 2, Ser-84 (TCA) to Ala (GCA), Ser-85 (TCT) to Pro (CCT), or Glu-88 (GAA) to Lys (AAA) in GyrA; group 3, Asp-437 (GAC) to Asn (AAC) in GyrB; group 4, Arg-458 (CGA) to Gln (CAA) in GyrB; and group 5, Ser-85 (TCT) to Pro (CCT) in GyrA and Asp-437 (GAC) to Asn (AAC) in GyrB. When the gyrA and/or gyrB mutants were transformed with the wild-type gyrA and/or gyrB plasmids, they became quinolone susceptible, but transformants with the plasmids having the same mutations on the gyrA and/or gyrB genes did not confer susceptibility. These results indicate that mutations in both gyrA and gyrB can be responsible for quinolone resistance in S. aureus.
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PMID:Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. 781 Oct 12

An allelic variant of the human TCR C alpha gene, designated C alpha AL, which encodes a structurally different protein product has been characterized. C alpha AL was independently sequenced using polymerase chain reaction (PCR)-amplified TCR C alpha cDNA from various T cell clones derived from a same individual. It differed from the most usual C alpha sequence by two non-synonymous base changes at codons 4 (AAC-->AAG) and 84 (GAA-->GCA) of the C alpha coding region. These changes imply amino acid substitutions Asn-->Lys and Glu-->Ala respectively. An oligotyping method, based on hybridization of allele-specific oligonucleotides to PCR-amplified C alpha DNA, is also described. It was used for differential typing of the two C alpha forms in family and population studies. In each of three T cell clones analyzed from the same donor having two rearranged TCR alpha chain transcripts, C alpha AL was found in only one of the transcripts. In addition, C alpha AL segregated as a co-dominant mendelian allele within the family of this donor. Population analysis was carried out in 73 spanish individuals. Twelve donors (16.4%) were heterozygous, implying that C alpha AL was present in this population sample with an allelic frequency of 0.08. The observed frequencies of C alpha genotypes were those expected for the two alleles being in Hardy-Weinberg equilibrium. This demonstration of structural polymorphism in the constant region of TCR alpha chains provides a useful genetic marker for TCR and disease association studies due to its precise mapping within the C alpha coding region, and its significant frequency in the analyzed population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allelic polymorphism in the coding region of human TCR C alpha gene and characterization of structural variability in the alpha chain constant domain. 815 98

ErbB-2 is overexpressed in several human cancers and conveys a transforming activity that is dependent on tyrosine kinase activity. Antibodies and T cells to ErbB-2 have been isolated from cancer patients, indicating ErbB-2 as a potential target of active vaccination. In this study, 3 mutant ErbB-2 DNA constructs encoding full-length, ErbB-2 proteins were tested as tumor vaccines. To eliminate tyrosine kinase activity, the ATP binding lysine residue 753 was substituted with alanine by replacing codon AAA with GCA in mutant ErbB-2A. To direct recombinant ErbB-2 to the cytoplasm where major histocompatibility complex (MHC) I peptide processing takes place, the endoplasmic reticulum (ER) signal sequence was deleted in cyt ErbB-2. The third construct cyt ErbB-2A contained cytoplasmic ErbB-2 with the K to A mutation. Expression of recombinant proteins was measured by flow cytometry in transfected murine mammary tumor cell line D2F2. Transmembrane ErbB-2 and ErbB-2A were readily detected. Cytoplasmic ErbB-2 and ErbB-2A were detected only after the transfected cells were incubated overnight with a proteasome inhibitor, indicating prompt degradation upon synthesis. ErbB-2 autophosphorylation was eliminated by the K to A mutation as demonstrated by Western blot analysis. Growth of ErbB-2-positive tumor in BALB/c mice was inhibited after vaccination with ErbB-2 or ErbB-2A, but not with cyt ErbB-2 or cyt ErbB-2A. ErbB-2A that is free of tyrosine kinase activity is a potential candidate for anticancer vaccination. The 3 mutant constructs should be useful tools to delineate the role of individual immune effector cell in ErbB-2-specific antitumor immunity and to develop strategies for enhancing such immunity.
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PMID:Protection against mammary tumor growth by vaccination with full-length, modified human ErbB-2 DNA. 1032 28

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.
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PMID:Mxi1 mutations in human neurofibrosarcomas. 1047 Feb 86

PTEN, a tumor suppressor gene, has been found to be inactivated by structural abnormalities or epigenetic changes in several types of human cancers. Recently, several studies have also suggested the possibility that the PTEN gene is a target of genomic instability in human cancers displaying microsatellite instability (MSI). To investigate the role of PTEN in human oral squamous cell carcinomas, we screened the entire coding region sequences and examined the expression of the PTEN gene in 81 oral cancers displaying microsatellite stability (MSS) and 5 oral cancers displaying MSI. Mutation of the PTEN gene was identified in one MSS cancer (1/81; 1.2%) and three MSI cancers (3/5; 60%). The MSS cancer harbored a missense mutation from Ala (GCA) to Val (GTA) at codon 137. Of the MSI cancers containing the PTEN mutation, case 36 had a missense mutation from Lys (AAA) to Glu (GAA) at codon 254, case 43 contained a frameshift mutation (one A deletion) in a 6 bp poly(A) tract affecting codon 265-267, and case 64 harbored two missense mutations from Val (GTG) to Ala (GCG) at codon 222, and from Gly (GGA) to Arg (AGA) at codon 230 indicating biallelic mutation of PTEN. Genomic deletion of exon 5, resulting in loss of PTEN mRNA, was observed in two MSS cancers. In spite of an intact PTEN gene, one MSS and one MSI cancer lacked PTEN mRNA. These findings suggest that the inactivation of PTEN by either mutation or loss of transcript plays a role in the pathogenesis of some oral cancers (8/86; 9.3%). Furthermore, inactivation of PTEN was far more frequent in MSI oral cancers (4/5; 80%) than in MSS oral cancers (4/81; 4.9%).
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PMID:Inactivation of the PTEN gene by mutation, exonic deletion, and loss of transcript in human oral squamous cell carcinomas. 1237 Jul 46

Thalassemias and hemoglobinopathies are very common among Southeast Asian populations, particularly in Thailand, where it is estimated that nearly 30% of the population carries at least one such disorder. Moreover, the heterogeneity of different mutant alpha- and beta-globin alleles contributes to the complexity in diagnosis and proper management, as more than 60 thalassemia syndromes and hemoglobinopathies have been described. Herein we report a further case of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] (also known as G-Saskatoon, G-Hsin Chu and G-Taegu) in a Thai family in which the mother was found to have an unusual hemoglobin (Hb) anomaly in combination with Hb E [beta26(B8)Glu-->Lys, GAG-->AAG]. We applied our recently described polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to scan the beta-globin genes and found an aberrant pattern in exon 1. The molecular analysis by direct genomic sequencing successfully identified the nucleotide mutation (codon 22, GAA-->GCA), and a novel amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for this variant is described.
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PMID:Further identification of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] in Thailand by the polymerase chain reaction-single-strand conformation polymorphism technique and by amplification refractory mutation system-polymerase chain reaction. 1736 10

The trans-translation system in bacteria promotes recycling of stalled ribosomes and targets incomplete peptides for proteolysis. In Escherichia coli, loss of trans-translation function has little effect on growth under normal laboratory conditions. Among the subtle phenotypes of tmRNA-deficient mutants is the inability to plate certain lambda imm(P22) phages. This phenotype is dependent on the ribosome recycling functions of the trans-translation system but is independent of its proteolysis-targeting activity. The experiments described here show that translation of the first (resume) codon of the tmRNA open reading frame by a tRNA is both necessary and sufficient for ribosome recycling. While a variety of sense codons can replace the naturally-occurring GCA alanine codon as the resume codon, both AAA and AAG lysine codons are non-functional resume codons. These results suggest that the main function of tmRNA in releasing stalled ribosomes is to supply a stop codon and so facilitate termination and subsequent ribosome recycling.
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PMID:Minimal translation of the tmRNA tag-coding region is required for ribosome release. 1741 10

The DNA triplet GCA is successfully used as a chiral selector for the chiral discrimination of amino acids using amino acids themselves as a co-selector. Chiral discrimination was achieved by investigating the collision-induced dissociation spectra of the [X(A) + X(R) + 2Y - 2H](2-) ion generated by electrospraying a mixture of analyte amino acid (X(A)), reference amino acid (X(R)) and GCA (Y). The relative abundances of fragment ions resulting from the competitive loss of reference and X(A)'s are considered for measuring the degree of chiral discrimination. GCA successfully shows D-selectivity for all the amino acids, except Tyr and Lys. The success of the method lies in the selection of a suitable 10(R) that has closer GCA binding affinity to that of analyte. The degree of discrimination by GCA is improved in the presence of the reference, and the chirality of the reference does not change the selectivity of GCA. The suitability of the method for the measurement of optical purity is also demonstrated.
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PMID:Chiral discrimination of alpha-amino acids by the DNA triplet GCA using amino acids as a co-selector. 1760 45

Ofloxacinresistance in Staphylococcus aureus is achieved through 2 sequential events of genetic alteration. The second-step mutation has been identified as that of DNA gyrase, but the first-step mutation for norfloxacin resistance and low-level ofloxacin resistance has not yet been identified. In this paper, we report that single point mutations of grIA, which encodes for the A subunit of topoisomerase IV (GrIA), are found in all of the norfloxacin-resistant first-step in vitro mutants of S. aureus as well as in quinolone-resistant clinical S. aureus strains. The amino acid substitution of the GrIA was Ser-80 (TCC) to Tyr (TAC) or the (TTC), Glu-84 (GAA) to Lys (AAA), or Ala-116 (GCA) to Glu (GAA). The GCA to GAA mutation at codon 116 is a novel mutation, and may be responsible for higher quinoloneresistance than with the other grIA mutations.
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PMID:The grIA Mutation in Norfloxacin-Resistant First-Step Mutants and Clinical Isolates of Staphylococcus aureus. 2968 57


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