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)

A novel spectrin variant carrying a truncated beta-chain and designated Spectrin Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the alpha I 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened beta-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta 220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.
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PMID:A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216). 139 62

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

The DNA undecamers GTACAAAGTAC (AAA 11-mer) and GTACGAGGTAC (GAG 11-mer) have been studied in solution by high-resolution NMR spectroscopy. Both duplexes form stable hairpins containing single deoxyadenosine loops and stems containing five base-pairs that are closed at the loop end by sheared AxA and GxC pairs, respectively. These molecules thus contain new AAA and GAG loop turn motifs. All protons, including the chiral H5'/H5" protons of the loop residues, were assigned using NOESY, DQF-COSY and heteronuclear 1H-31P COSY experiments. The backbone torsion angles were constrained using experimental data from NOE crosspeaks, three-bond 1H-1H coupling constants and four-bond 1H-31P coupling constants and four-bond 1H-31P coupling constants. The AAA and GAG 11-mers form similar structures in solution. The detailed structure of the AAA 11-mer was determined by the combined use of NMR, distance geometry and energy minimization methods. This structure exhibits good stacking of the loop adenosine base on the closing 5Ax7A sheared pair, with the 6A base stacking on the 5A base and the 6A deoxyribose stacking with the 7A base. All sugars in the AAA 11-mer hairpin adopt the typical DNA C2'-endo conformation and a sharp backbone turn occurs between residues 6A and 7A. This loop turn is brought about mainly by a change in the backbone phosphate torsion angles from zeta(g-) alpha(g-) to zeta(g+) alphat(g+) at the turn. The gamma torsion angle of residue 7A in the closing sheared pair also changes from gauche+ to trans. In Pu1NPu2 loop turns of the GCA, AAA and GAG types, the chemical shift of the H4' proton of the loop deoxyribose depends on the nature of Pu2; this reflects the stacking of the loop sugar on the Pu2 base and the different ring current effects of A or G in this position.
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PMID:Hairpin loops consisting of single adenine residues closed by sheared A.A and G.G pairs formed by the DNA triplets AAA and GAG: solution structure of the d(GTACAAAGTAC) hairpin. 900 Jun 25

Little is known about the presence of common medical pathogens in the human oral cavity. Using a 16S rRNA-based PCR identification method, this study determined the occurrence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in subgingival plaque from 50 adults with advanced periodontitis. Each patient contributed samples from 3 deep periodontal pockets collected by paper points. The PCR primers were for P. asaccharolytica 5'-CTC TAG CTA GAG TGT ACT GG-3' and 5'-ATA GGG TTT ATA GAT TAG CTC TCT-3', for B. fragilis 5'-AAT GAT TCC GCA TGG TTT CAT TA-3' and 5'-GCG GTG ATT GCT CAC TGA CA-3', and for C. pneumoniae 5'- TGA CAA CTG TAG AAA TAC AGC-3' and 5'-CGC CTC TCT CCT ATA AAT-3'. The primers yielded a single amplicon with the respective reference strains and produced no amplicon with colonies of 25 groups of oral organisms. None of the three test species were detected in any of the 50 pooled subgingival samples tested. P. asaccharyolytica, B. fragilis and C. pneumoniae do not seem to be part of the periodontopathic microbiota in humans.
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PMID:Absence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in human subgingival plaque. 957 14

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

A number of trinucleotide sequences in DNA can form compact and stable hairpin loops that may have significance for DNA replication and transcription. The conformational analysis of these motifs is important for an understanding of the function and design of nucleic acid structures. Extensive conformational searches have been performed on three experimentally known trinucleotide hairpin loops (AGC, AAA, and GCA) closed by a four-base-pair stem. An implicit solvation model based on the generalized Born method has been employed during energy minimization and conformational search. In addition, energy-minimized conformers were evaluated using a finite-difference Poisson-Boltzmann approach. For all three loop sequences, conformations close to experiment were found as lowest-energy structures among several thousand alternative energy minima. The inclusion of reaction-field contributions was found to be important for a realistic conformer ranking. Most generated hairpin loop structures within approximately 5 kcal x mol(-1) of the lowest-energy structure have a similar topology. Structures within approximately 10 kcal x mol(-1) could be classified into about five structural families representing distinct arrangements of loop nucleotides. Although a large number of backbone torsion angle combinations were compatible with each structural class, some specific patterns could be identified. Harmonic mode analysis was used to account for differences in conformational flexibility of low-energy sub-states. Class-specific differences in the pattern of atomic fluctuations along the sequence were observed; however, inclusion of conformational entropy contributions did not change ranking of structural classes. For an additional loop sequence (AAG) with no available experimental structure, the approach suggests a lowest-energy loop topology overall similar to the other three loop sequences but closed by a different non-canonical base-pairing scheme.
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PMID:Conformational analysis of DNA-trinucleotide-hairpin-loop structures using a continuum solvent model. 1132 35

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

The biopolymer chain elasticity (BCE) approach and the new molecular modelling methodology presented previously are used to predict the tri- dimensional backbones of DNA and RNA hairpin loops. The structures of eight remarkably stable DNA or RNA hairpin molecules closed by a mispair, recently determined in solution by NMR and deposited in the PDB, are shown to verify the predicted trajectories by an analysis automated for large numbers of PDB conformations. They encompass: one DNA tetraloop, -GTTA-; three DNA triloops, -AAA- or -GCA-; and four RNA tetraloops, -UUCG-. Folding generates no distortions and bond lengths and bond angles of main atoms of the sugar-phosphate backbone are well restored upon energy refinement. Three different methods (superpositions, distance of main chain atoms to the elastic line and RMSd) are used to show a very good agreement between the trajectories of sugar-phosphate backbones and between entire molecules of theoretical models and of PDB conformations. The geometry of end conditions imposed by the stem is sufficient to dictate the different characteristic DNA or RNA folding shapes. The reduced angular space, consisting of the new parameter, angle Omega, together with the chi angle offers a simple, coherent and quantitative description of hairpin loops.
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PMID:DNA tri- and tetra-loops and RNA tetra-loops hairpins fold as elastic biopolymer chains in agreement with PDB coordinates. 1256 May 7

The finding that a lens under oxidative stress accumulated free and protein-bound cysteine (protein-S-S-cysteine) in the fiber cells prompted us to examine if there is an alternative source for cysteine pools besides the active cysteine transport system in the lens, namely, the transsulfuration pathway of homocysteine-cystathionine-cysteine, which utilises methionine through transmethylation. We examined the presence of the gene for cystathionine-beta-synthase (CBS), the rate limiting enzyme that converts homocysteine to cystathionine in the transsulfuration pathway, in human lens epithelial (HLE) B3 cells using PCR with primers designed based on the sequence of human liver CBS (Forward 5'-CCA CAC TGC CCC GGC AAA AT-3'; Reverse 5'-CTG GCA ATG CCC GTG ATG GT-3'). The purified DNA fragment (586 bp) from PCR analysis was sequenced and confirmed the homology with CBS gene from other human tissues. The CBS protein band (67 kDa) was present in the HLE cells, which reacted positively with the human liver anti-CBS antibody. The enzyme protein was detected in the pig and human lenses with the highest intensity in the epithelial layer, lower but equal quantities of CBS was present in the cortical and nuclear regions. Human nuclear CBS increased while epithelial CBS decreased with aging. Oxidative stress transiently upregulated the gene expression of CBS both in HLE cells (0.1 mMH2O2) and in pig lens cultured in TC 199 medium (0.5 mMH2O2). The catalytic activity for CBS, which was assayed by measuring the production of C14-cystathionine from C14-serine in the presence of homocysteine, S-adenosyl-methionine and pyridoxal phosphate, was detectable in the HLE cells and transiently activated with H2O2. Free cystathionine accumulated when HLE B3 cells were treated with propargylglycine (PGG), an inhibitor of cystathionase, the downstream enzyme that converts cystathionine to cysteine. More cystathionine accumulation occurred when the cells were simultaneously exposed to PGG and 0.1 mMH2O2. We have shown that oxidative stress of H2O2 could increase the flux of this transsulfuration pathway by committing more homocysteine to cysteine and glutathione production as H2O2 (0.1 mM) inhibited the remethylation enzyme of methionine synthase while concurrently activating the CBS enzyme. This is the first evidence that a transsulfuration pathway is present in the lens, and that it can be upregulated under oxidative stress to provide additional redox potential for the cells.
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PMID:The presence of a transsulfuration pathway in the lens: a new oxidative stress defense system. 1564 25


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