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)

The J-variant of human serum butyrylcholinesterase (BChE) causes both an approximately two-thirds reduction of circulating enzyme molecules and a corresponding decrease in the level of BChE activity present in serum. Since the level of serum BChE activity and the duration of succinylcholine apnea are inversely correlated, this marked decrease in activity makes individuals with the J-variant more susceptible than usual subjects to prolonged apnea from succinylcholine. We reinvestigated the same family in which Garry et al. identified the J-variant phenotype. The atypical, fluoride, and K-variant mutations were also identified in members of the 47-person pedigree. DNA amplification by PCR, followed by direct sequencing of the amplified DNA, led to the finding that the J-variant phenotype of human serum BChE was associated with two DNA point mutations in the coding region. One of these was the mutation previously identified with the K-variant phenotype (GCA----ACA; Ala539----Thr). The other was an adenine-to-thymine transversion at nucleotide 1490, which changed amino acid 497 from glutamic acid to valine (GAA----GTA; Glu497----Val). This latter point mutation was named the J-variant mutation (formal name BCHE*497V). The J-variant mutation has not been identified without the K-variant mutation. The J-variant mutation created an RsaI-enzyme RFLP. Two additional point mutations, located in the noncoding regions of the gene, were also found to be linked with the J-variant and K-variant point mutations on the same allele. These noncoding polymorphic mutations had previously been found linked to the atypical and K-variant point mutations. A summary table shows dibucaine, fluoride, and Hoffmann-La Roche compound Ro 2-0683 inhibition numbers for 119 samples whose DNA has been sequenced. Eighteen BChE genotypes are represented.
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PMID:DNA mutations associated with the human butyrylcholinesterase J-variant. 134 96

An assay based on the initiation of protein synthesis in Escherichia coli has been used to explore the role of the anticodon in tRNA identity in vivo. Mutations were introduced into the initiator tRNA to change the wild-type anticodon from CAU (methionine) to GAU (isoleucine), GAC (valine), and GAA (phenylalanine), where each derivative differs from the preceding by a single base change in the anticodon (underlined). These changes were sufficient to cause the mutant tRNAs to be aminoacylated by the corresponding aminoacyl-tRNA synthetases based on the amino acid inserted into protein from complementary initiation codons. Construction of additional single base anticodon variants (GUU, GGU, GCC, GUC, GCA, and UAA) showed that all three anticodon bases specify isoleucine and phenylalanine identity and that both the middle and the third anticodon bases are important for valine identity in vivo.
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PMID:Anticodon-dependent aminoacylation of a noncognate tRNA with isoleucine, valine, and phenylalanine in vivo. 202 34

The nucleotide sequence of a 6.7 kb segment of the circular 73 kb DNA from Astasia longa has been determined. We identified genes for a tRNA-Ile (CAU), a tRNA-Phe (GAA), a tRNA-Cys (GCA) and the ribosomal proteins CS8, CL36, CS14 and CS2, that are normally encoded by plastid genomes. In addition, a gene for the chloroplast ribosomal protein CL5 was found that is not encoded by the plastome in either higher plants or a liverwort, but has recently been identified in Euglena chloroplast DNA. Transcripts of these protein genes, and of an unidentified open reading frame (ORF50), were detected. These results support our previous suggestion that the 73 kb DNA from Astasia is a truncated form of plastid DNA. The 73 kb DNA resembles the chloroplast DNA of Euglena gracilis but contains, almost exclusively, genes for a plastid-type translational (and presumably transcriptional) apparatus.
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PMID:Genes for ribosomal proteins are retained on the 73 kb DNA from Astasia longa that resembles Euglena chloroplast DNA. 207 69

Point mutations in factor IX genes of four unrelated Chinese patients with hemophilia B have been identified by direct sequencing of amplified genomic DNA fragments. These four mutations occur in exon 8 of the factor IX gene. A C to T transition at nucleotide 30,863 changes codon 248 from Arg (CGA) to a new Stop codon (TGA), described in a previous family as factor IXMalmo3 (Green P M et al., EMBO J 1989; 8: 1067). A G to A transition at nucleotide 31,051 changes codon 310 from Trp (TGG) to a nonsense or Stop codon (TGA; factor IXChongquing2). A G to A transition at nucleotide 31,119 changes codon 333 which is for Arg (CGA) in normal factor IX, to one for Gln (CAA) in the variant previously described as factor IXLondon2 (Tsang T C et al., EMBO J 1988; 7: 3009) in a patient with moderately severe hemophilia B. The fourth patient has a novel C to A transversion at nucleotide 31,290, which corresponds to replacement of codon 390 which is for Ala (GCA) in normal factor IX, to one for Glu (GAA) in a patient with moderately severe hemophilia B (factor IXChongquing3). DNA sequences of amplified fragments from mothers of three showed both their son's variant and a normal nucleotide at the appropriate position, indicating that they are carriers. The fourth patient's (factor IXMalmo3) mother, whose DNA was not evaluable, was most probably a carrier because of her low plasma factor IX levels.
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PMID:Point mutations in four hemophilia B patients from China. 227 May 38

DNA structural changes induced by bleomycin have been investigated using diethylpyrocarbonate and permanganate as probes under conditions in which the antibiotic binds to, but does not cut the DNA. Diethyl-pyrocarbonate shows an enhanced reaction with adenines in the presence of the antibiotic in the sequences GTA greater than GCA greater than GAA, on the 3' side of the drug cutting site (GPy). Permanganate ions display an enhanced reactivity at the second pyrimidine of the sequence GPyPy. The results are consistent with a model in which bleomycin distorts the structure of the base pair on the 3' side of its binding site.
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PMID:Diethylpyrocarbonate and permanganate provide evidence for an unusual DNA conformation induced by binding of the antitumour antibiotics bleomycin and phleomycin. 245 9

In the course of a systematic survey of wheat mitochondrial tRNA genes, we have sequenced chloroplast-like serine (trnS-GGA), phenylalanine (trnF-GAA) and cysteine (trnC-GCA) tRNA genes and their flanking regions. These genes are remnants of 'promiscuous' chloroplast DNA that has been incorporated into wheat mtDNA in the course of its evolution. Each gene differs by one or a few nucleotides from the authentic chloroplast homolog previously characterized in wheat or other plants, and each could potentially encode a functional tRNA whose secondary structure shows no deviations from the generalized model. To determine whether these chloroplast-like tRNA genes are actually expressed, wheat mitochondrial tRNAs were resolved by a series of polyacrylamide gel electrophoreses, after being specifically end-labeled in vitro by 3'-CCA addition mediated by wheat tRNA nucleotidyltransferase. Subsequent direct RNA sequence analysis identified prominent tRNA species corresponding to the mitochondrial and not the chloroplast trnS, trnF and trnC genes. This analysis also revealed chloroplast-like elongator methionine, asparagine and tryptophan tRNAs. Our results suggest that at least some chloroplast-like tRNA genes in wheat mtDNA are transcribed, with transcripts undergoing processing, post-transcriptional modification and 3'-CCA addition, to produce mature tRNAs that may participate in mitochondrial protein synthesis.
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PMID:Chloroplast-like transfer RNA genes expressed in wheat mitochondria. 276 45

The fusion-generating phage lambda plac Mu1 was used to produce fusions of lacZ to fhuA, the gene encoding the ferrichrome-iron receptor (FhuA protein) in the outer membrane of Escherichia coli K-12. Fusions to the fhuA gene in a delta (lac) strain were selected by their resistance to bacteriophage phi 80 vir. Ten independent (fhuA'-'lacZ) fusions were all Lac+ and were resistant to the lethal agents which require the FhuA protein as receptor, i.e., phi 80 vir, T5, T1, UC-1, and colicin M; none could utilize ferrichrome as the sole iron source. Specialized transducing phages were obtained by illegitimate excision from the chromosome of each of the fusion-bearing strains, and EcoRI fragments which encoded the fusions were subcloned into the high-copy plasmid pMLB524. Physical mapping of the fusion-containing plasmids confirmed the presence of three restriction sites which were also located on the chromosomal DNA of sequences near the fhuA gene. The direction of transcription of the fhuA gene was deduced from the direction of transcription of the (fhuA'-'lacZ) gene fusion. Identification of the chimeric proteins was made by both radiolabeling cells and immunoprecipitating the LacZ-containing proteins with antibody to beta-galactosidase and by preparing whole cell extracts from Lac+ cells containing the cloned gene fusions. Two sizes of (FhuA'-'LacZ) proteins were detected, 121 kDa and 124 kDa. The DNA sequences at the unique fusion joints were determined. The sequence information allowed us to identify three distinct fusion joints which were grouped as follows, type I fusions, 5'-ACT GCT CAG CCA A-3'; type IIa fusions, 5'-GCG GTT GAA CCG A-3'; and type IIb fusions: 5'-ACC GCT GCA CCT G-3'. To orient these fhuA fusion joints, the complete nucleotide sequence of the fhuA gene was determined from a 2,902-base-pair fragment of DNA. A single open reading frame was found which translated into a 747-amino acid polypeptide. The signal sequence of 33 amino acids was followed by a mature protein with a molecular weight of 78,992. Alignment of the amino acid sequence of the FhuA protein with the amino acid sequences presented for two other tonB-dependent receptor proteins in the outer membrane of E. coli showed an area of local homology at the amino terminus of all three proteins.
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PMID:Protein fusions of beta-galactosidase to the ferrichrome-iron receptor of Escherichia coli K-12. 307 47

The ancestral gene for immunoglobulin light-chain variable regions (Ig VLs) of the kappa as well as the lambda class apparently arose from about 12 tandem repeats of the 48-base-long primordial building block sequence TCT-TGC-GCA-GTA-AGT-CCA-CTC-CAG-GTC-ATA-TCC-AGT-CAG-GCT-GCT-GAA. Even today, amino acid residues 67 to 82 of each Ig V kappa L are still specified by a direct descendant in toto of the above-noted primordial building block, whereas amino acid residues 14 to 25 are invariably specified by its truncated copy. The Ig VL primordial building block presently identified is 100% complementary to the Ig VH (heavy-chain variable region) primordial building block previously identified. In the recognition of specific antigenic determinants by antibodies, Ig VL and Ig VH of light-chain--heavy-chain dimers have to complement each other. It is perhaps fitting that the primordial building blocks of the two are represented by the complementary strands of the same 48-base-pair-long DNA sequence.
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PMID:The 48-base-long primordial building block of immunoglobulin light-chain variable regions is complementary to the primordial building block of heavy-chain variable regions. 680 18

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


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