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 objective of this study was to explore the nature of the antigen-specific T cell response in giant cell arteritis by analyzing clonally expanded T cells in temporal artery specimens. In temporal artery tissue from eight patients, 10% of the T cell receptor beta chain repertoire was systematically screened for clonal T cells by reverse-transcriptase polymerase chain reaction with selected BV, BJ, and BC specific primers and by direct sequencing of the amplified product. In five additional patients tissue-derived T cell clones were characterized. All expanded clonotypes were analyzed for their presence at different sites of the inflamed artery. T cell lines were tested for their proliferation to autologous monocytes pulsed with temporal artery extracts from patients with giant cell arteritis, polymyalgia rheumatica, and unrelated diseases. Clonally expanded T cells were identified in 30% of the BV-J combinations of the sampled repertoire. A subset of these clones were encountered at different sites of the inflammation, but not in the peripheral blood. The T cell receptor beta chain sequences were diverse. The patients had between none and five such clonotypes in the sampled repertoire, suggesting that only few T cell specificities in each patient are involved in antigen recognition. One of these T cell clonotypes was shown to proliferate in response to an antigen selectively expressed in temporal artery specimens from giant cell arteritis and from polymyalgia rheumatica patients. Clonotypes with identical T cell receptor beta chain sequences can be found at distinct sites of the inflammation in giant cell arteritis, suggesting recognition of the same antigen at different locations. At least for some of these T cell clones the antigen is shared between different giant cell arteritis and polymyalgia rheumatica patients but not expressed in temporal arteries of patients with unrelated diseases. While different HLA-DR4+ patients utilize distinct T cell specificities, the actual number of responding T cells in individual patients is small and may be disease limiting.
J Mol Med (Berl) 1996 Nov
PMID:Recognition of tissue residing antigen by T cells in vasculitic lesions of giant cell arteritis. 895 56

We have recently characterized Nicotiana cytoplasmic (cyt) tRNA(GCA)Cys as a novel UGA suppressor tRNA. Here we have isolated its corresponding (NtC1) and a variant (NtC2) gene from a genomic library of Nicotiana rustica. Both tRNA(Cys) genes are efficiently transcribed in HeLa cell nuclear extract and yield mature cyt tRNAs(Cys). Sequence analysis of the upstream region of the RAD51 single-copy gene of the Arabidopsis thaliana genome revealed a cluster of three tRNA(Cys) genes which have the same polarity and comprise highly similar flanking sequences. Of the three Arabidopsis tRNA(Cys) genes only one (i.e. AtC2) appears to code for a functional gene which exhibits an almost identical nucleotide sequence to NtC1. These are the first sequenced nuclear tDNAs(Cys) of plant origin.
Plant Mol Biol 1996 Nov
PMID:Nucleotide sequences of nuclear tRNA(Cys) genes from Nicotiana and Arabidopsis and expression in HeLa cell extract. 898 May 5

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.
J Mol Biol 1996 Dec 20
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

In this paper we describe the peculiar structures and preferential codon usage found in wild silkworm fibroin genes. We determined a 1350 bp nucleotide sequence from the Chinese oak silkworm, Antheraea pernyi. The deduced amino acid sequence was partitioned into thirteen polyalanine-containing repetitive motifs, which was one of the characteristics of Antheraea fibroins. Eleven of these arrays can be classified into two types of motifs depending on difference in amino acid sequences following polyalanine. Repetitive motifs structurally similar to those of A. pernyi were detected in a homologue of the Japanese oak silkworm, Antheraea yamamai. The most remarkable feature of this study was preferential codon usage, especially seen in alanine synonymous codons within both homologues of Antheraea: isocodon GCA most frequently occurred in alanine isocodons. In contrast, GCU isocodon was the most abundant in Bombyx mori fibroin heavy chain that lacks polyalanine arrays. This result strongly suggests different modes of selective constraint between the two types of fibroin gene. The similar finding that GCA isocodon was most frequent in two dragline silk sequences of the spider, Nephila clavipes, is consistent with our results because of the repetitive polyalanine-containing arrays seen in spider dragline silk.
Insect Mol Biol 1997 Feb
PMID:Preferential codon usage and two types of repetitive motifs in the fibroin gene of the Chinese oak silkworm, Antheraea pernyi. 901 60

In addition to facilitating the nuclear export of incompletely spliced viral mRNAs, equine infectious anemia virus (EIAV) Rev regulates alternative splicing of the third exon of the tat/rev mRNA. In the presence of Rev, this exon of the bicistronic RNA is skipped in a fraction of the spliced mRNAs. In this report, the cis-acting requirements for exon 3 usage were correlated with sequences necessary for Rev binding and transport of incompletely spliced RNA. The presence of a purine-rich exon splicing enhancer (ESE) was required for exon 3 recognition, and the addition of Rev inhibited exon 3 splicing. Glutathione-S-transferase (GST)-Rev bound to probes containing the ESE, and mutation of GAA repeats to GCA within the ESE inhibited both exon 3 recognition in RNA splicing experiments and GST-Rev binding in vitro. These results suggest that Rev regulates alternative splicing by binding at or near the ESE to block SR protein-ESE interactions. A 57-nucleotide sequence containing the ESE was sufficient to mediate Rev-dependent nuclear export of incompletely spliced RNAs. Rev export activity was significantly inhibited by mutation of the ESE or by trans-complementation with SF2/ASF. These results indicate that the ESE functions as a Rev-responsive element and demonstrate that EIAV Rev mediates exon 3 exclusion through protein-RNA interactions required for efficient export of incompletely spliced viral RNAs.
Mol Cell Biol 2000 May
PMID:Binding of equine infectious anemia virus rev to an exon splicing enhancer mediates alternative splicing and nuclear export of viral mRNAs. 1077 44

The actual frequency of constitutively activating thyrotropin receptor or Gsalpha mutations in toxic thyroid nodules (TTNs) remains controversial as considerable variation in the prevalence of these mutations has been reported. We studied a series of 75 consecutive TTNs and performed mutation screening by the more sensitive method of denaturing gradient gel electrophoresis (DGGE) in addition to direct sequencing. Furthermore, the likelihood of somatic mutations occurring in genes other than that for the thyroid-stimulating hormone receptor (TSHR) and exons 7-9 of the Gsalpha protein gene was determined by clonality analysis of TTNs, which did not harbor mutations in the investigated genes. In 43 of 75 TTNs (57%) constitutively active TSHR mutations were identified. Six TSHR mutations were detected only by DGGE, underlining the importance of a sensitive screening method. Novel, constitutively activating mutations were identified at positions 425 (Ser-->Leu) and 512 (Leu-->Glu/Arg). Furthermore, a new base substitution was detected at position Pro639Ala (CCA-->GCA). Ten of 20 TSHR or Gsalpha mutation negative cases (50%) showed nonrandom X-chromosome inactivation, indicating clonal origin. In conclusion, somatic, constitutively activating TSHR mutations appear to be a major cause of TTNs (57%), while mutations in Gsalpha play a minor role (3%). The mutation negative but clonal cases indicate a probable involvement of somatic mutations other than in the TSH receptor or Gsalpha genes as the molecular cause of these hot nodules.
J Mol Med (Berl) 2001
PMID:Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. 1143 17

Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with inherited cancer syndromes of multiple endocrine neoplasia type 2 and familial MTC. Missense RET proto-oncogene mutations and small in-frame deletions are found in most of the cases. In a significant amount of sporadic MTC cases somatic mutation at codon 918 (exon 16), or at codons 609, 611, 618, 620 (exon 10), or codons 630, 634 (exon 11) appear. We report here on three new somatic cell missense mutations of the RET proto-oncogene associated with sporadic MTC. In one tumor mutation at codon 922 TCC(Ser)-->TTC(Phe) in exon 16 was found. In another tumor two mutations at codons 639 GCA(Ala)-->GGA(Gly) and 641 GCT(Ala)-->CGT(Arg) in the exon 11 were observed. Allele-specific PCR followed by sequencing demonstrated the presence of both mutations at the same allele.
J Mol Med (Berl) 2001 Oct
PMID:Three novel mutations in the RET proto-oncogene. 1169 59

Intron-encoded U17 RNA is a member of the H/ACA box class of small nucleolar RNAs (snoRNAs) involved in ribosomal RNA (rRNA) maturation. U17 snoRNA shows typical characteristics of guide RNAs, which specify sites of pseudouridylation on the precursor rRNA (pre-rRNA). However, in spite of the presence of H and ACA boxes and short regions complementary to the pre-rRNA, its secondary structure does not show any evident pseudouridylation pocket. Moreover, its length is larger than the typical one of snoRNAs and it shows a more complex secondary structure compared to the canonical hairpin-hinge-hairpin-tail architecture. Greater knowledge of eukaryotic U17 snoRNA structure is needed to understand its precise function. Comparative molecular studies of this snoRNA with different vertebrates is still limited to a few cases. With the aim of increasing our understanding of the U17 snoRNA secondary structure, we cloned the U17 snoRNA coding sequence from 10 additional vertebrate taxa. On the basis of structure homology derived from sequence comparison and thermodynamic prediction, we propose a vertebrate consensus secondary structure and novel conserved sequence boxes for U17 snoRNA. Host gene localization of U17 coding sequence and its ability to serve as a guide sequence for RNA/RNA interaction has been evolutionarily traced from fish to mammals. It is interesting to note that turtle U17 snoRNAs show a noncanonical ACA box, mainly consisting in the GCA box. Microinjections in X. laevis oocytes of in vitro synthesized turtle transcripts containing the U17 RNA sequence which have canonical ACA, wild-type GCA, and mutated CCA and UCA boxes resulted in efficient production of mature U17 snoRNA.
J Mol Evol 2002 Feb
PMID:Comparative structure analysis of vertebrate U17 small nucleolar RNA (snoRNA). 1182 10

The underlying basis of the genetic code is specific aminoacylation of tRNAs by aminoacyl-tRNA synthetases. Although the code is conserved, bases in tRNA that establish aminoacylation are not necessarily conserved. Even when the bases are conserved, positions of backbone groups that contribute to aminoacylation may vary. We show here that, although the Escherichia coli and human cysteinyl-tRNA synthetases both recognize the same bases (U73 and the GCA anticodon) of tRNA for aminoacylation, they have different emphasis on the tRNA backbone. The E. coli enzyme recognizes two clusters of phosphate groups. One is at A36 in the anticodon and the other is in the core of the tRNA structure and includes phosphate groups at positions 9, 12, 14, and 60. Metal-ion rescue experiments show that those at positions 9, 12, and 60 are involved with binding divalent metal ions that are important for aminoacylation. The E. coli enzyme also recognizes 2'-hydroxyl groups within the same two clusters: at positions 33, 35, and 36 in the anticodon loop, and at positions 49, 55, and 61 in the core. The human enzyme, by contrast, recognizes few phosphate or 2'-hydroxy groups for aminoacylation. The evolution from the backbone-dependent recognition by the E. coli enzyme to the backbone-independent recognition by the human enzyme demonstrates a previously unrecognized shift that nonetheless has preserved the specificity for aminoacylation with cysteine.
J Mol Biol 2002 May 17
PMID:Recognition of tRNA backbone for aminoacylation with cysteine: evolution from Escherichia coli to human. 1208 12

The aim of this prospective study was to compare fluorine-18 fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) with magnetic resonance imaging (MRI) in patients with early aortitis, at the time of initial diagnosis and during immunosuppressive therapy. The study population consisted of 15 patients (nine females and six males; median age 62 years, range 26-76 years) who presented with fever of unknown origin or an elevated erythrocyte sedimentation rate or elevated C-reactive protein and who showed pathological aortic [(18)F]FDG uptake. Fourteen of these patients had features of early giant cell arteritis (GCA), while one had features of early Takayasu arteritis. During follow-up, seven PET scans were performed in six patients with GCA 4-30 months (median 19 months) after starting immunosuppressive medication. The results of [(18)F]FDG imaging were compared with the results of MRI at initial evaluation and during follow-up and with the clinical findings. At baseline, abnormal [(18)F]FDG uptake was present in 59/104 (56%) of the vascular regions studied in 15 patients. Seven follow-up PET studies were performed in six patients. Of 30 regions with initial pathological uptake in these patients, 24 (80%) showed normalisation of uptake during follow-up. Normalisation of [(18)F]FDG uptake correlated with clinical improvement and with normalisation of the laboratory findings. All except one of the patients with positive aortic [(18)F]FDG uptake were investigated with MRI and MRA. Thirteen of these 14 patients showed inflammation in at least one vascular region. Of 76 vascular regions studied, 41 (53%) showed vasculitis on MRI. Of 76 vascular regions studied with both PET and MRI, 47 were concordantly positive or negative on both modalities, 11 were positive on MRI only and 18 were positive on PET only. MRI was performed during follow-up in six patients: of 17 regions with inflammatory changes, 15 regions remained unchanged and two showed improvement. Whole-body [(18)F]FDG PET is valuable in the primary diagnosis of early aortitis. The results of [(18)F]FDG PET and MRI in the diagnosis of aortitis in this study were comparable, but FDG imaging identified more vascular regions involved in the inflammatory process than did MRI. In a limited number of patients [(18)F]FDG PET was more reliable than MRI in monitoring disease activity during immunosuppressive therapy.
Eur J Nucl Med Mol Imaging 2003 May
PMID:Early diagnosis and follow-up of aortitis with [(18)F]FDG PET and MRI. 1267 2


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