ABSTRACT
BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Ulcer Agents/therapeutic use , Famotidine/therapeutic use , Histamine H2 Antagonists/therapeutic use , Omeprazole/analogs & derivatives , Omeprazole/therapeutic use , Peptic Ulcer/prevention & control , 2-Pyridinylmethylsulfinylbenzimidazoles , Aged , Arthritis, Rheumatoid/drug therapy , Female , Humans , Lansoprazole , Male , Middle Aged , Peptic Ulcer/chemically induced , Prospective Studies , Treatment OutcomeABSTRACT
A human cDNA encoding a novel zinc-finger protein, ZNF274, was identified by the "nuclear transportation trap" method (Ueki, N., Oda, T., Kondo, M., Yano, K., Noguchi, T., and Muramatsu, M., 1998, Nat. Biotechnol. 16: 1338-1342). Based on sequence analysis of the full-length cDNA, this novel gene has two alternative splicing forms, ZNF274a and ZNF274b, which encode putative proteins of 621 and 584 amino acids, respectively. ZNF274a contains five C2H2-type zinc-finger motifs, two KRAB-A (Kruppel-associated box) domains, and one leucine-rich domain. ZNF274b lacks the first KRAB-A domain at the N-terminus. ZNF274 mRNA is detected in various human tissues by Northern analysis. The ZNF274 gene is mapped distal to marker RP S28 1 in the human chromosome 19qter region, by RH mapping. The KRAB domains of ZNF274 exhibited transcription repressor activity when tested in GAL4 fusion protein assays. EGFP-ZNF274 fusion protein expressed in COS7 cells predominantly localized to the nucleoli. A series of deletion constructs revealed that a minimal domain consisting of the third and fourth zinc-fingers possesses nucleolar targeting ability. These results suggest that ZNF274 is a ubiquitous transcription repressor that plays a role in the nucleoli.
Subject(s)
Cell Nucleolus/metabolism , DNA, Complementary/genetics , DNA-Binding Proteins/genetics , Repressor Proteins , Transcription Factors/genetics , Zinc Fingers/genetics , Alternative Splicing , Animals , Base Sequence , Biological Transport , Blotting, Northern , COS Cells , Chromosome Mapping , Chromosomes, Human, Pair 19/genetics , DNA, Complementary/chemistry , DNA, Complementary/isolation & purification , DNA-Binding Proteins/metabolism , Female , Gene Expression , Green Fluorescent Proteins , Humans , Hybrid Cells , Kruppel-Like Transcription Factors , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Microscopy, Fluorescence , Molecular Sequence Data , Protein Isoforms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Analysis, DNA , Tissue Distribution , Transcription Factors/metabolismABSTRACT
A-kinase anchoring protein 95 (AKAP95) is a nuclear protein which binds to the regulatory subunit (RII) of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and to DNA. A novel nuclear human gene which shares sequence homology with the human AKAP95 gene was identified by a nuclear transportation trap method. By polymerase chain reaction (PCR)-based analysis with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid panel, the gene was mapped to the chromosome 19p13.11-p13.12 region between markers WI-4669 and CHLC.GATA27C12. Furthermore, alignment with genomic sequences revealed that the gene and human AKAP95 resided tandemly only approximately 250 bp apart from each other. We designated this gene as neighbor of AKAP95 (NAKAP95). The exon-intron structure of NAKAP95 and AKAP95 was conserved, indicating that they may have evolved by gene duplication. The predicted protein product of the NAKAP95 gene consists of 646 amino acid residues, and NAKAP95 and AKAP95 had an overall 40% similarity, both having a potential nuclear localizing signal and two C2H2 type zinc finger motifs. The putative RII binding motif in AKAP95 was not conserved in NAKAP95. A reverse transcription coupled (RT)-PCR experiment revealed that the NAKAP95 gene was transcribed ubiquitously in various human tissues.
Subject(s)
Carrier Proteins/genetics , Chromosomes, Human, Pair 19/genetics , DNA-Binding Proteins/genetics , Nuclear Proteins/genetics , Amino Acid Sequence , Chromosome Mapping , Cloning, Molecular , DNA, Complementary/genetics , Exons , Humans , Intracellular Signaling Peptides and Proteins , Introns , Molecular Sequence Data , Zinc FingersABSTRACT
A human cDNA, HFB30, encoding a novel protein that contains a RING finger (C3HC4-type zinc finger) motif was isolated. This cDNA clone consists of 3056 nucleotides and encodes an open reading frame of a 474 amino acid protein. From RT-PCR analysis, the messenger RNA was ubiquitously expressed in various human tissues. The gene was located to the chromosome 5q23.3-q31.1 region by PCR-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel. Furthermore, the gene consists of nine exons that span about 20 kb of genome DNA.