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A Muto

Publications and source records attributed to A Muto.

At least 19 recordsLinked to original sources
PubMed2006

Presence of prostacyclin receptor in arteriosclerotic human femoral artery.

AIM: Prostacyclin, which is mainly synthesized by vascular endothelial cells, exerts antiplatelet and smooth-muscle-relaxant effects, thereby maintaining cardiovascular homeostasis. Prostacyclin analogues have been clinically proven to improve ischemic symptoms and prevent the occurrence of vascular events in the lower extremities of patients with arteriosclerosis obliterans. We examined the presence of prostacyclin receptor (IP receptor) in an arteriosclerotic human femoral artery. METHODS: Specimens of the femoral artery were obtained at the time of limb amputation from an 83-year-old woman. Atherosclerotic lesions and associated changes such as calcification were evident. The specimens were stained with hematoxylin and eosin, and processed for immunohistochemistry. RESULTS: A monolayer of cells was observed on the luminal side of the femoral artery. Single immunohistochemistry showed the presence of the IP receptors on cells of the luminal side of the femoral artery. Triple-immunofluorescence staining revealed colocalization of IP-receptor-positive cells and cells positive for von Willebrand factor, a marker of vascular endothelial cells. CONCLUSIONS: We investigated the presence of the IP receptor in the human femoral artery immunohistochemically, and demonstrated their strong expression in endothelial cells. This finding suggests that prostacyclin or prostacyclin analogues may act on their receptors on endothelial cells in patients with arteriosclerosis obliterans.

Aged, 80 and over↗
PubMed2006

False aneurysm formation at proximal and distal ends of a stent graft: a rare complication in the repair of endovascular thoracic aortic aneurysm.

This case report demonstrates a rare complication of false aneurysm formation at the proximal and distal ends of a stent graft that was placed in the descending thoracic aorta to repair an atherosclerotic aneurysm with a fibrotic, solid aortic wall. This complication can develop not only in penetrating aortic ulcers and aortic dissections but also in atherosclerotic aneurysms.

Aged↗
PubMed2004

Isolation of eight novel Caenorhabditis elegans small RNAs.

Eight novel small RNAs that were encoded in the regions corresponding to the introns of protein-coding genes were isolated from Caenorhabditis elegans. Seven of them showed a typical snoRNA secondary structure: one C/D snoRNA and six H/ACA snoRNAs. The remaining one RNA did not show any homology to other RNAs in a database. Four of the seven isolated snoRNAs could form base pairings with parts of rRNAs, suggesting that they are potential pseudouridilation sites and methylation sites. The results of our study suggest that there are more as-yet-unidentified small ncRNAs of which genes are located in the intron regions of protein-coding genes in C. elegans.

Animals↗
PubMed2004

Abdominal aortic aneurysm with left-sided inferior vena cava. Report of a case.

The combination of abdominal aortic aneurysms and congenital anomalies of the inferior vena cava and its tributaries, such as double inferior vena cava, left-sided inferior vena cava, circumaortic renal collar, and retroaortic renal vein, are very rare but of clinical importance to vascular surgeons since these conditions can increase the difficulty of aneurysm resection as well as the risk of venous injury and subsequent excessive bleeding. This report describes a case of an abdominal aortic aneurysm with a left-sided inferior vena cava, and reviews of the incidence, diagnosis, and treatment of these conditions.

Aged↗
PubMed2001

Importance of the conserved nucleotides around the tRNA-like structure of Escherichia coli transfer-messenger RNA for protein tagging.

A bacterial RNA functioning as both tRNA and mRNA, transfer-messenger RNA (tmRNA) rescues stalled ribosomes and clears the cell of incomplete polypeptides. For function, Escherichia coli tmRNA requires an elaborate interplay between a tRNA-like structure and an internal mRNA domain that are connected by a 295 nt long compact secondary structure. The tRNA-like structure is surrounded by 16 unpaired nt, including 10 residues that are >95% conserved among the known 140 tmRNA sequences. All these residues were mutated to define their putative role(s) in trans-translation. Both the extent of aminoacylation and the alanine incorporation into the tag sequence, reflecting the two functions of tmRNA, were measured in vitro for all variants. As anticipated from the low sequence conservation, mutating positions 8-12 and position 15 affects neither aminoacylation nor protein tagging. Mutating a set of two conserved positions 13 and 14 abolishes both functions. Probing the solution conformation indicates that this defective mutant adopts an alternate conformation of its acceptor stem that is no more aminoacylatable, and thus inactive in protein tagging. Selected point mutations at the conserved nucleotide stretches 16-20 and 333-335 seriously impair protein tagging with only minor changes in their solution conformations and aminoacylation. Point mutations at conserved positions 19 and 334 abolish trans-translation and 70S ribosome binding, although retaining nearly normal aminoacylation capacities. Two proteins that are known to interact with tmRNA were purified, and their interactions with the defective RNA variants were examined in vitro. Based on phylogenetic and functional data, an additional structural motif consisting of a quartet composed of non-Watson-Crick base pairs 5'-YGAC-3':5'-GGAC-3' involving some of the conserved nucleotides next to the tRNA-like portion is proposed. Overall, the highly conserved nucleotides around the tRNA-like portion are maintained for both structural and functional requirements during evolution.

Acylation↗
PubMed2001

Determinants on tmRNA for initiating efficient and precise trans-translation: some mutations upstream of the tag-encoding sequence of Escherichia coli tmRNA shift the initiation point of trans-translation in vitro.

tmRNA facilitates a novel translation, trans-translation, in which a ribosome can switch between translation of a truncated mRNA and the tmRNA's tag sequence. The mechanism underlying resumption of translation at a definite position is not known. In the present study, the effects of mutations around the initiation point of the tag-encoding sequence of Escherichia coli tmRNA on the efficiency and the frame of tag translation were assessed by measuring the incorporations of several amino acids into in vitro poly (U)-dependent tag-peptide synthesis. One-nucleotide insertions within the tag-encoding region did not shift the frame of tag translation. Any 1-nt deletion within the span of -5 to -1, but not at -6, made the frame of tag translation heterologous. Positions at which a single base substitution caused a decrease of trans-translation efficiency were concentrated within the span of -4 to -2. In particular, an A-4 to C-4 mutation seriously damaged the trans-translation, although this mutant retained normal aminoacylation and ribosome-binding abilities. A possible stem and loop structure around this region was not required for transtranslation. It was concluded that the tag translation requires the primary sequence encompassing -6 to +11, in which the central 3 nt, A-4, G-3, and U-2, play an essential role. It was also found that several base substitutions within the span of -6 to -1 extensively shifted the tag-initiation point by -1.

Acylation↗
PubMed2001

A novel differentiation-inducing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF.

Arsenic trioxide (As2O3) effectively induces clinical remission via apoptosis in relapsed acute promyelocytic leukemia (APL). However, because this new anti-leukemic drug is also considered to be a poison, its possible adverse effects are a highly important issue related to its clinical use. We here investigated, both in vitro and in vivo, the effects of a combination of As2O3 and GM-CSF as a novel therapeutic approach for the treatment of APL. Treatment of both retinoic acid (RA)-sensitive and -resistant APL cell lines (NB4 and UF-1 cells, respectively), as well as primary APL cells with a combination of As2O3 and GM-CSF for 4 days resulted in inducing differentiation, but not apoptosis, to mature granulocytes. In addition, a combination of both agents induced degradation of the PML/RARalpha protein. GM-CSF was found to be associated with increased tyrosine phosphorylation of Jak2 kinase in both NB4 and UF-1 cells, and a specific inhibitor of Jak2, AG490, completely blocked the ability of GM-CSF to prevent apoptosis and induce differentiation of As2O3-treated UF-1 cells. In in vivo analysis, As2O3 induced differentiation of APL cells in a RA-resistant APL model of human GM-CSF-producing transgenic SCID mice that had a high level of human GM-CSF in their sera. In contrast, As2O3 alone diminished tumors in UF-1 cells transplanted into NOD/SCID mice via induction of apoptosis. In conclusion, a combination of As2O3 and GM-CSF appears to be a novel differentiation-inducing therapy in patients with APL, including relapsed or RA-resistant cases.

Animals↗
PubMed2001

Localization of mitochondrial ribosomal RNA on the chromatoid bodies of marine planarian polyclad embryos.

Electron-dense cytoplasmic structures, referred to as chromatoid bodies, are observed in the somatic stem cells, called neoblasts, and germline cells in adult planarians. Although it has been revealed that the chromatoid bodies morphologically resemble germline granules in Drosophila and Xenopus embryos, what essential role it plays in the planarian has remained unclear. In the present study, to examine whether chromatoid bodies in planarian embryos are responsible for germline formation, the presence and behavior of chromatoid bodies during embryogenesis were examined. Mitochondrial large ribosomal RNA and mitochondrial small ribosomal RNA were used as candidate markers for components of the chromatoid body. Starting from the fertilized egg, extramitochondrial signals of both RNA (mtrRNA) were observed. At the ultrastructural level, mtrRNA were localized on the surface of the chromatoid bodies. At subsequent stages, the signals of mtrRNA were observed in certain restricted blastomeres that contribute to the formation of larval structures. The signals gradually decreased from the gastrula stage. These results suggest that the chromatoid bodies associated with mtrRNA in embryogenesis are not germline granules. The chromatoid bodies of blastomeres may be concerned with the toti- or pluripotency and cell differentiation as proposed in adult planarian neoblasts.

Animals↗
PubMed2001

The promoter of mouse transcription repressor bach1 is regulated by Sp1 and trans-activated by Bach1.

The Maf recognition element (MARE) is regulated by both activators and repressors. Bach1 and Bach2 repress MARE-dependent transcription by forming heterodimers with Maf-related oncoproteins. In order to gain an understanding of the regulation of bach1 gene expression, we analyzed the structure of the mouse bach1 gene. Comparison of the exon-intron structure of the bach1 gene with those of other NF-E2-related genes indicated that bach1 and bach2 constitute an evolutionarily distinct subfamily among bZip factors. The bach1 promoter region contains two GC boxes that are important for its basal activity and are bound by Sp1 in K562 cell extracts. In addition, we found an evolutionarily conserved MARE-like element located downstream of the transcription initiation site. Deletion of this element resulted in a higher promoter activity in K562 cells. Bach1 trans-activated its own promoter depending on the presence of the MARE-like element in co-transfection assays. However, Bach1 did not bind to the MARE-like element in electrophoretic mobility shift assays (EMSA). These results suggest that Bach1 activates its own promoter indirectly by inhibiting the putative repressor. Such a positive feedback regulation by the repressor Bach1 may play an important role in maintaining the expression of Bach1 while consolidating repression of other genes with MARE.

Animals↗
PubMed2001

Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides.

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.

Adult↗
PubMed2000

Human Nod1 confers responsiveness to bacterial lipopolysaccharides.

The immune response to microbial pathogens is initiated by recognition of specific pathogen components by host cells both at the cell surface and in the cytosol. While the response triggered by pathogen products at the surface of immune cells is well characterized, that initiated in the cytosol is poorly understood. Nod1 is a member of a growing family of intracellular proteins with structural homology to apoptosis regulators Apaf-1/Ced-4 and a class of plant disease-resistant gene products. Here we show that bacterial lipopolysaccharides, but not other pathogen components tested, induced TLR4- and MyD88-independent NF-kappaB activation in human embryonic kidney 293T cells expressing trace amounts of Nod1. Nod2, another Nod family member, also conferred responsiveness to bacterial components but with a response pattern different from that observed with Nod1. As it was reported for plant disease-resistant R proteins, the leucine-rich repeats of Nod1 and Nod2 were required for lipopolysaccharide-induced NF-kappaB activation. A lipopolysaccharide binding activity could be specifically coimmunopurified with Nod1 from cytosolic extracts. These observations suggest that Nod1 and Nod2 are mammalian counterparts of plant disease-resistant gene products that may function as cytosolic receptors for pathogen components derived from invading bacteria.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15.

The transcription factor Bach2, a member of the BTB-basic region leucine zipper (bZip) factor family, binds to a 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and the related Maf-recognition element (MARE) by forming homodimers or heterodimers with Maf-related transcription factors. Bach2 regulates transcription by binding to these elements. To understand the function in hematopoiesis, we isolated a cDNA clone for human Bach2 (BACH2) encoding a protein of 841 amino acid residues with a deduced amino acid sequence having 89.5% identity to mouse homolog. Among human hematopoietic cell lines, BACH2 is expressed abundantly only in some B-lymphocytic cell lines. RT-PCR analysis of hematopoietic cells revealed that BACH2 mRNA is expressed in primary B-cells. Enforced expression of BACH2 in a human Burkitt cell line, RAJI that does not express endogenous BACH2, resulted in marked reduction of clonogenic activity, indicating that BACH2 possesses an inhibitory effect on cell proliferation. By fluorescent in situ hybridization, the BACH2 gene was localized to chromosome 6q15. Because deletion of the long arm of chromosome 6 (6q) is one of the commonest chromosomal alterations in human B-cell lymphoma, we examined for the loss of heterozygosity (LOH) of the BACH2 gene in human B-cell non-Hodgkin's lymphomas (NHL). Among 25 informative cases, five (20%) showed LOH. These results indicate that BACH2 plays important roles in regulation of B cell development.

Adult↗
PubMed2000

Three of four pseudoknots in tmRNA are interchangeable and are substitutable with single-stranded RNAs.

A novel translation, trans-translation, is facilitated by a highly structured RNA molecule, tmRNA. This molecule has two structural domains, a tRNA domain and an mRNA domain, the latter including four pseudoknot structures (PK1 to PK4). Here, we show that replacement of each of these pseudoknots, except PK1, in Escherichia coli tmRNA with a single stranded RNA did not seriously affect the functions as an alanine tRNA and as an mRNA. Furthermore, these three pseudoknots were interchangeable with only small losses of the two functions. These findings suggest that neither PK2, PK3 nor PK4 interacts in a functional manner with ribosome during the trans-translation process. Together with an earlier study showing the significance of PK1, it is concluded that among the four pseudoknots, PK1 is the most functional.

Acylation↗
PubMed2000

Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice.

Recent clinical studies in China and USA showed that arsenic trioxide (As2O3) is an effective treatment of acute promyelocytic leukemia (APL) patients refractory to all-trans retinoic acid (RA). We here investigate the effects of As2O3 on RA-resistant APL in vivo and in vitro using our RA-resistant APL model system. As2O3 can induce inhibition of cellular growth of both RA-sensitive NB4 and RA-resistant UF-1 APL cells via induction of apoptosis in vitro. The expression of BCL-2 protein decreased in a dose- and time-dependent manner in NB4 cells. Interestingly, the levels of BCL-2 protein were not modulated by As2O3, but it did upregulate BAX protein in UF-1 cells. UF-1 cells (1x10(7)) were transplanted into hGM-CSF-producing transgenic SCID mice and successfully formed subcutaneous tumors. After 40 days of implantation, mice were treated with As2O3, all-trans RA and PBS for 21 days. In all-trans RA- and PBS-treated mice, tumors grew rapidly, with a 4.5-fold increase in volume at day 21 compared to the initial size. In marked contrast, tumor size was decreased to half of the initial size by the treatment of As2O3, which resulted in cells with the typical appearance of apoptosis. Interestingly, one of the As2O3-treated mice showed mature granulocytes in the diminished tumor, suggesting that As2O3 had dual effects on RA-resistant APL cells in vivo: both inducing apoptosis and differentiation of the leukemic cells. We conclude that our RA-resistant APL model will be useful for evaluating novel therapeutic approaches to patients with RA-resistant APL, and for further investigation of the metabolism of As2O3 in vivo.

Animals↗
PubMed2000

Requirement of transfer-messenger RNA for the growth of Bacillus subtilis under stresses.

BACKGROUND: Bacterial transfer-messenger RNA (tmRNA, 10Sa RNA) is involved in a trans-translation reaction which contributes to the degradation of incompletely synthesized peptides and to the recycling of stalled ribosomes. However, its physiological role in the cell remains elusive. In this study, an efficient system for controlling the expression of the gene for tmRNA (ssrA), as well as a tmRNA gene-defective strain (ssrA:cat), were constructed in Bacillus subtilis. The effects of tmRNA on the growth of the cells were investigated under various physiological culture conditions using these strains. RESULTS: The cells were viable in the absence of ssrA expression under the usual culture conditions. However, the growth rate of cells without tmRNA expression, relative to that of the expressed cells, decreased with elevating temperature (> 45 degrees C), and at 52 degrees C, the highest temperature for growth of the wild-type, cells grew depending on the expression level of tmRNA. Furthermore, the transcription level of the ssrA from the authentic promoter at a high temperature (51 degrees C) was about 10-fold higher than that at a lower temperature (37 degrees C). tmRNA-dependent growth and an increase in tmRNA amount were also observed in cells under other stresses, such as high concentrations of ethanol or cadmium chloride. It is also shown that alanylated tmRNA rather than tmRNA-mediated proteolysis is required for growth at high temperature. CONCLUSION: The expression of tmRNA gene (ssrA) is required for the efficient growth of B. subtilis under several strong stresses. The transcription of ssrA increases under several stressful conditions, suggesting that it is a stress-response gene. Alanyl-tmRNA, probably via its ability of recycling stalled ribosomes via trans-translation, is involved in the stress tolerance of bacteria.

Alanine↗
PubMed2000

The structure and function of tRNA-like domain in E. coli tmRNA.

tmRNA has a dual function both as a tRNA and as an mRNA in trans-translation. tmRNA possesses structural elements similar to canonical tRNAs. Our mutation studies show that the tRNA-like structure is crucial for function as an mRNA as well as a tRNA.

Escherichia coli↗
PubMed2000

A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain.

Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the BTB/POZ domain, MAZR possesses Zn finger motifs that are closely related to those of the Myc-associated Zn finger (MAZ) protein. MAZR mRNA was coexpressed with Bach2 in B cells among hematopoietic cells and in developing mouse limb buds, suggesting a cooperative role for MAZR and Bach2 in these cells. MAZR forms homo- and hetero-oligomers with Bach2 through the BTB domain, which oligomers bind to guanine-rich sequences. Unlike MAZ, MAZR functioned as a strong activator of the c-myc promoter in transfection assays with B cells. However, it does not possess a typical activation domain, suggesting a role for it as an unusual type of transactivator. The fgf4 gene, which regulates morphogenesis of limb buds, contains both guanine-rich sequences and a Bach2 binding site in its regulatory region. In transfection assays using fibroblast cells, the fgf4 gene was upregulated in the presence of both MAZR and Bach2 in a BTB/POZ domain-dependent manner. The results provide a new perspective on the function of BTB/POZ domain factors and indicate that BTB/POZ domain-mediated oligomers of transcription factors may serve as combinatorial codes for gene expression.

Amino Acid Sequence↗