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Biomedical subjects

T Miyamoto

Publications and source records attributed to T Miyamoto.

At least 73 records · Page 4Linked to original sources
PubMed2002

[Experience with pyoktanin lavage for mediastinitis and prosthetic graft infection following thoracic aortic surgery].

Pyoktanin, a triphenylmethane dye, is known to have a potent bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). We used pyoktanin for irrigating wounds in 2 cases of mediastinitis and prosthetic graft infection following thoracic aortic surgery. Case 1 is mediastinitis and prosthetic graft infection due to Staphylococcus epidermidis following Cabrol procedure. After irrigating the anterior mediastinum with 0.1% pyoktanin solution twice a day for 8 days, omental transposition was performed, which let to cure of the infection. Case 2 is mediastinitis due to methicillin-resistant Staphylococcus epidermidis following ascending aortic and aortic arch replacement for acute type A aortic dissection. After irrigating the wound with 0.1% pyoktanin solution twice a day for 14 days, the wound was closed primarily, which resulted in cure of the infection of the wound. Using pyoktanin at low concentrations for irrigating wound for a short period of time is considered permissible and effective for mediastinitis and prosthetic graft infection due to Gram-positive bacteria including MRSA.

Anti-Infective Agents, Local↗
PubMed2002

[Acute aortic regurgitation due to localized aortic dissection adjacent to the commissure of the aortic valve].

A 78-year-old male with a sudden loss of consciousness and chest pain was transferred to our hospital. He presented heart failure due to severe aortic regurgitation. Cardiac ultrasonography and computed tomography (CT) scanning did not lead to an established diagnosis of acute aortic dissection. Aortic valve replacement was performed 24 days after the onset of the disease. The surgical findings showed prolapse of the aortic valve due to localized dissection adjacent to the commissure of the aortic valve.

Acute Disease↗
PubMed2001

Catalyzed Diels-Alder reaction of alkylidene- or arylideneacetoacetates and Danishefsky's dienes with lanthanide salts aimed at selective synthesis of cis-4,5-dimethyl-2-cyclohexenone derivatives.

The first successful example of the catalyzed Diels-Alder reaction of 1-methoxy-3-trimethylsiloxy-1,3-diene (Danishefsky's diene, 2a), giving the corresponding carbocyclic adducts, is described. The reaction of (Z)-ethylideneacetoacetate 1a with 2a is catalyzed with lanthanide salts such as Yb(OTf)(3) at 0 degrees C, affording the corresponding 2-cyclohexenone 3a in good yield with complete integrity of the starting geometry of 1a. The thermal version of the same cycloaddition results in a decrease in the cis arrangement of the 5-methyl and the 4-alkoxycarbonyl groups on 2-cyclohexenone. The catalyzed reaction of (E)-1a unexpectedly affords the cis-arranged 3a. The reaction path for the catalyzed Diels-Alder reaction is postulated on the basis of these results.

Journal Article↗
PubMed2001

Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling.

OBJECTIVES: We sought to examine the role of the pro-inflammatory cytokine, interleukin-1-beta (IL-1beta), in the process of left ventricular (LV) remodeling in the early phase after myocardial infarction (MI). BACKGROUND: Studies have shown that pro-inflammatory cytokines are closely related to the progression of LV remodeling after MI. METHODS: Mice underwent coronary artery ligation, and the time course of LV remodeling was followed up to 20 weeks. The gene expression level of IL-1beta was examined. In a second set of experiments, the mice underwent coronary artery ligation followed by treatment with anti-IL-1beta antibody (100 microg, intravenously), versus control immunoglobulin G (100 microg, intravenously) immediately after the operation. RESULTS: Rapid hypertrophy of noninfarcted myocardium was observed by four weeks, and interstitial fibrosis progressed steadily up to 20 weeks. Anti-IL-1beta treatment increased the occurrence of ventricular rupture and suppressed collagen accumulation in the infarct-related area. At four and eight weeks after the operation, total heart weight and LV end-diastolic dimension were significantly greater in the anti-IL-1beta-treated mice than in the other groups. In the infarct-related area, collagen accumulation was suppressed, whereas in the noninfarcted area, pro-collagen gene expression levels, particularly type III, were decreased in the anti-IL-1beta-treated mice. CONCLUSIONS: Anti-IL-1beta treatment suppressed pro-collagen gene expression and delayed wound healing mechanisms-properties that are likely to lead to progression of LV remodeling. In the acute phase of MI, IL-1beta appears to play a protective role.

Acute Disease↗
PubMed2001

Bifurcation of osteoclasts and dendritic cells from common progenitors.

Osteoclasts and dendritic cells are derived from monocyte/macrophage precursor cells; however, how their lineage commitment is regulated is unknown. This study investigated the differentiation pathways of osteoclasts and dendritic cells from common precursor cells at the single-cell level. Osteoclastogenesis induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha) is completely inhibited by addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 at early stages of differentiation. GM-CSF-treated cells express both c-Fms and RANK and also low levels of CD11c and DEC205, which are detected on dendritic cells. Addition of GM-CSF also reduces expression of both c-Fos and Fra-1, which is an important event for inhibition of osteoclastogenesis. Overexpression of c-Fos by retroviral infection or induction in transgenic mice can rescue a failure in osteoclast differentiation even in the presence of GM-CSF. By contrast, differentiation into dendritic cells is inhibited by M-CSF, indicating that M-CSF and GM-CSF reciprocally regulate the differentiation of both lineages. Dendritic cell maturation is also inhibited when c-Fos is expressed at an early stage of differentiation. Taken together, these findings suggest that c-Fos is a key mediator of the lineage commitment between osteoclasts and dendritic cells. The lineage determination of osteoclast progenitors seen following GM-CSF treatment functions through the regulation of c-Fos expression.

Animals↗
PubMed2001

ALCAM (CD166): its role in hematopoietic and endothelial development.

A critical role for the endothelium of yolk sac and dorsal aorta has been shown in embryonic hematopoiesis. A stromal cell line derived from yolk sac, YSCL-72, has been chosen to search for a novel molecule associated with embryonic hematopoiesis. Analysis between YSCL-72 and an adult aorta-derived endothelial cell line, EOMA, demonstrated that activated leukocyte cell adhesion molecule (ALCAM, or CD166) was specifically expressed in YSCL-72 but not in EOMA. Immunohistochemical study showed that ALCAM was expressed in the endothelium of yolk sac and dorsal aorta but not in adult aorta. ALCAM-transfected EOMA cells supported development of hematopoietic progenitor cells compared with vector-transfected EOMA cells, suggesting that ALCAM appeared to be crucial for hematopoiesis. In addition, ALCAM was found to be involved in capillary tube formation and hemangioblast differentiation. Taken together with these findings, ALCAM is highly associated not only with embryonic hematopoiesis but also vasculoangiogenesis.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2001

AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations.

The t(8;21) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). The translocation, which involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8, generates an AML1-ETO fusion transcription factor. To examine the effect of the AML1-ETO fusion protein on leukemogenesis, we made transgenic mice in which expression of AML1-ETO is under the control of the human MRP8 promoter (hMRP8-AML1-ETO). AML1-ETO is specifically expressed in myeloid cells, including common myeloid progenitors of hMRP8-AML1-ETO transgenic mice. The transgenic mice were healthy during their life spans, suggesting that AML1-ETO alone is not sufficient for leukemogenesis. However, after treatment of newborn hMRP8-AML1-ETO transgenic mice and their wild-type littermates with a strong DNA-alkylating mutagen, N-ethyl-N-nitrosourea, 55% of transgenic mice developed AML and the other 45% of transgenic mice and all of the wild-type littermates developed acute T lymphoblastic leukemia. Our results provide direct evidence that AML1-ETO is critical for causing myeloid leukemia, but one or more additional mutations are required for leukemogenesis. The hMRP8-AML1-ETO-transgenic mice provide an excellent model that can be used to isolate additional genetic events and to further understand the molecular pathogenesis of AML1-ETO-related leukemia.

Animals↗
PubMed2001

Production and characterization of monoclonal antibodies detecting chicken interleukin-2 and the development of an antigen capture enzyme-linked immunosorbent assay.

Eleven monoclonal antibodies (mAbs) which are specific for chicken interleukin-2 (chIL-2) were produced and characterized by enzyme-linked immunosorbent assay (ELISA), Western blotting and neutralizing assays. These mAbs were used to develop a mAb-based antigen capture ELISA specific for chicken IL-2 detection. Anti-IL-2 mAbs bound specifically to E. coli-derived rchIL-2 in ELISA and identified a 16kDa IL-2 polypeptide band in Western blot. Several mAbs were shown to neutralize the biological activities of both rchIL-2 and native chicken IL-2 as measured by concanavalin A (ConA)-induced lymphocyte proliferation assay, IL-2 bioassay, and natural killer cell assay. Among the neutralizing mAbs, the mAb chIL-2/11 was most potent in neutralizing IL-2 activity. To develop a sensitive ELISA for the detection of chicken IL-2, an antigen capture ELISA was developed using the mAb chIL-2/16 as the antigen capture antibody and rabbit anti-IL-2 peptide antibody as the detection antibody. Using the mAb-based antigen capture ELISA, significant correlation between the level of IL-2 detected in bioassays and in ELISA was observed. These results showed that the mAb-based antigen capture ELISA is less time-consuming and more reliable compared to a conventional IL-2 bioassay for chicken IL-2. These neutralizing mAbs will facilitate basic immunobiological studies of the role of IL-2 in normal and disease states in chickens.

Amino Acid Sequence↗
PubMed2001

Fetal liver myelopoiesis occurs through distinct, prospectively isolatable progenitor subsets.

Hematopoietic fate maps in the developing mouse embryo remain imprecise. Definitive, adult-type hematopoiesis first appears in the fetal liver, then progresses to the spleen and bone marrow. Clonogenic common lymphoid progenitors and clonogenic common myeloid progenitors (CMPs) in adult mouse bone marrow that give rise to all lymphoid and myeloid lineages, respectively, have recently been identified. Here it is shown that myelopoiesis in the fetal liver similarly proceeds through a CMP equivalent. Fetal liver CMPs give rise to megakaryocyte-erythrocyte-restricted progenitors (MEPs) and granulocyte-monocyte-restricted progenitors (GMPs) that can also be prospectively isolated by cell surface phenotype. MEPs and GMPs generate mutually exclusive cell types in clonogenic colony assays and in transplantation experiments, suggesting that the lineage restriction observed within each progenitor subset is absolute under normal conditions. Purified progenitor populations were used to analyze expression profiles of various hematopoiesis-related genes. Expression patterns closely matched those of the adult counterpart populations. These results suggest that adult hematopoietic hierarchies are determined early in the development of the definitive immune system and suggest that the molecular mechanisms underlying cell fate decisions within the myeloerythroid lineages are conserved from embryo to adult. (Blood. 2001;98:627-635)

Age Factors↗
PubMed2001

The role of hinge domain in heterodimerization and specific DNA recognition by nuclear receptors.

Four structural domains are characteristic of the members of the nuclear receptor superfamily. The hinge (D) domain which is located between the DNA binding (C) domain and the ligand binding (EF) domain, is less conserved among the nuclear receptors. In this study, we investigated the effects of the D domain on receptor function with regard to ligand binding, protein-protein interaction and DNA recognition. We found that EF domain of TR lacked T3 binding activity and additional D domain was required for its ligand binding. Using pull down assays and two-hybrid assays, we also demonstrated that the EF domain of TR did not dimerize with TR or RXR in solution, while the DEF domain was able to homo-and heterodimerize with RXR. In contrast, the RXR EF domain alone was able to heterodimerize with TR. The D domain of TR is required but that of RXR is not necessary for the interaction. We further demonstrated that the D domain was required for receptor specific DNA recognition. The ABC domain of vitamin D receptor (VDR) and TR(DEF) chimeric receptor could not bind to VDR response element (VDRE). Addition of own D domain of VDR to the ABC domain enables the chimeric receptor to bind VDRE and transactivate. The D domain of TR cannot substitute for that of VDR in context of specific DNA recognition. These data suggest that the D domain is important to maintain the integrity of the functional structure of the nuclear receptors.

Animals↗
PubMed2001

Dendritic cell potentials of early lymphoid and myeloid progenitors.

It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8alpha(+) DCs derived from the lymphoid lineage and CD8alpha(-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8alpha(+) and CD8alpha(-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs. Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP. In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8alpha(+) and CD8alpha(-) DCs with similar efficiency on a per cell basis. However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8alpha(+) and CD8alpha(-) subtypes, are of myeloid origin. (Blood. 2001;97:3333-3341)

Animals↗
PubMed2001

The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3- cells, as well as macrophages.

We identified an IL-7Ralpha(+)Sca-1(low)c-Kit(low) population in E14 fetal liver, which is the phenotypical analog of common lymphoid progenitors (CLP) in adult bone marrow. After transfer into newborn mice, the IL-7Ralpha(+)Sca-1(low)c-Kit(low) population rapidly differentiated into CD45(+)CD4(+)CD3(-) cells, which are candidate cells for initiating lymph node and Peyer's patch formation. In addition, this population also gave rise to B, T, NK, and CD8alpha(+) and CD8alpha(-) dendritic cells. The fetal liver precursors expressed a significantly lower level of the myeloid-suppressing transcription factor Pax-5, than adult CLP, and retained differentiation activity for macrophages in vitro. We propose that the transition from fetal liver IL-7Ralpha(+)Sca-1(low)c-Kit(low) cells to adult CLP involves a regulated restriction of their developmental potential, controlled, at least in part, by Pax-5 expression.

Animals↗
PubMed2001

O-Glycosylation of G-protein-coupled receptor, octopus rhodopsin. Direct analysis by FAB mass spectrometry.

In addition to the N-glycan that is evidently conserved in G-protein-coupled receptors (GPCRs), O-glycans in the N-terminus of GPCRs have been suggested. Using a combination of enzymatic and manual Edman degradation in conjunction with G-protein coupled receptor mass spectrometry, the structure and sites of O-glycans in octopus rhodopsin are determined. Two N-acetylgalactosamine residues are O-linked to Thr4 and Thr5 in the N-terminus of octopus rhodopsin. Further, we found chicken iodopsin, but not bovine rhodopsin, contains N-acetylgalactosamine. This is the first direct evidence to determine the structure and sites of O-glycans in GPCRs.

Animals↗
PubMed2001

Expression of dominant negative form of PAX4 in human insulinoma.

The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to beta cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.

Amino Acid Sequence↗
PubMed2001

Standalone cutting balloon angioplasty for the treatment of stent-related restenosis: acute results and 3- to 6-month angiographic recurrent restenosis rates.

Despite excellent acute reperfusion results, 20%-30% of patients who undergo coronary stent implantation will develop angiographic restenosis and may require same additional treatments. Cutting Balloon angioplasty (CBA) causes less histological damage outside of the incised area than a regular balloon. However, regular plain old balloon angioplasty is sometimes required before CBA, as is adjunctive stenting and adjunctive angioplasty. These adjunctive strategies may negate the advantages of CBA. There is little data available on CBA as a standalone therapy for stent-related restenosis (SRS). The aim of this study was to evaluate the acute and 3- to 6-month angiographic recurrent restenosis rates following standalone CBA in a patient population treated for SRS and in whom optimal acute results were obtained. In this study, 40 patients with SRS (54 lesions) underwent standalone CBA with optimal acute results. For all lesions, coronary angiography was conducted before and after a standalone CBA procedure for SRS and systematically during 3-6 months to assess recurrent angiographic restenosis rates in the study population. In the study lesions, SRS was either diffuse disease (> 15 mm; 52%) or focal type (48%). Cutting Balloon diameter was 3.20 +/- 0.44 mm and maximal inflation pressure 8.7 +/- 1.2 atm. Ratio of Cutting Balloon diameter to restenotic stent diameter was 0.996 +/- 0.487. Multiple inflations (6 +/- 3 times) were performed. Number of used Cutting Balloon was 1.02 +/- 0.14. Complications were as follows; one non-Q-wave MI (1.9%); 0 death (0%), and 17 repeat target lesion revascularizations (TLRs; 32%). Follow-up coronary angiography (CAG) was not attained for one patient. The angiographic recurrent restenosis rate was 34%, with a higher rate observed when the SRS was diffuse type, 50% vs. 16% for focal-type SRS (P < 0.01). The recurrent restenosis rate for smaller vessels (vessel diameter < or = 3.0 mm) was the same as for larger ones. At follow-up CAG, diffuse-type recurrent restenosis (56%) presented nearly as frequently as that presenting in the original SRS lesions (52%). But four diffuse-type SRS (29%) changed into focal-type recurrent stenosis. In this study, standalone CBA for SRS with optimal acute results was associated with an angiographic restenosis rate of 34%. Diffuse-type disease had a higher recurrent restenosis rate. When CBA achieves acute optimal results, adjunctive stenting or adjunctive PTCA are not always necessary, particularly when the SRS is focal. As a result of CBA, some diffuse-type SRS may change into focal-type recurrent stenosis by the time of the next intervention.

Adult↗
PubMed2001

Smad translocation and growth suppression in lens epithelial cells by endogenous TGFbeta2 during wound repair.

To determine whether endogenous TGFbeta affects lens epithelial cells during repair after an anterior capsule injury in mice, we studied translocation of Smad proteins, which carry the TGFbeta signal from cell surface receptors to promoters in nuclei. We immunolocalized Smads in murine lenses at intervals up to 8 weeks following capsular injury. Effects of injecting TGFbeta neutralizing antibodies on Smad4 location and cell proliferation were examined at 24 hr after injury. Finally, we examined whether exogenous TGFbeta2 induced Smad nuclear translocation in murine lenses in organ culture. Cell proliferation was quantitated by 5-bromo-2'-deoxyuridine (BrdU) labelling. In uninjured lenses, Smads were located in the cytoplasm. In injured lenses, nuclear localization of Smads was observed in cells next to the capsular break from 8 to 24 hr after the injury, and was observed peripheral to the break at 48 hr. Nuclear Smads then continued to be observed occasionally in a minority of cells. Injection of antibodies neutralizing TGFbeta2, but not TGFbeta1 or TGFbeta3, inhibited Smad4 nuclear translocation and resulted in the appearance of BrdU-positive anterior epithelial cells. With the lenses in culture, transient nuclear localization of Smads occurred between 3 and 24 hr in response to continuous exposure to TGFbeta2. No nuclear translocation was seen at 48 hr. Endogenous TGFbeta2 affects lens cells during wound repair after anterior capsule injury, inhibiting lens cell proliferation during the early phase. Nuclear translocation of Smads in lens epithelial cells is transient even with continuous exposure to TGFbeta2.

Animals↗
PubMed2001

High incidence of severe urologic complications following radiotherapy for cervical cancer in Japanese women.

BACKGROUND: Good results have been obtained with radiation therapy for cervical cancer, but many patients suffer radiation-induced complications of adjacent organs. Some authors have reported that about 10% of patients treated with radiotherapy experience radiation-induced complications. We have previously reported that the incidence of spontaneous rupture of the urinary bladder is high in Japan but extremely low in the United States and Europe. In this study, we examined whether incidence or type of radiation-induced complications differs between Japan and the United States and Europe. METHODS: A retrospective study was performed to determine the incidence among Japanese women of severe complications requiring surgical intervention following radiotherapy for cervical cancer. A total of 271 patients were treated at Kobe City General Hospital using external-beam therapy from December 1981 to March 1989. In 232 external-beam therapy was combined with high-dose-rate intracavitary brachytherapy with a remotely controlled afterloading system (RALS). The incidence and type of radiation-induced complications of the urinary tract, rectum, and intestine were determined following exclusion of 74 patients with evidence of disease recurrence or progression. RESULTS: A total of 16 patients (8.1%) had urologic complications that required surgical intervention following irradiation, while a total of 26 patients (13.2%) had complications of the rectum or intestine that required surgical intervention following irradiation. Urologic complications occurred significantly later than those of the rectum and intestine (6.4 and 2.2 years, respectively) (P < 0.0001). The overall incidence of severe complications was comparatively higher than reported in the United States and Europe. The incidence of spontaneous rupture of the urinary bladder was particularly high (2.0%) in Japan. CONCLUSIONS: The incidence of severe complications following radiotherapy is comparatively higher in Japan than in the United States and Europe. In particular, spontaneous rupture of the urinary bladder is common in Japan. This might be due to the use of high-dose-rate brachytherapy. Since brachytherapy is currently being used for prostate cancer, urologists and radiologists must consider the possibility of a high incidence of such severe complications, especially when using high-dose-rate brachytherapy.

Brachytherapy↗