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Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 109 records · Page 6Linked to original sources
PubMed2001

Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions.

Platelet-derived growth factor (PDGF) ligand is a potent glial cell mitogen. When its cognate receptor (PDGF-alphaR) is expressed on oligodendroglial lineage cells, such cells are considered capable of division, and the receptor thus serves as a phenotypic marker for oligodendrocyte precursor cells. Here we identify using immunohistochemistry a considerably enlarged, PDGF-alphaR-expressing oligodendrocyte cell population within multiple sclerosis (MS) white matter lesions compared to control brains. Numerous PDGF-alphaR-positive oligodendroglia also colabel heavily with the nuclear cell proliferation marker antibody Ki-67. Our finding of large numbers of proliferating oligodendroglia in MS brains expressing up-regulated PDGF-alphaR suggests that these progenitor-like cells represent an important source of regenerating cells for the healing MS lesion.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2001

Three-dimensional MR imaging of mammographically detected suspicious microcalcifications.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value and clinical significance of three-dimensional MR imaging of the breast in patients with mammographically detected suspicious microcalcifications. METHODS: Forty patients with suspicious microcalcifications on mammography were evaluated with three-dimensional MR imaging. MR findings were grouped mainly by distribution of abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental-stippled and diffuse-stippled). These findings were compared with the mammography findings according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven malignancies, most frequently ductal carcinoma in situ. For all the cases, linear (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a significantly higher risk for malignancy. Diffuse stippled type (7%) and no enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D-MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the breast can more accurately diagnose ductal carcinoma in situ. Combined with mammography, this procedure is useful for reducing the number of false-positive biopsies and helpful for deciding the better management of patients with mammographically detected suspicious microcalcifications.

Adult↗
PubMed2001

Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation.

We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression.

Antineoplastic Agents↗
PubMed2001

Cytomegalovirus enteritis after autologous peripheral blood stem cell transplantation.

A 61-year-old male with non-Hodgkin's lymphoma (peripheral T-cell lymphoma, unspecified, clinical stage IVb) received autologous peripheral blood stem cell transplantation (PBSCT) during first remission. He was seropositive for cytomegalovirus (CMV) prior to autologous PBSCT. His posttransplant clinical course was complicated by refractory CMV enteritis, which manifested persistent abdominal pain, diarrhea, and bloody stool. Generally, gastrointestinal CMV disease is relatively rare after autologous PBSCT. However, our case indicates that CMV infection must be considered as a differential diagnosis in cases of unexplained hemorrhagic enteritis following autologous PBSCT.

Abdominal Pain↗
PubMed2001

Combined resection of invaded organs in patients with T4 gastric carcinoma.

BACKGROUND: To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively. METHODS: The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed. RESULTS: In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively. CONCLUSIONS: Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.

Adenocarcinoma↗
PubMed2001

A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway.

In this study, five single clones were randomly established by limiting dilution method from each of the HTLV-I positive T cell lines - HUT 102 and ATL-2, and examined for the all-trans retinoic acid (ATRA) sensitivity, respectively. For each clone, we found a significant correlation between the reduction in 3[H]-thymidine incorporation and the reduction in CD25 expression (r=0.701, P<0.05) following treatment with 10(-5) M ATRA for 48 h. Agarose gel electrophoresis revealed DNA fragmentation of the cell lines treated with ATRA, indicative of apoptosis. These results suggested that the tax gene in the HTLV-I genome might be a key molecule involved in cell proliferation and CD25 expression. Thereafter, we transfected the tax gene in the expression vector (pCMV-Tax-neo) into the HTLV-I(-) T cell line Jurkat and examined the effects of ATRA on cell growth. The results showed that ATRA sensitivity was acquired by the Jurkat cells transfected with the tax gene expression vector, but not in those transfected with the control vector. We also observed NF-kappaB transcriptional activity on Jurkat cells transfected with the tax gene by CAT assay in the presence or absence of ATRA. NF-kappaB transcriptional activity was decreased significantly on Jurkat cells transfected with the tax gene after ATRA treatment. Taken together, these results indicate that ATRA may affect or block the Tax/NF-kappaB signaling pathway in ATL cells.

Adult↗
PubMed2001

Administration of granulocyte colony-stimulating factor induces hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function of peripheral blood monocytes.

OBJECTIVE: The incidence and severity of acute graft-vs-host disease after allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are not greater than those after conventional bone marrow transplantation despite infusion of more than one log greater number of donor T cells in PBSC. It has been postulated that monocytes from G-CSF-mobilized donors suppress alloreactivity of donor T cells. MATERIALS AND METHODS: We investigated the phenotype and function of monocytes in normal individuals receiving 10 microg/kg of G-CSF for 4 days. RESULTS: Monocytes were phenotypically and functionally different after G-CSF administration from steady-state monocytes. They were characterized by an increased CD14(+)CD16(+) subpopulation, reduced expression of HLA-DR, and diminished ability to produce tumor necrosis factor-alpha and interleukin-10 to lipopolysaccharide, compared with steady-state monocytes. These alterations were not replicated by culturing monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In addition, the antigen-presenting function of G-CSF-mobilized monocytes was impaired. CONCLUSION: Hyporesponsiveness of G-CSF-treated monocytes to lipopolysaccharide with regard to tumor necrosis factor-alpha production, together with impaired antigen-presenting function, may be responsible for the unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC transplantation.

Antigen Presentation↗
PubMed2001

Proper management of the rotational vertebral artery occlusion secondary to spondylosis.

A 66-year-old man with cervical spondylosis noticed severe vertigo when turning his head to the right. He underwent subclavian arteriography elsewhere, which showed a block of the contrast medium in the right vertebral artery (VA) at the C5/6 level when the patient turned his head to the right. After referral to our institute, however, postcontrast CT scan revealed an attenuated shadow of the venous plexus around the right VA at the C3/4 level. Repeated selective angiography with rotation of the head after visualization of the entire VA verified the level of obstruction to be at C3/4. Resection of the C4 transverse process through an anterior approach with drilling of the C3/4 spondylotic spur of the uncinate processi completely resolved the arterial impingement and the symptom. When evaluating rotational VA occlusion, dynamic angiography with selective catheterization is essential in determining which level is affected. The postcontrast CT scan is also useful because it suggests the level even without head rotation.

Aged↗
PubMed2001

Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis.

Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis.

Amino Acid Sequence↗
PubMed2001

Preparation of platinum nanoparticles by sonochemical reduction of the Pt(IV) ions: role of surfactants.

Sonochemical reduction processes of Pt(IV) ions in water have been investigated in the presence of various kinds of surfactants such as sodium dodecylsulfate (SDS) and sodium dodecylbenzenesulfonate (DBS) as anionic surfactants, and polyethylene glycol monostearate (PEG-MS) as non-ionic, dodecyltrimethylammonium chloride (DTAC) and bromide (DTAB) as cationic surfactants. An improved colorimetric determination reveals that Pt(IV) ion is reduced to zero valent metal in two steps: step (1)--Pt(IV) ion to Pt(II) ion, and step (2)--Pt(II) ion to Pt(0), and after the completion of step (1), step (2) sets in. It appears that rapid scrambling reactions among platinum ions and/or atoms, that is, Pt(I) + Pt(IV)-->Pt(II) + Pt(III), etc. take place. In the sonolysis of aqueous solutions of SDS, DBS or PEG-MS, two kinds of organic reducing radicals, R(ab) and R(py), are proposed to contribute to the reduction. Radical R(ab) is formed from the reaction of the surfactants with primary radicals such as hydroxyl radicals and hydrogen atoms originated from the sonolysis of water, and radical R(py) is formed from the direct thermal decomposition of surfactants in the interfacial region between the collapsing cavities and the bulk water. R(ab) is effective for both the reduction steps, whereas R(py) is involved only in the reduction step (1). This fact coincides with the previous reported sonochemical reduction of Pt(II) ions. Hydrogen atoms themselves scarcely participate in the reduction. The average diameter (1.0 nm) of platinum particles prepared from the system of PEG-MS is smaller than those from the aqueous solution of anionic surfactant SDS (3.0 nm) and DBS (3.0 nm).

Journal Article↗
PubMed2001

Adeno-associated virus-mediated transfer of endothelial nitric oxide synthase gene inhibits protein synthesis of rat ventricular cardiomyocytes.

We investigated whether nitric oxide (NO) synthase gene transfer could attenuate growth of cultured cardiac myocytes. First, we investigated the effects of exogenous NO and cGMP analog on protein synthesis of cultured neonatal rat cardiac myocytes. The NO donor 3-morpholino-sydnonimine-hydrochloride (SIN-1) and 8-bromo-cGMP caused concentration-dependent decreases in phenylephrine-stimulated incorporation of 3H-leucine into cardiac myocytes. We then transferred endothelial constitutive NO synthase (ecNOS) gene into cultured neonatal rat cardiac myocytes using adeno-associated virus (AAV) vectors. ecNOS gene transfer into cardiac myocytes induced 140 kD ecNOS protein expression and significantly increased cGMP contents of myocytes compared with control cells. ecNOS gene transfer inhibited 3H-leucine incorporation into cardiac myocytes in response to phenylephrine, which was significantly recovered in the presence of the NOS inhibitor N(G)-monomethyl-L-arginine acetate. These results indicate that endogenously generated NO by ecNOS gene transfer using AAV vectors inhibits the alpha-adrenergic agonist-induced cardiac protein synthesis at least partially via cGMP production.

Adenoviridae↗
PubMed2001

Human T-cell leukemia virus type-I (HTLV-I) tax is not the only one factor to enhance human immunodeficiency virus type-I (HIV-1) infection in culture-supernatants.

It is hypothesized that supernatants from cell cultures contain several factors to modify the human immunodeficiency virus type-1 (HIV-1) infection. Single round infection with pseudotyped viruses with envelope from HIV-1, amphotropic murine leukemia virus (A-MLV) and vesicular stomatitis virus G-protein (VSV-G) carrying luciferase reporter gene detected that not only human T-cell leukemia/lymphoma virus type-I (HTLV-1) transformed cells but also HTLV-I-unrelated T-cells and BJA-B cells released factors enhancing the infection with all pseudotyped viruses in their culture-supernatants. No supernatants upregulated the level of transcription from transfected DNA probe. suggesting that the action of supernatants is different from that of tumor necrosis factor (TNF) and Tax of HTLV-I. These results indicated that factors not always related to HTLV-I were ubiquitously produced and promoted viral infections, probably due to non-specific enhancement of early phase of the infection.

B-Lymphocytes↗
PubMed2001

Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides.

We have previously found by NMR and CD spectroscopic studies that the helical content of the sodium channel inactivation gate-related peptide (Ac-GGQDIFMTEEQK-NH2; MP-1A) in 80% trifluoroethanol solutions was increased by adding a pentapeptide, KIFMK. In order to study in further detail whether the presence of the IFM motif and the two lysine residues is a prerequisite for stabilizing the helical conformation, we examined interactions between various oligopeptides (RIFMR, KIFMTK, KIQMK, KAFAK, KIIIK) and MP-1A and its related peptides; that is, MP-2A in which Phe was replaced by Gln, MP-1MMA in which Thr was replaced by Met, MP-1TA in which Thr was removed from MP-1A, and MP-1A' in which L-Phe was replaced by D-Phe. It was found that the IFM motif was absolutely necessary in both the oligopeptide and the inactivation gate peptide. This finding means that hydrophobic interactions are operative between KIFMK and MP-1A. In contrast, KIFMK destabilized the helical structure of MP-1MMA, MP-1TA, and MP-1A', showing that the conformation around the IFM motif in the inactivation gate peptides is an important factor. It was concluded that the IFM motif and the two Lys residues are a prerequisite for effectively stabilizing the alpha-helix of MP-1A.

Amino Acid Motifs↗
PubMed2001

Hepatic graft-versus-host disease presenting as an acute hepatitis after allogeneic peripheral blood stem cell transplantation.

Hepatic graft-versus-host disease (GVHD) generally presents as cholestatic jaundice, and increased serum alkaline phosphatase (ALP) is followed by hyperbilirubinemia and clinical jaundice. Currently accepted standards for evaluating the clinical severity of GVHD are based not on serum aminotransferase levels but on the serum bilirubin level. We describe a 17-year-old Japanese female who had increased aminotransferases without cholestasis on day 23 after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Liver biopsy revealed lymphocytic infiltration of the portal tracts and pericentral necrosis of the lobuli. The limiting plates were not clearly defined due to cellular infiltrates. There was periductal lymphocytic infiltration and vacuolization of the biliary epithelial cells with exocytosis, compatible with GVHD of cholangiohepatitic type. These findings indicate that acute hepatic GVHD may present as acute hepatitis and this should be included in the differential diagnosis for patients with increased aminotransferases after allogeneic stem cell transplantation.

Acute Disease↗
PubMed2001

Efficient repetitive gene delivery to skeletal muscle using recombinant adenovirus vector containing the Coxsackievirus and adenovirus receptor cDNA.

To improve adenovirus-mediated gene delivery to skeletal muscle, we have used a recombinant adenovirus vector encoding the human Coxsackievirus and adenovirus receptor (hCAR). Because CAR is expressed at a lower level in rodent myoblasts and muscle fibers than in other tissues, we expected that elevated expression of CAR in skeletal muscle would improve the efficacy of adenovirus-mediated gene transfer. Since the mouse myoblasts, C2C12 cells, showed low sensitivity to infection by recombinant adenovirus 5, we initially infected these cells at a high multiplicity of infection (MOI) of 250 with the recombinant adenovirus containing hCAR cDNA and LacZ gene. Subsequent infection by recombinant adenovirus containing the marker gene, green fluorescence protein, became efficient even at a low MOI of 25. Thus, elevated hCAR expression in mouse muscle fibers made a second virus inoculation at low doses possible. We also demonstrated that the elevated hCAR expression did not influence muscle membrane integrity. Our results suggest that co-expression of CAR and a therapeutic gene by adenovirus vector constitutes a novel strategy to advance gene therapy for hereditary muscle diseases.

Adenoviridae↗
PubMed2001

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice.

We investigated genes expression by retrograde axonal transport of replication-defective adenoviruses carrying genes for LacZ (AdLacZ) and Bcl-2 in motor neurons of transgenic mice expressing mutant human Cu/Zn superoxide dismutase (SOD1) gene containing a substitution of alanine for glycine at position 93. We found that intramuscular injection of AdLacZ into the tongue of mutant SOD1 transgenic mice and their wild-type littermates at various ages results in high expression of the transgene and similar time course of expression in hypoglossal cranial nerve nuclei, suggesting no difference in the behavior of the transgene expression between the two groups. Subsequently, we employed a molecular switching cassette for Bcl-2 designed to express Bcl-2 by Cre-loxP recombination using adenoviral vectors, and examined the COS7 and primary neuronal cells with the mutant SOD1 gene. The overexpression of Bcl-2 in both cells and the neuronal protection against staurosporine-induced apoptosis were observed, after dual infection of adenoviral vectors with cassette for Bcl-2 (AxCALNLBcl-2) and Cre recombinase (AxCANCre). After inoculation of AxCALNLBcl-2 followed by AxCANCre into the tongue of both mutant SOD1 transgenic mice and wild-type littermates, Bcl-2 was detected in both the injection site and the hypoglossal nuclei of brainstems, suggesting that this was the result of retrograde transport of AxCALNLBcl-2 and AxCANCre and expression of Bcl-2 by Cre recombinase in the hypoglossal nuclei. This strategy for delivery of exogenous genes such as Bcl-2 will be useful for studying neuronal death/survival and introducing foreign genes into postmitotic motor neurons, and in gene therapy for motor neuron diseases such as ALS.

Adenoviridae↗
PubMed2001

Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells.

Human T lymphotropic virus type I (HTLV-I) induces HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). The development of HAM/TSP is associated with rapid maturation of dendritic cells (DCs), while ATL is accomplished with their maturation defect. The DC maturation is induced by cell-to-cell contact with CD4+ T cells expressing CD40 ligand (L). We determined the influence of CD40L expressed on various HTLV-I-infected T cells on the DC maturation. Around 60% of CD4+ T cells infected with HTLV-I for 1 week, expressed CD40L molecules involved in DC maturation. DCs matured by the CD40L+ T cells activated autologous CD4+ and CD8+ T cells. HTLV-I-immortalized T-cell lines established from healthy donors consistently expressed CD40L molecules for 3 months, however, some lines lost the expression soon thereafter. Interleukin (IL)-2-independent and transformed lines lacked that expression. Furthermore, T cells obtained from HAM/TSP patients expressed CD40L molecules for at least 3 weeks, whereas T cells from ATL patients did not express that. The CD40L T cells did not induce DC maturation, and required exogenous CD40L molecules for maturation. The CD40L+ T-cell-induced maturation was blocked by anti-CD40L antibody. Therefore, the lack of CD40L expression on HTLV-I-infected T cells may be associated with the development of ATL.

CD4-Positive T-Lymphocytes↗