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H Sugiyama

Publications and source records attributed to H Sugiyama.

At least 91 records · Page 5Linked to original sources
PubMed2000

Asymmetric total synthesis of (-)-mycothiazole.

[structure: see text] In this Letter we describe the first total synthesis of mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary alcohol. The skipped diene was constructed by the standard Stille coupling, and the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille coupling.

Animals↗
PubMed2000

Interaction of Vesl-1L/Homer 1c with syntaxin 13.

Vesl-1S/Homer 1a, reported originally as Vesl/Homer, was isolated as a synaptic plasticity-regulated gene. The expression of Vesl-1S/Homer 1a is regulated during long-term potentiation in the hippocampus. Vesl-1L/Homer 1c, which appears to be formed by a splicing event, shares the N-terminus with Vesl-1S/Homer 1a and also contains additional amino acids at the C-terminus. The short form and the long form of the family members both interact with group 1 metabotropic glutamate receptors (mGluRs). We herein report the identification of syntaxin 13 as a molecule that interacts with Vesl-1L using yeast two-hybrid screening. Syntaxin 13 is a member of the syntaxin family and is regarded as soluble N-ethylmaleimide-sensitive attachment proteins receptors (SNAREs) in the endosomal membranes. The interaction of Vesl-1L and syntaxin 13 was biochemically confirmed by in vitro binding assays. The coexpression of the two proteins in the transfected cells resulted in a colocalization in the intracellular vesicle-like structures. We thus propose that the association of Vesl-1L with syntaxin 13 plays a role in the translocation of Vesl-1L to the intracellular organelles.

Amino Acid Sequence↗
PubMed2000

Chromosomal differentiation of the Schistosoma japonicum complex.

The C-banding pattern, location of telomere sequence and chiasma frequency of four species of the Schistosoma japonicum complex were compared with those of two African species, Schistosoma mansoni and Schistosoma haematobium. In the six species, C-banding patterns of seven autosomes and the two sex chromosomes (Z and W) showed relatively species-specific and geographical (Asian and African) differences. Particularly, a plausible pathway of alteration of chromosome 2 revealed a direction from the A-chromosome to the M- chromosome in terms of rearrangements of pericentric inversion and elimination of constitutive heterochromatin (AM inversion). This chromosome change suggested hypothetically that the S. japonicum complex is the original type, and the African species represents the derived type. Moreover, the mosaic construct of the Asian and African types in Schistosoma sinensium chromosomes prompted us to propose that the species might have been formed by hybrid speciation of the genomes of Asian and African species. Localisation of telomeric repeats enabled Asian and African schistosomes to be distinguished clearly by simple terminal location and by terminal and interstitial locations, respectively. Change of chiasma frequency in the S. japonicum complex might be caused by the reduction of interstitial chiasmate (Xi) in the larger chromosomes, 1 and Z (or W), and the change seems to have progressed to Japan from South East Asia. These data enabled us to predict a tentative evolutionary pathway of schistosomes at the cytogenetic level.

Animals↗
PubMed2000

Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses.

Hippocampal CA3 pyramidal neurons receive synaptic inputs from commissural and associational fibers on both apical and basal dendrites. NMDA receptors at these synapses were examined in hippocampal slices of wild-type mice and GluRvarepsilon1 (NR2A) subunit knockout mice. Electrical stimulations at the CA3 stratum radiatum or stratum oriens activate both commissural and associational (C/A) synapses, whereas stimulations at ventral fimbria mainly activate commissural synapses. Ro 25-6981 and ifenprodil, the GluRepsilon2 (NR2B) subunit-selective NMDA receptor antagonists, suppressed NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) at the commissural-CA3 synapses on basal dendrites more strongly than those at the C/A-CA3 synapses on apical or basal dendrites. However, glutamate-evoked NMDA receptor currents were reduced by the GluRepsilon1 subunit knockout to a similar extent at both apical and basal dendrites. The GluRepsilon1 subunit knockout also reduced NMDA EPSCs at the C/A-CA3 synapses on basal dendrites, but did not affect NMDA EPSCs at the commissural-CA3 synapses on basal dendrites. These results confirmed our previous findings that NMDA receptors operating at different synapses in CA3 pyramidal cells have different GluRepsilon subunit compositions, and further show that the GluRepsilon subunit composition may be regulated depending on the types of synaptic inputs, even within a single CA3 pyramidal neuron.

Animals↗
PubMed2000

Cancer immunotherapy targeting Wilms' tumor gene WT1 product.

The Wilms' tumor gene WT1 is expressed at high levels not only in acute myelocytic and lymphocytic leukemia and in chronic myelocytic leukemia but also in various types of solid tumors including lung cancers. To determine whether the WT1 protein can serve as a target Ag for tumor-specific immunity, three 9-mer WT1 peptides (Db126, Db221, and Db235), which contain H-2Db-binding anchor motifs and have a comparatively higher binding affinity for H-2Db molecules, were tested in mice (C57BL/6, H-2Db) for in vivo induction of CTLs directed against these WT1 peptides. Only one peptide, Db126, with the highest binding affinity for H-2Db molecules induced vigorous CTL responses. The CTLs specifically lysed not only Db126-pulsed target cells dependently upon Db126 concentrations but also WT1-expressing tumor cells in an H-2Db-restricted manner. The sensitizing activity to the Db126-specific CTLs was recovered from the cell extract of WT1-expressing tumor cells targeted by the CTLs in the same retention time as that needed for the synthetic Db126 peptide in RP-HPLC, indicating that the Db126-specific CTLs recognize the Db126 peptide to kill WT1-expressing target cells. Furthermore, mice immunized with the Db126 peptide rejected challenges by WT1-expressing tumor cells and survived for a long time with no signs of autoaggression by the CTLs. Thus, the WT1 protein was identified as a novel tumor Ag. Immunotherapy targeting the WT1 protein should find clinical application for various types of human cancers.

Animals↗
PubMed2000

Peroxisome proliferator-activated receptors are expressed in mouse bone marrow-derived mast cells.

We examined the expression of peroxisome proliferator-activated receptors (PPARs) and the role of PPARs in cytokine production in mouse bone marrow-derived mast cells (mBMMCs). mBMMCs expressed PPARbeta strongly and gamma slightly, but not alpha. Activation of mBMMCs with antigen or calcium ionophore resulted in the increased expression of PPARgamma mRNA specifically. 15-Deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)) and troglitazone, all PPARgamma ligands, attenuated the antigen-induced cytokine production by mBMMCs. Carbaprostacyclin, a PPARbeta ligand, also inhibited cytokine production, whereas PPARalpha ligands did not. These results suggest that PPARbeta and gamma might be included in the negative regulation of mast cell activation.

Animals↗
PubMed2000

Peroxisome proliferator-activated receptors are expressed in human cultured mast cells: a possible role of these receptors in negative regulation of mast cell activation.

We investigated the expression of peroxisome proliferator-activated receptors (PPAR) in human cultured mast cells (HCMC) by using the reverse transcription-polymerase chain reaction. HCMC expressed mRNA of PPARbeta, gamma1, and gamma2 constitutively, whereas PPARalpha was not detected. Though PPARgamma2 was expressed weakly, activation of HCMC with anti-IgE after IgE sensitization or with calcium ionophore plus phorbol ester resulted in increased expression of PPARgamma2 specifically. These stimuli did not influence the expression of PPARalpha and beta. In addition, provocation of HCMC with IgE or with IL-4 increased the mRNA level of PPARgamma2, and a synergistic effect was observed with the combination of IgE plus IL-4. To investigate a possible role of PPAR in mast cells, we examined the effects of PPAR agonists on cytokine production by HCMC. Prostaglandin (PG) D(2), Delta(12)-PGJ(2), 15deoxy-Delta(12, 14)-PGJ(2) (15d-PGJ(2)), and troglitazone, all of which are PPARgamma agonists, attenuated the production of granulocyte-macrophage colony-stimulating factor by anti-IgE-stimulated HCMC. A similar effect was observed with carbaprostacyclin, a PPARbeta agonist, but not with PPARalpha agonists. Anti-IgE-induced expression of cytokine mRNA, such as TNF-alpha, IL-5 and macrophage inflammatory protein-1alpha mRNA, was also reduced by the treatment with these PPARgamma agonists. Though only Delta(12)-PGJ(2) and 15d-PGJ(2) revealed an inhibitory effect on histamine release, leukotriene C(4) release from HCMC was suppressed by all tested PPARgamma agonists. These results indicate that HCMC express PPARbeta and gamma1/2, which might negatively regulate the activation of HCMC.

Antibodies, Anti-Idiotypic↗
PubMed2000

MHC (major histocompatibility complex)-DRB genes and polymorphisms in common marmoset.

A New World monkey, the common marmoset (Callithrix jacchus), will be used as a preclinical animal model to study the feasibility of cell and gene therapy targeting immunological and hematological disorders. For elucidating the immunogenetic background of common marmoset to further studies, in the present study, polymorphisms of MHC-DRB genes in this species were examined. Twenty-one Caja-DRB exon 2 alleles, including seven new ones, were detected by means of subcloning and the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) methods followed by nucleotide sequencing. Based on the alignment of these allele sequences, we designed two pairs of specific primers and established a PCR-SSCP method for DNA-based histocompatibility typing of the common marmoset. According to the family segregation data and phylogenetic analyses, we presumed that Caja-DRB alleles could be classified into five different loci. Southern blotting analysis also supported the existence of multiple DRB loci. The patterns of nucleotide substitutions suggests that positive selection operates in the antigen-recognition sites of Caja-DRB genes.

Alleles↗
PubMed2000

Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1 ) product.

The product of the Wilms' tumor gene WT1 is a transcription factor overexpressed not only in leukemic blast cells of almost all patients with acute myeloid leukemia, acute lymphoid leukemia, and chronic myeloid leukemia, but also in various types of solid tumor cells. Thus, it is suggested that the WT1 gene plays an important role in both leukemogenesis and tumorigenesis. Here we tested the potential of WT1 to serve as a target for immunotherapy against leukemia and solid tumors. Four 9-mer WT1 peptides that contain HLA-A2.1-binding anchor motifs were synthesized. Two of them, Db126 and WH187, were determined to bind to HLA-A2.1 molecules in a binding assay using transporter associated with antigen processing-deficient T2 cells. Peripheral blood mononuclear cells from an HLA-A2.1-positive healthy donor were repeatedly sensitized in vitro with T2 cells pulsed with each of these two WT1 peptides, and CD8(+) cytotoxic T lymphocytes (CTLs) that specifically lyse WT1 peptide-pulsed T2 cells in an HLA-A2.1-restricted fashion were induced. The CTLs also exerted specific lysis against WT1-expressing, HLA-A2.1-positive leukemia cells, but not against WT1-expressing, HLA-A2.1-negative leukemia cells, or WT1-nonexpressing, HLA-A2. 1-positive B-lymphoblastoid cells. These data provide the first evidence of human CTL responses specific for the WT1 peptides, and provide a rationale for developing WT1 peptide-based adoptive T-cell therapy and vaccination against leukemia and solid tumors.

CD3 Complex↗
PubMed2000

Bacteremic Moraxella catarrhalis pneumonia in a patient with immunoglobulin deficiency.

A-75-year old woman with agammaglobulinemia developed Moraxella catarrhalis bacteremic pneumonia. M. catarrhalis pneumonia is rarely associated with bacteremia, and neutrophils have been reported as a significant factor in the host defense system against this bacteria. This case suggests that immunoglobulin also plays a key role in the host defense system against M. catarrhalis.

Agammaglobulinemia↗
PubMed2000

A new model of pulmonary superinfection with Aspergillus fumigatus and Pseudomonas aeruginosa in mice.

We have produced a new model of pulmonary super-infection with Aspergillus fumigatus and Pseudomonas aeruginosa in immunosuppressed mice. Male ICR mice were given an intratracheal inoculation of 4 x 10(5) conidia of A. fumigatus in agar beads, and were immunosuppressed with 100 mg/kg subcutaneous injections of cortisone acetate on days 7, 9, 12, 14, and 16 after inoculation. Twelve days after inoculation, with the agar beads, the mice were challenged with the intranasal instillation of 2 x 10(6) CFU of P. aeruginosa. The survival rates of superinfected, A. fumigatus-alone, P. aeruginosa-alone, and non-infected mice were 50%, 30%, 90%, and 100% 14 days after pseudomonal infection (26 days after inoculation of A. fumigatus), respectively. In the superinfected mice, both A. fumigatus and P. aeruginosa were detected more than 10 days after pseudomonal infection (22 days after inoculation of A. fumigatus). Histopathological examination revealed peribronchial necrosis around A. fumigatus hyphae and inflammation by P. aeruginosa. This infection model in mice would be useful for studying the pathogenesis of superinfection.

Animals↗
PubMed2000

Enhanced cytotoxicity in a Z-photoisomer of a benzopyran derivative of propolis.

(Z)-2,2-Dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (1) was isolated from Brazilian propolis, together with the known benzopyran derivative, (E)-2, 2-dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (2). The structure was determined by spectroscopic analyses, which included 1D and 2D (1)H and (13)C NMR experiments, as well as MS, IR, and UV spectroscopy. Compound 2 rapidly changed to 1 under UV irradiation conditions (365 nm), and the reverse reaction was also observed. The ratio of 1 to 2 reached 2.3 when the reaction began from either 1 or 2, indicating a photostationary state. Compound 1 displayed an approximate 7-fold stronger cytotoxicity against human lung carcinoma cells (HLC-2) compared with 2.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination.

We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the challenges of WT1-expressing tumor cells and survived with no signs of autoimmunity caused by the CTLs. These results demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rejection activity against challenges of WT1-expressing tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid tumors as well as leukemias.

Animals↗
PubMed2000

Hyperbaric oxygen (HBO) therapy for acute traumatic cervical spinal cord injury.

STUDY DESIGN: A retrospective study of spinal cord injury (SCI) treated with and without hyperbaric oxygen (HBO) therapy. OBJECTIVES: To report on the use of HBO in spinal cord injury. SETTING: Neurosurgical Unit, Tokyo, Japan. METHODS: Thirty-four cases of hyperextension spinal cord injury without bone damage and previous history of surgical intervention were divided into two groups, with (HBO) or without (non-HBO) therapy. The neurological findings at admission and their outcomes were evaluated by means of Neurological Cervical Spine Scale (NCSS)1 and the average improvement rates in individual groups were compared. RESULTS: The improvement rate ranged from 100% to 27.3% with the mean value of 75. 2% in the HBO group, while these values were 100%, 25.0% and 65.1% respectively in the non HBO group. CONCLUSION: In the HBO group, the improvement rate indicated effectiveness in acute traumatic cervical spinal cord injury.

Adult↗
PubMed2000

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.

Adolescent↗
PubMed2000

GC-->CG transversion mutation might be caused by 8-oxoguanine oxidation product.

Oxidation of d(A6GGA6)/d(T6CCT6) with sensitizer under different UV irradiation periods was examined. Enzymatic digestion of photolysate revealed that the amount of 8-oxoG initially increased with decrease of G and then decreased with the formation of Iz. In order to investigate whether Iz was formed by one electron oxidation of 8-oxoG through long-range hole migration, photoirradiation of anthraquinone-linked oligomer was examined. The results clearly demonstrated that 8-oxoG was efficiently converted to Iz under irradiation conditions. These results suggest that Iz generated from 8-oxoG induces GC->CG transversion under oxidative condition.

Base Pairing↗