Biomedical subjects

Hiroshi Uchiyama

Publications and source records attributed to Hiroshi Uchiyama.

6 recordsLinked to original sources

PubMed2006

Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis.

S-adenosyl-l-methionine: 2-hydroxyisoflavanone 4'-O-methyltransferase (HI4'OMT) methylates 2,7, 4'-trihydroxyisoflavanone to produce formononetin, an essential intermediate in the synthesis of isoflavonoids with methoxy or methylenedioxy groups at carbon 4' (isoflavone numbering). HI4'OMT is highly similar (83% amino acid identity) to (+)-6a-hydroxymaackiain 3-O-methyltransferase (HMM), which catalyzes the last step of (+)-pisatin biosynthesis in pea. Pea contains two linked copies of HMM with 96% amino acid identity. In this report, the catalytic activities of the licorice HI4'OMT protein and of extracts of Escherichia coli containing the pea HMM1 or HMM2 protein are compared on 2,7,4'-trihydroxyisoflavanone and enantiomers of 6a-hydroxymaackiain. All these enzymes produced radiolabelled 2,7-dihydroxy-4'-methoxyisoflavanone or (+)-pisatin from 2,7,4'-trihydroxyisoflavanone or (+)-6a-hydroxymaakiain when incubated with [methyl-(14)C]-S-adenosyl-l-methionine. No product was detected when (-)-6a-hydroxymaackiain was used as the substrate. HI4'OMT and HMM1 showed efficiencies (relative V(max)/K(m)) for the methylation of 2,7,4'-trihydroxyisoflavanone 20 and 4 times higher than for the methylation of (+)-6a-hydroxymaackiain, respectively. In contrast, HMM2 had a higher V(max) and lower K(m) on (+)-6a-hydroxymaackiain, and had a 67-fold higher efficiency for the methylation of (+)-6a-hydroxymaackiain than that for 2,7,4'-trihydroxyisoflavanone. Among the 15 sites at which HMM1 and HMM2 have different amino acid residues, 11 of the residues in HMM1 are the same as found in HI4'OMTs from three plant species. Modeling of the HMM proteins identified three or four putative active site residues responsible for their different substrate preferences. It is proposed that HMM1 is the pea HI4'OMT and that HMM2 evolved by the duplication of a gene encoding a general biosynthetic enzyme (HI4'OMT).

Amino Acid Sequence↗

PubMed2006

[Two cases of acute respiratory failure due to idiopathic interstitial pneumonia successfully treated with sivelestat sodium hydrate and steroid therapy].

We encountered two patients with clinically diagnosed idiopathic interstitial pneumonia with acute respiratory distress syndrome (ARDS). Both patients required mechanical ventilation within 24 hours after admission. We managed these patients using lower tidal volume ventilation (tidal volume: 5-6 ml/kg), antibiotics, sivelestat sodium hydrate and steroid pulse therapy followed by oral prednisolone therapy. Respiratory failure was relieved within 2 weeks following treatment There was no four-fold rise in screen viral titers and screening investigations of autoantibodies were negative. Based on these findings, we diagnosed these cases as having acute interstitial pneumonia (AIP). AIP represents a small subset of patients with ARDS without any associated or predisposing factor. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and is used for the treatment of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, sivelestat sodium hydrate may be one of the treatment options for acute respiratory failure due to idiopathic interstitial pneumonia.

Acute Disease↗

PubMed2005

Immunization with a gene encoding granulocyte-macrophage colony-stimulating factor inserted with a single helper T-cell epitope of an intracellular bacterium induces a specific T-cell subset and protective immunity.

We evaluated here the effect of immunization with a gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) inserted with a helper T cell (Th) epitope, listeriolysin O (LLO) 215-226 derived from Listeria monocytogenes on induction of a specific Th by gene gun bombardment. Immunization of C3H/He mice with pGM215m plasmid encoding murine GM-CSF inserted with LLO 215-226 Th epitope gave the epitope-specific proliferative responses of CD4(+) T lymphocytes. In addition, specific interferon-gamma production from the splenocytes was observed. Concomitantly, pGM215m-immunized mice showed significant protective immunity against lethal listerial challenge. These results suggest that immunization of a gene for GM-CSF inserted with a Th epitope is useful for eliciting a specific Th subset in vivo.

Animals↗

PubMed2005

Optimum dose of LH-RH analogue Fertirelin Acetate for the induction of superovulation in mice.

The optimum dose for establishing superovulation in mice of Fertirelin Acetate (FA), an LH-RH analogue, was examined. Mice were subcutaneously injected with 5 IU of hCG at 17:00 (Day 0), and with various doses of FA (0.001 to 1.0 microg) five times at 4 h intervals on and after 22:00 on Day 0. To induce ovulation, 5 IU of hCG was again injected subcutaneously at 17:00 on Day 2. In the groups administered with doses ranging from 0.01 to 0.5 microg of FA, the number of ovulated eggs was significantly (p<0.05) larger than in the control group (12.9 +/- 5.9). The greatest number of ovulated eggs (22.6 +/- 7.3) was obtained in the group administered with 0.025 microg of FA. The results indicate that the effective dose of LH-RH analogue, FA, is between 0.1 and 0.5 microg for superovulation induction in mice.

Animals↗

PubMed2005

Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis.

OBJECTIVE: To assess the difference in clinical features and prognosis of patients with interstitial lung disease (ILD) comparing polymyositis (PM) and dermatomyositis (DM). METHODS: Medical records of 28 ILD patients with PM/DM (16 PM-ILD, 12 DM-ILD) were reviewed retrospectively. RESULTS: Serum CPK concentrations were significantly higher in PM-ILD than in DM-ILD. Bronchoalveolar lavage analysis showed that the percentages of lymphocytes and eosinophils were significantly higher in DM-ILD than in PM-ILD. Ten patients (5 PM-ILD, 5 DM-ILD) underwent surgical lung biopsy, and 3 (3 DM-ILD) had an autopsy. Nonspecific interstitial pneumonia (NSIP) was found in 7 (4 PM-ILD, 3 DM-ILD) and usual interstitial pneumonia (UIP) in 3 (1 PM-ILD, 2 DM-ILD). Interestingly, diffuse alveolar damage (DAD) was found in 3 patients with DM-ILD, who all died of deterioration of ILD; but no one with PM-ILD had DAD. Corticosteroid treatment alone achieved a favorable response in 6 patients (37.5%) with PM-ILD, but in only one (8.3%) with DM-ILD. Administration of cyclosporine in the early phase of onset benefited 4 corticosteroid-resistant patients with DM-ILD. Conclusively, survival in DM-ILD was significantly worse than that in PM-ILD. CONCLUSION: DM-ILD is more refractory to corticosteroid therapy, resulting in poorer prognosis compared with PM-ILD. These data indicate that intensive therapy, including cyclosporine, should be considered for DM-ILD.

Bronchoalveolar Lavage Fluid↗

PubMed2002

Endosomal/lysosomal targeting of a single helper T-cell epitope of an intracellular bacterium by DNA immunisation induces a specific T-cell subset and partial protective immunity in vivo.

We evaluated here the effect of the intracellular targeting of a helper T-cell (Th) epitope, literiolysin O 215-226 derived from Listeria monocytogenes, on induction of a specific Th by gene gun immunisation. Immunisation of C3H/He mice with pE215LAMP plasmid encoding the Th epitope fused with the endosomal/lysosomal targeting signal of lysosome-associated membrane protein (LAMP)-1 gave the epitope-specific proliferative responses of CD4(+) T lymphocytes. In addition, specific interferon-gamma production from the splenocytes was observed. Concomitantly, pE215LAMP-immunised mice showed moderate, but significant protective immunity against listerial challenge. These results suggest that the intracellular targeting of a Th epitope to endosomal/lysosomal compartments by DNA immunisation is useful for eliciting a specific Th subset in vivo.

Animals↗