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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 181 records · Page 10Linked to original sources
PubMed1998

Effect of theophylline withdrawal on airway inflammation in asthma.

Theophylline has been used as a bronchodilator in acute and chronic asthma management, although there is accumulating evidence that it may have anti-inflammatory effects. We have investigated the effect of theophylline withdrawal for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were more than 80% of the predicted value and its variability was less than 20% (Green Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP), 400-800 microg/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum, and airway reactivity to histamine were investigated. One half of the patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when receiving treatment with theophylline were 8.08 microg/mL in the theophylline withdrawal group and 7.64 microg/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emerged in the theophylline group, there were no significant changes in the theophylline administration group. In the theophylline withdrawal group, there were small but significant falls in PEF in the morning, FEV1 and V50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2+) eosinophils only in those patients who withdrew from theophylline. These results indicate that chronic treatment with low dose theophylline exerts an anti-inflammatory effect and that the additional use of theophylline with inhaled corticosteroids provides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long-term beneficial effects on the chronic asthma management.

Administration, Oral↗
PubMed1998

Comparative study of two outer membrane protein genes from Porphyromonas gingivalis.

A periodontal pathogen, Porphyromonas gingivalis possesses either a 53 kD (Ag53) or a 67 kD (Ag67) outer membrane protein (OMP). Almost all sera from patients with periodontal diseases reacted strongly with either Ag53 or Ag67. In previous work the cloning and sequencing of the 53 kD outer membrane protein gene designated pga53 from P. gingivalis FDC381, was reported and the presence of a gene homologous to pga53 in P. gingivalis ATCC 33277 demonstrated. In the present work this pga53-homologous gene from P. gingivalis ATCC 33277 was isolated and characterized. Nucleotide sequence analysis revealed that this gene encoded Ag67, and the gene was designated pga67. The deduced amino acid sequence and composition of pga67 was similar to the amino acid composition and N-terminal partial sequence of Ag67. An open reading frame of pga67 consisted of 1,692 nucleotides encoded as 564 amino acids, including a 49 amino acid signal sequence. The comparative analysis between pga67 and pga53 revealed that (1) the deduced amino acid sequence showed a 30.1% homology; (2) signal sequence and proline-rich regions at the C-terminus were the most conserved regions; (3) considerable differences were found mainly in the middle part of the OMPs; and (4) obvious differences in the two-dimensional models were evoked. These differences between pga67 and pga53 may explain the antigenic diversity between Ag67 and Ag53 OMPs.

Amino Acid Sequence↗
PubMed1997

ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk.

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcepsilonRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-gamma1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor alpha were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-gamma1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcepsilonRI gamma subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igbeta ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcepsilonRI gamma phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcepsilonRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.

Acridines↗
PubMed1997

Effect of nitric oxide on the ligand-binding activity of albumin.

The redox state of the Cys-34 on albumin plays an important role in ligand binding of this plasma protein. We previously reported that mixed-disulfide formation of albumin with low molecular weight thiols, such as cysteine and glutathione, increased the affinity of this protein for phenolsulfophthalein (PSP) and Cu(II). Although nitric oxide (NO) and its metabolites easily react with various thiols, including that of albumin, and form S-nitrosothiol derivatives, the effect of such modification on the ligand-binding activity of this plasma protein remains to be elucidated. Kinetic analysis revealed that S-nitrosylation of Cys-34 on bovine serum albumin (BSA) decreased its binding activity for PSP. NO also decreased the ligand-binding activity of fresh plasma samples from rat and human. S-nitrosylation also decreased the binding activity of BSA for Cu(II). These results indicate that reversible modification of the Cys-34 by NO and oxidative stress might play regulatory roles in the binding and transport of organic anions and heavy metals in the circulation.

Animals↗
PubMed1997

Induction of transplantation tolerance in adult rats by vascularized spleen transplantation.

It was demonstrated by Bitter-Seurmann et al. that tolerance to subsequent skin allografts can be brought about, in some rat strain combinations, by heterotopic spleen allografts. We report here that in adult rats, tolerance can be also induced by vascularized spleen allografts using various strain combinations. DA (RT1av1) rats always accepted major histocompatible complex (MHC)-compatible but minor histocompatibility antigen (miH)-incompatible ACI (RT1av1) spleen grafts spontaneously, and further that those DA rats bearing ACI spleen grafts accepted subsequent ACI skin grafts indefinitely. In contrast, Fischer 344 (RT1lvl) rats always accepted not only the "weak" MHC-incompatible Lewis (RT1l) spleen grafts but also subsequent Lewis skin grafts indefinitely, when recipients were administered a short course of FK506 only at the time of primary spleen transplantation. Furthermore, in a number of MHC- and miH-incompatible strain combinations, recipients always accepted primary spleen grafts indefinitely when given a short course of FK506, but those recipients bearing donor spleens revealed split tolerance, that is, rejected subsequent donor-specific skin grafts but accepted heart grafts indefinitely. We conclude that the spleen seems to be a possible organ to induce transplantation tolerance, and that even if the MHC and miH are mismatched, unresponsiveness to at least heart grafts can be achieved by the administration of additional FK506 at the time of spleen transplantation.

Animals↗
PubMed1997

Identification and characterization of a novel human cortistatin-like peptide.

Expressed sequence tags (ESTs) that showed significant homology to rat cortistatin (CST) were found in a human fetal brain cDNA library. A protein coded by the cDNA showed 55% identity to rat preprocortistatin in amino acid. Similarly in the generation of mature peptides from rat preprocortistatin, it was expected that cleavage at dibasic amino acids in the C-terminal portion of the coded protein might produce at least two different sizes of mature peptides with 29 and 17 amino acid residues, respectively. We chemically synthesized the predicted mature peptide with 17 amino acid residues (hCS-17) and examined its biological activities. It bound to all human somatostatin receptor (SSTR) subtypes in almost the same manner as rat CST-14. It also inhibited cAMP production induced by forskolin through SSTRs. Administration of hCS-17 to the cerebral ventricle showed flattening of cortical and hippocampal electroencephalograms in rats. These results indicate that a bioactive peptide encoded by the cDNA is a human counterpart corresponding to rat CST.

Amino Acid Sequence↗
PubMed1997

Anticonvulsive and neuroprotective actions of a potent agonist (DCG-IV) for group II metabotropic glutamate receptors against intraventricular kainate in the rat.

Anticonvulsive and neuroprotective effects of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), a potent agonist for Group II metabotropic glutamate receptors, were examined in vivo against the excitotoxicity of kainic acid in the rat. Intraventricular injection of kainic acid (2 nmol) induced circling behavior and wet-dog shakes soon after injection, followed by episodes of limbic motor seizures at intervals of several minutes (sporadic limbic motor seizures). The frequency of sporadic limbic motor seizures gradually increased until seizures occurred incessantly (continuous limbic motor seizures). Intraventricular kainic acid also caused severe selective neuron damage in the hippocampal CA3 region, limbic lobe and medial geniculate body. Prolonged intraventricular infusion of DCG-IV (24-240 pmol/h) for 17 h before and 7 h after the application of kainic acid decreased the incidence of the continuous limbic motor seizures and the degree of neuronal damage in circumscribed brain areas. However, the behavioral changes observed immediately after the administration of kainic acid were unaffected by prolonged intraventricular infusion with DCG-IV (8-2400 pmol/h). Similarly, the occurrence of sporadic limbic motor seizures was only slightly reduced by the administration of DCG-IV (8-800 pmol/h). High doses of DCG-IV, greater than 800 pmol/h, afforded no protection against kainate-induced lesions; rather, the degradation of hippocampal CA1 pyramidal neurons was increased under such conditions. Single injections of DCG-IV (10-300 pmol/rat) in the lateral ventricle did not affect kainate neurotoxicity. Thus, prolonged infusion of DCG-IV showed a bell-shaped doso-response relationship with regard to protection against kainate-induced neurotoxicity.

Animals↗
PubMed1997

Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats.

To investigate the influence of cerebral hypoperfusion on learning behaviours, we developed a novel rat cerebral hypoperfusion model, in which the bilateral internal carotid arteries were permanently ligated to reduce the cerebral blood flow, and examined its behavioural and histopathological consequences in comparison to those occurring after bilateral common carotid ligation. In the Morris water maze task, rats with common carotid ligation exhibited a learning deficit, whereas rats with internal carotid ligation exhibited normal learning. Both models exhibited significant learning impairments in the eight-arm radial maze task, although the impairment was less severe in internal carotid-ligated rats than in common carotid-ligated rats. The cerebral blood flow of rats with common carotid ligation was reduced significantly both two and 10 days after ligation, and was still below normal three months after ligation. A milder, but significant reduction in the cerebral blood flow was observed in internal carotid-ligated rats. Shrinkage of the optic nerves and a circadian activity rhythm desynchronized to the light/dark cycle were exhibited by the rats with common carotid ligation, whereas these parameters remained unaffected in the rats with internal carotid ligation, suggesting that permanent ligation of common carotid arteries but not internal carotid arteries impairs visual functions. The main pathological changes observed in the brain following common carotid ligation were rarefaction and gliosis of the white matter and neuronal loss in the hippocampal CA1 region. On the other hand, the rats with internal carotid ligation had no significant brain damage. Chronic treatment with idebenone (1.5 and 15 mg/kg/day), a cerebral energy metabolism enhancer, over a three-month period, commencing five days after ligation, ameliorated the impairment of water maze learning in rats with common carotid ligation. The treatment also significantly improved the learning impairment in the radial maze task of internal carotid-ligated rats. Idebenone had no effect on the histopathological changes that followed cerebral hypoperfusion. It is concluded that cerebral hypoperfusion induced by permanent internal carotid ligation impairs the working memory without causing pathological damage to the brain tissues and the visual system, and the learning impairment can be ameliorated by a cerebral energy metabolism enhancer. These findings have the clinical implication that a reduction in blood flow may be an important factor that causes or exacerbates cognitive decline in dementias.

Animals↗
PubMed1997

Purification and carbohydrate-binding specificity of Agrocybe cylindracea lectin.

A lectin was isolated from fruiting bodies of Agrocybe cylindracea by two ion-exchange chromatographies and gel filtration on Toyopearl HW55F. The lectin was homogeneous on polyacrylamide gel electrophoresis and its molecular mass was determined to be 30000 by gel filtration, and 15000 by sodium dodecylsulfate polyacrylamide gel electrophoresis, signifying a dimeric protein. Its carbohydrate-binding specificity was investigated both by sugar-hapten inhibition of hemagglutination and by enzyme-linked immunosorbent assay. The inhibition tests showed the affinity of the lectin to be weakly directed toward sialic acid and lactose, and the enhanced affinity toward trisaccharides containing the NeuAc alpha2,3Gal beta-structure. Importantly, the lectin strongly interacted with glycoconjugates containing NeuAc alpha2,3Gal beta1,3GlcNAc-/GalNAc sequences.

Amino Acids↗
PubMed1997

Clonal accumulation of V beta 5.1-positive cells in the liver of a patient with autoimmune cholangiopathy.

We describe a 43-year-old woman with clinical features compatible with autoimmune cholangiopathy recently reported by Ben Ari et al. She was negative for anti-mitochondrial antibody, positive for high titer anti-nuclear antibody with homogeneous pattern, high levels of serum immunoglobulin G and nearly normal levels of serum immunoglobulin M for more than five years. In the early stages of the disease, the elevations of serum transaminase, alkaline phosphatase and gamma-glutamyl transpeptidase were well controlled by the administration of ursodeoxycholic acid. After five years of follow-up, she showed the second exacerbation of liver function tests, which then rapidly improved by prednisone administration. To analyze the antigen diversity recognized by T-cells in the liver, T-cell receptor repertoire was examined by immuno-histochemistry. The liver biopsy obtained in the early stage showed clonal accumulation of V beta 5.1-positive cells in portal areas, which was found in patients neither with primary biliary cirrhosis nor autoimmune hepatitis. In conclusion, these data suggest that T-cell response in autoimmune cholangiopathy is different from those two autoimmune liver diseases, which may imply a distinct entity of the disease.

Adult↗
PubMed1997

Mechanical workload-myocardial water content relationship in isolated rat hearts.

We tested the hypothesis that the mechanical workload of the heart inversely determines the rate of myocardial edema formation in an isolated, perfused rat heart preparation. Heart rate (HR) was varied in three groups by pacing at 125 (HR125), 250 (HR250), or 350 beats/min (HR350). Left ventricular pressure (LVP) was varied in two additional groups by pacing at 250 beats/min and with the addition of either epinephrine (Epi) or propranolol (Pro) to the perfusate. In five otherwise identical groups, variation of coronary vascular resistance was minimized by adenosine. Myocardial water content (MWC) varied significantly and inversely with HR in the HR125, HR250, and HR350 groups. MWC of the HR250 group was significantly less than that of the Pro group but did not differ from the Epi group. However, when adenosine was used, MWC had significant inverse relationships with HR and LVP. We concluded that the mechanical workload of the heart inversely determines the rate and degree of myocardial edema formation in this isolated heart preparation, and both HR and LVP are determinants of this relationship.

Adenosine↗
PubMed1997

Primary structure of base non-specific and acid ribonuclease from bullfrog (Rana catesbeiana).

A base non-specific acid ribonuclease (RNase RCL2) was purified from bullfrog liver [H. Yagi et al. Biol. Pharm. Bull., 18, 219-222 (1992)]. The sequence study and comparison of the amino acid sequence of the enzyme with homologous RNases from oyster, drosophila and chicken liver suggested that the RNase RCL2 consisted of two components, large protein fraction (182 amino acid residues) and peptide 2 (20 amino acid residues) or peptide 1 (18 amino acid residues), and that both components bind with disulfide bridge. The RNase preparation was probably formed from a single polypeptide protein by processing with some proteases. The amino acid sequence of RNase RCL2 showed that the RNase belongs to the RNase of RNase T2 family and its sequence most resembles chicken liver acid RNase. In RNase RCL2, the amino acid residues which consist of the active site and major base recognition site of RNase Rh, a typical RNase of RNase T2 family, are very well conserved except for Tyr57 (RNase Rh numbering), and part of the amino acid residues of the minor base recognition site (Phe101 and Pro92) are also conserved.

Amino Acid Sequence↗
PubMed1997

Design and preparation of gadolinium-reservoir microcapsules for neutron-capture therapy by means of the Wurster process.

Gadolinium (Gd)-containing microcapsules designed for neutron-capture therapy (NCT) were prepared by a spouted bed coating process. Microcapsules were designed as a Gd-reservoir. They were prepared with the following properties: particle size was smaller than 50 microns, Gd-content was as high as possible, and release of Gd was suppressed as long as possible. Calcium carbonate (20-32 microns) was selected as a speed particle. As a Gd-source, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) or a synthesized water-insoluble Gd-DTPA derivative, Gd-DTPA-distearylamide (Gd-DTPA-SA), was layered onto the seed particles. The release-suppressing layer was composed of aqueous acrylic latex of 9:9:4 poly(ethyl acrylate/methyl methacrylate/2-hydroxyethyl methacrylate). In preliminary studies, Gd-DTPA microcapsules with 41-45 microns (mass median diameter) were prepared; they released Gd with a short lag-time and 3h-prolongation. Complete release suppression was, however, difficult to achieve because of high water-solubility of Gd-DTPA. Hence, a hydrophobic derivative, Gd-DTPA-SA, was next used as a Gd source. Gd-DTPA-SA microcapsules could be prepared with a mass median diameter of 52 microns. Gd-DTPA-SA content of the microcapsules was 38% and release of Gd was suppressed to less than 0.2% over 60 d.

Acrylates↗
PubMed1997

Simple approach to optically active drimane sesquiterpenes based on enzymatic resolution.

When the beta-acyloxy esters (+/-)-10 and (+/-)-11 were exposed to the lipase OF-360 from Candida rugosa or immobilized lipase OF-360 in a water-saturated organic solvent, the hydrolyzed product (8aS)-6 was obtained in high chemical (40%) and optical (> 99% ee) yields. The absolute structure of (8aS)-6 was confirmed by the fact that (8aS)-6 was converted into an authentic sample gamma-keto nitrile (8aS)-17. Treatment of the diol (+/-)-12 with isopropenyl acetate in the presence of the lipase Godo E-4 from Pseudomonas sp. provided the unchanged (8aR)-12 (89% ee) in 42% yield.

Acetylation↗
PubMed1997

[The role of hepatic sinusoidal cells in homing of lymphocytes. Preferential hepatic trapping of PNA(+) lymphocyte and its modulation during liver regeneration].

It was demonstrated that the reaction of some cell species to peanut agglutinin (PNA) involved the maturity of the cells. We investigated the selective adhesion of circulating hemopoietic cells and lymphoid cells to hepatic sinusoidal cells. We experimented with thymocyte (TYC) models that could be easily isolated into PNA positive [PNA(+)] and PNA negative [PNA(-)] subsets, and transfused these subsets, labeled with 51Cr into the isogenic mice, then measured the radioactivity in the kidney, lung, spleen, liver, Peyer's patch (P.P.), and thymus, after 48 hrs. The radioactivity (% total dose recovered) in the liver and spleen represented the degree of cellular distribution and indicated that a significantly higher dose had accumulated in the liver and spleen than in other organs. Additionally, TYC-PNA(+), recognized to be immature cells, demonstrated high aggregation in the liver, while TYC-PNA(-), recognized to be mature cells, demonstrated high aggregation in the spleen. Similar results were observed in our subsequent experiment using wheat germ agglutinin (WGA), other indicator of maturity, and spleen cells (SPC). Next, we transfused TYC-PNA(+) to mice at various intervals after 70% hepatectomy. The degree of aggregation (radioactivity/weight) in the liver was reduced 1 day after hepatectomy, and that in the spleen increased proportionately. Whereas the aggregation degree of TYC-PNA(-) in the same experiment did not change significantly. We postulated that hepatic sinusoidal cells recognize and, sequentially, trap specific carbohydrates on lymphoid cells by a lectin, PNA or WGA, like receptor. Reviewing our previous report, adhesion to Kupffer cells induced SPC activation and proliferation, this recognition and trapping mechanism seems to play an important role of intrahepatic hematolymphoid system.

Animals↗
PubMed1997

Ascending myelitis in association with herpes simplex virus. A case report.

A 50 year old man developed ascending necrotizing myelitis without any associated disease. After admission due to gait disturbance, the symptoms progressed rapidly and quickly. Neurological disturbance had progressed to an incomplete paraplesia below C 4 level; incontinence and drowsiness developed. Herpes Simplex viral myelitis was suspected through virological tests, which showed higher specific HSV antibody values of HSV-1 IgG of 640-fold in serum. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) registered 24.3 ng/ml. When he was treated with Acyclovir for 17 days, his general and neurological status improved significantly. Virological examinations showed 50-fold HSV-1 IgG in serum, and MBP in the CSF was 3.3 ng/ml. The MBP measurement and virological tests of the CSF and serum prove extremely important in diagnosing an ascending myelitis of unknown cause.

Acyclovir↗
PubMed1997

Lectin histochemistry in rat liver fibrosis induced by heterologous serum sensitization.

The localization of carbohydrates in rat livers with fibrosis induced by heterologous serum was examined by lectin histochemical and biochemical techniques. Twenty-four lectins were used to visualize the different carbohydrates in paraffin sections of normal and fibrotic liver tissues. No differences in staining patterns of these lectins were observed between normal and fibrotic livers in hepatocyte cell membranes including bile canaliculi, sinusoidal endothelial, or bile ductal cells. Kupffer cells strongly stained with Vicia villosa agglutinin (VVA) were seen only in the periportal zone of the normal liver, but they were observed in the periportal zone and scattered throughout the pseudolobular zone in the fibrotic liver. The cytoplasm of some hepatocytes was strongly stained by Bandeiraea simplicifolia lectin-I (BSL-I). BSL-I positive hepatocytes in normal liver were localized in the periportal zone, but those in the fibrotic liver were scattered in the periportal and perifibrous zones. After polyacrylamide gel electrophoresis of liver glycoproteins, differences in molecular sizes of BSL-I positive glycoproteins (79 and 81 kD) were detected by lectin blotting. Cell density of perifibrous BSL-I positive hepatocytes may be useful as a diagnostic parameter for liver fibrosis and/or cirrhosis. Two distinct staining patterns with twelve lectins were observed in fibrotic septa of the fibrotic liver. The fibrotic septa were stained with six characteristic lectins, and the centrilobular septa were stained with all these twelve of lectins. Histopathological assessment of the centrilobular fibrotic septa stained with these characteristic lectins may contribute to the diagnosis and prognosis of hepatic fibrosis.

Animals↗