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M Miyata

Publications and source records attributed to M Miyata.

At least 19 recordsLinked to original sources
PubMed2000

Injection of plasmid DNA into the gastric mucosa induces mucosal and systemic immunity.

Nearly all mucosal surfaces participate in a common mucosal immune system, and application of an antigen to one mucosal surface elicits local as well as distant mucosal immune responses. However, whether the gastric mucosa is a part of this network has not been examined directly. We show here that the injection of plasmid DNA encoding beta-galactosidase into the gastric wall caused transfection of gastric mucosal epithelial cells, induced systemic and mucosal antibody responses at both local (digestive tract) and distant (genital and respiratory tracts) sites, and induced cytotoxic T lymphocyte responses in the spleen and the mesenteric and iliac lymph nodes.

Animals↗
PubMed2000

Takayasu's arteritis in a 69 year-old woman.

Takayasu's arteritis and temporal arteritis share many clinical and pathological features. The most discriminatory feature between the two diseases is the age at onset; the mean age at onset of the disease was reported as being 26 years for Takayasu's arteritis and 69 years for temporal arteritis. Here we report a 69-year-old woman who presented with a weak right radial artery pulse. The ethnic background and the presence of vascular insufficiency of the right upper extremity and the absence of clinical signs such as shoulder stiffness and tender scalp indicate that her diagnosis is Takayasu's arteritis. It must be emphasized that the two conditions could be differentiated based on the clinical findings even in a patient as old as 69 years old.

Age of Onset↗
PubMed1999

Adjuvant effect of a 14-member macrolide antibiotic on DNA vaccine.

Macrolide antibiotics have unique immunomodulatory actions apart from their antimicrobial properties. We examined the effect of erythromycin (EM), a 14-member macrolide, on the immune response to a DNA vaccine that induces a T-helper-1 (Th1)-biased immune response through a Th1-promoting adjuvant effect of unmethylated CpG motifs within plasmid DNA. EM enhanced Th1 responses in plasmid DNA-immunized mice as measured by antigen-specific IgG2a antibody production, interferon-gamma production by antigen-specific CD4(+) T cells, and cytotoxic T lymphocyte responses. EM augmented the accessory cell activity of unmethylated CpG DNA-stimulated antigen-presenting cells (APCs), suggesting that EM enhances Th1 responses to a DNA vaccine, possibly through augmentation of accessory cell activity of APCs stimulated with CpG motifs within plasmid DNA.

Adjuvants, Immunologic↗
PubMed1999

Regression and prevention of autochthonous tumors induced by 3-methylcholanthrene after injection of a T-cell receptor alpha /beta positive and CD4/CD8 double negative T-cells.

Both the therapeutic and preventative effects of a murine T-cell line, tMK-2, with T-cell receptor (TCR) alpha/beta positive and CD4-/8- double negative (DN) phenotype against autochthonously tumors induced by subcutaneous (s.c.) injection of 3-methylcholanthrene (MC) were examined. Complete regression of the tumor was observed when administration of tMK-2 cells was begun on tumors 5 mm in diameter. The tumor mass in five out of five mice was reduced in size after the administration of tMK-2 cells regardless of the routes of administration: s.c. injection of tMK-2 cells (5 x 10(7) cells) once a week around tumors, intraperitoneal (i.p.) injection (5 x 10(7) cells), or intravenous (i.v.) injection (1 x 10(7) cells). The tumors regressed to the status of a scar within 1 month of initial injection, and this status was maintained throughout the remainder of the 3 months period of tMK-2 cell injection. One month after discontinuation of tMK-2 cell administration, the diameter of the tumors had not increased regardless of the route of injection. The control groups consisted of either untreated mice, mice with i.v. injection of 1 microg of recombinant murine interleukin (IL)-12 once a week, or mice with s.c. injection of autologous splenocytes (5 x 10(7)) from BALB/c mice once a week. Continuous growth of tumors was observed in each group and all control mice died due to bleeding ulcerations of the tumors. Tumor development was effectively prevented when tMK-2 cells were administrated 1 week after the s.c. injection of MC. In the groups receiving s.c., i.p., and i.v. injection of tMK-2 cells, no MC-induced tumors developed, whereas four out of five of the control mice developed autochthonous tumors. The tMK-2 cells also exerted in vitro NK-like cytotoxic activity, and their killing activity was strongly increased in the presence of both IL-2 and IL-12. These results suggest that the injected T-cells with TCR alpha/beta positive and CD4- /8- DN phenotype and NK-like activity are important in the therapy as well as the prevention of tumor development.

Animals↗
PubMed1999

Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene.

Microsomal epoxide hydrolase (mEH) is a conserved enzyme that is known to hydrolyze many drugs and carcinogens, and a few endogenous steroids and bile acids. mEH-null mice were produced and found to be fertile and have no phenotypic abnormalities thus indicating that mEH is not critical for reproduction and physiological homeostasis. mEH has also been implicated in participating in the metabolic activation of polycyclic aromatic hydrocarbon carcinogens. Embryonic fibroblast derived from the mEH-null mice were unable to produce the proximate carcinogenic metabolite of 7,12-dimethylbenz[a]anthracene (DMBA), a widely studied experimental prototype for the polycylic aromatic hydrocarbon class of chemical carcinogens. They were also resistant to DMBA-mediated toxicity. Using the two-stage initiation-promotion skin cancer bioassay, the mEH-null mice were found to be highly resistant to DMBA-induced carcinogenesis. In a complete carcinogenesis bioassay, the mEH mice were totally resistant to tumorigenesis. These data establish in an intact animal model that mEH is a key genetic determinant in DMBA carcinogenesis through its role in production of the ultimate carcinogenic metabolite of DMBA, the 3,4-diol-1,2-epoxide.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Structure and expression of the rat CYP3A1 gene: isolation of the gene (P450/6betaB) and characterization of the recombinant protein.

A P450 gene (P450/6betaB) of the CYP3A subfamily was isolated from a rat genomic library. Nucleotide sequencing of the exons revealed a high similarity with P450PCN1 cDNA (Gonzalez et al. (1985), J. Biol. Chem. 260, 7345-7441), but differed in 41 nucleotides, resulting in 11 changes and 2 deletions of amino acid residues. The P450/6betaB spanned about 30 kbp and consisted of 13 exons, and was in exon number and size identical with CYP3A2 gene except in the 6th exon, which was shorter than that of CYP3A2. 6beta-B mRNA, which may be transcribed from P450/6betaB, was detected on Northern blotting and by reverse transcription-polymerase chain reaction (RT-PCR). Profiles of the developmental change and induction by a treatment with several chemicals were very similar to those of P450PCN1 mRNA reported previously. P450PCN1 mRNA and gene, however, were not detected by PCR in rats. To determine whether P450/6betaB encodes an active protein, a cDNA was isolated and expressed. Expression of 6beta-B cDNA in COS-1 cells was carried out and revealed that the recombinant protein comigrated with purified P4506beta-4 previously identified as CYP3A1. The recombinant 6beta-B protein showed similar turnover rate and regioselectivity for testosterone with purified P4506beta-4 by the simultaneous addition of NADPH-cytochrome P450 reductase and cytochrome b5. These data suggest that P450/6betaB encodes an active P450 form corresponding to CYP3A1 and P450PCN1 reported previously does not exist in rats.

Amino Acid Sequence↗
PubMed1999

Hepatocyte nuclear factor 4-mediated activation of rat CYP3A1 gene and its modes of modulation by apolipoprotein AI regulatory protein I and v-ErbA-related protein 3.

CYP3A1 gene (P450/6betaB) encodes testosterone 6beta-hydroxylase (EC 1.14.14.1) in rats. The promoter region of CYP3A1 gene contains three binding sites for nuclear factors: 6betaB-A (-105 to -86), 6betaB-B (-139 to -118), and 6betaB-C (-164 to -145). The 6betaB-A site shows a high degree of similarity to a consensus sequence of the binding site of hepatocyte nuclear factor 4 (HNF-4) and also to the 6betaA-A site on the rat CYP3A2 gene promoter region. Our previous study suggested an involvement of the 6betaA-A site in the basal transactivation of CYP3A2 gene using HepG2 cells. In the present study, transactivation through the 6betaB-A and 6betaA-A sites of CYP3A1 and CYP3A2 genes has directly been shown by coexpression of HNF-4 and CYP3A1 or CYP3A2 promoter-reporter fused genes. Similar experiments further showed that nuclear factor binding at the 6betaB-B site hampered HNF-4-mediated transactivation of CYP3A1 gene. Recombinant apolipoprotein AI regulatory protein I (ARP-1) and v-ErbA-related protein 3 (EAR-3) are shown to suppress HNF-4-mediated activation at the 6betaB-B site without competition of HNF-4.

Animals↗
PubMed1999

Functional and phenotypical characteristics of hepatic NK-like T cells in NK1.1-positive and -negative mouse strains.

We previously reported and partially characterized a unique monoclonal antibody (mAb), U5A2-13, which recognizes a T cell subset similar to NK1.1+ T cells, not only in NK1.1-positive mouse strains but also in NK1.1-negative strains. In NK1.1-positive C57BL/6 mice, U5A2-13+ TCRalphabeta+ cells produced abundant IL-4 as well as extremely high levels of IFN-gamma upon CD3 cross-linking, but this did not occur with U5A2-13- TCRalphabeta+ cells. In NK1.1-negative C3H/He mice, U5A2-13+ TCRalphabeta+ cells produced high levels of IL-4 and IFN-gamma upon CD3 cross-linking, but this was not observed with U5A2-13- TCRalphabeta+ cells. To the best of our knowledge, this is the first direct evidence of the presence of NK-like T cells defined phenotypically by U5A2-13 mAb and functionally by IL-4/IFN-gamma production in NK1.1-negative mouse strains. We also demonstrated that U5A2-13- NK1.1+ T cells and U5A2-13+ NK1.1- T cells in C57BL/6 mice could produce both IL-4 and IFN-gamma. In addition, Vbeta8 or Vbeta7 usage by U5A2-13+ NK1.1- T cells was lower than that by U5A2-13+ NK1.1+ T cells, but remained higher than that by U5A2-13- NK1.1- T cells. Based on the present results, U5A2-13 mAb appears to be a valuable tool in the study of NK-like T cells.

Animals↗
PubMed1999

Detection of melatonin, its precursors and related enzyme activities in rabbit lens.

Melatonin (N -acetyl-5-methoxytryptamine) was detected in extracts of albino rabbit lens using radioimmunoassay. Furthermore, melatonin precursors, tryptophan and serotonin (5-hydroxytryptamine), were found in the lens extracts by high-performance liquid chromatography coupled with fluorometric detection. Also, activities of two melatonin-synthesizing enzymes, serotonin N -acetyltransferase (NAT) and hydroxyindole- O -methyltransferase (HIOMT), were found in the lens. The apparent Michaelis constants (K m) for substrates of NAT in the lens were similar to those reported for the pineal gland, although the apparent K m values for substrates of HIOMT in the lens were 10-fold higher than those in the pineal gland. When the rabbits were entrained to a 14-hr light: 10-hr dark cycle, melatonin levels and NAT activity in the lens showed significant day/night changes with high levels during the dark period, but HIOMT activity did not show these changes. These findings strongly suggest that the rabbit lens may synthesize melatonin from serotonin by the sequential action of NAT and HIOMT, and that the melatonin synthesis may fluctuate in a diurnal and/or circadian manner.

Acetylserotonin O-Methyltransferase↗
PubMed1999

Guideline of surgical management based on diffusion of descending necrotizing mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis resulting from oropharyngeal abscess, is a serious, life-threatening infection. Exisiting strategies for surgical management, such as transcervical mediastinal drainage or aggressive thoracotomic drainage, remain controversial. METHODS: Four patients, (three males and one female) were treated for descending necrotizing mediastinitis resulting from oropharyngeal infection. Two had peritonsillar abscesses, while the others experienced dental abscess and submaxillaritis. Descending necrotizing mediastinitis received its classification according to the degree of diffusion of infection diagnosed by computed tomography. Mediastinitis in two cases, (Localized descending necrotizing mediastinitis-Type I), was localized to the upper mediastinal space above the carina. In the others, infection extended to the lower anterior mediastinum (Diffuse descending necrotizing mediastinitis-Type IIA), and to both anterior and posterior lower mediastinum (Diffuse descending necrotizing mediastinitis-Type IIB). The spread of infection to the pleural cavity occurred in three cases. RESULTS: The surgical outcome concerning each of the patients was successful. Radical cervicotomy (unilateral in three patients, bilateral in the other) in conjunction with mechanical ventilation with continuous postoperative positive airway pressure, was performed in all cases. Tracheostomy was established in three patients and pharyngostomy in two. The two descending necrotizing mediastinitis-Type I cases were successfully managed with transcervical mediastinal drainage. The descending necrotizing mediastinitis-Type IIA case received treatment through transcervicotomy and anterior mediastinal drainage through a subxiphoidal incision. The patient with descending necrotizing mediastinitis-Type IIB required posterior mediastinal drainage through a right standard thoracotomy followed by left minimal thoracotomy. CONCLUSIONS: The mediastinal infection, the extent of which has been accurately determined by computed tomograms, necessitates radical cervicotomy followed by pleuromediastinal drainage. Situations where infection has spread to posterior medisatinum, particularly when it reaches in the level of the carina (descending necrotizing mediastinitis-type I), may not always require aggressive mediastinal drainage. In comparison, diffuse descending necrotizing mediastinitis-Type IIB demands complete mediastinal drainage with debridement via thoracotomy. Subxiphoidal mediastinal drainage without sternotomy may provide adequate drainage in diffuse descending necrotizing mediastinitis-Type IIA.

Abscess↗
PubMed1999

Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by monocrotaline in rats.

The effect of administering prostaglandin E1 (PGE1) on the extent of monocrotaline (MCT)-induced pulmonary hypertension and cytokine production [interleukins (IL) 1 and 6 and tumor necrosis factor (TNF)] by macrophages during MCT induction of pulmonary hypertension was studied. Right ventricle/left ventricle plus septum weight ratios (RV/LV + S) were used as an index of the development of pulmonary hypertension. Administering PGE1 at a dose of 0.2 mg/kg/day for 4 weeks reduced significantly the RV/LV + S ratio from 0.428 +/- 0.070 to 0.243 +/- 0.059 (p < 0.01) and decreased the production of these cytokines: IL-1, from 4.675 +/- 3.558 to 1.800 +/- 0.722 units; IL-6, from 0.322 +/- 0.121 to 0.060 +/- 0.039 units; and TNF, from 0.578 +/- 0.369 to 0.004 +/- 0.004 units. In another series of experiments, a significant reduction of the RV/LV + S ratio was noted for only 1 week when we administered PGE1 immediately after the injection of MCT. We confirmed that histopathologic improvements of lungs were noted by administering 0. 2 mg/kg PGE1 for 4 weeks. In another experiment, PGE1 at a concentration of 2 microg/ml suppressed a rise in the cytosolic Ca2+ concentration of lipopolysaccharide-stimulated peritoneal macrophages of rats in vitro, suggesting that PGE1 suppressed cytokine production by macrophages through the suppression of the Ca2+ influx. These results suggest that administering PGE1 may be effective in the treatment of some forms of pulmonary hypertension in humans.

Alprostadil↗
PubMed1999

Development of Purkinje cells in humans: an immunohistochemical study using a monoclonal antibody against the inositol 1,4,5-triphosphate type 1 receptor (IP3R1).

Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.

Antibodies, Monoclonal↗
PubMed1999

Changes in fecal fat excretion from allo-intestine transplanted rats after discontinuance of immunosuppressive agents.

We have previously shown in a rat model of segmental small bowel transplantation, that an ileal graft was more favorable for lipid absorption than a jejunal graft. In the present study, we investigated changes in the lipid absorption of allo-ileal grafts after the withdrawal of an immunosuppressant (methyldeoxyspergualin; given for 1 or 2 weeks at 2.5mg/kg per day) and compared the findings with the results of histological examinations. Heterotopic segmental small bowel transplantation (SBT) was performed using cuff anastomoses in the inbred rat strain combination DA (RT1a) and LEW (RT1). Orthotopic SBT was performed as reconstruction SBT. Reconstruction after resection of the original intestinal tract of the recipient was performed on the seventh day after heterotopic segmental ileal grafting. For the histological evaluation of graft rejection, we performed biopsies in the heterotopic model and autopsies in the orthotopic model. Fecal fat excretion from the orthotopically reconstructed recipients was measured by Folch's method. One- and 2-week use of methyldeoxyspergualin allowed the heterotopic allografts to remain intact histologically for 16.8+/-5.6 and 25.3+/-3.3 (mean+/-SD) days, respectively, whereas the grafts were rejected at 7.3+/-1.1 days when the immunosuppressive drug was not used. All the recipients in the orthotopic group had died by 19 days after reconstruction. After discontinuance of the immunosuppressive agent, fat excretion in feces in the surviving orthotopic grafted rats had increased markedly prior to histologically assessed heterotopic graft rejection. Evaluation of fecal lipid excretion may be a useful parameter for detecting graft rejection in rats.

Animals↗
PubMed1999

Clinico-laboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease.

The clinico-laboratory features of 16 patients with dermatomyositis (DM) were compared between patients with accompanying rapidly progressive interstitial lung disease (RP-ILD, n = 7) and those with chronic interstitial lung disease (C-ILD, n = 9), and also between deceased (seven RP-ILD and three C-ILD) and living patients (six C-ILD). The extent of muscle weakness of the extremities and frequency of autoantibody positivity were significantly lower in DM patients with RP-ILD than in DM patients with C-ILD. Furthermore, significantly lower serum creatine kinase/lactate dehydrogenase levels (0.26+/-0.27) were found in the 10 patients who died than in the six living patients (1.21+/-1.09). A higher CD4+/CD8+ T-lymphocyte ratio in the peripheral blood (3.51+/-2.65) was detected in the four DM patients with RP-ILD who died than in the six living DM patients with C-ILD (1.22+/-0.49).

Adult↗
PubMed1999

Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft.

BACKGROUND/PURPOSE: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum. METHODS: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The short-gut rats, whose small bowel was totally resected, served as a control (n = 12). RESULTS: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one. CONCLUSION: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.

Animals↗
PubMed1999

Immunotherapy for experimental rat autoimmune thyroiditis using a novel immunosuppressant, FTY720.

While autoimmune disease needs to be continuously treated via long term, administration of immunosuppressants conventional immunotherapy using drugs such as cyclosporin and tacrolimus may cause adverse effects. Recently, a novel agent, FTY720, which was structurally modified from a natural product, has been shown to have a moderate and different immunosuppressive effect from conventional drugs. In this study, we examined the effect of FTY720 on experimental autoimmune thyroiditis (EAT), which was induced in rats by neonatal thymectomy, followed by subsequent sublethal irradiation. Thyroid stimulating hormone (TSH) was measured before and at the end of drug therapy. Histological and hematological examinations were performed using the samples from sacrificed animals. High TSH levels in the animals returned to the normal range following treatment with FTY720. The severity of the thyroiditis was lower in the FTY720 group than in the control group. FTY720 markedly decreased the number of circulatory lymphocytes, and no infections episodes were observed under this treatment. Thus, FTY720 treatment might be preferred for continuous immunotherapy for autoimmune disease without adverse effects.

Animals↗