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Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

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

Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleukin 10.

OBJECTIVE: To investigate the therapeutic efficacy as well as the immunological effects of inoculation of an expression vector encoding interleukin 10 (IL-10) in murine type II collagen induced arthritis (CIA). METHODS: CIA was induced in DBA/1 Lac/J mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant (FCA), followed by immunization of CII in Freund's incomplete adjuvant (FIA) 3 weeks later (CIA mice). The plasmid cytomegalovirus (pCMV) vector encoding IL-10 (pCMV-IL-10) was inoculated intradermally into DBA/1 Lac/J mice (pCMV-IL-10 CIA mice) one week prior to first immunization with CII. CIA mice inoculated with the backbone pCMV vector instead of pCMV-IL-10(pCMV CIA mice), mice inoculated with the pCMV vector alone, without subsequent immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C mice) were examined as controls. At the 3rd and 5th week after 2nd immunization with CII, booster injections of CII in FIA were administered. Foot pad thicknesses were measured weekly and the histopathological changes in the ankle joints and the titers of IgG1 (Th2 type) and IgG2a (Th1 type) isotype antibodies to CII were examined at the 10th week. RESULTS: pCMV-IL-10 CIA mice showed lesser foot pad thicknesses (p < 0.01 except at Weeks 1-3), less severe histopathological changes (p < 0.01 or 0.05) and lower IgG2a/IgG1 ratios of antibodies to CII (p <0.01) than CIA mice. CONCLUSION: Inoculation of pCMV-IL-10 suppressed CIA through suppression of the Th 1 type immune response in CIA, and offers promise as a potential therapeutic strategy for rheumatoid arthritis.

Animals↗
PubMed2000

[Video assisted thoracic surgery for the treatment of catamenial pneumothorax].

Video assisted thoracic surgery (VATS) was applied in 3 cases of pneumothorax combined with pathologic changes in the diaphragm (two cases of catamenial pneumothorax and one case of suspected catamenial pneumothorax). Case 1, 39-year-old woman, was preoperatively diagnosed as catamenial pneumothorax in the right lung. Thoracoscope was inserted through the 5th intercostal anterior axillary line and the lesion with the pathologic changes in the central tendon of the diaphragm was incised and sutured with Endo-GIA and Endo-STAPELAR. Case 2, 42-year-old woman, was confirmed to have pathologic changes in the central tendon after insertion of thoracoscope through the 5th intercostal anterior axillary line. Minithoracotomy of 50 mm in size was added close to the center of the diaphragm and direct incision and suture of that part were performed. Case 3, 47-year-old woman, underwent thoracoscopy through the 5th intercostal mid-axillary line and bulla in the S2 interlobar surface was incised with Endo-GIA. In this case, the diaphragm was partially incised through additional minithoracotomy because some lesions were detected on that part. VATS can fully be carried out for pathologic changes in the diaphragm in catamenial pneumothorax. Since catamenial pneumothorax may be complicated with another pathologic changes in the diaphragm (Case 1) or in the visceral pleura (Case 3), the whole thoracic cavity, including diaphragm and visceral pleura, should be carefully observed under thoracoscopy. Application of minithoracotomy-associated thoracoscopic surgery is a useful method in the case to whom catamenial pneumothorax is definite or suspected.

Adult↗
PubMed2000

Midgut malrotation in adulthood.

A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.

Abdominal Pain↗
PubMed2000

[A study of the minimum number of slices required for quantification of pulmonary emphysema by computed tomography].

We attempted to determine the minimum number of slices required for quantification of overall emphysema by computed tomography (CT). Forty-nine patients underwent CT scanning with a 15-mm slice interval, and 13 to 18 slices per patient were obtained. The percentage of low attenuation area (LAA%) per slice was measured with a method that we reported on previously, utilizing a CT program and NIH image. The average LAA% values for 1, 2, 3, and 6 slices evenly spaced through the lungs [LAA% (1), LAA% (2), LAA% (3), and LAA% (6)] were compared with those for all slices [LAA% (All)]. The correlation coefficients for LAA% (1), LAA% (2), LAA% (3), and LAA% (6) with LAA% (All) were 0.961, 0.981, 0.993, and 0.997, respectively. Mean differences +/- SD were -3.20 +/- 4.21%, -2.32 +/- 3.00, -0.20 +/- 1.84, and -0.16 +/- 1.26, respectively. From these results, we concluded that overall emphysema can be quantified by using at least three slices: one each of the upper, middle, and lower lung.

Adult↗
PubMed2000

[The value of serum C-reactive protein as a survival determinant in patients with advanced non-small-cell lung cancer].

We retrospectively reviewed the information in our data base concerning 127 patients with advanced non-small-cell lung cancer. Seventeen pretreatment clinical variables including serum C-reactive protein (CRP) were analyzed to determine the factors related to survival using Cox's proportional hazards model. Univariate analysis revealed that eleven explanatory variables were significant. In multivariate statistical technique for those variables, six were selected as significant factors. The highest hazard ratio was observed in the serum CRP (3.82). The other factors were therapy (2.52), serum lactate dehydrogenase (2.41), serum total protein (2.20), white blood cell counts (1.98) and performance status (1.80). Median survival times estimated by the Kaplan-Meier procedures in patients with normal CRP (CRP < 0.2 mg/dl) and high positive CRP (CRP > or = 3.0 mg/dl) were 24.9 months and 3.7 months, respectively. These results suggest that serum CRP is an independent survival determinant in advanced non-small-cell lung cancer.

Adult↗
PubMed2000

[A case of neurogenic bladder due to neuro-Behçet disease].

Behçet disease is a systemic vasculitis of unknown cause with variable clinical features. The central nervous system may also be involved in about 10% of the patients with Behçet disease. Half of them show marked central nervous system symptoms and are diagnosed as neuro-Behçet disease. Voiding symptom is seen in about 5% of the patients with neuro-Behçet disease. We report a case of neuropathic vesico-urethral dysfunction in a 39-year-old man with neuro-Behçet disease. Its radiological and urodynamic features and treatment are also presented with some discussion.

Adult↗
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↗