Biomedical subjects

M Miyazawa

Publications and source records attributed to M Miyazawa.

At least 37 records · Page 2Linked to original sources

PubMed2001

Biotransformation of (R)- and (S)-terpinen-4-ol by the larvae of common cutworm (Spodoptera litura).

(R)-Terpinen-4-ol was mixed in an artificial diet at a concentration of 1 mg/g of diet, and the diet was fed to the last instar larvae of common cutworm (Spodoptera litura). Metabolites were recovered from frass and analyzed spectroscopically. (R)-Terpinen-4-ol was transformed mainly to (R)-p-menth-1-en-4,7-diol. Similarly, (S)-terpinen-4-ol was transformed mainly to (S)-p-menth-1-en-4,7-diol. The C-7 position (allylic methyl group) of (R)- and (S)-terpinen-4-ol was preferentially oxidized.

Animals↗

PubMed2001

Suppression of chemical mutagen-induced SOS response by alkylphenols from clove (Syzygium aromaticum) in the Salmonella typhimurium TA1535/pSK1002 umu test.

A methanol extract from clove (Syzygium aromaticum) showed a suppressive effect of the SOS-inducing activity on the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) in the Salmonella typhimurium TA1535/pSK1002 umu test. The methanol extract was re-extracted with hexane, dichloromethane, ethyl acetate, butanol, and water. The hexane fraction showed a suppressive effect. Suppressive compounds in the hexane fraction were isolated by silica gel column chromatography and identified as trans-isoeugenol (1) and eugenol (2) by GC, GC-MS, IR, and (1)H and (13)C NMR spectroscopy. Compounds 1 and 2 suppressed the furylfuramide-induced SOS response in the umu test. Compounds 1 and 2 suppressed 42.3 and 29.9% of the SOS-inducing activity at a concentration of 0.60 micromol/mL. These compounds were assayed with other mutagens, 4-nitroquinolin 1-oxide (4NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, compounds 1 and 2 were assayed with aflatoxin B(1) (AfB(1)) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. These compounds showed suppressive effects of the SOS-inducing activity against furylfuramide, 4NQO, AfB(1), and Trp-P-1. To research the structure-activity relationship, methyl esters of 1 and 2 (1Me and 2Me) and o-eugenol (3), as compounds similar to 2, were also assayed with all mutagens. Compounds 1Me, 2Me, and 3 showed weak suppressive effects of the SOS-inducing activity against furylfuramide.

Chromatography, Gas↗

PubMed2001

Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy.

BACKGROUND: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. AIM: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori-colonized Mongolian gerbils. METHODS: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. RESULTS: In all H. pylori-inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). CONCLUSION: Polaprezinc inhibited H. pylori-associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils.

Animals↗

PubMed2001

Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes.

1. Oxidation of 1,4-cineole, a monoterpene cyclic ether, was studied in rat and human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes expressed in insect cells in which human P450 and NADPH-P450 reductase cDNAs have been introduced. On analysis with gas chromatography/mass spectrometry, 2-exo-hydroxy-1,4-cineole was identified as a principal oxidation product of 1,4-cineole catalysed by rat and human P450 enzymes. 2. CYP3A4 was a major enzyme involved in the 2-hydroxylation of 1,4-cineole by human liver microsomes, based on the following lines of evidence. First, 1,4-cineole 2-hydroxylation activities catalysed by human liver microsomes were inhibited by ketoconazole, a potent inhibitor of CYP3A activities, and an anti-CYP3A4 antibody. Second, there was a good correlation beteeen CYP3A4 contents and 1,4-cineole 2-hydroxylation activities in liver microsomes of eighteen human samples examined. Finally, of 10 recombinant human P450 enzymes examined, CYP3A4 had the highest activity for 1,4-cineole 2-hydroxylation. 3. Liver microsomal 1,4-cineole 2-hydroxylation activities were induced in rat by pregnenolone 16alpha-carbonitrile and dexamethasone and extensively inhibited by ketoconazole, indicative of the possible roles of CYP3A enzymes in this reaction. 4. Kinetic analysis showed that Vmax/Km for 1,4-cineole 2-hydroxylation catalysed by liver microsomes was higher in a human sample HL-104 (4.6 microM(-1) min(-1)) than those of rat treated with pregnenolone 16alpha-carbonitrile (0.49 microM(-1) min(-1)) and dexamethasone (0.36 microM(-1) min(-1)). 5. 1,8-Cineole, a structurally related monoterpene previously shown to be catalysed by CYP3A enzymes, inhibited 1,4-cineole 2-hydroxylation catalysed by human liver microsomes, whereas 1,4-cineole did not inhibit 1,8-cineole 2-hydroxylation activities. Both compounds caused inhibition of testosterone 6beta-hydroxylation by human liver microsomes, the former compound being more inhibitory than the latter. 6. These results suggest that 1,4-cineole and 1,8-cineole, two plant essential oils present in Citrus medica L. var. acida and Eucalyptus polybractea, respectively, are converted to 2-hydroxylated products by CYP3A enzymes in rat and human liver microsomes. It is unknown at present whether the 2-hydroxylation products of these compounds are more active biologically than the parent compound.

Adult↗

PubMed2001

Biotransformation of 1,8-cineole by human liver microsomes.

The biotransformation of 1,8-cineole has been investigated by using human liver microsomes. A single oxidized metabolite, 2-exo-hydroxy-1,8-cineole, was isolated. Its formation was investigated under various conditions by changing incubation time, P450 level in liver microsomes, and substrate concentration.

Biotransformation↗

PubMed2001

Headspace constituents of the tree remain of Cinnamomum camphora.

The volatile ingredients isolated from a fresh tree of Cinnamomum camphora (camphor tree) and from a tree remain of C. camphora were collected by using headspace techniques and analyzed by means of gas chromatography/mass spectrometry (GC/MS). 99.77% of the constituents consisting 23 components from the fresh tree, 98.68% of the constituents consisting 24 components from the tree remain were identified. Of these ingredients, camphor was obtained as the most abundant component.

Gas Chromatography-Mass Spectrometry↗

PubMed2001

Biological stereoselective reduction of 3,3,5-trimethylcyclohexanone by Glomerella cingulata.

The microbial transformation of 3,3,5-trimethylcyclohexanone was investigated using the plant pathogenic fungus, Glomerella cingulata. With this organism 3,3,5-trimethylcyclohexanone gave the corresponding cis- and trans-3,3,5-trimethylcyclohexanols with the ratio of 20:1 forming the cis-isomer highly stereoselectively, upon 5 days incubation together with 3,3,5-trimethyl-2-cyclohexen-1-one (isophrone) as a minor product.

Ascomycota↗

PubMed2001

Insecticidal diarylheptanoid from Alpinia oxyphylla against larvae of Drosophila melanogaster.

In the course of screening for novel naturally occurring insecticides from Chinese crude drugs, a MeOH extract of Alpinia oxyphylla was found to give an insecticidal activity against larvae of Drosophila melanogaster Meigen. From the extract, an insecticidal compound was isolated by bioassay-guided fractionation and identified as yakuchinone A (1) by GC, GC/MS, 1H and 13C NMR spectroscopy.

Animals↗

PubMed2001

Headspace constituents of Parkia speciosa seeds.

The headspace of Parkia speciosa seeds was analysed by means of GC and GC-MS and found to contain 21 volatile components. The main constituents were hydrogen sulphide (41.30%), ethanol (39.15%), 1,2,4-trithiolane (4.75%) and acetaldehyde (3.59%), of which 1,2,4-trithiolane was found as one of the main component for the characteristic odour.

Acetaldehyde↗

PubMed2001

Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

Inhibition of acetylcholinesterase (AChE) activity by essential oils of Citrus paradisi (grapefruit pink in USA) was studied. Inhibition of AChE was measured by the colorimetric method. Nootkatone and auraptene were isolated from C. paradisi oil and showed 17-24% inhibition of AChE activity at the concentration of 1.62 microg/mL.

Acetylcholinesterase↗

PubMed2001

Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage.

OBJECTIVE: To examine the changes in the number of T cells and macrophages in the mucosal lamina propria in the presence or absence of bile in the gastrointestinal tract. DESIGN: Clinical study. SETTING: University hospital, Japan. SUBJECTS: 6 patients with obstructive jaundice who had external biliary drainage (drainage group) and 6 patients with no signs of obstructive jaundice (control group). INTERVENTIONS: Gastrointestinal specimens were taken at the time of operation. MAIN OUTCOME MEASURES: The number of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the lamina propria mucosae in each group measured immunohistochemically. RESULTS: The numbers of CD8 T cells and CD68+ macrophages in the lamina propria of the patients treated by external drainage were significantly less than in the control group (p < 0.01). However, there was no difference in the number of CD4+ T cells between the groups (p = 0.45). CONCLUSIONS: In the absence of bile, mucosal immune function fails as a result of reduced numbers of CD8+ T cells and macrophages.

Aged↗

PubMed2001

Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.

Thrombus formation is a key component of the pathogenesis of restenosis after arterial balloon injury. The purpose of this study was to determine whether intimal hyperplasia could be attenuated by infusion of recombinant tissue plasminogen activator (tPA). Forty-two Kurosawa and Kusanagi hypercholesterolemic rabbits were divided into tPA (n = 20) and control (n = 22) groups, the former receiving 7 days of continuous tPA infusion (0.6 mg/kg/day) via ear veins. The walls of the common iliac arteries were injured using 2.5-mm balloon catheters and then examined histologically 7, 14, 21, and 28 days later. Cell proliferation was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and transforming growth factor (TGF)-beta immunohistochemistry was carried out to estimate cell proliferation and differentiation. It was observed that 28 days after balloon injury, intimal cross-sectional areas in the tPA group were significantly smaller than in controls (0.11 +/- 0.03 mm2 vs. 0.57 +/- 0.08 mm2, p < 0.01), as were ratios of the cross-sectional areas of the intima and media (0.21 +/- 0.07 vs. 1.06 +/- 0.18, p < 0.05). In addition, the numbers of PCNA-positive medial cells were significantly lower (0.06 +/- 0.01 vs. 0.36 +/- 0.08, p < 0.05) and TGF-beta-positive vessel wall areas were significantly smaller in tPA-treated animals 7 days after balloon injury (0.47 +/- 0.28% vs. 4.55 +/- 1.44%, p < 0.05). Thus infusion of tPA after arterial balloon injury appears to decrease medial cell proliferation and suppress intimal hyperplasia.

Animals↗

PubMed2001

Off-pump Coronary Artery Bypass Grafting in patients on chronic hemodialysis.

BACKGROUND: Off-pump Coronary Artery Bypass Grafting(CABG) has gained much support but has been scarcely reported in patients on chronic hemodialysis (HD). The details of CABG for such patients on chronic HD are presented. METHODS: Between January 1998 and December 1999, off-pump CABG was performed in 5 patients on chronic HD. All patients presented with unstable angina pectoris. The indication for off-pump CABG was suitable coronary anatomy (N = 5) and expected high risks associated with cardiopulmonary bypass due to reoperation (N = 1) and impaired cerebral blood flow (N = 2). The approach was median sternotomy (N = 4) and left anterior short thoracotomy (N = 1). The mean graft number was 2.0 +/- 1.0 (range, 1-3). In situ arterial grafts were mainly used: the in situ left internal thoracic artery was used in four patients, the in situ right gastroepiploic artery in two, the in situ right internal thoracic artery in two, and the saphenous vein in two patients. RESULTS: There were no deaths or complications. Nine of 10 grafts were confirmed fully patent by postoperative angiography before hospital discharge. In a mean follow-up of 17.2 months, no patients had developed recurrence of angina or any cardiac symptom. CONCLUSION: Off-pump CABG using in situ arterial grafts can be performed on patients on chronic hemodialysis subject to suitable anatomy of the target coronary arteries.

Adult↗

PubMed2001

Role of natural killer cells in resistance against friend retrovirus-induced leukemia.

We have previously shown that immunization with a synthetic peptide that contains a single CD4(+) T-cell epitope protects mice against immunosuppressive Friend retrovirus infection. Cells producing infectious Friend virus were rapidly eliminated from the spleens of mice that had been immunized with the single-epitope peptide. However, actual effector mechanisms induced through T-helper-cell responses after Friend virus inoculation were unknown. When cytotoxic effector cells detected in the early phase of Friend retrovirus infection were separated based on their expression of cell surface markers, those lacking CD4 and CD8 but expressing natural killer cell markers were found to constitute the majority of effector cells that lysed Friend virus-induced leukemia cells. Depletion of natural killer cells by injecting anti-asialo-ganglio-N-tetraosylceramide antibody did not affect the number of CD4(+) or CD8(+) T cells in the spleen, virus antigen-specific proliferative responses of CD4(+) T cells, or cytotoxic activity against Friend virus-induced leukemia cells exerted by CD8(+) effector cells. However, the same treatment markedly reduced the killing activity of CD4(-) CD8(-) effector cells and completely abolished the effect of peptide immunization. Although the above enhancement of natural killer cell activity in the early stage of Friend virus infection was also observed in mice given no peptide, these results have demonstrated the importance and requirement of natural killer cells in vaccine-induced resistance against the retroviral infection.

Amino Acid Sequence↗

PubMed2001

Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes.

1,8-Cineole, the monoterpene cyclic ether known as eucalyptol, is one of the components in essential oils from Eucalyptus polybractea. We investigated the metabolism of 1,8-cineole by liver microsomes of rats and humans and by recombinant cytochrome P450 (P450 or CYP) enzymes in insect cells in which human P450 and NADPH-P450 reductase cDNAs had been introduced. 1,8-Cineole was found to be oxidized at high rates to 2-exo-hydroxy-1,8-cineole by rat and human liver microsomal P450 enzymes. In rats, pregenolone-16alpha-carbonitrile (PCN) and phenobarbital induced the 1,8-cineole 2-hydroxylation activities by liver microsomes. Several lines of evidence suggested that CYP3A4 is a major enzyme involved in the oxidation of 1,8-cineole by human liver microsomes: (1), 1,8-cineole 2-hydroxylation activities by liver microsomes were inhibited very significantly by ketoconazole, a CYP3A inhibitor, and anti-CYP3A4 immunoglobulin G; (2), there was a good correlation between CYP3A4 contents and 1,8-cineole 2-hydroxylation activities in liver microsomes of eighteen human samples; and (3), of various recombinant human P450 enzymes examined, CYP3A4 had the highest activities for 1,8-cineole 2-hydroxylation; the rate catalyzed by CYP3A5 was about one-fourth of that catalyzed by CYP3A4. Kinetic analysis showed that K(m) and V(max) values for the oxidation of 1,8-cineole by liver microsomes of human sample HL-104 and rats treated with PCN were 50 microM and 91 nmol/min/nmol P450 and 20 microM and 12 nmol/min/nmol P450, respectively. The rates observed using human liver microsomes and recombinant CYP3A4 were very high among other CYP3A4 substrates reported so far. These results suggest that 1,8-cineole, a monoterpenoid present in nature, is one of the effective substrates for CYP3A enzymes in rat and human liver microsomes.

Animals↗

PubMed2001

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

Adenocarcinoma↗

PubMed2001

Immediate and long-term results of coronary artery bypass operation in hemodialysis patients.

This study evaluated the early and late results of coronary artery bypass grafting (CABG) in patients on long-term maintenance hemodialysis (chronic HD) at Teikyo University Ichihara Hospital between January 1996 and June 2000. Thirty-six patients on chronic HD underwent CABG. There were 26 males (72%) and 10 females (28%) ranging from 41 to 81 years (mean +/- SD, 61.8 +/- 9.2 years) of age. Twenty-one patients (58%) had unstable angina, 14 (39%) stable angina, and 1 acute myocardial infarction. Eleven patients (31%) had urgent or emergency CABG. The average graft number was 2.5 +/- 0.8 (arterial graft 1.3 +/- 0.7/patient). Six patients had concomitant cardiac operations. Three patients underwent re- or a second re-CABG. Five patients underwent off-pump CABG. Principally, HD was performed during cardiopulmonary bypass and was followed by continuous hemodiafiltration in the early postoperative period. The early mortality was 11%; 25% in emergency and urgent CABG and 4% in elective CABG. In the follow-up period between 1 and 53 months (mean +/- SD 21.9 +/- 15.1 months), 4 patients died, and 9 patients developed recurrence of angina pectoris (6, occlusion of saphenous vein graft and 3, native coronary progression). Six patients had coronary intervention. The postoperative angiogram showed that all arterial grafts were patent, but the patency of the vein grafts was only 61.5%. The early results of CABG in patients on chronic HD was satisfactory. The late recurrence of angina pectoris mostly was caused by occlusion of the saphenous vein graft. In conclusion, the aggressive use of arterial grafts is crucial in CABG for patients on chronic HD.

Adult↗

PubMed2001

Progress with inactivated poliovirus vaccines derived from the Sabin strains.

To produce a safe and effective inactivated poliovirus vaccine (IPV), we have developed S-IPV using Vero cells infected with the Sabin strains in a semi-production scale. All production steps including virus culture on microcarrier beads were highly reproducible. Mean recovery percents of infectious viruses or D-antigens during all processes for concentration, purification and inactivation were 30-50% in the three types. The S-IPV potency was adjusted for D-antigen content as determined by in-house ELISA and was comparable to WHO reference IPV derived from the virulent strains in immunogenicity tests in rats. Antibody development in more than 30 seronegative infant volunteers after two shots of S-IPV at four-week interval were 100% without notable adverse reactions. The mean antibody titres (log2) to Sabin 1, 2 and 3 viruses were 11.1, 8.3 and 8.9, respectively. The antibodies neutralized the Mahoney, MEF-1, and Saukett virulent strains with slightly inferior titres to those of the Sabin strains. D-antigens for each type of S-IPV were stable at 4 degrees C without any significant decrease over more than two years.

Adult↗