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Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 217 records · Page 12Linked to original sources

Analysis of the hypervariable region of hepatitis C virus E2/NS1 gene in an infant infected by blood transfusion.

We investigated the sequential change in the hypervariable region 1 (HVR 1) of hepatitis C virus (HCV) E2/NS1 gene in an infant. He was transfused with 160 mL of blood containing the HCV (0.7 Meq/mL) on the 6th d after birth and subsequently developed chronic viremia. At 16 mo, the HVR1 amino acid sequences of HCV observed in the infant's sera were very similar to those from the donor (his maternal grandfather) on the day of transfusion. However, highly variable amino acid sequences of HVR1 were observed throughout infancy. These results demonstrate that an adaptive response of HCV to evade host immunity seems to occur, as in adult cases, even in early infancy when the ability to produce humoral immunoglobulin is thought to be low.

Amino Acid Sequence↗

Inhibitory effect of dideoxyforskolin on cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin in MDCK cells.

We have found that 1,9-Dideoxyforskolin (DDF) strongly inhibited the cell death induced by ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in MDCK cells, suggesting that these protein toxins have a DDF-sensitive common pathway leading to cell death. However, no significant effect of forskolin on these toxins was observed, implying that cAMP-independent DDF specific mechanism is responsible for the inhibitory effect. The protective effect of DDF against ricin-induced cell death was significantly reversed by the increase in extracellular Ca2+ concentrations. The addition of brefeldin A (BFA) also reversed the protective effect of DDF, while BFA alone slightly increased the cytotoxicity of ricin. The protein synthesis inhibitory activity of modeccin was strongly inhibited by DDF, while only partial inhibition of the activities of ricin and diphtheria toxin was observed. However, the activity of Pseudomonas toxin was enhanced by DDF rather than inhibited. Thus, the process leading to cell death and protein synthesis inhibition by these toxins may be separately affected by DDF, and the protective effect of DDF against toxin-induced cell death is distinct from its effect on protein synthesis inhibition by toxins. Forskolin and DDF slightly increased rather than inhibited the binding and the internalization of ricin to MDCK cells. Despite the strong inhibitory effect of DDF on toxin-induced cell death, DDF did not block toxin-induced DNA fragmentation. These results suggest that DNA fragmentation and cell death may be triggered through separate pathways during apoptosis caused by these toxins, and that a DDF-sensitive specific step may be present in the pathway leading to cell death.

Animals↗

Synthesis and antitumor activity of fused quinoline derivatives. IV. Novel 11-aminoindolo[3,2-b]quinolines.

Indolo[3,2-b]quinoline derivatives (1) having various amine moieties were prepared and their antitumor activities against P388 leukemia in mice were evaluated, for the purpose of gaining an insight into the role of the amine moiety in the antitumor activity and searching for an effective amine moiety. Introduction of a methylene group between the phenyl group and amino or methanesulfonamido group resulted in decrease or loss of activity.

Animals↗

Generation of reactive oxygen species by raphidophycean phytoplankton.

Chattonella marina, a raphidophycean flagellate, is one of the most toxic red tide phytoplankton and causes severe damage to fish farming. Recent studies demonstrated that Chattonella sp. generates superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH), which may be responsible for the toxicity of C. marina. In this study, we found the other raphidophycean flagellates such as Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica also produce O2- and H2O2 under normal growth condition. Among the flagellate species tested, Chattonella has the highest rates of production of O2- and H2O2 as compared on the basis of cell number. This seems to be partly due to differences in their cell sizes, since Chattonella is larger than other flagellate species. The generation of O2- by these flagellate species was also confirmed by a chemiluminescence assay by using 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA). All these raphidophycean flagellates inhibited the proliferation of a marine bacterium, Vibrio alginolyticus, in a flagellates/bacteria co-culture system, and their toxic effects were suppressed by the addition of superoxide dismutase (SOD) or catalase. Our results suggest that the generation of reactive oxygen species is a common feature of raphidophycean flagellates.

Animals↗

Cell lysis induced by ricin D and ricin E in various cell lines.

Ricin D, one of the two isolectins from small caster beans showed stronger cytotoxicity than another one, ricin E, based on the inhibition of colony formation and the inhibition of protein synthesis. Both ricin D and ricin E induced cell lysis to different extents in each cell line tested, albeit ricin E was slightly less effective than ricin D. DNA fragmentation, a characteristic feature of apoptosis, was also induced by ricin D and ricin E in Vero cells. Scatchard plot analysis showed that ricin D binds to cells with higher affinity than ricin E, while the number of binding sites per cell was not much different, suggesting that the differences in the cytotoxicity between ricin D and ricin E is mainly due to their differential binding affinity to cells. In Vero cells, the cytolytic activities of ricin D and ricin E were inhibited by brefeldin A (BFA), which is known to effect the Golgi apparatus, but not significant effect of BFA was observed in a BFA-resistant cell line, MDCK cells. These results suggest that the Golgi apparatus may be involved in ricin-induced cell lysis.

Animals↗

Novel extracellular alkaline metalloendopeptidases from Vibrio sp. NUF-BPP1: purification and characterization.

We found two types of novel alkaline metalloendopeptidases (AP1 and AP2) from a marine bacterium, isolated from the intestine of a five-barred goatfish (Parupeneus trifasciatus) and identified as Vibrio sp. (NUF-BPP1). We studied the structure-function relationship of these marine bacterial proteases. The electrophoretically homogeneous proteases had a molecular mass of 48 kDa for AP1 and 36 kDa for AP2 on SDS-PAGE, and showed optimum activity at around pH 9.5-10.0 (casein as substrate). Calcium chloride (5 mM) stabilized the activities over pH 6-11, but o-phenanthroline and EDTA inhibited the activities of both AP1 and AP2. The EDTA-inactivated proteases were partly restored to activity by addition of either zinc or calcium. Sodium chloride (3.5 M) increased the activities toward Z-Gly-Leu-NH2. N-Terminal sites of hydrophobic amino acid residues (Leu, Ile, Phe, Tyr, and Trp) of the peptide substrates were cleaved by AP1 and by AP2. Autolysis of AP1 in the absence of calcium ion probably produced AP2 by releasing a fragment (molecular mass of about 12 kDa) from the C-terminal end of AP1.

Amino Acid Sequence↗

N-type calcium channel blockers from a marine bacterium, Cytophaga sp. SANK 71996.

N-(3-Acyloxyacyl)glycines were isolated as N-type calcium channel blockers from a marine bacterium Cytophaga sp. SANK 71996. The identification and fermentation of the producing strain and structure characterization of N-(3-acyloxyacyl)glycines by spectral analyses and chemical syntheses are described together with their antagonistic activities.

Animals↗

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗

[Heart valvular disease in patients 70 years old and older].

From June 1986 to December 1996, 69 patients older than 70 years old underwent AVR (29 cases), MVR (21 cases), MVP (5 cases), DVR (10 cases), aortic root replacement (3 cases), repair of PVL (1 case) in our hospital. There are five (7.2%) operative and hospital deaths. The survival rate was 88.4% at 10 year after surgery and three (4.7%) late deaths. The factors associated with early deaths were renal dysfunction and DVR. Our surgical results suggest that open heart surgery can be performed safely even elderly patients, in spite of their precarious physiologic homeostasis. Not the chronological age but the physiological age is important determinant for surgical indication. If quality of life (QOL) can be expected to be enhanced, we recommend an aggressive surgical approach.

Age Factors↗

Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression.

Ropivacaine, a new local anesthetic, is currently being investigated for the treatment of ulcerative colitis, with promising results so far. The aim of this study was to examine anti-inflammatory properties of ropivacaine with regard to its effects on vascular permeability and inflammatory leukocyte behavior in vivo. The effects on leukocyte rolling, firm adhesion and vascular permeability were examined in the hamster cheek pouch microvasculature via intravital microscopy, and the effects on leukocyte adhesion molecules were examined in vitro by means of flow cytometry. In large venules, leukocyte adhesion induced by topical leukotriene B4 (LTB4) was almost completely inhibited during the combined application of ropivacaine and LTB4. The spontaneous rolling leukocyte flux was reduced by 72%, the rolling leukocyte fraction by 47% and the total leukocyte flux, which reflects blood flow, by 47%. In postcapillary venules, ropivacaine abolished rolling and LTB4-induced firm adhesion of leukocytes. LTB4 challenge also resulted in increased plasma exudation that was almost completely inhibited by ropivacaine. Moreover, ropivacaine inhibited the tumor necrosis factor alpha-induced up-regulation of CD11b/CD18 and L-selectin shedding by human leukocytes in vitro. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated to a significant extent by inhibition of both leukocyte rolling and adhesion.

Amides↗

Ectopic bone formation after total hip arthroplasty.

Two hundred and forty consecutive Japanese patients with 280 primary total hip arthroplasties (THA) were analyzed to clarify the incidence of ectopic bone formation and its predisposing factors and to examine its effect on the clinical results. Ectopic bone formation after THA was found in 61 joints (22%). The predisposing factors were male patients and a hypertrophic type of osteoarthritis. It was revealed that extensive ectopic bone formation, class 3 according to Brooker's classification, restricted flexion and abduction motion of the hip joint.

Adult↗

Concentration of levofloxacin in cervical mucus and its clinical effects on cervicitis.

An investigation was made on the concentration of levofloxacin (LVFX) in cervical mucus and its clinical effects on cervicitis. The results were as follows: 1) The concentrations of orally administered LVFX in the cervical mucus of 110 subjects were determined by HPLC. During 1-4 hour after the administration the mean concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g, which was higher than the serum level. The transfer of LVFX to the cervical mucus was almost the same as that to other genital organs. 2) When LVFX was given to 102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was evaluated with clinical improvement, the clinical efficacy rate of LVFX was 72/102 (70.6%). Significant bacteriological effects were observed in 70/73 (95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%). 3) The administration LVFX did not cause any subjective or objective side effects and any abnormalities were not detected in the laboratory test done in this study. These results demonstrate that LVFX can be sufficiently transferred to the cervical mucus for the treatment of cervicitis due to the infection of C. trachomatis etc.

Adult↗

Purification and characterization of a (1-->3)-beta-D-glucan-binding protein from horseshoe crab (Tachypleus tridentatus) amoebocytes.

A novel (1-->3)-beta-D-glucan-binding protein (T-GBP) has been purified from the amoebocyte lysate of the Japanese horseshoe crab, Tachypleus tridentatus. It is a basic protein (pI 9.2) which appears to be a homotetramer composed of subunits with an apparent mol wt of 168000 and with an amino-terminal sequence (20 residues) KSGFILTAPKSLTLGRNNRL. T-GBP exerted an inhibitory effect on the (1-->3)-beta-D-glucan-initiated coagulation cascade reconstituted with purified preparations of factor G and the proclotting enzyme from the lysate. The binding of (1-->3)-beta-D-glucans to T-GBP was evaluated by measuring the residual amidolytic activity of the clotting enzyme, the product of the coagulation cascade, using Boc-Leu-Gly-Arg-4-nitroanilide as the chromogenic substrate. The binding specificity of a wide range of (1-->3)-beta-D-glucans and other polysaccharides towards T-GBP was expressed by the relative inhibition (%) of the activation of factor G, the first protease zymogen in the pathway, which is activated by binding to (1-->3)-beta-D-glucans. T-GBP was found to have a high affinity for linear (1-->3)-beta-D-glucans, e.g. pachyman, curdlan, and paramylon. It was able to bind to (1-->3)-beta-D-glucans with side-chain branches and mixed linkage such as schizophyllan, lentinan, laminarins, yeast beta-D-glucan, and (1-->3),(1-->4)-beta-D-glucans such as lichenin and barley beta-D-glucan. Binding of pachyman to T-GBP was demonstrated by an enzyme-linked immunosorbent assay using a specific antibody (rabbit IgG) raised against T-GBP.

Amino Acid Sequence↗

In vitro association with peroxisomes and conformational change of peroxisomal serine:pyruvate/alanine:glyoxylate aminotransferase in rat and human livers.

To understand the targeting mechanisms of peroxisomal serine:pyruvate aminotransferase, in vitro import experiments were carried out using this 43 kDa peroxisomal enzyme, which was synthesized in a coupled transcription/translation system. Being different from other peroxisomal enzymes, such as acyl-CoA oxidase and urate oxidase used in previous in vitro import experiment, the soluble form of peroxisomal serine:pyruvate aminotransferase was fairly resistant to proteinase K digestion. However, the enzyme recovered in the peroxisomal fraction was proteinase K sensitive. This indicates that the association of peroxisomal serine:pyruvate aminotransferase with the peroxisomal membrane causes a marked conformational change in the structure of this protein.

Alanine Transaminase↗

Mutual sensitization of ATP and GTP in driving F-actin on the surface-fixed H-meromyosin.

Using an in vitro motility assay on acto-H-meromyosin, we studied the sliding velocity of an actin filament driven by two kinds of H-meromyosin heads: H-meromyosin head with ATP bound (fast motor) and with GTP bound (slow motor). We found a significant increase in the sliding velocity owing to the coexistence of the fast motor and the slow motor. This phenomenon may give an important suggestion with regard to the integration over multiple interactions of H-meromyosin heads along the actin filament.

Actins↗

Lack of mutagenicity of diethylstilbestrol metabolite and analog, (+/-)-indenestrols A and B, in bacterial assays.

Indenestrol A (IA), one of metabolites of the indanyl group of diethylstilbestrol, has a stronger binding affinity for the estrogen receptor and also a weaker uterotropic activity than endogenous estradiol. We tested the microbial mutagenicity of structural isomers of indenestrol A and indenestrol B (IB) in Salmonella typhimurium TA100 and TA98 and in Escherichia coli WP2 uvrA to investigate whether the interaction of diethylstilbestrol or IA with genomic DNA has any part in their carcinogenicity and other biological activities. In the absence of S9 mix, (+/-)-IA was cytotoxic at higher doses (1 and 10 mumol/plate), and both (+/-)-IA and (+/-)-IB were non-mutagenic at lower doses (0.1-100 nmol/plate). In the presence of S9 mix, (+/-)-IA was cytotoxic at higher doses (0.5 and 1 mumol/plate), and at the other doses, (+/-)-IA and (+/-)-IB did not show any distinct increase in revertants. Although (+/-)-IA and (+/-)-IB showed a slight increase in the revertants in strain TA100 by the preincubation method without S9 mix, these results were considered to be negative, because no reproducible dose-revertants relationship necessary for a chemical to be determined as mutagenic was obtained. The S9 fraction interacted with (+/-)-IA or (+/-)-IB enzymatically or non-enzymatically, and weakened its cytotoxicity, so that the toxic dose was higher in the presence of S9 mix than in its absence. Both the plate incorporation and preincubation methods were used with a wide range of concentrations of (+/-)-IA and (+/-)-IB in the present experiment. No clear positive mutagenic data were obtained. These results are the first reports on the mutation assays of (+/-)-IA and (+/-)-IB, and suggest that they were non-mutagenic towards the bacterial strains tested. The study revealed that the cytotoxic activity of (+/-)-IA and (+/-)-IB did not correlate with DNA interaction, but was the result of a direct effect on microtubule polymerization, although indenestrols are known to have strong binding affinities for estrogen receptors.

Animals↗