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Biomedical subjects

M Taniguchi

Publications and source records attributed to M Taniguchi.

At least 865 records · Page 48Linked to original sources

Effects of N-nitrosodimethylamine (NDMA) on the oxidative status of rat liver.

To investigate oxidative effects of N-nitrosodimethylamine (NDMA) on the liver, rats were challenged by the reagent with a dose range of 10 to 40 mg/kg. With lower dose levels, protective responses were prominent, such as elevation of the hepatic glutathione and metallothionein (MT) levels. Increased activities were also evident of gamma-glutamylcysteine synthetase, glucose-6-phosphate dehydrogenase (G6PD), and malic enzyme. In the high dose range, however, toxic responses, such as increases in lipid peroxide levels in liver and serum, and glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and ketone bodies in serum became marked. Some of the protective responses became less marked at the highest dose. Catalase and glutathione peroxidase activities in the liver were also inhibited by NDMA treatment. On the other hand, when NDMA was injected as a series of doses (10 mg/kg on four separate occasions), the effects were less marked, and the hepatic levels of MT and lipid peroxide remained unchanged even after the 4th injection. Only the increase in G6PD activity was more marked after four times repeated injection than after a single injection. These results suggest that oxidative and hepatotoxic effects of NDMA are more moderate when given in repeated doses than in a single dose. In contrast to the liver, elevation of MT levels was the only detectable change in the kidney.

Animals↗

NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.

Complementary and genomic DNAs isolated from the fibroblasts of 10 Japanese (7 late infantile, 2 juvenile, and 1 adult form of the disease) and one Caucasian patient with Niemann-Pick disease type C were analyzed for mutations in the NPC1 gene. Fourteen novel mutations were found including small deletions and point mutations. A one-base deletion and a point mutation caused splicing errors. The mutations were not clustered in any particular region of the gene and were found both in and out of the transmembrane domains. Three patients were homozygous, five were compound heterozygous, and the remaining three were suspected of being compound hetrozygous with an unknown error in one of their NPC1 alleles. Of the 14 mutations, the G1553A substitution that caused a splicing error of exon 9 appeared to be relatively common in Japanese patients, because two patients were homozygous and one patient was compound heterozygous for this mutation.

Adolescent↗

Bupivacaine-induced convulsion is suppressed by MK-801.

BACKGROUND AND OBJECTIVES: Not only the facilitation of inhibitory synapses but also the suppression of excitatory synapses may be effective in treating convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and hemodynamic changes were studied. METHODS: Cortex and hippocampal (A4; L5.5; H8) electroencephalogram (EEG), heart rate, and mean arterial pressure were measured in 21 cats anesthetized with urethane. Blood samples were obtained when cats demonstrated arrhythmias, convulsed, and became hypotensive. In the control group (n = 7), bupivacaine was continuously infused until a hypotensive state of 40 mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously 15 minutes before the bupivacaine injection. In the MK-801 treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the appearance of convulsive EEG after the bupivacaine injection. RESULTS: Bupivacaine produced convulsion in the control group (17.1 +/- 2.4 microg/mL), but not in the MK-801 pretreated group. In the treatment group, convulsive EEG was suppressed gradually after injection of MK-801. The mean plasma bupivacaine concentrations (microg/mL) reaching arrhythmia and hypotension were 9.5 +/- 2.9 and 23.0 +/- 3.0, respectively, in the control group; 10.9 +/- 3.5 and 22.5 +/- 4.9, respectively, in the MK-801 pretreated group; and 7.5 +/- 1.6 and 21.0 +/- 3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and heart rate did not differ among the three groups. CONCLUSIONS: These results demonstrated that one mechanism of bupivacaine-induced convulsion is the excitatory neurotransmitter system in central nervous system and that MK-801 is effective in suppressing the convulsion without any effects on hemodynamics.

Anesthetics, Local↗

Polygodial, an antifungal potentiator.

A series of sesquiterpene dialdehydes was isolated from the East African medicinal plants Warburgia stuhlmannii and Warburgia ugandensis (Canellaceae) as antibiotics, particularly against Saccharomyces cerevisiae, Candida utilis, and Sclerotinia libertiana. Among these sesquiterpene dialdehydes, polygodial [1] exhibited the most potent activity. When tested on S. cerevisiae, polygodial proved to be fungicidal rather than fungistatic. When the cells of S. cerevisiae are treated in vitro with polygodial for 10 min, the cell membrane becomes severely damaged, and many vesicles, possibly formed from the fragmented cell membrane, can be observed within the cytoplasm. The observation of cell membrane lesions led us to propose a rather innovative hypothesis: the use of polygodial to facilitate the transmembrane transport of exogenous chemicals into cells. For example, polygodial could be combined with an antibiotic having poor cell membrane permeability in an effort to increase its antibiotic activity by increasing its ability to gain entrance into the cell. We report here that a remarkably enhanced efficacy was obtained when actinomycin D was used in combination with polygodial. We believe polygodial may be acting as an "advance scout," punching holes in the plasma membrane and gaining an entrance into the cell for an antibiotic previously less effective because of problems with cell membrane permeability.

Antifungal Agents↗

I-J as an idiotype of the recognition component of antigen-specific suppressor T-cell factor.

The I-J determinant of membrane glycoprotein is known to be expressed exclusively on suppressor T cells (TS), which have a crucial role in the regulation of immune responses. I-J also comprises part of the soluble factor (TSF) with suppressor activity which is secreted from TS. Gene-mapping experiments have indicated that the I-J gene lies between the I-A and I-E subregions of the mouse major histocompatibility complex (MHC) and is defined by the H-2 congeneic pair, that is, B10.A(3R) and B10.A(5R). In fact, antibodies raised in the reciprocal combinations of B10.A(3R) and B10.A(5R) define the I-Jb and I-Jk alleles, and are able to detect the I-J determinants on TS and TSF. Biochemical and functional analyses, using I-J-positive TS clones and hybridomas, have demonstrated that monoclonal anti-I-J antibodies precipitate I-Jk or I-Jb with a relative molecular mass of 25,000-28,000 (25-28K) and that the I-J+ molecule mediates the restriction specificity of TSF in association with an antigen-binding protein (45K). However, molecular genetic studies on the I-J gene reveal no genetic difference between B10.A(3R) and B10.A(5R) and also that there is no room to accommodate a gene encoding I-J in the expected I region. These discrepancies between the molecular genetic and serological/functional data require explanation. Here we demonstrate that TS and TSF expressing I-J of the host type were produced by fully allogeneic bone marrow cells of donor origin in chimaeric mice, when the chimaeras received the host antigen-presenting cells (APC) at the time of immunization. The results show that APC are necessary for the activation and clonal expansion of TS and also support the notion that I-J is an idiotypic determinant of the recognition component of TS and TSF.

Animals↗

Syngeneic monoclonal antimelanoma antibodies and their application for analysis of tumor antigens, gene cloning, and in vitro/in vivo diagnosis.

In this article, we summarized syngeneic monoclonal antimelanoma antibodies and their application for chemical characterization of mouse melanoma antigens, cloning of genomic DNA controlling antigen expression, and in vivo/in vitro tumor diagnosis. The melanoma antigen is composed of a protein complex in association with GM3(NeuAc)-like sugar moiety. The GM3 structure expresses the cross-species epitopes shared in various mammalian species, whereas the mouse specific melanoma epitope is present on protein molecules. By using the monoclonal antimelanoma reactive with GM3 epitope, we developed a very sensitive sandwich radioimmunoassay system detecting soluble melanoma antigens equivalent to 10(2)-10(3) cells/ml. The antibody was also useful in imaging tumor in vivo. These results indicate that the antibody with cross-species reactivity has a potential for tumor targeting. The monoclonal antibody M562 recognizing protein molecule with species specific epitope but not other antimelanoma antibodies, however, effectively inhibited experimental lung metastasis of melanoma cells, indicating that the M562 epitope seems to possess important biological functions. Recently, the genomic DNA controlling the antigen expression was successfully isolated by DNA transfection and expression technique with monoclonal anti-melanoma M562 and the fluorescence-activated cell sorter. We also found that genomic DNA possesses transformation-related activity in NIH3T3 cells.

Amino Acids↗

The role of alpha-galactosylceramide-activated Valpha14 natural killer T cells in the regulation of Th2 cell differentiation.

Valpha14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-gamma upon stimulation with a ligand, alpha-galactosylceramide (alpha-GalCer), and play a crucial role in various immune responses, including allergic diseases. Interestingly, Valpha14 NKT cells are not essential for the induction of IgE responses but rather induce suppression of specific IgE production upon activation. The suppression in the IgE production is not detected either in Valpha14 NKT cell-deficient mice or in IFN-gamma-deficient mice. Thus, activated Valpha14 NKT cells are likely to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-gamma. In marked contrast, little regulatory effect of IL-4 produced by Valpha14 NKT cells on Th2 cell differentiation is suggested.

Animals↗

Middle cerebral artery occlusion: correlation of computed tomography and angiography with clinical outcome.

The clinical outcome of 40 cases with middle cerebral artery (MCA) occlusion was examined in relation to the site of occlusion and the findings on computed tomography (CT). Patients were treated conservatively without surgery. A few had decompressive craniotomy when necessary. Outcome in 7 (18%) was good, in 6 (15%) moderate, and in 15 (38%) severe; 12 (30%) died by the follow-up at 3 months. In cases with occlusion at the origin of the MCA, hypodensity on CT scan was usually localized to the basal ganglia, presumably because of collateral circulation through the anterior cerebral arteries; the outcome in these patients was not always favorable. Cases with occlusion of the trunk or branch vessels always showed marked CT hypodensity, and clinical outcome was poor. To assess quantitatively the extent of collateral circulation, the conduction time of contrast medium from the intracranial siphon (IC) to the insular portion of the MCA (M2) through the anterior cerebral arteries was calculated on serial carotid angiograms obtained within 24 hours after stroke onset. An IC-M2 time of 5 seconds was a critical indicator of whether extensive CT hypodensity would develop (the rule of 5 seconds). Furthermore, this method predicted the appearance and extent of infarction before CT revealed hypodensity. The significance of acute reconstructive surgery is also discussed.

Aged↗

A new apparatus for chronic intravenous infusion in unrestrained rats.

A new apparatus incorporating a unique type of swivel device was devised for chronic intravenous infusion in unrestrained rats. The swivel requires very little torque for rotation, ie, one-fourth that of the standard swivel, yet is 1/30 as expensive. A coil spring tube, located between the swivel and the catheter, allows the rat unhampered movement within the metabolic cage. Because the catheter follows the rats' movements freely, only two silk sutures are required to secure it to the animal. No statistically significant differences between experimental and control rats were observed in terms of body weight gain, food intake, nitrogen balance, or caloric efficiency. This apparatus should prove useful in many areas of research.

Animals↗

Localization of the bronchodilatory effects of isoproterenol and aminophylline in patients with bronchial asthma: an investigation using selective alveolobronchography.

The effect of isoproterenol (isoprenaline) and aminophylline on airway calibre in 18 adult patients with bronchial asthma was measured directly using selective alveolobronchography. Isoproterenol caused a significant dilation in the maximal calibre of the central airway from bifurcation numbers 1-5 (P < 0.05) and number 6 (P < 0.01). There was no change in bifurcation number 0 (trachea). Aminophylline caused a significant dilatation in bifurcation numbers 3 and 4 (P < 0.01), with no change in bifurcation numbers 0-2 and 5-6. In the minimal calibre of the central airway, both drugs displayed a significant dilatory effect only at bifurcation number 3 (P < 0.05). These results indicate that the central airway is the main site of the dilatory effects of these drugs. Although their precise mechanisms of action are not known, these results suggest that mechanisms of action of the two drugs are different. Isoproterenol acts on the whole region of the central airway, while the action of aminophylline tends to be limited to bifurcation numbers 3 and 4.

Adult↗

Prevention of azoxymethane-induced intestinal tumors by a crude ethyl acetate-extract and tryptanthrin extracted from Polygonum tinctorium Lour.

The effect of a crude ethyl acetate (AcOEt)-extract and tryptanthrin extracted from the Indigo plant (Polygonum tinctorium Lour.) on azoxymethane (AOM)-induced intestinal tumors was examined in F344 rats. The rats were given subcutaneous (s.c.) injections of either AOM (15 mg/kg body weight (b.w.)) once a week for 3 weeks to induce atypical crypt foci (ACF) as a known cancer precursor, or AOM (7.5 mg/kg b.w.) once a week for 10 weeks to induce intestinal tumors. The rats were also administered the AcOEt-extract (500 mg/kg b.w.) or tryptanthrin (50 mg/kg b.w.) orally, 5 days a week, for 7 or 30 weeks, starting two days before the first administration of AOM. All rats were killed 4 or 20 weeks after the last treatment. In the short-term experiment, the incidence of ACE and atypical crypts (AC) in the groups receiving the AcOEt-extract and tryptanthrin was significantly lower than in the control group. In the tumor-inducing experiment, intestinal tumor incidence in the tryptanthrin group was lower than in the AOM-control group (5% versus 26%), and small intestine tumor incidence in the AcOEt-extract and tryptanthrin groups were lower than in the AOM-control group (0% and 0% versus 23%). These results show that the AcOEt-extract of Indigo and tryptanthrin have cancer chemopreventive activity.

Acetates↗