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Biomedical subjects

S Tanabe

Publications and source records attributed to S Tanabe.

At least 289 records · Page 16Linked to original sources

Decreased hypothalamic and medullary GABA turnover in spontaneously hypertensive rats.

OBJECTIVE: The aim was to assess whether Gamma-aminobutyric acid (GABA) neurone activities in the central nervous system, especially in the hypothalamus and medulla oblangata, are altered in hypertension. METHODS: Central GABA content and turnover rate were measured in spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY). GABA content was determined with high performance liquid chromatography, and in vivo GABA turnover rates were estimated by GABA accumulation after injection of amino-oxyacetic acid, a selective inhibitor of GABA degrading system. Two groups of nine week old male rats (32 SHR and 32 WKY) were used. RESULTS: GABA concentrations in cerebrospinal fluid were lower in SHR than in WKY. Since hypothalamus and medulla oblongata are the possible active sites of this system, basal GABA contents and in vivo GABA turnover rates were measured in hypothalamus and medulla oblongata. Basal GABA content in the medulla oblongata and hypothalamus was almost equal in SHR and WKY. On the other hand, GABA turnover rates were significantly lower in SHR than in WKY in both the hypothalamus and the medulla. CONCLUSIONS: Since it is known that GABA is an inhibitory neurotransmitter in the central nervous system and that it controls autonomic and cardiovascular activities, the findings suggest that the decreased hypothalamic and medullary GABAergic activities may permit sympathetic hyperactivity to contribute to the increase in blood pressure in SHR.

Aminooxyacetic Acid↗

Biochemical studies on oral toxicity of ricin. IV. A fate of orally administered ricin in rats.

After oral administration of ricin in rats, its distribution in the gastrointestinal tract, body fluids and principal organs was determined by an enzyme immunoassay, and the immunoreactive ricin detected was identified by gel filtration followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, protein blotting and the immunobinding method. When ricin D (10 mg/kg rat) was given orally to a rat, which dose is equivalent to 1/3 LD50, about 75% of the ricin was found in the stomach and small intestine within 2 h, and most of it was transferred to the large intestine after 24 h. It was also demonstrated by an in vitro toxicity test of immunoreactive ricin in the blood and lymph obtained from the intoxicated rats that a part of the ricin was absorbed from the small intestine into the tissues and organs via the circulatory systems (lymphatic and blood vessels) as the active ricin. The participation of the blood vessels was greater in the absorption of ricin from the gastrointestinal tract than that of the lymphatic system. Ricin, after absorption, was detected in liver and spleen and ricin found in the liver was predominantly in the form of intact ricin, although an undetectable amount of ricin in other organs cannot be eliminated. These results infer that a small fraction of orally-given ricin was transferred to the circulating system and was responsible for rat's death as in the case of i.p. administration.

Administration, Oral↗

Biochemical studies on oral toxicity of ricin. V. The role of lectin activity in the intestinal absorption of ricin.

In order to investigate a possible role of lectin activity of ricin in its absorption from the small intestine, we prepared two ricin derivatives. BMH-ricin, prepared by crosslinking A and B chains of ricin with 1,6-bismaleimidohexane, was nearly non-toxic but the lectin activity was unaltered. And, NBS-ricin, prepared by the oxidation of tryptophanyl residues of ricin with N-bromosuccinimide, was not only non-toxic but also non-lectinic. After the oral administration of ricin derivatives to rats, their interaction with the digestive tract and absorption into the circulatory systems have been compared with those of ricin, immunochemically and histologically. It was shown by immunostaining that ricin and BMH-ricin could bind to the intestinal mucosa, whereas NBS-ricin could not. No appreciable damage in the small intestine from rats treated with either BMH-ricin or NBS-ricin has been observed, in contrast to ricin treatment where severe impairment of the small intestinal tissues resulted after 5 h. Immunoreactive ricin in the liver has been determined with the ricin enzyme immunoassay (EIA). When compared at 48 h after oral administration, NBS-ricin was not detected, whereas BMH-ricin was found to be 38 micrograms/liver and ricin 100 micrograms/liver. From these results, it was inferred that the lectin activity of ricin plays an important role in the absorption of ricin from the small intestine and that the absorption of ricin protein was enhanced by its high toxicity.

Administration, Oral↗

Effects of calphobindin II (annexin VI) on procoagulant and anticoagulant activities of cultured endothelial cells.

Effects of human placental calphobindin II (CPB-II) on the protein C activation and prothrombin activation on the cell surface of cultured calf pulmonary arterial endothelial cells have been investigated. CPB-II inhibited thrombin generation by factor Xa bound to the surface of the cultured endothelial cells in a dose-dependent manner. The amount (IC50) of CPB-II causing the inhibition at 50% was estimated to be approximately 10 nM. CPB-II was found to be ineffective, however, in the protein C activation by thrombin-thrombomodulin (TM) complex on the cell surface. Assay using purified TM revealed that CPB-II was able to exhibit the inhibitory potency for the protein C activation exclusively in the reconstituted system with negatively charged phospholipids. These results suggest that the neutral phospholipids participate in the protein C activation through the thrombin-TM system on the endothelial cell surface. The ability of CPB-II to inhibit procoagulant activity without affecting anticoagulant activity on the cultured endothelial cells is probably related to its potential physiological function, while it is able to exert various degrees of influence upon these activities in blood coagulation by interacting with negatively charged phospholipids in vitro.

Amino Acid Sequence↗

High performance liquid chromatographic determination of bound sulfide and sulfite and thiosulfate at their low levels in human serum by pre-column fluorescence derivatization with monobromobimane.

A sensitive and specific high performance liquid chromatographic method for the determination of sulfide, sulfite, and thiosulfate was established. Inorganic sulfur anions were converted into fluorescent derivatives with monobromobimane. The derivatives were separated on a coupled column chromatography with a reversed-phase octadecyl silica column connected with a weakly basic anion exchanger column by isocratic elution with acetic acid solution (pH 3)-acetonitrile (13:3, v/v) containing 25 mM NaClO4. The method was applied to the determination of bound sulfide and sulfite and thiosulfate in normal human serum. Thiosulfate could be determined directly by use of an ultrafiltered sample. For the determination of bound sulfide and sulfite, the pretreatment step with continuous flow gas dialysis was effective for the sample after releasing sulfide and sulfite by reduction with dithiothreitol. The limits of quantification by the present method were 0.05 microM for thiosulfate, 0.5 microM for bound sulfide, and 0.2 microM for bound sulfite.

Bridged Bicyclo Compounds↗

Interaction of toxic lectin ricin with epithelial cells of rat small intestine in vitro.

To clarify the mechanism of oral toxicity of ricin, the interaction of ricin with the epithelial cells isolated from rat small intestine was compared in vitro with those of other plant lectins by two different determinations, i.e., viability and cytotoxicity. After incubation of the cells for 1 h at 37 degrees C with ricin, B-chain, castor bean hemagglutinin (CBH), soybean agglutinin (SBA), wheat germ agglutinin (WGA), concanavalin A (Con A), and peanut agglutinin (PNA), respectively, followed by staining with trypan blue, ricin and ricin B-chain as well as CBH and SBA were found to have effectively reduced the number of viable cells. On the contrary, only ricin inhibited protein synthesis in the cells and the effect was blocked by D-galactose. Additional experiments employing [125I]-labeled ricin strongly suggested that ricin was first bound via its B-chain to the galactosyl residues on the cell surface followed by internalization into cells as the whole 62 kDa molecule. These results infer first that ricin, as well as other lectins mentioned above, was able to reduce viability of the epithelial cells of rat small intestine by direct binding to the cell surface. The second effect, specific to ricin, was the inhibition of cellular protein synthesis.

Animals↗

Role of sympathetic nerve inhibition in the vasodepressor effect of bromocriptine in normotensive and hypertensive rats.

This study aimed to elucidate the mechanism of the hypotensive effect of bromocriptine (BRC), and to investigate whether or not the effects of BRC on the sympathetic nervous system are altered in hypertension. BRC was administered intravenously to normotensive and spontaneously hypertensive rats (SHR). It elicited hypotensive effects dose-dependently in urethane-anaesthetized normotensive rats, an effect which was antagonized with metoclopramide. Pretreatment with intravenous hexamethonium attenuated the hypotensive effect of BRC. BRC decreased plasma norepinephrine (NE) without inhibiting the sympathetic nerve spikes recorded from the postganglionic sympathetic nerve bundle. The hypotensive effect of BRC was significantly greater in SHR than in Wistar Kyoto Rats (WKY). Decrease in NE by BRC was also significantly greater in SHR than in WKY. These results suggest that the hypotensive effect of BRC is induced by suppression of NE release, not by inhibition of sympathetic nerve spikes, and that the dopaminergic presynaptic inhibition is attenuated in SHR.

Animals↗

[The limits of recovery in hydronephrosis. An experimental pathological study].

The object of this experimental study is to elucidate the limits of recovery in hydronephrosis. Hydronephrosis in the rabbit kidney was made by left ureteric ligation for 1, 2, 3 and 4 weeks, followed by relief of obstruction with uretero-ureteric anastomosis. Two and 4 weeks after relief, histopathological examination was performed. In proportion to the obstructive period, both proximal tubule and thin portion of Henle's loop showed atrophy of epithelial cells, multi-laminar thickening of basement membranes, and splitting between epithelium and basement membranes. The interstitium showed edema and subsequent fibrosis. These damages were thought to be due to severe ischemia, which such tubules did not recover and even showed more advanced damages after relief. On the other hand, thick portion of Henle's loop, distal tubule and collecting duct showed advanced compression atrophy and dilated lumen, while no severe ischemic damage was demonstrated. Therefore, after relief, they showed recovery, and, even in the case of no recovery, they showed no advanced damages. In hydronephrosis, severe ischemic damages brought about a loss of the ability of recovery.

Animals↗

Cytoprotective effect of dilazep on hydrogen peroxide-perturbed vascular endothelial cells.

The effect of dilazep and dimethyl thiourea (DMTU) on the hydrogen peroxide-derived injury of culture pulmonary artery epithelial cells (CPAEC) was assessed by colorimetric assay of MTT formazan (MTT formazan assay). When CPAEC were treated with hydrogen peroxide, neither cell lysis nor detachment of the cells from surface of the well was observed. However, the MTT formazan formation was decreased in a time and dose dependent manner. The decrease in the formation was significantly suppressed in the presence of dilazep (0.1 to 10 microM) or DMTU (0.01 to 0.3 microM). CPAEC treated with hydrogen peroxide in the same way enhanced an activation of prothrombin, and this enhancement was significantly inhibited in the presence of dilazep (1 to 3 microM). These data indicate that dilazep exerts a cytoprotective effect against challenges of intracellular oxidant produced by hydrogen peroxide and suppresses augmented procoagulant activity of injured cells.

Animals↗

Effect of manidipine on cardiac hypertrophy and coronary circulation in DOCA/salt hypertensive rats.

The effect of manidipine on cardiac hypertrophy, coronary circulation, left ventricular weight and maximal coronary flow in hypertension was measured in DOCA/salt treated systolic hypertensive rats with and without manidipine treatment. Normotensive rats were used as controls. After feeding with 0.05% manidipine-containing food, blood pressure was reduced only in DOCA/salt hypertensive rats, but not in control rats. After 3 weeks of treatment, sodium excretion was significantly increased in DOCA/salt-treated rats with or without manidipine treatment. Hearts were removed and perfused with modified Krebs-Henseleit solution with adenosine (5 x 10(-5) M) in a Langendorff apparatus. Maximal coronary flow (MCF) was significantly decreased only in DOCA/salt hypertensive rats without treatment, while manidipine treatment restored MCF. Left ventricular weight/body weight was also markedly greater in DOCA/salt-treated rats not given manidipine. Left ventricular weight in DOCA/salt-treated rats given manidipine was significantly reduced compared with DOCA/salt hypertensive rats without treatment, although it was heavier than in the control animals. Morphological examination showed that the increased wall/lumen ratio in DOCA/salt hypertensive rats was reduced by manidipine treatment. These findings suggest that treatment with manidipine in DOCA/salt hypertensive rats lowered high blood pressure and improved impaired coronary circulation with a reduction in left ventricular and vascular hypertrophy.

Aldosterone↗

3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors.

An amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluR1. Apparent EC50 of DHPG for mGluR1 was slightly lower than that of (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD). DHPG responses were partially inhibited by 2-amino-3-phosphonopropionic acid (AP-3). DHPG had no effect on ionotropic glutamate receptors whose expression was induced in the oocytes following injection of poly(A)+ mRNA of rat brains. In hippocampal slices, DHPG produced slow excitation of pyramidal cells, resulting from a depression of Ca(2+)-dependent K+ current and a voltage-dependent K+ current. These results indicate that DHPG is a specific and potent agonist of mGluRs.

2-Amino-5-phosphonovalerate↗

Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin's B-cell lymphomas.

Using three separate bcl-2 probes, we examined involvement of the bcl-2 gene in Japanese patients with non-Hodgkin's B-cell lymphomas. Of 52 patients with follicular lymphoma (FL), 24 had rearrangements. In a group of 50 patients with diffuse lymphoma, three of 32 patients with diffuse large cell lymphoma had rearrangements. The frequency of rearrangements in each of these groups, as detected by both major and minor breakpoint cluster region probes, was compatible with that found in other Far Eastern studies. However, the difference in frequency between the groups studied in the Far East and the West was significant, and these two geographically distinct populations also displayed a difference in the breakpoint distribution. In the immunophenotype study of 33 patients with FL, the expression of CD10 antigen correlated with bcl-2 involvement, whereas none of the other B markers emerged as parameters to distinguish between the two lymphoma groups; those with, and without, the rearrangements.

Humans↗

[Assessment of left ventricular function with ESS-ESVI relationship in patients undergoing aortic valve replacement for aortic regurgitation].

Aortic valve replacement (AVR) for aortic regurgitation (AR) results in the reduction of left ventricular dimensions. But postoperative death or congestive heart failure may occur in patients with left ventricular dysfunction. Pre- and postoperative stress (ESS)-volume (ESVI) relationship by M-mode echocardiography was examined in 30 patients undergoing AVR. Postoperatively, 23 patients (Group A) achieved a normal left ventricular dimension (LVDd less than 55 mm, LVDs less than 45 mm) and 7 patients (Group B) had persistent left ventricular dilation (LVDd greater than or equal to 55 mm, LVDs greater than or equal to 45 mm). Correlation between preoperative ESS and ESVI was significant (r = 0.92, p less than 0.001), and the ESS/ESVI was greater in Group A of 1.62 +/- 0.29 kdy/cm2/ml/m2 than in Group B of 1.18 +/- 0.19 kdy/cm2/ml/m2 (p less than 0.001). Three patients with ESVI greater than 180 ml/m2 and ESS/ESVI less than 1.2 kdyn/cm2/ml/m2 died after operation. Echocardiographic variables correlated with ESS/ESVI were ESVI (r = -0.57), FS (r = -0.53) and CSA (r = -0.47). The changes in LVDs (delta Ds) after AVR correlated with ESS/ESVI in 12 patients with severe left ventricular dilatation. Postoperative left ventricular function could be predicted by ESS-ESVI relationship by preoperative DBcAMP infusion test. ESS/ESVI is sensitive to changes in the left ventricular contractility. The patients with ESVI greater than 180 ml/m2 and ESS/ESVI less than 1.2 kdyn/cm2/ml/m2 may result in poor prognostic outcome.

Adolescent↗

Genomic organization of IgH gene compared with the expression of Bcl-2 gene in t(14;18)-positive lymphoma.

In three lymphoma cell lines carrying t(14;18), named FL-18, FL-218, and FL-318, the genomic organization of IgH gene was compared with the expression of bcl-2 gene; the t(14;18) of the FL-18 cells occurred downstream from the major breakpoint cluster region (mbr) of a bcl-2 gene, and that of the FL-218 and FL-318 cells within the mbr. The FL-318 expressed the normal-sized bcl-2 transcript of 8.5-kb mRNA having the noncoding region 3 to the mbr, which was found in the FL-18, and the FL-218 lacking the intact bcl-2 gene did not. This finding suggests that in t(14;18)-positive lymphoma having the breakpoint within the mbr, transcription of the nontranslocated bcl-2 allele is not necessarily silent. In addition, the FL-218 and FL-318 expressed aberrant bcl-2 transcripts and heterogenous IgH transcripts lacking the VH region, and the bcl-2 transcripts each comigrated with parts of the sterile IgH mRNAs. The FL-318, which did not exhibit switch recombination on either IgH allele, contained abundant amounts of l gamma mRNAs, a prerequisite for the recombination into the C gamma locus. One of the I-mRNA species comigrated with the aberrant bcl-2 transcript. The FL-18 and FL-218 lacking the I gamma mRNAs had completed switch recombination of both IgH alleles. This result raises a possibility that deregulated bcl-2 transcription caused by t(14;18) is capable of playing a role in class switch recombination of IgH gene.

DNA Probes↗

Experimental and clinical studies on heater probe hemostasis for upper gastrointestinal bleeding with special reference to comparison with ethanol injection.

The hemostatic effects in patients with upper gastrointestinal bleeding was evaluated using an endoscopic heater probe method and ethanol injection method. The heater probe method was effective in 94.4% of patients with few complications. The ethanol injection method was effective in 86.5% of patients. The heater probe method is considered to be an effective and safe technique in the treatment of upper gastrointestinal bleeding.

Adolescent↗

Continuous cardiac output determination by thermodeprivation.

A modified thermodilution catheter (KATS catheter) capable of monitoring continuous cardiac output by thermodeprivation and preserving its conventional function was devised. The KATS catheter has a thermistor incorporated closer to the tip of the catheter in addition to the usual thermistor used for conventional thermodilution. This additional thermistor is heated by a constant electric current but is capable of measuring its own temperature. The degree of heat deprivation is detected as the cooling of the thermistor, which is proportionally larger with larger blood velocity. Since blood flow is not the only source of heat deprivation, the actual formula was empirically derived by performing in vitro studies. Cardiac output can be determined by assuming the cross sectional area of the pulmonary artery is stationary. Calibration can be derived from a cardiac output measurement by the usual thermodilution method with the same catheter. The KATS catheter readings correlated significantly with conventional thermodilution values and electromagnetic flowmeter readings in anesthetized dogs. Continuous cardiac output measurement by the KATS catheter appears to be a promising technique.

Journal Article↗

Possible heterogeneity of metabotropic glutamate receptors induced in Xenopus oocytes by rat brain mRNA.

Pharmacological properties of metabotropic glutamate receptors were studied in Xenopus oocytes injected with rat brain mRNA. trans-1-Amino-cyclopentyl-1,3-dicarboxylic acid (t-ACPD), a conformationally restricted analog of glutamate, induced oscillatory inward currents in mRNA-injected oocytes. These t-ACPD responses showed several characteristics identical to those of the other metabotropic responses including the metabotropic glutamate responses stimulated by quisqualate. D,L-2-Amino-3-phophonopropionate (D,L-AP3) effectively suppressed the t-ACPD and ibotenate responses. However, quisqualate responses were not affected substantially by D,L-AP3. These findings suggest that the metabotropic glutamate receptors in the oocytes may be classified into at least two subtypes according to their pharmacological properties: one preferentially activated by quisqualate and insensitive to AP3, and the other activated by t-ACPD and ibotenate and antagonized by AP3.

Alanine↗

Distribution and behaviour of persistent organochlorine insecticides in paddy soil and sediments in the tropical environment: a case study in South India.

Paddy soil and sediment samples collected from the Vellar River watershed, Tamil Nadu state, South India from December, 1987 to January, 1989 were analysed to understand the comprehensive behaviour of organochlorine insecticides (HCH and DDT) in the tropical environment. HCH (BHC) showed higher levels in soil during wet season, reflecting the application of technical HCH largely during the flowering season of rice. On the other hand, DDT residues were low and did not show a significant seasonal trend in soil or sediment, indicating small quantities of DDT utilized at present for agricultural purposes in India. When compared to soil, the residue levels in sediments are low and the seasonal variation is less pronounced. This indicates that in tropical watersheds, the relative flux of residues into the aquatic environment is smaller than the amount volatilized to the atmosphere.

Journal Article↗