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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 325 records · Page 18Linked to original sources
PubMed1996

Lead nitrate inhibits the induction of CYP1A mRNAs by aromatic amines but not by aryl hydrocarbons in the rat liver.

The effects of lead nitrate on the induction of hepatic cytochrome P450IA (CYP1A) isoforms, mainly CYP1A2, by aromatic amines (2-methoxy-4-aminoazobenzene, 2-amino-3-methyl-9H-pyrido [2,3-b]indole and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and aryl hydrocarbons (3-methylcholanthrene, benzo[a]pyrene and beta-naphthoflavone) in male F344 rats were examined at the levels of mRNA, protein and activity of the enzymes. Pretreatment of rats with lead nitrate suppressed the expression of hepatic CYP1A enzyme(s), especially CYP1A2, at both levels of protein and activity of the enzyme(s) by treatment with an aromatic amine or an aryl hydrocarbon. On the other hand, the lead nitrate pretreatment suppressed the induction of CYP1A mRNA(s) by an aromatic amine but not by an aryl hydrocarbon. These findings indicate that lead nitrate suppresses the expression of CYP1A enzymes at both stages of post-translation of mRNAs and transcriptional activation of the genes, and further suggest that the pathway for the transcriptional activation of the CYP1A genes by the aromatic amines is different from that by the aryl hydrocarbons.

Animals↗
PubMed1996

Crystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins.

The crystal structure of Escherichia coli B glutathione synthetase (GSHase) has been determined at the optimal catalytic condition pH 7.5. The most significant structural difference from the structure at pH 6.0 is the movement of the central domain towards the N-terminal domain almost as a rigid body. As a result of this movement, new interdomain and intersubunit polar interactions are formed which stabilize the dimeric structure further. The structure of GSHase at optimal pH was compared with 294 other known protein structures in terms of the spatial arrangements of secondary structural elements. Three enzymes (D-alanine: D-alanine ligase, succinyl-CoA synthetase and the biotin carboxylase subunit of acetyl-CoA carboxylase) were found to have structures similar to the ATP-binding site of GSHase, which extends across two domains. The ATP-binding sites in these four enzymes are composed of two antiparallel beta-sheets and are different from the classic mononucleotide-binding fold. Except for these proteins, no significant structural similarity was detected between GSHase and the other ATP-binding proteins. A structural motif in the N-terminal domain of GSHase has been found to be similar to the NAD-binding fold. This structural motif is shared by a number of other proteins that bind various negatively charged molecules.

Acetyl-CoA Carboxylase↗
PubMed1996

Protection against reperfusion-induced arrhythmias by human thioredoxin.

Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-active half-cysteine residues in an exposed active center. Human thioredoxin has many biological activities, including growth promotion, cell activation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x 10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence of ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of 75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively (NS). During the entire reperfusion period, the incidence of VF in the SOD group was 79%, as compared to 83% in the control group. In the catalase and TRX-II groups, the incidence of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of approximately 0.1 micro was the most effective.

Animals↗
PubMed1996

Endothelium-dependent relaxation by alpha 2-adrenoceptor agonists in spontaneously hypertensive rat aorta.

Differences in alpha(2)-adrenoceptor-induced relaxation of the aorta between stroke-prone spontaneously hypertensive rats (SHRSP) and control normotensive Wistar Kyoto rats (WKY) were studied. Changes in the tension of ring preparations of the aortas were measured isometrically. Relaxation was observed in the preparations precontracted in the presence of ONO-11113, a thromboxane A(2) analogue. The alpha(2)-agonist clonidine and UK-14304 induced dose-dependent relaxation in both the WKY and SHRSP preparations. The relaxation was impaired in the SHRSP preparation. A modified sandwich experiment showed that the relaxing substance from the SHRSP endothelium was decreased. Acetylcholine (ACh) also induced dose-dependent relaxation, and the relaxation was impaired in the SHRSP preparations. alpha(2)-Agonists induced a greater degree of impairment in the relaxation than did ACh. The relaxation induced by alpha(2)-agonists and by ACh was blocked by N G-nitro-L-arginine (L-NNA). Indomethacin improved the relaxation induced by ACh but not that induced by alpha(2)-agonists in the SHRSP aortas. These results suggest that the impairment of relaxation by alpha(2)-agonists in SHRSP is not caused by the increase in the release of endothelium-derived contracting factor (EDCF) but by the reduction in the release of nitric oxide (NO). Alteration of the alpha(2)-adrenoceptors and/or the intracellular mechanism through which NO is synthesized by stimulation of the alpha(2)-adrenoceptors may be the cause of the reduction in relaxation.

Acetylcholine↗
PubMed1996

Proposal for a new comprehensive classification of V-Y plasty and its analogues: the pros and cons of inverted versus ordinary Burow's triangle excision.

Burow's triangle excision is often used in V-Y plasty to facilitate the advancement of the V flap. The technique also seems to help reduce unsightly scarring. We devised an alternative technique to Burow's triangle excision, i.e., an inverted Burow's triangle excision. Sometimes the inverted Burow's triangle excision seems to be more effective for both purposes. In this paper we propose a new comprehensive classification of V-Y plasty and its analogues such as V-M, V-W, or five Z-plasty based on a new concept, the appropriate use of Burow's and inverted Burow's triangle excision and other criteria. The applications of these designs are discussed.

Burns↗
PubMed1996

Role of cell surface glycosaminoglycans of human T cells in human immunodeficiency virus type-1 (HIV-1) infection.

To investigate the role of cell surface glycosaminoglycans (GAGs), including heparan sulfate (HS), on HIV-1 infection in human T cells, HIV-1 binding and infection were determined after treatment of T-cell lines and CD4+ T cells from normal peripheral blood mononuclear cells (PBMC) with GAG-degrading enzyme or a GAG metabolic sulfation inhibitor. Heparitinase I (hep I) and sodium chlorate prevented binding of HIV-1/IIIB to MT-4 cells as revealed by indirect immunofluorescence procedures, thereby inhibiting infection. Hep I was less effective in the binding inhibition of the macrophage-tropic strain HIV-1/SF162 than that of the T-cell line-tropic strain HIV-1/IIIB. The binding of HIV-1/SF162 was about 100-fold less dependent on cell surface HS than HIV-1/IIIB. Human HTLV-I positive T-cell lines expressed more HS than HTLV-I negative T-cell lines or normal CD4+ T cells when stained with anti-HS mAbs against either native or heparitinase-treated HS. With the exception of endo-beta-galactosidase (endo-beta-gal), GAG-degrading enzymes, including hep I, chondroitinase ABC (chon ABC), chondroitinase AC II (chon AC II) and keratanase, did not prevent the binding of HIV-1/IIIB to CD4+ T cells from normal PBMC. These results indicate that the cell surface HS of human T cells participates in HIV-1 infection by facilitating HIV-1/IIIB binding to MT-4 cells. In particular, the sulfation of HS chains is critical. Since the expression of cell surface HS varies among T cells, which are not consistently sensitive to hep I treatment in HIV-1 binding inhibition, other GAG-like molecules may also be involved.

CD4-Positive T-Lymphocytes↗
PubMed1996

A new magnetically suspended centrifugal pump: in vitro and preliminary in vivo assessment.

To overcome problems derived from the shaft within the conventional centrifugal pump, we have been developing a new centrifugal pump, namely a magnetically suspended centrifugal pump (MSCP), which has no shaft and operates as a noncontacting and bearingless pump. The impeller is suspended magnetically between the magnetic bearing and the driving motor. Hemolysis tests were performed in comparison with the Biopump (BP80, BioMedicus). The index of hemolysis (IH) was significantly lower in the MSCP than in the Biopump. In addition, a smaller gap in the MSCP induced lower hemolysis. In preliminary studies using mongrel dogs, the layer of thrombus adherent to the impeller was observed in a few hours, which impaired the pumping efficiency. However, by using an impeller coated with silicone, no aggregations of platelets or fibrin on the impeller were observed in 24 h of continuous pumping. In conclusion, the MSCP had a gentler influence on blood cells than the Biopump, and the impeller coated with silicone may contribute to the long-term pumping of the MSCP.

Animals↗
PubMed1996

Recommendation of early surgery from the viewpoint of daily quality of life.

We surveyed pre- and postoperative levels of satisfaction with a range of the daily quality-of-life (QOL) domains in 132 sets of epilepsy surgery patients and their families. All patients underwent resective surgery for temporal lobe epilepsy and were monitored for > 2 years. Patient and family assessments showed patients' overall QOL markedly improves after surgery, depending on freedom from seizures. However, factors such as social contacts, family relations, or financial status improved little. Some families and patients were not satisfied with the postsurgical status, despite freedom from seizures. Patients who had surgery at a later age were not so satisfied with their postsurgical status as were patients who had surgery at a younger age, particularly on the QOL domains of role activities, memory function, leisure activities, or emotional well-being. This lower satisfaction level in older patients likely results from a variety of problems affecting patients during the long-lasting epileptic process; social handicaps, psychologic conflicts, and deterioration of cognitive/behavioral functions. Based on each case, we recommend that investigations start at an early stage of the illness, so that surgical intervention may be considered as early as possible.

Activities of Daily Living↗
PubMed1996

Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway.

We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes.

Alternative Splicing↗
PubMed1996

Natriuretic peptide receptors in human artery and vein and rabbit vein graft.

Natriuretic peptides elicit their biological effects by elevation of cGMP through activation of two biologically active receptors: natriuretic peptide A receptor, which shows high affinity to atrial and brain natriuretic peptides, and natriuretic peptide B receptor, which is specific to C-type natriuretic peptide. To elucidate the implications of the natriuretic peptide system in arteries and veins, we examined the cGMP production in response to atrial and C-type natriuretic peptide and gene expressions of biologically active natriuretic peptide receptors in human gastroepiploic artery, internal mammary artery, and saphenous vein. Atrial natriuretic peptide augmented cGMP production more potently by one order of magnitude in arteries than in veins. C-type natriuretic peptide stimulated cGMP production weakly and equally in these vessels. Analyzed by reverse transcription-polymerase chain reaction, gene expression of natriuretic peptide A receptor was four times more abundant in arteries than in veins. Gene expression of natriuretic peptide B receptor was approximately the same between these vessels. We also studied the responsiveness to atrial and C-type natriuretic peptide in rabbit jugular vein grafted into carotid artery. In arterialized vein grafts 4 weeks after operation, the effects of atrial and C-type natriuretic peptides on cGMP production did not change from those in jugular veins. In conclusion, atrial natriuretic peptide stimulates cGMP production more potently in arteries than in veins due to the preferential expression of natriuretic peptide A receptor in arteries. These observations support the distinct roles of natriuretic peptides in cardiovascular homeostasis.

Aged↗
PubMed1996

Dose-dependent gastrointestinal absorption of 5-fluorouracil in rats in vivo.

Dose-dependent gastrointestinal absorption of 5-fluorouracil (5-FU) was kinetically evaluated in rats in vivo by analyzing gastrointestinal disposition after oral administration, where a linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (Ka). With an increase in dose from 1.5 nmol/rat (low dow) to 15 mumol/rat (high dose), the Ka decreased from 5.95 to 0.55 min-1, suggesting the involvement of carrier-mediated transport. This study is the first to demonstrate the dose-dependent gastrointestinal absorption of 5-FU in vivo, though it has long been suggested in situ and in vitro. Meanwhile, at both the low and high doses, the Kg values, which were unaffected by dose (0.069 and 0.082 min-1, respectively, for the low and high doses), were smaller than the Ka values by an order of magnitude or more and the recovery of 5-FU was negligible, compared with that of inulin (a nonabsorbable marker), in the most distal segment of ileum. These results suggest that, regardless of dose, 5-FU is highly absorbable in a gastric emptying-limited manner. Thus, well-publicized bioavailability problems (low and erratic) of 5-FU may be attributable to extensive and variable first-pass metabolism rather than poor and variable gastrointestinal absorption.

Animals↗
PubMed1996

Disposition of intravenously administered adenosine 5'-phosphosulfate (APS) in rats.

The disposition of adenosine 5'-phosphosulfate (APS), an endogenous nucleotide, was investigated in rats. The degradation of APS in rat plasma was very rapid. APS was degraded in rat plasma to AMP and ATP, and these nucleotides were further degraded through adenosine. The degradation kinetics was examined. For the in vivo study, the method to protect APS from degradation in blood was examined, and it was found that the addition of EDTA to APS-containing blood and storage at 4 degrees C can protect against APS degradation. After intravenous bolus injection, APS in plasma declined rapidly and the rate of elimination was dose-dependent: the biological half-life was about 2s at the dose of 0.3 mg/kg and was longer at 3 mg/kg. When APS was administered by intravenous infusion, the plasma level rapidly reached a steady-state, which then rapidly declined after the infusion was stopped. The total body clearance of APS could not be fully explained by metabolism in plasma or glomerular filtration, therefore the contribution of other elimination processes to the total body clearance was suggested.

Adenosine Phosphosulfate↗
PubMed1996

Blood pressure and age-dependent changes of endothelium-dependent tension oscillations in different strains of spontaneously hypertensive rats.

The influence of blood pressure and age of spontaneously hypertensive rats on endothelium-dependent tension oscillation of aortic preparation were studied. Rats with different blood pressures, normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and malignant type of SHRSP (M-SHRSP), were used. The effects of antihypertensive treatment of SHRSP on the tension oscillation were also studied. High doses of noradrenaline induced tension oscillations in endothelium-intact preparations of all strains of young rats. The rate of the occurrence of the tension oscillation decreased age-dependently. The decrease was faster when the blood pressure of the rats was higher. Application of acetylcholine in the presence of noradrenaline induced a relaxation and tension oscillations, both of which were negatively dependent on age and blood pressure. Antihypertensive treatment of hypertensive rats with hydralazine or captopril prevented a decrease in incidence of the tension oscillation. These influences of age and blood pressure as well as antihypertensive treatments on the tension oscillation resembled those on the endothelium-dependent relaxation and are thought to be brought about by functional changes of the endothelium.

Acetylcholine↗
PubMed1996

Evaluation of mental strain by palm sweating during short-term memory task.

This paper reports on the investigation of palm sweating during short-term memory tasks and testing the availability of the amount of palm sweating for an index evaluating mental strain. Six male subjects performed sets of thirty tasks with digit strings ranging from 4 to 9 digits at random order. The correctness of recalled answer, subjective difficulty for mental stress and palm sweating at each task were recorded. The amount of palm sweating (PS) was measured using hygrometry with a ventilated capsule attached on the left palm. Correct answer rates suddenly decreased over 7 digits. Subjective difficulty tended to increase with an increase in string-length. PS tended to decrease exponentially with the repetition of tasks at each string-length, and the exponential regression curve was fitted between PS and order in tasks at each string-length. Estimated PSs were obtained at 1st, 15th, and 30th tasks from the regression curves. Estimated PS at 1st task tended to increase in proportion to string-length. Each estimated PS at both 15th and 30th tasks had a threshold for increasing. Also, estimated PS increased in proportion to the string-length at no less than the threshold. The thresholds were 5 digits at 15th and 6 digits at 30th task. These present findings suggest that PS is an index available for measuring mental strain. Also, this index describes the level quantitatively in adaptation for mental stress.

Adult↗
PubMed1996

Changes in tissue contents of zinc, copper and iron in rats and beagle dogs treated with polaprezinc.

Zinc, copper and iron levels of tissues in rats or beagle dogs were measured after a 13- or 52-week toxicity study of polaprezinc, which contains a zinc element. The zinc content in almost all rat tissues remarkably increased with a conspicuous decrease of copper and various changes of iron at doses of 600 mg/kg/day or more. Zinc and copper levels increased and decreased respectively, at 300 mg/kg/day. At a dose of 150 mg/kg/day, there was a slight increase of zinc in some tissues at 52-weeks, but no copper decrease. The results obtained from beagle dogs differed somewhat from that in rats. Dogs treated with polaprezinc at 50 mg/kg/day or more accumulated zinc in some tissues. A copper decrement was seen only in the liver and heart from the group given 300 mg/kg/day, whereas copper levels in the kidney of all treated groups were higher than that in the control, suggesting that canine polaprezinc toxicity is due to direct zinc toxic effects.

Animals↗
PubMed1996

Effect of food intake on the delivery of fluorescein as a model drug in colon delivery capsule after oral administration to beagle dogs.

The effect of food on the release time of a model drug, fluorescein (FL), has been studied after oral administration to beagle dogs in colon delivery capsule in comparison to conventional gelatin capsule and enteric capsules. The dose of FL was 30 mg for each animal. After oral administration of each test preparation in fasted or postprandial condition (100 grams of commercial solid food was given at 30 min before drug administration), blood samples were collected and plasma FL concentrations were measured spectrofluorometrically. Pharmacokinetic analysis was performed with plasma FL concentration vs. time data and the following parameters were determined; Tmax (the time when plasma FL concentration reaches to its maximum concentration), Cmax (peak plasma FL concentration), Tlag (the time when FL appeared at first into the systemic circulation), AUC (area under the plasma FL concentration vs. Time curve) and MRT (mean residence time). For gelatin capsule, mean Tmax appeared at 0.83 +/- 0.33 (S.E.) h after administration and MRT was 2.67 +/- 0.21 h in fasted condition. By feeding, Tmax and MRT increased to 1.50 +/- 0.76 h and 3.09 +/- 0.49 h. For two enteric HPMCP and Eudragit S capsules, MRT were 2.90 +/- 0.48 h and 5.24 +/- 0.32 h in fasted condition, and 11.30 +/- 1.10 h and 12.83 +/- 0.34 h in postprandial condition, respectively. Tlag also increased by postprandial administration. As colon delivery capsule, time-controlled release capsule (TCC) and two types of intestinal inner pressure-controlled release capsules (PCC) (#1 is a separate type and #2 is a seamless one) were tested. MRT of TCC was 4.76 +/- 0.29 h and 6.43 +/- 0.66 h in fasted and postprandial conditions, respectively. This capsule did not receive the effect of food intake. For #1 PCC, MRTs were 5.32 +/- 0.22 h and 12.28 +/- 0.26 h in fasted and postprandial conditions, respectively. For #2 PCC, MRTs were 5.51 +/- 0.26 h and 13.36 +/- 0.84 h in fasted and postprandial conditions, respectively. In addition, the effect of two times feedings was studied with two PCCs and longer MRTs, 28.44 +/- 1.39 h and 26.32 +/- 1.64 h, were obtained. The release time of FL from PCCs increased by postprandial administration. As compared to the results on two enteric capsules, these PCCs are thought to disintegrate in the colon. However, TCC is thought to disintegrate in the stomach after postprandial administration.

Administration, Oral↗
PubMed1996

Attenuation of intrinsic active tone by endothelium-derived nitric oxide in aortae of spontaneously hypertensive rats with different levels of blood pressure.

The influences of endothelium on the basal tone of aortae from various strains of spontaneously hypertensive rats with different blood pressure (SHR, SHRSP, M-SHRSP) were studied. Endothelium-intact preparations of aortae from spontaneously hypertensive rats exhibited spontaneous active tone, which was greater in the order of SHR < SHRSP < M-SHRSP. The active tone of the M-SHRSP preparations was about 40% of high-K(+)-induced contraction, while that of normotensive WKY was less than 5%. The active tone was enhanced by the removal of endothelium. The active tone was sensitive to extracellular Ca2+ and abolished by verapamil. The application of N(G)-monomethyl-L-arginine caused the increase in the active tone which was counteracted by L-arginine. These results indicate that the active tone of smooth muscle increases as the blood pressure of the rat increases, and that endothelium attenuates the active tone by releasing nitric oxide (NO) spontaneously. It was also demonstrated that the attenuating action of endothelium was impaired depending on the blood pressure level.

Animals↗