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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 1,081 records · Page 60Linked to original sources
PubMed1987

Expression of a provirus of human T cell leukaemia virus type I by DNA transfection.

We isolated the full length provirus of human T cell leukaemia virus type I (HTLV-I) from MT-2, a lymphoid cell line producing HTLV-I. In three non-lymphoid cell lines (COS7, human osteosarcoma HOS cells, and HeLa) this provirus expressed a trans-acting activity after co-transfection with a recombinant plasmid carrying a bacterial chloramphenicol acetyltransferase gene under the control of a long terminal repeat of HTLV-I provirus. The trans-acting protein p40 was detected by immunoprecipitation in transfected HOS cells. Structural proteins of HTLV-I, the gag and env products, were also formed and processed in the same manner as observed in MT-2 cells. In transfected HeLa cells, the p40 protein was mainly localized in the nucleus, while other structural proteins were detected in the cytoplasm and/or the membrane by indirect immunofluorescence. Syncytium formation was observed in HeLa cells after transfection. These results demonstrated that non-lymphoid cells could produce the major proteins of HTLV-I after DNA transfection of the cloned provirus.

Antigens, Viral↗
PubMed1987

Identification of a temperature-resistant bacteriophage phi X174 mutant.

Bacteriophage phi X174am3trD, a high temperature-resistant mutant of phi X174am3, was 10(4) times more stable than phi X174am3 as judged by its survival ratio after heat treatment at 54 degrees C for 120 min. Complementation tests showed an involvement of gene G. Sequence analysis of this gene revealed three mutation sites, one transition and two insertions. The first was a silent mutation and the others brought about a change in one amino acid and an addition of another, respectively, in the gene G protein. These changes in amino acid sequence resulted in a change in the secondary structure of the protein. A beta-turn region in part of the gene G protein of phi X174am3 was changed to an alpha-helix in phi X174am3trD. These results indicate that the temperature resistance of phi X174am3trD may be caused by elevated hydrophobicity in the mutated region or by strong interaction between the mutated gene G protein and other capsid proteins.

Amino Acid Sequence↗
PubMed1987

Cardiac function of patients with essential hypertension during exercise and isoproterenol infusion.

The left ventricular function of patients with essential hypertension was examined during exercise and isoproterenol (ISP) infusion echocardiography. Twenty-eight hypertensive patients without cardiac hypertrophy (Group NH), 20 patients with cardiac hypertrophy (Group HH), 7 patients with cardiac dilatation (Group D), and 13 normotensives (Group N), were studied during multistage exercise using a supine bicycle ergometer. In addition, 23 hypertensives (Group NH: 13 patients, Group HH: 10 patients) and 10 normotensives were studied during ISP infusion (0.005 microgram/kg/min, and 0.01 microgram/kg/min, respectively, for 5 min). To assess the left ventricular function, an M-mode echocardiogram was utilized at rest and during exercise and ISP infusion. At rest, the isovolumic relaxation time (IRT) of each hypertensive group was significantly longer than that of Group N. IRT of Group HH and Group D was significantly longer than that of Group NH. Only the shortening fraction (SF) of Group D was significantly smaller than that of Group N. During exercise the SF increased in all groups, and only the SF of Group D was significantly smaller than that of Group N at a load of 75 W as well as at rest. The SF of Group HH tended to be smaller. There was no significant difference in peak negative dD/dt (-dD/dt) between any of the groups at rest; however, the -dD/dt of Group HH was significantly smaller than that of Group N during ISP infusion. We concluded that left ventricular diastolic function was disturbed in each hypertensive group at rest. Diastolic dysfunction worsened in Group HH and Group D. Only the left ventricular systolic function of Group D was already depressed at rest. Furthermore, unmanifested systolic dysfunction of the left ventricle seemed to be present in Group HH, because SF during exercise tended to be smaller and -dD/dt during ISP infusion was significantly smaller than that of Group N.

Adult↗
PubMed1987

16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.

The protective effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) against early damage induced by indomethacin in the rat gastric mucosal surface epithelial cells was studied using a scanning electron microscope. Indomethacin (10 or 25 mg/kg, p.o.) induced a widespread exfoliation of the surface epithelial cells and an exposure of the lamina propria both in the corpus and antrum within 1 hr after the administration. Pretreatment with dmPGE2 (0.3, 3 or 30 micrograms/kg, p.o.) 30 min before indomethacin (25 mg/kg) dose-dependently inhibited these damages. The effects of dmPGE2, at least on the surface epithelial cells in the corpus, appear to be related to the prevention of damage formation itself and is unrelated to the enhancement of reconstitution of once damaged mucosa. Enhanced gastric motility by indomethacin was potently inhibited by pretreatment with 3 and 30 micrograms/kg of dmPGE2, but not with 0.3 micrograms/kg. dmPGE2 pretreatment (30 micrograms/kg) significantly decreased the absorption of indomethacin (25 mg/kg) when determined 10 min after giving indomethacin, but did not affect it when determined 30 and 60 min later. We conclude that dmPGE2 protects gastric mucosal surface epithelial cells from indomethacin injury at an early stage, partly by inhibiting gastric motility.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Comparison of agonistic and antagonistic actions of guanabenz and guanfacin on alpha 1 and alpha 2-adrenoceptors in isolated smooth muscles.

The effects of guanabenz, guanfacine and clonidine on alpha-adrenoceptors were investigated in isolated rat vas deferens and rabbit aortic strip. All 3 drugs at low concentrations (10(-9)-10(-8) M) caused inhibition of twitch responses of the rat vas deferens induced by nerve stimulation. These effects were competitively antagonized by yohimbine. Guanfacine and clonidine at relatively high concentrations (10(-6)-10(-4) M) produced contractions of the rat vas deferens which were antagonized by prazosin. These contractile responses were not much affected by denervation. Prazosin-sensitive contractions by guanfacine and clonidine were also observed in the rabbit aortic strip, which were not affected by reserpine pretreatment. In both tissues, the intrinsic activity of guanfacine was almost identical to that of norepinephrine, whereas that of clonidine was less than one half. Guanabenz and clonidine showed a competitive antagonistic effect against norepinephrine and phenylephrine in both the rat vas deferens and rabbit aorta, the antagonisms being similar in potency. The results indicate that all 3 drugs are potent agonists on the presynaptic alpha 2-adrenoceptor. In contrast, on the postsynaptic alpha 1-adrenoceptor, guanfacine and guanabenz showed only agonistic and antagonistic actions, respectively, whereas clonidine exhibited partial agonistic characteristics.

Adrenergic alpha-Agonists↗
PubMed1987

Effects of prostaglandin biosynthesis inhibitors and ouabain on duodenal mucosa and HCO3- secretion in rats.

A single injection (s.c.) of prostaglandin biosynthesis inhibitors such as indomethacin (5 mg/kg), aspirin (200 mg/kg) and quinacrine (100 mg/kg) or a Na+.K+ ATPase inhibitor such as ouabain (10 mg/kg) significantly reduced the adaptive increase of HCO3- output caused by acid in the duodenum of anesthetized rats. These agents had no effect on basal duodenal HCO3- secretion and histamine-stimulated gastric acid secretion. Either of these agents, when given alone, had no effect on the duodenal mucosa of conscious rats, but produced damage in the proximal duodenum within 8 hr when given together with histamine (40 mg/kg X 3, s.c., every 2.5 hr). A significant relationship was found between the degrees of inhibition of acid-induced HCO3- output and the severity of duodenal lesions induced by these drugs (r = 0.8620, P less than 0.01). These results suggest that an impairment of the mechanisms related to acid-induced HCO3- secretion may be particularly relevant to the pathogenesis of duodenal lesions.

Animals↗
PubMed1987

Impairment of acid-neutralizing capacity and lesion formation in the rat duodenum during hemorrhagic shock: comparative study with indomethacin.

The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10(-4) M HCl, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCl. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (approximately 8 microEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16-dimethyl prostaglandin E2 (16-dmPGE2: 30 micrograms/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCl for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 significantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of HE on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins.

Acid-Base Equilibrium↗
PubMed1987

Roles of gastric motility changes in cytoprotection induced by acetazolamide and cysteamine in rats.

The present study was undertaken using acetazolamide (AZ) and cysteamine (Cys) to investigate the relationship between gastric motor activity and the phenomenon of "cytoprotection" in rats. Both AZ (10-100 mg/kg) and Cys (10-100 mg/kg), given either p.o. or s.c., significantly reduced the formation of gastric mucosal injury caused by HCl-ethanol (1 ml of 60% ethanol in 150 mM HCl, p.o.). The protective effect of Cys appeared within 10 min, reached the maximal levels 30 min later, while that of AZ appeared from 30 min after administration and became potent with a latency period after treatment. Neither indomethacin (IM: 5 mg/kg, s.c.) nor N-ethylmaleimide (NEM: 5 mg/kg, s.c.) significantly affected the protective effect of Cys, whereas that of AZ was almost totally antagonized by IM. Both AZ and Cys, given either intragastrically or s.c., significantly inhibited gastric motor activity measured as intraluminal pressure recordings, but had minimal effect on acid and alkaline secretion. IM significantly attenuated the inhibitory effect of AZ on the motor activity, while NEM did not affect the inhibited motor responses caused by AZ and Cys. A significant relationship was found between the inhibitory effects of these two drugs on gastric motor activity and HCl-ethanol-induced mucosal injury, the correlation coefficient being 0.819 (P less than 0.01). When the mucosal folds were visualized with Gentian Violet (1 ml of 0.5% v/v, p.o.), both AZ and Cys significantly prevented the localized staining along the mucosal folds, suggesting dissolution of the folds. These results suggest that both AZ and Cys protect the gastric mucosa against injury caused by HCl-ethanol, probably through a dissolution of mucosal folds due to inhibition of gastric motor activity.

Acetazolamide↗
PubMed1987

Cytoprotective action of histamine against 0.6 N HCl-induced gastric mucosal injury in rats; comparative study with adaptive cytoprotection induced by exogenous acid.

We examined the effects of histamine 2HCl (a stimulator of endogenous acid production) and exogenous acid on transmucosal potential difference (PD) and pH of anesthetized rat stomachs, in order to investigate the mechanism underlying the protective action of histamine against 0.6 N HCl-induced gastric mucosal injury in conscious rats. Subcutaneously administered histamine (3-20 mg/kg) dose-dependently produced a decrease in the PD and pH, and it reduced the severity of gastric mucosal injury caused by 0.6 N HCl. Both indomethacin (5 mg/kg, s.c.) and cimetidine (100 mg/kg, s.c.) completely reversed the protection afforded by histamine (20 mg/kg), although the decreased PD and pH responses were unaffected or inhibited, respectively, by indomethacin or cimetidine. Protective action of histamine was also partially mitigated by omeprazole (30 mg/kg, s.c.) which completely abolished histamine-induced acid secretion. On the other hand, exposure of the stomach for 10 min to exogenous acid (0.1-0.35 N HCl) caused a PD reduction and an increase of pH, in a concentration-related manner. The injury caused by 0.6 N HCl was prevented by prior exposure to these low concentrations of HCl, and the degrees of inhibition were associated with the concentration of HCl and the magnitude of PD reduction caused by HCl. The pretreatment with indomethacin, but not cimetidine or omeprazole, significantly antagonized the increased pH and mucosal protection induced by 0.35 N HCl. These results suggest that histamine protected the gastric mucosa against 0.6 N HCl-induced injury by two different ways, mediated with endogenous prostaglandins, (a) mainly through stimulation of H2-receptors and (b) partly through adaptive cytoprotection induced by acid.

Adaptation, Physiological↗
PubMed1987

Effect of 16,16-dimethyl prostaglandin E2 on gastric surface epithelial cell damage induced by 20% ethanol in rats.

Prostaglandins protect against the gross damage of gastric mucosa induced by 50-100% ethanol, but do not protect surface epithelial cells (SEC) from necrosis. Since this induced damage to SEC is so severe, we attempted to determine the effects of a prostaglandin on slightly induced SEC damage and gastric potential difference (PD) in response to low concentrations of ethanol. The necrotizing effects of graded concentrations of ethanol (10-50%) to SEC on the rat gastric mucosa were studied by scanning electron and light microscopy. Intragastric instillation of 20% ethanol (v/v, 1 ml/100 g body wt.) to pylorus-ligated rats for 10 min induced slight and reproducible SEC damage consisting mainly of the apical cell membrane erosion of SEC. Pretreatment with 16,16-dimethyl prostaglandin E2 (dmPGE2, 3 or 30 micrograms/kg, p.o. or s.c.) afforded protection of the SEC from 20% ethanol-induced damage. However, the cytoprotective effects of dmPGE2 were abolished when gastric contents were emptied prior to 20% ethanol instillation. Intragastric instillation of ethanol immediately reduced PD in a concentration-related manner. dmPGE2 (3 or 30 micrograms/kg, s.c.) had no effect on the reduction of gastric PD after 20% ethanol treatment and the recovery of reduced PD to normal levels. We conclude that dmPGE2 has no cytoprotective effect on 20% ethanol-induced SEC damage in rat gastric mucosa.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Long-term effects of aldosterone on kallikrein, prostaglandin E2 and sodium in rats.

To assess the long-term effects of mineralocorticoids on the regulation of the synthesis or release of kallikrein and prostaglandin E2 in the renal kallikrein-kinin-prostaglandin E system, we studied the effects of chronic infusion of aldosterone (50 micrograms/kg/day) on urinary excretion of total and active kallikrein, and prostaglandin E2 for 10 days in conscious rats on regular intakes of sodium and on sodium loading with 1% NaCl as a drinking water. Chronic infusion of aldosterone induced a prompt and transient decrease in the ratio of sodium to potassium and a sustained increase in urinary prostaglandin E2 excretion in rats on regular diets, whereas urinary total and active kallikrein excretion did not increase significantly until the 4th day of aldosterone infusion. In rats loaded with sodium, aldosterone did not induce any changes in urinary total and active kallikrein excretion, whereas it induced similar changes in the ratio of sodium to potassium and urinary prostaglandin E2 excretion to those in rats on regular diets. Thus, the present results suggest that aldosterone might stimulate the synthesis or release of renal prostaglandin E2 independent of sodium balance. Furthermore, it is also suggested that aldosterone might stimulate the synthesis or release of kallikrein, at least partly, via the same pathway as sodium loading does.

Aldosterone↗
PubMed1987

Mutagenicity tests of the antithyroid agent thiamazole. Cytogenetic studies on male mice.

The mutagenic potential of thiamazole, an antithyroid agent, was investigated by an in vivo cytogenetic test and was compared with those of mitomycin C and vincristine. These drugs were subcutaneously injected into slc-ICR male mice either as a single dose or as multiple doses for 5 successive days. Thiamazole (90 or 180 mg/kg) did not increase the number of micronuclei in bone marrow cells. This drug also did not induce chromosomal aberrations in spermatogonium, spermatocyte, or bone marrow cells. On the other hand, mitomycin C (3.0 mg/kg) increased the appearance of chromosomal aberrations and micronuclei. Vincristine (0.2 mg/kg) induced bone marrow cells with a so called large micronucleus (d greater than or equal to D/4). These results suggest that thiamazole may not have significant effects on the genetic systems of mice.

Animals↗
PubMed1987

Cytogenic analysis of dominant lethal effects of mitomycin C and ethyl methanesulfonate.

To gain further insight into the mechanism of induction of dominant lethal mutations, the relationship between chromosome aberrations in bone marrow and in male germ cells after treatment with mitomycin C (MMC) and ethyl methanesulfonate (EMS) was examined. In addition, we obtained fertilized eggs from the oviducts of crossbred female mice in the same way as in the dominant lethal mutation test, and examined chromosome aberrations in male pronuclei. MMC 2.5 and 5.0 mg/kg, EMS 175 and 350 mg/kg were given subcutaneously to slc-ICR mice. It was concluded that MMC causes a decrease in the sperm count by killing germ cells, which in turn causes an increase in the number of unfertilized eggs and preimplantation egg loss. MMC seems also to cause invisible damages in the chromosomes of spermatocytes which lead to dominant lethality. EMS induced chromosome damage in the post-meiotic germ cells, and this damage, in turn, produced chromosome aberrations in the eggs, resulting in a high incidence of dominant lethality.

Animals↗