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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 901 records · Page 50Linked to original sources

Increased microvascular permeability and lesion formation during gastric hypermotility caused by indomethacin and 2-deoxy-D-glucose in the rat.

The relationship between lesion formation, gastric motility, and vascular permeability was examined in rats using indomethacin and 2-deoxy-D-glucose (2DG). Both indomethacin (25 mg/kg s.c.) and 2DG (100 mg/kg/h i.v.) produced gastric hypermotility and induced lesions, mostly confined to the rugal crests of the mucosal folds; the onset of hypermotility preceded appearance of the lesions in both cases. The mucosal microvascular permeability as determined by the amount of extravasated dye (Evans blue) was increased in response to these two agents, and the permeability responses also preceded appearance of the lesions. Both the increased vascular permeability and the severity of lesions were significantly reduced when the hypermotility was inhibited by pretreatment with atropine (3 mg/kg s.c.). The severity of the lesions were also markedly reduced or worsened, respectively, by hydrocortisone (10 mg/kg s.c.) or N-ethylmaleimide (10 mg/kg s.c.) at the doses that significantly decreased or enhanced the vascular permeability responses caused by indomethacin and 2DG. These results suggest that the enhanced gastric motility as induced by indomethacin and 2DG may cause microcirculatory disturbances in the specific sites of the mucosa (mucosal folds), probably by abnormal compression of the gastric wall, leading to the increased microvascular permeability and cellular damage.

Animals↗

Congenital fistula of the dural carotid-cavernous sinus: case report and review of the literature.

The case of a 2-month-old boy with a congenital fistula of the dural carotid-cavernous sinus is presented. This is a rare vascular anomaly in infancy, and it may cause acute changes in vision. The child was initially followed up for 1 year to see if spontaneous thrombosis would occur. The symptoms persisted, however, and intravascular surgery using platinum coils was performed for closure. After treatment, the symptoms completely resolved. Literature pertaining to this anomaly has been reviewed with particular emphasis on dural fistulas of the cavernous, transverse, sigmoid, and straight sinuses in infancy.

Arteriovenous Fistula↗

The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers.

cDNA fragments of a 5'-terminal region of the hepatitis C virus (HCV) genome were isolated by the reverse polymerase chain reaction from RNA extracted from plasma samples of healthy Japanese carriers. Their nucleotide sequence was compared with that of the original isolate which had been passaged twice in chimpanzees. No deletions or insertions were observed between the two sequences in the regions examined. Both the 5' untranslated and putative nucleocapsid (core) protein regions were highly conserved (99% and 91% nucleotide identities, respectively). In contrast, the region immediately downstream which encodes a putative envelope glycoprotein(s) showed only 74% nucleotide identity between the two isolates. At the polypeptide level, the core and envelope domains showed 97% and 75% amino acid identities, respectively. This envelope variation may reflect the adaptation of HCV to the different hosts and/or the result of immunological selection. The highly conserved nucleotide sequence of the 5' untranslated and core regions may play an important regulatory role in the life cycle of HCV.

Amino Acid Sequence↗

Role of accumulated gastric content in the pathogenesis of cysteamine- and mepirizole-induced duodenal ulcers in the rat.

Subcutaneous administration of cysteamine and mepirizole (at ulcerogenic and non- or weakly ulcerogenic doses) to fasted rats induced villous damage to the duodenum within 4 h. Only the damage induced by ulcerogenic doses progressed to macroscopically visible ulcers 10-12 h later. A considerable increase in gastric content was observed for more than 6-8 h after administration of the ulcerogenic dose of agents, but normal contents were noted 12 h later. The intraduodenal pH remained low for up to 16-20 h when ulcerogenic doses were given, but returned to control levels within 8-12 h when non-ulcerogenic doses were given. Histamine similarly caused villous damage to the duodenum, yet there was no progression to an ulcer. Accumulation of gastric contents and a lower intraduodenal pH with histamine persisted for only 2 h and 1 h, respectively. We conclude that prolonged accumulation of gastric contents for up to 8 h together with a decreased lower intraduodenal pH for 16-20 h are necessary for the developmental progression of villous damage to well-defined ulcers in the presence of ulcerogens.

Acid-Base Imbalance↗

Depressor mechanism of enalapril in rats made hypertensive by norepinephrine or vasopressin.

We evaluated the antihypertensive mechanism of enalapril, a long-lasting inhibitor of angiotensin-converting enzyme, in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The hypertensive effect of norepinephrine (1.8 mg/kg/day intraperitoneal (i.p.] or vasopressin (7.2 U/kg/day i.p.) was completely abolished by simultaneous administration of enalapril (6 mg/kg/day i.p.). The antihypertensive effect of enalapril was not reversed by simultaneous administration of subpressor doses of angiotensin II (36 and 100 micrograms/kg/day i.p.). However, the hypertensive effects of angiotensin II at pressor doses (600 and 900 micrograms/kg/day i.p.) in enalapril-infused rats were not different from those in vehicle-infused rats. These results indicate that the hypotensive effect of enalapril may in part depend on a reduced sensitivity of the vasculature to norepinephrine and vasopressin, independent of inhibition of angiotensin II formation.

Angiotensin II↗

Effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses in the rat.

The effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses were examined in rats and compared with those of ornoprostil, a PGE1 derivative. Orally administered TY-10957 dose dependently prevented gastric lesions induced by ethanol/HC1 (60% ethanol in 150 mM HCl) and duodenal ulcers induced by mepirizole (200 mg/kg); a significant effect was obtained at 3 micrograms/kg or greater in the former and at 300 micrograms/kg in the latter. Intraduodenally administered TY-10957 had minimal effects on gastric acid secretion, and at the highest dose (300 micrograms/kg) both the basal acid output and that stimulated by histamine (20 mg/kg) were significantly reduced by about 40%. TY-10957 (30-300 micrograms/kg s.c.) produced a marked increase of alkaline secretion in both stomach and duodenum of anesthetized rats, and these effects were significant at 30 micrograms/kg in the stomach and at 100 micrograms/kg in the duodenum. On the other hand, ornoprostil produced a potent and significant inhibition against ethanol/HCl-induced lesions (greater than 1 microgram/kg), but had no effect on mepirizole-induced duodenal ulcers. This PGE1 derivative had no influence on both basal and stimulated acid secretion and did not significantly affect alkaline secretion even at 100 micrograms/kg. These results suggest that TY-10957 has a protective action on both gastric and duodenal mucosa. The mechanism of duodenal antiulcer effect may involve both inhibition of acid and stimulation of alkaline secretion, while the gastroprotective action of this agent may be attributed to other factors.

Alprostadil↗

Retinal pigment epithelial tear in reactive lymphoid hyperplasia of uvea.

A 76-year-old patient developed cystic exudative retinal detachment with many yellowish subretinal precipitates and a large retinal pigment epithelial (RPE) tear in midperiphery of the right eye in the course of polyclonal hypergammaglobulinemia. The left eye showed localized RPE detachment in the posterior pole which gradually extended. Systemic steroid administration reduced the subretinal precipitates to some extent, but suspicion of malignancy led to enucleation of the right eye after unsuccessful diagnostic vitrectomy. A histopathological study revealed massive infiltration of the uvea with plasma cells and small lymphocytes but no abnormal cells. This is the first report to show the association of an RPE tear with reactive lymphoid hyperplasia of the uvea.

Aged↗

The complement system in ischemic heart disease.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.

Angina Pectoris↗

Effects of orally administered drugs on dynamic viscoelasticity of human nasal mucus.

The effects of orally administered drugs on rheologic properties of nasal mucus were investigated in adult chronic sinusitis patients. The elastic modulus G' and the dynamic viscosity eta' of nasal mucus were determined by an oscillating sphere magnetic rheometer. Both G' and eta' values of the mucus before drug administration were much higher than optimal viscoelasticity for mucociliary transport. Norfloxacin, an antibacterial agent, reduced the G' but not the eta' of nasal mucus. Serratiopeptidase, a proteolytic enzyme, reduced eta' but did not reduce G'. S-carboxymethylcysteine, a blocked thiol derivative of cysteine, did not change either G' or eta'. L-cysteine ethyl ester hydrochloride, a sulfhydryl type of agent, reduced both G' and eta'. The results indicate that some of the orally administered mucokinetic agents can improve the abnormal rheologic properties of nasal mucus in chronic sinusitis.

Administration, Oral↗

[Bicarbonate secretion in the mucosal defensive mechanism of the duodenum. Acid neutralization with HCO3- in the lumen and mucus gel].

Bicarbonate secretion from the surface epithelial cells in the duodenum is an active process depending on tissue metabolism and blood flow, and regulated by humoral and neuronal factors as well as endogenous prostaglandins (PGs). The duodenal mucosa has been also able to respond luminal acid by a significant rise in alkaline secretion, mediated mainly by PGs, and the impairment of this process is involved in the pathogenic mechanism of various duodenal ulcer models. The mechanism of mucosal protection by HCO3- secretion is two ways: one is neutralization of luminal acid, and the other the establishment of pH gradient in the mucus gel with the aid of the physicochemical property of mucus. Although the majority of H+ is neutralized by secreted HCO3- in the lumen and mucus gel, the ultimate mucosal protection is ensured by removal of back-diffused H+ through intramucosal neutralization with HCO3- and translocation by blood flow. Thus, HCO3- secretion in collaboration with mucus plays an important role as the first line of defense (pre-epithelial barrier) in the duodenal mucosal protection.

Animals↗

Significance of Q wave disappearance in the chronic phase following transmural acute myocardial infarction.

The mechanism and prognostic implications of Q wave regression following transmural acute myocardial infarction (AMI) were assessed in 54 patients. Of these subjects, 14 lost their Q waves. Exercise myocardial thallium-201 (201Tl) scintigraphy and two-dimensional echocardiography were performed before the patients were discharged from hospital. Two-dimensional echocardiography and electrocardiography were simultaneously repeated about 18 months after AMI. Both the relative 201Tl activity in the infarcted area and the improvement of echocardiographic wall motion index were higher in patients who had lost their Q waves than in those with retained Q waves (70 +/- 14% vs 58 +/- 13%, p less than 0.01; 5.2 +/- 3.0 vs 2.0 +/- 3.4, p less than 0.01, respectively). The prevalence of post-infarction angina pectoris was significantly higher in the former (29% vs 0%, p less than 0.01). We concluded that remnants of viable myocardial muscle might be responsible for Q wave regression following transmural acute myocardial infarction, and the prevalence of post-infarction angina pectoris was high among these patients.

Adult↗

[Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (3). Effects on type I-type IV allergic reaction].

Effects of Glyteer (GL, 5%) on Type I-Type IV allergic reactions were investigated by its topical application to rats and mice, and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), indomethacin (ID, 1%), and bufexamac (BM, 5%), which were all prepared with the same ointment base. Type I: GL showed inhibitory effects on the 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibitory activity of GL on the PCA had the same potency as that of BV (0.12%). GL also inhibited the degranulation of mast cells induced by PCA. Type II: GL did not exert an inhibitory effect on the reversed cutaneous anaphylaxis (RCA) in rats, but BM, ID and BV had an inhibitory activity on the RCA. Type III: BV markedly inhibited the direct passive Arthus reaction in rats. On the other hand, GL, BM and ID had not an inhibitory activity on it. Type IV: GL (0.2, 1 and 5%) showed a concentration-dependent inhibition on the delayed-type hypersensitivity response induced by oxazolone in mice, and the activity was stronger than those of ID and BM. From these results, it is suggested that GL applied externally possesses a potent effect as an anti-allergic drug on Type I and Type IV allergic reactions.

Animals↗

Determination of bicarbonate output using pH deflection in the rat duodenum: influences of prostaglandins and cholinergic agents.

We set up a system to measure the luminal pH, potential difference (PD) and bicarbonate output in the anesthetized rat duodenum, and investigated these responses caused by prostaglandins (PGs) and cholinergic agents. When the proximal duodenum (1.7 cm) was perfused at a flow rate of 0.7 ml/min with saline adjusted to pH 4.5, the duodenal pH, PD and HCO3- output were 5.5 to 6.0, -4 to -6 mV and 1.2 to 1.6 muEq/10 min, respectively; they were markedly reduced by i.v. injection of saturated KCl. Both natural (PGE1, PGE2) and synthetic (PGE2, PGl2) PGs, given either s.c. or i.v., significantly elevated all these parameters, while indomethacin (s.c.) decreased the pH as well as the PD. Small but significant increases of the pH were observed after i.v. administration of cholinergic agents (carbachol, bethanechol), a GABAergic agent (baclofen) and an analogue of thyrotropin releasing hormone (YM-14673), with a temporal elevation of the PD; the degree of net HCO3- output caused by these agents was 20-50% of the values obtained with PGE2 (100 micrograms/kg, i.v.), and they were significantly reduced in the presence of atropine. These results suggest that (a) the system using pH deflections can be used to sensitively detect HCO3- output in the rat duodenum, and (b) duodenal acid neutralizing capacity may be regulated by central and peripheral cholinergic systems as well as endogenous PGs.

Alprostadil↗

Stimulation by prostaglandin E2 of alkaline secretion in the rat duodenum: comparative study with hypertonic NaCl.

Possible involvement of increased mucosal permeability in the stimulation by prostaglandin E2 (PGE2) of duodenal HCO3- secretion was investigated in rats. PGE2 (0.3, 1 mg/kg, s.c.) dose-dependently increased HCO3- secretion in the duodenum with a significant elevation of transmucosal potential difference (PD); the PD was increased from -4.5 +/- 0.3 mV to -10.0 +/- 1.5 mV (mucosa negative) at 1 mg/kg. These responses caused by PGE2 were abolished by sacrificing the animals with saturated KCl (i.v.). Although a significant increase of HCO3- output was observed after exposure of the mucosa to 1 M NaCl (0.5 ml), this response was accompanied by a significant reduction of PD and was not abolished after KCl injection. The mucosal permeability determined by Evans blue (1%, i.v.) was not affected by PGE2, while 1 M NaCl markedly elevated the amount of extravasated dye in both the luminal content and the mucosa. Stimulation of HCO3- output by PGE2 was significantly mitigated by ouabain (3 mg/kg, s.c.) or prior exposure of the mucosa to 1 M NaCl. These results suggest that stimulation by PGE2 of duodenal HCO3- secretion is not simply due to the increased mucosal permeability, but depends rather on both the Na/K ATPase activity and the intact perfusion of the organ. The HCO3- response as induced by 1 M NaCl may result from the increased permeability and is accompanied by a marked reduction of PD.

Animals↗

Effects of topical application of KT1-32 on transmucosal potential difference and acid secretion in the rat stomach.

Effects of intragastric application of azuletil sodium (KT1-32), a novel antiulcer drug, on transmucosal potential difference (PD) and acid secretion were investigated in the rat stomach. The stomach was mounted on a Lucite chamber and perfused with saline before and after exposure to KT1-32 for 10 min. KT1-32 (3-30 mg/kg) produced an elevation of PD in a dose-dependent manner with a rise of the luminal pH. The increased PD response caused by KT1-32 (10 mg/kg) persisted after removal of the agent from the stomach, but this PD generating effect was significantly mitigated by pretreatment with omeprazole (60 mg/kg, i.p.). KT1-32 raised PD under basal conditions, but did not significantly affect the reduced PD response caused by 30% ethanol. In addition, topical application of KT1-32 significantly reduced acid secretion caused by histamine (4 mg/kg/hr, i.v.) and carbachol (20 micrograms/kg/hr, i.v.). In the in vitro study, KT1-32 at 3.9 x 10(-4) M showed 50% inhibition of the H/K ATPase activity prepared from the hog gastric mucosa. These results suggest that KT1-32 exerts locally antisecretory and PD generating effects. The latter may be accounted for by the antisecretory action, which is probably related to the H/K ATPase inhibition.

Administration, Topical↗

Calcium channel blockers reverse the sustained elevation of blood pressure induced by chronic infusion of endothelin in conscious rats.

To determine whether endothelin could act as a circulating hormone in the regulation of blood pressure and sodium-water excretion, we assessed the chronic effects of synthetic endothelin on systolic blood pressure, urine volume and urinary sodium excretion in conscious rats, and also evaluated the effects of benidipine or nilvadipine, newly developed calcium channel blockers, in rats infused chronically with synthetic endothelin. Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. On the contrary, the infusion of endothelin at a rate of 6 micrograms/kg/day did not induce any significant changes in systolic blood pressure, urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure rose on Day I to only 137.0 +/- 2.4 mmHg (p less than 0.05) and 119.7 +/- 5.9 mmHg (p less than 0.05) compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. The present results suggest that endothelin can act as a circulating hormone and might be involved in the regulation of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.

To investigate the interaction of cardiac glycosides with vasoconstrictors, we examined the effects of short term treatment with the cardiac glycoside digoxin (6 mg/kg/day, i.p., for 6 days) in rats made hypertensive by chronic infusion of norepinephrine (NE), angiotensin II (A II) or vasopressin (VP). When digoxin was administered simultaneously with NE at 1.8 mg/kg/day (i.p.) by use of osmotic minipumps in conscious rats, systolic blood pressure decreased to 120 +/- 3 mmHg on Day 1 whereas it rose to 148 +/- 2 mmHg in rats given NE alone (p less than 0.01). The antihypertensive effect of digoxin was sustained for the entire experimental period and was not associated with any change in urinary sodium excretion. When the same dose of digoxin was administered simultaneously with A II at 900 micrograms/kg/day (i.p.) in conscious rats, systolic blood pressure rose to a greater extent than in those given A II alone. The administration of digoxin had no effect on the blood pressure elevation induced by chronic infusion of VP at a rate of 7.2 U/kg/day (i.p.). It is concluded that short term treatment with digoxin has a variety of effects on blood pressure in rats; pressor, depressor, or is no effects depending upon vasoconstrictor used.

Angiotensin II↗

[Clinicopathological study on low grade glioma. In relation to malignant transformation].

The clinical status of patients with glioma is influenced by 1) the histological malignancy of the tumor, 2) the tumor volume, 3) secondary status such as brain edema or intracranial hypertension due to the tumor, and 4) the host immunity. Due to some improvement in at least 2) and 3) by the initial treatment, most low grade glioma cases pass through a clinically silent postsurgical period. However, at a certain point, transition to a high grade tumor malignant transformation may occur with exacerbation of the symptoms. Twenty-two cases of histologically established low grade glioma experienced over the past 7 years, in which immunological status was evaluated, were analyzed. Nine cases (41%) showed malignant transformation. Characteristic pictures of the clinical symptoms, computed tomography (CT) scan findings, immunological status, and morphological findings (mainly immunohistochemical examination) in nine cases were delineated. The findings at the time of exacerbation of the symptoms were as follows. In all cases CT scan demonstrated the change in the main lesion from low density to mixed density and were compatible with a high grade glioma. Reduction in host immunity was verified. Morphological increase in the tumor volume, increase in histological malignancy and deterioration in the secondary status due to the tumor were confirmed. Necrosis of the tumor cells as well as increase in giant cells and gemistocytes were observed. Immunohistochemical analysis revealed a decrease and irregularity in glial fibrillary acidic protein positive cells and positive processes as well as increase in vimentin intensity. These findings demonstrate change in the biological characteristics of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗