Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,135 records · Page 63Linked to original sources

PubMed1994

Contraction-excitation feedback in atrial reentry: role of velocity of mechanical stretch.

To determine the effects of atrial stretch on atrial flutter, we analyzed variations in atrial flutter cycle length (CL) caused by ventricular contraction in five dogs with artificially induced atrioventricular block. In contrast to absence of variations in CL during sustained ventricular asystole, atrial stretch by ventricular contraction consistently produced phasic variations in CL. The variations were not confined to any specific atrial sites, but depended on the time of ventricular contraction relative to atrial activation phase. The phase-response curve of the variations was closely related to that of the velocity of changes in the atrial pressure with no time lags, but not to that of the atrial pressure itself. Pharmacological denervation did not abolish the variations. Conventional electrophysiological study revealed greater changes in intra-atrial activation time by atrial stretch at a short pacing cycle length than at a longer one, suggestive of changes in repolarization by mechanical stretch. In conclusion, atrial stretch caused by ventricular contraction produces phasic variations in CL, the extent of which depends on the velocity of the mechanical stretch of atrial muscles.

Animals↗

PubMed1994

Case of cough syncope with seizure.

A rare case of cough syncope accompanied by seizure is presented. Interseizure electroencephalogram revealed in this 55-year-old man spikes and sharp waves over the bilateral temporal regions. Bronchodilators and antiepileptic medication effectively controlled cough syncope and seizure in this patient.

Bronchial Provocation Tests↗

PubMed1994

Possible mechanisms of airway hyperresponsiveness after late asthmatic response in guinea pigs.

To elucidate the mechanism of airway hyperresponsiveness after late asthmatic response (LAR), we analyzed bronchoalveolar lavage fluid (BALF) and examined the airway smooth muscle contractility to acetylcholine (ACh). On day 1 after LAR, there was a significant positive correlation between the number of neutrophils in BALF and the increase in airway responsiveness after LAR (r = 0.82, p < 0.01). In the in vitro study, the dose response curve to ACh was significantly shifted to the left after removal of the epithelium in control guinea pigs. However, in hyperresponsive animals after LAR, removal of the epithelium had no significant effect on ACh-induced response. These results indicate that infiltration of neutrophils and other inflammatory cells induce epithelial damage and hence the development of airway hyperresponsiveness after LAR.

Acetylcholine↗

PubMed1994

Paratesticular myxoma.

We report a case of paratesticular myxoma. These tumors, which arise from mesenchymal tissues, occur in a variety of sites, the most common being subcutaneous tissues and skeletal muscles but they rarely have been reported to originate in the paratesticular region. The differential diagnosis of other mesenchymal neoplasms of the paratesticular area is discussed.

Diagnosis, Differential↗

PubMed1994

Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

To investigate whether increased release of acetylcholine may be involved in propranolol-induced bronchoconstriction (PIB), the inhibitory effect of pilocarpine (Pilo), an agonist of M2-muscarinic receptors that in 11 stable asthmatic subjects. The bronchial responsiveness to Pilo was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase. In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalation for 1 min was measured. Atropine reversed PIB. After pilocarpine pretreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs decreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/- SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pilo to PIB without Pilo correlated inversely according to the pretreatment dose (Dmin) of Pilo (p < 0.05). These results suggest increased release of acetylcholine in PIB and that M2-muscarinic receptors are at least in part functioning in stable asthmatic airways.

Acetylcholine↗

PubMed1994

Bradykinin-induced airway inflammation. Contribution of sensory neuropeptides differs according to airway site.

We examined the mechanisms of bradykinin-induced airway microvascular leakage in guinea pig airways by measuring extravasation of Evans blue dye. Animals were pretreated with propranolol (1 mg/kg, intravenous) and atropine (1 mg/kg, intravenous) to block the beta-adrenergic and muscarinic responses, respectively. Bradykinin (250 nmol) instillation into airways significantly increased the leakage of dye in the trachea, main bronchi, and intrapulmonary airways to the same degree. The bradykinin B2-receptor antagonist HOE140 (500 nmol/kg, intravenous) did not alter basal leakage but almost completely inhibited bradykinin-mediated leakage. By contrast, the neurokinin NK1 antagonist FK888 (10 mg/kg, intravenous) partially inhibited bradykinin-induced leakage in trachea (p < 0.01) and main bronchi (p < 0.01), but had no significant effect on intrapulmonary airways. Indomethacin (5 mg/kg, intravenous) had no effect on the plasma leakage after instilled bradykinin. We concluded that the airway inflammatory response to bradykinin administered directly into the airways is mediated by bradykinin B2 receptors and partially mediated by tachykinin release from sensory nerve terminals, whereas cyclooxygenase products have no important role in the response. In the central airways, the contribution of sensory neuropeptides to the bradykinin response is greater than that caused by direct stimulation of the B2 receptor on the endothelium at the postcapillary venule of the bronchial circulation. In contrast, in the peripheral airways, the contribution of direct B2-receptor stimulation on the airway vasculature is greater than that involving sensory neuropeptides.

Animals↗

PubMed1994

Antigen-induced airway responses are inhibited by a potassium channel opener.

We have investigated the effect of a potassium channel opener, BRL 38227, on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs by simultaneously measuring pulmonary resistance (Rl) and extravasation of Evans blue dye. Guinea pigs were sensitized 3 wk before experimentation with ovalbumin (OA) and aluminum hydroxide. The trachea was cannulated, and lungs were mechanically ventilated. All animals were pretreated 30 min before experimentation with atropine (1 mg/kg intravenously) and propranolol 1 mg/kg to block muscarinic and beta-adrenergic responses, respectively. BRL 38227 (200 micrograms/kg) was administered intravenously 1 min before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an ultrasonic nebulizer (for 30 s) 1 min after dye injection. BRL 38227 significantly inhibited OA-induced bronchoconstrictor response (p < 0.01) and plasma leakage in trachea (p < 0.05) and main bronchi (p < 0.05). BRL 38227 also had an inhibitory effect on exogenous histamine- and leukotriene-induced bronchoconstriction and microvascular leakage. However, BRL 38227 did not affect OA-induced histamine release from minced lung tissues in sensitized guinea pigs. We conclude that the allergic bronchoconstrictor response and airway plasma leakage are inhibited by a potassium channel opener, possibly as a result of its effect on the airway smooth muscle and the postcapillary venule level.

Administration, Inhalation↗

PubMed1994

Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils.

Neutrophils may play important roles in chronic airway diseases. Pseudomonas is a common pathogen in some chronic airway diseases, and expression of the neutrophil chemoattractant interleukin-8 (IL-8) is induced by Pseudomonas in various cells in vitro. Here we examine the localization of IL-8 mRNA expression after incubating human and dog bronchi with Pseudomonas supernatant in vitro. To examine IL-8 expression in recruited neutrophils, we also superfused the dog bypassed tracheal segment with Pseudomonas supernatant in vivo and measured neutrophil number and IL-8 concentration in luminal fluid; simultaneously, we introduced Pseudomonas supernatant by catheter in a peripheral airway. After 6 h, we analyzed IL-8 mRNA expression and localization in removed tissue. Unincubated bronchi showed no IL-8 mRNA expression, but incubation with Pseudomonas supernatant in vitro resulted in IL-8 mRNA expression in surface epithelial, gland duct, and a subpopulation of serous gland cells. In vivo, introduction of Pseudomonas supernatant into dog trachea and peripheral airways caused IL-8 mRNA expression in epithelial and gland duct cells but also in the recruited neutrophils. Pseudomonas lipopolysaccharide alone was without effect in vitro and in vivo. We conclude that Pseudomonas products, but not lipopolysaccharide, stimulate IL-8 expression in airways and that this expression occurs primarily in surface epithelial and gland duct cells, thus bringing the chemoattractant to the bacterial site. Furthermore, IL-8 expression in recruited neutrophils provides a potential mechanism for positive feedback of this protective antibacterial response.

Adult↗

PubMed1994

Novel Pseudomonas product stimulates interleukin-8 production in airway epithelial cells in vitro.

Because high concentrations of IL-8 are found in the sputum of cystic fibrosis patients, we hypothesized that Pseudomonas aeruginosa (PA) induces the production of IL-8 in airway epithelial cells and in monocytes. Therefore, we incubated the supernatant from PA culture with human transformed bronchial epithelial cells (16-HBE) or with monocytes. The culture medium of 16-HBE cells that had been incubated with PA supernatant for 6 h had chemotactic activity that was inhibited by an antibody to human IL-8. The PA supernatant induced IL-8 production by primary bronchial epithelial cells, by 16-HBE cells, and by monocytes. After incubation with PA supernatant, 16-HBE cells showed a marked increase in the levels of IL-8 gene expression. The PA product responsible for IL-8 production resisted freezing, boiling, and proteolysis. This product was not lipid extractable and was present in a 1-kD filtrate. We conclude that a small molecular mass product of PA stimulates IL-8 production by 16-HBE cells and by monocytes, and that the chemotactic activity produced by 16-HBE cells after exposure to PA is due principally to IL-8.

Blotting, Northern↗

PubMed1994

Long-term results of the anterior cervical spondylodesis.

From 1974 to 1992, anterior cervical spondylodesis was performed in 163 patients of cervical spondylotic myelopathy, cervical spondylotic radiculopathy, traumatic spinal injury, ossification of the posterior longitudinal ligament, or cervical spondylitis. Forty-five of these patients were followed for more than 4 years. To analyze the long-term results of anterior cervical spondylodesis, a radiological examination was performed in these 45 patients and magnetic resonance imaging was conducted in 41 of them. Postoperative spondylotic changes were observed radiologically in 23 (51.1%) of the 45 patients. Anterior bony spur was more frequently observed than posterior bony spur in these postoperative spondylotic changes. Postoperative canal stenosis caused by the bulging of the discs and the ligamentum flavum was frequently demonstrated with hypo- or isointense signal on T2-weighted images by magnetic resonance imaging in patients followed long term after surgery and in patients with malalignment of the cervical spine due to kyphosis of the fused vertebrae and multisegmental fusion. Neurological improvement was less in patients with bulge of the discs and the ligamentum flavum seen in magnetic resonance imaging than in patients without it. The bulge of the ligamentum flavum was histopathologically defined as hypertrophy of the ligament.

Adolescent↗

PubMed1994

4-acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and inhibitory effect on 5-lipoxygenase and leukotriene B4 production.

Structure-activity relationships in the inhibitory effects of 4-acylaminophenol derivatives on the 5-lipoxygenase (5-LOX) from RBL-1 cells and leukotriene B4 (LTB4) production by guinea pig neutrophils were studied. When the N-acyl group was n-octanoyl or 2-thiophenecarbonyl and the size of the two ortho substituents of phenol was varied, the substituents bulkier than isopropyl, i.e., 2,6-di-tert-butyl and 2,6-dicyclohexyl, substantially weakened the inhibitory activity in both enzymatic and cellular systems. Among the 2,6-dimethyl derivatives with an acyl group of various carbon-chain lengths (C1-13), those with a n-alkyl chain of C5 to C12 showed similarly potent inhibitory activities toward 5-LOX with an IC50 ranging from 0.27 to 0.66 microM; in contrast, maximal inhibitory activities toward LTB4 production were observed in a narrower range of the serial compounds: i.e., those with a n-hexyl, n-heptyl, or n-octyl chain on the carbonyl carbon formed by far the most inhibitory group of the series and the inhibitory activity sharply decreased on either side of the chain length. Nearly all the active compounds also inhibited cyclooxygenase (COX), but the IC50 values for COX inhibition were more than ten times higher than the corresponding IC50 values for 5-LOX inhibition in most cases, indicating that the acylaminophenols are relatively selective 5-LOX inhibitors.

Aminophenols↗

PubMed1994

Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a suppository form using rats.

The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28, it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository," made by solidifying molten RK-28, was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository," resulted in an absolute bioavailability of 76%.

Administration, Oral↗

PubMed1994

Preparation and evaluation of suppositories for RK-28 (a new radiosensitizer) using rabbits.

The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy)methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.

Administration, Oral↗

PubMed1994

Synthesis of the metabolites of clentiazem.

The metabolites of clentiazem in the urine or bile of rats and dogs were investigated. Fifteen basic, 6 acidic, 2 neutral and 4 conjugated metabolites were isolated. In the present paper, fourteen reference compounds as shown in Charts 1, 2 and 3 were synthesized to identify the structures of the metabolites in procedures fundamentally similar to those employed in the synthesis of the corresponding metabolites of diltiazem.

Animals↗

PubMed1994

[Synthesis and antiulcer activity of 2-amino-8H-indeno[1,2-d]thiazole derivatives].

A series of 8H-indeno[1,2-d]thiazoles containing various N-substituted amino groups at the 2 position were synthesized by the reaction of 2-bromo-indanones and N-substituted thioureas. Their anti-ulcerous activity was evaluated. Alkylamino derivatives have a more potent inhibitory behavior on ethanol-induced gastric ulcers compared with arylamino derivatives. We also studied the effect of various substituents on the both benzene and pyridine ring of 2-pyridylamino derivatives on ethanol-induced gastric ulcers. However no clear effects were observed. Among 3-morpholinopropylamino derivatives, 5-isopropyl- (21) and 7-chloro-2-(3-morpholinopropyl)amino-8H-indeno[1,2-d]thiazole (25) showed a considerably stronger inhibitory behavior on hydrochloric acid-induced gastric ulcers than cetraxate hydrochloride. Furthermore, 3-morpholinopropylamino derivatives have potent inhibitory effects on gastric acid secretion in pylorus ligated rats.

Animals↗

PubMed1994

The relationship between the sialic acid concentrations in the serum and whole saliva in rats with naturally occurring gingivitis.

Pocket probing depth was correlated with the amount of salivary sialic acid in pilocarpine-stimulated saliva in ODU plaque-susceptible rats (ODUS/Odu) (r = 0.657, P < 0.01), but not with the content of serum sialic acid. There was no difference in the amount of serum sialic acid content between ODUS/Odu and plaque-resistant rats. These results suggest that the amount of sialic acid in the saliva can be a useful index of the severity of periodontal disease.

Animals↗

PubMed1994

Insulin-like effects of vanadate on rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA and protein inductions in diabetic rats.

Effects of vanadate on liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF-2-K/F-2,6-P2ase) mRNA and protein inductions were examined in streptozotocin (STZ)-induced diabetic rats. In diabetic rats at one week after STZ (60 mg/kg body weight), the liver 6PF-2-K activity was decreased to 22% of the control. The enzyme protein was also decreased to 31% of the control, but the reduction in mRNA was not significant. Treatment of diabetes with vanadate (10 mg/kg BW, i.v., every 8 h), as well as insulin (10 u/kg BW, s.c., every 8 h), increased the 6PF-2-K activity and the enzyme protein content, though it was not completely restored to the control level. 68% of the control was the figure for enzyme activity and 65% of the control for protein content after 24-h of treatment. On the other hand, vanadate, like insulin, increased enzyme mRNA content to a higher level than the control (140% of the control). The present results indicate that vanadate, like insulin, modulates the liver 6PF-2-K/Fru-2,6-P2ase gene expression, and stimulated protein induction contributes to the regulation of its enzyme activity, resulting in amelioration of the deranged carbohydrate metabolism in the diabetic state.

Animals↗

PubMed1994

Collagen framework of the volar plate of human proximal interphalangeal joint.

The functional roles of the three-dimensional fibrillar ultrastructure of the proximal interphalangeal joint volar plates of human fingers were studied by light microscopy and scanning electron microscopy. The results revealed that the volar plate consists of three layers of fibers. The first layer forms an intracavity wall with two parts, the proximal "membranous portion", and the distal "meniscoid protrusion" that is separated from the middle phalangeal base by a "recess". The second layer contains the "check ligament", which lies parallel to the fibers of the tendon, anchors tightly into the middle phalangeal base, and protects the joint from hyperextension. The third layer connects to the fibers from the accessory ligament and ligamentous tendon sheath of the A3 pulley, perpendicularly crosses the fibers of the tendon, becomes the periosteum of the middle phalangeal base, and functions as a hanging support for the volar plate and as a gliding floor for the flexor tendon.

Adult↗