Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 325 records · Page 18Linked to original sources

PubMed1991

Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.

Alkaloids↗

PubMed1991

Inhomogeneous response of expiratory muscle activity to cold block of the ventral medullary surface.

We assessed the effects of cooling the ventral medullary surface (VMS) on the activity of chest wall and abdominal expiratory muscles in eight anesthetized artificially ventilated dogs after vagotomy and denervation of the carotid sinus nerves. Electromyograms (EMGs) of the triangularis sterni, internal intercostal, abdominal external oblique, abdominal internal oblique, and transversus abdominis muscles were measured with EMG of the diaphragm as an index of inspiratory activity. Bilateral localized cooling (2 x 2 mm) in the thermosensitive intermediate part of the VMS produced temperature-dependent reduction in the EMG of diaphragm and abdominal muscles. The rib cage expiratory EMGs were little affected at 25 degrees C; their amplitudes decreased at lower VMS temperatures (less than 20 degrees C) but by significantly fewer degrees than the diaphragmatic and abdominal expiratory EMGs at a constant VMS temperature. With moderate to severe cooling (less than 20 degrees C) diaphragmatic EMG disappeared, but rib cage expiratory EMGs became tonic and resumed a phasic pattern shortly before the recovery of diaphragmatic EMG during rewarming of the VMS. These results indicate that the effects of cooling the VMS differ between the activity of rib cage and abdominal expiratory muscles. This variability may be due to inhomogeneous inputs from the VMS to expiratory motoneurons or to a different responsiveness of various expiratory motoneurons to the same input either from the VMS or the inspiratory neurons.

Animals↗

PubMed1991

Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats. Relation to gastric hypermotility.

The relationship of gastric hypermotility to mucosal hemodynamics, lipid peroxidation and vascular permeability changes was investigated in the pathogenesis of indomethacin-induced gastric lesions in rats. Subcutaneous administration of indomethacin (25 mg/kg) produced an increase in both the amplitude and frequency of stomach contraction from 30 min after treatment, resulting in hemorrhagic damage 2 h later. Gastric mucosal blood flow measured by a Laser flowmetry showed oscillatory fluctuations under hypercontractile states: a decrease during contraction followed by an increase during relaxation. Mucosal lipid peroxidation and vascular permeability were significantly increased with time after indomethacin treatment, and these changes preceded the appearance of hemorrhagic damage. All these events were prevented when gastric hypermotility was inhibited by atropine or 16,16-dimethyl prostaglandin E2. Pretreatment of the animals with allopurinol and hydroxyurea or continuous infusion of superoxide dismutase and dimethyl sulfoxide during a test period also attenuated these functional changes and mucosal lesions induced by indomethacin, without affecting the motility response. We conclude that oxygen free radicals may play a role in the development of mucosal lesions associated with gastric hypermotility in indomethacin-treated rats.

16,16-Dimethylprostaglandin E2↗

PubMed1991

Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea.

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors.

A series of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines (3) was synthesized and evaluated for its biological activity against gastric H+/K(+)-ATPase prepared from rabbit stomach and gastric acid secretions in Heidenhain pouch dogs. Monoalkyl substituents on the nitrogen atom of the aniline moiety markedly inhibited the enzyme activity to the same degree as omeprazole, a representative H+/K(+)-ATPase inhibitor. Most of these compounds, administered at 3 mg/kg i.v. inhibited histamine-stimulated gastric acid secretion. The inhibitory activity of these derivatives on the enzymes at pH 6.0 was more potent than that at pH 7.4, and was distinctly correlated to stability in aqueous solution at pH 5.0.

Adenosine Triphosphatases↗

PubMed1991

[Healing promoting effect of azuletil sodium (KT1-32) on experimental chronic gastric ulcers and acceleration of healing in SPF environment].

We examined the healing promoting effects of azuletil sodium on acetic acid and clamping cortisone-induced gastric ulcer in rats. For the experiments on clamping-cortisone gastric ulcer, we used not only conventional rats in conventional conditions but also specific pathogen free (SPF) rats on SPF environment in order to prevent infection. The following results were obtained. 1) In acetic acid ulcer, azuletil sodium (AZE) (greater than or equal to 90 mg/kg/day, p.o.) significantly decreased ulcer index. As estimated on the basis of stage analysis (Ulcer, Healing, Scar), AZE (greater than or equal to 30 mg/kg/day, p.o.) significantly promoted the healing of ulcers. 2) In clamping cortisone ulcer (conventional), AZE (100 mg/kg/day, p.o.) significantly promoted the regeneration of blood vessels. 3) In clamping cortisone ulcer (SPF), AZE at greater than or equal to 30 mg/kg/day and 100 mg/kg/day significantly increased the healing index and mucosal regeneration index, respectively. 4) In clamping cortisone ulcer (SPF), the infection that was observed in the conventional test was not seen at all and the acceleration of healing was observed. Furthermore, the extent of adhesion was also reduced, and the standard errors of various healing indices were smaller. From these results, it is concluded that AZE accelerated the healing of experimentally-induced gastric ulcers in rats.

Animals↗

PubMed1991

Gastric motility changes in capsaicin-induced cytoprotection in the rat stomach.

We have examined the effect of orally administered capsaicin on gastric motility in the rat to investigate a possible relationship between motility change and cytoprotection induced by this agent. Capsaicin, given orally (1-30 mg/kg), dose-dependently inhibited hemorrhagic band-like lesions induced by ethanol (60% in 150 mM HCl). This protection was significantly mitigated by desensitization of afferent neurons following capsaicin pretreatment 2 weeks before the experiment, and it was also significantly attenuated by prior administration of indomethacin, but not by spantide. Intragastric administration of capsaicin (30 mg/kg) significantly inhibited gastric motility and increased the mucosal blood flow, but had no effect on the transmucosal potential difference of the stomach. These functional changes induced by capsaicin were also less marked in the afferent neuronal desensitized rat, and they were significantly attenuated by indomethacin but not by spantide. These results suggest that the mucosal protection by intragastric capsaicin may be associated with the inhibition of gastric motility and the increase of mucosal blood flow. These responses may be induced by activation of primary afferent neurons which are probably sensitized by endogenous prostaglandins.

Animals↗

PubMed1991

Capsaicin-sensitive afferent neurons in adaptive responses of the rat stomach induced by a mild irritant.

Exposure of rat stomach to 1 M NaCl reduced the transmucosal potential difference (PD) followed by an increase of luminal pH and gastric mucosal blood flow (GMBF). Desensitization of capsaicin-sensitive afferent neurons significantly mitigated the increase in GMBF without affecting PD and pH responses. Mucosal application of capsaicin increased GMBF with no effect on PD and pH. The findings suggest that capsaicin-sensitive afferent neurons may be involved in the regulatory mechanism of GMBF responses induced by a mild irritant.

Adaptation, Physiological↗

PubMed1991

Effects of MCI-727, a new antiulcer agent, on various gastric and duodenal lesions in experimental animals.

Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water-immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone.

Animals↗

PubMed1991

Effects of a new benzimidazole derivative, NC-1300-O-3, on gastric secretion and gastroduodenal lesions in rats.

We examined the effects of a new compound, NC-1300-O-3 (2-[2-N-methyl-N-(2-methylpropyl) amino] benzylsulfinyl benzimidazole), on the gastric mucosal proton pump (H+, K(+)-ATPase) activity, gastric secretion and gastroduodenal lesions in rats. The compound potently inhibited the enzyme activity in a concentration-dependent manner, the IC50 being 5.3 x 10(-6) M at pH 6.0 and 1.4 x 10(-5) M at pH 7.4. NC-1300-O-3 markedly and persistently (for more than 24 hr) inhibited basal gastric secretion in male or female animals when administered by the p.o. route. The compound also significantly inhibited gastric secretion by the intraduodenal (i.d.), intragastric (after pylorus ligation) and i.p. routes, but only weakly by the s.c. route. Repeated p.o. administration of the compound for 1 week also significantly inhibited gastric secretion. Histamine-stimulated gastric secretion was also significantly inhibited by the i.d. administration of the compound. NC-1300-O-3, administered p.o., potently prevented water-immersion stress-, histamine-, indomethacin-, prednisolone- and compound 48/80-induced gastric lesions. In addition, it also significantly prevented the formation of gastric lesions induced by various necrotizing agents. Mepirizole- and cysteamine-induced duodenal ulcers were also prevented by the compound. The antisecretory and antilesion activities of NC-1300-O-3, administrated p.o., were not altered on its combination with 2% NaHCO3.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1991

Characterization of gastric mucosal blood flow response induced by intragastric capsaicin in rats.

Gastric mucosal blood flow (GMBF) was measured in the ex vivo stomachs of anesthetized rats simultaneously with mean arterial blood pressure (MBP), luminal pH and transmucosal potential difference (PD) in an attempt to characterize these responses induced by capsaicin. The stomach was mounted on a Lucite chamber, perfused with saline at the flow rate of 1 ml/min, and GMBF was measured by Laser flowmetry. Under these conditions, the pH, PD and GMBF were 3.5 to 4.0, -30 to -35 mV and 8-12 ml/min/100 g, respectively. Mucosal application of capsaicin (0.03 - 1 mg/ml for 10 min) increased GMBF in a concentration-dependent manner, without any change in PD, pH and MBP. The increased GMBF response caused by capsaicin was abolished by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg), significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.) or ruthenium red (300 micrograms/kg, i.v.), but was not affected by spantide (100 micrograms/kg, i.v.), atropine (300 micrograms/kg, i.p.) or disodium cromoglycate (30 mg/kg, i.p.). In addition, when the mucosa was exposed to capsaicin repeatedly, this response showed a marked tachyphylaxis at a high concentration (6 mg/ml). These results suggest that intragastric capsaicin increased GMBF selectively through capsaicin-sensitive sensory neurons, and this action may involve endogenous prostaglandins.

Animals↗

PubMed1991

Duodenal ulcers induced by diethyldithiocarbamate, a superoxide dismutase inhibitor, in the rat: role of antioxidative system in the pathogenesis.

Pathogenesis of duodenal ulcers induced by diethyldithiocarbamate (DDC), a superoxide dismutase (SOD) inhibitor, was investigated in the rat. Repeated s.c. administration of DDC (750 mg/kg) every 12 hr induced duodenal ulcers in the fed rats, and the severity of the ulcers reached the maximum after three injections. DDC not only reduced basal acid output but also impaired duodenal alkaline secretion. These ulcers were significantly prevented by antioxidative agents such as SOD (50000 units/kg, s.c.), allopurinol (50 mg/kg, s.c.) or glutathione (200 mg/kg, s.c.) as well as the antisecretory agent cimetidine (100 mg/kg, s.c.). The impaired HCO3- response caused by DDC was partially but significantly reversed by either SOD (15000 units/kg/hr, i.v.), allopurinol or glutathione; and SOD by itself significantly elevated the rate of basal alkaline secretion. 16,16-Dimethyl prostaglandin E2 (10 micrograms/kg, s.c.) increased duodenal HCO3- output in the presence of DDC and significantly prevented the development of duodenal ulcers in response to DDC. These results suggest that the mucosal antioxidative system including SOD may play a role in the regulatory process of alkaline secretion and contribute to the mucosal defensive ability in the duodenum. The insufficiency of this system may be involved in the pathogenesis of DDC-induced duodenal ulcers.

Allopurinol↗

PubMed1991

Actin dynamics in growth cones.

The mechanism of actin incorporation and turnover in the nerve growth cone was examined by immunoelectron microscopy and low-light-level video microscopy of cultured neurons injected with biotin-labeled actin or fluorescently labeled actin. We first determined the sites of actin incorporation into the cytoskeleton of growth cones by immunoelectron microscopy of cultured neurons injected with biotin-labeled actin and reacted with an anti-biotin antibody and a gold-labeled secondary antibody. Shortly after the injection, biotin-actin molecules incorporated into the cytoskeleton were localized in the distal part of actin bundles in the filopodia and at the membrane-associated fringe of the actin filament network. With longer incubation, most actin polymers in the growth cones were labeled uniformly, suggesting that actin subunits are added preferentially at the membrane-associated ends of preexisting actin filaments. We then determined whether actin filaments translocate within the growth cones by low-light-level video microscopy of living neurons injected with fluorescently labeled actin and photobleached with a laser beam. When actin fluorescence at the leading edge of a growth cone was bleached, a rearward translocation of the bleached spot toward the base of the growth cone was observed. This observation suggests the presence of a rearward flow of actin polymers within growth cones. Taken together, these results indicate that there is a continuous addition of actin monomers at the leading edge of the growth cone and a successive rearward translocation of the assembled filaments.

Actins↗

PubMed1991

Stimulation of gastric bicarbonate secretion by an analog of thyrotropin-releasing hormone, YM-14673, in the rat.

The effects of YM-14673, a thyrotropin-releasing hormone analog, on gastric alkaline secretion were investigated in the anesthetized rat pretreated with omeprazole (60 mg/kg, intraperitoneally) by measuring the luminal pH, transmucosal PD and HCO3- output. The whole stomach was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5) in the absence of acid secretion, the pH of the perfusate and PD were continuously monitored and the HCO3- output was measured as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. YM-14673, given intravenously at the doses (0.1-1 mg/kg) that stimulated acid secretion, increased the pH and HCO3- output in a dose-dependent fashion, but did not significantly affect the PD. Prostaglandin E2 (1 mg/kg) elevated the pH and HCO3- output with concomitant decrease in the PD, whereas carbachol (4 micrograms/kg), similar to YM-14673, produced an increase of the pH and HCO3- output with no change in the PD. The net HCO3- output (4.3 +/- 0.3 muEq) induced by 0.3 mg/kg of YM-14673 was about 60 and 150% of that induced by prostaglandin E2 and carbachol, respectively. The increased pH and HCO3- responses caused by YM-14673 were almost completely abolished by vagotomy, significantly inhibited by atropine (0.3 mg/kg, intravenously) and indomethacin (5 mg/kg, subcutaneously) but not affected by pirenzepine (1 mg/kg, intravenously). These results suggest that YM-14673, a thyrotropin-releasing hormone analog, produced vagally mediated HCO3- secretion in the rat stomach, and the mechanism may involve the cholinergic system, which is mediated with muscarinic M2 receptors and interacts with endogenous prostaglandins.

Animals↗

PubMed1991

Effect of indomethacin on gastric mucosal blood flow around acetic acid-induced gastric ulcers in rats.

Repeated administration of indomethacin markedly delays spontaneous healing of experimental gastric ulcers induced in rats. To elucidate the underlying mechanism, the effect of indomethacin on the gastric mucosal blood flow around ulcers was examined. Gastric ulcers were induced 5 days after submucosal injection of an acetic acid solution into the stomachs of rats. Blood flow was determined by the hydrogen gas clearance method. The blood flow around ulcers was significantly higher than that in rats without ulcers up to 2 weeks after ulceration but had returned to within the normal range 3 or 4 weeks later. Indomethacin, administered SC at 1 mg/kg once or repeatedly for 1-4 weeks, had little or no effect on the blood flow in normal rats. However, such treatment significantly reduced the blood flow by 20%-30% of the corresponding control levels in rats with ulcers. Prostaglandin E2, administered SC at 3 mg/kg once, markedly prevented the reduction in the blood flow due to indomethacin. The administration of prostaglandin E2, with indomethacin for 4 weeks resulted in a significantly higher blood-flow level than the control and prevented the delay in ulcer healing. Omeprazole, administered SC at 30 mg/kg once or repeatedly with indomethacin for 4 weeks, had an insignificant effect on the blood flow around ulcers but prevented the delay in ulcer healing. In conclusion, the delayed ulcer healing caused by indomethacin might be partly related to the reduced blood flow around the ulcers.

Acetates↗

PubMed1991

[Restrictive lung disease].

It was found that functional residual capacity (FRC) invariably decreased during inspiratory elastic loaded breathing and that its magnitude increased progressively with an increase in the intensity of the load. This response could not be explained by chemoreflexes nor neural reflexes. Because the sensation of dyspnea decreased at lowered FRC (FRC-0.5 liter) than that at FRC during elastic loading, we speculate that FRC decreased behaviorally during elastic loading to reduce the sensation of dyspnea. We found that the respiratory muscle became fatigued more easily at FRC than at lowered FRC during elastic loading. We therefore conclude that the decrease in FRC may be one of the compensatory mechanisms during elastic loaded breathing.

Functional Residual Capacity↗

PubMed1991

[Epidemiologic study on urolithiasis in Mie prefecture. 2. Present status in 1988].

To determine the current status of urolithiasis in 1988, in comparison with that in 1985, we analyzed the 1937 patients of urolithiasis at 17 departments of urology in Mie Prefecture and 2 departments of urology in Wakayama Prefecture. The ratio of male to female patients was 2.6 to 1.0. Geographically, the number of urolithiasis patients was most frequently distributed in Matsusaka City. The frequency of urolithiasis in the urban area was almost the same as that in the rural area. Most of the stones (96.3%) were in the upper urinary tract. The frequency of lower urinary tract calculi tended to be high in southern Mie Prefecture. The ratio of the upper urinary tract calculi to the lower urinary tract calculi in the urban area was higher than in the rural area. The age distribution in males was in the forties, while that in females was in the fifties. The average age was 46.4 years old. The surgical treatment was performed in 671 patients (34.6%) and the extracorporeal shock wave lithotripsy (ESWL) was the most frequent mode of treatment (85.0%), followed by cysto-lithotripsy (4.2%) and percutaneous nephro-uretero-lithotripsy (2.4%). The most frequent component of the urinary tract calculi was calcium oxalate and/or calcium phosphate (81.7%). The stone patient increased in the number during the summer season (July, August and September). In conclusion, in 1988 when the ESWL treatment started in Mie Prefecture, the epidemiologic features of urolithiasis was characterized as follows: the number of patients increased and the broad application of the ESWL treatment resulted in the decreased number of patients with spontaneous discharge and the increased number of patients with recurrent stones and with bilateral or multiple complex stones.

Adolescent↗

PubMed1990

Turnover of fluorescently labelled tubulin and actin in the axon.

The cytoskeleton has an important role in the generation and maintenance of the structure of the axon. Microtubules, neurofilaments and actin, together with various kinds of associated proteins, form highly organized dynamic cytoskeletal structures. Because tubulin and actin molecules are essential cytoskeletal components and are transported down the axon, it is important to understand their dynamic behaviour within the axon. Although previous pulse-labelling studies have indicated that the axonal cytoskeleton is a static complex travelling down the axon, this view has been challenged by the results of several recent experiments. We have now addressed this question by analysing the recovery of fluorescence after photobleaching fluorescent analogues of tubulin and actin in the axons of cultured neurons. We did not observe movement or spreading of bleached zones along the axon, both in neurons injected with fluorescein-labelled tubulin and actin. All bleached zones recovered their fluorescence gradually, however, indicating that microtubules and actin filaments are not static polymers moving forward within the axon, but are dynamic structures that continue to assemble along the length of the axon.

Actins↗