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Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 217 records · Page 12Linked to original sources

Effect of intramedullary procaine injection on tracheal tone and phrenic neurogram.

To map the superficial locations which are involved in the control of respiration and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized, paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial layer (from the rostral part of the trapezoid body to the caudal hypoglossal rootlets and lateral from the pyramids to 5.5 mm from the midline), which included rostral, intermediate and caudal areas, and the area lateral to the hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was decreased by procaine injection to the intermediate area and the area lateral to the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to the intermediate area. In the intermediate area, some injections decreased either phrenic output alone or tracheal tone alone. These results suggest that the two ventral medullary areas, i.e. the intermediate and caudolateral parts, contain neural structures which are involved in the shaping of phrenic output, but only the intermediate area is involved in the regulation of tracheal tone. It is also suggested that, in the intermediate area, the structures responsible for the maintenance of respiration and tracheal tone are, at least in part, separable.

Animals↗

Submental stimulation and supraglottic resistance during mouth breathing.

We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals and 6 patients with obstructive sleep apnea. We then examined the most effective sites of stimulation in the submental regions, and the relationships between Rsg and stimulation frequency and voltage in the supine position. Inspiratory and expiratory Rsg's were obtained as the slope of the linear portion of the pressure-flow relation determined at zero flow. Before stimulation, inspiratory and expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L-1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L-1.sec, respectively, in patients. Stimulation in the proximal half submental region with surface electrodes 1 cm apart decreased inspiratory and expiratory Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in this submental region showed a stimulation frequency-and voltage-dependency in both groups, but expiratory Rsg did not. These findings suggest that submental stimulation in the proximal half region widens the supraglottic airway during mouth breathing and probably involves the upper airway muscles.

Adult↗

Polarity orientation and assembly process of microtubule bundles in nocodazole-treated, MAP2c-transfected COS cells.

Microtubule bundles reminiscent of those found in neuronal processes are formed in fibroblasts and Sf9 cells that are transfected with the microtubule-associated proteins tau, MAP2, or MAP2c. To analyze the assembly process of these bundles and its relation to the microtubule polarity, we depolymerized the bundles formed in MAP2c-transfected COS cells using nocodazole, and observed the process of assembly of microtubule bundles after removal of the drug in cells microinjected with rhodamine-labeled tubulin. Within minutes of its removal, numerous short microtubule fragments were observed throughout the cytoplasm. These short fragments were randomly oriented and were already bundled. Somewhat longer, but still short bundles, were then found in the peripheral cytoplasm. These bundles became the primordium of the larger bundles, and gradually grew in length and width. The polarity orientation of microtubules in the reformed bundle as determined by "hook" procedure using electron microscope was uniform with the plus end distal to the cell nucleus. The results suggest that some mechanism(s) exists to orient the polarity of microtubules, which are not in direct continuity with the centrosome, during the formation of large bundles. The observed process presents a useful model system for studying the organization of microtubules that are not directly associated with the centrosomes, such as those observed in axons.

Animals↗

Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-alpha release in mouse lung tissues.

Cord factors are mycoloyl glycolipids in cell walls of bacteria belonging to Actinomycetales, such as Mycobacterium, Nocardia and Rhodococcus. They induce granuloma formation in the lung and interstitial pneumonitis, associated with production of macrophage-derived cytokines. We studied how cord factors induce biological activities in the cells. Cord factors isolated from M. tuberculosis, trehalose 6-monomycolate (mTMM) and trehalose 6,6'-dimycolate (mTDM), enhanced protein kinase C (PKC) activation in the presence of phosphatidylserine (PtdSer), diacylglycerol and Ca2+, and mTMM activated PKC alpha more strongly than PKC beta or gamma under the same assay conditions. Kinetic studies of mTMM in response to PKC activation revealed that mTMM increased the apparent affinity of PKC to Ca2+ in the presence of both PtdSer and diolein. Although this is similar to observations with unsaturated fatty acids, such as arachidonic acid, mTMM was synergistic with PtdSer for PKC activation, but arachidonic acid was not. mTMM was also different as regards PKC activation, as phorbol ester was. A single i.p. administration of mTMM to mouse induced tumor necrosis factor-alpha (TNF-alpha) in serum and in the lung, which is a unique target tissue of cord factors. Based on our recent finding that TNF-alpha is an endogenous tumor promoter, the correlation between lung cancer and pulmonary tuberculosis is discussed.

Animals↗

Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea.

BACKGROUND: Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS: The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS: The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS: The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea.

Adult↗

Stress in middle-aged women: influence of Type A behavior and narcissism.

The authors examined (1) strength of stress, (2) awareness of stress, and (3) influence of type A behavior and narcissistic personality on stress and its related factors in a sample of 500 middle-aged women. Compared to 400 middle-aged working men, the women scored lower on the type A and coping scales, suggesting the possibility that women with high scores on type A behavior cope better with stress. Moreover, type A behavior in women was related to narcissistic personality. The strength of stressors and stress coping in type A women are affected by the severity of narcissism.

Adult↗

Hypoglossal nerve stimulation affects the pressure-volume behavior of the upper airway.

To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.

Animals↗

Role of the sympathetic nervous system in gastric functional changes induced by thyrotropin-releasing hormone in rats.

We determined the changes in gastric functions and systemic blood pressure in response to thyrotropin-releasing hormone (TRH) simultaneously in anesthetized rats and examined the role of the sympathetic nervous system in these changes. TRH injected i.c. increased gastric acid secretion, contraction and mucosal blood flow, and produced hemorrhagic lesions in the glandular stomach. These responses to TRH were almost completely inhibited by bilateral cervical vagotomy or atropine. The increased gastric acid secretion and contraction in response to TRH were significantly augmented by pretreatment with yohimbine but not with prazosin. Bilateral adrenalectomy also potentiated the gastric acid secretory and contractile responses to TRH. Neither prazosin, yohimbine nor adrenalectomy had any appreciable effect on the increased gastric mucosal blood flow induced by TRH. TRH-induced gastric mucosal lesions were significantly aggravated by yohimbine and adrenalectomy. In vagotomized rats, TRH significantly suppressed the gastric functional changes induced by electrical stimulation of the vagus nerves. These data suggest that while gastric functional changes and mucosal lesions induced by TRH mainly occur through stimulation of the vagus nerves, these responses are extensively modified by the sympathetic nervous system including the adrenal glands.

Adrenergic Fibers↗

Desensitization of capsaicin-sensitive sensory neurons in rat stomachs on chronic treatment with sodium taurocholate.

We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4- or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin gene-related peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.

Animals↗

Enhanced gastric mucosal damage in rats after chronic treatment with sodium taurocholate.

We examined whether or not 4-week treatment with 10 mM sodium taurocholate (TC) weakens the mucosal defensive mechanism in rat stomachs. The ex vivo stomachs of anesthetized animals were perfused with 100 mM HCl. In the control tap water group, mucosal application of 10 mM TC dissolved in 100 mM HCl for 30 min caused a marked increase in gastric mucosal blood flow (GMBF), a reduction in transmucosal potential difference (PD), acid loss and visible mucosal damage. In the TC group, however, acidified TC applied for 30 min caused only a slight increase in GMBF, a reduction in PD, significant acid loss and severe mucosal damage. These results indicate that the mucosal defensive mechanism was extensively weakened after chronic treatment with TC.

Action Potentials↗

Changes in gastric function and healing of chronic gastric ulcers in aged rats.

The present study was designed to determine the relationship between changes in gastric function caused by aging and the healing of gastric ulcers. Male Fischer-344 rats (young, 2 months; aged, 24-26 months) were used. Gastric ulcers were induced by luminal application of an acetic acid solution (60%, 0.2 ml, 45 sec). The basal and histamine-stimulated gastric acid secretions in aged animals were significantly lower than those in young animals. However, the serum gastrin levels were almost the same in the two groups. Gastric mucosal blood flow and mucosal cell proliferation were also decreased in aged animals. Gastric contractile activity induced by electrical vagal stimulation was almost the same in the two groups, while the gastric relaxative response was significantly reduced in aged animals. The development and healing rate of gastric ulcers in aged animals were almost the same as those in young animals. Histologically, regeneration of the ulcerated mucosa was significantly reduced and tissue contraction occurred in aged animals, as compared to in young animals. We concluded that aging had little or no influence on the development and healing rate of gastric ulcers in rats, but the quality of ulcer healing was quite different between young and aged animals, probably resulting from various gastric dysfunctions related to ulcer healing.

Acetates↗

Mucosal protective effect of leminoprazole on reflux esophagitis induced in rats.

We examined the effect of leminoprazole (an acid pump inhibitor) on reflux esophagitis induced in rats. Intragastrically administered leminoprazole significantly and dose-dependently protected the esophageal mucosa against the reflux of gastric contents, without affecting gastric acid secretion. However, it had no effect on the esophagitis when administered intraduodenally, despite its significant inhibition (about 40%) of gastric acid secretion. Omeprazole significantly prevented the development of esophagitis, most probably through potent inhibition of gastric acid secretion. Indomethacin significantly reduced the synthesis of prostaglandin E2 in the esophagus. Since indomethacin pretreatment had no effect on the esophageal protection by leminoprazole, omeprazole or sucralfate, the involvement of endogenous prostaglandins can be ruled out as a possible underlying mechanism. Intragastrically, but not intraduodenally, administered sucralfate significantly prevented the esophagitis even at a dose not affecting gastric acid secretion. These results strongly suggest that both leminoprazole and sucralfate protect the esophageal mucosa directly.

Animals↗

Antisecretory effect of leminoprazole on histamine-stimulated gastric acid secretion in dogs: potent local effect.

Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for > 26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8-10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.

Animals↗

Enterogenous cyst in the fourth ventricle--case report.

A 53-year-old male presented with a rare enterogenous cyst in the fourth ventricle associated with repeated ventriculoperitoneal shunt malfunction. Surgical excision of the cyst resolved the shunt problems. Electron microscopy findings of the surgical sample were microvilli covered with electron-dense coating materials, basement membrane, and several intercellular junctional devices, suggesting the cyst was derived from the endodermal structure. The viscous and gelatinous contents of the cyst might be responsible for the shunt malfunction.

Cerebral Ventricles↗

Nitric oxide and prostaglandins in regulation of acid secretory response in rat stomach following injury.

The gastric mucosa responds to taurocholate (TC) by significantly decreasing acid secretion. We examined the role of nitric oxide (NO) in this phenomenon in comparison with endogenous prostaglandins. A rat stomach was mounted in an ex-vivo chamber and perfused with saline, and the potential difference, luminal pH and acid responses were measured before and after the application of 20 mM TC for 30 min with or without pretreatment with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. Exposure of the stomach to TC caused a reduction in potential difference, a decrease in acid secretion and an increase in luminal HCO3-. Pretreatment with L-NAME or indomethacin did not affect potential difference and HCO3- responses, but it significantly attenuated the decrease in acid secretion caused by TC. The effect of L-NAME was more potent than that of indomethacin, and, especially in the presence of L-NAME, acid secretion was actually enhanced after exposure to TC. Aminoguanidine, the selective inhibitor of inducible NO synthase, did not have any significant effect on either parameter. This effect of L-NAME was antagonized by the simultaneous administration of L-arginine but not by that of D-arginine, whereas the effect of indomethacin was reversed by PGE2. Acid secretion in normal stomachs was significantly reduced by nitroprusside and PGE2 but was not affected by either L-NAME or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulatory effect of leminoprazole on secretion and synthesis of mucus by rabbit gastric mucosal cells.

We examined whether leminoprazole (an acid pump inhibitor) enhances the secretion and synthesis of gastric mucus in vitro. Mucosal cells were prepared from male rabbit stomachs, and the amounts of secreted and synthesized mucus were determined by the [3H] glucosamine labeling method. Exposure of gastric mucosal cells to leminoprazole at 1 to 100 microM for 8 hr caused significant increases in the secretion and synthesis of mucus in a dose-related manner, but omeprazole was not effective. The stimulatory effects of leminoprazole on secretion and synthesis were observed 4 hr and 6 hr later, respectively. In contrast, both 16,16-dimethyl prostaglandin E2 and nitroprusside, a nitric oxide (NO) generator, caused marked increases in mucus secretion and synthesis even after 2-hr incubation. The effects of leminoprazole on gastric mucus were strongly inhibited by NO synthase inhibitors such as NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine and by the NO scavenger oxyhemoglobin. However, neither indomethacin (an inhibitor of cyclooxygenase), aminoguanidine (an inhibitor of inducible nitric oxide synthase) nor cycloheximide (a protein synthesis inhibitor) could suppress its effects. These results suggest that leminoprazole stimulates the secretion and synthesis of gastric mucus after a lag period, probably through NO produced by constitutive NO synthase.

Animals↗

[Assessment of disturbance of urinary bladder function after an operation for rectal cancer].

Disturbance of urinary bladder function occurs frequently after operations on rectal cancer. Clinical studies of 15 male patients with resected rectal cancers revealed a close relationship between the disturbance of urinary bladder function and the extent to which the autonomic nerves in the pelvis were disturbed. Clinically, transection of the hypogastric nerve did not affect urinary function. Branches to the urinary bladder in the pelvic plexus controlled bladder function bilaterally. Transection of one side of the pelvic splanchnic nerve (PSN) did not affect bladder function. Partial transection of the bilateral PSN strongly affected bladder function, but in these cases, compensation by the non-disturbed PSN improved urinary bladder function 3 months after the operation. It seems possible that the lower-grade branches to the urinary bladder in the PSN may control bladder function. Uroflowmetry, amount of residual urine, cystometry, and urinary bladder compliance were all useful in assessing disturbance of branches to the urinary bladder in the PSN. To assess the grade of severe Clinical cases, it proved the most convenient to examine the uroflowmetry and amount of residual urine.

Adult↗

Variation in the primary structure of waxy proteins (granule-bound starch synthase) in diploid cereals.

The molecular weights of waxy proteins, by SDS-PAGE, and the N-terminal amino acid sequences of mature protein and of V8 protease-induced fragments were determined in diploid cereals. The homology of the primary structure was relatively high among cereals examined here, and there appeared to be a common sequence, V-F-V-G-A-E-M-A, in the vicinity of the N terminus. Based on the amino acid sequences, these cereals could be divided into two groups, including corn and rice in one and diploid wheat, four Aegilops species, rye, and barley in the other. In diploid wheat and Aegilops species there were substitutions of amino acids in the primary structure. Variations of this sort suggest that the primary structure of waxy proteins would provide clues to the phylogenetic relations in the wheat group.

Amino Acid Sequence↗