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S Okabe

Publications and source records attributed to S Okabe.

At least 289 records · Page 16Linked to original sources
PubMed1993

[Studies on insecticidal ingredients from culture supernatant of Bacillus thuringiensis].

Studies on the insecticidal activity of culture supernatant of Bacillus thuringiensis var. kurstaki HD-1, by centrifugation, column chromatography, protein sequence determination, bioassay and other methods. Found that insecticidal activity of culture supernatant appeared on synchronism with cells lysis. Main insecticidal ingredients of culture supernatant is toxin protein of 60 kilodaltons (kDa). Analyse hat purified the toxin protein, we find that its amino acid composition was similar with 135-kDa P1 protein, and its sequence of N-terminal 18 amino acid was same with that of part of the P1 protein. The results presented here provided that the toxin protein was the same source with the P1 protein. Further found that supernatant have synergizing action on the sediment of culture.

Amino Acid Sequence↗
PubMed1992

Immunocytochemical localization of 205 kDa microtubule-associated protein (205 kDa MAP) in the guinea pig organ of Corti.

We have studied the immunocytochemical localization of microtubule-associated proteins (MAPs) in the guinea pig organ of Corti. Using immunological methods with antibodies against MAP1A, MAP1B, MAP2, tau and 205 kDa MAP, we have identified 205 kDa MAP as a major MAP of the sensory epithelium in the organ of Corti. Immunoperoxidase microscopic study has shown that both cochlear hair cells and supporting cells reacted with anti-205 kDa MAP antibody. Immunoelectron microscopy revealed that 205 kDa MAP was associated with most microtubules in the sensory epithelial cells. It was also associated with the microtubules of bundle structures within supporting cells, suggesting that this MAP might form a part of cross-bridges between microtubules and between microtubules and actin filaments in the bundle structure. In contrast, MAP1A, MAP1B and tau, which are known to be expressed in neuronal tissue, were localized only in nerve fibers in the organ of Corti, not in the sensory epithelium. MAP2, which is known to be localized in dendrites and soma of nerve cells, was not distributed in nerve fibers in the organ of Corti. These results suggest possible roles of the 205 kDa MAP in the formation and maintenance of the highly polarized morphology of the epithelial cells of the organ of Corti, through stabilization and modulation of microtubule networks of these cells.

Animals↗
PubMed1992

The Saccharomyces cerevisiae NPS1 gene, a novel CDC gene which encodes a 160 kDa nuclear protein involved in G2 phase control.

We have cloned the gene NPS1 (nuclear protein of Saccharomyces) which encodes a nuclear protein of mol. wt 156 735 Daltons (1359 amino acids) essential for cell growth. NPS1 contains a 2 kb sequence that is highly homologous to the S. cerevisiae SNF2/GAM1 gene known as a transcriptional regulator for multiple genes. However, the NPS1 gene was found to have a distinct function from SNF2/GAM1. The growth of the cells carrying a nps1 delta :: URA3 deletion allele and galactose-inducible NPS1 on a plasmid was arrested under NPS1-repressed conditions with a cell cycle arrest phenotype, being arrested at the large-bud stage with a single nucleus that had a DNA content of G2/M phase. When the arrested cells were further incubated under NPS1-repressed conditions, re-replication of DNA occurred in some of the arrested cells without passage through mitosis. In the predicted amino acid sequence of NPS1, sequences homologous to the catalytic domain of protein kinases were found. We constructed a mutation which results in the substitution of a highly conserved lysine residue (Lys792) in the presumed ATP-binding site of this kinase-like domain with a glutamic acid codon. The mutant gene failed to rescue the growth defect caused by NPS1 disruption, suggesting that Lys792 is essential for the function of NPS1.

Amino Acid Sequence↗
PubMed1992

Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants.

The role of capsaicin-sensitive sensory nerves in gastric mucosal blood flow (GMBF) responses to mild irritants was investigated in the rat stomach mounted on a lucite chamber using hypertonic NaCl and 0.2 N HCl. Exposure of the mucosa to hypertonic NaCl (0.5, 0.75, 1 M) for 10 min caused a reduction in the transmucosal potential difference (PD) in a concentration-related manner, followed by an increase of luminal pH and GMBF. In contrast, mucosal application of 0.2 N HCl caused no or little change in PD and pH, but increased GMBF significantly. Functional ablation of capsaicin-sensitive sensory nerves significantly inhibited the increase of GMBF after exposure to these irritants, although the PD and pH responses induced by 1 M NaCl remained unaltered by this treatment. Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly attenuated the GMBF responses to 1 M NaCl and 0.2 N HCl and inhibited the increase of pH caused by 1 M NaCl. Mucosal application of capsaicin (0.1 mg/ml for 10 min) produced an increase of GMBF without being accompanied by change in PD and pH, and this effect was significantly blocked by either indomethacin or chemical deafferentation. These results suggest that capsaicin-sensitive sensory nerves as well as endogenous prostaglandins may be involved in the mechanism of GMBF responses induced by mild irritants, and the latter might sensitize these nerves to mucosal irritation. PD reduction may be obligatory for pH but not GMBF responses.

Animals↗
PubMed1992

Role of capsaicin-sensitive sensory nerves in acid-induced bicarbonate secretion in rat stomach.

The effect of capsaicin-sensitive afferent nerves on the alkaline secretory response induced by mucosal acidification was investigated in the ex vivo stomachs of anesthetized rats. The stomach was mounted on a Lucite chamber and perfused with saline (pH 4.5) in the absence of acid secretion (omeprazole pretreatment: 60 mg/kg, intraperitoneal), and luminal pH and transmucosal potential difference (PD) were monitored simultaneously. Under these conditions the gastric mucosa responded to intravenous injection of prostaglandin E2 (PGE2: 300 micrograms/kg) and mucosal acidification (0.2 N HCl for 10 min) by a significant increase of pH with a slight decrease of PD; the HCO3- output was 9.2 +/- 0.7 mumol and 8.4 +/- 0.8 mumol, respectively. The increased pH and HCO3- responses were significantly inhibited by prior administration of indomethacin (5 mg/kg, subcutaneously) or chemical deafferentation following capsaicin injections (total dose: 100 mg/kg, subcutaneously), whereas those induced by PGE2 remained unchanged after either treatment. On the other hand, the mucosal application of capsaicin (0.3-6 mg/ml) increased the luminal pH and HCO3- output in a concentration-related manner, and this action was also significantly attenuated by either indomethacin or chemical deafferentation of capsaicin-sensitive sensory neurons. These results suggest that capsaicin-sensitive sensory nerves may be involved in the mechanism of acid-induced HCO3- secretion in the stomach, in addition to endogenous PGs, and these two pathways may interact somewhere in the stimulatory process.

Animals↗
PubMed1992

Structurally different members of the okadaic acid class selectively inhibit protein serine/threonine but not tyrosine phosphatase activity.

The relative potencies of four main types of okadaic acid class compounds as inhibitors of the catalytic subunits of protein serine/threonine phosphatases 1 and 2A and the protein tyrosine phosphatase 1 were determined. These four types of compounds are okadaic acid, calyculin A, microcystin-LR, and tautomycin, which are isolated from different natural sources, a black sponge Halichondria okadai, a marine sponge Discodermia calyx, a blue-green alga Microcystis aeruginosa, and Streptomyces spirover ticillatus, respectively. While okadaic acid was a more effective inhibitor of protein phosphatase 2A (IC50, 0.07 nM) than protein phosphatase 1 (IC50, 3.4 nM), other compounds of the okadaic acid class were equally effective against the two protein serine/threonine phosphatases. The order of potency was microcystin greater than calyculin A greater than tautomycin, and the IC50S ranged from 0.1 to 0.7 nM. None of the okadaic acid class compounds inhibited protein tyrosine phosphatase 1 activity at concentrations up to 0.01 mM. These results indicate that the compounds of the okadaic acid class are selective inhibitors of protein serine/threonine but not tyrosine phosphatases.

Animals↗
PubMed1992

Anticarcinogenic effects of (-)-epigallocatechin gallate.

BACKGROUND: Our research objective is to develop nontoxic cancer chemopreventive agents and to apply these agents in treating humans. We are identifying agents that inhibit the process of tumor promotion in two-stage carcinogenesis experiments on mouse skin. METHODS: We review (a) the inhibitory effect of penta-O-galloyl-beta-D-glucose (5GG) on tumor promotion by teleocidin, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (5GG is structurally similar to (-)-epigallocatechin gallate (EGCG) and is isolated from hydrolyzed tannic acid); (b) the inhibitory effects of EGCG, the main constituent of Japanese green tea, on tumor promotion with two tumor promoters, teleocidin and okadaic acid, a non-TPA-type tumor promoter; (c) the mechanisms of action of EGCG, a single application of which reduced the specific binding of [3H]TPA and [3H]okadaic acid to a particulate fraction of mouse skin; and (d) the anticarcinogenic effects of EGCG on duodenal carcinogenesis induced by N-ethyl-N'-nitro-N-nitrosoguanidine in male C57BL/6 mice. EGCG is a nontoxic compound. CONCLUSION: We believe that the main constituent of Japanese green tea, EGCG, is a practical cancer chemopreventive agent available in everyday life.

Animals↗
PubMed1992

Differential behavior of photoactivated microtubules in growing axons of mouse and frog neurons.

To characterize the behavior of axonal microtubules in vivo, we analyzed the movement of tubulin labeled with caged fluorescein after activation to be fluorescent by irradiation of 365-nm light. When mouse sensory neurons were microinjected with caged fluorescein-labeled tubulin and then a narrow region of the axon was illuminated with a 365-nm microbeam, photoactivated tubulin was stationary regardless of the position of photoactivation. We next introduced caged fluorescein-labeled tubulin into Xenopus embryos and nerve cells isolated from injected embryos were analyzed by photoactivation. In this case, movement of the photoactivated zone toward the axon tip was frequently observed. The photoactivated microtubule segments in the Xenopus axon moved out from their initial position without significant spreading, suggesting that fluorescent microtubules are not sliding as individual filaments, but rather translocating en bloc. Since these observations raised the possibility that the mechanism of nerve growth might differ between two types of neurons, we further characterized the movement of another component of the axon structure, the plasma membrane. Analysis of the position of polystyrene beads adhering to the neurites of Xenopus neurons revealed anterograde movement of the beads at the rate similar to the rate of microtubule movement. In contrast, no movement of the beads relative to the cell body was observed in mouse sensory neurons. These results suggest that the mode of translocation of cytoskeletal polymers and some components of the axon surface differ between two neuron types and that most microtubules are stationary within the axon of mammalian neurons where the surface-related motility of the axon is not observed.

Animals↗
PubMed1992

An alternative theory of tissue specificity by tumor promotion of okadaic acid in glandular stomach of SD rats.

To challenge the theory of tissue specificity of tumor promoters, the biochemical and tumor promoting effects of okadaic acid (OA), a potent tumor promoter on mouse skin, were studied in the mucosa of rat glandular stomach. OA strongly inhibited protein phosphatases 1 and 2A, and increased 4-fold the phosphorylation of elongation factor 2 in vitro in the mucosa. Intubation of 10 micrograms (12.4 nmol) OA induced ornithine decarboxylase in the mucosa. Tumor promotion of OA was studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a two-stage carcinogenesis experiment. OA in drinking water, 10 micrograms (12.4 nmol) per rat per day from weeks 9-55 of the experiment, and 20 micrograms (24.8 nmol) from weeks 56-72, significantly enhanced development of the neoplastic changes in the glandular stomach (P < 0.05). The neoplastic changes included adenomatous hyperplasias and adenocarcinomas, both of which correspond to papillomas and carcinomas in a two-stage mouse skin carcinogenesis experiment. The percentages of neoplastic change-bearing rats of the groups treated with MNNG plus OA, MNNG alone or OA alone were 75.0, 46.4 and 0% respectively. OA enhanced tumorigenesis in the MNNG-initiated glandular stomach of rats through the same mechanisms of action as in mouse skin. The OA pathway mediated through inhibition of protein phosphatases 1 and 2A is applicable to various organs as a general mechanism of tumor promotion.

Animals↗
PubMed1992

Induction of duodenal ulcers in sensory deafferented rats following histamine infusion.

We used capsaicin as a selective probe for sensory neuronal mechanisms and examined in rats whether defunctionalization of the sensory nerves caused duodenal ulcers in the presence of acid hypersecretion. Chemical deafferentation was performed by subcutaneous injection of capsaicin for 3 days (total dose: 100 mg/kg) 2 weeks before the experiment. This treatment did not cause by itself any damage in the duodenum. However, intravenous infusion of histamine (4, 8 and 16 mg/kg/h) in these animals caused hemorrhagic lesions in the proximal duodenum within 6 h in a dose-dependent manner with an incidence of 100%. Histamine alone in the control animals did not induce macroscopically visible lesions at lower doses and caused only slight damage at the highest dose (16 mg/kg/h), although acid secretion was stimulated to the maximal degree at 8 mg/kg/h. Ablation of capsaicin-sensitive sensory neurons did not have any effect on acid secretion induced by histamine (8 mg/kg/h), but significantly inhibited the increase in duodenal HCO3- secretion in response to mucosal acidification. We conclude that functional ablation of capsaicin-sensitive sensory nerves impairs duodenal HCO3- secretory response to acid and results in duodenal ulcers if acid hypersecretion is present. These sensory nerves may be important in the defense mechanism of the duodenum against luminal acid.

Animals↗
PubMed1992

Prostaglandin E2 inhalation increases the sensation of dyspnea during exercise.

To clarify the role of vagal afferents from the lung in the sensation of dyspnea, we examined the effects of prostaglandin E2 (PGE2) inhalation on the sensation of dyspnea during exercise in eight normal male subjects. This intervention was chosen because inhaled PGE2 is known to stimulate vagal afferent receptors in the lung, in particular C-fiber endings, without a significant increase in airway resistance. After either physiologic saline or PGE2 aerosol (100 micrograms/ml) inhalation through a Bird nebulizer for 2 min, exercise tests were performed on a bicycle ergometer. The tests consisted of 3 min at rest followed by graded work loads (zero to 150 watts, 50-watt increments). Minute ventilation (VE) and respiratory rate were monitored from an expiratory line through a face mask. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated from samples of mixed expired gas. The sensation of difficulty in breathing (dyspnea) was measured on a modified Borg scale at rest and at the end of each work load. We found that although airway resistance and lung volume did not change significantly between saline and PGE2 inhalations, inhaled PGE2 significantly increased the magnitude of the dyspneic sensation when compared with inhaled saline at the same levels of work load, ventilation, and oxygen consumption. These results suggest that in addition to probable roles of motor command and chemical drive, afferent vagal activity from the lung also contributes to the sensation of dyspnea during exercise.

Adult↗
PubMed1992

Effects of repetitive airway obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs.

We examined the effects of multiple repetitive airway obstruction (RAO) on arterial oxygen saturation (SaO2) and pulmonary and systemic arterial pressure in eight anesthetized spontaneously breathing dogs. SaO2 was monitored at the tongue with a pulse oximeter. RAO created by an electrical valve that was attached to a tracheal cannula was alternated with seven consecutive spontaneous breaths until the nadir SaO2 (nSaO2) became constant or decreased to less than 35%. Tracheal occlusion durations of 15, 30, 45 and 60 s were chosen arbitrarily. In each animal nSaO2 decreased with every trial number in an exponential fashion, and the rate of nSaO2 fall was greater for the longer occlusion duration. In each animal the increases in pulmonary arterial pressure (PAP) and systemic arterial pressure (SAP) were inversely related to the nSaO2 values, and the relationship between nSaO2 and PAP or SAP was identical for all occlusion durations. Moreover, when the animals breathed pure oxygen and SaO2 did not decrease, there were no significant increases in the PAP and SAP at similar levels of pleural pressure (Ppl). In another six dogs, the effects of RAO on PAP and SAP were compared with those of intermittent hypoxic exposure without apnea, which was achieved by the inhalation of hypoxic gas (4 to 6% O2, 5% CO2 in N2) instead of RAO, to examine the effects of interruption of ventilation. The relationships between nSaO2 and both pressures did not differ significantly from those during RAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1992

Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or tau.

We previously transfected MAP2, tau and MAP1B cDNA into fibroblasts and have studied the effect of expression of these microtubule-associated proteins on microtubule organization. In this study, we examined some additional characteristics of microtubule bundles and arrays formed in fibroblasts transfected with these microtubule-associated proteins. It was found that microtubule bundles formed in MAP2c- or tau-transfected cells were stabilized against microtubule depolymerizing reagents and were enriched in acetylated alpha tubulin. When mouse MAP1B cDNA was expressed following transfection into COS cells, MAP1B was localized along microtubule arrays, but no extensive reorganization of microtubules such as bundle formation was observed, in agreement with our previous finding using HeLa and 3T3 cells. However, stabilization of microtubules was indicated: (a) microtubules in MAP1B-transfected cells were stabilized against a microtubule depolymerizing reagent, although stabilization was less efficient than that seen in MAP2c- or tau-transfected cells, and (b) microtubules in MAP1B-transfected cells were enriched in acetylated alpha tubulin. These results suggest that neuronal microtubule-associated proteins introduced into fibroblasts by cDNA transfection stabilize microtubules and affect the state of post-translational modification of tubulin.

Acetylation↗
PubMed1992

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

A series of 2-[(2-imidazolylsulfinyl)methyl]anilines (2) having various substituents on their imidazole and aniline rings was synthesized and examined for their H+/K(+)-ATPase (adenosine triphosphatase) inhibitory effects and antisecretory activity against histamine-stimulated gastric acid secretions in Heidenhain pouch dogs. Although substitutions on the imidazole ring did not enhance biological activity, substitutions on the aniline ring by electron-donating substituents potently enhanced the enzyme inhibitory activity and also showed an inhibitory effect on histamine-stimulated gastric acid secretion after oral administration. In particular, the in vitro activity of the dimethyl (2u--w) and trimethyl (2ac) derivatives was about 10 times that of omeprazole. Also, 4-methyl (2k), 4-methoxy-5-methyl (2y) and 3,5-dimethyl-4-methoxy (2ab) derivatives showed a potent antisecretory effect of more than 80% after oral administration at 6 mg/kg. Although these aniline derivatives have relatively low stabilities in aqueous solution, replacement of the isobutyl group at the aniline nitrogen atom with N-(2-methoxyethyl) group enhanced the stability.

Adenosine Triphosphatases↗
PubMed1992

[Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric secretion and gastric and duodenal lesions induced in rats. Comparison with roxatidine].

A new compound, IGN-2098 [5,6-dimethyl-2-[4-<3-(1-piperidinomethyl) phenoxy>cis-butenylamino]-4-(1H)-pyrimidone.2HCl], was found to be a potential histamine H2-receptor antagonist in the guinea pig atrium. IGN-2098, given p.o., significantly and persistently (for more than 12 hr) inhibited the basal gastric secretion in pylorus-ligated rats. The agent also significantly inhibited the basal gastric secretion when given by the s.c.-, i.d.- or i.p.-route. Stimulated gastric secretion in fistula rats in response to histamine, carbachol or pentagastrin was also significantly inhibited with IGN-2098 given s.c. Pretreatment with IGN-2098 (p.o.) significantly protected the gastric mucosa against pylorus ligation-, water-immersion stress-, histamine-, indomethacin-, HCl.aspirin-, and HCl.ethanol-induced gastric lesions. In addition, the agent significantly protected the duodenal mucosa against mepirizole-induced ulcers. Based upon the ED50 values, the antisecretory effects on histamine, carbachol or pentagastrin-stimulated acid secretion were 6.0, 37.0 or 80 times more potent than roxatidine, respectively. As to the anti-lesion effects on HCl.aspirin-induced gastric lesions or mepirizole-induced duodenal ulcers, IGN-2098 was 8.1 or 14.8 times more potent than roxatidine, respectively. These results suggest that IGN-2098 will be a useful drug for the treatment of gastric and duodenal lesions in man.

Animals↗
PubMed1992

Effects of sulfhydryl-related compounds on indomethacin-induced gastric lesions in rats: role of endogenous sulfhydryls in the pathogenesis.

The role of mucosal sulfhydryl (SH) in the pathogenesis of indomethacin-induced gastric lesions was investigated in rats. Indomethacin (25 mg/kg, s.c.) caused high-amplitude gastric contractions, resulting in linear hemorrhagic lesions in the corpus mucosa within 4 hr, but did not induce any changes in the mucosal SH levels. These lesions were prevented significantly by prior s.c. administration of cysteamine, glutathione (GSH) or diethylmaleate (DEM), irrespective of whether the mucosal SH was increased by the former two agents or reduced by the latter. N-Ethylmaleimide (NEM) tended to worsen such lesions without any effect on the mucosal SH contents. Gastric hypermotility caused by indomethacin was inhibited significantly by DEM, cysteamine and GSH, while acid secretion was reduced by DEM and NEM. Both cysteamine and GSH prevented the indomethacin-induced linear lesions even in the stomach perfused with 150 mM HCl, whereas in the animals treated with DEM, nonlinear damage was induced exclusively in the antrum by indomethacin in the presence of acid. We conclude that the mucosal SH has no relation to the ulcerogenicity of indomethacin in the gastric corpus mucosa.

Animals↗
PubMed1992

Stimulation by capsaicin of gastric alkaline secretion in anesthetized rats.

Effects of mucosal application of capsaicin on alkaline secretion were examined in the stomachs of anesthetized rats and compared with those in the duodenum. The stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5); both the pH of the perfusate and transmucosal potential difference (PD) were continuously monitored; and the HCO3- output was determined by the pH change. Under these conditions, the mucosal application of capsaicin (0.3-6 mg/ml for 30 min) caused significantly increased pH and HCO3- output in a concentration-related manner in both tissues, while PD increased in the duodenum and decreased in the stomach. The HCO3- stimulatory action of capsaicin was markedly attenuated by sensory deafferentation, significantly mitigated by prior administration of indomethacin, and exhibited a marked tachyphylaxis after the repeated exposure at a high concentration (6 mg/ml). None of these treatments had any effect on the pH, PD and HCO3- responses induced by prostaglandin E2 (300 micrograms/kg, i.v.) in these tissues. These results indicate that mucosal application of capsaicin increased the gastroduodenal HCO3- output by stimulation of capsaicin-sensitive sensory neurons. This action may be in part mediated by endogenous prostaglandins.

Afferent Pathways↗