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Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 307 records · Page 17Linked to original sources
PubMed1992

Effect of ketotifen on acute gastric lesions and gastric secretion in rats.

Ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, significantly protected the rat gastric mucosa against lesions induced by necrotizing agents, histamine or compound 48/80. The agent significantly inhibited the basal gastric acid secretion, but had little or no effect on the histamine-stimulated secretion. The mucosal protective effect was observed even at a dose that had little or no effect on gastric acid secretion, suggesting that ketotifen exhibits so-called cytoprotective activity.

Animals↗
PubMed1992

Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine.

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.

Acetamides↗
PubMed1992

Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.

Amino Acid Oxidoreductases↗
PubMed1992

Induction of gastric lesions by 2-deoxy-D-glucose in rats following chemical ablation of capsaicin-sensitive sensory neurons.

Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification.

Animals↗
PubMed1992

Marine natural products against tumor development.

This review article deals with significant effects of marine natural products in carcinogenesis, namely as chemical probes to understand the process of carcinogenesis and as possible cancer preventive agents in humans.

Amphibian Proteins↗
PubMed1992

[Bronchial asthma].

In the first study, to clarify whether increased vagal afferent activity contributes to the increase in ventilatory response to CO2 in patients with asthma, we examined the effects of prostaglandin E2 (PGE2) inhalation on the respiratory response to CO2 in seven normal subjects. After PGE2 inhalation, the ventilatory and occlusion pressure responses to CO2 increased significantly compared with those after saline inhalation, with no increase in respiratory resistance. These results suggest that increase in vagal afferent activity may play a role in the increased hypercapnic response during acute exacerbations of asthma. In the second study, to clarify the reduced respiratory chemosensitivity associated with asthma-related deaths, we examined the hypercapnic and hypoxic ventilatory responses in five patients with near-fatal asthma who were given artificial ventilation and/or became unconsciousness during an acute exacerbation of asthma. Hypoxic ventilatory response was significantly lower in these subjects than in patients with uncomplicated asthma and normal subjects, suggesting that lowered hypoxic ventilatory response may be related to death from asthma.

Asthma↗
PubMed1992

[Home oxygen therapy using liquid oxygen system].

Home oxygen therapy (HOT) for patients with chronic respiratory failure has been believed to increase the quality of life and to improve the prognosis of such patients. In Japan, HOT for chronic respiratory failure has been supported by health insurance since March 1985. Since then, patients with HOT have increased progressively, and it has been reported that there are now over 20,000 patients with HOT. The oxygen concentrator which extracts oxygen from atmospheric air has been commonly used as the oxygen delivery system. Recently the liquid oxygen system has provided an attractive, convenient source of oxygen. Since April 1990, HOT using liquid oxygen system has been supported by health insurance, and its use will become widespread in Japan. A major characteristic of this system is that oxygen condensed into a liquid form allows storage of a larger supply. This system consists of two parts: stationary type which stores the liquid oxygen, and a portable type which can easily be refilled with oxygen a larger source. In the present study, we examined the efficacy of portable liquid oxygen in 50 patients with chronic pulmonary diseases including patients with chronic respiratory failure who had PaO2 < 55 mmHg during air breathing. We measured changes of ten minutes walking distance (10 MD) and blood gas analysis with and without portable liquid oxygen. We also performed on estimation of efficacy of liquid oxygen by questionnaires in patients receiving liquid oxygen for HOT. We did not find a significant improvement of 10 MD with portable liquid oxygen, but found a significant improvement of arterial oxygen tension at the end of walking.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1992

[Discovery and development of the proton pump inhibitor].

Gastric (H+/K+)-ATPase, the proton pump of the parietal cell, is responsible for the final step of acid secretion in the stomach. In 1981, picoprazole, a substituted benzimidazole, was found to inhibit (H+/K+)-ATPase. It was reported in 1983 that omeprazole has the most potent efficacy among the substituted benzimidazoles and today, omeprazole has been used for treatment of gastroduodenal disease. Recently, lansoprazole, similar to omeprazole in chemical structure, was developed in Japan, and several other compounds, such as pantoprazole, E-3810 and NC-1300-O-3, have also been reported to suppress acid secretion through inhibition of (H+/K+)-ATPase. In the present paper the background of the discovery of (H+/K+)-ATPase and development of proton pump inhibitors is reviewed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

[Electrophysiological identification of the cochlear and vestibular nerves in the cerebellopontine angle: experimental study and clinical implication].

Electrical stimulation was applied on the surface of the eighth cranial nerve in the cerebellopontine angle of dogs and the evoked potentials were recorded with surface electrodes on the scalp. The shape of the evoked potentials recorded was different according to the portion of the nerve stimulated electrically. It was, therefore, possible to precisely identify the nerve stimulated from the surface recorded evoked potentials. This electrophysiological method may be helpful for the surgeon to precisely locate the cochlear and vestibular nerves in various operations in the cerebellopontine angle in human. Our preliminary experience of this monitoring method in acoustic neuroma excision was presented.

Animals↗
PubMed1992

[Controversy on therapeutic modality to early colorectal carcinomas from the viewpoint of histopathological features].

We have investigated prognostic factors of early colorectal carcinoma mainly based on pathological aspects. We have experienced 175 lesions of early colorectal carcinomas, in which 116 lesions were obtained by operation and 59 lesions were endoscopically resected. Histologically, well differentiated adenocarcinoma was subclassified into two types, pure type and combined type. We expressed extent of submucosal invasion by sm depth and sm width. We represented specific pathological features in the invasive margin as single cell infiltration (SCI) and mucinous component (MUC), which were indicating biological invasiveness of submucosal invasive carcinomas. As a result of this research, we concluded that minimal submucosal invasion of early colorectal carcinoma should be defined as carcinoma having sm depth less than 1 mm and sm width less than 5 mm, on the contrary, sm massive invasion as sm depth above 1 mm or sm width above 5 mm. We guessed that SCI was good parameter of lymphatic invasion because of their correlation to other adverse prognostic factors. We make a policy that subsequent intestinal resection should be performed to early colorectal carcinomas, which having SCI or MUC concomitant with the degree of submucosal invasion more than our standard despite of absence of vascular permeation.

Adenocarcinoma↗
PubMed1991

Role of thyrotropin-releasing hormone in acid secretory response induced by lowering of body temperature in the rat.

Acid secretory and mucosal ulcerogenic responses to hypothermia (36-24 degrees C) were examined in anesthetized rats, and the role of thyrotropin-releasing hormone (TRH) in these responses was investigated. Lowering of body temperature (less than 32 degrees C) induced acid hypersecretion and damage in the gastric mucosa. These responses reached a maximum at a body temperature of 28 degrees C and were completely abolished by bilateral cervical vagotomy and significantly inhibited by intracerebroventricular (i.c.v.) administration of TRH antiserum (10 microliters/rat). TRH (10 micrograms/rat) given i.c.v. to the normothermia rat, caused an increase of acid secretion with a pattern similar to those observed during hypothermia. The blood levels of thyroid-stimulating hormone rose significantly during exposure of cold, and this response preceded the onset of acid hypersecretion and lesion formation. Thus, lowering of body temperature induces vagal-dependent gastric acid secretion, probably mediated by TRH released in response to cold exposure, and may be an important element in the etiology of stress ulceration.

Animals↗
PubMed1991

Molecular cloning of hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger.

Roots of several solanaceous plants produce anticholinergic alkaloids, hyoscyamine and scopolamine. Hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase (EC 1.14.11.11), catalyzes hydroxylation of hyoscyamine in the biosynthetic pathway leading to scopolamine. We report here on the isolation of cDNA clones encoding the hydroxylase from a cDNA library made from mRNA of the cultured roots of Hyoscyamus niger. The library was screened with three synthetic oligonucleotides that encode amino acid sequences of internal peptide fragments of the purified hydroxylase. Nucleotide sequence analysis of the cloned cDNA revealed an open reading frame that encodes 344 amino acids (Mr = 38,999). All 12 internal peptide fragments determined in the purified enzyme were found in the amino acid sequence deduced from the cDNA. With computer-aided comparison to other proteins we found that the hydroxylase is homologous to two synthases involved in the biosynthesis of beta-lactam antibiotics in some microorganisms and the gene products of tomato pTOM13 cDNA and maize A2 locus which had been proposed to catalyze oxidative reactions in the biosynthesis of ethylene and anthocyan, respectively. RNA blotting hybridization showed that mRNA of the hydroxylase is abundant in cultured roots and present in plant roots, but absent in leaves, stems, and cultured cells of H. niger.

Amino Acid Sequence↗
PubMed1991

Dual effects of N-ethylmaleimide on ethanol-induced gastric lesions in rats.

The effects of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, on ethanol-induced gastric lesions were investigated in rats by varying the route of administration. Oral administration of acidified ethanol (60% ethanol in 150 mM HCl, 1 ml) produced hemorrhagic bandlike lesions in the gastric mucosa. Pretreatment of the animals with orally administered NEM (0.1-10 mg/kg) dose-dependently inhibited these lesions (the inhibition was over 80% at 1 mg/kg or greater), and the effects were partially reversed by indomethacin (5 mg/kg, subcutaneous). However, when NEM (10 mg/kg) was given subcutaneously, this agent significantly worsened the lesions. Intragastrically applied NEM produced a dose-dependent reduction of the transmucosal potential difference (PD) and the mucosal nonprotein SH levels, an increase of the volume of gastric contents, and an inhibition of gastric motility, while these parameters remained unaltered after subcutaneous administration of the agent. The microvascular permeability in the mucosa was significantly increased by both oral and subcutaneous administration of NEM (10 mg/kg) but remained unchanged in response to lower doses of orally administered (less than 3 mg/kg). These results suggest that NEM given orally is cytoprotective to the stomach against ethanol, probably by acting as a mild irritant and due to dilution of an irritant and inhibition of gastric motility (muscle relaxation), but when given subcutaneously it aggravates the lesions by unknown mechanisms.

Administration, Oral↗
PubMed1991

Vagally mediated acid hypersecretion and lesion formation in anesthetized rat under hypothermic conditions.

The pathophysiological changes associated with hypothermia were investigated in the rat stomach under anesthetized conditions. The animal was placed in a styrene foam box and the core body temperature was kept between 24 and 36 degrees C using a heat lamp and refrigerant pack. Lowering of body temperature (less than 30 degrees C) produced acid hypersecretion and induced hemorrhagic lesions in the gastric mucosa; these responses reached the maximum at 28 degrees C, and a significant relationship was found between acid output and lesion score. Hypothermia (28 degrees C) also caused a marked increase of gastric contractile activity and mucosal blood flow (MBF), but the ratio of acid output to MBF became greater when compared to that obtained under normothermic conditions. These changes induced by hypothermia (28 degrees C) were completely blocked by vagotomy and were significantly inhibited by atropine, hexamethonium, clonidine, or TRH antiserum. However, lowering body temperature did not significantly affect acid secretory, motility, and ulcerogenic responses induced by carbachol in the vagotomized rat, excluding local mechanisms (suppression of the inhibitory nerves) in the hypothermia-induced changes. We conclude that hypothermia alone stimulates vagally dependent acid secretion and motility, resulting in damage in the gastric mucosa. These changes may be centrally mediated by TRH, which is released in association with the thermogenic response to hypothermia.

Animals↗
PubMed1991

Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum.

The role of capsaicin-sensitive afferent neurons in acid-induced HCO3- secretion was investigated in the duodenum of anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential differences were continuously monitored, and HCO3- output was determined by pH change. Under these conditions, duodenal pH, potential difference, and HCO3- output were significantly increased in response to IV injection of prostaglandin E2 (300 micrograms/kg) and luminal acidification (10 mmol/L HCl, 10 minutes). These responses induced by luminal acid were significantly attenuated by SC pretreatment with indomethacin (5 mg/kg), preexposure of the mucosa to lidocaine (4%, 15 minutes), functional ablation of capsaicin-sensitive afferent neurons, or even prior application of capsaicin (6 mg/mL, 30 minutes) to the duodenum. Although capsaicin application by itself (0.3-6 mg/mL) produced a concentration-dependent increase of HCO3- output, this effect was significantly reduced by lidocaine, indomethacin, or chemical deafferentation and exhibited a tachyphylaxis after repeated application at a high concentration (6 mg/mL). Neither of these treatments significantly affected the HCO3- response induced by prostaglandin E2. It was concluded that stimulation of capsaicin-sensitive afferent neurons increased duodenal HCO3- secretion and that these neurons may be involved in the mechanism of HCO3- response induced by luminal acid in the duodenum.

Animals↗
PubMed1991

Effects of focal cooling of the ventral medullary surface on breathing pattern and blood pressure in dogs.

We assessed the effect of focal graded cooling of the ventral medullary surface (VMS) on breathing pattern and blood pressure in 15 anesthetized, vagotomized and artificially ventilated dogs. Diaphragmatic electromyogram or phrenic neurogram, referred to as Ec, and blood pressure (BP) were obtained during localized (2 x 2 mm2) cooling of the VMS. Greatest depression of both Ec and BP was obtained by cooling in the areas located 4-9 mm caudal to the foramen cecum (Fc) and lateral to the pyramids. Mild cooling in these intermediate areas decreased both inspiratory duration (Ti) and the rate of rise of Ec (Ec/Ti), but respiratory rate was unchanged. Cooling of the rostral areas (0-3 mm from Fc) induced mild depression of Ec amplitude due to reduction in Ec/Ti without changing Ti, and prolonged expiratory duration (Te) significantly. Cooling of the caudal areas (12-18 mm from Fc) reduced Ec amplitude mildly due to reduction in Ti without affecting Ec/Ti, and shortened Te greatly. Cooling of the rostral areas produced mild fall in BP, but cooling of the caudal areas did not affect BP significantly. It is suggested that rostral and intermediate parts of the VMS participate in the shaping of inspiratory drive, whereas wide areas of the VMS including caudal part are involved in the determination of respiratory timing. It is also suggested that the rostral and intermediate parts, and not the caudal part, of the VMS are important in the regulation of vasomotor tone.

Animals↗
PubMed1991

Leukemia cutis in acute myelomonocytic leukemia: infiltration to minor traumas and scars.

We describe a patient with acute myelomonocytic leukemia who demonstrated leukemic cell infiltration to scratched wounds and scars from trauma. A 65-year-old Japanese woman developed low grade fever, headache and exanthema. Hematology testing disclosed leukocytosis of 95,600/mm3 with 65% monocytes and 9% blast cells. Infiltrated erythema and nodules were disseminated over most of her body. Moreover, linear scratched wounds and traumatic scars were indurated. Skin biopsy showed dense atypical mononuclear cell infiltration with monocytic characteristics. We discuss the possible reasons for the infiltration of leukemia cells into the wounds and scars from trauma.

Aged↗