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Biomedical subjects

H Muto

Publications and source records attributed to H Muto.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Effects of Helicobacter pylori(Hp) eradication on gastric mucosal pathophysiology in Hp-positive, NSAIDs-induced gastric ulcer].

It has been suggested that the mechanisms of NSAIDs-induced peptic ulcer disease are totally different from those induced by Hp. Although a number of studies have examined the effects of Hp eradication on pathophysiology of NSAIDs-induced ulcer diseases, the results have been controversial. At present, therefore, we do not know whether Hp should be eradicated in Hp-positive NSAIDs-induced ulcer patients. Recent studies have shown that both Hp eradication and NSAIDs treatment increases gastric acid secretion, and often causes mucosal lesions in upper GI tract. Based on this back ground, we have decided to review pathophysiology of the Hp-dependent ulcer, and the NSAIDs-induced ulcer. We also discussed the merit and demerit of Hp eradication on gastric mucosal pathophysiology in Hp-positive, NSAIDs-induced ulcer.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Hydrogen peroxide-induced cellular injury is associated with increase in endogenous fluorescence from rat gastric mucosal epithelial cell culture: A new method for detecting oxidative cellular injury by fluorescence measurement.

To develop a new method of detecting cellular injury caused by oxygen radicals, we studied endogenous fluorescence from the cultured cells of a rat gastric mucosal epithelial cell line. Measurement with an ultra-high sensitivity camera-image processor system under an inverted epifluorescence microscope showed that the fluorescence intensity of the cells increased time- and dose-dependently after the addition of hydrogen peroxide (H2O2), an oxygen radical precursor, to the medium. This increase was inhibited by the presence of catalase. Phase-contrast and fluorescence microscopy revealed that the fluorescence was emitted from granular substances in the cytoplasm of the injured cells. The spectral pattern of excitation and emission indicated that the fluorescent substances were flavins. In cell-free experiments, glutathione reductase which has flavin adenine dinucleotide (FAD) at the active site, increased in fluorescence after incubation with H2O2 in the presence of reduced glutathione and glutathione peroxidase. These findings indicate that FAD in the cytoplasm of cells injured by H2O2 increased in endogenous fluorescence according to the extent of injury, and suggest that fluorescence measurement may be a simple method in cellular toxicology to detect oxygen radical-induced injuries.

Animals↗
PubMed1998

Pancreaticoduodenal artery aneurysms associated with celiac axis stenosis due to compression by median arcuate ligament and celiac plexus.

Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation.

Adult↗
PubMed1998

Steroid-refractory severe ulcerative colitis responding to cyclosporine and long-term follow-up.

We report a case of steroid-refractory ulcerative colitis, treated with cyclosporine, in a 38-year-old woman with a 13-year history of ulcerative colitis. No remission was achieved with treatments that included intravenous hyperalimentation, sulfasalazine, and intensive parenteral prednisolone therapy for 4 weeks. Intravenous infusion of cyclosporine was performed because the patient refused to undergo surgery. Her condition improved dramatically and colectomy was avoided. She has been maintained on oral cyclosporine and azathioprine since steroids were discontinued, and she has remained in clinical and endoscopic remission for 2 years. The side effects were not significant, but mild paresthesia in both hands and mild hypertension, which was controlled by anti-hypertensives. Cyclosporine seems to be an effective treatment for patients with steroid-refractory severe active ulcerative colitis in whom colectomy seems inevitable. We believe further clinical trials of the treatment are warranted.

Adult↗
PubMed1998

Phosphoramidon, an inhibitor of endothelin-converting enzyme, prevents indomethacin-induced gastric mucosal damage in rats.

Endothelin-1 (ET-1) is produced from inactive precursor big ET-1 by endothelin-converting enzyme-1 (ECE-1), a membrane-bound metalloprotease, structurally similar to another metalloprotease, neutral endopeptidase 24.11 (NEP). Although both phosphoramidon and thiorphan are metalloprotease inhibitors, the ECE activity is inhibited by phosphoramidon but not by thiorphan, a specific inhibitor of NEP. Therefore, to investigate whether an ECE inhibitor can prevent indomethacin-induced gastric mucosal damage in rats, we compared the effects between the two metalloprotease inhibitors on both gastric mucosal integrity and the levels of ET-1 and big ET-1 in gastric tissue. Phosphoramidon significantly decreased ET-1 levels, causing a concomitant big ET-1 increase and dose-dependently attenuated indomethacin-induced gastric mucosal damage. By contrast, thiorphan neither changed the ratio of ET-1/big ET-1 nor attenuated the damage. In conclusion, the prevention of gastric mucosal damage by an ECE inhibitor indicates that endogenous ET-1 may play an important role in the pathogenesis of indomethacin-induced gastric mucosal damage.

Animals↗
PubMed1998

[Food and food additives hypersensitivity in adult asthmatics. III. Adverse reaction to sulfites in adult asthmatics].

OBJECTS: Many studies show that sulfites cause multiple atopic manifestations by oral challenge in USA and Europe, however, there are few reports of sulfites sensitivity in Japan. The aim of this study establishes the presence of sulfites hypersensitivities in asthmatic subjects in Japan. SUBJECTS AND METHOD: Twenty adult asthmatic patients, who were non-steroid-dependent and without a suggestive history of sulfite sensitivity, underwent challenge with oral solution of metabisulfite. RESULT: Of 12 patients reacted to metabisulfite. They demonstrated airway obstruction 5 (41.7%), urticaria 4 (36.7%), skin manifestation 2 (16.7%) and nasal congestion 1 (8.3%). All patients who demonstrated airway obstruction, were sensitive to aspirin. CONCLUSION: Oral sulfite challenge should be made in patients with urticaria, that are not able to find out causative antigen, even though no suggestive history of sulfite sensitivity.

Adult↗
PubMed1997

Direct detection of hepatitis B virus gene integrated in the Alexander cell using fluorescence in situ polymerase chain reaction.

Prolonged infection of hepatitis B virus (HBV) is reported to cause hepatocellular carcinoma (HCC) via liver cirrhosis. However, it is still unknown whether the HCC is induced by the HBV DNA integration or by inflammatory stimulation during the phase of liver cirrhosis. The aim of this study is to determine the intracellular or intranuclear distribution of HBV DNA with a highly sensitive assay. Here we directly detected the integration of HBV DNA by fluorescence in situ polymerase chain reaction (FISPCR). Since FISPCR products directly incorporate rhodamine-4-dUTP, the nucleus of Alexander cells integrated with HBV gene reacted with the HBV primers emits obvious fluorescence. The fluorescence values which were measured with an imaging analyzer show a significant difference between Alexander cells as compared to the controls. In conclusion, the target sequences of HBV were specifically amplified as fluorescent DNA after the present FISPCR procedure. This method could provide a novel and simple strategy for determining the quantitative role of viral DNA integration in oncogenesis.

Carcinoma, Hepatocellular↗
PubMed1997

Bosentan, a novel synthetic mixed-type endothelin receptor antagonist, attenuates acute gastric mucosal lesions induced by indomethacin and HCl in the rat: role of endogenous endothelin-1.

Endothelin-1 has been reported to be responsible for gastric mucosal damage in various experimental models. We evaluated the role of endogenous endothelin-1 in the pathogenesis of gastric mucosal damage induced by indomethacin and HCl in the rat. Rats were given indomethacin (25 mg/kg) subcutaneously, and 15 min later, 0.2N HCl intragastrically. Gastric mucosal damage, gastric endogenous endothelin-1, and gastric mucosal hemodynamics were measured. The effects of bosentan, a mixed endothelin receptor antagonist, on gastric mucosal integrity and hemodynamics were assessed. Gastric endogenous endothelin-1 was significantly elevated at 20 min, gastric mucosal blood flow began to decrease significantly at 25 min, and gastric damage occupied 52.2% of the total glandular mucosa at 135 min after injection of indomethacin. Intragastric pretreatment with bosentan (5, 10, 30, and 60 mg/kg) significantly attenuated gastric damage, to 26.1%, 7.7%, 3.6%, and 1.6%, respectively, of the total glandular mucosa. Bosentan (60 mg/kg) prevented the initial decrease of blood flow and, even at 135 min, improved blood flow and hemoglobin oxygen saturation significantly. We suggest that indomethacin-induced endogenous endothelin-1 diminishes gastric mucosal blood flow and tissue oxygenation and ultimately causes gastric damage. Endogenous endothelin-1 may play an important role in the pathogenesis of the acute gastric mucosal lesions induced by indomethacin and HCl.

Animals↗
PubMed1997

Phosphoramidon, an endothelin converting enzyme inhibitor attenuates local gastric ischemia-reperfusion injury in rats.

Recently increased production of endothelin-1 has been implicated in the pathogenesis of gastric ischemia-reperfusion injury. We have investigated the effects of endothelin converting enzyme inhibition on local gastric ischemia-reperfusion injury in rats by using two metalloprotease inhibitors, phosphoramidon and thiorphan. In presence of exogenous 0.15M HCI intragastrically, local ischemia was induced by the clamping of left gastric artery for 15 min and reperfusion was done for 30 min. In separate group of rats, phosphoramidon (10-60 mg/kg) or thiorphan (60 mg/kg) were given as i.v. bolus injection immediately before the induction of ischemia. Phosphoramidon dose dependently attenuated the macroscopic and microscopic mucosal injuries while thiorphan did not. These results indicate that phosphoramidon-sensitive endothelin converting enzyme activity is highly present in stomach and phosphoramidon, by inhibiting the conversion of big endothelin-1 to endothelin-1 attenuated the gastric mucosal damage in this model.

Animals↗
PubMed1997

Gastric mucosal injury induced by local ischemia-reperfusion in rats. Role of endogenous endothelin-1 and free radical.

We investigated the role of an endogenous vasoconstrictor peptide endothelin-1 (ET-1) and free radicals in local gastric ischemia-reperfusion injury in rats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min and reperfusion was done for 10-30 min in the presence of 150 mM exogenous HCl intragastrically. Local gastric ischemia and reperfusion resulted in significant macroscopic and microscopic gastric mucosal damage together with elevation of gastric tissue ET-1 concentration. Gastric tissue ET-1 was found to increase after 15 min of ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptor antagonist, bosentan, or a combination of radical scavengers (superoxide dismutase, catalase, and deferoxamine) both attenuated gastric mucosal injury. However, the greater protection observed with bosentan than with radical scavengers might reflect a preferential role of endothelin-1 in this type of injury.

Animals↗
PubMed1997

Quantitative scintigraphic analysis of 123I-MIBG by polar map in patients with dilated cardiomyopathy.

To evaluate sympathetic dysfunction of the heart, one of the factors responsible for heart failure in patients with dilated cardiomyopathy (DCM), we performed 123I-metaiodobenzylguanidine (123I-MIBG) myocardial single photon emission tomography (SPET) in 22 cases of DCM. There were significant relationships between severity scores and defect scores for the early and delayed images. When the data acquired by 123I-MIBG myocardial SPET were compared with left ventricular function, the extent score (r = -0.754, P < 0.01) and severity score (r = 0.693, P < 0.01) for the early images were both significantly correlated with left ventricular ejection fraction (LVEF). For the delayed images also, a good correlation was obtained between LVEF and extent score (r = -0.704, P < 0.01) and between LVEF and severity score (r = -0.801, P < 0.01). the washout rate for the entire left ventricle, calculated from the early and delayed images, also correlated with LVEF (r = -0.643, P < 0.01). Since the 123I-MIBG defect on the early images was shown to be significantly related to left ventricular function, a decrease in neuronal uptake at sympathetic nerve endings appears in the main to account for the 123I-MIBG defect on the early images. The regional washout rate was increased compared to that in the control group (P < 0.01). It was particularly high in the inferior wall, suggesting that acceleration of turnover and poor retention in the area of the 123I-MIBG defect on the early images and then the entire left ventricle was strongly associated with the 123I-MIBG defect on the delayed images. Our results suggest that 123I-MIBG myocardial SPET may be useful in determining the severity of DCM.

3-Iodobenzylguanidine↗
PubMed1997

A repeated-dose dermal toxicity study of hydrophobically modified hydroxypropyl methylcellulose in rats.

A six-month repeated-dose dermal toxicity study followed by a 30-day recovery test of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, was conducted using rats. Aqueous paste of HM-HPMC was applied to the skin of rats once daily at dose levels up to 60 mg/kg/day, which was the highest dose that could be administered. Items checked included general signs, urinalysis, hematology, ophthalmology, and histopathology. One rat died during the administration period owing to a malignant tumor in the hemopoietic system, which was not attributed to the test substance. Statistically significant differences were found in some test results, but those were not dose-dependent and were considered to be incidental or spontaneous. It was concluded that the test substance was not toxic upon chronic dermal administration at dose levels up to 60 mg/kg/day.

Administration, Cutaneous↗
PubMed1996

Clinical application of three-dimensional myocardial imaging: evaluation of efficacy of medical treatment on myocardial perfusion.

To investigate the clinical applicability of the three-dimensional (3D) myocardial imaging using a newly developed system (the Application Visualization System-Medical Viewer), thallium-201 myocardial single photon emission computed tomography was performed in 19 patients with previous myocardial infarction before and after treatment with nisoldipine. We have developed a new method for automatically reconstructing 3D imaging for the stereoscopic evaluation of myocardial perfusion. The left ventricular myocardial volume with a radioisotope count > or = 50% of maximum was calculated by using the conventional surface rendering method. With these images, the effect of nisoldipine on myocardial perfusion was assessed and the myocardial volume with a radioisotope count > or = 50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine significantly increased the myocardial volume with a radioisotope count > or = 50% of maximum from 141 +/- 17 to 153 +/- 18 ml on the stress 3D imagings. These findings indicate that nisoldipine improved myocardial perfusion during exercise. 3D imaging provided stereoscopic assessment of the changes in myocardial perfusion following treatment with nisoldipine and also detected transient enlargement of the left ventricular lumen induced by exercise.

Aged↗
PubMed1996

Role of transforming growth factor-beta in the restitution of injured guinea pig gastric mucosa in vitro.

The role of transforming growth factor-beta (TGF-beta) in restitution was examined in intact sheets of injured guinea pig gastric mucosa in which the epithelial cell-collagen interaction can be quantitatively evaluated. The luminal surface of intact sheets of in vitro guinea pig gastric mucosa was injured by exposure to 1.25 mol/l NaCl for 10 min. Restitution was evaluated by measurement of transmucosal electrical resistance and [3H]mannitol flux before and after injury. Recovery of electrical resistance and [3H]mannitol flux was retarded by inhibition of endogenous TGF-beta with either aprotinin or anti-TGF-beta antibody; effects were restored by human recombinant TGF-beta1. During inhibition of endogenous TGF-beta, type IV collagen accelerated the recovery. Inhibition of reconstruction of the basement membrane by simultaneous addition of cis-4-OH-L-proline and anti-type IV collagen completely abolished the enhancement of the recovery by TGF-beta 1. These results suggest that endogenous TGF-beta is required for restitution to occur in guinea pig gastric mucosa and that type IV collagen plays an important role in TGF-beta-abetted restitution.

Animals↗
PubMed1996

[Short- and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension].

Prostacyclin (PGI2) is a bioactive substance produced by vascular endothelial cells, which exerts powerful vasodilative and anti-platelet actions. Patients with pulmonary hypertension have an imbalance between vasodilative PGI2 and vasoconstrictive thromboxane B2 (TXB2). Treatment with vasodilative agents is essential for such patients. Continuous intravenous infusion of PGI2 is an effective treatment of primary pulmonary hypertension in terms of exercise capacity and survival rate. We tested a new stable PGI2 analogue, beraprost sodium (Procyclin, Dornar) suitable for oral administration, in patients with primary and secondary pulmonary hypertension. A short-term study of cardiac catheterization in four patients with primary pulmonary hypertension showed a 15 +/- 12% reduction in mean pulmonary artery pressure in three of the four patients, and a 24 +/- 22% decrease in pulmonary vascular resistance in all four patients. Cardiac index increased by 27 +/- 14% in three of the four patients. Among three patients with secondary pulmonary hypertension, there was a 7% reduction in pulmonary artery pressure in one patient, and a 24 +/- 14% decrease in pulmonary vascular resistance in all three patients. In a long-term study (23 +/- 11 months), NYHA functional class improved from 3.0 +/- 0.7 to 2.4 +/- 0.5 in two of the five patients with primary pulmonary hypertension. Although the radiographic cardiothoracic ratio was not significantly improved, cardiac index increased by 78 +/- 60% in four of the five patients. Only two patients, one with primary and one with secondary pulmonary hypertension, died during the long-term follow-up period. Plasma TXB2/6-keto prostaglandin F1 alpha ratio decreased from 8.1 +/- 8.7 to 1.5 +/- 0.4. The optimal dose remains uncertain, but the initial dosage of 40-60 micrograms/day given in three to four doses for adult patients is considered to be acceptable. Side effects such as flushing face, headache, vomiting, and nausea were mild and resolved when the dose was reduced. Oral PGI2, beraprost, appears to be an effective and possibly adequate substitute for intravenous vasodilators in pulmonary hypertension for both short- and long-term management.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Role of nitric oxide in restitution of injured guinea pig gastric mucosa in vitro.

The role of nitric oxide (NO) in restitution was examined in intact sheets of in vitro guinea pig gastric mucosae after mucosal injury induced by exposure of the luminal surface to 1.25 M NaCl for 10 min. The recovery of transmucosal electrical resistance and [3H]mannitol flux after the injury were significantly greater at luminal pH (pH1) 7.0 than 3.0. The recovery was abolished by pretreatment with 1 mM NG-nitro-L-arginine methyl ester (L-NAME), only at pHL 3.0, an effect reversed by 1 mM L-arginine. Enhancement of the recovery by L-arginine at pHL 3.0 was abolished by 50 microM methylene blue (MB), an effect restored by 1 mM N6,2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP). In L-arginine- but not L-NAME-treated tissues, recovery was enhanced further by an increase in serosal [HCO3-] and was inhibited by 5% N-acetyl-L-cysteine in the luminal solution or by the removal of serosal HCO3-. Morphological examination showed the formation of a thick "mucoid cap" in L-arginine-but not L-NAME-treated tissues. These results suggest that, in the presence of luminal acid, endogenous NO contributes to restitution in injured gastric mucosa at least in part by facilitating the formation of the mucoid cap.

Animals↗
PubMed1995

[Effects of azithromycin on fecal flora of healthy adult volunteers].

New macrolide antibiotic, azithromycin (AZM), was administered to six healthy male volunteers and its effects on their intestinal microflora were investigated. Each volunteer was given 500 mg of AZM orally, once a day for 3 consecutive days. Stool samples were obtained from them prior to the medication and 1, 7, 14 and 28 days after the third day the medication. A slight decrease in the total aerobic bacterial count was observed. Also, several species of anaerobic bacteria showed slight decreases through the 14th day post medication. Individual variances were observed, however. A marked decrease in the number of Bifidobacterium was found for each of the volunteers. Clostridium difficile was detected from one of the volunteers on the 28th day post medication without diarrhea related symptoms.

Adult↗