[Gastric emptying by the barium marker method].
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Biomedical subjects
Publications and source records attributed to O Kawamura.
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Endoscopic ultrasonography of the lower esophagus was performed in 25 patients with reflux esophagitis and 13 age-matched controls. Thickening of the esophageal wall and abnormalities of its architecture were detected. As these morphological changes became more extensive, the lower esophageal sphincter pressure and the decrease of sphincter pressure on relaxation were both progressively reduced. There was a significant correlation between morphological abnormalities and lower esophageal function. Our results suggest that inflammatory damage to the muscle layer of the lower esophagus may impair lower esophageal sphincter function further, especially in patients with advanced esophagitis.
We report a rare case of benign esophagobronchial fistula associated with achalasia. The fistula healed spontaneously after esophagocardioplasty with a gastric patch, suggesting the utility of this procedure.
The involvement of adhesion molecules in the accumulation of inflammatory cells in the glomeruli and subsequent glomerular injury was examined in accelerated-type anti-GBM nephritis in rats. This animal model is known to be manifested by progressive and irreversible glomerular damage with rapid influx of monocytes/macrophages into the glomeruli. Up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in this model. Therefore we examined the effect of ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) in the pathogenesis of this nephritis. Four groups of rats with accelerated-type anti-GBM nephritis were investigated. The first group was the control group injected with normal mouse IgG 2mg/Kg. The second group was administered mouse anti-rat ICAM-1 monoclonal antibody (1A-29) 2 mg/Kg. The third group was administered mouse anti-rat LFA-1 beta monoclonal antibody (WT-3) 2mg/Kg. The fourth group received both 1A-29 1mg and WT-3 1mg/Kg. Proteinuria and the influx of monocytes/macrophage in this model were decreased after the administration of 1A-29 or WT-3. Simultaneous administration of both antibodies showed intense suppression of the proteinuria and marked reduction of the infiltrating cells. These results suggested that the ICAM-1/LFA-1 pathway is critically involved in the pathogenesis of accelerated-type anti-GBM nephritis in rats.
We investigated the effect of an erythromycin derivative, EM523L, on interdigestive gastrointestinal motor activity and plasma motilin concentrations in three healthy volunteers using an infused catheter system. We administered doses of 500, 1000, and 2000 micrograms of EM523L to each subject as well as physiological saline. EM523L induced interdigestive migrating contractions (IMCs) that originated in the stomach and migrated to the duodenum. This response was noted in all three subjects after each dose of EM523L, while no IMCs were induced by saline. There were no significant differences in the characteristics of the EM523L-induced IMC and the spontaneous IMC. The initiation time, ie, the interval between the start of EM523L infusion and the onset of the IMC became shorter in a dose-dependent manner. Plasma motilin concentrations increased significantly after EM523L administration, suggesting that motilin is involved in the mechanism of IMC induction by this drug.
Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.
The effects of erythromycin (EM) on gastrointestinal contractile activity during the interdigestive period were investigated in seven healthy subjects using an infused catheter system, and the changes in the plasma motilin concentration were also determined. Graded EM doses (0.1-1.5 mg/kg) were administered intravenously over 5 min, usually during gastric phase I. EM induced interdigestive migrating contractions (IMCs). Their induction rate was low after low doses of EM, but gradually increased as the dose increased to reach 71.4% at an EM dose of 0.375 mg/kg. Strong contractions, which were quite similar to phase III activity of the stomach but did not migrate or migrated incompletely to the duodenum, were observed at EM doses above 0.375 mg/kg. Therefore, the optimum dose of EM for inducing an IMC was established to be 0.375 mg/kg. In comparison with spontaneous IMCs, EM-induced IMCs had a significantly longer duration in the stomach and a significantly lower amplitude in the duodenum. These observations indicate that EM induced phase III activity more intensively in the stomach than in the duodenum. The plasma motilin concentration increased significantly during EM-induced IMCs, and this suggested a close relationship between this hormone and induction of the IMC. The increase in motilin levels was also observed of the strong gastric contractions which did not migrate or migrated incompletely to the duodenum. Therefore, it seems reasonable to suggest that motilin is involved in phase III activity of the stomach rather than in that of the duodenum.
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The effects of rhG-CSF on T-2-induced leukopenia and lethal toxicity in mice were investigated. First, T-2 was administered by gavage to adult male mice at a dose of 3 mg/kg b.w. daily for 7 days, and rhG-CSF was given i.p. in daily dose of 10 or 30 micrograms/kg b.w./day, beginning on the 2nd day, for 5 days. The peripheral WBC of mice receiving T-2 alone was decreased to one fourth of control counts, and bone marrow (BM) cell counts were also markedly diminished. The administration of rhG-CSF prevented those T-2-induced depressions. Histologically, the delation of the hematopoietic cells from BM and spleen of mice given T-2 was remarkably counteracted by administration of rhG-CSF. In the other experiment, rhG-CSF was injected i.p. for 5 days beginning on the next day of the 7-day T-2 administration. The recovery of WBC and BM cell counts was hastened by rhG-CSF reaching the control level in 6 days, and differential leukocyte analysis revealed an increase of neutrophils. Furthermore, simultaneous administration of rhG-CSF depressed the T-2-induced lethal toxicity, dose-dependently. The results revealed that rhG-CSF possesses a potent ability to protect T-2-induced leukopenia and lethality in mice, and it could be as an antidote against T-2 and related trichothecene-induced acute intoxication.
By an introduction of sodium dodecylsulfate for cell lysis and immunomicroplate for mass assay, the modified SOS microplate assay method was established and applied for the evaluation of genotoxicity of mycotoxins and fungal cultures. Among 20 mycotoxins, the carcinogenic dihydrobisfuranoids such as aflatoxin B1, sterigmatocystin, and versicolorin A were positive in the presence of the activation system. While, the carcinogenic anthraquinones and lactones such as luteoskyrin, rugulosin, ochratoxin A, patulin, and citrinin were negative. The survey on genotoxic fungi revealed that, among 15 fungal isolates Aspergillus versicolor, Emericella acristata, and others were positive. Additional survey on 265 fungal isolates have revealed that various Aspergillus genera such as A. flavus, A. parasiticus, A. ustus, A. nidulans, and others were positive for SOS induction, along with several isolates of Fusarium moniliforme. The chemical analysis revealed that the dihydrobisfuranoids such as aflatoxin B1, and sterigmatocystin were the major genotoxic metabolites of several Aspergillus species. The SOS microplate assay system is a simple and rapid procedure for the mass screening of genotoxic fungi, particularly of the dihydrobisfuranoids-producing strains.
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The 24-hr gastric and duodenal pressure measurement was performed in 5 patients with non-ulcer dyspepsia (NUD). The reduction of incidence of IMC and prolongation of the first appearance of IMC after evening meal were observed in NUD patients. The gastroprokinetic agent, cisapride 5 mg, 3 times a day for 7 days significantly increased the incidence of IMC and shortened the time before the first appearance of IMC after evening meal. This result indicates that in NUD patients impaired gastrointestinal motility is present in fasting phases and cisapride may be useful for correcting motility disorders.
Ochratoxin A, produced by a number of fungal species, has been found in many milieu, including porcine sera and coffee beans. It was therefore analysed by enzyme-linked immunosorbent assay (ELISA) in porcine sera, coffee products and fungal cultures, using monoclonal antibodies, a monoclonal antibody-linked immunoaffinity column (IAC) and high-performance liquid chromatography (HPLC). The chloroform extracts of acidified porcine sera were assayed directly by ELISA, with alkaline phosphatase and horseradish peroxidase as marker enzymes, at detection limits of 0.1 and 0.01 ng/ml, respectively. The presence of ochratoxin A in ELISA was confirmed by HPLC. The average contents in the five different lots tested were: 0.4 ng/ml in lot A (19 samples), 0.36 ng/ml in lot B (104 samples), 5.20 ng/ml in lot C (17 samples), 1.24 ng/ml in lot D (23 samples) and 0.22 ng/ml in lot E (24 samples). ELISA of methanol extracts of rice cultures showed the presence of more than 0.1 ng/g in 3 of 15 isolates of Aspergillus, in 16 of 67 isolates of Penicillum and in 7 of 17 isolates of Eupenicillum; none was found in an isolate of Emericella. IAC-HPLC analysis revealed that P. foetidus, which is similar to A. niger and is used for the production of a Japanese alcoholic drink (shou-chuu), also produced ochratoxin A. Use of IAC-HPLC to analyse coffee beans and instant coffee power resulted in the sharp resolution of ochratoxin A without complicated clean-up steps. The IAP-HPLC technique could thus be used for mass surveys of ochratoxin A residues in biological specimens.
The relationship between interdigestive gallbladder and gastroduodenal motility simultaneously with the behavior of plasma motilin and CCK levels in 20 subjects was investigated. We used an infusion catheter method for the measurement of gastroduodenal motility, and real-time ultrasonography for the measurement of gallbladder size. In gastric phase II, the gallbladder contracted with extension of the major axis and shrinking of the minor axis, with its minimum volume being 84% of the volume in phase I. The gallbladder then filled rapidly assuming a sphere-like shape with extension of the minor axis and shrinking of the major axis in gastric phase I. This motility was recognized only during the gastrointestinal interdigestive migrating complex (GI-IMC) cycle, originating in the stomach, and was associated with an increase of motilin levels, it was not seen before or after the intestinal IMC (I-IMC), which originated in the duodenum without contraction of the stomach or an increase of motilin levels. Furthermore no apparent relationship was recognized between CCK and gastric or gallbladder motility. Our findings suggest that gallbladder motility in the interdigestive period has a close relationship with gastroduodenal motility and is related to the appearance of the GI-IMC.
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T-2 toxin (T-2(4)), one of the trichothecene mycotoxins produced by various gerera of Fusarium spp., is a potent inhibitor to the syntheses of protein and DNA in mammalian cells. The selective cytotoxicity of T-2 toxin-conjugated anti-EL-4 monoclonal antibodies (T-2-mAb) was investigated against murine thymoma EL-4 cells in vitro and in vivo systems. At first T-2 was converted to T-2 hemiglutarate by glutaric anhydride. Then T-2 hemiglutarate was activated to 3-[4-(N-succinimidoxycarbonyl)-butyryl]-T-2 (T-2-G-OSu) by N-hydroxysuccinimide. Thus obtained T-2-G-OSu was conjugated with mAb specific for EL-4 cells. The T-2-mAb markedly inhibited the proliferation of cultured EL-4 cells, but no such cytotoxic effect was observed against irrelevant SP2/0 cells. The cytotoxicity of T-2-conjugated normal gamma globulin (T-2-nGG) against EL-4 cells was far less than that of the above T-2-mAb. Ammonium chloride and monensin, inhibitors of lysosomal enzymes, enhanced the cytotoxicity of T-2-mAb. The presence of both 2-deoxyglucose together with sodium azide, inhibitors of energy-dependent reaction, reduced the cytotoxicity of T-2-mAb. Therefore, the selective binding to the target cells followed by an energy-dependent endocytosis and an intracellular liberation of T-2 by hydrolysis may account for the cytotoxicity of the T-2-mAb. In mice pre-transplanted with EL-4 cells, T-2-mAb increased the mean survival time (MST) with a direct dosage dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
We prepared seven monoclonal antibodies (mAbs, OTA.1, 2, 3, 4, 5, 6 and 7) which were reacted with ochratoxin A (OTA), and have developed a specific and highly sensitive enzyme-linked immunosorbent assay (ELISA) for detection of OTA. The mAbs, OTA.1, 3, 4, 5 and 7, specifically reacted with OTA but much less with its analogs, ochratoxin B (OTB, about 1% of OTA) and ochratoxin alpha (OT alpha, less than 0.1% of OTA). One of the mAbs, OTA.2, equally reacted with OTA and OTB but hardly at all with (4R)-4-hydroxyochratoxin A or OT alpha (less than 0.1% of OTA). All of the mAbs reacted with ochratoxin C. None of the mAbs reacted with coumarin, 4-hydroxycoumarin or L-beta-phenylalanine. In the competitive ELISA with OTA.1 and OTA.7, the lowest detectable amount of standard OTA in solution was 50 pg/ml (2.5 pg per assay). This assay was applied for the quantitation of OTA added to chicken meat, wheat flour, porcine plasma and bovine serum. With minimal sample preparation, reliable and reproducible determinations were possible when concentrations of OTA were higher than 0.1-1 ng/g.