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Biomedical subjects

Y Takeyama

Publications and source records attributed to Y Takeyama.

At least 55 records · Page 3Linked to original sources

Control of gastric pH with ranitidine in patients with Crohn's disease receiving total parenteral nutrition. Comparison of two intravenous regimens.

Eleven patients with Crohn's disease in remission who were receiving total parenteral nutrition (TPN) underwent continuous intragastric 24-h pH monitoring before and during ranitidine administration. The patients were randomly allocated to receive 200 mg/day (group 1) or 400 mg/day (group 2) of ranitidine by continuous infusion. The mean basal 24-h gastric pH was sustained at a low value. After raintidine administration, the mean pH increased significantly both in group 1 (from 2.13 to 3.28) and in group 2 (from 1.91 to 3.36), with the mean holding-time at pH-3 also increasing significantly in both groups. There were no differences in the mean pH or holding-time at pH-3 between the two groups during ranitidine administration; however, the plasma ranitidine concentration was significantly higher in group 2. These findings indicate that the continuous infusion of a standard dose of ranitidine exerted a maximal inhibitory effect on the sustained hyperacidity induced by TPN, but that this infusion was unable to maintain the intragastric pH level at above 3.5.

Adolescent↗

Possible involvement of Rab11 p24, a Ras-like small GTP-binding protein, in intracellular vesicular transport of isolated pancreatic acini.

Rab11 p24 is a Ras-like small guanosine triphosphate (GTP)-binding protein, and specific antibodies against it were newly developed to explore its function. Using the antibody, Rab11 p24 was shown to be abundant in rat pancreas as well as in most rat tissues. To explore the involvement of Rab11 p24 into the exocytotic process, the subcellular distribution of Rab11 p24 in rat pancreatic acini was evaluated also by use of the antibody. When the isolated acini were incubated with 1 x 10(-10) M cholecystokinin octapeptide (CCK-8) that induced the maximal stimulation, the amount of Rab11 p24 increased in the fractions of plasma membrane and zymogen granules, but decreased in the cytosol fraction. This redistribution was time-dependent and occurred within 1 min after the CCK-8 stimulation and reached a maximal level within 2 min after the stimulation. Moreover, a light microscopic immunolabeling technique on the isolated rat pancreatic acini also revealed that higher immunoreactivity with Rab11 p24 was observed over the zymogen granule membrane under CCK-8 stimulation. The present results indicate that Rab11 p24 is translocated from cytosol to the membrane fraction during stimulation with CCK-8 and suggest that Rab11 p24 is involved in the intracellular vesicular transport of isolated acini.

Animals↗

Significant elevation of serum human hepatocyte growth factor levels in patients with acute pancreatitis.

Serum levels of human hepatocyte growth factor (HGF) were determined in 38 patients with acute pancreatitis by an enzyme-linked immunosorbent assay. The mean value of serum HGF levels on admission in the 38 patients was 1.69 +/- 0.40 (SEM) ng/ml. In 35 patients, serum HGF levels were found to be positive (> 0.39 ng/ml), with an incidence of 92.1%. In 17 patients, they were > 1.0 ng/ml, which was the cutoff value for fulminant hepatic failure. Serum HGF levels in the patients with severe acute pancreatitis (2.30 +/- 0.61 ng/ml; mean +/- SEM) were significantly higher than those in the patients with mild and moderate acute pancreatitis (0.63 +/- 0.06 ng/ml). Sixteen of seventeen patients whose serum HGF levels were > 1.0 ng/ml were evaluated as severe acute pancreatitis. Serum HGF levels were significantly elevated in the patients with higher Ranson scores, higher APACHE II scores, or higher computed tomography grades. Serum HGF levels in the patients with organ dysfunction (liver, kidney, or lung) were significantly higher than those in the patients without organ dysfunction. Moreover, serum HGF levels on admission in the nonsurvivors (3.17 +/- 1.30 ng/ml) were significantly higher than those in the survivors (1.22 +/- 0.33 ng/ml). The mortality rate of the patients showing serum HGF levels > 2.0 ng/ml on admission was 50%. In the patients with a lethal outcome, the mean serum HGF level remained constantly > 2.50 ng/ml during hospitalization. The serum HGF level reflected the clinical course of the disease rapidly and distinctly. Serum HGF levels increased with complications such as organ failure, infected pancreatic necrosis, and sepsis and decreased with successful intensive and surgical treatments. These results suggest that serum human HGF levels may reflect the severity, organ dysfunction, and prognosis in acute pancreatitis.

Acute Disease↗

Changes in myocardial lactate metabolism during ramp exercise in patients with effort angina and microvascular angina.

Changes in myocardial lactate metabolism during ramp exercise were investigated through great cardiac vein catheterization in 15 patients with effort angina (EA) and 7 patients with microvascular angina (MVA). The exercise test was performed using a supine bicycle ergometer. Blood samples were obtained from the great cardiac vein (GCV) and the radial artery each minute during exercise. Patients in the EA group showed a point at which the lactate extraction ratio (LER) and the ST level decreased rapidly during exercise. This point was clearly recognized in 12 of 13 patients, and may represent the ischemic threshold. Both the LER and ST level showed similar changes during exercise, and these values were significantly different between the ischemic threshold and peak exercise (p < 0.01). Both the LER and ST level were strongly correlated with the duration of exercise until the threshold (r = 0.703). In the MVA group, both the LER and ST level during exercise continuously decreased throughout exercise without an ischemic threshold in all of the subjects. Endomyocardial biopsy revealed sclerosis of small arteries in the myocardium in all of the patients. In both effort angina and microvascular angina, a close correlation was noted between the change in ST and that in the myocardial lactate extraction ratio.

Adult↗

Role of Kupffer cell-derived reactive oxygen intermediates in alcoholic liver disease in rats in vivo.

The pathophysiology of alcoholic liver disease (ALD) remains largely unknown. In this work, we have developed an experimental rat model to elucidate the mechanism of liver injury, including ALD, in which Kupffer cell-derived reactive oxygen intermediates (ROIs) might be involved. Groups of male Wistar rats were pair-fed on a liquid high-fat diet containing ethanol (36% of total calories) or isocaloric carbohydrate with or without dietary carbonyl iron (0.5% w/v) for 3 weeks. In this rat model, we investigated Kupffer cell-derived ROI generation, which affected hepatocellular injury and hepatic fibrosis in ALD. The production of ROIs in Kupffer cells isolated from the iron-fed, the ethanol-fed, and the ethanol plus iron-fed rats were significantly increased, compared with that in Kupffer cells isolated from control rats (iron > ethanol+iron > ethanol > > control). However, hepatic vitamin E content in the ethanol plus iron-fed rats was decreased rather than that in the iron-fed rats. Then, lipid peroxidation of isolated microsomes was assessed as malondialdehyde equivalents determined by thiobarbituric acid assay. Compared with controls, the malondialdehyde equivalents were elevated in experimental groups (ethanol+iron > ethanol > iron > control). Serum ALT levels were greatly elevated in rats fed a diet containing both ethanol and iron (ethanol+iron > iron > ethanol > control). Hepatic content of hydroxyproline was significantly increased in ethanol plus iron-fed rats, compared with rats other than the ethanol plus iron-fed group (ethanol+iron > iron > ethanol > control). These results suggested that the enhanced Kupffer cell-derived ROI generation could itself contribute to the increased susceptibility to lipid peroxidation, which might cause hepatocellular injury and lead to hepatic fibrosis in ALD.

Animals↗

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells.

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.

Acute Disease↗

Familial pericentric inversion incidentally detected at prenatal diagnosis.

A case of familial heterozygous pericentric inversion of chromosome 1 [inv(1)(p13q23)] is presented. The inversion was incidentally detected in a fetus whose mother received prenatal chromosomal diagnosis due to her age (40 years old), and thereafter the same inversion was detected in the father whose phenotype was normal. No abnormalities were found in the phenotype of the newborn carrier. Semen analysis of the father revealed normal findings. The couple had no history of spontaneous abortion.

Adult↗

Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol.

Effects of colchicine, a microtubule-disrupting agent, on rate exocrine pancreas were examined in comparison with the microtubule stabilizer Taxol for the purpose of analyzing the pathogenesis of cerulein-induced acute pancreatitis. Taxol ameliorated the inhibition of pancreatic secretion, elevation of serum amylase level, pancreatic edema, and histological alterations induced by supramaximal cerulein stimulation. In contrast, colchicine by itself and colchicine followed by cerulein stimulation (maximal and supramaximal) inhibited pancreatic secretion but did not induce the hyperamylasemia, pancreatic edema, or formation of large vacuoles, which characterized cerulein-induced pancreatitis. Electron microscopic studies in the colchicine-treated rats revealed that transport vesicles were accumulated in the supranuclear region and that no large vacuoles were observed in the apical lesion. Immunofluorescence studies confirmed that colchicine inhibited pancreatic secretion and disrupted the arrangement of microtubules. Posttreatment of colchicine did not prevent the development of cerulein-induced pancreatitis. Vinblastine, another microtubule-disrupting drug, as well as colchicine, inhibited pancreatic secretion but did not induce acute pancreatitis. The results obtained in this study suggest that microtubule disorganization at a specific step in the process of intracellular vesicular transport causes cerulein-induced pancreatitis and that this step is more apical than that at which colchicine inhibits secretion in the pancreatic acinar cell.

Acute Disease↗

In vivo and in vitro evaluation of bilirubin removal in postoperative hyperbilirubinemia patients.

The effect of plasma adsorption (PA) on bilirubin removal by a porous type anion exchange resin (Medisorba BL, Kuraray) was evaluated in vitro PA and in vivo PA and plasma exchange (PE) in postoperative hyperbilirubinemia patients. Serum and plasma bilirubin were measured by routine biochemical tests, fractionated by high-performance liquid chromatography, and its reduction and rebound were compared. In vitro and in vivo PA indicated the selectivity in bilirubin removal against measured molecules. Changes in bilirubin fractions after PA showed higher adsorbance of conjugated bilirubin (21.4-30.8%) and less adsorbance of delta (85.7%) and unconjugated bilirubin (73.7%). These differences were not observed after PE. But rebound of serum total bilirubin levels after PA was more than that after PE. It is suggested that PA by the resin is selective and has a different metabolic effect on bilirubin during and after PA as compared with PE.

Adsorption↗

Effects of zinc on production of active oxygen species by rat neutrophils.

The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemiluminescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O2- and H2O2 production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O2- and H2O2 production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O2- production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O2- production through the classical signal transduction pathway, and by increasing H2O2 not via O2-.

Animals↗

[Risk of chromosomally unbalanced progeny in prenatal diagnoses of reciprocal translocation carrier].

To obtain new criteria for presuming the existence of chromosomally unbalanced progeny in reciprocal translocation carrier couples, the obstetrical histories of 57 couples were analysed. The chromosomally unbalanced progeny who had been prenatally or postnatally diagnosed were mainly partial trisomies. In contrast with partial trisomies, there were only a few cases of partial monosomies and there were only two cases of chromosomal imbalance derived from 3:1 segregation in gametogenesis. Moreover, the percentage of haploid autosome length (%HAL) of the maternal carriers whose progeny had suffered from chromosomal imbalance was significantly smaller than those of the maternal carriers who had not had progeny with chromosomal imbalance. Based on these results, the following criteria were obtained: 1) Partial trisomies tend to be maintained in pregnancy but partial monosomies do not; Most chromosomally unbalanced zygotes which were induced by 3:1 segregated gametes tend to be spontaneously selected in early pregnancy; 3) When interchanged segments of chromosomes are small in maternal reciprocal translocation carriers, chromosomally unbalanced fetuses tend to be maintained in pregnancy.

Female↗

[Predictable factors in healing of gastric ulcer, comparative analysis of local morphologic factor of gastric ulcer and suppression of intragastric pH].

Predictable factors in healing of 48 patients with gastric ulcer by PPI or H2-RA on 4 and 8 weeks of treatment were investigated. We evaluated the following factors such as patient's profile, local morphologic factors of gastric ulcer and suppression rate of 24 hr intragastric pH between healed and unhealed patients using single and multiple variable analysis. Results obtained from multiple variable analysis, the significant and independent factors of intractable gastric ulcers on the 4th week of treatment were ulcer size in over 20 mm and solitary ulcer. On the contrary, those of 8th week of treatment were shortage of holding time of intragastric pH over pH4 (less than 16.7 hrs) during treatment, the site of ulcer at lesser curvature of gastric angle and the shape of ulceration which showed mucosal overhanging. Considering with single and multiple variable analysis, we concluded that, in early phase, local shapes of the ulceration were important predictors in the healing of gastric ulcer, and the after that, the inhibition of intragastric acidity were significant factors in healing process of gastric ulcer.

Female↗

Ultrastructural changes of blood capillaries in patients with microvascular angina, hypertrophic cardiomyopathy, and dilated cardiomyopathy.

Blood capillary abnormalities accompanied by intramural small arterial lesions were reported in patients with microvascular angina (MVA), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). We compared the ultrastructural changes of blood capillaries in myocardial biopsy samples from MVA, HCM, and DCM patients using electron microscopy and ultrastructural morphometry. Ten cross-sectioned views were selected from each patient at random, and the degree of cytoplasmic swelling of the endothelial cells was measured (transverse area of endothelial cell cytoplasm (E)/transverse area of the blood capillary (C)). The thickness of the basal lamina was also assessed (transverse area of basal lamina (BL)/C). The average value of the E/C ratio was in the order of control group < HCM < MVA < DCM, with significant differences among the groups (p < 0.001). The average value of the BL/C ratio was in the order of control group < MVA < HCM < DCM, with significant differences (p < 0.001) among the groups except between the HCM and DCM groups. In conclusion, swelling of the endothelial cells as well as luminal stenosis of small arteries and arterioles may be related to disturbed microcirculation in these patients.

Adult↗

Zinc hydroxide induced respiratory burst in rat neutrophils.

The effects of zinc hydroxide on the respiratory burst and phagocytosis by rat neutrophils were examined. Zinc hydroxide induced an increase in oxygen consumption and O2- production. Electronmicroscopy showed that neutrophils engulfed zinc hydroxide particles by phagocytosis. Pertussis toxin (0.25, 0.5, 1.0 micrograms/ml) and EGTA (1, 2, 5 mM) inhibited zinc hydroxide-induced O2- production in a dose-dependent manner. The inhibitors of protein kinase C, 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide inhibited zinc hydroxide-induced O2- production with IC50 values ranging between 10 microM and 25 microM. The inhibitory study using an inhibitor of myosin light chain kinase, 1-(5-iodo-naphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine, showed IC50 values ranging from 5 microM to 10 microM. These findings indicate that zinc hydroxide induces respiratory burst and phagocytosis by rat neutrophils.

Animals↗

Coronary spasm in patients with coronary ectasia.

The incidence of coronary ectasia (CE) and the relationship between CE and coronary spasm that was said not to be apt to occur in patients with CE were studied. The study consisted of 1,373 patients (including 1,008 patients with ischemic heart disease) who underwent cardiac catheterization. In 74 patients with CE, coronary spasm was tested in 33 patients subjected to acetylcholine (ACh) provocation and in 17 patients subjected to ergonovine (Ergo) provocation. CE was found in 74 patients (5.4%), and its incidence was significantly higher (6.7%) in patients with ischemic heart disease. In addition, ACh and Ergo provocation tests gave positive results in 12 (36%) and 4 patients (24%), respectively. Spasm was not provoked as frequently in the ectatic portion as elsewhere. In addition, spasm was often found at the borders of the ectatic portion in both provocation tests. The incidence of coronary ectasia was higher than that described in previous reports, and coronary spasm was more often observed at the borders between ectatic and normal portions than elsewhere.

Acetylcholine↗

Paracentric inversion of chromosome 14: a case report.

A new case of familial heterozygous paracentric inversion in the long arm of chromosome 14 [inv(14)(q22q32)] is presented. The rearrangement was first ascertained in a fetus examined due to advanced maternal age, and then detected in the father. The phenotypes of the newborn and the father were completely normal. The parents had no history of spontaneous abortion. With reference to previous reports, the risk of clinical abnormalities are discussed for both de novo and familial paracentric inversions of chromosome 14.

Adult↗