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Biomedical subjects

M Asaka

Publications and source records attributed to M Asaka.

At least 235 records · Page 13Linked to original sources

[Proton pump inhibitors in the treatment of peptic ulcers resistant to H2-receptor antagonists].

The aim of this study is to evaluate the therapeutic effect of proton pump inhibitors on peptic ulcers resistant to H2-receptor antagonists. Patients with ulcers resistant to at least 3 months treatment with standard or greater doses of H2-receptor antagonists were treated with 20 mg of omeprazole or 30 mg of lansoprazole, once daily, for 2 to 8 weeks. Endoscopy was performed every 2 weeks to confirm ulcer healing. Eleven of 28 (39%) gastric ulcers healed within 4 weeks and 20 (71%) within 8 weeks with omeprazole. Eight of 19 (42%) gastric ulcers healed within 4 weeks and 14 (74%) within 8 weeks with lansoprazole. All of the duodenal ulcer healed within 6 weeks with omeprazole or lansoprazole. No adverse effects were observed in this study. These results suggest that proton pump inhibitors are highly effective in the treatment of peptic ulcer resistant to H2-receptor antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Total and regional bone mineral density by dual photon absorptiometry in patients on maintenance hemodialysis.

To evaluate bone loss in renal osteodystrophy, we measured total and regional (head, trunk, pelvis, leg and arm) bone mineral density (BMD) by dual photon absorptiometry in 72 patients on maintenance hemodialysis (HD). We also examined the validity of serum carboxy-terminal parathyroid hormone (C-PTH) and intact-PTH as an indicator of secondary hyperparathyroidism. Total BMD correlated inversely with age in female patients (r = -0.57, p less than 0.01), but not in male patients. Female patients older than 50 years were omitted from analysis to exclude the effect of menopause on bone. Among clinical and biochemical parameters, only trunk BMD correlated inversely with the duration of HD (r = -0.26, p less than 0.05). Head, trunk and total BMD correlated inversely with serum alkaline phosphatase, C-PTH and intact-PTH, while pelvis BMD did not. Leg and arm BMD also correlated inversely with serum intact-PTH, but not with serum C-PTH. The serum level of C-PTH correlated positively with the duration of HD (r = 0.40, p less than 0.005), while intact-PTH did not. As compared with 18 control male volunteers aged 25-42 years, trunk, pelvis, leg, arm and total BMD were significantly lower in male patients on HD aged 22-49 years, whereas head BMD did not differ significantly between the two groups. The percent decrease of BMD was most prominent in the trunk (-19.6%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Clinical efficacy of sucralfate in the treatment of gastric ulcer.

We performed a randomized, single-blind study in Japan to investigate the efficacy and safety of two dosage regimens of sucralfate granules, 2 g, twice daily (b.i.d. group, n = 30) and 1 g, 4 times daily (q.i.d. group, n = 27), on ulcer healing in 57 patients with endoscopically proven gastric ulcer. Endoscopy was performed after 4 weeks and, if complete healing was not achieved, again after an additional 4 weeks. Of 57 patients, 11 were excluded from the statistical analysis because of protocol violation (six in b.i.d. group, five in q.i.d. group). Of 46 patients eligible for the analysis of healing rates, four patients in the b.i.d. group (all at 8 weeks) and five patients in the q.i.d. group (two at 4 weeks and three at 8 weeks) were withdrawn due to patients' inconvenience. As the possibility that the withdrawals were due to the treatment failures could not be denied, we used the Kaplan-Meier method and generalized Wilcoxon test/logrank test for the calculation and evaluation of healing rates in this study, respectively. Healing rates at 4 and 8 weeks were 50% and 94% in the b.i.d. group and 35% and 68% in the q.i.d. group. There was no significant difference in healing rates between the groups. No serious adverse effect was observed in either group. These results suggest that the 2 g b.i.d. dose of sucralfate in granule form is at least as effective as the conventional dose of 1 g q.i.d. in the treatment of active gastric ulcers and could lead to better patient compliance.

Administration, Oral↗

Effect of the immunosuppressive agent, ciclosporin, on experimental immune complex glomerulonephritis in rats.

Effect of the immunosuppressive agent, ciclosporin (CS), on bovine serum albumin (BSA) nephritis in rats was evaluated. Eight weeks after immunization, 19 male Wistar rats received a daily intravenous dose of BSA (2 mg). Two weeks later, 11 rats received BSA and an oral dose of CS (10 mg/kg), and 8 rats received only BSA for 2 weeks. Urinary protein was measured weekly and serum anti-BSA antibody was measured by passive hemagglutination biweekly. The animals were killed at the 12th experimental week and blood samples and kidney specimens were obtained. BUN and serum creatinine were measured at the time of sacrifice. Kidney specimens were processed for light and immunofluorescent microscopic examination. Urinary protein excretion was significantly less in CS-treated rats than in nontreated controls at the 2nd week after treatment (5.3 +/- 1.3 vs. 25.6 +/- 10.3 mg/day, p less than 0.05). Anti-BSA antibody titers were lower in treated rats than in controls at the 2nd week after the treatment. There were no significant differences in the levels of BUN and serum creatinine between two groups. Glomerular hypercellularity and mesangial widening were milder in treated rats than in controls, and glomerular deposition of BSA was less intense in treated rats than in controls. These results suggest that CS suppressed the antibody production and the development of glomerular changes in rats with immune complex glomerulonephritis.

Animals↗

Serum aldolase isozyme levels in patients with cerebrovascular diseases.

A subunit specific radioimmunoassay was developed for the quantification of human aldolase A, B, and C. The method used was a double antibody radioimmunoassay using radioiodinated purified aldolase A, B, or C subunits as the ligand, specific chicken antibodies to aldolase isozymes and rabbit antibodies to chicken IgG. The Iodogen method was used for iodination of the purified isozyme subunits in this study. Human brain tissue contained similar concentrations of aldolase A and aldolase C, and a smaller amount of aldolase B, which was the main isozyme of liver tissue. Levels of serum aldolase A were greater than 203 ng/ml, the upper limit of normal, in six of 24 patients with cerebral infarction and in 11 of 31 patients with cerebral hemorrhage. Nine of 24 patients with cerebral infarction and 16 of 31 patients with cerebral hemorrhage had serum aldolase C levels greater than 4.1 ng/ml, the upper limit in normal sera. These data suggest that serum aldolase C may be a more specific and sensitive marker of cerebrovascular diseases than aldolase A. We also demonstrated that serial measurement of serum aldolase C in patients with cerebrovascular diseases might be useful in estimating prognosis, since serially increasing serum aldolase C levels during the course of these diseases were correlated with a high mortality rate.

Adult↗

IgA nephropathy and hepatitis B virus. IgA nephropathy unrelated to hepatitis B surface antigenemia.

The incidence and pathogenetic role of hepatitis B surface antigen (HBsAg) were evaluated in patients with IgA nephropathy. Among 130 consecutive patients with IgA nephropathy, HBs antigenemia was detected in 4 patients (3.1%). Serum antibody to hepatitis B core antigen was positive in these 4 patients indicating that they were persistent carriers of hepatitis B virus. Serum hepatitis B e antigen (HBeAg) was detected in 1 patient, and antibody to HBeAg was positive in the other 3 patients. The incidence of HBs antigenemia was not significantly higher than the 2.0% of the general population. An immunofluorescent study in the renal tissues from the 4 IgA-nephritic patients with HBs antigenemia did not demonstrate HBsAg or HBeAg in the glomeruli. These findings suggest that HBsAg appears to play no role in the pathogenesis of IgA nephropathy.

Adolescent↗

[The study on descriptive epidemiology of peptic ulcer in Hokkaido].

We previously reported that the reported that the ratio of gastric ulcer to duodenal ulcer in Hokkadio was higher than that in other area of Japan. This time, we analysed peptic ulcer cases of five hospitals in Hokkaido on the point of geographical and pathological distribution. When we divided these hospitals into two groups (in Sapporo city and other provincial areas) and calculated the sex and age adjusted ratio of gastric ulcer to duodenal ulcer in each group, we found the difference between the two groups (in Sapporo city: 2.26, other provincial area: 5.86) and thought the feature of high ratio the feature of the provincial hospitals. This difference in Hokkaido may be due to the environmental factors for peptic ulcer or the biased sampling of the study. The further study is needed to reveal the geographical and pathological distribution of this disease.

Adolescent↗

Decreased serum aldolase B levels in patients with malignant tumors.

Serum aldolase B levels were determined in patients with malignant tumors using a radioimmunoassay method. Thirty-one of 52 patients with malignant tumors had decreased serum aldolase B levels of less than 20 ng/ml, whereas almost all of the normal subjects and the patients with liver diseases and other benign diseases showed serum aldolase B levels of more than 20 ng/ml. The decreased aldolase B levels observed in cancer patients were unrelated to the clinical stage of their disease. The decrease of aldolase B correlated well with the decrease of fructose-1-phosphate (F1P)-aldolase activity, but not with fructose-1,6-diphosphate (FDP)-aldolase activity in the sera of cancer patients. Mixing experiments did not identify an inhibitor of aldolase B in sera of cancer patients. Furthermore, recovery of serum aldolase B levels after successful surgical resection in cancer patients suggested that the low levels of aldolase B in sera of cancer patients was not of genetic origin. The mechanism responsible for the decrease of aldolase B in sera of cancer patients is unclear.

Adult↗

A role for Ca2+ in mediating hormone-induced biphasic pepsinogen secretion from the chief cell determined by luminescent and fluorescent probes and X-ray microprobe.

In isolated chief cells from the guinea pig, cholecystokinin (10 nM) and a high concentration of ionomycin each caused a biphasic pattern of pepsinogen secretion. The initial fast response to cholecystokinin was not dependent on medium Ca2+ ans was mimicked by low concentration of ionomycin (100 nM). Inositol 1,4,5-trisphosphate caused a similar fast release from permeabilized cells. The slow component of release was dependent on medium Ca2+, however, and was mimicked by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) (100 nM) or the diacylglycerol analogue 1-oleoyl-2-acetylglycerol (OAG) (100 microM). Ionomycin (100 nM) and TPA (and/or OAG), when applied together, reproduced the biphasic pattern of pepsinogen secretion, suggesting that the signalling pathways utilized by both types of agonist contribute to the response evoked by cholecystokinin-hormone stimulation. Both fura-2 and aequorin were used to monitor changes of intracellular Ca2+. Three pathways were found to contribute to the Ca2+ transient. A rapid release of Ca2+ from intracellular store(s), a rapid Ca2+ entry from the extracellular space, and a more sustained Ca2+ entry from the extracellular space. Cholecystokinin induced a rapid increase in cytoplasmic Ca2+ ([Ca2+]i) as estimated with fura-2 and aequorin. This rise was reduced but not abolished upon removal of extracellular Ca2+, suggesting that both Ca2+ entry from the extracellular space and Ca2+ mobilization from the intracellular store(s) contribute to the initial, fast component of the Ca2+ transient. A second, more sustained component of the Ca2+ transient induced by cholecystokinin was abolished by lanthanum. TPA and OAG induced a biphasic Ca2+ transient that could be detected only with aequorin. The late, sustained component of this response was again abolished by lanthanum as well as by removal of extracellular Ca2+. It appears that the late component of the Ca2+ transient is dependent on Ca2+ influx from the extracellular space and is too localized to be detected by fura-2. Prestimulation of cells with TPA or OAG prevented the aequorin transient caused by cholecystokinin and vice versa, suggesting that TPA, OAG and cholecystokinin activate the same pathways of Ca2+ entry into the cytosol from the intracellular store(s) or the extracellular space. The stimulation-sensitive Ca2+ pool was examined with electron probe X-ray microanalysis. It appears to be restricted to an area enriched in secretory granules or peripheral endoplasmic reticulum just beneath the apical plasma membrane and in close association with the microtubular-microfilamentous system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Initial and sustained calcium mobilizations in the parietal cell during stimulations with gastrin, inositol trisphosphate, phorbol ester and exogenous diacylglycerol.

Electron probe X-ray microanalysis revealed that cytoplasmic Ca2+ concentration increased in the restricted apical cytoplasm during stimulation of isolated guinea pig parietal cells with gastrin. Furthermore, this study, using 45Ca2+, aequorin and fura-2, revealed the mechanism involved in intracellular Ca2+ shifts caused by gastrin and the involvements of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol in producing those shifts. The gastrin-mediated and IP3-sensitive Ca2+ pool was located in the smooth-surfaced membrane-enriched areas and released Ca2+ in the initial phase. Gastrin-mediated Ca2+ mobilization was also evoked by diacylglycerol, comprising an intracellular Ca2+ mobilization followed by a late, sustained and more localised Ca2+ entry from the extracellular space.

Adenosine Triphosphate↗

Intracellular Ca2+ shift and signal transduction from the tubulovesicular portion of gastric parietal cells during gastrin stimulation or Ca2+ ionophore treatment: comparison between luminescent and fluorescent probes, and electron probe X-ray microanalyzer.

In gastrin-stimulated, aequorin-loaded parietal cells from guinea pig gastric mucosa, a rapid but transient increase in the cytosolic free Ca2+ concentration ([Ca2+]i), owing to Ca2+ released from the store(s), and a more prolonged Ca2+ entry from outside the cells were observed. However, there was a little increase in [Ca2+]i when similar measurements were assessed by quin 2 or fura-2 in physiological saline. However, depletion or elimination of Na+ from the incubation medium caused a significant increase in the [Ca2+]; response to gastrin as measured by quin 2. These findings suggest that aequorin and quin 2 (or fura-2) provide information about different aspects of Ca2+ homeostasis and that there is an inhomogeneity of [Ca2+]i in the cytoplasm during gastrin stimulation. By the gastrin stimulation, the intracellular Ca2+ gradients were shifted from the unidentified portion(s) to the restricted apical cytoplasm, as determined by electron probe X-ray microanalysis. Therefore, localization and identification of the source of intracellular Ca2+ as a pool were determined by an X-ray microanalyzer. In the resting state, the tubulovesicle had high Ca2+ concentration compared with the level in the apical cytoplasm. Cells treated with the Ca2+ ionophore ionomycin had a decreased tubulovesicular Ca2+ level, followed by a reciprocal increase in area of the canalicular membrane. The secretory canaliculus in stimulated cells had lower Ca2+ or higher K+ and Cl- concentrations than that of tubulovesicles or cytoplasm in the resting state, respectively. These findings suggest that the Ca2+ pool of the parietal cell is in the tubulovesicles and (or) luminal cell membrane and that the Ca2+ released from the store(s) may mediate a flow of K+ or Cl- into the secretory canaliculus.

Aequorin↗

Depressed natural killer cell activity in uremia. Evidence for immunosuppressive factor in uremic sera.

We investigated the natural killer (NK) cell activity of peripheral blood mononuclear cells (PBMC) and the suppressive factor of NK cell activity in patients on maintenance hemodialysis (HD). NK cell activity was significantly lower in patients on HD than in healthy controls (20.2 +/- 16.5 vs. 31.0 +/- 13.2%, p less than 0.01). There was no difference in NK cell activity between patients treated with cuprophane and high-permeability membrane. NK cells from patients on HD showed a poor response to interleukin-2, and uremic sera significantly suppressed NK cell activity of normal PBMC. Although urea, creatinine, methylguanidine or guanidinosuccinic acid alone did not suppress the NK cell activity of normal PBMC, the guanidino compound did so significantly. It is suggested that defective NK cell activity in uremic patients explains in part their susceptibility to malignancy and infection. The immunosuppressive effect may be exhibited by synergism or mosaic of uremic toxins.

Adult↗

[Studies on the clinical significance concerning the changes in serum pepsinogen-I and gastrin levels in aged patients with chronic gastritis].

Of 86 cases of aged patients with chronic gastritis treated with Trimebutine or Flutazolam, we evaluated the changes of serum pepsinogen-I and gastrin levels in their clinical courses from the points of the correlation with severity of chronic gastritis, aging phenomenon and the changes of symptom and endoscopic findings. In order to elucidate the multidimensional interrelation among these items, we used Hayashi's quantification theory II as a conventional analysis method. In aged patients, generally, although the serum gastrin levels were rather high compared with younger generation, the serum pepsinogen-I levels were consistently low throughout their clinical courses. There were some correlation between the levels of serum gastrin and the severity of chronic gastritis. When the drugs were effective on improving the condition of the disease, the level of gastrin revealed gradual decrease. These changes of gastrin were more typical in patients treated with Trimebutine.

Aged↗