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Biomedical subjects

N Okabe

Publications and source records attributed to N Okabe.

At least 55 records · Page 3Linked to original sources

A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate.

To elucidate whether pretreatment with omeprazole decreases the cure rate of Helicobacter pylori infection with a new quadruple therapy, and thus, whether this pretreatment should not be used in clinical practice, we conducted a randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for 2 weeks (days 1-14), and 500 mg amoxicillin granules and 250 mg metronidazole thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8-14), Group 2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1-7), in addition to omeprazole treatment for 2 weeks (days 1-14). Four weeks after the treatment ended, endoscopy was repeated, with two biopsy specimens each taken from the antrum and the corpus (total of four specimens) for a urease test, histological analysis, and culture to establish cure of infection. A patient was regarded as cured only if all three methods gave negative results for H. pylori. In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence intervals [CI], 81.7%-98.6%) in group 1 were cured compared with 43 of 45 patients (95.6%; 95% CI, 84.9%-99.5%) in group 2. In the per-protocol analysis, the corresponding figures were 42/44 (95.5%; 95% CI 84.5%-99.4%) and 43/44 (97.7%; 95% CI, 88.0%-99.9%). There were no significant differences in the cure rate between the two groups on either analysis. All patients, except for one who had an allergic reaction, completed the treatment regimens. Fifty to sixty percent of the patients had no side effects while the rest had mild to moderate side effects. The new quadruple therapy consisting of omeprazole, amoxicillin, metronidazole, and roxithromycin appears suitable for use in clinical practice, as the cure rate was 95% and no severe side effects were observed. Pretreatment with omeprazole did not reduce the cure rate for this new quadruple therapy.

Adult↗

Stability of metallothionein isoforms by capillary zone electrophoresis.

Stability of isoforms on storage of metallothionein (MT) was investigated by capillary zone electrophoresis (CZE) at neutral pH. The mouse liver was removed 1 day after injection of zinc, and homogenized in 0.25 M sucrose with 100 mM TRIS-HCl buffer, pH 7.4. The specimens for MT analysis were obtained by two partial purification methods, i.e., heat treatment (HT) and ethanol/chloroform precipitation (ECP) methods. The specimens were stored at either 4 degrees C or -80 degrees C for 1 and 3 days, and peak areas of MT-1 and MT-2 isoforms obtained by CZE were compared. When specimens were obtained by HT method, both MT isoforms were stable at -80 degrees C within 3 days. However, the peak area of MT-1 stored at 4 degrees C was gradually decreased to one third on the 3rd day. The MT-2 peak did not decrease the next day, but decreased to 57% on the 3rd day. In contrast, peak areas of both MT isoforms decreased remarkably the 1st day, when specimens obtained from ECP method were stored at 4 degrees C and -80 degrees C. From these results, we conclude that stability of MT isoforms is different depending on the purification methods, and MT isoforms are not stable after partial purification, especially by ECP method, even if stored at -80 degrees C.

Animals↗

Identification of metallothionein isoforms with capillary zone electrophoresis using a polyacrylamide-coated tube.

Metallothionein (MT) isoforms from various liver tissues were separated with capillary zone electrophoresis (CZE) using a polyacrylamide-coated tube at neutral pH. The electrophoresis was performed on MT-1 and MT-2 purified from mouse, rat, rabbit and human livers. The retention times of mouse and rat MT-1 coincided, while the retention times of rabbit and human MT-1 were longer. The retention times of MT-2 purified from the four sources were the same. MT-1 and MT-2 separated more definitely with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-Tris buffer (25 mM, pH 7.4) than with N-tris(hydroxymethyl)methyl-3-aminopropane sulfonic acid (TAPS)-Tris buffer (25 mM, pH 7.7) or with N-(2-acetamido)iminodiacetic acid (ADA)-Tris buffer (25 mM, pH 7.4). In addition, liver MT isoforms prepared from Zn- or Cd-administered mice could be separated.

Acrylic Resins↗

Vitamin B6 deficiency accelerates metabolic turnover of cystathionase in rat liver.

Although most of cystathionase was found to exist as an inactive apoenzyme in the liver of vitamin B6-deficient rats, the concentrations of the immunoreactive enzyme protein were virtually the same for control and vitamin B6-deficient livers. Under vitamin B6 deficiency, however, the rate of synthesis of cystathionase, measured by incorporation of labeled amino acid into the immunoprecipitated enzyme, was increased severalfold due to an increased level of cystathionase mRNA. Western blot analysis of lysosomal proteins showed that the amount of cystathionase in the lysosomes from the liver of vitamin B6-deficient rats was also increased severalfold. This observation suggests that lysosomes specifically recognize the apocystathionase for sequestration in preference to the holoenzyme. The present study provides the molecular basis for dual roles of vitamin B6 in controlling the metabolic turnover of cystathionase; it regulates synthesis of the enzyme by modulating the expression of cystathionase gene, and it regulates degradation of the enzyme by different susceptibilities of apo- and holoenzymes to lysosomal proteolysis.

Animals↗

Analysis of interaction between cadmium and metallothionein isoforms by capillary zone electrophoresis.

The effects of cadmium on the peak area of metallothionein (MT) protein were studied by capillary zone electrophoresis with a polyacrylamide-coated tube at neutral pH. When cadmium was added to a commercial standard MT-1 isoform prepared from rabbit liver, the peak are of the MT-1 isoform decreased in a time- and dose-dependent manner. The MT-2 isoform also decreased with time, but the rate of decrease was lower than that of the MT-1 isoform. When ethylene glyco-bis-(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA) was added to a solution containing cadmium and MT-1, the peak area recovered with increasing concentration of EGTA. Zinc caused a slight decrease in the peak areas of MT-1 and MT-2 compared with cadmium, while addition of sodium did not decrease the areas. Furthermore, the peak areas of MT isoforms of the crude extract prepared from zinc-treated mice also decreased with increasing concentration of cadmium. These results indicate that cadmium may changed the charge of MT, which may account for the observed differences in electrophoretic behavior.

Animals↗

Effect of the eradication of Helicobacter pylori on duodenal ulcer healing and ulcer relapse: randomized controlled study in Japan.

To investigate the effect of the eradication of Helicobacter pylori on the healing and relapse of duodenal ulcers. 50 patients with active duodenal ulcer and H. pylori infection were randomly allocated to two treatment groups. One group (cimetidine group) received cimetidine 400 mg twice daily for 6 weeks and the other group (double-therapy group) received 300 mg amoxicillin granules and 250 mg metronidazole thrice daily for 2 weeks, in addition to the same regimen of cimetidine as the cimetidine group. Forty-two patients completed the study. After confirmation of ulcer scar, all patients were followed up for 6 months while receiving treatment with teprenone, an agent that does not affect acid secretion or the eradication of H. pylori. The healing rates at 6 weeks were 90% in the cimetidine group and 95.5% in the double-therapy group. H. pylori eradication occurred in 0% of the cimetidine group and in 73.7% of the double-therapy group (P = 0.004). The cumulative relapse rates in the two groups at 6 months were 64.3% and 11.1%, respectively (P = 0.0007). In the double-therapy group, the cumulative relapse rate at 6 months in the patients in whom H. pylori persisted was 50% (2/4); the rate was 0% (0/14) in the patients in whom H. pylori had been eradicated (P = 0.005). Histological gastritis significantly improved compared with the baseline in the double-therapy group, but no such improvement was seen in the cimetidine group. White scarring was found in 7.1% of the cimetidine group and in 83.3% of the double-therapy group after 6 months (P < 0.0001). The eradication of H. pylori markedly decreased the relapse rate in duodenal ulcer patients, and it significantly improved both the grade of gastritis and the quality of the ulcer scar.

Adult↗

[Study on septicaemia in infants and children in the past 20 years. Part 1. An analysis of causal organisms].

Causal organisms and their changes were evaluated in 158 cases of septicaemia admitted to Jikei University Hospital from 1975 to 1994. Eighty patients (50.6%) were aged less than 1 year, and 37 patients (23.4%) were newborns. The average mortality rate was 18.4%. The mortality rate between 1975 and 1984 was 26.8%, and that of the past 10 years (from 1985 to 1994) decreased to 13.7%. Staphylococcus aureus (29 cases, 19.4%) was the most common pathogens isolated, followed by Pseudomonas sp. (24 cases, 15.2%), Escherichia coli (19 cases, 12.0%), and Haemophilus influenzae (18 cases, 11.4%). H. influenzae, Acinetobacter sp., Streptococcus pneumoniae and Group B streptococcus (GBS) increased in the past 10 years (from 1985 to 1994), compared with the preceding 10 years (from 1975 to 1984). The mortality rate of Klebsiella sp. septicaemia (28.6%) was highest, followed by Pseudomonas sp. (25.0%), S. aureus (24.1%), S. pneumoniae (22.2%). H. influenzae and Acinetobacter sp. septicaemia were not fatal. E. coli and GBS were common among neonates and patients aged less than 1 year. H. influenzae septicaemia occurred mainly in patients with meningitis, in those younger than school age. Acinetobacter sp. was common among neonates and children with leukaemia Pseudomonas sp., Klebsiella sp., and Acinetobacter sp. were mainly detected in patients with underlying diseases. E. coli, H. influenzae, S. pneumoniae and GBS were mainly detected in patients without underlying diseases.

Adolescent↗

[Study on septicaemia in infants and children in the past 20 years. Part 2. An analysis of factors that prescribe for the prognosis].

Underlying diseases, complications, clinical findings, and laboratory findings were evaluated in 158 cases of septicaemia admitted to Jikei University Hospital from 1975 to 1994, in order to conjectured factors that prescribe for the prognosis. 50% of the patients had underlying diseases. Malignancy including leukaemia (31 cases, 39.2%) was the most common underlying disease, followed by low birth weight infant (17 cases, 21.5%), aplastic anemia (9 case, 11.4%), and congenital heart disease (7 cases, 8.9%). The death rate for patients with underlying disease (27.8%) was significantly greater than the mortality for normal patients with septicaemia (8.9%) (p < 0.05). Meningitis (24.7%) was the most common complication, followed by DIC (19.6%), shock (15.2%), and pneumonia (10.8%). The mortality rate of septicaemia complicated by shock was 66.7% (p < 0.01), and that complicated by DIC was 45.2% (p < 0.01). The mortality rate for patients with the clinical findings of respiratory distress, cough, abdominal distention, cyanosis, splenomegaly, or peripheral coldness was more than 40% and significantly greater (p < 0.01). Mortality rate in patients with granulocyte counts of < 4.000/mm3, platelet counts of < 5 x 10(4)/ mm3, total protein of < 5.0 g/dl, or ESR of < 20 mm/hr were significantly greater (p < 0.01) than those in patients with normal laboratory findings. Coincidence rate of blood and stool cultures was 57.9% for E. coli, and 28.6% for Klebsiella sp., and that of blood and throat cultures was more than 30% for Pseudomonas sp., Haemophilus influenzae, and Staphylococcus aureus. In the study of antimicrobial susceptibility for microorganisms isolated, the number of drug resistant S. aureus had increased in the last 10 years.

Adolescent↗

Thyroxine binding properties of glycosylated human serum albumin as measured by fluorescence.

Thyroid hormone, thyroxine (T4) binding to glycosylated human serum albumin (G-HSA), and native human serum albumin (HSA) were studied as a function of pH using the fluorescence method. T4 binding affinity for G-HSA was remarkably reduced in an alkaline pH as compared with the native HSA. The thermodynamic parameters for binding are estimated at pH 7.5: (a) for G-HSA, delta G = -8.50 +/- 0.04 kcal mol-1 (30 degrees C), delta H = -5.2 kcal mol-1, delta S = +11 e.u.; (b) for HSA, delta G = -8.89 +/- 0.04 kcal mol-1 (30 degrees C), delta H = -3.5 kcal mol-1, delta S = +18 e.u. These results suggest that the glycosylation of HSA causes a variation in the electrostatic interaction between T4 and HSA.

Glycosylation↗

Evaluation of disease activity in patients with moderately active ulcerative colitis: comparisons between a new activity index and Truelove and Witts' classification.

OBJECTIVES: We have recently proposed a new activity index (AI) for ulcerative colitis. The aim of this study was to examine how AI would reflect the effect of medical therapy in comparison with Truelove and Witts' criteria. METHODS: In this trial, we studied 35 patients with extensive colitis who persisted with moderate disease for 2 wk. They showed no change in disease activity according to Truelove and Witts' classification despite 2 wk of corticosteroid therapy. Nine of the 35 patients underwent surgery (operated group), and 26 responded to the medical therapy and went into remission (nonoperated group). RESULTS: In the nonoperated group, AI values significantly decreased at 1 and 2 wk after treatment compared with pretreatment values, whereas there was no significant change in AI in the operated group during the clinical course. Remission occurred in all patients indicating below 180 of AI values 2 wk after therapy, whereas approximately 65% of patients indicating above 180 of AI values subsequently needed colectomy. CONCLUSIONS: This study suggests that AI will be useful in evaluation of response to medical therapy and prediction of remission and colectomy in patients with moderately active ulcerative colitis.

Adult↗

Clinical course and long-term prognosis of Crohn's disease in Japan.

The long-term outcome of Crohn's disease was reviewed in 74 patients who had a history of more than 10 years (range 10.8-27.3) since disease onset. The observation period was between 4.3 and 18.5 years, the mean and SD being 10.6 +/- 3.1 years. The means and SD of age at onset and final observation were 21 +/- 7 and 37 +/- 8 years, respectively. Fifty-eight of the 74 patients had not undergone bowel resection at the time of diagnosis; of these 58, 31 (53.4%) had an operation for the disease during the follow-up period. Thus, of the 74 patients, 47 (63.5%) (these 31, plus the 16 who had undergone bowel resection at the time of diagnosis) had an operation at least once during a follow-up period of 10 years or more. The cumulative operation rates 5, 10, and 15 years after onset in the 74 and 58 patients above were 18.9%, 6.9%, and 40.8%, and 34.8%, 49.1%, and 46.0%, respectively. The corresponding figures 5 and 10 years after diagnosis in all 74 patients and the 58 patients were 32.3% and 28.6% and 47.3% and 46.3%, respectively. There were no significant differences in the incidence of operation rate in relation to anatomical involvement. Cumulative reoperation rates 1, 3, 5, and 10 years after the first operation in the 31 patients who were operated on during the follow-up period were 3.4%, 6.9%, 25.5%, and 51.7%, respectively. Three patients died, the causes of death in one being directly related to Crohn's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunological studies on Crohn's disease. X. Conclusion: a new tentative hypothesis.

Although much progress has been made in understanding the pathogenesis of Crohn's disease, the precise etiology of Crohn's disease still remains unknown. In our serial studies on Crohn's disease, we found a decrease in NK and ADCC activities as well as a decrease in the phagocytic activity by monocytes, whereas an increased superoxide production activity by monocytes was evident. On the other hand, the characterization of lymphocyte subpopulations has demonstrated no abnormalities. According to these findings, we would like to propose a new tentative hypothesis for the pathogenesis of Crohn's disease. It has been suggested that impaired killing system activities, such as phagocytic activity as well as NK and ADCC activities, are primarily responsible for the promotion and perpetuation of chronic inflammation and ulceration. When our attention is directed to the most common target substances of these protective mechanisms, viral antigens appear as the most likely causative organism. Therefore, a lot of attention has been focused on viral infection as a causative factor. Furthermore, based on this hypothesis, strategies for effective treatment of this disease are also discussed.

Antibody-Dependent Cell Cytotoxicity↗

A case of cytomegalovirus mononucleosis associated with pleural effusion.

A 5 year old boy had a spiky fever accompanied by a mild pharyngitis, cervical lymphadenopathy and hepatosplenomegaly. Laboratory findings revealed leukocytosis with 26% atypical lymphocytes, and liver dysfunction. A chest X-ray showed pneumonia and a considerable amount of pleural effusion. Serum antibody titers for cytomegalovirus (CMV) were elevated significantly and CMV-DNA (polymerase chain reaction) was detected in the pleural effusion. Only 13 cases of pleural effusion associated with infectious mononucleosis have been reported previously in the literature, but there was no documentation that proved CMV infection. The case reported here suggests that the pleural effusion was caused by the infiltration of mononuclear cells to the pleura as a result of systemic inflammation, and the possible alternative of host immune response against CMV was related to recent Varicella zoster virus infection.

Antibodies, Viral↗

Drug binding properties of glycosylated bovine serum albumin as measured by circular dichroism.

The binding properties of Sudlow's site-specific drugs to glycosylated bovine serum albumin (G-BSA) (1.25 mol glucose per mol of albumin) have been investigated using the circular dichroism (CD) method. Site I-specific drugs, phenylbutazone and warfarin, and site II-specific drugs, flufenamic acid and ibuprofen, were used. The induced ellipticities of phenylbutazone, flufenamic acid and ibuprofen-G-BSA complexes diminished and those of warfarin complex were enhanced in comparison with those for the intact bovine serum albumin (BSA) complexes. These CD change suggests that the glycosylation of BSA at the primary modification site influences the binding properties of the site-specific drugs to serum albumin.

Binding Sites↗