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K Noda

Publications and source records attributed to K Noda.

At least 253 records · Page 14Linked to original sources

[Serotypes of urease producing Vibrio parahaemolyticus and their relation to possession of tdh and trh genes].

We analysed 467 isolates of Vibrio parahaemolyticus for possession of tdh/trh gene in comparison with urease production and serotypes. Strains possessing tdh+/trh-, tdh+/trh+, tdh-/trh-, and tdh-/trh- show positive urease production 2.1, 100, 65.7, 100%, respectively. Serotypes of O1:K69, O3:K6, O3:K72, O6:K18, O6:K46 and O1:KUT were frequently positive (100% except 91.7% of the latest one) in urease production. All isolates of O3:K6 prossessed trh, whereas all isolates of certain serotypes including O1:K69 and O3:K72 possessed both trh and trh and tdh genes. Among these, most of O1:K69 and O3:K72 were urease producer. From these results, we speculate that urease production is closely related to the presence of the trh gene or/and lesser production of TDH. We also found the new combination of serovar, O3:K25, O4:K37 and O13:K72 in Kanagawa phenomenon-positive strains.

Genes, Bacterial↗

Isolation and characterization of an alicyclic amine N-sulfotransferase from female rat liver.

An alicyclic amine N-sulfotransferase sulfonating 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) was purified from female rat liver cytosol and showed a homogenous band with a molecular weight of 30500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme, designated NST-1, catalyzed sulfonation not only of the alicyclic amine but also dehydroepiandrosterone, a typical substrate of hydroxysteroid sulfotransferase (STs), but had little sulfonating activity towards 2-naphthol, a typical substrate of aryl STs. The N-terminal amino acid sequence for the first 24 residues had a high homology with those of rat liver hydroxysteroid STs. Therefore, it is suggested that NST-1 is classified as a member of the hydroxysteroid ST. Immunoblot analysis of male and female rat liver cytosol, carried out by using rabbit antisera raised against NST-1, indicated that the female cytosol contained a higher level of the enzyme than that of male. The marked sex difference in the expression level of NST-1 was in good accordance with the previous demonstration that female rat liver cytosol catalyzed sulfonation of PTHP to a greater extent than that of male.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Antinociceptive effects of counterirritants].

Counterirritants such as l-menthol, methyl salicylate, camphor, thymol and capsaicin are widely used in the treatment of mild pains and itches by topical application. However, little experimental research on counterirritants has been reported. In the present study, we investigated the antinociceptive effects and mechanisms of topically applied counterirritants, especially those of l-menthol. From the formalin test in mice, l-menthol (at a concentration of 1-30% in ethanol) showed a major effect in the early phase of pain response (0-5 min). In contrast, the antinociceptive effects of indomethacin (10 mg/kg, p.o.) were found only in the late phase of pain response (15-25 min). Furthermore, morphine (0.75-6 mg/kg, s.c.) dose-dependently inhibited both phases. l-Menthol-induced analgesia during the early phase was significantly blocked by naloxone and potentiated by bestatin. The antinociceptive effects of l-menthol were furthermore examined in dexamethasone-treated mice. l-Menthol also produced antinociceptive effects in the hot plate test of mice and hind paw pressure test of rats. l-Menthol showed mild surface and infiltrating anesthetic effects in guinea pigs. l-Menthol did not inhibit both carrageenin-induced paw edema of rats and the synthesis of prostaglandin E2 in vitro. Based on these findings, we proposed that l-menthol produces antinociceptive effects by activation of the endogenous opioid system and/or partially by local anesthetic actions without anti-inflammatory effects.

Administration, Topical↗

20 alpha-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasms.

20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activities in 57 neoplastic tissues surgically removed from dogs were measured. Forty-eight of 57 tumor samples were shown to possess 20 alpha-HSD activity. These tissues were histopathologically classified into 22 benign and 26 malignant tumors. Among these tumors, mixed tumor types demonstrated the higher 20 alpha-HSD activity than epithelial and non-epithelial types, and malignant tumors of each tissue type showed slightly but not significantly higher 20 alpha-HSD activities comparing with the corresponding benign ones. Comparing with the activity of normal tissues examined, the corresponding tumor tissues showed significantly higher 20 alpha-HSD activities. Thus, 20 alpha-HSD activity was found in neoplastic tissues at a considerable high rate and the activity seemed to be higher in pathologically malignant tumors.

20-Hydroxysteroid Dehydrogenases↗

Influence of HLA antigens on reproduction among Japanese population: study of haplotypes in 247 families.

Although an increased incidence of shared HLA antigens among couples experiencing recurrent spontaneous abortion or infertility has been observed, antigenic effects remain to be clarified. These effects, which are suspected to exist among fertile couples, were examined in this study. A group of 247 healthy Japanese families and their 682 children, whose HLA antigen haplotypes could be determined, were studied. Haplotypes of the fathers were compared with those of the mothers, and the combination of HLA antigens in the A, B, C and DR loci was determined as antigenic patterns against the mother. Patterns inherited by children were examined and deviations of the patterns were studied according to the natural rule that either of the haplotypes should be inherited at equal rates. Lower rates of children with antigens common with those of the mother, which may show a result of reproductive selection, were observed among only the first born children in the A (p < 0.05) and DR loci (p < 0.01), but rates similar to those expected were observed among the second born and later children. Lower rates were also observed in the B and C loci among all children with no significant difference between groups of the children. The necessity of differing antigenic factors in order to achieve pregnancy in the population was shown. Important effects of HLA antigenicity in reproductive failure are suggested.

Adult↗

Preparation of unfixed and undecalcified frozen sections of adult rat periodontal ligament during experimental tooth movement.

The upper first molars of adult male rats were moved for 7 days and unfixed, undecalcified frozen sections of the molar periodontal ligament were prepared and observed. The upper jaws of the rats were immersed rapidly in liquid nitrogen and sectioned with a cryostat using a super hard knife. Five micrometer serial sections were cut, collected, freeze-dried and observed with both light and scanning electron microscopy. Electron probe microanalysis (EPMA) was also performed on the sections. On the tension side of the periodontal ligament, periodontal fibers were stretched and the osteoblasts were aligned on the osteoid, which showed metamasia with the toluidine blue stain. On the pressure side where the periodontal ligament was extremely compressed, tissue degeneration was caused by tooth movement and the osteoclasts were observed on the bone surface adjacent to the degenerating tissues. Scanning electron microscopy revealed a network arrangement of the collagen fiber bundles on the tension side, but not on the pressure side of the periodontal ligament. The spectrum obtained from EPMA of the osteoid demonstrated X-ray (Ka) peaks of Na, P, S, K and Ca.

Animals↗

[Phase I clinical trial of RP 56976 (docetaxel) a new anticancer drug].

A multicenter phase I clinical trial of RP 56976 (docetaxel), a new anticancer drug, was performed with single and repeated doses. Based on the results of phase I clinical trials conducted in the United States and Europe, the starting dose was 10 mg/m2. The dose was subsequently increased to 20, 50, 70 and 90 mg/m2. A dose of 60 mg/m2 was additionally tested. Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour. Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner. The dose limiting factor (DLF) of docetaxel is leukopenia (especially, neutropenia). Based on the observation of the DLF, the maximum tolerated dose (MTD) was determined to be 70-90 mg/m2. The white blood cell count reached a nadir about 9.5-19.5 days (median) after administration, and took 7-11 days (median) to recover. Other adverse reactions observed were nausea/vomiting anorexia, alopecia, diarrhea, fatigue and fever, which were all acceptable. The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial.

Adolescent↗

[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group].

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adenocarcinoma, Clear Cell↗

[Phase II clinical study of RP56976 (docetaxel) in patients with carcinoma ovarii or carcinoma colli uteri].

An early phase II clinical study of RP56976 (docetaxel), a new semisynthetic agent, in patients with carcinoma ovarii or carcinoma colli uteri was undertaken by a cooperative study group of 23 institutes. Docetaxel was administered at an initial intravenous dose of 60 mg/m2 with dose-free intervals of 3-4 weeks, and its efficacy and safety were evaluated. Of the 47 patients with carcinoma ovarii enrolled, 44 patients were eligible and 36 patients completed the scheduled course of treatment. Of the 23 patients with carcinoma colli uteri enrolled, 20 patients were eligible and 15 patients completed the scheduled course of treatment. For antitumor efficacy in patients with carcinoma ovarii, 1 patient showed partial response (PR), 10 showed no changes (NC) (2 showed minor response (MR)), and 25 had progressive disease (PD). The overall response rate was 2.8% (1/36). Of patients with carcinoma colli uteri, 7 patients showed no changes (NC) (1 patient showed minor response (MR)), 8 patients had progressive disease (PD). Major adverse reactions included 64/65 (98.5%) leukopenia, 56/59 (94.9%) neutropenia, 40/60 (61.5%) decrease of hemoglobin, 12/64 (18.8%) thrombocytopenia, 30/65 (46.2%) anorexia, 23/65 (35.4%) nausea/vomiting, 37/65 (56.9%) alopecia, and 26/65 (40.0%) fatigue, all of which were mild.

Adenocarcinoma, Clear Cell↗

Cytochrome c oxidase activity in osteoclasts appeared in an early stage of parathyroid hormone treatment.

Osteoclasts which appeared in an early stage of parathyroid hormone (PTH) administration were examined using cytochrome c oxidase activity. In the period of 1-2 hr after intraperitoneal administration of PTH, two types of osteoclasts were observed. The first type had a well-developed ruffled border characterized by deeply infolded extracellular channels, and many endocytic vacuoles were observed, as seen in control osteoclasts. Many of the mitochondria contained in the first type were with the reaction products of the enzyme on the crystal membrane and within the intermembrane space (type 1 mitochondria), and the distribution of type 1 mitochondria was similar to that seen in control osteoclasts. The second type had a ruffled border characterized by unclear extracellular channels and cytoplasmic projections. The numerical percentage of type 1 mitochondria in the second type of osteoclasts (45.3%) was significantly smaller than that in the first type (79.9%). Mitochondria which had the reaction products of the enzyme only on the crystal membrane including those with no reaction product (type 2 mitochondria) were predominant in the second type of osteoclasts. These results include two possible ways in which a morphologically regressive change of the ruffled border can occur in osteoclasts during an early stage of PTH treatment, and cytochrome c oxidase activity is closely associated with the change in the ruffled border.

Animals↗

Effect of repeated injection of somatomedin C on drug metabolizing enzyme activities in rats.

The effect of somatomedin C on the hepatic drug-metabolizing enzyme system in rat liver after sc injection, a clinically applicable dosing route, was studied. Although liver weight was slightly increased after somatomedin C (1 mg/kg) was injected for 7 days, no significant changes were observed in other dosing group (0.1 and 10 mg/kg). There were no significant effects of somatomedin C on cytochrome P-450 and b5 contents, and NADPH-cytochrome c reductase, aminopyrine demethylase, aniline hydroxylase, and ethoxyresorufin deethylase. Additionally, somatomedin C treatment did not affect the activities of 2 alpha-, 2 beta-, 6 beta- and 16 alpha-hydroxytestosterone and androstenedione formation from testosterone. Changes relation to dosing period were also examined with 1 mg/kg of somatomedin C. In this case, hepatic levels of cytochrome P-450 and b5, NADPH-cytochrome c reductase and drug oxidations did not differ significantly among groups treated for 3, 7, or 14 days. These results suggest that somatomedin C has no effect on the hepatic mixed-function oxidase system.

Animals↗

Serum glucose and insulin levels and erythritol balance after oral administration of erythritol in healthy subjects.

OBJECTIVES: To investigate the effect of an oral administration of erythritol on serum glucose and insulin levels in healthy subjects and estimate available energy of erythritol in human. DESIGN: Ingestion of erythritol (0.3 g/kg body weight) or the same dose of glucose as a control. SETTING: Omiya Research Lab., Nikken Chemicals Co., Japan. SUBJECTS: 5 healthy male volunteers aged 45-58 years. MAIN OUTCOME MEASURES: Serum glucose, insulin and erythritol levels after erythritol ingestion. Urinary erythritol excretion. RESULTS: Erythritol did not increase serum levels of glucose or insulin, while the same dose of glucose increased rapidly glucose and insulin levels within 30 min. Erythritol did not induce any significant effects on serum levels of total cholesterol, triacylglycerol, free fatty acids, Na, K and Cl. Also, urinary Na, K and Cl were not affected by erythritol ingestion. Serum levels of erythritol reached the maximum concentration of 426.5 +/- 113.4 micrograms/ml at 30 min and declined to 13.5 +/- 3.2 micrograms/ml at 24 h. Total urinary excretion of erythritol was 85.8 +/- 4.6% for 24 h and 90.3 +/- 4.5% for 48 h, respectively. CONCLUSIONS: Erythritol did not affect serum levels of glucose, insulin or other serum constituents. More than 90% of ingested erythritol was readily absorbed and excreted in urine without degradation. This fact suggests that available energy of erythritol in human is less than 1.7 kJ/g (0.4 kcal/g). DESCRIPTORS: erythritol, glucose, insulin, low energy sweetener.

Administration, Oral↗

[Phase I clinical study of 21-consecutive-day oral administration of etoposide].

We conducted a multi-institutional phase I clinical study on a 21-consecutive-day oral administration of etoposide in 12 patients with malignant tumor. The initial dose was 25 mg/body/day and then raised to 50 mg/body/day and eventually to 75 mg/body/day. The dose limiting factor was leukopenia and the maximum tolerated dose (MTD) was 75 mg/body/day. Leukopenia was observed in all 4 patients registered at 75 mg/body/day. Two of 4 patients showed WBC count nadirs of less than 2,000/microliters. The two patients had less than 1.5 m2 body surface area. Thrombocytopenia and hemoglobin decrease were mild compared to leukopenia. Other adverse reactions were as follows; anorexia (75.0%), nausea/vomiting (58.3%) alopecia (46.1%). No sign of accumulation after 21-consecutive-day oral administration of etoposide was seen on pharmacokinetic parameters. As for anti-tumor efficacy, a partial response was noted in a patient with lung metastasis of cervical cancer at the 75 mg/body/day dose level. A recommended dose for phase II study was 75 mg/body/day for 21 consecutive days with a one-week interval. However, for a patient with a body surface area less than 1.5 m2 or with a severe prior chemotherapy, 50 mg/body/day would be considered appropriate.

Administration, Oral↗

[Long-term administration of carmofur as a post-operative adjuvant chemotherapy for cervical adenocarcinoma. Cervical Adenocarcinoma Cooperative Research Association].

Cervical adenocarcinoma and adenosquamous cell carcinoma are low in radiation sensitivity, and the prognosis is said to be inferior to that of squamous cell carcinoma. Eleven facilities nationwide participated in the historical control study on the recurrence prevention effect of carmofur (HCFU) administered at 300 mg/day for more than two years postoperatively as an adjuvant chemotherapy to patients with cervical adenocarcinoma or adenosquamous cell carcinoma for which radical operation is possible. Registered for the study was a total of 252 patients: 77 patients for whom administration of carmofur was begun during the period from January 1987 and March 1989, 71 patients (control 1) who were treated for the cancer after January 1982 but did not receive adjuvant chemotherapy, and 104 patients who received adjuvant chemotherapies with other than carmofur (control 2). In analyses with the Kaplan-Meier method, the carmofur administration group demonstrated a better cumulative survival rate and disease free rate than control 1 (no adjuvant chemotherapy), suggesting carmofur was effective in preventing the recurrence of cervical adenocarcinoma and adenosquamous cell carcinoma.

Adenocarcinoma↗

[Clinical significance of galactosyltransferase associated with tumor (GAT), a new tumor marker for ovarian cancer--with special reference to the discrimination between ovarian cancer and endometriosis].

We examined GAT, a newly developed tumor marker, in serum samples collected from 1,503 females in six institutions: 387 healthy females, 1,052 patients with gynecological diseases including 311 ovarian cancers, and 64 with nongynecological diseases. Based on the mean value + 2 SD for the healthy females, the cut-off value was set at 16 U/ml. The positive rate of GAT was 2.6% for the healthy females, 7.1% for patients with benign ovarian tumor, 5.6% for those with endometriosis, 47.9% for those with ovarian cancers, 9.3% for those with cervical cancer, and 13.3% for those with endometrial cancer. The false-positive rate of GAT for endometriosis was very low compared with that of the other markers such as CA 125, CA 602, CA 54/61, CA 72-4, STN, SLX examined in this study. The positive predictive value between ovarian cancer and endometriosis was the highest with GAT among the evaluated markers. In the cases in which the CA 125 (CA 602) value is relatively low, discrimination between ovarian cancer and endometriosis is difficult, because these cases include many patients with endometriosis. GAT showed the highest positive predictive value in such cases, so GAT proved to play a complementary role with CA 125 (CA 602). Combination assay with GAT and CA 54/61/CA 72-4/STN or SLX showed higher diagnostic efficiency between ovarian cancer and endometriosis. These results suggest the usefulness of GAT for discrimination between ovarian cancer and endometriosis.

Antigens, Tumor-Associated, Carbohydrate↗

Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene.

The primary structure of human xanthine dehydrogenase (hXDH) was determined by cloning and sequence analysis of the cDNAs encoding the enzyme. The nucleotide (nt) sequence has an open reading frame of 3999 nt encoding a protein of 1333 amino acids (aa) with a calculated M(r) of 146,604. The deduced aa sequence of hXDH is homologous to the previously reported rat XDH (rXDH) and Drosophila melanogaster XDH sequences with identities of 90.2 and 52.0%, respectively. The aa residues involved in both the reversible and the irreversible conversion from the dehydrogenase type to the oxidase type of rXDH are completely conserved between the rat and the human enzymes. This implies that the molecular mechanisms of the conversion of hXDH from dehydrogenase to oxidase are common to those of the well-characterized rXDH. Five sequence variations were detected in the isolated cDNA clones. Spot blot hybridization using flow-sorted human chromosome revealed that the hXDH-encoding gene (hXDH) was located on chromosome 2.

Amino Acid Sequence↗

Sensitive determination of bisoprolol enantiomers in plasma and urine by high-performance liquid chromatography using fluorescence detection, and application to preliminary study in humans.

A sensitive, stereoselective high-performance liquid chromatographic method with fluorescence detection for the measurement of bisoprolol enantiomers in human plasma and urine has been developed. Bisoprolol was extracted at alkaline pH with chloroform, followed by solid-phase extraction. The effluent was evaporated, and the reconstituted residue was chromatographed on a Chiralcel OD column with a mobile phase of hexane-2-propanol (10:0.9, v/v) containing 0.01% (v/v) diethylamine. Within the plasma and urine enantiomeric concentration ranges of 5-100 ng/ml and 25-1250 ng/ml, respectively, a linear relationship was obtained between the peak-height ratios and the corresponding concentrations. The limit of quantitation, defined as three times the baseline noise, was 2 ng/ml for each enantiomer in plasma. A preliminary pharmacokinetic study was undertaken in three healthy male volunteers following an oral dose of 5 mg of racemic bisoprolol. The results confirm that this assay is suitable for pharmacokinetic studies of bisoprolol enantiomers in humans following oral administration of the therapeutic dose.

Bisoprolol↗