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Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 325 records · Page 18Linked to original sources
PubMed1992

Effect of repeated oral doses of a novel immunosuppressive macrolide lactone on hepatic mixed-function oxidase system in the rat. Comparative study with ciclosporin.

Effect of pretreatment of rats with FK506((-)-(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-allyl-1,14- dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3methoxycyclohexyl]-1- methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0(4.9)]octacos-18-ene-2,3,10,16-tetrone hydrate, CAS 104987-11-3) on microsomal cytochrome P-450 system and oxidations of the administered drug and other model substrates were studied and compared with those of a pharmacologically related drug, ciclosporin (cyclosporin A). Oral treatment of male Sprague-Dawley rats with FK506 (0.4, 2 or 10 mg/kg/d) for 7 days did not decrease microsomal content of total cytochrome P-450 in livers, but rather increased the content in groups with the dose of 0.4 or 10 mg/kg to the levels of 126-130% of the control. Microsomal NADPH-cytochrome c reductase activities were decreased up to 67% of the control with the increasing dose of FK506 and to 62% in a group treated orally with cyclosporin A (25 mg/kg/d for 7 days), although another microsomal electron-transport component, cytochrome b5, was rather increased in all the treated groups. Treatment with FK506 or cyclosporin A did not reduce but slightly increased microsomal activities of aniline hydroxylation, p-nitroanisole O-demethylation and O-ethoxyresorufin O-deethylation. Microsomal depropylation of 7-propoxycoumarin, a typical P-450IIIA-substrate, was also not reduced in all dose groups of FK506, while it was decreased by the treatment with 25 mg/kg cyclosporin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cardioprotection of ACE inhibitor in ischemic heart is not dependent on the local angiotensin II formation.

Angiotensin II (AII) and bradykinin (BK) release into anterior interventricular vein (AIV) increased significantly 30 minutes after left anterior descending artery (LAD) occlusion in the absence of kidneys. Captopril enhanced BK release, but did not suppress the increase of AII release. Nafamostat suppressed both releases. Infarct size was significantly reduced by captopril but not by nafamostat. These results suggest that cardioprotective effect of captopril might be dependent on local BK accumulation, but not on suppression of local AII generation.

Angiotensin II↗
PubMed1992

[A group study on prognosis of ovarian cancer in Japan].

An assessment has been made, with the cooperation of 22 institutes, of 1,185 cases of ovarian cancer as subjects who were treated in the period from January, 1980, to December, 1987. As a result, (1) As for distribution by clinical staging at the initial examination, the cases in Stage III were the most numerous, followed by those in Stage I, and if classified according to the histological type, serous cystadenocarcinoma was the most frequently observed in Stage III, and undifferentiated and unclassified carcinomata were observed in Stages III and IV. (2) In the examination of prognostic factors, it was confirmed that the clinical stage, histological type and diameter of the remaining tumor after the initial operation were important factors. (3) A significant difference was observed between the grade of histomorphological differentiation and prognosis, the difference was chiefly due to the deviated distribution of clinical staging in each group of differentiation. (4) A favorable trend was observed in the prognosis by patient's age toward the younger layer. (5) When the starting time of the therapy is considered, a trend toward improvement has been seen year by year, and it is considered that the beneficial effect of chemotherapy with CDDP contributes to this.

Adult↗
PubMed1992

Clinical effect of sizofiran combined with irradiation in cervical cancer patients: a randomized controlled study. Cooperative Study Group on SPG for Gynecological Cancer.

To evaluate the clinical effect of a biological response modifier (BRM), sizofiran (SPG), combined with irradiation, a randomized controlled study was performed in patients with stage II or III cervical cancer involving the collaboration of 52 institutes throughout Japan. Patients were randomly allocated to the control group (radiotherapy only) and the SPG group (radiotherapy + SPG). SPG was given intramuscularly, 40 mg once and 20 mg twice, a week concomitantly with radiotherapy. A total 315 patients were enrolled for the study but 23 were excluded from analysis. Of the remaining 292 patients, 121 were of stage II (43 controls and 78 SPG) and 171 of stage III (49 controls and 122 SPG). The results were as follows. (1) The complete response (CR) rate among stage II patients was higher in the SPG group (91.0%) than in the control group (79.1%); also the CR rate among stage III patients was significantly higher in the SPG group (77.9%) than in the control group (61.2%). (2) The SPG group showed a significantly rapid recovery from the decreased lymphocyte counts due to radiotherapy (P less than 0.05). (3) Side effects, probably associated with SPG administration, were observed in 11 cases (5.2%).

Adult↗
PubMed1992

[Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer].

A phase II study of 254-S was conducted in 134 patients with gynecological malignancies by the gynecology section of the 254-S cooperative study group. The drug was administered at least twice at a dose of 100 mg/m2 by intravenous infusion at 4 week intervals. Forty-two of the 102 evaluable patients responded, including 8 CRs and 34 PRs, with a response rate of 41.2%. The response rate was 37.7% for ovarian cancer and 46.3% for cervical cancer. The response rate of 46.3% for cervical cancer was the highest reported for any single anticancer agent available in Japan. The major side effect was hematotoxicity, in particular thrombocytopenia and leukopenia, while nephrotoxicity was rarely observed. These results suggest that 254-S is an active cisplatin analogue with reduced nephrotoxicity and is a very promising anticancer agent for the treatment of ovarian and cervical cancer.

Adult↗
PubMed1992

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus].

A phase II clinical study of 254-S, a new anticancer platinum complex, for cervical cancer was conducted by the 254-S Cervical Cancer Study Group consisting of 10 institutions. 254-S was administered at 80 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals, in principle. Forty of 45 patients registered, were eligible and 38 were evaluable for tumor response (complete cases). Complete response (CR) and partial response (PR) were obtained in 4 (10.5%) and 9 patients (23.7%), respectively, for a 34.2% response rate. Against squamous cell carcinoma, a 38.2% response rate (4 CR and 9 PR in 34 patients) was obtained. The response rate obtained in patients with no prior chemotherapy was 40.0% (2 CR and 8 PR in 25 patients), while that in patients with prior chemotherapy was 23.1% (2 CR and 1 PR in 13 patients). Major toxic effects observed were hematotoxicity, including thrombocytopenia (35.1%), leukopenia (73.0%), anemia (75.7%), gastrointestinal toxicity such as nausea and vomiting (83.8%) and anorexia (83.8%). Nephrotoxicity observed was in the form of an elevation of serum creatinine with an incidence of 2.7% and a decrease in creatinine clearance with an incidence of 21.7%. In comparison with the results obtained in the phase II clinical study for gynecological cancers in which 254-S was administered at 100 mg/m2, the response rate obtained in this study was slightly lower but thrombocytopenia and leukopenia observed were less frequent and milder. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of cervical cancer.

Adenocarcinoma↗
PubMed1992

[HTLV-I associated myelopathy with bilateral abductor vocal cord paralysis--case report].

We have reported a 50-year-old woman with HTLV-I associated myelopathy (HAM) who had bilateral abductor vocal cord paralysis. The symptoms and signs were slowly progressive spastic paraplegia, dysuria, inspiratory stridor, and snoring during sleep. She had no hoarseness. Titers of anti-HTLV-I antibody were elevated in both the serum and cerebrospinal fluid. FEV1.0% on the spirogram was reduced to 66%. The fiberscopic examination demonstrated the abductor limitation of the vocal cords during the inspiratory phase. During induced sleep after the intravenous administration of thiopental sodium, this abductor paralysis was worsened, producing a high pitched inspiratory stridor. The adduction was not disturbed at all. Needle electromyogram of the posterior crico-arytenoid muscle which is a sole abductor muscle revealed the high amplitude up to approximately 1.0 mV (normal less than 0.8 mV) with poor interference pattern, indicating neurogenic changes. After 2 months course of prednisolone (60 mg/alternative day), FEV1.0% was recovered to be 92% with the improvement of the gait disturbance, which suggests the abductor vocal cord paralysis is related to HAM. The abductor vocal cord paralysis in HAM would require a careful follow-up observation to protect the respiratory failure in the advanced stage.

Electromyography↗
PubMed1991

Purification and amino acid sequence of a bitter gourd inhibitor against an acidic amino acid-specific endopeptidase of Streptomyces griseus.

An inhibitor (BGIA) against an acidic amino acid-specific endopeptidase of Streptomyces griseus (Glu S. griseus protease) was isolated from seeds of the bitter gourd Momordica charantia L., and its amino acid sequence was determined. The molecular weight of BGIA based on the amino acid sequence was calculated to be 7419. BGIA competitively inhibited Glu S. griseus protease with an inhibition constant (Ki) of 70 nM, and gel filtration analyses suggested that BGIA forms a 1:1 complex with this protease. However, two other acidic amino acid-specific endopeptidases, protease V8 from Staphylococcus aureus and Bacillus subtilis proteinase (Glu B. subtilis protease), were not inhibited by BGIA. BGIA had no inhibitory activity against chymotrypsin, trypsin, porcine pancreatic elastase, and papain, although subtilisin Carlsberg was strongly inhibited. The amino acid sequence of BGIA shows similarity to potato chymotrypsin inhibitor, barley subtilisin-chymotrypsin inhibitor CI-1 and CI-2, and leech eglin C, especially around the reactive site. Although the residue at the putative reactive site of these inhibitors is leucine or methionine, the corresponding amino acid in BGIA is alanine.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of rat ovarian 20 alpha-hydroxysteroid dehydrogenase.

To investigate the regulatory mechanism of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) (EC 1.1.1.149) activity in ovarian tissue, the enzyme was purified from ovaries of normal mature female rats. Column chromatography of the cytosolic fraction from ovaries on DEAE-Toyopearl 650M revealed two peaks of the 20 alpha-HSD activity at different ionic strengths. These peaks were designated HSD1 and HSD2, respectively. Each of the active fractions was further purified to homogeneity by dye-affinity chromatography using Matrex Green A and AF Red-Toyopearl. Both the fractions appeared as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (at Mr = 33,000 under reducing conditions). Under non-reducing conditions, similar values were obtained on gel-exclusion HPLC, indicating that the enzyme fractions were single-stranded, monomeric polypeptides. Homogeneous HSD1 and HSD2 were purified 361-fold and 509-fold, respectively, and differed in their substrate preference. The two enzyme fractions had Km values of 4.75 microM and 5.16 microM for 20 alpha-dihydroprogesterone, respectively, and showed almost the same RF values on reverse-phase HPLC and free-zone capillary electrophoresis. However, amino acid composition was slightly different, i.e. lysin content was higher in HSD1 than HSD2. Thus, it was clarified that two types of 20 alpha-HSD with very similar molecular structures are present in the rat ovary.

20-Hydroxysteroid Dehydrogenases↗
PubMed1991

Cloning and characterization of human papillomavirus type 52 from cervical carcinoma in Indonesia.

Human papillomavirus (HPV) type 52 from a cervical carcinoma in Indonesia was molecularly cloned and characterized. By hybridization with cervical carcinoma DNAs from Indonesian patients, HPV 52 was detected in 3 of 52 cases (6%), whereas HPV 16 and 18 were detected in 8 and 7 cases, respectively (15% and 13%). Sequence analysis revealed that the E6-E7 ORFs contained several DNA binding motifs (Cys-X-X-Cys) like previously sequenced HPVs. The E6 ORF also contained splice donor and acceptor signals, which may allow the expression of E6* protein. The E7 ORF encoded an amino acid sequence that is conserved in some DNA tumor viruses and is involved in binding to Rb protein and in cellular transformation. Transfection of a subgenomic fragment of HPV 52 under the control of a heterologous promoter showed that the E7 ORF alone induced anchorage-independent growth of established rodent cells and immortalized primary rat embryo fibroblasts (REF), and that in cooperation with activated ras, it induced malignant transformation of REF. The E6 ORF also induced, less efficiently, anchorage-independent growth. These results strongly suggest that HPV 52, like HPV 16 and 18, has oncogenic potential.

Amino Acid Sequence↗
PubMed1991

Replacement of P1 Leu18 by Glu18 in the reactive site of turkey ovomucoid third domain converts it into a strong inhibitor of Glu-specific Streptomyces griseus proteinase (GluSGP).

Turkey ovomucoid third domain with P1 Leu18 at its reactive site is an excellent inhibitor of chymotrypsin and elastase and of many other serine proteinases with related specificities. Semisynthetic replacement of P1 Leu18 by Lys18 causes the expected change into a trypsin inhibitor. Strikingly, semisynthetic replacement P1 Leu18 to Glu18 changes turkey ovomucoid third domain into a powerful inhibitor of Glu-specific Streptomyces griseus proteinase, GluSGP. Of the 131 natural avian ovomucoid third domains we have sequenced none have P1 Glu18, but several avian ovomucoid first domains have P1 Glu24. They are weak to moderate inhibitors of GluSGP.

Amino Acid Sequence↗
PubMed1991

Magnesium content of erythrocytes in patients with vasospastic angina.

The possibility that a magnesium deficiency might be the underlying cause of vasospastic angina (VA) and the efficacy of Mg administration in its treatment were studied. Subjects included 15 patients with VA and 18 healthy subjects as the control group. The erythrocyte Mg content was measured by atomic absorption, and serum Mg was measured by conventional chemical assay. The efficacy of Mg administration was studied in seven patients with VA. The results were as follows: a) The mean erythrocyte Mg content was less in the group with frequent episodes of angina (1.59 +/- 0.11 mg/dl) than in the group without angina (2.11 +/- 0.38 mg/dl, p less than 0.01) and in the control group (2.22 +/- 0.29 mg/dl, p less than 0.01). There was no significant difference between the control group and patients of each group with respect to serum Mg. b) Coronary arterial spasm was induced by ergonovine maleate in seven patients and was completely inhibited by the administration of Mg sulfate (40-80 mEq, hourly) in six of these patients; in the remaining patient neither obvious ST change nor chest pain occurred. Thus, it was concluded that the measurement of erythrocyte Mg content is useful to determine how easily vasospasm might occur in VA and that the administration of Mg might be developed as a new therapy for spasm associated with a low erythrocyte Mg content.

Aged↗
PubMed1991

Human renin activation by protease from the renin granule fraction of the dog kidney cortex.

To clarify the possible conversion of prorenin in renin granules where conversion reportedly occurred, we investigated whether the renin granule fraction of the kidney could activate prorenin to the active form. Renin granules were isolated from the dog kidney cortex by discontinuous sucrose density gradient centrifugation. Human active renin was quantified by immunoradiometric assay which could detect only the human active renin but not the inactive human renin or dog renin. Inactive renin from human amniotic fluid was incubated with the subcellular fraction of the dog kidney cortex. The renin granule fraction that showed the highest renin activity stimulated the inactive renin to become the active form. The membrane preparation obtained from the renin granule fraction by freezing and thawing the fraction in low osmolarity retained the activity of renin activation. Other subcellular fractions showed less renin activation. The optimal pH for renin activation by the membrane was pH 5.0 to 6.0. The activation depended on the time of incubation and concentration. The activation was inhibited by N-ethylmaleimide but not by EDTA or serine protease inhibitors. These results suggest that renin is processed by a membrane bound protease in renin granules.

Amniotic Fluid↗
PubMed1991

Subsite mapping of an acidic amino acid-specific endopeptidase from Streptomyces griseus, GluSGP, and protease V8.

The substrate specificities of an acidic amino acid-specific endopeptidase of Streptomyces griseus, GluSGP, and protease V8 [EC 3.4.21.19] were investigated with peptide p-nitroanilide substrates which have a Glu residue at the P1 position. GluSGP and protease V8 favored Pro and Leu residues at S2, respectively, while the S3 subsite of GluSGP preferred Phe over either Ala or Leu. The S3 subsite of protease V8 preferred Leu over either Ala or Phe. The best substrates for GluSGP and for protease V8 were Boc-Ala-Phe-Pro-Glu-pNA with a Km value of 0.41 mM (0.1 M Tris-HCl, pH 8.8) and Boc-Ala-Leu-Leu-Glu-pNA with a Km value of 0.25 mM (0.1 M phosphate, pH 7.8), respectively. The kcat/Km values for these substrates obtained with GluSGP were about one hundred to twenty thousand times larger than those obtained with protease V8. Protease V8 exhibited a single optimal pH of around 8 for the hydrolysis of Boc-Ala-Ala-Leu-Glu-pNA and Boc-Ala-Leu-Leu-Asp-pNA.

Amino Acid Sequence↗
PubMed1991

Effects of l-menthol and dl-camphor on the penetration and hydrolysis of methyl salicylate in hairless mouse skin.

Plasters containing methyl salicylate with and without l-menthol and dl-camphor were prepared and topically applied on hairless mouse skin to investigate the effects of l-menthol and dl-camphor on the skin penetration and hydrolysis of methyl salicylate in the skin. The in vitro hydrolysis of methyl salicylate was also investigated using the skin homogenate. It was found that l-menthol with dl-camphor enhanced the skin penetration of methyl salicylate, and they inhibited both the in vivo and in vitro hydrolysis of methyl salicylate to salicylic acid.

Administration, Topical↗
PubMed1991

Cytosolic 20 alpha-hydroxysteroid dehydrogenase activity in spontaneous neoplasms in the dog and cat.

Steroid-producing tissues such as ovary, placenta, testis and adrenal gland and non-steroid-producing cells including lymphocytes are known to contain 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). In the present study, we measured and partially characterized the 20 alpha-HSD in 11 neoplastic tissues surgically removed from dogs and a cat. The tissues were pathologically classified as 4 benign and 7 malignant. The enzyme activities in the cytoplasmic fraction were positive in 6 of the 7 malignant tissues and 2 of the 4 benign ones. Following DEAE chromatography analysis of 2 malignant tumour samples, multiple forms of enzyme activities with different electric charges were detected. Furthermore, 20 alpha-HSD activity in the cytosol fraction from malignant tumours was increased dramatically by passage through the DEAE column, suggesting that the enzyme is present in the cytosol as an inactive or sequestered form.

20-Hydroxysteroid Dehydrogenases↗
PubMed1991

[Phase II study of 5'-DFUR in uterine cervical cancer and ovarian cancer].

A phase II study of 5'-DFUR was conducted in uterine cervical cancer and ovarian cancer by the cooperative study group consisting of 26 institutions. Forty-four cases with uterine cervical cancer and 40 cases with ovarian cancer were enrolled. A daily dose of 800-1,200 mg was administered orally for more than 8 weeks. In 34 evaluable cases with uterine cervical cancer, the overall efficacy rate was 20.6%: CR was shown in 2 cases, PR in 5 cases, MR in 2 cases, NC in 17 cases and PD in 8 cases. Histologically, the response rate was 27.3% in large cell non-keratinizing type, 20.0% in small cell non-keratinizing type and 15.4% in keratinizing type of squamous cell carcinoma. The overall response rate was 20.7% in squamous cell carcinoma, while 25.0% in adenocarcinoma. In 31 evaluable cases with ovarian cancer, the overall efficacy rate was 16.1%: PR was shown in 5 cases, MR in 3 cases, NC in 11 cases and PD in 12 cases. Histologically, the response rate was 16.7% in serous cystadenocarcinoma, 25.0% in endometrioid adenocarcinoma and 33.3% in undifferentiated carcinoma. No responses were observed in cases with mucinous cystadenocarcinoma, clear cell adenocarcinoma, mature cystic teratoma with malignant transformation and mesodermal mixed tumor. Some adverse effects were observed in 43.2% (32 out of 74 cases evaluated for adverse effects), but those of grade 4 were not observed. Most of them were gastro-intestinal disturbances such as diarrhea and anorexia. Diarrhea of grade 3 was observed in 12.2% and anorexia of grade 3 in 5.4%. Severe myelosuppression or hepatic toxicity was not observed. These results suggested that 5'-DFUR is a useful anticancer drug against uterine cervical cancer and ovarian cancer.

Adenocarcinoma↗