Search PubMed⌕ Search

Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 271 records · Page 15Linked to original sources
PubMed1993

Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study.

BACKGROUND: The failure rate with radiation therapy alone for Stage III cervical cancer is quite high, and therefore other modalities are being pursued as adjuvants to radiation therapy in hopes of improving the results. METHODS: A randomized, controlled, comparative study on the efficacy and safety of radiation therapy combined with LC9018 (a biologic response modifier prepared from heat-killed Lactobacillus casei YIT9018) was conducted using 228 patients with Stage IIIB cervical cancer. RESULTS: LC9018 enhanced tumor regression (P < 0.1) by radiation after both 30 Gy of external radiation and at the completion of radiation therapy. The combination therapy also prolonged survival and the relapse-free interval (P < 0.05) compared to radiation alone. Analysis of survival using the Cox proportional hazard model indicated that use of LC9018 was a significant factor related to survival duration. Major side effects of combined LC9018 included fever and skin lesions at the injection site, but no severe symptoms were noted. Radiation-induced leukopenia was significantly less severe (P < 0.05) in the LC9018-combined group than in the radiation-alone group, suggesting that this agent might help to prevent leukopenia during radiation therapy. CONCLUSIONS: LC9018 was shown to be an effective agent for adjuvant immunotherapy when combined with radiation therapy.

Adjuvants, Immunologic↗
PubMed1993

Determination of the R,R- and S,S-enantiomers of vamicamide in human serum and urine by high-performance liquid chromatography on a Chiral-AGP column.

An enantioselective liquid chromatographic assay for the determinations of the R,R- and S,S-enantiomers of vamicamide, a potent anticholinergic drug, in human serum and urine is described. Racemic vamicamide and internal standard were purified from biological fluids using a two-step extraction procedure involving diethyl ether and 0.1% phosphoric acid. The overall recoveries of racemic vamicamide and internal standard were greater than 80%. The purified samples were measured by high-performance liquid chromatography on a Chiral-AGP column with ultraviolet absorbance detection at 260 nm. The standard curves for the analytes were linear from 10 to 200 ng/ml in serum and from 0.25 to 50 micrograms/ml in urine. The quantification limit of both enantiomers was 10 ng/ml for serum and 250 ng/ml for urine. Both intra-day and inter-day accuracy and precision data showed good reproducibility of the method. The assay has been applied for the analysis of vamicamide enantiomers in serum and urine samples from a healthy volunteer.

Chromatography, High Pressure Liquid↗
PubMed1993

Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene deficiency.

Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged < or = 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negative genotype detected by polymerase chain reaction. The prevalence of the GSTmu negative genotype was 45.3% in the community control group and 68.4%, 69.2%, 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. Odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81), respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype.

Adult↗
PubMed1993

Highly sensitive determination of imidapril, a new angiotensin I-converting enzyme inhibitor, and its active metabolite in human plasma and urine using high-performance liquid chromatography with fluorescent labelling reagent.

A method for the simultaneous determination of imidapril and its active metabolite in human plasma and urine has been developed using high-performance liquid chromatography with a fluorescent labelling reagent, 9-anthryldiazomethane. Imidapril and its active metabolite were extracted from human plasma and urine using a solid-phase extraction cartridge (Bond Elut C18). Two compounds in the eluate were derivatized with 9-anthryldiazomethane and purified with a solid-phase extraction cartridge (Bond Elut SI). The derivatives were analysed using high-performance liquid chromatography with fluorometry. The detection limits of imidapril and its active metabolite were 0.2 ng/ml in plasma and 10 ng/ml in urine. This method could be applied to the pharmacokinetic study of imidapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors.

Using 11 restriction fragment length polymorphism markers, we examined loss of heterozygosity on the long arm of chromosome 17, where one or more genes responsible for hereditary breast and ovarian cancers may be present, in sporadic forms of 94 ovarian and 246 breast cancers. Loss of heterozygosity was observed in 33 of 84 (39.3%) ovarian and in 88 of 214 (41.1%) breast cancers that were informative with at least one marker. Detailed deletion mapping of chromosome 17q in these cancers identified two distinct, commonly deleted regions. One was located between 17q12 and 17q21.3 and the other between 17q25.1 and 17q25.3. In breast cancers, the proximal commonly deleted region was between two loci defined by markers CI17-701 and CI17-730 at 17q21.3, which are 2.4 cM apart. This segment overlaps the region that includes the putative gene for hereditary breast and ovarian carcinomas. The results suggest that at least two tumor suppressor genes associated with sporadic ovarian and breast cancers are present on chromosome 17q and that one of them may be the same gene that is responsible for the hereditary form.

Adenocarcinoma↗
PubMed1993

Increased plasma apolipoprotein E-rich high-density lipoprotein and its effect on serum high-density lipoprotein cholesterol determination in patients with familial hyperalphalipoproteinemia due to cholesteryl ester transfer activity deficiency.

Plasma apo E-rich HDL was studied in regard to its quantity and chemical composition in the members of a family with cholesteryl ester transfer activity deficiency, exhibiting familial hyperalphalipoproteinemia. The approach involved a simple precipitation method established in our laboratory. Serum apo E-rich HDL concentrations for two homozygous members were elevated up to 66 and 60 mg/dl in terms of cholesterol (normal, 6.7 +/- 2.3 mg/dl, n = 38), and to 9.4 and 10.8 mg/dl in terms of apo E (normal, 2.6 +/- 1.5 mg/dl, n = 38). The cholesterol/apo E ratio (mole/mole) of apo E-rich HDL was higher in two homozygotes (669 and 531) than in two cholestatic patients with elevated apo E-rich HDL (268 and 149) and in normal subjects (242 +/- 115, n = 38). Chromatographic studies of the serum from a homozygote showed enlargement of all HDL subclasses and apo E in the larger HDL subclass. These facts indicate that the increase of apo E-rich HDL in this disease occurs secondarily to the enlargement of HDL particles, which require substances to cover their cores, having expanded due to the accumulation of cholesteryl ester. The sera from the homozygotes gave HDL cholesterol concentrations which were remarkably discrepant among commercial precipitating reagents, because of the difference in recovery of apo E-rich HDL with these reagents.

Adult↗
PubMed1993

Evaluation of DNA ploidy in endometrial cancer.

We performed a study to evaluate the relationships between the surgical stage (FIGO, 1989), histological tumor grade, myometrial invasion, peritoneal cytology, lymph node metastasis and prognosis, and DNA ploidy determined by flow cytometry in paraffin-embedded blocks of resected cancer lesions from 76 patients with uterine corpus cancer (adenocarcinoma endometrial type) who had been surgically treated in our hospital. The coefficient of variation was 5.00% on average (3.40 to 5.30%) in DNA histograms of the 76 patients. DNA aneuploid was detected in 18 patients (24%) and tended to be more frequently found in association with advanced surgical stage, higher histological tumor grade, deeper myometrial invasion, positive lymph node metastasis, and positive peritoneal cytology. Kaplan-Meier method was used to analyze the relationship between prognosis and DNA ploidy in 76 patients with uterine corpus cancer, in 36 with surgical stage III, and in 26 with surgical stage IIIa, resulting in prognosis which was significantly better in patients with DNA diploid. The results of multivariate analysis also indicate that DNA ploidy is an independent prognostic factor of uterine corpus cancer. These results suggest that DNA ploidy should be an important parameter for predicting prognosis of uterine corpus cancer.

DNA, Neoplasm↗
PubMed1993

Carbonic anhydrase II deficiency in three unrelated Japanese patients.

Three Japanese patients with carbonic anhydrase II (CAII) deficiency from three families were described. The parents of one patient were unrelated, the parents of each of the other two patients were first cousins. All the patients had renal tubular acidosis, osteopetrosis, symmetrical cerebral calcification and mental retardation. They exhibited poor activity and poor appetite in the neonatal period, and then developed psychomotor retardation. Two of them were diagnosed as having osteopetrosis at 10 months and 36 years of age, respectively, and the other as having osteomalacia at 28 years of age. All patients had recurrent episodes of muscle weakness. The CAII enzyme activity and protein levels in red blood cells in each of the three patients were deficient. Their parents exhibited approximately 50% normal levels of CAII activity and protein. This is the first report of patients with CAII deficiency in the Japanese population.

Acidosis, Renal Tubular↗
PubMed1993

Laparoscopic evaluation of the onset and progression of endometriosis.

OBJECTIVE: To clarify the pathogenesis of endometriosis on the basis of analysis of primary lesion sites, age at onset, rate of progression, and response to drug treatment. STUDY DESIGN: The clinical records of 690 women with laparoscopically confirmed endometriosis were retrospectively analyzed based on the revised American Fertility Society point system. RESULTS: The primary site of endometriosis was the uterosacral ligament and pelvic peritoneum/pouch of Douglas in 73% of patients with stage I disease, whereas only 16% had ovarian lesions. However, disease progression was associated with an increasing frequency of ovarian lesions. In terms of the revised American Fertility Society score, endometriosis progressed at a mean rate of 0.3 point per month. Thus the earliest onset of endometriosis was estimated at 3 to 4 years after menarche. Drug therapy improved the revised American Fertility Society score by about 50%. Patients with a low response to an initial cycle of therapy generally showed further improvement after an additional treatment cycle. CONCLUSIONS: Because endometriosis may occur as early as 3 to 4 years after menarche and gradually progresses, drug therapy, including long-term treatment, should be carried out in women with definitive evidence of endometriosis who must maintain their reproductive potential.

Adolescent↗
PubMed1993

Pharmacokinetics of diltiazem and its metabolites in dogs after oral administration of a multiparticulate sustained-release preparation.

Pharmacokinetics of diltiazem and its six metabolites were compared after oral administration in dogs of a multiparticulate sustained-release diltiazem preparation (HER-SR, QD) and a conventional diltiazem preparation (HER, TID). The plasma concentration of diltiazem, its two active basic metabolites (M1, N-monodesmethyl diltiazem; M2, deacetyl diltiazem), and four acidic metabolites [A1, (+)-(2S,3S)-2-(4-methoxyphenyl)-3-acetoxy-4-oxo-2,3,4,5,-tetrahydro-1,5- benzothiazepin-5-acetic acid; A2, 3-deacetyl-A1; A3, O-demethyl-A1; A4, O-demethyl-3-deacetyl-A1] following several administration routes were determined using high-performance liquid chromatography with UV detector (UV-HPLC). Following the oral administration of HER to dogs, plasma concentrations were in the descending order of A2, diltiazem, M1, and M2. The absolute bioavailability of diltiazem was about 30%. Diltiazem conversion to its metabolites (M1, M2, A2) was 31.0, 2.1, and 14.6%, respectively. Following intraduodenal and mesenteric venous administration of diltiazem, M1 and A2 were produced mainly in the intestine and liver. Oral administration of HER-SR and HER to dogs resulted in almost-identical plasma concentrations of A2, diltiazem, M1, and M2 (descending order). Supported evidence was the effective absorption of diltiazem from all gastrointestinal tract regions and similar formation ratios of diltiazem basic metabolites (M1, M2) from the duodenum, ileum, and colon.

Administration, Oral↗
PubMed1993

Pharmacokinetic analysis of an oral sustained-release diltiazem preparation using multifraction absorption models.

Application of multifraction absorption models to pharmacokinetic analysis of an oral sustained-release diltiazem preparation (HER-SR) was investigated. The plasma diltiazem concentrations after oral administration of the HER-SR preparation were analyzed using both the two-fraction absorption model and the two-step discontinuous absorption model. The two-fraction absorption model was suitable for the pharmacokinetic analysis of the HER-SR preparation, whereas the two-step discontinuous absorption model is often unsuitable for the analysis of sustained-release preparations which disintegrate into fractions with different release characteristics in the gastrointestinal tract. The two-step discontinuous absorption model is usually not applicable to plasma concentration data when the first peak is sharp. MFA-MULTI(V) was shown to be useful for the prediction of the bioavailability in each fraction of HER-SR. It was further demonstrated that a two-fraction absorption model is useful for the comparison of in vitro and in vivo release profiles or evaluating the influence of food on the absorption behavior of HER-SR. In addition, the application of a two-fraction absorption model to population pharmacokinetics of HER-SR was investigated.

Administration, Oral↗
PubMed1993

Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs.

OBJECTIVE: The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size. METHODS: Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique. RESULTS: Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group. CONCLUSIONS: Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation.

Angiotensin II↗
PubMed1993

Determination of carboxyl-terminal residue and disulfide bonds of MACIF (CD59), a glycosyl-phosphatidylinositol-anchored membrane protein.

MACIF (CD59) is a glycosyl-phosphatidylinositol (GPI)-anchored membrane glycoprotein which inhibits the formation of membrane attack complex of human complement. MACIF prepared from human erythrocyte membranes was digested with pronase. When the digest was subjected to two-phase partition with butanol and 0.1 N HCl, the carboxyl-terminal peptide was recovered in the butanol phase because of the attachment of the highly hydrophobic GPI. The amino acid sequence of the peptide was determined to be Asn72 at its amino-terminus and up to Glu76, while the presence of Asn77 was ambiguous. To allow unequivocal determination of the carboxyl-terminus, a soluble form of MACIF was prepared from human urine on a large scale. The carboxyl-terminal peptide from the soluble form was prepared by tryptic digestion followed by reversed-phase HPLC. The sequence and composition of the peptide unequivocally revealed Asn77 as the carboxyl-terminus. The pattern of disulfide bonds of MACIF was also determined with the membrane form as well as the soluble form. Cystine-containing peptides were prepared by chymotryptic and tryptic digestion, purified by HPLC, and their amino acid sequences were determined. The results indicated that disulfide bonds were formed at Cys3-Cys26, Cys6-Cys13, Cys19-Cys39, Cys45-Cys63 (or 64), and Cys63 (or 64)-Cys69.

Amino Acid Sequence↗
PubMed1993

Further evaluation of a new penetration enhancer, HPE-101.

The penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), significantly enhanced the excretion of topically applied [14C]indomethacin when dissolved in dipropylene glycol, triethylene glycol, diethylene glycol, 1,3-butylene glycol, trimethylene glycol, glycerin, water, silicone or triethanolamine, but not when dissolved in ethanol, isopropyl alcohol, oleyl alcohol, olive oil, peppermint oil, isopropyl myristate or hexylene glycol. HPE-101 significantly enhanced the excrection of [14C]indomethacin, [14C]nicotinic acid, [14C]5-fluorouracil, [3H]oestradiol and [3H]triamcinolone acetonide, but not that of [3H]testosterone. HPE-101 also significantly enhanced the excretion of [14C]indomethacin applied to intact skin of rabbit, guinea-pig and rat, and to tape-stripped skin of guinea-pig, but did not enhance the excretion of [14C]indomethacin applied to tape-stripped skin of rat or rabbit.

Administration, Cutaneous↗
PubMed1993

Statistical test of the shortening of latent periods in experimental radiation carcinogenesis under competing risks.

The mean life span of animals killed by a specific type of tumor is influenced by competing risks. The parametric inference method of Noda et al. was applied to a set of mouse experimental data in order to correct for the appearance of observed life span distribution under competing risks and to test statistical significances of difference between corrected mean life spans. Data were from an experiment on tumors induced in mice by X-rays: whole body irradiated with 600 R; head with 800 R; trunk or lower body with 800 R. The statistically significant changes were found: Whole body irradiation shortened the mean latent period of malignant lymphomas whereas the head irradiation shortened the latent periods of none of tumors. Trunk irradiation shortened mean latent periods of lung tumors. Lower body irradiation showed a tendency to shorten the mean latent periods of mammary tumors. Results that differed from the above were obtained when there was no correction for competing risks.

Animals↗
PubMed1993

20 alpha-Hydroxysteroid dehydrogenase activity in rat placenta.

20 alpha-Hydroxysteroid dehydrogenase (20 alpha-HSD) (EC.1.1.1.149) is the enzyme which catabolizes progesterone to 20 alpha-dihydroprogesterone (20 alpha-OHP), a biologically inactive steroid, and is distributed in a variety of tissues including non-steroid-producing tissues. In the present study, changes in cytosolic 20 alpha-HSD activity were investigated in rat placental tissues and its relationship to embryonic mortality was considered; the mesometrial endometrium (including the ectoplacental cone) on days 8-11 of pregnancy (day 0 = estrus), and the chorioallantoic placenta and visceral yolk sac (vitelline membrane) on days 12-21 were separately subjected to measurement of the enzyme activity. 20 alpha-HSD activity was not detected in the chorioallantoic placenta until day 20 and then increased dramatically on day 21. Interestingly, considerable activity of the enzyme was found in the visceral yolk sac from days 14 to 21 and in the mesometrial endometrium from days 8 to 10, whereas it was undetectable in these tissues on days 11 and 12. Analysis of DEAE column chromatography revealed that these tissues contain two different types of 20 alpha-HSD (HSD-1 and HSD-2). By an immunohistochemical method, with polyclonal antiserum to rat 20 alpha-HSD, decidual cells and trophoblastic giant cells adjacent to the ectoplacental cone (day 10), spongiotrophoblasts and visceral yolk sac cells (days 21) were positively stained. The number of fetuses on day 10 of pregnancy was 15.4 and decreased significantly to 12.9 on day 12.(ABSTRACT TRUNCATED AT 250 WORDS)

20-Hydroxysteroid Dehydrogenases↗