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K Noda

Publications and source records attributed to K Noda.

At least 217 records · Page 12Linked to original sources

The structure of chicken liver xanthine dehydrogenase. cDNA cloning and the domain structure.

The amino acid sequence of chicken liver xanthine dehydrogenase (EC 1.1.1.204) was determined by cDNA cloning and partial amino acid sequencing of the purified enzyme. The enzyme consisted of 1358 amino acids with calculated molecular mass of 149,633 Da. In order to compare the structure of the chicken and rat enzymes, limited proteolysis was performed with the purified chicken liver xanthine dehydrogenase. When the enzyme was digested with subtilisin, it was not converted from the NAD-dependent dehydrogenase type to the O2-dependent oxidase type, in contrast with the mammalian enzyme. However, the enzyme was cleaved mainly into three fragments in a manner similar to that for the rat enzyme at pH 8.2 (20, 37, and 84 kDa) and retaining a full complement of redox centers. The cleavage sites were identified by determination of amino-terminal sequences of the produced fragments. It was concluded that the 20-kDa fragment was amino-terminal, the 84-kDa fragment carboxyl-terminal, and the 37-kDa fragment an intermediate portion in the enzyme protein. On the other hand, when the enzyme was digested with the same protease at pH 10.5, the sample contained only the 20- and 84-kDa portions and lacked the 37-kDa portion. The resultant sample possessed xanthine dichlorophenol indophenol reductase activity, indicating that the molybdenum center remained intact. The absorption spectrum showed the sample was very similar to deflavo-enzyme. From these results and sequence analyses, the domain structure of the enzyme is discussed.

Amino Acid Sequence↗

Tetrazole and carboxylate groups of angiotensin receptor antagonists bind to the same subsite by different mechanisms.

To identify specific interactions between either the tetrazole or carboxylate pharmacophores of non-peptide antagonists and the rat AT1 receptor, 6 basic residues were examined by site-directed mutagenesis. Three of the mutants (H183Q, H256Q, and H272Q) appeared to be like wild type. Lys102 and Arg167 mutants displayed reduced binding of the non-peptide antagonist losartan. Examination of their properties employing group-specific angiotensin II analogues indicated that their effects on binding were indirect. Interestingly, the affinity of losartan was not altered by a K199Q mutation, but the same mutation reduced the affinity of angiotensin II, the antagonist [Sar1,Ile8]angiotensin II, and several carboxylate analogues of losartan. An Ala199 substitution reduced the affinity of peptide analogues to a larger extent as compared to the affinity of losartan. Thus, the crucial acidic pharmacophores of angiotensin and losartan appear to occupy the same space within the receptor pocket, but the protonated amino group of Lys199 is not essential for binding the tetrazole anion. The binding of the tetrazole moiety with the AT1 receptor involves multiple contacts with residues such as Lys199 and His256 that constitute the same subsite of the ligand binding pocket. However, this interaction does not involve a conventional salt bridge, but rather an unusual lysine-aromatic interaction.

Amino Acid Sequence↗

Dysplasia and HPV infection initially detected by DNA analysis in cytomorphologically normal cervical smears.

OBJECTIVE: We examined the relationship between the risk of dysplasia and human papillomavirus (HPV) infection initially detected by DNA analysis in Japanese women with cytomorphologically normal cervical smears. METHOD: We applied the polymerase chain reaction method to detect HPV DNA in 800 women and subsequently followed up 49 women positive for HPV DNA. RESULTS: HPV 16 or HPV 18 DNA was detected in 53 (6.6%) of 800 women with normal smears (negative). During the follow-up period (23 months), the presence of HPV DNA could not be detected in 41 (83.7%) of 49 women after its initial presence. The remaining eight women had repeated HPV DNA, and four of these eight women had lesions that progressed to mild dysplasia. CONCLUSION: The results indicated that some women with cytomorphologically normal smears may have HPV DNA which can be transient, and persistence of HPV types 16 or 18 DNA plays an important role in the pathogenesis of cervical dysplasia.

Adolescent↗

Distribution of heavy metals in muscle, liver and kidney of northern fur seal (Callorhinus ursinus) caught off Sanriku, Japan and from the Pribilof Islands, Alaska.

The concentrations of iron, manganese, zinc, copper, cadmium, and mercury were determined in muscle, liver and kidney of 67 northern fur seals (Callorhinus ursinus) collected off Sanriku, Japan, and from the Pribilof Islands, Alaska. Almost all the elements except cadmium were highest in liver. Cadmium levels in kidney were higher than those in liver and muscle for all animals analyzed. Concentrations of mercury increased significantly with age in muscle, liver and kidney, as did iron levels in muscle and liver and cadmium levels in muscle, while manganese concentrations decreased with age in muscle and kidney. The kidney also showed decreased copper concentration with age. Cadmium concentrations of the northern fur seals in this study were higher than the other otariids, reflecting a predominantly squid diet. Concentrations of manganese and mercury were found to be higher in the fur seals caught off Sanriku than in animals from the Pribilof Islands, while those of zinc and cadmium were found to be lower. Variable concentrations of cadmium might have been attributed to those in seawaters. Discriminant analysis of heavy metal concentrations was used to identify habitat. Sixty-three of 67 animals (94%) were correctly classified using this technique. Heavy-metal concentrations in tissues may provide a useful method to elucidate the primary feeding grounds of fur seals.

Journal Article↗

Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population.

Genes for cytochrome P4501A1 (CYP1A1) and glutathione S-transferase class mu (GSTM1) have been shown to be polymorphic, and have been implicated in tobacco-related carcinogenesis. In the present study, the role of the combined genotypes CYP1A1 and GSTM1 as a possible modulator of smoking related lung cancers was studied in relation to the tobacco smoke exposure level in 118 Japanese patients aged < 70 with squamous or small cell carcinomas of the lung. Among male smoking patients, the overall proportion of the GSTM1 null genotype (GSTM1[-]) was slightly higher than among healthy male smoker controls (56.7% versus 48.1%, P = 0.17). Little difference was observed between smoker patients and corresponding controls in overall frequencies of m2 mutant allele homozygotes (CYP1A1[m2/m2]) (16-18%) and Val encoding allele homozygotes (5-6%). However, when subjects were categorized by both CYP1A1 genotype (MspI polymorphism) and GSTM1 genotype, GSTM1(-) became markedly more expressed in patients with CYP1A1(m2/m2) when compared to the corresponding smoker controls (81.3% versus 39.4%, P < 0.01). When odds ratios were estimated using nonsmoking patients and healthy controls as a reference, the relative risk for developing lung cancer was found to increase in a cigarette dose-dependent manner across all combinations of genotypes. Furthermore, a 7- to 8-fold variation in risk was found among the various combinations; 3.2 in individuals with combined GSTM1(+) and CYP1A1(m2/m2) and 21.9 in those with combined GSTM1(-) and CYP1A1(m2/m2) genotype when the smoking index (sigma cigarettes smoked per day x years of smoking) was set at > or = 800. The results suggest that individuals having CYP1A1(m2/m2) are relatively resistant to tobacco-related lung cancers when combined with GSTM1(+), but are highly susceptible when combined with GSTM1(-). Combined CYP1A1 and GSTM1 genotype is thus a potential predictor of genetic susceptibility to smoking-related lung cancers in populations where CYP1A1 m2 or Val alleles are common.

Aged↗

Morphology of a cytochrome c-adsorbed stearic acid monolayer on Brewster angle microscopy.

The morphologies of stearic acid and cytochrome c (cyt.c)-adsorbed stearic acid monolayers were investigated by Brewster angle microscopy (BAM) with various molecular areas of stearic acid. With an area of more than 0.38 nm2/molecule, many blight island domains and some bright circles were observed in the BAM image of the stearic acid monolayer. The blight site part became to occupy all the surface with compression, and then became more closely packed with an area of 0.22 nm2/molecule. On the other hand, a different BAM image was obtained for the cyt.c-adsorbed stearic acid monolayer, as follows: (i) a striped pattern was only observed in the presence of cyt.c; (ii) the number of bright circles in the presence of cyt.c was less than that in its absence. Furthermore, when a uniform BAM image was observed for the stearic acid monolayer with cyt.c, the intensity of the absorbance at 409 nm of cyt.c was the highest. By calculating the amount of cyt.c adsorbed on a stearic acid monolayer from the absorbance value, it was shown that cyt.c was most closely packed when an uniform BAM image was observed. These results suggest that the use of BAM and visible absorption spectroscopy together is useful for studying the morphology of a monolayer.

Adsorption↗

Expression of P450 17 alpha-hydroxylase and P450aromatase genes in isolated granulosa, theca interna, and theca externa layers of chicken ovarian follicles during follicular growth.

Concentrations of estradiol (E), testosterone (T), and progesterone (P) and levels of the 1.9-kb and 4.0-kb mRNA encoding P450 17 alpha-hydroxylase (P450 17 alpha) and P450aromatase (P450arom), respectively, were measured in the isolated granulosa, theca interna, and theca externa of the largest preovulatory (F1-F4) follicles of the chicken 20 h and 3 h before expected ovulation of F1. In the granulosa layer, E and T concentrations remained low throughout this period of follicular growth, whereas P concentrations were high 3 h before ovulation in F2 and F1 follicles. E levels were highest in the theca interna and externa of the smallest (F4) follicle, decreasing progressively with follicular growth. T content of theca interna and granulosa was greater in less mature F4-F2 follicles than in the most mature (F1) follicle, whereas theca externa contained little T. P was quantifiable in significant amounts only in granulosa tissue, peaking in F2 and F1 follicles at 3 h before ovulation, at which time plasma levels of steroids also rose significantly. P450 17 alpha was expressed mainly in theca interna, whereas the P450arom mRNA levels found in theca externa reflected the pattern of E in this compartment. Expression of these two genes was very low in granulosa tissue, remaining unchanged during follicular growth. These results indicate that E and T synthesis in the chicken ovary is regulated, at least in part, at mRNA levels of P450 17 alpha and P450arom in the theca interna and theca externa layers during follicular growth.

Animals↗

Distribution of GSTM1 null genotype in relation to gender, age and smoking status in Japanese lung cancer patients.

GSTM1 gene deficiency has been shown to occur in approximately half of the populations of various ethnic origins and has been implicated as a factor for elevated risk for lung cancers. However the results have been variable or even conflicting between the studies. In an attempt to explore the reason for such a diversity, we studied the distribution of GSTM1 genotypes in relation to gender, age and smoking status in 447 Japanese lung cancer patients and 469 community controls. We found: (1) that in squamous and small cell carcinomas GSTM1 null genotype distributed markedly more in females than males especially among the patients aged < 70 years (male 57.4%, female 100.0%); (2) that GSTM1 null genotype distributed generally more in patients aged < 70 years (58.3%) than those aged > or = 70 years (50.0%) irrespective of histologies except for small cell carcinoma; and (3) that proportion of GSTM1 null genotype increased dependent on the extent of tobacco smoke exposure in male patients having squamous and small cell carcinomas aged < 70 years, and remained high but independent of the smoking index in adenocarcinoma and unchanged in never- or exsmokers from the control level (48.6%). The present study thus suggests that composition of GSTM1 genotypes in patients is significantly affected by gender, age and smoking status, which should be taken into consideration in any attempt to determine the association of GSTM1 genotypes for risk assessment. With the diverse of GSTM1 null genotype variability between patients of different histologies, our results were also suggestive of different carcinogenic involvement of GSTM1 deficiency among different histological cell types.

Age Factors↗

Placental Na+, K+ activated ATP-ase activity in SHRSP in connection with pregnancy induced hypertension and intra-uterine growth retardation.

1. Placental Na+, K+ -ATPase activities were measured in connection with the active transport of amino acid, intra-uterine growth retardation (IUGR) or small for date infants (SFD) in salt-loaded pregnant SHRSP. 2. All parameters such as fetal weight, placental weight and Na+, K+ -ATPase activity in the placental tissue were significantly depressed in SHRSP, especially in the salt-loaded SHRSP compared with WKY. 3. Besides a decrease of blood flow, a decline of Na+, K+ -ATPase activity associated with an active transport of amino acid in the placenta would cause IUGR and SFD in the salt-loaded pregnant SHRSP. 4. Pregnant SHRSP given water containing salt would be a good model for pregnancy induced hypertension in humans.

Animals↗

Studies on pregnancy hypertension and IUGR-SFD: effects of drugs on the blood vessels in the placenta of pregnant SHRSP.

1. Based upon our previous work, we came to the conclusion that a decrease in placental blood volume was a possible factor behind intrauterine growth retardation (IUGR) in pregnancy-induced hypertension. 2. In a second study, we used an image analysis system to measure cross-sectional areas and wall thicknesses of central blood vessels of the spiral artery, the so-called 'central artery'. 3. It was thought that one of the more basic factors behind IUGR in pregnancy-induced hypertension might possibly be narrowings and spasms of the maternal placental blood vessels. 4. In this study, we found that the three drugs we used (MgSO4 center dot 7H2O, Solcoseryl and KCl) all resulted in an enlargement of the cross-sectional areas of the maternal blood vessels, and that MgSO4 center dot 7H2O, in particular, also relaxed maternal blood vessel spasms in SHRSP placenta.

Animals↗

A saturable tissue-angiotensin I converting enzyme (ACE) binding model for the pharmacokinetic analysis of imidapril, a new ACE inhibitor, and its active metabolite in human.

In order to obtain a rational explanation and analytical method of the unique pharmacokinetic behaviors of imidapril and imidaprilat in human, a new pharmacokinetic model was designed by introducing a saturable-reversible angiotensin I converting enzyme (ACE)-imidaprilat binding process and a linear imidapril-imidaprilat conversion process. According to the new model, six differential equations were given which considered the mass balance of both compounds in each component. Various pharmacokinetic parameters were estimated by the simultaneous curve fitting method using the plasma concentration data and the urinary excretion data of imidapril and imidaprilat in a multiple dosing study of healthy human volunteers. To validate the value of each parameter, this pharmacokinetic model was also applied to analyze the various plasma concentration data of both compounds in the single dosing studies with four different dosages, 2.5,5, 10, and 20 mg. Excellent curve fitting was obtained in every case, suggesting that the proposed pharmacokinetic model is applicable for predicting the plasma concentrations of imidapril and imidaprilat under various dosage conditions of clinical use.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical experience with the ACS RX Lifestream coronary dilatation catheter: a new low profile perfusion balloon catheter.

BACKGROUND: Although the use of the perfusion balloon catheter (PBC) has been widely accepted, there are some indicational limitations in percutaneous transluminal coronary angioplasty (PTCA). A new low profile perfusion balloon catheter, the ACS RX Lifestream Coronary Dilatation Catheter, was developed by Advanced Cardiovascular Systems, Inc. in which material and structures were improved to reduce previous limitations. PURPOSE AND STUDY DESIGN: In order to evaluate the ACS RX Lifestream Catheter's performance not only in PTCA but also in stent implantation, we used the catheter in 45 consecutive patients (male = 35, mean age 66 years) with combined use of 6F guiding catheter. Exclusions included total occlusions, long diffuse and acute MI lesions. There were 4 with Left Main Trunk Disease (LMTD), 15 with single vessel disease, 26 with multi-vessel disease, 20 with prior MI, 4 with prior CABG, and 10 with unstable angina. In bare stent procedures, a Johnson & Johnson metal stent was mounted on an ACS RX Lifestream Catheter previously used for predilation. Stent delivery and post-dilatation were performed using the same balloon. RESULTS: Forty-nine lesions in 45 cases (de novo lesion-31) including 7 of Type A, 15 of Type B1, 19 of Type B2, and 8 of Type C lesions were successfully dilated without any complications. Primary guiding catheter use was 6F in 40, 7F in 2 and 8F in 3 cases. The perfusion balloon was used alone in 30 cases and combined with stent placement in 15 cases. In 40 cases of 6F use, the ACS RX Lifestream Catheter could not cross the lesion in 3 cases at first attempt, of which 2 cases were successfully dilated with the balloon after predilatation with standard low-profile balloon catheters. Two cases with 7F use were bail-out cases after PTCA for long diffuse lesions. In one case of 8F guide use, flow patterns of ACS RX Lifestream Catheters and ACS RX Flowtrack Coronary Dilatation Catheters were examined with a flow-wire in the same lesion for comparison. All 15 stent cases performed using bare technique (10 with 6F, 2 with 7F and 3 with 8F guiding catheters) including 7 primary and 8 secondary use, were successful. Percent diameter stenosis pre-dilatation was 81% and 12.8% post-procedure. CONCLUSION: ACS RX Lifestream Catheter is a useful device in both PTCA and bare stent procedures. Consequently, it is possible to expand its indications to more difficult types of lesions.

Aged↗

[Bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease: a case report].

A 42-year-old man diagnosed with von Willebrand disease 7 years earlier visited his home doctor with a chief complaint of gross hematuria. Abdominal ultrasonography showed bilateral renal tumors. He was referred to our hospital on June 15, 1993. His mother also had von Hippel-Lindau disease and was treated by hemodialysis after bilateral nephrectomy. The examination and imaging revealed bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease. Partial nephrectomy and enucleation for a small tumor on the right side and enucleations for five tumors on the left side were performed. Histological diagnosis of all tumors were renal cell carcinoma, clear cell subtype, grade 1 approximately 2. The patient has been well without local recurrence or distant metastasis for 16 months since the operation. This is the first case of bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease in Japan.

Adult↗

[Prognostic factors in uterine cervical and corpus cancer].

We have studied the prognostic factors for cancer of uterine cervix and corpus. Prognostic factors for cervical cancer include clinical stage, histological type, pelvic and paraaortic lymph node metastasis and CPL classification of carcinoma. Prognostic factors for cancer of uterine corpus are concerned with clinical stage, histological type and histological differentiation, muscle invasion, lymph node metastasis, perineal washing cytology and so forth. The clinical stage of course, reflects the prognosis. Although one of the important prognostic factors is lymph no metastasis, there may be recurrence in patients with a poor prognosis in cases in which lymph node metastasis has not been observed. In order to distinguish such cases and to improve their prognosis, it is important to provide treatment individually but combined chemotherapy or radiation therapy, for example, with efforts to detect various prognostic factors.

Female↗

[Angiocentric lymphoma associated with anemia secondary to parvovirus B19 infection].

A 50-year-old woman was admitted to our hospital in May 1993 because of papules, cervical lymphadenopathy and interstitial pneumonia. Oxygen inhalation and pulse therapy of corticosteroid were started. A biopsy of the left inguinal lymphnode showed T zone enlargement and marked vascularization with polymorphous atypical lymphoblasts, consistent with angiocentric lymphoma (immunohistochemically T cell type). In situ hybridization with EBER-1 did not show association of EB virus. She was subsequently treated with ProMACE-CytaBOM successfully, but anemia had progressed before that treatment showing a reticulocyte count 0/1000, LDH 870 U/l, positive direct Coombs test. Bone marrow aspiration revealed red cell aplasia and the existence of giant pronormoblasts. The hemoglobin dropped to the level of 4.7 g/dl, requiring anabolic steroid and frequent blood transfusion. Parvovirus B19-specific antibodies were negative initially by western blot assay, but IgM antibody appeared after 35 days and IgG after 71 days. In August anemia improved following a reticulocyte burst and recovery of bone marrow erythroblasts. This patient is the first reported case of angiocentric lymphoma complicated with severe anemia, perhaps resulting from autoimmune hemolytic process and parvovirus B19 infection.

Anemia↗

Proliferative potential and p53 overexpression in precursor and early stage lesions of bronchioloalveolar lung carcinoma.

To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we evaluated the lesion size, growth fraction, and p53 overexpression of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classified as showing low grade or high grade atypia. AAH-like carcinoma, presumably very early stage BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive of malignant potential and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determined immunohistochemically in terms of the Ki-67 labeling index. The overexpression of p53 was evaluated by assessing the nuclear accumulation of immunoreactive p53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of p53 in AAH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-like carcinoma, and overt BAC represent different categories, although the cellular events occurring in these lesions presumably represent a continuous spectrum of the changes that are reflected in the cytomorphology and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representing different steps toward overt BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗

Flower colour intensity depends on specialized cell shape controlled by a Myb-related transcription factor.

Flower colour is determined primarily by the production of pigments, usually anthocyanins or carotenoids, but the shade and intensity of the colour are often changed by other factors such as vacuolar compounds, pH and metal ions. Pigmentation can also be affected by the shape of epidermal cells, especially those facing prospective pollinators. A conical shape is believed to increase the proportion of incident light that enters the epidermal cells, enhancing light absorption by the floral pigments, and thus the intensity of their colour. We have identified a gene (mixta) that affects the intensity of pigmentation of epidermal cells in Antirrhinum majus petals. The cells of the corolla lobes fail to differentiate into their normal conical form in mixta mutants. We have cloned the mixta gene by transposon tagging; its sequence reveals that it encodes a Myb-related protein that probably participates in the transcriptional control of epidermal cell shape.

Amino Acid Sequence↗