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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 271 records · Page 15Linked to original sources

Angiotensin II promotes remodelling-related events in cardiac fibroblasts.

Remodelling is a fundamental cardiac response to injury, and involves cardiac fibroblast proliferation and extracellular matrix production. Angiotensin II (A II) directly promotes these changes in cardiac fibroblasts, and is thus a critical element in cardiac hypertrophy and a processor of wound healing. Osteopontin mRNA was readily detectable in total RNA harvested from cultured neonatal and adult cardiac fibroblasts. Immunocytochemical staining of cultured adult cardiac fibroblasts grown on coverslips revealed the presence of beta 3 integrin on the surfaces of the cells. In the present study, we investigated the role of A II in a model of wound healing using floating collagen gels harboring adult rat cardiac fibroblasts. The presence of a monoclonal antibody against osteopontin, MPIIIB10, at 7.2 micrograms/ml, or the arginine-glycine-aspartate (RGD) peptide (10(-4) M), had no effect on gel contraction. Osteopontin itself induced fibroblast gel contraction (79.1 +/- 3.8%). But this effect of osteopontin was completely neutralized by MPIIIB10 (7.2 micrograms/ml), RGD peptide (10(-4) M), and monoclonal antibody against rat beta 3 integrin (25 micrograms/ml). These results suggest that A II promotes cardiac wound healing and remodelling processes by inducing osteopontin and beta 3 integrin in cardiac fibroblasts.

Angiotensin II↗

Thrombin-binding properties of thrombin aptamer derivatives.

We synthesized a single-stranded DNA with triple G-quartet structure and found that its thrombin-binding activity at 37 degrees C is as much as that of thrombin aptamer with double G-quartet structure which is a product of in vitro selection and amplification. This result suggests that the sequence motifs obtained by in vitro selection and amplification method might not be the only answer.

Base Sequence↗

Evaluation of glycogen level in human lung carcinoma tissues by an infrared spectroscopic method.

Glycogen levels in the tissue samples obtained from carcinomas and normal sections of human lungs (26 patients) were studied by measuring the infrared band intensity at 1045 cm(-1) due to glycogen. As an internal standard peak, the band at 1545 cm(-1) (amide II) was chosen, and the ratios of these band areas (A1045/A1545) were compared with histological classification and differentiation of tumors. The glycogen level in the carcinoma tissues was significantly higher than that in the normal tissues (P < 0.01, n = 26). Further, the ratio of amounts of glycogen in the carcinomas and in the normal tissues for adenocarcinoma was higher than that for squamous cell carcinoma (P < 0.01). The increased degree of differentiation of the squamous cell carcinomas appeared to be correlated with an increase in the glycogen level. These results suggest that comparison of glycogen levels in the tumor and normal section of human lung may be used as a differentiating parameter for abnormality and histological classification of tumors. The present Fourier transform-infrared spectroscopy (FT-IR) method may become of wide application for studying various tissue samples.

Adenocarcinoma↗

Acculturation and prevalence of diabetes among Japanese-American men in Hawaii.

The association between acculturation to a Western lifestyle and prevalence of diabetes was examined among 8,006 Japanese-American men in Hawaii with varying degrees of exposure to traditional Japanese social and cultural lifestyles in 1965-1968. A reduced prevalence of diabetes was observed among the men who had retained a more Japanese lifestyle. These men also reported higher levels of physical activity and consumed more carbohydrates and less fat and animal protein in their diet. An inverse association between diabetes and being born in Japan was observed independent of age, body mass index, physical activity, and percentages of calories from fat or carbohydrates (odds ratios = 0.67 and 0.66, 95% confidence intervals 0.49-0.93 and 0.48-0.91, respectively). The number of total years lived in Japan was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.81, 95% confidence interval 0.68-0.96). Current Oriental diet (compared with Western diet) was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.71, 95% confidence interval 0.50-0.98). These findings suggest that living a Japanese lifestyle is associated with a reduced prevalence of diabetes.

Acculturation↗

Fish intake may limit the increase in risk of coronary heart disease morbidity and mortality among heavy smokers. The Honolulu Heart Program.

BACKGROUND: Research has shown that fish consumption limits damage to the lungs caused by cigarette smoking, possibly by the effects of fish on arachidonic acid metabolism. We explored this fish-smoking interaction using coronary heart disease (CHD) incidence and mortality as the outcome. METHODS AND RESULTS: The Honolulu Heart Program began in 1965 to follow a cohort of 8006 Japanese-American men aged 45 to 65 years who lived on Oahu, Hawaii, in 1965. Fish intake was measured at baseline by use of a questionnaire. For current smokers at baseline (n = 3310) who reported low fish intake (< 2 times/wk), age-adjusted 23-year CHD mortality rates increased with the number of cigarettes smoked per day (2.3, 3.1, and 6.9 per 1000 person-years for men who smoked < 20, 20 to 30, and > 30 cigarettes/d, respectively; trend test P < .0001). Among current smokers whose fish intake was high (> or = 2 times/wk), CHD mortality rates showed no relation with cigarettes/d (3.7, 3.2, and 3.7 per 1000 person-years for the corresponding levels of smoking). A Cox proportional hazards model based on current smokers, adjusted for age, years in Japan, calories/d, alcohol intake, physical activity index, years smoked, hypertension, and serum cholesterol, blood glucose, and uric acid levels, was examined. In the high-smoking group, the risk factor-adjusted relative risk (RR) for CHD mortality among those with high fish intake was half that of those with low fish consumption (RR = 0.5, 95% confidence interval = 0.28 to 0.91). A Cox model that adjusted for similar risk factors confirmed a significant interaction of cigarettes/d and fish intake (P < .01) on CHD mortality. Analyses for CHD incidence showed similar results. CONCLUSIONS: Despite the findings of this investigation, the public health message for smokers continues to be to stop smoking. However, an interaction between fish intake and cigarette smoking is biologically plausible and deserves further investigation. The study of this phenomenon may shed light on the biological mechanisms by which cigarette smoking leads to CHD.

Aged↗

Optimization of the rate of DNA hybridization and rapid detection of methicillin resistant Staphylococcus aureus DNA using fluorescence polarization.

The hybridization rate of two complementary single-stranded DNA 24-mers was determined at various NaCl concentrations using a fluorescence polarization method. The rate was taken as the rate constant of the second order reaction, obtained by mathematical fitting of the time course curves of hybridization. The rate increased with the NaCl concentration, plateauing in the concentration range of about 1-2 M. Over the temperature range of 46 degrees C to 56 degrees C, it was found that in 0.8 M NaCl, hybridization was complete in under 10 min and that the difference in the polarization values between specific hybridization and non-specific binding was greater at lower temperatures. Under the optimized conditions of 0.8 M NaCl at 46 degrees C, the time for DNA hybridization to reach 90% completion decreased to less than 5 min. The assay time for one sample was 10 min and the detection limit was of the order of 10(-10) M (40 fmol per assay). Under the optimized conditions, the DNA of methicillin resistant Staphylococcus aureus (MRSA), which had been multiplied by PCR, could be detected within 10 min.

Base Sequence↗

Correlation between systolic blood pressure and physical development in adolescence.

Although the close relation between blood pressure and physical development in adolescence has been established in cross-sectional and comparative cross-sectional studies, the entire trend of systolic blood pressure (SBP) during adolescence has not been elucidated in conjunction with physical development in a longitudinal study. Blood pressure (mmHg), body weight (kg), and body height (m) were measured annually for 418 subjects in Hiroshima and Nagasaki, Japan, from age 10 (1955 or 1956) through 18 years (1963 or 1964). The Gompertz growth model was used to determine the velocity of weight increase (VEL) during that age period. The relations between SBP from age 10 to 18 and VEL, weight, height, body mass index (BMI; weight/height2, kg/m2), and the age at which the measurements were made were investigated individually using random-coefficient growth-curve analysis. The SBP trend for the 10- to 18-year age period could be shown by the following prediction equations: for the 163 Hiroshima males, SBP = 82.38 + 0.89 VEL at age 1.15 years prior to the current examination (VEL (age - 1.15)) + 1.40 BMI; for the 57 Nagasaki males, SBP = 92.70 + 1.07 VEL (age - 1.15) + 0.79 BMI; for the 148 Hiroshima females, SBP = 104.88 + 1.63 VEL (age - 1.15) + 0.05 BMI; for the 50 Nagasaki females, SBP = 113.62 + 1.67 VEL (age - 1.15) - 0.59 BMI. VEL 1.15 years prior to the current examination was significantly and positively related to SBP in each city by sex group (p < 0.01), and current BMI was significantly related to SBP for males in Hiroshima (p < 0.01) and nearly so in Nagasaki (p = 0.06), but not for females in either city (p = 0.84 and 0.13, respectively). Because the plot of VEL was a convex curve, SBP peaked approximately 1-2 years after the peak in VEL and then decreased in both sexes. The entire SBP trend during adolescence can be expressed as an equation of VEL and BMI in males and of VEL in females. SBP does not increase linearly with age.

Adolescent↗

Effects of menopause on trends of serum cholesterol, blood pressure, and body mass index.

BACKGROUND: To elucidate the impact of menopause on coronary risk factors, we determined the trends of serum cholesterol (mg/dL), blood pressure (BP, mm Hg), and body mass index (BMI, kg/m2) and investigated whether menopause affects these trends in women in Nagasaki, Japan. METHODS AND RESULTS: Trends of cholesterol, systolic BP (SBP), and BMI from 9 years before menopause through 9 years after menopause in 579 women with natural menopause (ranging in age from 40.2+/-3.1 to 57.9+/-3.1 years; age at menopause, 49.4+/-3.0 years) and 134 women with surgical menopause (hysterectomy with or without bilateral oophorectomy; ranging in age from 34.9+/-4.5 to 51.7+/-5.1 years; age at menopause, 42.9+/-5.0 years) and those in 579 and 134 age- and time-matched male subjects (ranging in age from 40.1+/-3.1 to 57.8+/-3.2 years and from 35.2+/-4.5 to 51.6+/-5.0 years, respectively) in Nagasaki were determined by rearrangement of the data from 1958 to 1989 with time of menopause as the datum line. Although cholesterol tended to increase with age in both sexes, it increased significantly in women from 3 years before natural menopause to 1 year after natural menopause and from 1 year before surgical menopause to 1 year after surgical menopause. SBP and BMI did not exhibit a significant increase in relation to natural or surgical menopause. In male subjects, no significant increase of cholesterol, SBP, or BMI was observed at the age corresponding to natural or surgical menopause. CONCLUSIONS: Natural menopause and surgical menopause exert an effect only on cholesterol, and an increase in cholesterol precedes natural menopause by 3 years and occurs at the time of surgical menopause.

Adult↗

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.

Aged↗

Mean red cell volume as a correlate of blood pressure.

BACKGROUND: Clinical studies suggest that hypertensives have lower mean corpuscular volume (MCVs) than do normotensives. Epidemiological studies show no relation or higher MCVs. In the present study of elderly men (71 to 93 years of age) of the Honolulu Heart Program, elements of both findings are confirmed. METHODS AND RESULTS: Three groups are identified: (1) those receiving no hypertension treatment, (2) those receiving treatment with any diuretic, and (3) those receiving treatment with nondiuretics only. MCV is lower in group 3 than in group 1 (-0.85 fL, P<.001) but the same in groups 1 and 2. Within groups 1 and 3, inverse relations of -0.22 and -0.09 mm Hg/fL (P<.05) are noted for systolic (SBP) and diastolic (DBP) blood pressures. No relations are observed in group 2. MCV and red blood cell count (RBC) are inversely correlated (r=-.45). In group 2, adjustment for RBC unmasks a direct relation between MCV and SBP (0.5 mm Hg/fL, P=.02) and DBP (0.3 mm Hg/fL, P=.02). In groups 1 and 3, relations between SBP and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding RBC plus an MCV x RBC interaction is significant (P<.001). DBP is 5 mm Hg greater in the highest RBC quartile than in the lowest. A +3 mm Hg difference between extreme MCV quartiles is noted only at high RBC levels. CONCLUSIONS: The relation between blood pressure and red cell measures is probably mediated by whole blood viscosity. Hematocrit is a determinant of whole blood viscosity. Viscosity affects peripheral resistance to blood flow, and peripheral resistance affects DBP. At high RBC levels, MCV may be "downregulated." This may lower whole blood viscosity and partially reduce DBP without compromising flow.

Aged↗

RNA polymerase I associated factor 53 binds to the nucleolar transcription factor UBF and functions in specific rDNA transcription.

Mouse RNA polymerase I (Pol I) has, besides its 11 bona fide subunits, three polymerase associated factors, termed PAF53, 51 and 49 with respect to the size of each molecule. In order to analyze the function of PAFs, cDNA encoding PAF53 was isolated using an oligonucleotide probe derived from an oligopeptide sequence. The cDNA of PAF53 predicts a polypeptide of 434 amino acids with a sequence similarity to yeast Pol 1 49 kDa subunit. Anti-PAF53 antibody does not block the random transcription activity of Pol I, but blocks specific transcription from mouse ribosomal RNA promoter, demonstrating the requirement of PAF53 in the accurate initiation of Pol I transcription. Moreover, PAF53 interacted with mouse UBF in vitro, as revealed by Far-Western blotting and GST pull down assays. These results, together with the accumulation of PAF53 in the nucleolus of growing cells, suggest that PAF53 is involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBF for the active rRNA synthesis.

3T3 Cells↗

Pulmonary function measures as predictors and correlates of cognitive functioning in later life.

The relation between pulmonary function and cognitive functioning was investigated in a cohort of 3,036 Japanese-American men living in Hawaii. Pulmonary function, as indicated by forced expiratory volume in 1 second (FEV1), was measured at the baseline examination from 1965 to 1968. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) test at least 23 years later (1991-1993). Baseline FEV1 was significantly correlated with follow-up CASI score (r = 0.22, p = 0.0001). Although the strength of the association was reduced by controlling for the effects of other factors, stepwise multiple linear regression showed that FEV1 during middle age was a significant predictor of CASI in later life, after taking into account the effects of age, education, stroke, sedentary job activity, nonmanual occupation, height, generation, and Japanese speaking ability. The mean CASI value was significantly greater for men whose FEV1 exceeded 2.8 liter compared with those whose FEV1 levels were in the lowest (<2.5 liters) quartile. Furthermore, the test on the effect of interaction between FEV1 and age was statistically significant (p = 0.0024), with subjects less than 55 years of age at the baseline examination showing a stronger direct association of FEV1 with CASI than the men aged 55 or older. These findings suggest that pulmonary function impairment may be associated with cognitive function impairment in later life.

Aged↗

A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene.

We describe a Japanese patient with male-limited precocious puberty who has a heterozygous thymine to cytosine (T to C) transition at nucleotide 1193; the mutation encodes a methionine to threonine substitution in residue 398 (M398T) of transmembrane helix 2 of the luteinizing hormone/choriogonadotropin receptor. Transfected into COS-7 cells, M398T exhibited constitutively high basal cAMP levels but retained an agonist-induced cAMP response. The constitutively higher cAMP levels caused by M398T are consistent with Leydig cell activation and precocious puberty in the patient. By comparison to wild type receptor, M398T transfectants have significantly lower agonist-induced inositol phosphate (IP) levels at > 10(-10) M hCG concentrations and a higher apparent affinity for binding hCG. These data suggest that the M398T substitution alters Gq coupling and phospholipase-C activation, as well as Gs, coupling and adenylyl cyclase activity, and changes the conformation of the extracellular domain of the receptor.

Amino Acid Sequence↗

Potential advantages in therapeutic index of OK-432 ointment to abdominal skin over systemic applied in a mouse model.

A mixture of OK-432 powder and an ointment base, lanolin, was applied to mouse abdominal skin. After application of the mixture of 5 KE OK-432 and 0.2g lanolin, the leucocyte count and IL-b content in the abdominal cavity increases to up to 3.6 x 10(6) cells and 1.4 ng, respectively. INF-gamma content in the cavity after application of a mixture of 10 KE OK-432 and 0.2 g lanolin also increases, although not after application of the 5 KE OH-432 mixture of dorsum subcutaneous injection of a saline solution of 5 KE OK-432. These results indicate that an application of OK-432 mixed in lanolin to the mouse abdomen is able to exert an influence on the immunomodulatory effect in the abdominal cavity. The concentrations of IL-6 in serum after applying the ointment mixture, and subcutaneous of intraperitoneal injection of the saline solution of 5 KE OK-432, were <20, 370, and 430 pg/ml, respectively. After application of the ointment mixture of 5 KE OK-432, serum IL-6 did not increase. IL-6 levels in the abdominal cavity after 5 KE OK-432 ointment of subcutaneous injection increases to up to 1.4 and 2.1 ng/cavity. From these results, the immunomodulatory systemic response of OK-432 brought about by applying OK-432 ointment to the abdominal skin is lower than that brought about by injecting OK-432 subcutaneously. Therefore, it is thought that application of OK-432 ointment might be most suitable for potentiating local immune response.

Abdominal Muscles↗

Three-dimensional structures of free form and two substrate complexes of an extradiol ring-cleavage type dioxygenase, the BphC enzyme from Pseudomonas sp. strain KKS102.

The crystal structure of an enzyme having polychlorinated-biphenyl degrading activity, the BphC enzyme from Pseudomonas sp. strain KKS102, has been solved as a free form at 1.8 A resolution. This is the first three-dimensional structure among the extradiol-type dioxygenases. Based on 34,387 reflections (10.0 to 1.8 A, completeness 87.8%), a current R-factor of 20.4% (with a free R-factor of 24.3%) was obtained with a model obeying standard geometry within 0.011 A in bond lengths and 1.91 degrees in bond angles. The BphC enzyme is a homo-octamer and each subunit is composed of two domains: Domain 1 (N-terminal part) and Domain 2 (C-terminal part). Each domain contains two repetitions of a novel folding motif (the "beta alpha beta beta beta" motif) each consisting of ca 55 amino acid residues. A single Fe ion in the active site coordinates the side-chains of three amino acid residues (His145, His209 and Glu260) and two solvent molecules. The coordination geometry is that of a square pyramid. In addition to the free form of the BphC enzyme, we have solved two three-dimensional structures of the BphC enzyme complexed with its substrates, 2,3-dihydroxybiphenyl (2,3-DHBP) or 3-methylcatechol (3-MCT). These substrates were found intact in the active site probably because of the oxidation of the Fe ion into ferric form (as judged by EPR spectra) in the present crystals. In both of the two substrate complexes, the two hydroxyl groups of the substrate, together with the three enzymatic side-chain ligands, were found to form a penta-coordinated system around the Fe ion roughly arranged in a trigonal bipyramidal configuration. The active site structures appear to be essentially consistent with the reaction mechanism proposed so far.

Amino Acid Sequence↗

Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by in situ hybridization.

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

Aged↗