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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 235 records · Page 13Linked to original sources

Variability in systolic blood pressure--a risk factor for coronary heart disease?

Among 1,433 men of Japanese ancestry living in Hawaii with blood pressure measured at four different physical examinations over a 10-year period, 110 events of definite coronary heart disease (CHD) occurred during 11.6 years of subsequent follow-up. Each subject's mean blood pressure, the slope of the regression of his blood pressure on age, and the variance of blood pressure about this regression line were tested for association with subsequent incident definite CHD. Adjusted for mean systolic blood pressure (SBP), the variance of SBP was significantly associated with CHD (p < 0.001); however, the slope was not significantly associated with CHD. Variation in body weight was an independent risk factor for CHD. The effect of variation in SBP was significantly higher among men not taking antihypertensive medication; among men taking antihypertension medication, the standardized relative risk was 1.00. Comparing men in the highest quintile of SBP variation with those in the lowest quintile, the relative risk of CHD was 2.0 among all subjects and 5.3 among the 1,007 men not taking antihypertensive medication (95% confidence interval 1.8-15.4). Some of the beneficial effect of taking antihypertensive medication may have been due to reducing the effect of SBP variance rather than simply lowering the average SBP.

Antihypertensive Agents↗

The bphDEF meta-cleavage pathway genes involved in biphenyl/polychlorinated biphenyl degradation are located on a linear plasmid and separated from the initial bphACB genes in Rhodococcus sp. strain RHA1.

The bphACB genes responsible for the initial oxidation of the aromatic ring of biphenyl/polychlorinated biphenyls (PCB) to meta-cleavage product in Rhodococcus sp. RHA1 have been characterized. We cloned the 6.1 kb EcoRI fragment containing another extradiol dioxygenase gene (etbC) which was induced during the growth on ethylbenzene. The bphD, bphE and bphF encoding 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HOPD) hydrolase, 2-hydroxypenta-2,4-dienoate hydratase and 4-hydroxy-2-oxovalerate aldolase, respectively, were found downstream of etbC. The deduced amino acid (aa) sequence of RHA1 bphD and bphE had 27-33% and 32-38% identity, respectively, with those of the corresponding genes in Pseudomonas. BphE and BphF are closely related to the corresponding homoprotocatechuate meta-cleavage pathway enzymes of Escherichia coli C. The bphD and bphF were expressed in E. coli and the BphD activity was detected. The etbCphDEF genes were transcribed in biphenyl and ethylbenzene growing cells. Pulsed field gel electrophoresis (PFGE) analysis indicated that RHA1 contains three large linear plasmids. Southern blot analysis indicated that the meta-cleavage pathway for biphenyl/PCB catabolism in RHA1 is directed by the 390 kb plasmid borne bphDEF genes located separately from bphACB gene cluster on the 1100 kb plasmid.

Benzene Derivatives↗

Galactose-dependent reversible interaction of Gal3p with Gal80p in the induction pathway of Gal4p-activated genes of Saccharomyces cerevisiae.

When galactose is added to logarithmically growing culture of the yeast Saccharomyces cerevisiae, a set of genes encoding galactose-metabolizing enzymes (GAL genes) starts to be transcribed within a few minutes. This rapid induction involves a serial interplay of Gal3p, Gal80p, and Gal4p. Recent experiments have indicated that a direct interaction between Gal3p and Gal80p plays a pivotal role in an early step of GAL induction. Here we demonstrate that complex of Gal3p and Gal80p, otherwise unstable, is stabilized in the presence of 0.1 mM galactose and 0.5 mM ATP. The requirement for galactose and ATP for stable complex formation is also observed by using highly purified Gal3p and Gal80p from yeast. We further show that thus formed Gal3p/Gal80p complex can easily be dissociated when it is washed with buffer lacking galactose. Finally, we show that mutant proteins encoded by GAL80S or GAL80DE21, which confer galactose-uninducible phenotype, fail to interact with Gal3p. These results strongly suggest that Gal3p functions as the sensor and transducer of galactose signal in the induction pathway of Gal4p-activated genes.

Adenosine Triphosphate↗

Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.

BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.

Alleles↗

Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety.

Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4-benzothiazine or dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro antiproliferative activities against human synovial cells (hSC) and human peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid arthritis and healthy volunteers, respectively. In vivo antiarthritic activities of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4-[(2,4-Diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzoxazin-7-yl]carbonyl]-L-homoglutamic acid (3b) and N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-homoglutamic acid (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds 3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68) completely suppressed this progression at the dose of 2.5 mg/kg (po). Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did not undergo polyglutamation, a process which may be responsible for the associated side effects of MTX. These results suggest that 3d (MX-68) is a potent and safe candidate antirheumatic agent, absent of the side effects of MTX.

Animals↗

Adsorption Characteristics of Silica Gels Treated with Fluorinated Silylation Agents

Branched-chain polyfluorosilane (monochlorodimethyl[4,4-bis(trifluoromethyl)-5,5,6,6,7,7,7-heptafluoroheptyl)-bonded silica gels were prepared. The surface properties of the silica gels modified with various organic silanes were evaluated by the adsorption density of polar and nonpolar gases calculated from adsorption isotherms of nitrogen, carbon dioxide, and normal butane gases. The polyfluorocarbon-bonded silica gel surface was found to be both hydrophobic and oleophobic in nature, whereas the hydrocarbon-bonded silica gel surface was characterized only as hydrophobic. The trifunctional fluorinated silane provides the silica gel surface with a more hydrophilic nature than the monofunctional silane because of the formation of a denser polymeric coating layer with a larger number of silanols.

Journal Article↗

Proliferative activity of esophageal carcinomas and their lymph node metastases: comparison using argyrophilic nucleolar organizer region staining.

BACKGROUND: Many reports have concluded that quantification of the argyrophilic nucleolar organizer regions (AgNORs) measures proliferative activity and is a prognostic indicator in malignant disease. This retrospective study set out to evaluate the relationship between the AgNORs of the primary tumors and those of lymph node metastases in esophageal carcinoma. METHODS: Using a one-step silver staining technique, AgNORs were counted in surgical specimens from 54 patients with squamous cell carcinomas. RESULTS: The AgNOR scores of the lymph nodes metastases were significantly lower than those of the primary tumor (P = 0.0001). In 53 of 54 cases (98%), the AgNOR scores in the nodal metastases were lower than those of the primary tumor. The survival of 22 patients with AgNOR scores > or =4.0 for the primary tumor was significantly less than that of 32 patients with AgNOR scores <4.0 for the primary tumor (P = 0.0014). CONCLUSIONS: The AgNOR score of the lymph node metastases had no prognostic significance. The AgNOR score of esophageal primary cancer reflects the prognosis of patients. Scores for lymph node metastases were lower and did not reflect prognosis. The lower score in the lymph node metastases may result from the antitumor activity of macrophages in the lymph nodes.

Aged↗

Unmasking of fast and slow atrioventricular nodal pathways by successful radiofrequency ablation of two accessory atrioventricular connections.

Electrophysiologic findings suggesting the coexistence of dual atrioventricular (AV) nodal pathways and accessory AV connections have been previously described. Anterograde conduction through the accessory pathway (AP) may preclude the diagnosis of AV nodal dual pathway physiology during atrial stimulation. This study reports on a patient with manifest Wolff-Parkinson-White syndrome with clinically documented paroxysmal atrial fibrillation, in whom dual AV nodal pathways were unmasked after successful radiofrequency ablation of two accessory AV connections. In spite of detailed investigation, fast and slow AV nodal pathways were not detected in the first electrophysiologic study 8 years before ablation, nor were they detected during preablation study because of exclusive anomalous anterograde conduction. The anterograde AP effective refractory period was shorter than that of the fast and slow AV nodal pathways, and was limited by atrial refractoriness at 190 ms. The present findings strongly suggest the necessity for a careful postablation eletrophysiologic study before and after isoproterenol administration with specific evaluation of AV nodal conduction. This is the first documented report on the finding of AV nodal dual pathway physiology and reentry after successful radiofrequency ablation of two APs. This finding may be of great therapeutic significance in light of the feasibility of slow pathway ablation also during a single session, had AV nodal reentry been induced in a sustained manner after ablation of the AP to prevent late recurrence of tachycardia.

Adult↗

A comparison of open and laparoscopic cholecystectomy for patients with cirrhosis.

To evaluate the benefits of performing laparoscopic cholecystectomy (LC) in patients with cirrhosis, data on 13 patients with liver cirrhosis who underwent cholecystectomy for gallstones between 1989 and 1995 were retrospectively collected from charts filed at Fukuoka City Hospital. These 13 patients were classified into two groups; one, comprised of 7 who underwent LC, and another, comprised of 6 who underwent open cholecystectomy (OC). No statistical differences were observed in the duration of surgery or the intraoperative blood loss between the two groups; however, the C-reactive protein (CRP) level in the serum was significantly higher in the OC group than in the LC group. LC was followed by a significantly earlier resumption of a normal diet (P < 0.05) and a shorter hospital stay (P < 0.05) in comparison to OC. All of the patients who underwent OC had an uneventful clinical course; however, one of the patients who underwent LC suffered from intractable ascites postoperatively. The difference in the cost of hospitalization between the two groups was not statistically significant. These findings suggest that the therapeutic significance of performing LC in patients with cirrhosis should be assessed after carefully evaluating all factors including mortality, morbidity, and cost-effectiveness. Thus, further controlled trials are necessary.

Aged↗

Obesity, alcohol consumption, smoking, and mortality.

PURPOSE: The goals of this study were to assess prospectively the impact of obesity, alcohol use, and smoking on total mortality and to test the etiologic hypothesis that subjects with two or more of these risk factors may experience an elevated risk of overall mortality. METHODS: Information on body mass index (BMI), alcohol intake, cigarette smoking, and other life-style factors was obtained from a cohort of 8006 Japanese-American men living in Hawaii. They were between 45 and 68 years of age at the initial examination (1965-1968). After 22 years of follow-up that included nearly 159,000 person-years of observation, 2667 deaths from all causes were identified. RESULTS: There was a significant quadratic (J-shaped) relation between BMI and overall mortality. A weaker J-shaped pattern in risk was also present for the intake of alcohol. A strong positive association was observed with pack-years of cigarette smoking. A synergistic interaction between BMI and alcohol was statistically significant (P = 0.0017). Specifically, men who had the lowest body mass (BMI < 21.21 kg/m2) and drank moderately to heavily (> or = 25 oz/mo) experienced a 63% excess risk (relative risk, 1.63; 95% confidence interval; 1.33 - 1.99) compared to a reference group composed of men who had intermediate body mass (BMI, 21.21 - 26.30 kg/m2) and drank occasionally to lightly (0.01 - 24.99 oz/mo). The increase in risk due to the interactive effect of low BMI and high alcohol intake was stronger (and statistically significant) than when each of these risk factors was considered separately (excess risk, 28% and 2%, respectively). There was no significant interaction for BMI and cigarette smoking, for alcohol and cigarette smoking, or for the three factors combined. CONCLUSIONS: The most important finding of this study was that, in addition to confirming that cigarette smoking could shorten life, extreme (high or low) BMI values and high alcohol consumption are each potentially harmful to health, but even more so if moderate or heavy drinking is concomitant with low body mass, a possible indicator for low intake of nutrients.

Age Distribution↗

Cross-sectional and longitudinal changes in total and high-density-lipoprotein cholesterol levels over a 20-year period in elderly men: the Honolulu Heart Program.

PURPOSE: The purpose of this report is to describe levels of total cholesterol and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to compare these levels to those that were observed 20 years earlier. METHODS: From 1965-1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary heart disease and stroke. This report presents data for 971 men who participated in a separate fasting study of lipids and lipoproteins that first occurred from 1970-1972 and in those who received repeat examinations 10 and 20 years later. Men were aged 71-93 years at the last examination. RESULTS: Over the 20-year period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per year (P < 0.001), from average baseline values of 44-46 mg/dL. After adjustment for baseline cholesterol levels, men with prevalent coronary heart disease at the end of the 20-year follow-up experienced significantly greater reductions in total cholesterol levels than men without disease (P < 0.001). Men who developed coronary heart disease within the first 10 years of follow-up had the greatest yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL). Differences between men with recent and earlier disease were not statistically significant, although men without coronary disease experienced a significantly smaller decrease in total cholesterol than either of these groups (P < 0.05). CONCLUSIONS: Changes in total cholesterol and HDL-C levels with advancing age may be part of a natural aging process. Some changes, however, such as large reductions in total cholesterol, may signal occult disease or declines in overall health. Selective survival may contribute to these findings since improvements in lipid and lipoprotein levels that are beneficial in younger ages were common in this long-lived cohort of men.

Aged↗

Perfusion cells for studying regional variation in oral-mucosal permeability in humans. I: Kinetic aspects in oral-mucosal absorption of alkylparabens.

PURPOSE: To evaluate regional differences in permeability of human oral mucosa. METHODS: Newly designed perfusion cells were used for the investigation. The cells were applied to 5 different sites, i.e., dorsum of tongue, ventral surface of tongue, labial mucosa, floor of mouth and buccal mucosa of human volunteers. Model drugs used were methyl-, ethyl-, propyl- and butylparaben, which are passively absorbed from oral mucosa and have different lipophilicities. Biexponential disappearance profiles of the alkylparabens were analyzed kinetically using a two-compartment linear open model. RESULTS: Both the partitioning parameters to the oral mucosa and the absorption rate constants to the blood circulation correlated to the lipophilicities of the compounds in all mucosa. As to the former parameter, no significant difference was recognized in all mucosa. While, the latter parameter exhibited the regional difference; the absorption rate constants in buccal mucosa were approximately one-half of those estimated in other oral mucosa. A positive relation was recognized between the retention in oral-mucosal compartment and the drug lipophilicity. CONCLUSIONS: The newly designed perfusion cells used in this study were useful to examine the regional variations of drug absorption from oral mucosa in humans. The absorption rate constant, the partition to oral mucosa and the residence time in oral mucosa increased with lipophilicity of the compound. The regional difference in the drug absorption process was demonstrated; the slow absorption and the prolonged retention were demonstrated in buccal mucosa.

Administration, Oral↗

Pitted keratolysis: clinical manifestations in 53 cases.

Pitted keratolysis (PK) has been reported to be more common among bare-footed people living in tropical regions. It is now known that the disease is not limited to the tropics but has a world-wide distribution. However, no study has previously been performed analysing the clinical manifestations of the disease in temperate countries. A survey of 53 patients revealed several distinctive clinical features. Hyperhidrosis is the most frequently observed symptom of this condition. Malodour and sliminess of the skin are also distinctive features, evident in 88.7% and 69.8% of the cases, respectively. The most common sites of onset of PK are the pressure-bearing areas, such as the ventral aspect of the toe, the ball of the foot and the heel. The next most common site is a friction area, the interface of the toes. Lesions are rarely seen on the non-pressure-bearing locations. Some of the primary lesions originate as a small defect along the plantar furrow, which gradually grows into the characteristics crateriform pit. Several clinical features are helpful in diagnosing PK.

Adolescent↗

Quantitative morphology of Auerbach's plexus in rat intestinal wall undergoing ischemia.

To clarify the causes of abnormal peristalsis after free jejunum transplantation, the authors focused on Auerbach's plexus inducing peristalsis, and conducted an experimental study to investigate the relationship between the morphologic changes and intestinal ischemic time. Results showed that the sectional area per one ganglion cell was reduced statistically significantly at 2 and 4 hr of ischemic time, and subsequently remained almost constant. Therefore, it was assumed that atrophy of the ganglion cells might occur and might effect abnormal peristalsis.

Animals↗

Nuclear factor 1 family proteins bind to the silencer element in the rat glutathione transferase P gene.

We have previously identified a silencer region in the glutathione transferase P (GST-P) gene, of which the expression is completely repressed in liver of the rat. At least three trans-acting factors bind to multiple cis-elements in this region. Since GST-P silencer 4 (GSP4) is a dominant element in this silencer, we purified the GSP4 binding protein, called Silencer Factor A (SF-A). Purified SF-A was separated into several proteins on an SDS-polyacrylamide gel, and the amino acid sequences of four major components of SF-A were determined. The amino acid sequences of three fragments were identical to those of rat NF1-L, and that of the other fragment was the same as that of hamster NF1/Red1. It is known that nuclear factor 1 (NF1) family proteins are encoded by at least four independent genes in vertebrates, and NF1-L and NF1/Red1 are derived from different genes, NFI-A and NFI-B, respectively. The microsequencing of SF-A revealed that at least two types of NF1 existed in rat liver. Functional analysis by using GAL4-fusion protein in HepG2 cells revealed that NFI-A represented the transcription activity from human metallothionein IIA promoter. Our findings indicate that multiple forms of the NF1 family bind to the silencer region and contribute to the negative regulation of the GST-P gene expression.

Amino Acid Sequence↗

Evidence of three clinical subgroups in patients with dual atrioventricular nodal pathways.

We attempted to test the hypothesis that dual atrioventricular (A-V) nodal pathways with second-degree atrioventricular block (2nd A-V block) present as a different clinical entity from those with A-V nodal reentranttachycardia (AVNRT). By evaluation with Holter monitoring (2.9 +/- 2.5 recordings/patient) and 12-lead electrocardiogram (11.9 +/- 11.6), 177 patients with dual A-V nodal pathways could be divided into three subgroups. Thirty-two patients had 2nd A-V block only (2nd A-V block group), 57 had AVNRT only (AVNRT group), 88 had neither 2nd A-V block nor AVNRT (silent group), and none had 2nd A-V block and AVNRT both. Electrophysiologic studies showed that the atrio-His interval was significantly greater (P < 0.0001) and the maximal 1:1 atrioventricular conduction rate was lower (P < 0.0001) in the 2nd A-V block group than in the other two groups. These differences were nullified after the administration of atropine. These results suggest that patients with dual A-V nodal pathways can be classified into three clinical subgroups based on the presence of either 2nd A-V block or AVNRT. We suggest also that patients of the 2nd A-V block group may have a more augmented vagal tone on the A-V node than the other two groups.

Adolescent↗

Centrally administered calcium increases the maximum vagal activation of baroreceptor reflex control of heart rate in spontaneously hypertensive rats.

Baroreceptor reflex control of heart rate (HR) was examined before and 15 min after intracerebroventricular infusion (i.c.v.) of 10 microliters of high-Ca2+ solution (Ca2+, 16.3 mM) in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). The slope of the individual regression line of the relation between reflex HR changes (delta HR) and changes in mean arterial pressure (delta MAP) produced by bolus injections of phenylephrine or sodium nitroprusside (delta HR/delta MAP; beats/min/ mm Hg) for bradycardia was significantly less in SHR (-0.60 +/- 0.30; n = 10) than in WKY (-1.78 +/- 0.27; n = 10; p < 0.01) at baseline. The slope increased in SHR during administration of high Ca2+ to -1.39 +/- 0.17 (p < 0.01) but not in WKY: In contrast, no significant changes were observed for the reflex tachycardia both in SHR (n = 7) and WKY (n = 10). Further, we analyzed sigmoidal MAP-HR reflex curves in SHR with i.c.v. of either high Ca2+ (n = 6) or artificial cerebrospinal fluid (aCSF; n = 5). Administration of high Ca2+ reduced the bradycardic plateau and increased HR range without changes in average gain. Our results suggest a modulatory role for central Ca2+ in the baroreceptor reflex control of HR in SHR.

Animals↗

Enhanced depressor effect of centrally administered high-calcium solution in salt-loaded experimental hypertension.

The depressor effect by oral calcium supplementation is known to be more pronounced in salt-dependent than in renin-dependent hypertension. This study was conducted to investigate the role of central calcium on two different pathophysiologic subtypes of experimental hypertension; (a) salt-dependent, deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin-dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high-calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p < 0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p < 0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12 beats/min) with shorter duration (for 20 min) than in DOCA. This significant depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+ i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/- 81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays a more important role in regulating sympathetic nerve activity and BP in salt-dependent than in renin-dependent experimental hypertension.

Animals↗