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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 451 records · Page 25Linked to original sources

Electrophysiological effects of a new class III antiarrhythmic agent (E-4031) on the conduction and refractoriness of the in vivo human atrium.

OBJECTIVE: The aim was to test the efficacy of a new class III drug, E-4031, on human atrial muscle in vivo. METHODS: Electrophysiological measurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 microgram.kg-1.min-1) which followed an initial dose of 9 micrograms.kg-1 x 5 min-1. Extrastimuli at 500 ms were delivered from the right atrial appendage, high lateral right atrium, and low lateral right atrium. The effective refractory period, repetitive atrial firing zone, and fragmented atrial activity zone were assessed at three sites in the right atrium. The conduction delay zone from the stimulus artefact to the distal electrode pair at the coronary sinus was also measured. RESULTS: E-4031 caused a significant increase in overall right atrial effective refractory period from 210(SD 29) to 232(26) ms (p < 0.001, n = 30 sites). There were significant decreases in the incidence of repetitive atrial firing (67% to 37%: p < 0.005), in the repetitive atrial firing zone [23(20) to 11(22) ms: p < 0.01], and in the fragmented atrial activity zone [15(22) to 3(8) ms: p < 0.005], but no significant change in the conduction delay zone. However, E-4031 significantly prolonged the longest coupling interval that elicited conduction delay, from 249(31) ms to 267(28) ms (p < 0.01). E-4031 had no effect on the conduction time except at coupling intervals close to the atrial effective refractory period. CONCLUSION: These results suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.

Anti-Arrhythmia Agents↗

Augmented central pressor action of magnesium in SHR.

This study attempted to determine whether central magnesium (Mg) influences the regulation of blood pressure (BP). An intracerebroventricular (icv) injection of a high Mg2+ solution (190.0 mEq/L, 10 microL), made by adding MgC12 to artificial cerebrospinal fluid, increased the mean BP in both conscious spontaneously hypertensive rats (SHR; n = 17, p < 0.001) and Wistar Kyoto rats (WKY; n = 8, p < 0.005). Spontaneously hypertensive rats showed a greater pressor response than WKY (+11.7 +/- 0.9 mm Hg versus +3.5 +/- 1.1 mm Hg, p < 0.001). This pressor response to Mg2+ given icv was dose-dependent in the range of Mg2+ concentration between 47.5 and 190.0 mEq/L in SHR. A high Mg2+ solution (190.0 mEq/L), made by adding MgSO4 given icv, also increased the mean BP in SHR (n = 7, p < 0.001) and WKY (n = 6, p < 0.01), whereas the high osmolarity solution (340 mOsm/kg H2O) given icv did not change the mean BP in either SHR or WKY. Also administered was a high Mg2+ solution icv after either hexamethonium bromide (Hx; 50 mg/kg intravenously) or arginine vasopressin antagonist (aAVP, (CH2)5Tyr(Me)AVP, 30 micrograms/kg i.v.). The pressor response to the high Mg2+ solution was abolished by arginine vasopressin antagonist both in SHR and WKY, although it was not canceled by Hx. A high Mg2+ solution administered icv caused a 3.5-fold increase in plasma arginine vasopressin concentration in SHR (n = 5, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epidermal cell viability in rat skin preserved at 4 degrees C.

To determine the longest storage period for the clinical application of epidermal cells and a better method of preservation at 4 degrees C, we stored skin in various fluids and assessed the changes in epidermal cell viability. The time course of changes in the viability of epidermal cells from skin in various preservation fluids was similar to the results obtained with whole skin in previous studies. The best preservation fluid was found to be RPMI 1640 medium, and the best method of preservation was immersion in RPMI 1640 at 4 degrees C with a medium change every 3 days.

Animals↗

Electrophysiologic effects of a new class III antiarrhythmic agent, E-4031, on atrial flutter, atrial refractoriness, and conduction delay in a canine sterile pericarditis model.

Numerous studies have shown that E-4031 generally prolongs the atrial effective refractory period (AERP) without affecting cardiac conduction. The effects of E-4031 on AERP and cardiac conduction at short cycle lengths (CLs) close to the AERP were measured in 12 dogs with sterile pericarditis. Three pairs of electrodes were sutured at three sites in the atria 4 days after the model was created. We measured AERP and maximum conduction delay (MCD) after 8 beats train at CLs of 400, 300, 200 and 150 ms before and during continuous infusion of E-4031 (0.1 microgram/kg/min) that followed an initial dose of 10 micrograms/kg/min/5 min. E-4031 interrupted sustained atrial flutter (AF) (> or = 10 min) in 4 of 5 episodes and atrial fibrillation (> or = 10 min) in 4 of 4. The CL of AF defined as a rapid atrial rhythm (rate > or = 240 beats/min) in five episodes studied in the sterile pericarditis model was significantly (p < 0.005) prolonged from 120 +/- 8 to 160 +/- 17 ms. There were significant (p < 0.005) increases in AERP at each CL, and prolongation of AERP was 39 +/- 18, 31 +/- 14, 23 +/- 14, and 16 +/- 14 ms at CL 400, 300, 200, and 150 ms, respectively. E-4031 produced less prolongation of AERP at short pacing CLs and had no effect on conduction time during atrial rapid pacing at CLs > 150 ms. E-4031 did not prolong MCD at CL 400 ms, but did prolong MCD at CLs of 300, 200, and 150 ms, despite prolongation of AERP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Double response of the ventricle during transient entrainment in a common atrioventricular nodal reentrant tachycardia.

We report a patient with slow-fast atrioventricular (AV) nodal reentrant tachycardia, in which double ventricular response was demonstrated during rapid pacing at cycle length of 300 msec or less from the high right atrium. The determinants of double ventricular response during transient entrainment in the present case were: (1) a crucial conduction delay in the slow pathway; (2) the collision between the activation via the antegrade fast pathway (antidromically) of the last paced beat and the activation via the antegrade slow pathway (orthodromically) of the previous paced beat, instead of the unidirectional block in the slow pathway; and (3) the enhanced AV nodal conduction over the antegrade fast pathway.

Adult↗

Cloning and sequencing of a dehalogenase gene encoding an enzyme with hydrolase activity involved in the degradation of gamma-hexachlorocyclohexane in Pseudomonas paucimobilis.

In Pseudomonas paucimobilis UT26, gamma-hexachlorocyclohexane (gamma-HCH) is converted by two steps of dehydrochlorination to a chemically unstable intermediate, 1,3,4,6-tetrachloro-1,4-cyclohexadiene (1,4-TCDN), which is then metabolized to 2,5-dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL) by two steps of hydrolytic dehalogenation via the chemically unstable intermediate 2,4,5-trichloro-2,5-cyclohexadiene-1-ol (2,4,5-DNOL). To clone a gene encoding the enzyme responsible for the conversion of the chemically unstable intermediates 1,4-TCDN and 2,4,5-DNOL, a genomic library of P. paucimobilis UT26 was constructed in Pseudomonas putida PpY101LA into which the linA gene had been introduced by Tn5. An 8-kb BglII fragment from one of the cosmid clones, which could convert gamma-HCH to 2,5-DDOL, was subcloned, and subsequent deletion analyses revealed that a ca. 1.1-kb region was responsible for the activity. Nucleotide sequence analysis revealed an open reading frame (designated the linB gene) of 885 bp within the region. The deduced amino acid sequence of LinB showed significant similarity to hydrolytic dehalogenase, DhlA (D. B. Janssen, F. Pries, J. van der Ploeg, B. Kazemier, P. Terpstra, and B. Witholt, J. Bacteriol. 171:6791-6799, 1989). The protein product of the linB gene was 32 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Not only 1-chlorobutane but also 1-chlorodecane (C10) and 2-chlorobutane, which are poor substrates for other dehalogenases, were good substrates for LinB, suggesting that LinB may be a member of haloalkane dehalogenases with broad-range specificity for substrates.

Amino Acid Sequence↗

cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs.

E4TF1 was originally identified as one of the transcription factors responsible for adenovirus E4 gene transcription. It is composed of two subunits, a DNA binding protein with a molecular mass of 60 kDa and a 53-kDa transcription-activating protein. Heterodimerization of these two subunits is essential for the protein to function as a transcription factor. In this study, we identified a new E4TF1 subunit, designated E4TF1-47, which has no DNA binding activity but can associate with E4TF1-60. We then cloned the cDNAs for each of the E4TF1 subunits. E4TF1 was purified, and the partial amino acid sequence of each subunit was determined. The predicted amino acid sequence of each cDNA clone revealed that E4TF1-60 had an ETS domain, which is a DNA binding domain common to ets-related transcription factors. E4TF1-53 had four tandemly repeated notch-ankyrin motifs. The putative cDNA of E4TF1-47 coded almost the same amino acid sequences as E4TF1-53. Three hundred and thirty-two amino acids of the N termini of E4TF1-47 and -53 were identical except for one amino acid insertion in E4TF1-53, and they differ from each other at the C terminus. These three recombinant cDNA clones were expressed in Escherichia coli, and the proteins behaved in the same manner as purified proteins in a gel retardation assay. Nucleotide and predicted amino acid sequences were highly homologous to GABP-alpha and -beta, which is further supported by the observation that GABP-specific antibody can recognize human E4TF1.

Adenoviridae↗

Determinants of the prognosis after a first myocardial infarction in a migrant Japanese population. The Honolulu Heart Program.

BACKGROUND: Although numerous studies have been published on the prognostic assessment of myocardial infarction, little is known about determinants of the prognosis after a first myocardial infarction, especially regarding the role of standard risk factors for coronary heart disease (CHD) measured before the development of myocardial infarction. METHODS AND RESULTS: In a prospective study of CHD among men of Japanese ancestry living in Hawaii, 457 patients with a first myocardial infarction (age range, 46 to 84 years) were identified during 20 years of follow-up. The relations of clinical variables and CHD risk factors to mortality in early (< 30 days) and two stages of late (30 days to 5 years and 5 to 10 years) periods after myocardial infarction in these patients were investigated. In multivariate analyses using logistic regression models (for early mortality) and Cox regression models (for late mortality), age at myocardial infarction and severe complications (Killip classes 3 and 4) were independent predictors of both early and late mortality (up to 5 years after myocardial infarction). In addition, ventricular arrhythmias predicted only early mortality, whereas anterior myocardial infarction, radiological evidence of cardiomegaly and/or pulmonary congestion, and intraventricular block predicted only late mortality (up to 5 years after myocardial infarction). Only age was an independent predictor of all-cause mortality more than 5 years after myocardial infarction. After adjusting for age at myocardial infarction and these clinical variables, preinfarction-measured risk factors such as 1-hour postload serum glucose (positively) and 1-second forced expiratory volume (inversely) were significantly associated with late mortality up to 5 years, whereas systolic blood pressure was the only independent predictor of late mortality after 5 years. CONCLUSIONS: This study has confirmed the importance of age at myocardial infarction and clinical indicators of complications such as Killip class 3 or 4, radiological evidence of pulmonary congestion, and ventricular arrhythmias or intraventricular block as the prognostic determinants of myocardial infarction. In addition, some of the preinfarction-measured standard risk factors for CHD were found to predict long-term prognosis independent of age and clinical factors.

Age Factors↗

Hormonal regulations of alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase activities in adult rat hepatocytes cultured in serum-free medium on collagen gel.

Primary hepatocytes were cultured on collagen gel in serum-free, alpha-modified Eagle's minimum essential medium containing 0.1 microM insulin, 0.1 microM dexamethasone, 10 mM pyruvate and supplements such as glucagon, epinephrine or growth hormone. The activities of alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase were assayed in cell extracts prepared from the cultures. All three enzyme activities were induced by glucagon, epinephrine or dibutyryl cAMP. The maximally effective concentration of glucagon was 5-10 nM for both alkaline phosphatase and 5'-nucleotidase and 100 nM for gamma-glutamyltransferase. Only alkaline phosphatase activity was suppressed by growth hormone, which caused marked suppression at about 1 microU (0.25 ng)/ml. Taurocholate also induced both alkaline phosphatase and gamma-glutamyltransferase activities at 1 mM.

5'-Nucleotidase↗

Isolation and characterization of Tn5-induced mutants of Pseudomonas paucimobilis UT26 defective in gamma-hexachlorocyclohexane dehydrochlorinase (LinA).

Pseudomonas paucimobilis UT26 grows on gamma-hexachlorocyclohexane (gamma-HCH) as a sole source of carbon and energy. Tn5 mutation was introduced into UT26, and two kinds of mutants defective in gamma-HCH degradation were phenotypically isolated; one (UT64) completely lacked the activity to degrade gamma-HCH, while the other (UT61) retained a very low level of activity. Tagging and sequencing analysis showed that both mutants had a Tn5 insertion at the same site of the linA (gamma-HCH dehydrochlorinase encoding) gene. However, UT61 had an additional rearrangement, which could be the cause of its retaining a low level of activity. An in vitro complementation test with a crude extract from UT64 plus partially purified LinA protein showed that LinA was essential not only for the first-step reaction (gamma-HCH to gamma-pentachloro-cyclohexene; gamma-PCCH), but also for the second-step reaction (gamma-PCCH to compound B) of gamma-HCH degradation in UT26.

Amino Acid Sequence↗

Angina pectoris caused by dynamic exercise in hypertrophic cardiomyopathy with normal coronary arteries.

To evaluate the relationship between angina pectoris caused by dynamic exercise and the time course of heart rate (HR) and hemodynamics during dynamic exercise in 15 patients with hypertrophic cardiomyopathy (HCM) with normal epicardial coronary arteries, the supine ergometer exercise test was performed during cardiac catheterization. The HCM patients were divided into a chest pain group (n = 6) and a no chest pain group (n = 9) based upon the results of the ergometer exercise test. There was no significant difference in the level of ST-segment depression after exercise in both the chest pain and no chest pain groups (-2.1 +/- 0.6 mm vs -2.6 +/- 1.1 mm, NS). Increase in heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) in the early phase of the exercise test was significantly greater in the chest pain group compared with the no chest pain group. These observations suggest that in HCM patients, the occurrence of exertional chest pain has a close relationship with the rapid increase in HR and LVEDP in the early phase of dynamic exercise, but does not have a relationship with the gradual increase in these parameters.

Angina Pectoris↗

Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT.

Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD > or = 10 and age < 15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD > or = 10 and age > or = 15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD < 10 and age > or = 15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients.

Child↗

Effect of a new calcium antagonist on hemodynamics at rest and exercise loading in patients with essential hypertension.

MPC-1304 ((+-)-methyl 2-oxopropyl 1,4-dihydro 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 86780-90-7), a new calcium antagonist, was orally administered to 10 outpatients with mild essential hypertension. It was observed that MPC-1304 inhibited elevations of blood pressure both at rest and under exercise loading without any adverse hemodynamic effects. The findings obtained indicated that MPC-1304 would be clinically useful in the treatment of hypertensive patients undergoing therapy while continuing normal everyday activities including physical exertion.

Aged↗

The sensitivity of hyperthermo-chemo-radiotherapy for neoplastic cells in vitro on contact-sensitive plates.

On plastic dishes, the Chinese hamster cell line (V-79) easily formed colonies and enabled us to examine the effects of various treatments utilizing a colony formation assay while a different human cancer cell line (KSE-1) was found to have a low colony-forming ability which made it difficult to examine when using only a small number of cells. However, on the contact-sensitive plate (CSP), the KSE-1 line was able to form a sufficient amount of colonies in order to conduct examinations. Using CSPs, we were able to investigate the killing effects of various treatments on two malignant cells (V-79 and KSE-1). For the V-79 cells, hyperthermo-chemo-radiotherapy (HCR) was observed to be more effective than any other treatment. For KSE-1 cells, on the other hand, bleomycin had little killing effect, while both radiotherapy alone or hyperthermo-radiotherapy in doses of more than 4 Gy X-ray were found to be effective. These results indicated that it is necessary to examine the sensitivities of cells to different treatments in clinical cases in order to avoid non-effective treatments. In this report, we suggest that the use of CSPs allows for the effective examination of the effects of HCR while using only a small number of malignant cells, which have a low cloning efficiency on plastic surfaces.

3T3 Cells↗

[Clinical features of heart failure induced by pericarditis and myocarditis].

The clinical condition of heart failure induced by pericarditis is expressed as cardiac tamponade or constrictive pericarditis. In both conditions, cardiac filling is impaired either by pericardial fluid or nonelastic pericardial sac under increased diastolic pressure and cardiac output is reduced. Patients show signs of right side heart failure. Immediate pericardiocentesis or pericardiotomy is required for cardiac tamponade, and pericardiectomy is essential for constrictive pericarditis. The clinical expression of myocarditis ranges from asymptomatic state to fulminant fatal congestive heart failure. Recently, identification of viral infection, using polymerase chain reaction (PCR), has contributed to the diagnosis of myocarditis, involving cases of idiopathic congestive cardiomyopathy.

Cardiac Tamponade↗

[Athyreotic congenital hypothyroidism in two sisters].

Two sisters with athyreotic congenital hypothyroidism are described. This is the fifth report on athyreotic congenital hypothyroidism in siblings. The elder sister is 14 years old and the younger one is 12. The parents have no consanguinity or family history of thyroid disease. Both of the patients were born before the start of neonatal screening tests for congenital hypothyroidism. After birth, they had jaundice, abdominal distention and constipation, which are typical symptoms of congenital hypothyroidism. Serum T4 levels were decreased, and the serum TSH levels were markedly increased. Therefore we diagnosed them as having congenital hypothyroidism. They have received replacement therapy with thyroxine since diagnosis and have shown normal development physically and psychologically. They were tested for thyroid scintigram when the elder sister was 9 years old and the younger one was 7. 123I thyroid uptakes were 0.69% and 0.64%, respectively. The thyroid scans demonstrated no focus of accumulation of 123I. They do not have trapping defect of iodine, because 123I ratio of saliva and serum were 41.3 and 46.3, respectively. From these results, we diagnosed them as having athyreotic congenital hypothyroidism. They and their mother do not have any antithyroid antibodies. We suppose that some genetic factor is responsible for the athyreotic congenital hypothyroidism.

Child↗