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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 217 records · Page 12Linked to original sources

Left ventricular geometry as an independent predictor for extracardiac target organ damage in essential hypertension.

Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. It has not been established, however, whether left ventricular geometry is an independent predictor of extracardiac target organ damage in essential hypertension. Study groups were classified according to relative wall thickness: 27 patients with concentric LVH and 50 patients with eccentric LVH. Age and left ventricular mass indexes of two groups were matched. As indexes of extracardiac target organ damage, retinal funduscopic grade, and serum creatinine level were measured. The severity of hypertensive retinopathy and the renal involvement were more severe in patients with concentric LVH than in patients with eccentric LVH. Extracardiac target organ damage was consistently higher in patients with concentric LVH than in those with eccentric LVH. Systemic hemodynamics paralleled ventricular geometric patterns, with higher peripheral resistance and lower aortic compliance in patients with concentric LVH, whereas end-diastolic volumes and stroke volumes were higher in patients with eccentric LVH than in patients with concentric LVH. In addition, total peripheral resistance was related to retinal fundoscopic grade (r = 0.41, P < .01), and serum creatinine level (r = 0.28, P < .05). Even in the presence of an identical degree of LVH, echocardiographically determined left ventricular geometry may provide a further independent stratification of extracardiac target organ damage in essential hypertension.

Aged↗

Bradykinin B2-receptor-mediated modulation of membrane currents in guinea-pig cardiomyocytes.

1. In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)-induced positive inotropic and chronotropic responses in isolated guinea-pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques. 2. BK (0.1-1000 nM) increased the L-type Ca2+ current (I(Ca)), which was recorded from enzymatically-dissociated atrial myocytes by the nystatin-perforated patch method, in a concentration-dependent fashion, and the calculated EC50 value for increasing I(Ca) was 5.2 nM. In conventional ruptured patch experiments, BK inhibited the muscarinic acetylcholine receptor-operated K+ current (I(K.ACh)) that was activated by the muscarinic agonist carbachol (1 microM) with an EC50 value of 0.57 nM. Both the increase in I(Ca) and the decrease in I(K.ACh) were blocked by HOE140, a selective bradykinin B2 receptor antagonist. 3. The BK-induced inhibition of I(K.ACh) was significantly attenuated by staurosporine and calphostin C, protein kinase C inhibitors. In addition, the I(K.ACh) inhibition by BK was also attenuated by the tyrosine kinase inhibitor genistein or tyrphostin but not by daidzein, an inactive analogue of genistein. However, neither protein kinase C inhibitor nor tyrosine kinase inhibitor affected the BK-induced increase in I(Ca). 4. In the presence and absence of muscarinic stimulation, BK prolonged the action potential recorded from the atrial cells in the current clamp mode. 5. We conclude that BK increases I(Ca) and decreases I(K.ACh) in atrial cells, resulting in positive inotropic and chronotropic responses in atrial preparations. Protein kinase C activation, and possibly tyrosine kinase activation, may be involved in the B2-receptor-mediated I(K.ACh) inhibition.

Action Potentials↗

Serum substances that interfere with thyroid hormone assays in patients with chronic renal failure.

OBJECTIVE: Serum thyroid hormone concentrations in patients with chronic renal failure are usually low, despite normal serum TSH levels. We investigated the effect on thyroid hormone assays of serum dialysable organic acids that are elevated in uraemic patients. PATIENTS: Serum samples from 42 patients with chronic renal failure who were receiving haemodialysis and 37 sex- and age-matched healthy subjects were examined. DESIGN AND MEASUREMENTS: Serum thyroid hormone concentrations were measured with an analogue radioimmunoassay (RIA), a labelled antibody assay, and an equilibrium dialysis/RIA method. Serum concentrations of organic acids were determined with high performance liquid chromatography. RESULTS: Serum thyroid hormone levels determined by an analogue RIA and a labelled antibody assay in uraemic patients increased, and serum concentrations of organic acids decreased following haemodialysis. A significant association existed between serum free T3 (FT3) levels determined by an analogue RIA and serum concentrations of indoxyl sulphate (IS) prior to dialysis. There was also a significant association between serum free T4 (FT4) levels determined by an analogue RIA and serum concentration of IS and hippuric acid (HA) prior to dialysis. There was a significant association between the changes of serum concentrations of indole acetic acid (IAA) and FT4 concentrations prior to and following haemodialysis when determined by an analogue RIA. Serum FT3 and FT4 levels significantly decreased after the addition of IS to serum from healthy subjects when determined by an analogue RIA but not by a labelled antibody assay. Serum FT4 levels, but not FT3 levels, decreased after addition of IAA when determined by an analogue RIA. Serum FT4 concentrations determined by an equilibrium dialysis/RIA were significantly higher than those determined by the other two methods. The addition of IS, IAA, and HA to serum samples from healthy subjects significantly increased FT4 concentrations when determined by an equilibrium dialysis/RIA method. CONCLUSIONS: Increased serum levels of indoxyl sulphate, indole acetic acid and hippuric acid in sera of uraemic patients may interfere with thyroid hormone measurements when an analogue radioimmunoassay is used. In contrast, there was little Interference with a labelled antibody assay. Dialysable organic acids may also interfere with thyroid hormone assays determined by an equilibrium dialysis/radioimmunoassay method.

Aged↗

Diazepam potentiates the positive inotropic effects of histamine and forskolin in guinea-pig papillary muscles.

There have been diverse reports on the effects of diazepam on cardiac contractility. The purpose of this study was to examine whether diazepam modifies the inotropic response elicited by histamine on an isolated guinea-pig papillary muscle. The responses of electrically driven papillary muscle to histamine and cyclic AMP-related inotropic agents were recorded in the absence and in the presence of diazepam. Histamine and forskolin, which directly stimulate adenylate cyclase, significantly increased the contractile force in the papillary muscle in a concentration-dependent manner. A histaminergic H2-receptor antagonist, cimetidine, but not a H1-receptor antagonist, diphenhydramine, at 10 microM produced a rightward shift in the concentration-response curve for histamine. Diazepam (10 microM) shifted the concentration-response curve for histamine and forskolin to the left by 1.8 and 1.6 times, respectively. Neither a central type (fulmazenil) nor a peripheral type (PK11195) of benzodiazepine receptor antagonist modified the effect of diazepam on the histaminergic-evoked contraction. Phosphodiesterase blockade by 3-isobutyl-1-methylxanthine shifted the concentration-dependent curve for histamine to the left. A combination of 3-isobutyl-1-methylxanthine also produced a leftward shift of the curve. However, there was no significant difference between the 3-isobutyl-1-methylxanthine only group and the combination group. These results indicate that diazepam potentiates the positive inotropic effect produced by histamine, probably mediated via an increase in cyclic AMP levels induced by histamine.

Anesthetics, Intravenous↗

Additive effects of medroxyprogesterone acetate and 5-fluorouracil derivative on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil suppressed thymidylate synthetase (TS) gene expression followed by reduction of TS activity in rat mammary tumors induced with 7,12-dimethylbenz[a]anthracene. Addition of medroxyprogesterone acetate (MPA) to the anticancer drug caused an additional decrease in TS and thymidine kinase activities in the tumor growth and restoration of bone loss. These results suggest that the simultaneous administration of MPA and anticancer drugs causes increased inhibition of mammary tumor growth and also diminishes the bone loss.

9,10-Dimethyl-1,2-benzanthracene↗

Transvenous dual chamber pacing via a unilateral left superior vena cava.

A 74-year-old woman with a unilateral left superior vena cava required dual chamber permanent pacing after a radical cardiac operation for an incomplete from of endocardial cushion defect. An active fixation ventricular lead was used to prevent the instability induced by the strange course of the electrode. For atrial pacing, a ventricular passive fixation lead was used. A transvenous dual chamber pacemaker was successfully inserted via a unilateral left superior vena cava.

Aged↗

[Bactericidal and anti-toxin activities of catechin on enterohemorrhagic Escherichia coli].

We examined the bactericidal activity of catechin, an astringent ingredient of tea, on enterohemorrhagic Escherichia coli (EHEC) O157:H7 and the anti-toxin activity of catechin on vero toxin (VT), the main pathogenic factor of EHEC O157:H7. To examine bactericidal activity, we added 1 X 10(4) CFU/ml bacteria to 1.25 to 20 W/V% of green tea extract or the PBS solution containing 25 to 400 micrograms/ml of (-) epigallocatechin gallate (EGCg), which is the main catechin ingredient of green tea leaf, and counted the number of live bacteria at various intervals. After 3 to 5 hours, no live bacteria were seen in 1.25 to 2.5 (regular drinking concentration) % green tea extract. In the high concentrations of 100 to 400 micrograms/ml EGCg the number of live bacteria decreased with time and after 24 hours no survivors were seen. In the low concentrations of 25 to 50 micrograms/ml EGCg, however, no change was observed in the number of live bacteria during 5 hours. After 24 hours the bacteria in 50 micrograms/ml were killed and the number of bacteria in 25 micrograms/ml decreased to one tenth of that at the start. To examine the anti-toxin activity, we mixed equal volumes of 2 ng/0.1 ml VT2 and 0.5 to 2 mg/0.1 ml catechin in vitro and incubated them at 37 degrees C for various times. Then we inoculated 0.2 ml of the mixture intraperitonealy to BALB/c mice. One mg of catechin inhibited by 100% the lethal toxicity of 2 ng of VT2 (LD 100) to mice. The inhibition of lethal toxicity of VT2 by catechin depended on the incubation time. The rate of inhibition was 0, 40 and 100% for 9, 12 and 18-24 hours incubation, respectively. These results suggest that catechin has not only bactericidal activity on EHEC O157:H7 but also anti-toxin activity on vero toxin.

Animals↗

Regulation of a new cell wall hydrolase gene, cwlF, which affects cell separation in Bacillus subtilis.

Bacillus subtilis produces a 35-kDa cell wall hydrolase, CwlF, during vegetative growth. The CwlF protein was extracted from B. subtilis cwlB sigD mutant cells and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-terminal amino acid sequencing revealed that its sequence is completely identical to that of the internal region of the papQ gene product. Disruption of the papQ gene in the B. subtilis chromosome led to the complete loss of CwlF, indicating that papQ is identical to cwlF. CwlF exhibits high sequence similarity to the p60 proteins of Listeria species, NlpC proteins of Escherichia coli and Haemophilus influenzae, and Enp2 protein of Bacillus sphaericus. The beta-galactosidase activity of the cwlF-lacZ transcriptional fusion and Northern blot analysis of the cwlF gene indicated that the gene is expressed as a monocistronic operon during the exponential growth phase, and primer extension analysis suggested that the cwlF gene is transcribed mainly by EsigmaA RNA polymerase and weakly by EsigmaH RNA polymerase. While the cells of the cwlF-deficient mutant were about twice as long as those of the wild-type strain, the cwlF sigD double mutant cells exhibited extraordinary microfiber formation, in contrast to the filamentation of the sigD mutant. The CwlF production was not affected by the pleiotropic mutations flaD1 and degU32(Hy), which endow cells with the ability of extensive filamentation.

Amino Acid Sequence↗

Genetic and epigenetic alterations of the estrogen receptor gene and hormone independence in human breast cancer.

The existence of hormone-independent tumors is a substantial problem for the present endocrine treatment of breast cancers. Estrogen receptor (ER) gene mutation can change the biochemical activity of the protein and can affect hormone responsiveness. However, quite a few mutations of significance have been described in breast cancer. Recently, numerous variant ERs have been detected at the mRNA level with alternative splicing, yielding deletion of exon 3, 5, or 7. The truncated ER protein induced from variant mRNA could mainly be exhibited as a repressor through dominant negative effects on normal ER protein. The mechanism of the loss of hormone dependency is, however, still very complex. Further work to assess the correlation between clinical behavior and ER variants is required to determine whether these variants play a role in hormone-resistant disease. Additionally, the DNA methylation of the ER gene itself may control ER expression. These epigenetic changes can play an important role in the loss of hormone dependence in breast cancer.

Alternative Splicing↗

Beneficial hemodynamic effects of oral prostacyclin (PGI2) analogue, beraprost sodium, on a patient with primary pulmonary hypertension--a case report.

A 65-year-old woman was admitted to our hospital because of exertional dyspnea in 1987. A diagnosis of primary pulmonary hypertension was confirmed by right heart catheterization. She had received conventional therapy in the outpatient clinic. She was readmitted with the deterioration of exertional dyspnea in 1995. Stabilization of pulmonary hemodynamics, while not achieved with conventional therapy, was achieved with additive administration of an oral prostacyclin (PGI2) analogue, beraprost sodium.

Administration, Oral↗

Coronary vasospasm at the site of myocardial bridge--report of two cases.

Two patients with angina pectoris and postmyocardial infarction angina due to coronary vasospasm at the site of myocardial bridge are described. Intracoronary injection of isosorbide dinitrate led to resolution of coronary vasospasm on acetylcholine provocation test, and vasospastic angina pectoris has been well controlled after treatment with calcium channel blockers.

Angina Pectoris↗

Serum or growth factor deprivation induces the expression of alkaline phosphatase in human gingival fibroblasts.

We have previously reported that the increased expression of alkaline phosphatase (ALP) activity is a phenotypic characteristic of gingival fibroblasts present in chronic inflammatory periodontal lesions. We hypothesized that ALP might be induced in gingival fibroblasts by environmental factors. In the present study, we investigated the factors influencing the induction of ALP expression in fibroblasts derived from healthy human gingiva. The withdrawal of serum from confluent cultures of fibroblasts increased the number of cells positive for ALP activity and protein, without their proliferation. Suramin, a growth factor antagonist, induced ALP expression in cells cultured with serum. Serum re-addition or exposure to platelet-derived growth factor-AB and/or insulin-like growth factor I suppressed ALP induction and caused cell growth. ALP-positive cells could survive for up to 6 weeks after serum deprivation, a condition inducing cell death via apoptosis. These results demonstrate that serum or growth factor deprivation induces the expression of ALP in gingival fibroblasts. ALP expression is negatively correlated with cell growth and accompanied by a change into serum-growth-factor-independent survival.

Adult↗

An early systolic sound associated with midventricular obstruction in a patient with hypertrophic cardiomyopathy.

A 57-year-old woman was admitted for examination because of chest discomfort. Transthoracic echocardiography was performed and she was diagnosed as having hypertrophic cardiomyopathy. An echocardiogram also revealed that she had midventricular obstruction with a pressure gradient of 125 mmHg determined by Doppler echocardiography. A phonocardiogram showed an early systolic sound and the beginning of the sound coincided with the time of septal-posterior wall contact. In addition, the timing also corresponded to the sudden obstruction of blood flow in the region of the midventricular narrowing. Furthermore, this sound markedly decreased with the reduction in pressure gradient caused by cibenzoline treatment. Thus, it was concluded that the early systolic sound was associated with midventricular obstruction and produced by a rapid deceleration of the interventricular flow caused by midventricular obstruction.

Anti-Arrhythmia Agents↗

Increased circulating soluble form of Fas in patients with dilated cardiomyopathy.

To examine the prognostic role of the circulating soluble form of Fas (sFas), circulating sFas levels were measured in 33 patients with dilated cardiomyopathy (DCM) and 12 age-matched normal control subjects (NC) using an enzyme-linked immunosorbent assay (ELISA). Circulating sFas levels in DCM were significantly higher than those in NC (2.42+/-1.02 vs 1.66+/-0.20 ng/ml, p=0.015). Patients with DCM were stratified into 2 groups [group I (n=15): sFas > or =2.06 ng/ml; group II (n=18): sFas <2.06 ng/ml] on the basis of the mean value plus 2SD of circulating sFas level in NC. The circulating sFas level was significantly increased in relation to the severity of heart failure and correlated positively to left ventricular end-diastolic pressure in DCM. However, there were no significant differences in left ventricular dimension between the 2 groups. There were 5 deaths from worsening heart failure in group II, but there were no deaths in group I during the follow-up period. In conclusion, circulating sFas levels were increased in patients with DCM. Circulating sFas levels are increased in proportion to the severity of heart failure and may provide prognostic information independent of left ventricular geometry.

Cardiomyopathy, Dilated↗

Relation between coronary blood flow and left ventricular mass in hypertension: noninvasive quantification of coronary blood flow by thallium-201 myocardial scintigraphy.

This study was conducted to quantify coronary blood flow (CBF) noninvasively according to the fractionation principle and to elucidate the relation between CBF and left ventricular hypertrophy. CBF/cardiac output (CO), estimated on the basis of the ratio of myocardial uptake/total injected dose of thallium-201 (% cardiac uptake), was determined in 14 control subjects and 40 patients with essential hypertension. CBF and CBF per 100 g of myocardium (unit CBF) were calculated according to the following formulas: CBF= % cardiac uptake x CO, and unit CBF = (CBF/LVM) X 100, where CO and left ventricular mass (LVM) are echocardiographically determined. There was good reproducibility of % cardiac uptake (r = 0.983, p < 0.0001). Percent cardiac uptake was greater in hypertensive patients (4.65+/-1.44%) than in control subjects (3.64+/-0.64%), and there was a positive correlation between % cardiac uptake and LVM. CBF (ml/min) was greater in hypertensive patients (240.7+/-80.5) than in control subjects (194.9+/-36.9), but unit CBF (ml/min/100 g) was less in hypertensive patients (102.2+/-26.7) than in control subjects (150.3+/-30.5). Multiple regression analyses showed that LVM was the most potent independent predictor of resting CBF in hypertension. Our results indicate that CBF, determined by thallium-201 myocardial scintigraphy, increases parallel to the increase in LVM, but unit CBF decreases even in the resting condition in patients with essential hypertension.

Adult↗

Tonic block of the sodium and calcium currents by ketamine in isolated guinea pig ventricular myocytes.

Effects of ketamine on the sodium (INa) and L-type calcium currents (ICa) were examined by using whole-cell patch clamp techniques in guinea pig single ventricular myocytes. The mode of action of ketamine was compared with those of quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker. Ketamine (30-300 microM) inhibited both INa and ICa in a concentration-dependent manner. Quinidine (30 microM) and verapamil (0.1 microM) produced use-dependent depression of INa and ICa, respectively. The amplitude of INa elicited by the first depolarizing pulse after a long quiescent period was slightly decreased by quinidine. During a train of depolarizing pulse the current amplitude decreased gradually, and reached a steady state level in the quinidine-treated cell (use-dependent block, UDB). Verapamil produced a similar mode of inhibition of ICa, i.e., UDB. In contrast, ketamine produced significant decrease in INa and ICa elicited by the first depolarizing pulses and the decreases of both currents were not augmented during a train of depolarizing pulses. From these results, it can be concluded that ketamine produces tonic block of the cardiac sodium and calcium channels and the mode of inhibition is clearly different from UDB by quinidine and verapamil.

Animals↗

Recombinant human basic fibroblast growth factor accelerates fracture healing by enhancing callus remodeling in experimental dog tibial fracture.

Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 micrograms. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.

Absorptiometry, Photon↗