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T Ohkusa

Publications and source records attributed to T Ohkusa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Helicobacter pylori DNA in drinking water in Japan.

Helicobacter pylori has been detected in drinking water in Peru and Sweden, suggesting the possibility of water-borne transmission. To date there have been few reports of H. pylori being detected in water; one was of the ureA gene of H. pylori in wells and springs in rural Japan. We examined water sampled in or near urban areas of Japan for H. pylori DNA by three assays using the polymerase chain reaction (PCR). Near Tokyo, samples were obtained: 10 of tap water, 6 of well water, 10 of river water, and 10 of sea water. Samples were filtered with membranes with 0.05- or 0.22-microm pores, which bacterial cells are caught by. Bacterial nucleic acids were extracted and purified and the PCR was done to amplify adhesin specific for H. pylori and the ureA gene, if present. Real-time PCR that measured the yield in terms of fluorescence was done with primers for 16S rRNA. None of the samples of tap, river, or sea water contained adhesin, ureA or 16S rRNA. None of the 6 samples of well water contained adhesin or ureA, but 2 of the 6 samples contained 16S rRNA. Some of the users of the well had had H. pylori infection in the past. H. pylori DNA was detected in well water and the users had been infected, so water-borne transmission via well water may occur even in towns in Japan.

Adhesins, Bacterial↗
PubMed2001

Influence of timing and magnitude of arterial wave reflection on left ventricular relaxation.

The influence of timing and magnitude of arterial wave reflection (WR) on afterload-dependent relaxation was evaluated in patients with a variety of heart diseases (group 1, age < 30 yr; group 2, age > 40 yr) and in dogs. While both femoral arteries were compressed (FC), WR returned just after the dicrotic notch (early diastole) in group 1 but before the dicrotic notch (late systole) in group 2. The time constant of the left ventricular pressure decay (tau) was shortened during FC in group 1, whereas it was prolonged in group 2. In dogs, a constriction of the thoracic aorta induced a late systolic augmentation of WR with a prolongation of tau (cf. group 2), whereas constriction of the lower abdominal aorta induced an early diastolic augmentation of WR with a shortening of tau (cf. group 1). With aortic constriction, coronary flow increased, and there was a close correlation between the peak change in backward aortic pressure and that in coronary flow regardless of the timing of WR. Thus the time at which WR returns during the cardiac cycle may have an important effect on left ventricular relaxation and coronary flow.

Adult↗
PubMed2001

Syncope induced by tobacco smoking in the head-up position.

A 26-year-old man had a loss consciousness for a few minutes while smoking in the standing position, and was referred to hospital. No abnormalities were found in a computed tomography examination of his head, in a 24-h electrocardiogram or in an exercise tolerance test. The head-up tilt test (HUT) while tobacco smoking elicited a positive response in the tilted position, but the HUT without tobacco smoking was negative. The most noteworthy effect of tobacco smoking during the HUT was the high level of plasma epinephrine compared to the levels seen during supine smoking or the HUT alone. Syncope induced by tobacco smoking in the standing position is rare and the mechanism may be the same as that underlying neurally mediated syncope.

Adult↗
PubMed2001

Effects of cardioplegic arrest and reperfusion on rabbit cardiac ryanodine receptors.

Calcium overload is considered to be a primary contributor to ischemia-reperfusion injury. Cardiac sarcoplasmic reticulum (SR), the main regulator of intracellular Ca2+ concentration under normal conditions, is a target for ischemic myocardial injury. The ryanodine receptor (RyR) is the SR Ca2+ release channel. Previous reports have shown that a reduction in RyR activity during global myocardial ischemia correlates with concomitant myocardial dysfunction. Crystalloid cardioplegia, a technique for myocardial protection during heart operations, reduces Ca2+ accumulation during global ischemia. Hence, the effects of cardioplegia on RyR in isolated rabbit hearts was investigated. The study also compared [3H] ryanodine binding before ischemia (control group), after 30 min of ischemia (either global ischemia (GI group) or cardioplegic arrest (CA group)), and after 20 min of reperfusion. The GI group, but not the CA group, showed a significant reduction in the maximum number of binding sites (Bmax) for RyR compared with the control group (Control vs GI group: after ischemia, 1.33+/-0.27 vs 0.83+/-0.12 pmol/mg protein, p<0.05; after reperfusion, 1.33+/-0.27 vs 0.80+/-0.08 pmol/mg protein; p<0.05). CA group: after ischemia, 1.22+/-0.20 pmol/mg protein; after reperfusion, 1.15+/-0.28 pmol/mg protein). The affinity (Kd) values for [3H] ryanodine binding were not different among the 3 groups at any point. The preservation of RyR numbers during cardioplegia correlated with the concomitant preservation of cardiac functions. The results indicate that number of functional RyR was much better preserved during cardioplegia than during global ischemia. It is postulated that cardioplegia-induced protection of cardiac RyR may result in the protection of SR function during ischemia-reperfusion.

Animals↗
PubMed2001

[A strategy for second-line anti-Helicobacter pylori therapy in patients with previously failed treatment].

Highly effective H. pylori eradication therapies are currently used in Japan. However, eradication failures still appear in a considerable proportion of cases. In such refractory cases, several second-line eradication therapies and therapeutic efficacies have been only exceptionally studied. Our aims were to analyze the reasons and evaluate the second-line therapies when first-line eradication therapies fail. We make a strategy for second-line anti-H. pylori therapy in patients with previously failed treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Animals↗
PubMed2000

Altered interaction of FKBP12.6 with ryanodine receptor as a cause of abnormal Ca(2+) release in heart failure.

OBJECTIVE: Little information is available as to the Ca(2+) release function of the sarcoplasmic reticulum (SR) in heart failure. We assessed whether the alteration in this function in heart failure is related to a change in the role of FK binding protein (FKBP), which is tightly coupled with the cardiac ryanodine receptor (RyR) and recently identified as a modulatory protein acting to stabilize the gating function of RyR. METHODS: SR vesicles were isolated from dog LV muscles [normal (N), n=6; heart failure induced by 3-weeks pacing (HF), n=6]. The time course of the SR Ca(2+) release was continuously monitored using a stopped-flow apparatus, and [3H]ryanodine-binding and [3H]dihydro-FK506-binding assays were also performed. RESULTS: FK506, which specifically binds to FKBP12.6 and dissociates it from RyR, decreased the polylysine-induced enhancement of [3H]ryanodine-binding by 38% in N (P<0.05) but it had no effect in HF. In HF, the rate constant for the polylysine-induced Ca(2+) release from the SR was 61% smaller than in N. FK506 decreased the rate constant for the polylysine-induced Ca(2+) release by 67% in N (P<0.05) but had no effect in HF. The [3H]dihydro-FK506-binding assay revealed that the number (B(max)) of FKBPs was decreased by 83% in HF (P<0.05), while the K(d) value was unchanged. FK506 did not significantly change SR Ca(2+.)-ATPase activity in either N or HF. CONCLUSIONS: In HF, the number of FKBPs showed a tremendous decrease; this may underlie the RyR-channel instability and the impairment of the Ca(2+) release function of RyR seen in the failing heart.

Analysis of Variance↗
PubMed2000

Development of gap junctional channels and intercellular communication in rat liver during ontogenesis.

BACKGROUND/AIMS: We investigated the expression of connexin (Cx) 32 and 26 subunit proteins of the gap junction (GJ) in the rat liver during ontogenesis to clarify their roles in control of growth and differentiation, and observed their channels in association with development of gap junctional intercellular communication (GJIC). METHODS: The expression of Cx32 and 26 in prenatal and postnatal livers was examined by Western blot and immunofluorescence. GJ channels were investigated not only by double immunofluorescence study but also by immunogold electron microscopy. The spread of lucifer yellow 5 min after its microinjection was examined in the cultured liver tissues. RESULTS: 1) Western blot showed the expression of both Cx from the late stage of gestation and their peak a week after birth. 2) Cx32- or 26-positive plaques were scattered on hepatocytes of the fetal liver and some of them were colocalized; both were increased just after birth. On day 7 after birth, Cx32-positive plaques were present on all hepatocytes within a lobule, and Cx26-positive plaques were distributed in the periportal area. 3) Double-immunogold electron microscopy just after birth showed that most GJ channels were homotypic type of Cx32 or 26, and that few were heterotypic. On day 7 after birth, most channels had the homotypic type of type of Cx32 in the middle and pericentral areas, and there was a heterotypic type of Cx32 and 26 in the periportal area. 4) The dye transfer of lucifer yellow showed a wider spread in the liver tissues on day 7 after birth than on day 1. CONCLUSION: Increased GJ formation and compatibility or incompatibility of GJ channels are closely associated with development of GJIC, and GJIC may develop at cytodifferentiation during ontogenesis.

Animals↗
PubMed2000

Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system.

OBJECTIVE: Our aim was to identify endoscopic features associated with Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: A total of 50 infected patients with nonulcer dyspepsia who underwent endoscopy with antral and corporal biopsies and 50 patients matched for age and sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively by three endoscopists blinded to the H. pylori status and the patient's history. The endoscopic findings of gastritis, classified by a modification of the Sydney system as present or absent, were evaluated, and the histological severity was graded by the updated Sydney system. RESULTS: For endoscopic features, the odds ratio was 53.1 (95% confidence interval, 6.8-414.9) for edema, 18.8 (5.8-60.5) for erythema with reddish streaks excluded, 0.0275 (0.0002-0.477) for reddish streaks, 17.4 (0.97-313.7) for friability, 14.2 (5.1-40.0) for exudate, 17.2 (2.2-137.6) for flat erosions, 2.54 (0.81-7.94) for raised erosions, 40.1 (2.3-694.5) for rugal hypertrophy, 19.1 (2.4-151.6) for rugal atrophy, 96.2 (23.4-395.9) for a vascular pattern, 0.125 (0.010-1.06) for bleeding spots, and 21.0 (2.6-166.5) for nodularity. The histological severity of inflammation, neutrophil activity, and atrophy in the antrum and corpus and of metaplasia in the antrum was greater in the infected patients than in the noninfected patients. CONCLUSIONS: Endoscopic features associated with H. pylori were a vascular pattern, edema, rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks excluded, flat erosions, and exudate. These endoscopic features were associated with the histological findings of inflammation, neutrophil activity, atrophy, and metaplasia.

Atrophy↗
PubMed2000

Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.

In tachycardia-induced heart failure (HF), positive lusitropic effects of milrinone or dobutamine were assessed by evaluating the time constant of left ventricular (LV) pressure decay (tau) and Ca(2+)-ATPase activity of the sarcoplasmic reticulum (SR). The peak value of the positive first derivative of LV pressure (+dP/dt) was less increased, either by dobutamine (2-10 microg x kg(-1) x min(-1)) or by milrinone (4-20 microg/kg), in HF than in control (P < 0.05), whereas tau was shortened to an extent similar to that in control with dobutamine [P = not significant (NS)] and to an even greater extent with milrinone (P < 0.05). Ca(2+)-ATPase activity increased similarly in HF and control with dobutamine (1 microM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 microM; +19% in HF vs. +11% in control, P < 0.05). Ca(2+)-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca(2+)-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.

Animals↗
PubMed2000

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum.

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.

Adrenergic beta-Agonists↗
PubMed2000

Infective endocarditis with extensive calcified granulation of the mitral annulus and valve--a case report.

Mitral annular calcification, a degenerative process usually seen in the elderly or in chronic renal failure, is rarely seen in an extensive form. A 69-year-old man with no history of renal failure, rheumatic fever, or heart disease had mitral valve vegetation and regurgitation, together with extensive mitral annuls and valve calcification, which may or may not have been secondary to the infective endocarditis.

Aged↗
PubMed2000

Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice.

Intestines of mice with colitis caused by dextran sulfate sodium (DSS) contain more Bacteroidaceae cells than untreated controls. We investigated the roles of intestinal bacteria and succinic acid, a by-product of Bacteroidaceae metabolism, in this model of colitis. CBA/J mice were given 3% DSS in water for 14 days. After mice were anesthetized and killed, concentrations of organic acids in stools from the cecum and colon were measured. The resected rectum and colon were washed with sterile saline; some specimens were incubated with imipenem in saline for 1 h to kill bacteria on the surfaces and others were not. Their homogenates were cultured anaerobically and aerobically. Separately, 1 mL of 20 mM succinic acid was infused into the rectum of mice, whose anal verge was glued. Animals were anesthetized and killed the next day. The rectum and colon were examined histologically. Concentrations of succinate were higher everywhere in the colon of mice with colitis than in controls. Mice with colitis had more Bacteroidaceae cells, especially B. caccae, than controls. Mice given succinate enemas had focal erosions of the mucosa and edema of the submucosa. Succinic acid, produced abundantly by members of the family Bacteroidaceae, especially B. caccae, may be the ulcerogenic agent in DSS colitis.

Acetates↗
PubMed1999

Abnormal Ca2+ release from cardiac sarcoplasmic reticulum in tachycardia-induced heart failure.

OBJECTIVE: In heart failure, little information is available as to the Ca2+ release function of sarcoplasmic reticulum (SR), which plays a major role in cardiac contractile function. Here, we assessed the rapid kinetics of drug-induced Ca2+ release from cardiac SR in combination with a measurement of ryanodine binding in heart failure. METHODS: The SR vesicles were isolated from dog left ventricular (LV) muscles (normal (N), n = 10; pacing induced heart failure (HF), n = 10). The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus using arsenazoIII as a Ca2+ indicator, and Ca2+ uptake and [3H]ryanodine binding assays were done using a filtration method. RESULTS: The amount of Ca2+ uptake was reduced in HF to 55% of N (P < 0.05). Even the more marked and earlier appeared decrease was seen in the rate constant and the initial rate of polylysine (PL; a specific release trigger)-induced Ca2+ release (P < 0.05). However, the PL concentration dependency of the initial rate shifted towards lower concentrations of PL in HF than in N ([PL] at half maximum stimulation = 0.13 vs. 0.35 microM). The [3H]ryanodine binding assay revealed a lower Bmax (pmol/mg) in HF than in N (0.91 +/- 0.19 vs. 2.64 +/- 0.59, P < 0.05), but no difference in Kd (nM) (0.95 +/- 0.29 vs. 0.90 +/- 0.11, P = n.s.). The [PL] dependency on the enhancement of [3H]ryanodine binding again showed a shift towards lower [PL] in HF than in N. CONCLUSIONS: In pacing-induced heart failure, the Ca2+ releasing function of SR is disturbed, which may result in an intra-cellular Ca2+ transient that was slowed down.

Animals↗
PubMed1999

Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation.

OBJECTIVES: Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium. BACKGROUND: Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF. METHODS: We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS: In AF patients, 1) Bmax was significantly lower in each atrium (0.21+/-0.03 pmol/mg [right], 0.16+/-0.04 pmol/mg [left]) than in the right atrium (0.26+/-0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2)+/-1.28 x 10(-2)) and right (1.70 x 10(-2)+/-1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2)+/-2.79 x 10(-2)); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10(-2)+/-4.01 x 10(-2)) and right (7.71 x 10(-2)+/-3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2)+/-3.92 x 10(-2)) of NSR patients. CONCLUSIONS: These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.

Aged↗
PubMed1999

Effect of angiotensin II receptor antagonism on vascular hypertrophy and aortic impedance in abdominal aortic-banded rat.

Vascular hypertrophy is considered to be an adaptive response to increased arterial wall stress in hypertension. Although there are several reports concerning the effect of angiotensin II inhibition on the development of vascular hypertrophy, little information is available as to its effect on vascular hypertrophy in parallel with the evaluation of arterial wall characteristics. The goal of this study was to evaluate the effect of angiotensin II type 1 receptor antagonist TCV-116 on pressure overload-induced vascular hypertrophy in parallel with the assessment of aortic impedance. Low dose (LD; 0.3 mg/kg/day) or high dose (HD; 3.0 mg/kg/day) of TCV-116 was administered to abdominal aortic-banded rats over 4 weeks; then hemodynamics and morphology were evaluated. In both the LD and HD groups, blood pressures were decreased to a similar extent compared with those of the vehicle-treated group (P < .05). Left ventricular (LV) weight and LV weight/body weight ratio was inhibited in both TCV-116-treated groups (P < .05), whereas the media cross-sectional area of the aorta was inhibited only in the HD group (P < .05). After the treatment of TCV-116 (LD, HD), total systemic resistance was decreased compared with the vehicle-treated group (P < .05), but there was no significant difference between the TCV-116-treated groups. In contrast, the first harmonic of the impedance modulus revealed the decrease only in the HD group (P < .05). TCV-116 attenuated the development of pressure overload LV hypertrophy and vascular hypertrophy as well; however, the dose of TCV-116 required for the inhibition of vascular hypertrophy was significantly higher than that for LV hypertrophy. Vascular hypertrophy may be less pressure dependent than cardiac hypertrophy. On chronic addition of high dose of TCV-116, arterial wave reflection was decreased in association with the attenuation of vascular hypertrophy.

Angiotensin Receptor Antagonists↗