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Biomedical subjects

Y Kakuta

Publications and source records attributed to Y Kakuta.

At least 73 records · Page 4Linked to original sources

Induction of granule release by intracellular application of calcium and guanosine-5'-O-(3-thiotriphosphate) in human eosinophils.

The roles of Ca and G proteins in granule release from human eosinophils were examined by use of a patch-clamp technique in single cells. The morphologic changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. In addition, the expression of small molecular weight guanine nucleotide binding protein (small G protein) mRNA (smg p25A [rab 3] and smg p21 [rab 1]) was investigated. The intracellular application of Ca, 10 mumol/L, and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), 100 mumol/L, induced fusion of EPO containing granules with the surface membrane, which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A. These results provide direct evidence of granule fusion by intracellular application of Ca and GTP-gamma-S. In addition, Ca dependent proteins and G proteins act cooperatively in granule release, and these proteins likely regulate the different processes of degranulation. Furthermore, a protein, encoded by smg p21, may be involved in the granule release process in human eosinophils.

Calcium↗

[A case of congenital long QT syndrome associated with T wave alternans].

A case was presented in which a rare T wave alternans occurred in association with congenital long QT syndrome. A 71-year-old woman, who had experienced several syncopal attacks per year for the previous forty years, was admitted for further evaluation of the syncope. She had a family history of sudden death (sister) and QT prolongation (son). Electrocardiogram showed a corrected QT interval of 0.68 seconds. Treadmill exercise-tolerance test revealed both T wave alternans immediately after exercise and torsades de pointes 150 seconds after exercise. The syncope was induced by the mental excitation. A prolonged corrected QT interval reduced from 0.70 seconds to 0.58 seconds by the correction of her serum potassium and magnesium. The effect of propranolol, verapamil, phenytoin or mexiletine on T wave alternans and ventricular arrhythmia was evaluated by the treadmill exercise-tolerance test. The treatment with propranolol was most effective.

Adrenergic beta-Antagonists↗

[Exercise-induced left bundle branch block in treadmill exercise test: clinical significance and prognosis].

Exercise induced left bundle branch block (LBBB) is poorly understood. We investigated its clinical characteristics and prognosis. The records of 3,459 consecutive patients who underwent treadmill exercise testing were reviewed. Exercise induced LBBB was identified in 6 patients (0.17%). Three out of six patients had underlying cardiac disease; two had coronary artery disease and one dilated cardiomyopathy. Three out of five had redistribution on Tl-201 myocardial scintigraphy. In one of these three patients, however, coronary angiography demonstrated no significant narrowings. Tl-201 myocardial scintigraphy in patients with exercise induced LBBB may be undetermined for coronary artery disease. During follow-up, one of six patients had depressed left ventricular function and was diagnosed as having dilated cardiomyopathy. It is thus obvious that exercise induced LBBB without a specific underlying heart disease should be followed up carefully.

Aged↗

Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment.

A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells.

Adenocarcinoma↗

Effect of artificial surfactant on ciliary beat frequency in guinea pig trachea.

This study defines the effect of artificial surfactant on ciliary beat frequency. We employed guinea pig tracheal rings and a photomultiplier which allows in vitro measurement of ciliary beat frequency. The beat frequency without surfactant decreased continuously while surfactant caused a relative increase in beat frequency. The difference between the relative beat frequency in the presence and absence of surfactant was significant. The effect of surfactant was dose dependent. Fifteen minute treatments with 2 mM hydrogen peroxide reduced the beat frequency. The reduction partially recovered in the absence of surfactant. In contrast, surfactant markedly accelerated the recovery of the beat frequency. Surfactant did not influence the effect of terbutaline (a beta 2-adrenergic agonist) on beat frequency. These results indicate that artificial surfactant can, in some circumstances, promote ciliary beat frequency. This concept is important to the clearance mechanism of the airways, and its application to some pathophysiological states such as chronic bronchitis and bronchial asthma should be considered.

Animals↗

Two cases of bi-ventricular dysplasia associated with ventricular tachycardia and familial occurrence of sudden death.

Two strikingly similar patients with arrhythmogenic right ventricular dysplasia which severely impaired not only the right ventricle but also the left ventricle are described in association with familial occurrence of sudden death. A 49-year-old man experienced syncope which was due to ventricular tachycardia. Electrocardiography revealed a first degree atrioventricular block, incomplete right bundle-branch block, T wave inversions in leads II, III, a VF and V1 to V5, and multiformal ventricular extrasystoles. Echocardiography and ventricular cineangiography showed not only the right ventricular dilatation with an aneurysm in the right ventricular apex, inflow and outflow tracts, but also mild dilatation of the left ventricle with left ventricular apical and posterior aneurysms. Radionuclide angiography also disclosed dysfunction of both ventricles, especially during exercise. His family history revealed that 3 members of his family died of sudden deaths. A 56-year-old woman experienced syncope secondary to ventricular tachycardia, with left bundle-branch block. Electrocardiography showed complete right bundle-branch block, left axis deviation, and T wave inversions in leads V1 to V4. Echocardiography and ventricular cineangiography revealed not only marked right ventricular dilatation with the "triangle of dysplasia", but also a left ventricular aneurysm in the apex and posterior portion. Her elder brother died of a sudden death, and electrocardiograms of 2 members of her family showed ventricular extrasystoles and T wave inversions. These 2 cases may well be termed "familial bi-ventricular dysplasia".

Cardiac Complexes, Premature↗

[Eosinophilic heart disease with favorable courses: report of two cases].

Two cases of eosinophilia-associated acute peri-myocarditis which coursed favorably are reported. Case 1 was a 47-year-old man whose ECG revealed QS, ST-T change, bundle branch block, and arrhythmias. Case 2 was a 30-year-old man whose ECG showed ST segment depression. The chest radiographs of both patients revealed enlarged hearts. Left ventriculography showed abnormal regional wall motion. Their endomyocardial biopsies revealed eosinophilic infiltration of the myocardium, but few eosinophils were degranulated. In Case 1, the development of eosinophilia preceded perimyocarditis and the eosinophilia continued even after the symptoms of peri-myocarditis were improved. In conclusion, it seems that eosinophilia did not have specific relation to the initial manifestation of the disease but that it occurred as a secondary reaction to peri-myocarditis of unknown etiology in these cases.

Adult↗

[Development of severe mitral regurgitation following percutaneous transvenous mitral valve commissurotomy].

The purpose of this study was to analyze the risk factors of unexpected occurrence of mitral regurgitation (MR) following percutaneous transvenous mitral valve commissurotomy (PTMC) in patients with mitral stenosis. The analyzed factors were clinical pictures, hemodynamic findings, echocardiographic findings and balloon inflation techniques during PTMC. Among 24 patients undergoing successful PTMC using an Inoue's balloon, severe MR developed in five patients (21%). No significant correlation in the occurrence of MR was observed in clinical findings, hemodynamic data and balloon inflation techniques including the times and size of ballooning. Echocardiographic findings of the mitral valve including the pliability of the mitral leaflet and localized calcification of the mitral orifice were the most contributory factors to the occurrence of severe MR. The localized alternation of valve stiffness produced localized tear or excessive dilatation of the mitral leaflet during PTMC, resulting in severe MR. Hemodynamic results and calculated mitral valve areas after PTMC showed significant improvement in both groups with and without MR. However, symptomatic improvement in patients with severe MR was less prominent when compared to the patients without MR. Thus, the complete echocardiographic evaluation of the mitral valve apparatus before PTMC is important to prevent severe MR.

Aged↗

[Influence of Lp(a) on restenosis after coronary angioplasty].

We clarified the relationship between lipoprotein (a) concentration and restenosis after coronary angioplasty (PTCA). The lipoprotein (a) concentration in patients with restenosis after PTCA was significantly higher than in patients without restenosis after PTCA (33.0 +/- 19.8 mg/dl vs 19.1 +/- 17.4 mg/dl, p less than 0.05]. Moreover, patients with a lipoprotein (a) concentration of more than 30 mg/dl had a high rate of restenosis after PTCA. Restenosis after PTCA is related to lipoprotein (a) concentration.

Aged↗

Ion transport in rat tracheal epithelium in vitro. Role of capsaicin-sensitive nerves in allergic reactions.

Tracheas from control rats or rats sensitized to egg albumin (EA) were studied in vitro in Ussing chambers, and changes in short-circuit current (Isc) induced by the addition of antigen or agonists on the mucosal (luminal) side were recorded. Addition of EA (100 micrograms/ml) to tracheas from sensitized but not from control rats caused a slow increase of Isc beginning after 15 to 30 s and maximal at 3 to 4 min. This response was inhibited in the presence of doxantrazole, a mucosal mast-cell-stabilizing agent, but not by sodium cromoglycate. A separate group of rats was treated neonatally with capsaicin to deplete peptide neurotransmitters. Responses to EA were significantly lower in capsaicin-treated, sensitized rats than in untreated, sensitized control littermates. No difference was seen in the level of serum EA-specific IgE in these two groups. In tracheas from untreated rats, addition of substance P, capsaicin, platelet-activating factor, and acetylcholine caused an immediate and marked increase in Isc. Responses to substance P and acetylcholine were unaffected by capsaicin treatment. However, responses to capsaicin itself and also to PAF were reduced. These data indicate that changes of net ion transport across the airway epithelium are early phenomena of local hypersensitivity reactions, and that neurotransmitters such as substance P may play an important role in the control of these phenomena.

Animals↗

[Clinical evaluation of severe idiopathic tricuspid regurgitation].

This study clarified the clinical profile and echocardiographic findings of severe idiopathic tricuspid regurgitation (TR). Among 8,538 consecutive ultrasonic examinations, a total of 63 patients had severe TR, which was depicted by color flow mapping as a regurgitant signal more than 4 cm from the tricuspid valve orifice. Thirteen of the 63 patients had no underlying diseases, and these patients with severe idiopathic TR were the subjects of the present study. All 13 patients were over 66 years of age (mean 77.3 +/- 5.6 years old) and had had episodes of right heart failure which responded effectively to diuretics. All 13 patients had atrial fibrillation. Using two-dimensional echocardiography, thickening (77%), prolapse (69%) and malaligned coaptation (54%) of the tricuspid valves were observed. The tricuspid annular diameters, cross-sectional areas of the right and left atria and the right ventricular end-diastolic dimensions were significantly greater than those of the age-and-gender-matched lone atrial fibrillation group and the normal control group (p less than 0.01). The left ventricular dimension and ejection fraction did not differ from those of the matched lone atrial fibrillation group. Other valvular regurgitations were also detected (AR 77%, MR 100%, PR 69%), but the degrees of regurgitation were minimal. We proposed severe TR with tricuspid annular dilatation, right atrial and right ventricular dilatation observed in the aged as a distinct cardiac disease entity.

Aged↗

[Acute and chronic effects of a new oral inotropic agent, ibopamine hydrochloride, on hemodynamic and metabolic responses to ergometer exercise in patients with severe congestive heart failure].

The hemodynamic and metabolic effects of ibopamine, an orally active 3,4-diisobutylic ester of N-methyl-dopamine, at rest and during exercise, were evaluated in 8 patients with severe congestive heart failure, initially at 2 hrs after oral 100 mg and after 4 weeks of maintenance therapy (100 mg, 3 times a day). At rest, a single dose of ibopamine increased CI, SVI and SWI, and reduced PCWP, PAm, RA and PVR. These beneficial hemodynamic effects were maintained during supine bicycle exercise: CI and SVI increased markedly (p less than 0.05) and PCWP, PAm, RA and SVR increased at a lower extent (p less than 0.05) after ibopamine than on control conditions. After chronic therapy with the drug, LVDd and CTR decreased (p less than 0.05) and exercise tolerance time increased (p less than 0.01). HR, BPm, double product, norepinephrine, epinephrine, renin activity, aldosterone and lactate/pyruvate did not change significantly after administration of ibopamine. Clinical responses after 4 weeks of maintenance therapy were good in 4 cases and fair in 1 case. No adverse effects were observed. Therefore, ibopamine seems to have not only a positive inotropic action, but also a potent vasodilating action, leading to both afterload and preload reduction and so to be useful for the treatment of severe congestive heart failure at rest and during exercise after acute and chronic therapy with the drug.

Administration, Oral↗

K channels of human alveolar macrophages.

The activation of macrophages has been reported to be associated with Ca-activated K permeability change. In order to study this permeability change in human alveolar macrophages, we examined alveolar macrophages electrophysiologically at a single channel level. We observed two types of Ca-activated K channel currents having conductances of 218 +/- 2 and 32 +/- 0.6 picosiemens in symmetrical 154 mmol/L KCl solutions. The characteristics, such as voltage dependency and Ca sensitivity, as well as channel conductance, were different between these two types of channel currents. Quinine (a blocker of Ca-activated K conductance), 0.5 mmol/L, reduced these channel currents by 45 +/- 8% and 31 +/- 8%. Quinine, 0.5 mmol/L, also inhibited chemiluminescence and leukotriene B4 release by 82 +/- 6 to 88 +/- 3% and 88 +/- 2%, respectively. These results suggest the presence of two types of Ca-activated K channels, which may be related to the release of inflammatory mediators from human alveolar macrophages.

Calcium↗

Effect of ketotifen on human alveolar macrophages.

In order to examine the possibility of human alveolar macrophages being an effector site of an antiasthmatic drug, we studied the effect of ketotifen on chemiluminescence and Ca-activated K conductance at single channel level because they are associated with the activation of macrophages. Peak chemiluminescence response, induced by a single concentration of phorbol myristate acetate (0.5 micrograms/ml), was inhibited by 28 +/- 3, 51 +/- 8, and 76 +/- 7% by ketotifen concentrations of 0.02, 0.12, and 0.24 mmol/L, respectively. The inhibition of chemiluminescence by ketotifen concentrations of 0.12 and 0.24 mmol/L was also observed in macrophages stimulated with zymosan activated serum (54 +/- 7 and 80 +/- 6%, respectively). Moreover, ketotifen, 0.24 mmol/L, inhibited Ca-activated K channel currents by 44 +/- 7% (large currents) and 48 +/- 13% (small currents). These results may explain, at least partly, antiasthmatic effects of ketotifen.

Acridines↗

Effects of qing-fei-tang (seihai-to) and baicalein, its main component flavonoid, on lucigenin-dependent chemiluminescence and leukotriene B4 synthesis of human alveolar macrophages.

A traditional Chinese remedy, Qing-Fei-Tang (Seihai-to, T90), has been used for treatment of chronic respiratory diseases with long-lasting cough and sputum, e.g. chronic bronchitis. We examined the effect of T90 and its main component flavonoid, baicalein, on the lucigenin-dependent chemiluminescence (CL) and leukotriene B4 (LTB4) synthesis of human alveolar macrophages (AM). AM were obtained by bronchoalveolar lavage from patients with various respiratory diseases, including sarcoidosis, idiopathic pulmonary fibrosis, bronchial asthma, chronic bronchitis and lung cancer. CL were observed by stimulating 1 x 10(5) AM with phorbol myristate acetate in the presence of lucigenin. LTB4 were generated by incubating 1 x 10(6)/ml AM with Ca ionophore A23187 for 30 min and determined by reverse phase high performance liquid chromatography and radioimmunoassay. T90 (0.2-2.0 mg/ml) and baicalein (0.1-100 microM) inhibited both CL and LTB4 production of AM in a dose-dependent fashion. These inhibitory effects were not due to cytotoxic effects of the procedure because neither 2 mg/ml T90 nor 100 M baicalein affected the viability of AM nor lactate dehydrogenase release from AM. These results suggest that T90 exerts its effect on inflammatory lung diseases through the anti-inflammatory action, i.e. inhibiting the oxidative and arachidonate metabolism of local inflammatory lung cells.

Acridines↗