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Biomedical subjects

M Fukazawa

Publications and source records attributed to M Fukazawa.

At least 19 recordsLinked to original sources
PubMed1999

The anti-ischemic effects of CP-060S during pacing-induced ischemia in anesthetized dogs.

CP-060 S, (-)-( S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3 ,4-methylenedioxyphenoxy)ethyl]-amino]propyl]-1,3-thiazolidin++ +-4-one hydrogen fumarate, is a novel cardioprotective drug which prevents Na+-, Ca2+-overload and has Ca2+ channel blocking activity. We compared the anti-ischemic effects of CP-060S with those of diltiazem, a Ca2+ channel blocker, and R56865, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine, a Na+-, Ca2+-overload inhibitor, in a canine pacing-induced ischemia model. CP-060S 100 microg kg(-1) significantly suppressed the pacing-induced ischemic epicardial ST-segment elevation by maximally 75%, while diltiazem 100 microg kg(-1) suppressed it by maximally 35%. R56865 100 microg kg(-1) significantly suppressed the ST-segment elevation by maximally 30%. In addition, diltiazem 100 microg kg(-1) caused synergistic suppression of ST-segment elevation by 70% when administered simultaneously with R56865 100 microg kg(-1). These results suggest that a Na+-, Ca2+-overload preventive action and a Ca2+ channel blocking action independently contribute to the suppression of the ST-segment elevation. Therefore, CP-060S may suppress pacing-induced ST-segment elevation by a dual action by preventing Na+-, Ca2+-overload and the Ca2+ channel blockade.

Anesthesia↗
PubMed1998

Osteoma with cholesteatoma in the external auditory canal.

We report an unusual case of a 13-year-old girl with a benign osteoma associated with a cholesteatoma in the external auditory canal and serous otitis media. The osteoma was located in the antero-inferior wall of the right external auditory canal. A cholesteatoma was present between the osteoma and the tympanic membrane. Computed tomography revealed a soft tissue density within the external auditory canal and in the middle ear cleft. The shadow in the middle ear cleft was considered to represent the serous otitis media. Surgical removal of the osteoma and cholesteatoma proved successful, and no recurrences or complications have occurred in the first year postoperatively.

Adolescent↗
PubMed1998

CP-060S interacts with three principal binding sites on the L-type Ca2+ channel.

CP-060S, (-)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxypheny1]-3-[3-[N-met hyl-N-[2-(3,4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thi azolidin-4-one hydrogen fumarate is a novel cardioprotective drug, which is able to prevent Na+-, Ca2+-overload and also has Ca2+ channel blocking activity. The latter action of CP-060S was characterized by radioligand binding experiments with rat cardiac membranes in terms of the interaction with the three principal binding sites on the L-type Ca2+ channel, which bind such drugs as the 1,4-dihydropyridines, phenylalkylamines and benzothiazepines. CP-060S exhibited complete and concentration-dependent inhibition of [3H](+)-PN200-110, [3H](-)-desmethoxyverapamil and [3H]cis-(+)-diltiazem binding to their specific binding sites. Saturation studies showed that CP-060S increased the Kd of [3H](+)-PN200-110 and [3H](-)-desmethoxyverapamil without causing a significant change in the maximum binding density. The dissociation kinetics of the three radioligands were accelerated by CP-060S. These results suggest that CP-060S interacts with a novel binding site on the L-type Ca2+ channel and has a negative allosteric interaction with the three principal binding sites for the 1,4-dihydropyridines, phenylalkylamines and benzothiazepines.

Animals↗
PubMed1998

Lectin-gradient gel affinity electrophoresis of glycoproteins.

Lectin-gradient agarose gel affinity electrophoresis was developed for identification of glycoforms of glycoproteins in lectin affinity electrophoresis. Gradation of lectin was done by stacking agarose gel blocks with increasing concentrations of lectin (discontinuous system) and by keeping the plate in a moist chamber at 4 degrees C overnight (continuous system) before electrophoresis. On the visualization of separated glycoform lines, the antibody-affinity blotting was superior for low concentrations of alpha-fetoprotein. Fluoresceine isothiocyanate (FITC) labeling of whole serum proteins, enzyme activity staining for alkaline phosphatase, and prestaining for lipoproteins were also applicable for visualization of proteins at higher concentrations. The conventional Western blotting can not be recommended because of the competition between lectin and glycoproteins in binding to nitrocellulose membrane. Lectin-gradient affinity electrophoresis also had a wide application for optimization of the condition of lectin affinity electrophoresis.

Adult↗
PubMed1998

Long-term prognosis of non-shunt operation for idiopathic portal hypertension.

This report presents 46 Japanese patients with idiopathic portal hypertension (IPH) in whom non-shunt operation was performed for the management of esophageal varices. Non-shunt operation included transthoracic esophageal transection (Sugiura's procedure) in 37 patients, transabdominal esophageal transection (TAET) in 3 patients, and Hassab's procedure in 6 patients. Rates of postoperative variceal eradication were: 78.4% by Sugiura's procedure; 100% by TAET; and 50% by Hassab's procedure. The cumulative rates for recurrent varices and recurrent bleeding were 3.9%, and 5.1%, respectively, at 5 years, and 8.9% and 9.8% at both 10 and 15 years. Only 3 patients required additional endoscopic injection sclerotherapy to treat recurrent varices. Although 3 patients developed upper gastrointestinal bleeding, the source of hemorrhage was esophageal varices in 1, and portal hypertensive gastropathy in 2; none of the patients died from bleeding. Actuarial survival for all patients was 87.5% at 5 years, 77.9% at 10 years, and 58.8% at 15 years. There were no deaths within the first 30 days after surgery. These results show that non-shunt operation is useful in preventing bleeding from esophageal varices in patients with IPH.

Adolescent↗
PubMed1998

The protective effects of CP-060S on ischaemia- and reperfusion- induced arrhythmias in anaesthetized rats.

1. CP-060S is a novel sodium and calcium overload inhibitor, and is also characterized as a calcium channel blocker. As these activities have each been shown independently to ameliorate ischaemia damage in the myocardium, the combination may synergistically exert cardioprotection. In this study, therefore, the protective effect of CP-060S against ischaemia- and reperfusion-induced arrhythmia was evaluated in anesthetized rats. 2. Rats were anaesthetized with pentobarbitone, and the left anterior descending coronary artery was occluded for either 5 min with subsequent reperfusion (a reperfusion-induced arrhythmia model) or 30 min without (an ischaemia-induced arrhythmia model). All drugs were intravenously administered 1 min before the onset of occlusion. 3. In the reperfusion-induced arrhythmia model, the animals in the vehicle-treated group exhibited ventricular tachycardia (VT) in 100%, ventricular fibrillation (VF) in 89%, and death caused by sustained VF in 56%. CP-060S (30-300 microg kg(-1)) dose-dependently suppressed the incidences of arrhythmias. Significant decreases occurred at 100 microg kg(-1) in VF (incidence: 42%) and mortality (8%), and at 300 microg kg(-1) in VT (50%), VF (33%) and mortality (8%). This protective effect of CP-060S was 10 times more potent than that of a pure calcium channel blocker, diltiazem (30-1000 microg kg(-1)) we tested, in terms of effective dose ranges. As both drugs decreased myocardial oxygen consumption estimated by rate-pressure product to a similar extent, the calcium channel blocking activity of CP-060S would not seem to be sufficient to explain its potency. 4. In the same model, co-administration of ineffective doses of diltiazem (300 microg kg(-1)) and a sodium and calcium overload inhibitor, R56865 (100 microg kg(-1)), produced significant suppression of VT (incidence: 62%), VF (46%) and mortality (8%). By contrast, co-administration of R56865 at the same dose with CP-060S (300 microg kg(-1)) did not add to the effect of a single treatment of CP-060S. 5. In the ischaemia-induced arrhythmia model, CP-060S (300 microg kg(-1)) significantly decreased the incidence of VF from 75% to 29%, whereas diltiazem (1 mg kg(-1)) was ineffective. 6. These results suggest that CP-060S inhibits both ischaemia- and reperfusion-induced arrhythmia. The combination of the calcium channel blocking effect and the calcium overload inhibition was hypothesized to contribute to these potently protective effects.

Animals↗
PubMed1998

CP-060S, a novel cardioprotective drug, limits myocardial infarct size in anesthetized dogs.

The myocardial infarct size (IS)-limiting effect of CP-060S, a novel cardioprotective drug that prevents Na+-, Ca2+-overload and has Ca2+ channel-blocking activity, was compared with that of diltiazem, a pure Ca2+ antagonist, to determine whether the prevention of Na+-, Ca2+-overload contributes to this IS-limiting effect. Dogs were subjected to 90 min of left circumflex coronary artery (LCx) occlusion followed by 5 h of reperfusion. Either CP-060S (300 microg/kg) or diltiazem (600 microg/kg) was administered intravenously 20 min before the occlusion. CP-060S significantly limited IS compared with that of vehicle (percentage of the area at risk: vehicle, 50.64 +/- 6.08%; CP-060S, 21.13 +/- 3.75%; p < 0.01 vs. vehicle). Although diltiazem exerted a significant decrease in rate-pressure product (RPP; an index of myocardial oxygen consumption) during occlusion equal to that of CP-060S, diltiazem did not significantly reduce IS (33.90 +/- 4.30%). Regional myocardial blood flow (RBF) was not significantly different between any of the groups. Therefore the IS-limiting effect of CP-060S cannot be explained in terms of changes in RPP or RBF. Thus the IS limitation induced by CP-060S is probably the consequence of a direct cardioprotective effect on myocytes. The prevention of Na+-, Ca2+-overload may be the primary reason for this IS-limiting effect.

Animals↗
PubMed1998

Adenocarcinoma of the lung in a Steller sea lion (Eumetopias jubatus).

The histological and ultrastructural characteristics of an adenocarcinoma of the lung are described in an about 16-year-old female Steller sea lion with a 1.5 month history of cough and anorexia. The animal had multiple neoplastic nodules in the lungs and diaphragmatic pleura. The bronchial and mediastinal lymph nodes were replaced by neoplastic tissue, and there were several metastatic lesions in the liver and spleen. The lung tumor was characterized by accumulations of encapsulated lesions with central necrosis, and the neoplastic cells showing a papillary growth pattern produced small amounts of mucin. Ultrastructurally, some cells contained basal bodies, and cilia were rarely seen. This neoplasm was considered to be of ciliated bronchial or bronchiolar epithelium origin.

Adenocarcinoma↗
PubMed1998

[Portal hypertensive gastropathy and colopathy].

Gastrointestinal bleeding in patients with portal hypertension is usually secondary to esophageal varices, but massive bleeding from gastric mucosal lesions and colonic mucosal lesions including colorectal varices, have been variably described. These lesions are called portal hypertensive gastropathy and colopathy. The incidence and profile of portal hypertensive gastropathy (PHG) has been frequently reported during the last decade, and many studies showed that development of PHG is influenced by coexisting esophageal varices, absence of major portal systemic shunts, severity of liver disease and sclerotherapy and is directly correlated with portal venous pressure. Although hyperdynamic congestion seems to be the underlying mechanisms for the development of PHG, results of gastric mucosal blood flow in patients with PHG is controversial. The treatment can be currently recommended to prevent bleeding, is oral administration of propranolol which decreased portal venous pressure. The clinical feature and profile of portal hypertensive colopathy is classified two groups, which are named colorectal varices and colonic mucosal lesions including vascular spider, dilated fine branching vessels. Although colorectal varices are usually seen at rectum and sigmoid colon, colonic mucosal lesions are seen all part of colon. Significant relationship between colorectal varices and liver disease has been reported and colorectal varices is highly appeared in patients with extrahepatic portal obstruction. Such patients are revealed arteriovenous communications at angiogram. In general, colonic resection or transanal ligation should be the first option for treatment of bleeding colonic varices and colonic mucosal lesions. Transendoscopic sclerotherapy may be an alternate choice.

Colonic Diseases↗
PubMed1997

Stimulation of angiotensin subtype 2 receptor reduces basal cGMP levels in the neointima of rat aorta after balloon injury.

1. The association between the stimulation of the angiotensin subtype 2 receptor (AT2-R) and the change in tissue levels of cyclic nucleotide was assessed on neointima formation in rat aorta following aortic balloon injury. 2. Tissue levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate levels (cAMP) in the injured and uninjured aorta was determined by enzyme immunoassay at baseline and again 30 s after administration of 10(-7) M angiotension II. 3. Injured and uninjured aorta showed no difference in basal levels of cGMP. Angiotension II reduced the basal level of cGMP in the injured aorta only. 4. This decrease was blocked by a selective AT2-R antagonist (PD123319) and by a nonselective angiotensin II antagonist (angiotensin II antipeptide), but not by a selective angiotensin subtype 1 antagonist (CV-11974). 5. Stimulation with a selective AT2-R caused no change in the level of cAMP in the injured or uninjured aorta. 6. Results suggest that stimulation of AT2-R in proliferative neointima leads to a decreased tissue level of cGMP.

Angiotensin II↗
PubMed1996

Bilateral congenital cholesteatoma.

We report a case of bilateral congenital cholesteatoma in a 6-year-old boy. Cholesteatoma was present in both ears around the tympanic isthmus (the only open passage from the tympanic cavity to the attic), extending to behind the horizontal portion of the facial nerve. This patient underwent a total of three canal wall up operations on each side to remove the cholesteatoma completely and improve hearing. This case fulfills the criteria proposed by Derlacki and Clemis in 1965. Bilateral congenital cholesteatoma is a rare condition, but the incidence of congenital cholesteatoma in children has increased recently for the following reasons: Reassessment of the criteria, the introduction of computed tomography, and increased awareness of congenital cholesteatoma. When operating on patients with bilateral cholesteatoma, the best method for preservation of hearing should be chosen. We discuss these problems in the present report.

Cartilage↗
PubMed1996

Effect of endothelin on angiotensin converting enzyme activity in cultured vascular smooth muscle cells.

We evaluated the effect of endothelin-1 (ET) on the angiotensin converting enzyme (ACE) activity in rat aortic smooth muscle cells (VSMCs). ACE activity was determined by radioimmunoassay of the amount of angiotensin II generated after the addition of angiotensin I (500 pg/ml) to cultured VSMCs. The antibody used had less than 0.1% cross-reactivity with angiotensin I. ACE activity increased 1.9-fold 5 hr after the addition of 10(-6) M ET under serum-free conditions. This stimulatory effect of ET on ACE activity in VSMCs was completely inhibited by 10(-7) M captopril. Results suggested that the ACE present in SMCs is stimulated by ET.

Angiotensin II↗
PubMed1996

Vascular smooth muscle relaxation by alpha-adrenoceptor blocking action of dobutamine in isolated rabbit aorta.

We investigated the mechanism of vascular relaxation produced by dobutamine, a positive inotropic agent with beta 1-adrenergic action. Dobutamine concentration-dependently (10 nM-10 microM) relaxed ring segments of rabbit aorta partially precontracted with 1 microM phenylephrine (PE) but did not relax those precontracted with 40 mM K+ or 5 microM prostaglandin F2 alpha (PGF2 alpha). The relaxation was not completely inhibited by pretreatment with 10 microM propranolol. Dobutamine did not significantly increase tissue cyclic AMP levels concomitantly with relaxation as does isoproterenol (ISO) in rabbit aorta. Dobutamine produced a parallel rightward shift in concentration-response curves to PE. The Schild plot analysis resulted in a linear regression of a slope of 1.077 +/- 0.077, which was not significantly different from unity. The pA2 value of dobutamine as compared with PE in rabbit aorta was 6.81 +/- 0.03. Dobutamine causes arterial dilatation mediated not only through a beta-adrenergic action but also through an alpha-adrenergic blocking action in rabbit aorta.

Abortifacient Agents↗
PubMed1995

[Prostaglandin E1 bladder instillations for late-onset hemorrhagic cystitis following allogeneic bone marrow transplantation].

Between July, 1990 and March, 1994, 31 patients with hematological malignancies or severe aplastic anemia underwent allogeneic bone marrow transplantation (BMT) at the Second Department of Internal medicine, Chiba University Hospital. Among the 29 evaluable patients who survived over 100 days after transplant, 11 patients (37.9%) developed late-onset hemorrhagic cystitis with a median time of onset of 57 days (range 11-205) from BMT. Adenovirus type 11 was isolated from the urine of 4 patients. Five patients recovered with fluid hydration and forced diuresis, while 6 patients had persistent gross hematuria with clot formation, 5 of whom also developed hydronephrosis. Seven-day courses of 500 micrograms prostaglandin E1 (PGE1) bladder instillations was initiated to control hematuria in these 6 patients. Complete resolution of gross hematuria was achieved in 4, and partial response with decreased clot formation and partial clearing of the urine was observed after 4 of 9 courses of the treatment. Although all patients experienced bladder spasm or lower abdominal pain during the PGE1 instillations, these symptoms were manageable with sedative drugs and morphine. No systemic side effect was apparent. PGE1 bladder instillations is a safe and useful treatment for severe, life-threatening late-onset hemorrhagic cystitis after allogeneic BMT.

Administration, Intravesical↗
PubMed1995

[A case of pentalogy of Cantrell with tetralogy of Fallot and left ventricular diverticulum].

We report a successful repair of tetralogy of Fallot and left ventricular diverticulum associated with pentaology of Cantrell. The repair consisted of partial infundibular septectomy, closure of ventricular septum, reconstruction of right ventricular outlet using monocuspid transjunctional patch, and resection of left ventricular diverticulum. The infundibulum was extremely elongated, caused by ventricular dextroversion, and the hypoplasia of pulmonary trunk was absent. Therefore, transjunctional patch was longer, even after infundibular septectomy. This report discuss the pathogenesis of these cardiac anomalies and surgical imlication.

Abnormalities, Multiple↗