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Biomedical subjects

A Kanda

Publications and source records attributed to A Kanda.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of semotiadil fumarate, a novel calcium antagonist, on blood pressure and heart rate in conscious spontaneously hypertensive rats.

The acute antihypertensive effects of orally administered semotiadil, a novel calcium antagonist, were compared with those of nifedipine and diltiazem in conscious, unrestrained spontaneously hypertensive rats (SHRs). Semotiadil (10 and 30 mg/kg) produced a dose-dependent hypotension that persisted for 18 hr at 30 mg/kg. Diltiazem (30 and 100 mg/kg) and nifedipine (1 and 3 mg/kg) also exhibited hypotension dose-dependently, but their durations of actions were shorter than that of semotiadil. Semotiadil caused a slight increase in heart rate, while diltiazem and nifedipine caused a bradycardia and a marked tachycardia, respectively. These results suggest that semotiadil has a beneficial property as an antihypertensive drug.

Animals↗
PubMed1993

[Alterations of hemostatic markers in elderly patient with atrial fibrillation without a history of stroke].

To evaluate whether hemostatic abnormalities contribute to the increased risk of stroke, the authors prospectively studied the hemostatic markers (HM) (beta-TG, PF4, FPA, TAT, PIC, D-dimer) in 34 elderly patients with atrial fibrillation (Af) without a history of stroke (mean age 79.2) and 14 age-matched controls. In the Af group FPA was significantly higher than in the control group (p < 0.05). Among them, 8 patients showed a similar abnormal HM pattern as in cardioembolic is chemic stroke and in these, 4/8 patients had valvular disease (VD), 2/8 had hypertension (HT), 2/8 had congestive heart failure (CHF), 1/8 had diabetes mellitus (DM) and 1/8 had hyperlipidemia (HL). Eight patients showed the same abnormal HM pattern as atherothrombotic is chemic stroke and of these, 2/8 had HT as complications. Five patients showed combination of a HM abnormal pattern, that was observed in cardioembolic and atherothromboic ischemic stroke. The other 13 patients showed a normal HM pattern, were in these patients, 4/13 had HT, 1/13 had DM, 1/13 had VD, and 1/13 had CHF. The patients with VD complication tended to have embolic HM abnormality. Contrary to previous reports, nonvalvular Af patients do not necessarily tend to have high risk of cardioembolic stroke. Our data suggest difficulties in clinical diagnosis among Af patients with ischemic stroke whether it is cardio embolic or atherothrombotic.

Aged↗
PubMed1993

[Evaluation of coronary flow and myocardial ischemia by transvenous and intracardiac two-dimensional echocardiography].

The purpose of this study was to observe ventricular wall motion in myocardial ischemia and to image coronary artery flow by transvenous intracardiac two-dimensional echocardiography. Ten mongrel dogs (body weight 24-34 kg) were anesthetized by intravenous sodium pentobarbital (25 mg/kg) and ventilated using a Harvard respirator after tracheotomy. Real-time Doppler two-dimensional echocardiography (ALOKA SSD-870) and a transesophageal probe (5 MHz, 24 elements, diameter 6.8 mm, phased array transducer) were used. The probe was introduced into the right atrium via the femoral vein. Myocardial ischemia was induced under fluoroscopic control by the inflation of a balloon catheter in the coronary artery, or by beads embolization of the coronary artery in closed-chest dogs, or by ligation of the coronary artery after a left or right thoracotomy. The wall motion of the right and left ventricles was observed by using the probe positioned in the lower right atrium. Visualization of the coronary artery and the flow velocity were studied with the probe in the mid right atrium. 1) Imaging: The left coronary artery, left main coronary artery and left anterior descending artery were easily observed by the probe positioned in the mid right atrium. The blood flow velocity in the left main coronary artery was consistently recorded. Changes in the blood flow velocity by coronary vasodilators such as dipyridamole, isosorbide dinitrate and nicorandil were clearly detected. 2) Detection of the myocardial ischemia: During the right coronary artery occlusion the right ventricle showed marked dilatation and hypokinesis, and the interventricular septum showed paradoxical movement and was displaced towards the left ventricular cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Clinically diagnosed corticobasal degeneration (CBD)].

We reported a 67-year-old male, who suffered from apraxia and amnesia for 2 years and for muscle rigidity of right extremities for a year. Neurological examination revealed dysarthria, dysphagia, marked dystonia of right arm, hyperreflexia of all limbs and ataxic gait. He also had dementia and many other higher cortical dysfunction mostly due to left hemisphere damage. No impairment of eye movement was disclosed. Brain MRI as well as CT showed the significant brain atrophy in the left parieto-occipital region. A degenerative atrophy was suspected by 123I-IMP-SPECT and 18F-FDG-PET. By FDG-PET, the decrease of cerebral blood flow and glucose metabolism was detected not only affected unilateral cerebral cortex including primary motor area but ipsilateral basal ganglia and thalamus. Although, it is difficult to distinguish clinically CBD from atypical case of Alzheimer's disease, we speculated that in early stage of dementia, significant unilateral hypoperfusion and hypometabolism of basal ganglia and thalamus is characteristic of CBD.

Aged↗
PubMed1992

Characterization of recombinant human and rat pancreatic phospholipases A2 secreted from Saccharomyces cerevisiae: difference in proteolytic processing.

An expression plasmid for human pancreatic phospholipase A2 in Saccharomyces cerevisiae was constructed by insertion of cDNA encoding its preprophospholipase A2 into a yeast expression vector pAM82. The resulting product secreted in the yeast culture medium was mainly prophospholipase A2, which was the same as the natural proenzyme in all aspects examined, including the higher order structure. However, when the rat preprophospholipase A2 cDNA was manipulated in the same manner, the active phospholipase A2 of the intact mature form was secreted with the proenzyme being hardly detected in the medium. This unexpected favorable result would occur due to cleavage of rat phospholipase A2 pro-peptide by a trypsin-like proteinase in S. cerevisiae. Based on this finding, we constructed a plasmid carrying the sequence coding for the prepro-peptide of rat pancreatic phospholipase A2 behind the PHO5 promoter in the pAM82 vector, which leads to the secretion of heterologous proteins as their mature form. The use of this plasmid led to secretion of biologically active human pancreatic secretory trypsin inhibitor and a glutamic acid-specific endopeptidase from Staphylococcus aureus ATCC 12600, which are eukaryote and prokaryote proteins, respectively, in the culture medium of S. cerevisiae.

Amino Acid Sequence↗
PubMed1992

[Serum alpha 1-antichymotrypsin in senile dementia].

To evaluate the clinical significance of serum alpha 1-Antichymotrypsin (ACT) as an early diagnostic marker of senile dementia of Alzheimer type (SDAT), we measured 333 healthy and not demented elderly subjects, 27 cases SDAT and 25 cases of vascular dementia (VD). For the measurement, a new high-sensitivity method, double antibody radioimmunoassay method was developed. In healthy elderly subjects, the mean value of serum ACT was 0.229 mg/ml. A tendency towards increase of ACT with aging was noted but was not significant. The serum level of ACT in the SDAT patients was significantly higher (0.309 mg/ml) compared with the healthy elderly subjects and the VD patients (0.226 mg/ml) (p < 0.01). We concluded that in the patients with SDAT, there was an overproduction of ACT and the serum value of ACT was markedly elevated. The measurement of serum ACT is very useful (sensitivity = 88.9%, specificity = 68.7%; cut-off value = 0.250 mg/ml) for the early differential diagnosis of senile dementia.

Aged↗
PubMed1992

Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs.

Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension.

Administration, Oral↗
PubMed1992

[A case of nonobstructive hypertrophic cardiomyopathy associated with ventricular tachycardia and sick sinus syndrome].

We examined, a 64 year old man with hypertrophic nonobstructive cardiomyopathy (HNCM) accompanied with dizziness. Twenty-four hour ECG monitoring showed sinus bradycardia and sinoatrial block. Electrophysiologic study demonstrated inducible sustained ventricular tachycardia (VT) by continuous rapid high right atrum pacing during which systolic blood pressure fell to 40 mmHg. Induced VT degenerated into ventricular fibrillation in ten seconds. We implanted a DDD pacemaker for sick sinus syndrome (SSS) and administrated 90mg/day of diltiazem for VT. Treadmill exercise test was carried out while the patient was taking diltiazem and no arrhythmia was induced. This case of HNCM is rare in that he presented both sick sinus syndrome and sustained VT.

Aged↗
PubMed1991

[Virological evaluation of mumps meningitis following vaccination against mumps].

1) We report 5 cases of aseptic meningitis following vaccination against mumps. Of the 5 cases, 4 cases were diagnosed as mumps meningitis. 2 cases received monovalent mumps vaccine and the other 2 MMR vaccine. They consisted of 2 boys and 2 girls, aged 2 years and 2 months to 4 years and 5 months. The period between vaccination and symptoms ranged from 15 days to 20 days (mean 18 days). Cerebrospinal fluid of the cases contained 507 to 2688 cells/mm3. Eruption was observed in the 2 cases who received MMR vaccine, while parotid swelling was not seen in any case. 2) In all 4 cases, IgM antibody to mumps virus in the cerebrospinal fluid was detected by the ELISA or EIA methods. Causative organism of the fifth case was obscure. 3) PCR (Polymerase Chain Reaction) tests revealed that mumps virus isolated from 2 cases were of vaccine strain origin. 4) To evaluate the frequency of mumps meningitis following vaccination, it seems important to investigate carefully the number of children who received the vaccine and to exclude the cases of aseptic meningitis caused by other agents. On the other hand, cases of young infants tend to be overlooked because of atypical signs.

Child, Preschool↗
PubMed1991

Development of a radioimmunoassay for human group-II phospholipase A2 and demonstration of postoperative elevation.

A radioimmunoassay (RIA) for the determination of human group-II phospholipase A2 (M-PLA2) has been developed. M-PLA2 was purified from human spleen. Monoclonal antibody (IgG) was prepared by fusion of splenic cells from immunized mice with M-PLA2 and the mouse myeloma cell line NS-1. The RIA was carried out by a single antibody method. The assay is sensitive (0.78 micrograms/l), reproducible and specific. In healthy individuals, the serum M-PLA2 concentration ranges from 1.4 to 4.2 micrograms/l, the average being 2.2 +/- 0.1 micrograms/l (mean +/- SE). Using the RIA, we found increased serum M-PLA2 in patients with various infections and malignant tumors. We also showed the postoperative transient elevation of serum M-PLA2 in cases without any infectious complications. The elevation was independent of the surgical procedure or site. The maximum serum M-PLA2 level was seen on the 2nd to 4th postoperative day. In these patients, the serum M-PLA2 and C-reactive protein levels were significantly correlated. The present study indicated that serum M-PLA2 is an acute phase reactant.

Acute-Phase Proteins↗
PubMed1991

Features of the acute hypotensive action of carvedilol and its ameliorating effect on myocardial ischemia.

The objective of the present experiment was to investigate the following parameters concerning carvedilol: (a) the time course of acute hypotensive effect, (b) the influence of alpha 1-adrenoceptor blockade on the acute hypotension induced by carvedilol, and (c) the effect of carvedilol on myocardial ischemia. In conscious, catheter-implanted spontaneously hypertensive rats, carvedilol at the doses of 10 and 30 mg/kg, p.o., dose-dependently decreased mean arterial blood pressure (MAP). At 10 mg/kg, MAP was significantly decreased for 16 h, and at 30 mg/kg, it was significantly decreased until 24 h after administration. Thus, carvedilol shows long-lasting antihypertensive effects by a single oral administration. In anesthetized Wistar rats, intravenous administration of carvedilol (0.3 mg/kg) produced an immediate decrease in blood pressure. On the other hand, in phentolamine-pretreated rats whose blood pressure was restored by prostaglandin F2 alpha, the acute hypotension produced by carvedilol was abolished similarly to the case with labetalol (0.6 mg/kg) and prazosin (0.01 mg/kg). The hypotensive effect of either hydralazine (0.2 mg/kg) or nitroprusside Na (0.005 mg/kg) was attenuated by about 20%, whereas the effect of diltiazem (0.2 mg/kg) was not attenuated. These results indicate that alpha 1-adrenoceptor blocking action of carvedilol contributes to a large extent to the acute hypotensive effect of this drug. In anesthetized open-chest dogs, myocardial ischemia was produced by partial occlusion of the left anterior descending coronary artery. Myocardial pH of the ischemic region was decreased by about 0.7 units. Carvedilol at the doses of 0.1 and 0.3 mg/kg, i.v., dose-dependently attenuated the decrease in myocardial pH accompanied with decreases in MAP and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

Uricosuric and diuretic activities of DR-3438 in dogs and rabbits.

The purpose of this study was to evaluate the uricosuric and diuretic properties of the new diuretic agent DR-3438. In the conventional clearance studies in urate-loaded dogs, intravenous injection of DR-3438 (3-30 mg/kg) resulted in dose-related increases in fractional excretion of urate (FEua), urine flow and sodium excretion. At doses causing similar natriuresis, tienilic acid (50 mg/kg, i.v.) markedly increased the FEua value, whereas indacrinone (1 mg/kg, i.v.) had no significant effect on it. Trichloromethiazide (1 mg/kg, i.v.) and furosemide (0.3 mg/kg, i.v.) tended to decrease the FEua. Thus, the uricosuric activity of DR-3438 (30 mg/kg) was 0.6-fold that of tienilic acid and 3.4-fold that of indacrinone. In contrast, in urate-loaded rabbits that exhibit net tubular secretion of urate, intravenous DR-3438 (30 mg/kg) produced a significant decrease in FEua. Stop-flow studies in dogs revealed that DR-3438 (30 mg/kg) blocks both urate reabsorption and p-aminohippurate secretion in the proximal segment of the nephron and strongly inhibits reabsorption of water, sodium and potassium in the distal segments. These results suggest that DR-3438 exerts uricosuric activity through blocking urate transport in the proximal tubules and diuretic and saluretic activities by inhibiting water and sodium reabsorption in the distal segment of the nephron.

Animals↗
PubMed1989

The primary structure of a membrane-associated phospholipase A2 from human spleen.

The complete primary structure of membrane-associated phospholipase A2 purified from a human splenic membrane fraction was determined by sequence analysis of the peptides generated by lysyl endopeptidase and Staphylococcus aureus V8 protease cleavage. The enzyme consists of 124 amino acid residues corresponding to a molecular weight of 13,904. The primary structure reveals the characteristics of Group II phospholipases A2 and a large ratio of basic amino acid residues to acidic ones, that ratio being 3.4 : 1.

Amino Acid Sequence↗
PubMed1989

cDNA cloning and sequence determination of rat membrane-associated phospholipase A2.

Based on the partial amino acid sequences of membrane-associated phospholipase A2 (PLA2M), belonging to group II, purified from rat spleen, the cDNA encoding PLA2M was cloned by a new cloning strategy utilizing enzymatic cDNA amplification. At the N-terminus of the coded 146 residues, which were deduced from the cDNA sequence, the putative signal peptide was found despite the tight adherence of this enzyme to the membrane. The sequence of rat PLA2M exhibits 75% homology with that of human group II PLA2 in the protein-coding region. The result of RNA blot analysis showed that rat ileal mucosa contains the largest amount of the PLA2 transcript among the tissues examined.

Amino Acid Sequence↗
PubMed1989

Inhibition of vagal transmission by cardiac sympathetic nerve stimulation in the dog: possible involvement of opioid receptor.

The inhibitory effect of cardiac sympathetic nerve stimulation (SNS) on bradycardic response to vagal nerve stimulation was examined in anesthetized dogs pretreated with atenolol or propranolol to prevent tachycardia caused by SNS or norepinephrine infusion. The amplitudes of vagal bradycardia (0.5, 1, 2, and 4 Hz) during 10 and 30 Hz of SNS were significantly smaller than those during the resting state. The inhibitory effect of 10 Hz of SNS was neither affected by prazosin (10, 30 and 100 micrograms/kg i.v.) nor by yohimbine (10, 30 and 100 micrograms/kg i.v.). The SNS-induced inhibition of vagal bradycardia was inhibited by naloxone (0.3 and 1 mg/kg i.v.) or by naltrexone (0.3 and 1 mg/kg i.v.). Vagal bradycardia was unaffected by intracoronary infusion of norepinephrine (3 micrograms/min) into the right coronary artery, whereas it was effectively inhibited by leu-enkephalin (10, 30 and 100 micrograms/kg i.v.). Bradycardia induced by intracoronary injection of methacholine (0.3, 1 and 3 micrograms) was unaffected by SNS. These results suggest that a presynaptic alpha adrenoceptor mechanism is not involved in the SNS-induced inhibition of vagal bradycardia in the dog, and suggest further that an opioid receptor mechanism may be responsible for the inhibition.

Blood Pressure↗
PubMed1988

Analysis of the mechanism underlying the vasodilator action of carvedilol in pithed spontaneously hypertensive rats.

The present experiments were carried out to examine the vasodilator mechanism(s) of carvedilol by use of pithed spontaneously hypertensive rats (SHR). Animals were pithed and the dose-pressor response curves to various agonists were obtained 0.5 or 1 hour after oral administration of either carvedilol (30 mg/kg), labetalol (60 mg/kg), prazosin (0.1 mg/kg) or hydralazine (3 mg/kg). These doses of drugs caused approximately equihypotensive responses in the conscious state. Carvedilol significantly shifted the dose-pressor response curve to the right for phenylephrine but not for B-HT 920, angiotensin II and vasopressin. Labetalol and prazosin also significantly shifted the dose-response curve to the right for phenylephrine but not for angiotensin II. The rank order of inhibitory action on the phenylephrine response was prazosin greater than labetalol greater than carvedilol. In addition, carvedilol produced a slight but significant inhibition of the pressor responses to serotonin (5-hydroxytryptamine), which was nearly identical in magnitude to that seen with hydralazine. These results suggest that the vasodilator action of carvedilol is mainly attributed to alpha 1-adrenoceptor blockade, although additional non-adrenergic mechanism(s) of action cannot be excluded.

Adrenergic beta-Antagonists↗
PubMed1987

Enhancement by yohimbine of nicotine- and dimethylphenylpiperadinium-induced release of norepinephrine from cardiac sympathetic nerves of the dog: interaction of presynaptic alpha and nicotinic receptors.

The effect of yohimbine on nicotine- and dimethylphenylpiperadinium (DMPP)-induced release of norepinephrine (NE) from sympathetic cardiac nerves of the dog was examined in order to elucidate the interaction of presynaptic alpha and nicotinic receptors. Intracoronary infusion of nicotine (300 or 500 micrograms/min) or DMPP (100 or 300 micrograms/min) into the left circumflex artery increased coronary sinus output of NE (NE output), left ventricular dp/dt maximum (LV dp/dt max) and coronary sinus blood flow. The nicotine-induced increases in NE output, LV dp/dt max and coronary sinus blood flow were enhanced by simultaneous yohimbine infusion in doses of 10 and 30 micrograms/min into the same artery, and were attenuated by the drug in a dose of 100 micrograms/min. The DMPP-induced increases were enhanced by 10 micrograms/min of yohimbine infusion, but the enhancement was decreased by 30 and 100 micrograms/min. Yohimbine did not modify increases in NE output, LV dp/dt max and coronary sinus blood flow induced by intracoronary infusion of tyramine (100 micrograms/min). We have reported previously that yohimbine in the dose range used enhanced cardiac sympathetic nerve stimulation-induced increases in these parameters in a dose-dependent manner in the same preparation. The enhancement by yohimbine of nicotinic receptor-mediated NE release would be due to the blockade of presynaptic alpha-2 adrenoceptors. Therefore, it is suggested that presynaptic alpha-2 adrenoceptor-mediated feedback control operates on the process of NE release induced by nicotinic receptor activation as well as nerve stimulation. Although the mechanism of loss of the enhancement of the nicotinic effect by the large dose of yohimbine is not known, the possible mechanisms are discussed.

Animals↗