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Biomedical subjects

K Minami

Publications and source records attributed to K Minami.

At least 127 records · Page 7Linked to original sources

Functional and binding studies of insurmountable antagonism of 606A, a novel AT1-receptor antagonist in rabbit tissues.

Angiotensin AT1-receptor antagonists can be classified into two types, surmountable and insurmountable ones, based on the way they inhibit angiotensin II (AII)-induced vasoconstriction. To elucidate the causes of the difference, we studied how several antagonists associate with and dissociate from AT1-receptor sites by using rabbit adrenal cortical membrane. Four antagonists, 606A, EXP3174, CV11974, and E4177, showed equipotent competitive antagonism when they were added simultaneous with [125I]-AII in binding experiments. However, in AII-induced contraction studies with rabbit aorta, 606A, EXP3174, and CV11974 inhibited the contraction noncompetitively, whereas E4177 inhibited competitively. The longer the pretreatment period with EXP3174 or CV11974, the more effectively the antagonists suppressed AII-induced contraction. However, the suppression of contraction by 606A and E4177 changed little with the length of the pretreatment period. AII-induced contraction of 606A- or E4177-treated aorta recovered easily by washout, but that of CV11974-treated aorta was hard to recover by washout. These results obtained in the aorta were consistent with their characteristics observed in the AII binding study in the rabbit adrenal cortical membrane in cases of EXP3174 and CV11974. The differences between association rate with and dissociation rate from the AT1 receptor of E4177 and 606A were slight, in spite of the clear difference between their action in the contraction study. Because of the variations observed with the four compounds, mechanisms of insurmountable antagonism may not be uniform among AT1-receptor antagonists.

Angiotensin II↗

A case of Pai syndrome.

A fourth patient suspected of having Pai syndrome is described. The female baby had a median cleft of the upper lip, a polypoid skin mass in the right nostril, and a conjunctival lipoma in the right eye. A median alveolar cleft was in the oral cavity. The polypoid skin mass was attached to the nasal septum, and a histologic examination disclosed mature adipose tissue with normal skin and no cartilaginous tissue. A computed tomographic scan revealed a lipoma of the corpus callosum. However, the patient was neurologically normal, and her electroencephalogram was also normal. Her growth and development have been within normal limits, and no convulsions have occurred.

Brain Neoplasms↗

Real-time discrimination of ventricular tachyarrhythmia with Fourier-transform neural network.

We have developed a method to discriminate life-threatening ventricular arrhythmias by observing the QRS complex of the electrocardiogram (ECG) in each heartbeat. Changes in QRS complexes due to rhythm origination and conduction path were observed with the Fourier transform, and three kinds of rhythms were discriminated by a neural network. In this paper, the potential of our method for clinical uses and real-time detection was examined using human surface ECG's and intracardiac electrograms (EGM's). The method achieved high sensitivity and specificity (> or = 0.98) in discrimination of supraventricular rhythms from ventricular ones. We also present a hardware implementation of the algorithm on a commercial single-chip CPU.

Algorithms↗

Comparative study of TA-606, a novel angiotensin II receptor antagonist, with losartan in terms of species difference and orthostatic hypotension.

Losartan is a prodrug type Angiotensin II (Ang II) AT1-receptor antagonist whose efficacy depends on the oxidase activity of individuals. In addition, losartan affects the normal blood pressure and can potentially cause orthostatic hypotension. In this report, we examined effects of TA-606 [(3-pentyloxy)carbonyloxymethyl-5-acetyl-2-n-propyl-3-[2'(1H -tetrazole-5-yl)biphenyl-4-yl]methyl-4,5,6,7-tetrahydro imidazo[4,5-c]pyridine-4-carboxylate hydrochloride], a prodrug type AT1-receptor antagonist, on the Ang II-induced pressor response and hypertension in a dog model, which is known to have lower oxidase activity than other species, and orthostatic hypotension in the rat tilting model. The results indicated that TA-606 was immediately converted to its active form, 606A, after oral administration, and it demonstrated potent inhibition of the Ang II-induced pressor response in conscious normotensive dogs (0.3-3 mg/kg, p.o.). It also had a potent hypotensive effect in conscious 2K,1C-renal hypertensive dogs (0.3-10 mg/kg, p.o.). These effects of TA-606 were 32 and 30 times more potent than those of losartan, respectively. In addition, EXP3174 (1, 10 mg/kg, i.v.), an active metabolite of losartan, but not 606A (1-30 mg/kg, i.v.) showed an orthostatic hypotensive effect in the rat tilting model. These results suggest that TA-606 is an effective Ang II receptor antagonist without the drawbacks of losartan.

Angiotensin II↗

Protective action of angiotensin converting enzyme inhibitors on cardiac hypertrophy in the aortic-banded rat.

Imidapril, enalapril and quinapril were subcutaneously administered to aortic-banded rats by osmotic minipumps to compare the suppressive actions of these angiotensin converting enzyme (ACE) inhibitors on pressure-induced cardiac hypertrophy. Among the three drugs tested, imidapril was most potent for the prevention of cardiac hypertrophy, although equipotent hypotensive doses were used. Imidapril reduced both serum and cardiac ACE activities, while enalapril reduced only the former. Quinapril also reduced both, however, it was less potent at reducing the former compared to imidapril. Moreover, only imidapril significantly decreased left ventricular end diastolic pressure, which tended to be increased by aortic-banding. The lipophilicity of ACE inhibitors could not explain the more potent suppressive action of imidapril on cardiac hypertrophy because the lipophilicity of imidaprilat, an active metabolite of imidapril, was as low as an active metabolite of enalapril; i.e., much lower than an active metabolite of quinapril. The efficacy of ACE inhibitors on pressure-induced cardiac hypertrophy depends not only on an inhibitory effect on cardiac ACE activity, but also on other actions such as their effect on left ventricular end diastolic pressure.

Angiotensin-Converting Enzyme Inhibitors↗

[Descending aorta perfusion through median sternotomy in primary repair of aortic interruption complex].

Circulatory arrest is frequently used in aortic arch reconstruction in pediatric cardiac surgery. However, risks of postoperative acute renal failure and neurological deficit can not be ignored. We performed primary repair of aortic interruption in one-month old girl. After commencing extracorporeal circulation with bicaval venous cannulae and with arterial cannulae into the pulmonary trunk and the innominate artery, the descending aorta was cannulated just superior to the diaphragm. The cannula in the pulmonary trunk was then removed. Arch reconstruction and closure of the ventricular septal defect were performed with continuous perfusion to the brain and the lower body. The extracorporeal circulation time and the aortic cross-clamp time were 117 min and 21 min, respectively. Postoperative renal function was excellent, and there was no finding of neurological deficit. Cannulation of the descending aorta is a simple and useful technique with safety, in arch reconstruction in infants.

Aorta, Thoracic↗

[Prolonged effects of vecuronium in a patient with Crow-Fukase syndrome].

We gave anesthesia to a patient with the Crow-Fukase syndrome. A patient with this syndrome shows polyneuropathy, endocrinological symptoms, skin change, hypertrichosis, organomegaly and osteosclerotic change. We monitored the effects of vecuronium using a neuromuscular blockade monitor. The patient with this syndrome was hypersensitive to vecuronium and its effects lasted longer than usual. It is important to monitor neuromuscular blockade carefully in patients with this syndrome.

Anesthesia, General↗

Hemodynamic follow-up of cardiac allografts from poisoned donors.

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.

Follow-Up Studies↗

Pharmacological analysis of protein kinases responsible for chemotaxis of rat peritoneal neutrophils.

Several types of kinase inhibitors were used to investigate the possible signaling pathways leading to the chemotaxis of rat peritoneal neutrophils toward macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant-1, and platelet-activating factor. The chemotaxis and shape changes induced by each of these chemoattractants were strongly inhibited by a tyrosine kinase inhibitor (herbimycin A) and protein kinase C inhibitors (H-7 (1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride) and calphostin C). The formation of phosphatidyl 3,4,5-triphosphate in chemoattractant-stimulated neutrophils was completely inhibited by 100 nM of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, whereas the chemotaxis toward each of these chemoattractants was partially inhibited (50% inhibition). The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK-1) inhibitor PD 98059 did not inhibit the neutrophil chemotaxis. These findings suggest that the activation of tyrosine kinase and protein kinase C strongly participates in neutrophil chemotaxis and that the activation of phosphatidylinositol 3-kinase is partially involved, but that the activation of mitogen-activated protein kinase is not involved in neutrophil chemotaxis. The cross-linking of the signaling pathways for chemotaxis toward each chemoattractant was also examined.

Animals↗

Extended donor criteria: hemodynamic follow-up of heart transplant recipients receiving a cardiac allograft from donors > or = 60 years of age.

BACKGROUND: Heart transplantation (HT) has become a therapeutic option for patients suffering from endstage heart failure. The increasing demand for cardiac allografts has led to a shift toward extended donor criteria. In a retrospective analysis of 859 HT recipients, we report on the hemodynamic outcome of 19 HT patients who received cardiac allografts from donors > or =60 years of age. METHODS: From March 1989 to December 1997, we performed 883 orthotopic HT in 74 children and 809 adults at our transplant center. Within this period, 19 patients (17 women and 2 men) received cardiac allografts from donors > or =60 years of age. Recipient age ranged from 57 to 78 years (mean, 65+/-5 years). RESULTS: HT could be performed successfully in 19 cases. The early mortality rate was 16% (n=3). The late mortality rate was 37% (n=7). All long-term survivors are stable at New York Heart Association classification II (New York Heart Association Class II = resting hemodynamics: cardiac output normal; left ventricular end diastolic filling pressure elevated; clinically not compromised during mild to moderate workout). Although only 19 patients were retrospectively evaluated, there was a statistically significant (P<0.05) difference in survival among patients who received organs from male (11 vs. 8*) compared with female (8 vs. 2*) (*=death) donors. CONCLUSION: In our experience, it is possible to increase the cardiac donor pool by accepting allografts from donors, preferably female, > or =60 years of age in selected cases without a coronary angiogram, if hemodynamic parameters are in a normal range on mild-to-moderate inotropic support. We do not recommend cardiac allografts from donors > or =60 if there are signs of coronary insufficiency in the electrocardiogram, if left ventricle filling pressures are above normal on mild-to-moderate inotropic support and optimum hemodynamic management, or if there are signs of segmental dysfunction or mitral insufficiency >I in the echocardiogram.

Age Factors↗

Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle.

We have reported that human chymase specifically cleaves big endothelins (ETs) at the Try31-Gly32 bond, and produces novel trachea-constricting 31-amino-acid-length ETs, ETs(1-31). In this study, we investigated the effect of synthetic ETs(1-31) on the contractile activity toward porcine coronary arteries and rat aortae. Although ETs(1-31) exhibited less potent vasoconstrictile activity in these tissues than 21-amino-acid-length ETs(1-21), or a similar extent, ET-1(1-31) caused significantly slower-developing and longer-lasting contraction than ETs(1-21). The ETA receptor antagonist, BQ485, completely inhibited the activity of ET-1(1-31). The ETB receptor antagonist, BQ788, also inhibited the activity of ET-1(1-31) toward rat aortae more efficiently than that ET-1(1-21). Therefore, trachea-constricting peptides ETs(1-31) play roles as vasoconstrictors in a different manner from ETs(1-21).

Animals↗

Sites of volatile anesthetic action on kainate (Glutamate receptor 6) receptors.

Molecular mechanisms of anesthetic action on neurotransmitter receptors are poorly understood. The major excitatory neurotransmitter in the central nervous system is glutamate, and recent studies found that volatile anesthetics inhibit the function of the alpha-amino-3-hydroxyisoxazolepropionic acid subtype of glutamate receptors (e.g. glutamate receptor 3 (GluR3)), but enhance kainate (GluR6) receptor function. We used this dissimilar pharmacology to identify sites of anesthetic action on the kainate GluR6 receptor by constructing chimeric GluR3/GluR6 receptors. Results with chimeric receptors implicated a transmembrane region (TM4) of GluR6 in the action of halothane. Site-directed mutagenesis subsequently showed that a specific amino acid, glycine 819 in TM4, is important for enhancement of receptor function by halothane (0. 2-2 mM). Mutations of Gly-819 also markedly decreased the response to isoflurane (0.2-2 mM), enflurane (0.2-2 mM), and 1-chloro-1,2, 2-trifluorocyclobutane (0.2-2 mM). The nonanesthetics 1, 2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane had no effect on the functions of either wild-type GluR6 or receptors mutated at Gly-819. Ethanol and pentobarbital inhibited the function of both wild-type and mutant receptors. These results suggest that a specific amino acid, Gly-819, is critical for the action of volatile anesthetics, but not of ethanol or pentobarbital, on the GluR6 receptor.

Amino Acid Sequence↗

Aortic valve surgery following previous coronary artery bypass grafting. Impact of calcification and leaflet movement.

We reviewed the reports of 27 patients who had an aortic valve replacement after previous coronary artery bypass grafting. The aortic valve disease -- mainly aortic stenosis -- showed a rapid rate of progression. In the time interval between coronary artery bypass grafting and aortic valve replacement of 4.6+/-2.2 years the peak-to-peak pressure gradient of the aortic valve rose from 20.2+/-14.3 to 63.0+/-22.7 mmHg. As there is a great interest to identify the patients with a high risk of a rapid progression because of a high mortality of an aortic valve replacement as the second cardiac operation following a coronary artery bypass grafting we also reviewed the cardiac catheterisation films and found a high incidence of calcification and impaired aortic valve motion (81.5% of the patients had already calcified aortic valves and 81.5% had a impaired valve motion) at the time of coronary artery bypass grafting. We concluded that if a patient has to be operated for coronary artery disease an aortic valve replacement should be considered not only according to hemodynamic criteria but also when the aortic valve is calcified or its leaflets' motion is impaired.

Aged↗

Stimulatory effect of lymphocyte-derived factor on catecholamine efflux from cultured bovine adrenal medullary cells.

The effects of lymphocytes and their conditioned medium on catecholamine efflux and uptake were examined in cultured bovine adrenal medullary cells. Co-culture of adrenal medullary cells with lymphocytes for 3 days caused an increase in appearance of catecholamines in the culture medium. Treatment of adrenal medullary cells with a conditioned medium prepared from lymphocytes also enhanced the appearance of catecholamines in culture medium in time- (8-48 h) and concentration-dependent manners. Heat treatment of the conditioned medium at 60 and 100 degrees C for 10 min reduced its stimulatory effect to 59 and 20% of control, respectively. After gel filtration on a Sephadex G-25 column or dialysis (<8 kDa molecular mass cutoff), the stimulatory activity of the conditioned medium was found in a high molecular fraction. The conditioned medium had little effect on the activity of lactate dehydrogenase in the medium of cultured adrenal medullary cells and on desipramine-sensitive [3H]norepinephrine uptake by the cells. These findings suggest that lymphocytes release a heat-sensitive factor(s) (molecular mass of more than 8 kDa) which increases efflux of catecholamines from cultured adrenal medullary cells.

Adrenal Medulla↗

Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine.

We tested the influence of blocking sarcoplasmic reticulum (SR) function with ryanodine (1 microM) on stimulation rate-dependent changes of intracellular Ca2+ transients and twitch force in failing human myocardium. Isometrically contracting, electrically stimulated muscle strips from ventricles of 10 end-stage failing human hearts were used. Muscles were loaded with the intracellular Ca2+ indicator aequorin. At stimulation rates from 0.5-3 Hz, intracellular Ca2+ transients and twitch force were simultaneously recorded before and after ryanodine exposure (37 degrees C). Ryanodine significantly reduced twitch force at 1 Hz by 46 +/- 9% and aequorin light by 57 +/- 10% in failing human myocardium (P < 0.05). The blunted or inverse aequorin light- and force-frequency relation became positive after ryanodine: in failing human myocardium, twitch force and aequorin light before ryanodine did not increase with increasing frequency and force decreased significantly at 3 Hz (P < 0.05). After ryanodine, twitch force (P < 0.05) and aequorin light increased with increasing stimulation frequency and were maximum at 2 Hz. The data indicate that inhibition of SR function significantly reduces twitch force and Ca2+ transients in failing human myocardium, but converts the blunted or inverse Ca(2+)- and force-frequency relation into a positive one. We infer that Ca2+ responsible for approximately 50% of twitch force is derived from the SR and approximately 50% from sarcolemmal Ca2+ influx in failing human myocardium. This sarcolemmal component increases at higher stimulation frequencies.

Calcium↗

[A case report of aortoesophageal fistula due to thoracoabdominal aortic aneurysm].

Aortoesophageal fistulas due to thoracic aneurysms are usually fatal, with few reported survivors. A 57-year-old man with aortoesophageal fistula due to thoracoabdominal aortic aneurysm underwent the graft replacement of thoracoabdominal aorta. In the postoperative course, prosthetic graft infection had occurred in the result of residual esophageal fistula. On the 32nd postoperative day (POD), a subtotal esophagectomy was performed and the esophagus was reconstructed by gastrointestinal interposition technique via a retrosternal route. Following the second operative procedure, inflammatory reactions had been improved with systemic administration of antibiotics and continuous irrigation of the infected cavity. On 77th POD, he was discharged.

Aortic Aneurysm, Abdominal↗

Aortic valve replacement after previous coronary artery bypass grafting in a patient with antiphospholipid syndrome.

We report a 55-year-old female patient with antiphospholipid syndrome secondary to systemic lupus erythematosus. The patient had undergone coronary artery bypass grafting for myocardial infarction due to left main trunk stenosis at the age of 52. Subsequently, she developed aortic insufficiency and underwent aortic valve replacement without any hemodynamic or hemostatic problems. Both coronary and valve disease should be considered in patients with antiphospholipid syndrome secondary to systemic lupus erythematosus.

Antiphospholipid Syndrome↗

[A case report of gastric perforation after coronary artery bypass grafting with right gastroepiploic artery].

A 71-year-old man, who had received coronary angioplasty to right coronary artery 1 year before, was admitted because of unstable angina. An urgent CABG was performed using the left internal thoracic artery and the right gastroepiploic artery. Coronary anastomosis was performed under ventricular fibrillation due to porcelain aorta. Seven days after surgery, abdominal pain was suddenly experienced. A chest X-P showed subphrenic free air. So an emergent laparotomy was performed, and a 2 x 2 cm gastric perforation was found on the anterior wall of the greater gastric curvature. Partial gastrectomy was performed. However, he unfortunately died on the 58th postoperative day for multiple organ failure. Pathological examination of the excised gastric wall revealed ischemic change, not ulcer. This gastric perforation was possibly caused by ischemia after harvesting the right gastroepiploic artery.

Aged↗