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Biomedical subjects

M Imai

Publications and source records attributed to M Imai.

At least 163 records · Page 9Linked to original sources

beta-Adrenoreceptor antagonistic actions and mutagenicities of R(+)- and S(-)-enantiomers of N-desisopropylpropranolol and its N-acetyl conjugate.

Enantiospecific acetyl conjugation was examined in the rat liver 105000 x g supernatant (cytosol) system using racemic 1-amino-3-(1-naphthyloxy)-2-propanol (NDP), a N-desisopropyl metabolite of propranolol. From the results of chiral separative determination of the samples by HPLC using a Chiralcel OD-R column, more remarkable enantiospecificity was observed in the R(+)-enantiomer on NDP elimination and N-acetyl conjugate (AcNDP) formation. Next, the strength of beta-adrenoceptor antagonistic actions and mutagenicities was compared between R(+)- and S(-)-enantiomers of NDP and AcNDP, respectively. In the case of NDP, both enantiomers possessed weak beta1-adrenoceptor antagonistic effects on isoproterenol-induced positive inotropic and chronotropic actions in the left and right atria isolated from a guinea pig. These actions of R(+)- and S(-)-NDP were 1700-times and 100-times less potent, respectively, than those of propranolol. beta2-Adrenoceptor antagonistic actions of R(+)- and S(-)-NDP in the trachea were 1600-times and 200-times less potent, respectively, than those of propranolol. Enantiospecificity was observed in the beta-adrenoceptor antagonistic action of S(-)-NDP, while R(+)-NDP and both enantiomers of AcNDP appeared to be negligible in this action. On the other hand, the mutagenicities of each enantiomer were examined by the Ames method using 13 kinds of Salmonella typhimurium strains. In the case of AcNDP, the numbers of colonies increased according to the substrate concentration only when rat liver 9000 x g supernatant fraction (S-9 mixture) was added to the plates containing TA100, YG1029, TA104 and YG3003, and then enantiospecificity was observed in the mutagenicity of S(-)-AcNDP. Thus, the ultimate mutagen might be an active metabolite formed mainly from S(-)-AcNDP. Despite of the addition of rat liver S-9 mixture, R(+)-AcNDP and both enantiomers of NDP did not indicate mutagenicity.

Adrenergic beta-Antagonists↗

CP2289, a new 5-HT3 receptor ligand: agonistic activities on gastroenteric motility.

A new 5-HT3 receptor ligand, CP2289, was synthesized and pharmacologically tested. Although CP2289 inhibited the Bezold-Jarisch reflex, it contracted the excised ileal muscle of mice, rats and guinea pigs. This response may reflect a partial agonist character of CP2289 in the gut. In vivo antiemetic and gastric emptying tests gave similar results.

Animals↗

Idiopathic restrictive cardiomyopathy with diffuse perimyocytic fibrosis--a rare observation.

Idiopathic restrictive cardiomyopathy (RCM) is rare. Even today little is understood of its etiology or underlying mechanisms, and definitive diagnostic criteria are lacking. In this report, we describe a case of idiopathic RCM in a young Japanese woman who died while awaiting cardiac transplantation during the 5-year course of the disease. Rare pathologic findings of diffuse perimyocytic fibrosis were revealed at autopsy.

Adult↗

Measurement of reverse transcriptase of feline immunodeficiency virus by poly A-linked colorimetric assay.

The method of the poly A-linked colorimetric reverse transcriptase assay (PAC-RTA) was developed and evaluated for the measurement of Mg(2+)-dependent reverse transcriptase (RT) activity of feline immunodeficiency virus (FIV). PAC-RTA was first evaluated for the detection of RT activity in the culture supernatant of FIV Petaluma strain. The detection limit of RT activity by PAC-RTA was about 10-fold better than that by the conventional non-radioisotopic RT assay kit. Then, PAC-RTA was evaluated for the indication of FIV isolation from cats naturally infected with FIV. FIV was isolated from peripheral blood mononuclear cells of 9 FIV-seropositive cats. The time course appearance of RT activity measured by PAC-RTA corresponded with the analysis of FIV antigen expression by indirect immunofluorescence. Finally, PAC-RTA evaluated the drug susceptibility of FIV. MYA-1 cells (feline T-lymphoblastoid cells) were infected with FIV and were cultured in the presence of various concentrations of anti-human immunodeficiency virus agents such as azidothymidine (AZT) or dextran sulfate. An inverse relationship between the RT activities and the concentrations of these agents in the culture supernatant was confirmed by PAC-RTA. PAC-RTA is easy to perform without using radioactive materials, and one plate can handle 96 samples at one time. By monitoring the RT activity, this assay is a useful method for FIV studies such as viral replication and drug susceptibility.

Animals↗

Quantitative measurement of antibody inhibiting reverse transcriptase activity in cats naturally infected with feline immunodeficiency virus.

Quantitative measurement of reverse transcriptase-inhibiting (RTI) antibodies in Japanese household cats naturally infected with feline immunodeficiency virus (FIV) was performed by poly A-linked colorimetric reverse transcriptase assay (PAC-RTA). Eight FIV-seropositive plasma samples were diluted twofold from 1:10 to 1:160 and incubated with FIV RT. Fifty percent RTI activity (RTI50) was calculated from a dose response PAC-RTA curve. The plasma of FIV-seropositive cats showed different RTI activities against two Japanese isolates and Petaluma strain. Six of eight plasma samples showed RTI activities against the Japanese isolates (subtype B), but only one showed RTI activity against Petaluma strain (subtype A). It is important to use the appropriate strain as a source of RT for detection of RTI antibody in cats.

Animals↗

Recovery of iodine-123 metaiodobenzylguanidine uptake associated with left ventricular functional recovery in a patient with dilated cardiomyopathy. Endomyocardial histological findings before and after the improvement of uptake.

A 58-year-old man with idiopathic dilated cardiomyopathy was treated with incremental administration of a beta-blocker (metoprolol) and an angiotensin converting enzyme inhibitor (enarapril). The left ventricular end-diastolic dimension and ejection fraction improved in 8 months from 83.3 mm and 17.3% to 46 mm and 69%, respectively. The washout ratio and heart-to-mediastinum ratio depicted on the delayed image for iodine-123 metaiodobenzylguanidine 123I-MIBG) uptake improved from 61.7% and 1.34 to 23.1% and 1.85, respectively, in association with improvement of left ventricular indices. Successive endomyocardial biopsy specimens disclosed reduction of the degrees of vacuolation, staining irregularity, and deformity of myocyte cytoplasm and nucleus compared to the findings before therapy. In this patient with dilated cardiomyopathy 123I-MIBG scintigraphy was useful for the evaluation of the effects of therapy. We conclude that it may be informative in the estimation of the histopathological abnormalities of the myocardium.

3-Iodobenzylguanidine↗

An overview of animal toxicology studies with bicalutamide (ICI 176,334).

The toxicological profile of bicalutamide in animals following acute and chronic dosing is closely associated with the drug's non-steroidal anti-androgenic pharmacological activity. Bicalutamide produces typical effects of an anti-androgen, including atrophy of the prostate, testis and seminal vesicles and Leydig cell hyperplasia resulting from inhibition of pituitary feedback by testosterone. Subsequent benign Leydig cell tumors were seen in rats, but Leydig cell hyperplasia has not been observed in patients. Bicalutamide causes liver enlargement and is a mixed function oxidase inducer in rodents and dogs, but not man. These effects lead to thyroid hypertrophy and adenoma in the rat and hepatocellular carcinoma in the male mouse. In vitro and in vivo genotoxicity studies have all given negative results. Bicalutamide also caused a reversible shortening of the electrocardiographic P-R interval in the dog without any associated pathology. This change was not detected in ECG monitoring during clinical trials. In conclusion, bicalutamide produced a range of pharmacological effects, as well as liver enlargement with enzyme induction and dog ECG changes in preclinical toxicity studies in rodents and dogs. Only the pharmacological changes were found to be relevant to human usage.

Androgen Antagonists↗

A new trocar approach insertion site for laparoscopic surgery: the xiphoidal approach.

Laparoscopic cholecystectomy (LC) has become the standard treatment for removing a diseased gallbladder. Endoscopic surgical techniques are used to perform appendectomies, bowel resections, and gastrectomies. This minimally invasive surgery is favored because it decreases the patients' postoperative pain and length of hospitalization. However the incidence of complications with this technique is not negligible. As a new technique is evolving, the potential for complications is high. This increase in complication rate is undoubtedly due to inexperience during the initial phase of the surgeon's learning curve. Demand for the procedure has required rapid training and credentialing of many surgeons with limited experience in endoscopy and the use of instruments that allow only limited viewing of abdominal structures.

Journal Article↗

[Mitral valve replacement and closure of ventricular septal defect in the first two months of life].

A 2-month-old female infant weighing 4.2 kg was admitted with severe congestive heart failure and respiratory distress. The patient was operated upon under a diagnosis of severe congenital mitral regurgitation and ventricular septal defect. There was thickening of the anterior leaflet and short thickened chordae. The valve was judged not amenable to repair and it was replaced with a 17 mm St. Jude Medical valve. She was extubated on the 5th postoperative day. Post operative anti-coagulant therapy was initiated with warfarin potassium, dipyridamole and ticlopidine hydrochloride. The postoperative course was uneventful and the patient is doing well 9 months after the operation.

Female↗

[The HIV/AIDS Epidemic in Cambodia].

In December 1995 and March 1996, we visited institutes which were conducting epidemiological studied of HIV/AIDS in Cambodia, and obtained data for further collaborative study between Japan and Cambodia. Data included information on AIDS patients and HIV infected persons, and behavioral epidemiology of CSWs (Commercial Sex Workers). The cumulative reported number of AIDS patients and HIV infected persons in Cambodia was 86 and 2,536 cases respectively in 1995. The cause of infection was mostly heterosexual contact with very few cases from injecting drug use (IDU) and other causes. The seroprevalence rate of HIV antibody among donated blood rapidly increased from 0.08% in 1991 to 4.47% in 1995, and those among CSWs and pregnant women were 37.9% and 2.6%, respectively, in 1995. The average rate of condom use among CSWs was 66%, but the rate of usual usage was only 14%. These results indicate that the HIV/AIDS epidemic had spread rapidly through CSWs, that it had been spread among peoples in communities, and that usage of condoms among CSWs was insufficient in Cambodia. Without strong countermeasures against HIV/AIDS in this country, HIV/AIDS epidemic may spread significantly to not only peoples in this country but also those in neighbouring countries in the future.

Acquired Immunodeficiency Syndrome↗

[DDD pacemaker implantation--cardiac pacemaker tips in the left atrium and ventricle by the left thoracotomy].

Recently DDD pacemaker implantation for the children has undergone trials world wide; though regarding the approach, ways and positions of the epicardial lead, a few problems are still remained to be discussed. Now we report 9 cases (5 males, 4 females) of DDD pacemaker implantations by the left anterolateral thoracotomy approach. The 9 patients weighing 6.5 to 33 kg, were aged 11 months to 12 years (mean 6 years) of whom male 5, female 4 with degree of Block; 2 and 7. To all patients the stab-in type epicardial tips were implanted in the left atrium, the screw-in type ventricular epicardial tips were in the left ventricle by the 4th intercostal thoracotomy, and the pacemaker generators were beneath the fascia of the abdominal rectus muscle. We have no sensing and pacing failure, all pacemakers are working in the DDD mode well.

Child↗

Unifocalization and systemic-to-pulmonary shunt using internal mammary artery for tetralogy of Fallot and pulmonary atresia with diminutive pulmonary artery and arborization anomaly.

We report successful palliation of tetralogy of Fallot and pulmonary atresia with diminutive pulmonary arteries and arborization anomaly. Unifocalization and systemic-to-pulmonary artery shunt using an internal mammary artery were successfully performed. The internal mammary artery shunt provided a sufficient blood supply for a diminutive and fragile pulmonary artery, and brought a progressive improvement of exercise intolerance and polycythemia probably due to the growth potential.

Cardiovascular Surgical Procedures↗

[Hemodynamic effects of amrinone in children during cardiopulmonary bypass and postoperative 12 hours].

Hemodynamic effects of amrinone in children during cardiopulmonary bypass (CPB) and postoperative 12 hours were studied. In 10 patients undergoing open heart surgery, 1 mg/kg of amrinone was infused as the initial CPB dose and 5 - 10 micrograms/kg/min of amrinone was continuously administered as the maintenance dose during CPB and postoperative 12 hours. Amrinone levels ranged from 0.9 to 1.4 micrograms/ml during CPB and postoperative 12 hours. After infusion of amrinone, mean arterial blood pressure decreased significantly, but other parameters did not show remarkable change. The administration of amrinone during CPB showed enough vasodilating effect and decreased the need of conventionally used other vasodilators (nitroglycerin or prostaglandin E1). The postoperative course of 10 patients was clinically uneventful. The administration of amrinone in 10 patients did not produce thrombocytopenia compared with the control group (5 patients) in the postoperative period. In conclusion, the administration of amrinone during CPB and postoperative 12 hours in children was useful in producing enough vasodilating effect without major side effect.

Amrinone↗

[Effects of aprotinin on blood loss reduction in children undergoing repair of tetralogy of Fallot].

The effect of aprotinin on the blood loss reduction was studied in children undergoing repair of tetralogy of Fallot. We administered aprotinin to consecutive 21 patients during the repair of tetralogy of Fallot and examined the blood loss and operative time in comparison with that in a control group of 20 patients. 30,000 KIU/kg of aprotinin was infused as the initial cardiopulmonary bypass (CPB) dose and 10,000 KIU/kg/hr was continuously administered as the maintenance dose during CPB. There was no resternotomy case due to bleeding and no operative death in both groups. Blood loss after CPB during operation and total blood loss during operation were significantly lower in aprotinin group than in control group. There were no differences between two groups in the volume of chest tube drainage in the postoperative 24 hours and the duration of chest tube drainage. Time from cessation of CPB to skin closure and total operative time were significantly shorter in aprotinin group than in control group. In conclusion, aprotinin was effective on the reduction of blood loss and the shortening of operative time in children undergoing repair of tetralogy of Fallot.

Aprotinin↗

[A case of PEHO (progressive encephalopathy with edema, hypsarrhythmia and optic atrophy) syndrome: changes in clinical and neuroradiological findings].

We reported serial clinical, radiological, and neurophysiological findings of a patient with PEHO (progressive encephalopathy with edema, hypsarrhythmia and optic atrophy) syndrome. The case was a 4-year-and-8-month-old boy. He had no apparent problems during pregnancy, but after his birth severe hypotonia and developmental delay were evident. Infantile spasms appeared at 3 months of age, and progressive opisthotonic posture and loss of his visual acuity at 8 months. Eye fixation was lost, and optic atrophy was observed. Seizures and progressive atrophy of the cerebellum and brainstem developed during the same period. These findings of our case support the hypothesis that brainstem lesions are related to infantile spasms.

Brain Diseases↗