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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 595 records · Page 33Linked to original sources

Tolbutamide inhibits cAMP-dependent phosphorylation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

The activity of a bifunctional enzyme, liver 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (F-2,6-Pase), which regulates the level of liver fructose-2,6-bisphosphate (F-2,6-P2), the most potent activator of PFK, is modulated by its phosphorylation rate mainly catalyzed by cAMP-dependent protein kinase A (PKA). To elucidate the action mechanism of sulfonylurea on liver F-2,6-P2 production, effects of tolbutamide on PKA-dependent phosphorylation of purified liver PFK-2/F-2,6-Phase protein and on kinase and phosphatase activities of the purified enzyme were examined in vitro. The purified enzyme was phosphorylated in the presence of the catalytic subunit of PKA, and tolbutamide inhibited the enzyme phosphorylation catalyzed by PKA in a dose-dependent manner. By adding the same dosages of tolbutamide used in the phosphorylation experiment, reduced activity of PFK-2 and increased activity of F-2,6-Pase in the presence of PKA were restored to the levels observed in the absence of PKA. On the other hand, carboxytolbutamide, an inactive metabolite of tolbutamide, had little effect on enzyme phosphorylation and activity. Our results indicate that tolbutamide inhibits a phosphorylation of the liver PFK-2/F-2,6-Pase catalyzed by PKA along with an activation of PFK-2 and an inactivation of F-2,6-Pase, leading to liver F-2,6-P2 production.

Animals↗

[Proposal for the nosocomial infection control of methicillin-resistant Staphylococcus aureus (MRSA)].

To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospital environments, quantitative isolation of MRSA from environmental and human specimens was performed. It was found that as many as 6 x 10(4) colony forming units (CFU)/100cm2 of MRSA and also methicillin-resistant coagulase-negative Staphylococcus (MRCNS) were isolated from 1) 25-100% of the bed-mattresses tested in 10 out of 11 (90%) hospitals, and also 2) bed sheets for patients, floors of patient wards, laundry, bath-room, toilet and laundry storage-room. And seven and eight palms of 20 patients were contaminated with MRCNS and MRSA, respectively, and MRCNS contamination was revealed in six of medical staffs. These results indicate that hospital environments, especially the mattresses and hospital floors are highly contaminated with MRCNS and MRSA, and sanitation and cleanliness of mattresses and floors are necessary to prevent the dissemination of both MRCNS and MRSA in hospital.

Cross Infection↗

Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.

The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.

Animals↗

Fluorescent-labeled oligonucleotides that exhibit a measurable signal in the presence of complementary DNA.

Oligonucleotide derivatives with a fluorescent dye were designed for exhibiting a measurable signal only when they bind to complementary DNA in aqueous solution. The oligonucleotide with a dansyl group at the specific 2'-sugar residue was synthesized by using the protected 2'-dansylaminouridine phosphorobisamidite. The dansyl-oligonucleotide conjugate binds to its complementary DNA to form duplex with a normal stability and exhibits enhanced fluorescence together with a blue-shift in emission maxima after the hybridization. Another possible candidate involved the use of pyrene-excimer emission upon forming ternary complex between two pyrene-labeled oligonucleotide probes with target DNA. A new and general method for introduction of a pyrene fluorophore into the 3'- or 5'-terminal hydroxyl group of oligonucleotides via different linkers was developed.

DNA↗

Effect of antibody to leukocyte adhesion molecule CD18 on recovery of neonatal lamb hearts after 2 hours of cold ischemia.

BACKGROUND: Prior studies have shown that leukocytes are important in reperfusion injury after normothermic ischemia, and recently discovered leukocyte adhesion molecules that bind to endothelial ligands may be involved in this process. No studies on the role of leukocyte adhesion molecules in hypothermic ischemia are available. METHODS AND RESULTS: We assessed the effect of preischemic administration of monoclonal antibody to the leukocyte adhesion molecule CD18 on recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15 degrees C K+ cardioplegic solution by comparing nine antibody-treated and nine control hearts. At 30 minutes after reperfusion, antibody-treated hearts compared with control hearts had better percent recovery of maximum left ventricular (LV) developed pressure (83.9 +/- 2.2% versus 73.6 +/- 3.0%, mean +/- SEM), LV dP/dt (78.4 +/- 3.3% versus 67.4 +/- 3.4%), coronary blood flow (159.5 +/- 12.2% versus 84.4 +/- 3.5%), and myocardial oxygen consumption (129.8 +/- 16.5% versus 71.2 +/- 6.2%) (all p < 0.05). In each heart, we also tested coronary vascular resistance (CVR) response to 10(-6) mol/l acetylcholine (ACh) infusion to assess endothelial function. Percent recovery of CVR response to ACh was higher in antibody-treated hearts (38.4 +/- 4.3%) than control hearts (13.4 +/- 12.8%) (p = 0.08). CONCLUSIONS: These results suggest that leukocyte adherence to endothelium mediated by CD18 plays an important role in reperfusion after hypothermic ischemia. Antibody to CD18 may be useful in myocardial and endothelial protection during surgically induced ischemia.

Animals↗

The immunosuppressive effect of FK 506 on canine lung transplantation.

The immunosuppressive potency of FK 506 was studied after left lung transplantation in adult mongrel dogs in comparison with cyclosporine. Fiberoptic bronchoscopy, bronchial mucosal blood flow measurement with laser Doppler velocimetry, and chest x-ray and pathologic examinations were performed. Group A had no immunosuppression (n = 5); group B received FK 506 (0.10 mg/kg/day intramuscularly (n = 5); group C received cyclosporine (20 mg/kg/day orally) (n = 5). In group A four dogs died of rejection on the seventh to the twenty-first postoperative days. Another one was killed on the fourteenth postoperative day because bronchial dehiscence occurred at the anastomosis. In group B one died of alveolar rejection on the seventh postoperative day. The remaining four survived 28 days and were put to death. In group C all five dogs survived 28 days and were put to death. In group A bronchial stenosis or dehiscence at the anastomosis was found in every one during the early postoperative period. In group B stenosis did not develop in any of the dogs, including the one that died on the seventh postoperative day. In group C slight stenosis was seen in one dog, severe narrowing in another, and good healing in the remaining three. The transplanted lungs were almost normal histologically in four animals of group B, and one showed alveolar phase rejection. In all animals of group A severe rejection was observed, and in group C two of five animals showed vascular phase rejection, two latent phase, and one fibrosis. Histologic examination of the bronchial anastomosis in group B showed almost normal bronchial epithelium and slight submucosal infiltration of mononuclear cells. In group A there was desquamation of epithelium and mild to moderate mononuclear cell infiltration. In group C hyperplasia of the epithelium was observed in two animals, an abscess at the site of anastomosis in one, and mild to moderate mononuclear cell infiltration in all five. With use of laser Doppler velocimetry, bronchial blood flow in group B was found to be the same as in group C. Laser Doppler velocimetry values reached preoperative levels by the twenty-eighth postoperative day in both groups. Although diarrhea developed in two dogs of group B, no other significant side effect of FK 506 was seen.

Animals↗

[Elimination of tuberculosis in Japan].

According to the operational definition adopted at Wolfheze Workshop held in March 1991 (Table 1), tuberculosis low incidence countries are defined as those where the incidence of all forms of tuberculosis is less than 1 per 100,000. The incidence was 41.9 in 1990 in Japan, so that Japan cannot be considered as a low incidence country. Why is the incidence of tuberculosis so high in Japan? What part of population is affected by the tuberculosis disease? To solve these questions and to make clear the mode of development of tuberculosis, a study was carried out. Fortunately, both the annual risk of tuberculosis infection and the prevalences of persons with healed and/or fibrotic lesion in the lung are known from the results of the National Tuberculosis Prevalence Surveys carried out in 1963 and 1973 as shown in Figures 1 and 2. From these data, the number of newly infected within 5 years and that of remote infections by age group were estimated. The former was divided into BCG vaccinated and non-vaccinated and the latter into persons with fibrotic lesion, with healed foci and without abnormality in the lung. (Table 2). The rates of development of tuberculosis disease according to the X-ray findings of the lung were observed at the five-years follow-up study of all the examinees at the Prevalence Survey carried out in 1968. The ratio of development of the disease in those with recent infections, remote infections with fibrotic lesion, those with healed foci and those without abnormality was estimated as 20 : 10 : 2 : 1. (Table 3)(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Coronary endothelial injury by cold crystalloid cardioplegic solution in neonatal lambs.

BACKGROUND: Hypothermic cardioplegia generally improves the recovery of the mechanical function of the heart after ischemia, but some components of cold cardioplegia may produce endothelial injury that can offset the protective effects of cardioplegia. This study was undertaken to evaluate the effect of extremely hypothermic cardioplegia on the recovery of coronary endothelial and cardiac mechanical function after ischemia in the immature heart. METHODS AND RESULTS: Three groups of eight isolated, blood-perfused, neonatal lamb hearts each had myocardial temperature maintained at 10 degrees C during 2 hours of global ischemia but received hourly doses of crystalloid cardioplegic solution at temperatures of 10 degrees C (group A), 4 degrees C (group B), and 2 degrees C (group C). The percent recovery of isovolumic left ventricular maximum developed pressure in groups A (86.6 +/- 7.7) and B (90.5 +/- 7.5) was higher than in group C (78.6 +/- 6.3), and maximum dP/dt in groups A (89.6 +/- 8.6) and B (89.5 +/- 5.7) was higher than in group C (79.4 +/- 9.0) at 30 minutes of reperfusion (p < 0.05). Groups A (136.8 +/- 20.9) and B (142.8 +/- 27.7) achieved higher recovery of coronary blood flow (as percentage of baseline) at 15-minute reperfusion than group C (108.5 +/- 26.2), and myocardial oxygen consumption was higher in groups A (68.3 +/- 14.6, 92.1 +/- 21.1) and B (68.8 +/- 19.9, 85.3 +/- 25.5) than in group C (46.3 +/- 14.7, 57.2 +/- 14.2) at 15 and 30 minutes of reperfusion, respectively (p < 0.05). Percent recovery of the coronary vascular resistance responses to 10(-7) M concentration of an endothelium-dependent vasodilator (acetylcholine) in groups A (71.9 +/- 9.0) and B (66.2 +/- 23.1) was higher than in group C (24.2 +/- 14.3) (p < 0.05), whereas responses to 3 x 10(-5) M concentration of endothelium-independent vasodilator (nitroglycerin) were the same. CONCLUSIONS: Excessively cold cardioplegic solution may cause endothelial dysfunction (reduced acetylcholine response) and reduced recovery of mechanical function in the neonatal heart.

Acetylcholine↗

[Congenital absence of the right main pulmonary artery--a case report].

A 32-year-old man was admitted to hospital for investigation of bloody sputum. Chest roentgenogram showed a decrease in the volume of the right lung, with mediastinal shift to the right. Chest CT examination revealed narrowing of the right main pulmonary artery. Bronchofiberscopic examination was normal. Pulmonary arteriogram demonstrated complete absence of the right pulmonary artery. Cardiac catheterization showed no concomitant cardiac malformation. Therefore, this case was diagnosed as congenital absence of the right main pulmonary artery.

Adult↗

[Surgical treatment for tuberculous spondylitis; a case report].

A 64-year-old woman was admitted with the chief complaints of severe back pain. Chest X-ray film on admission showed an abnormal mass lesion in the right upper mediastinum. Chest tomography and chest CT films revealed destruction of thoracic vertebrae (Th 2 and 3) and paravertebral abscess. Chemotherapy containing RFP was started under diagnosis of active tuberculous spondylitis of thoracic vertebrae. Three months later, curative operation for spondylitis were performed. She underwent the resection of necrotic bone and the anterior spinal fusion using transplanted bone autograft. Her post-operative course was good and she discharged three months after curative operation. Tuberculous spondylitis is still important diseases at the differential diagnosis from metastatic vertebral tumors. This report describes a successful case of surgical treatment for tuberculous spondylitis of thoracic vertebrae.

Female↗

In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption.

To explore the feasibility of in vivo 17O NMR for the estimation of cerebral blood flow and oxygen consumption, in vivo 17O NMR spectroscopy and imaging were employed in animal models. In the spectroscopy, the changes in the 17O NMR signal intensity after the injection of H2(17)O and the inhalation of 17O2 gas were obtained every 4 seconds with sufficient signal-to-noise ratios for the quantification of cerebral blood flow and oxygen consumption. In the imaging, although the time and spatial resolutions were insufficient for the quantification of H2(17)O, 17O NMR images of rabbit brain could be obtained, indicating that it is possible to map cerebral blood flow and oxygen consumption by 17O NMR imaging.

Animals↗

An observation on hitherto unknown corticospinal fibers that descend between the tractus corticospinalis lateralis and ventralis in the cat.

Following injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the pericruciate (sensorimotor) cortex on one side in the cat, we found labeled fibers surrounding the ventral horn of the spinal cord bilaterally, in addition to the crossed and the uncrossed lateral, ventral and dorsal corticospinal tracts (CSTs). These hitherto unknown fibers, which could be traced to the caudal end of the L2 segment, were predominantly contralateral to the WGA-HRP injection side. This study indicates the presence of newly recognized CST fibers in the cat.

Animals↗