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Biomedical subjects

T Aoyama

Publications and source records attributed to T Aoyama.

At least 19 recordsLinked to original sources

Ultra-early MRI showing no abnormality in a fall victim presenting with tetraparesis.

STUDY DESIGN: Case report. SETTING: Department of Neurosurgery, Sapporo Azabu Neurosurgical Hospital and Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. CASE REPORT: A patient presented to us with complete C4 tetraplegia after a 3-m fall. MRI performed 120 min after his fall showed spinal canal stenosis due to disk protrusion at the C3/4 level without spinal cord signal changes on T1- and T2-weighted images. He underwent laminoplasty between C2 and C6. Intraoperative ultrasound, performed 6 h after his fall, disclosed a hyperechoic lesion at the C3/4 level of the cervical cord; postoperative T2-weighted MRI, obtained at 8 h after his fall, showed high intensity at the same level. CONCLUSION: In patients with cerebral infarction, approximately 6 h between the insult and the acquisition of T2-weighted MRI are required to detect signal changes. We postulate that the time course on MRI scans obtained immediately after spinal cord injury is similar in patients with spinal cord injury and cerebral infarction and suggest that the absence of spinal cord abnormalities in the ultra-early post-injury stage is not always predictive of a good prognosis.

Accidental Falls↗

Expression of the cadherin-11 gene is a discriminative factor between articular and growth plate chondrocytes.

OBJECTIVE: Calcification of hypertrophic chondrocytes is the final step in the differentiation of growth plates, although the precise mechanism is not known. We have established two growth plate-derived chondrocyte cell lines, MMR14 and MMR17, from p53-/- mice (Nakamata T, Aoyama T, Okamoto T, Hosaka T, Nishijo K, Nakayama T, et al. In vitro demonstration of cell-to-cell interaction in growth plate cartilage using chondrocytes established from p53-/- mice. J Bone Miner Res 2003;18:97-107). Prolonged in vitro culture produced calcified nodules in MMR14, but not in MMR17. Factors responsible for the difference in calcification between the two cell lines may also be involved in the physiological calcification in growth plate. DESIGN: Gene expression profiles of MMR14 and MMR17 were compared using a cDNA microarray to identify candidate genes involved in the calcification process. RESULTS: Forty-five genes were identified as upregulated in MMR14, including the cadherin-11 (Cdh-11) gene. The expression of Cdh-11 in MMR14 was detected in cell-cell junctions, while no expression was observed in MMR17. Primary cultured chondrocytes from growth plate (GC) also expressed the Cdh-11, and the staining of Cdh-11 was observed in the late hypertrophic zone of growth plate. Cell aggregation assays showed that chondrocytes required Ca2+ to form nodules, and knockdown of the Cdh-11 gene expression using short interfering RNA inhibited the formation of calcified nodules in MMR14. The introduction of Cdh-11 into MMR17 failed to produce calcified nodules indicating that Cdh-11 is one, but not the sole, factor responsible for the production of calcified nodules. CONCLUSION: Although the physiological role is still unclear, Cdh-11 is a discriminative factor between articular and growth plate chondrocytes.

Animals↗

[Coronary artery bypass grafting in a patient with right aortic arch; report of a case].

A 60-year-old man was admitted to another hospital because of chest oppression on effort. Chest X-ray showed radiographic evidence of a right aortic arch and double vessel coronary artery disease with 50% stenosis in the left main trunk was diagnosed by coronary angiography. He was transferred to our institute for surgical treatment of angina pectoris. Preoperatively, multi-detector row computed tomography (CT) was performed and it revealed a right aortic arch and an aberrant left subclavian artery with narrow left internal thoracic artery. A right internal thoracic artery was well demonstrated. Therefore, conventional coronary artery bypass grafting using a right internal thoracic artery and a saphenous vein graft was performed and his postoperative course was uneventful.

Aorta, Thoracic↗

Surgical treatment for bilateral carotid arterial stenosis.

Carotid endarterectomy (CEA) is a beneficial procedure for patients with high-grade carotid stenosis. However, patients with bilateral carotid stenosis have a higher surgical risk during CEA. Since the introduction of carotid stenting (CAS) may decrease some of the surgical complications of CEA, a combined treatment using CEA and CAS may be favorable for patients with bilateral carotid stenosis. We analyzed the safety and efficacy of this treatment strategy. Eighteen patients with bilateral carotid stenosis were treated from January 2000. Bilateral CEA was performed on the first two patients, CAS then CEA of contra-lateral symptomatic side in 13 patients, and bilateral CAS in three patients. There were no perioperative neurological complications or strokes during the follow-up period (mean 17 months). The combined treatment of CAS and CEA was a safe and effective strategy for bilateral carotid stenosis.

Aged↗

Stenting for vertebrobasilar artery stenosis.

We report our experience with stenting for symptomatic vertebrobasilar artery stenosis. One hundred and sixteen patients with vertebrobasilar artery stenosis (101 vertebral ostial stenosis, 15 intracranial vertebrobasilar artery stenosis) were treated with stenting. Indication criteria of treatment were 1) symptomatic lesion, 2) angiographical stenosis more than 60%. Under local anesthesia, pre-dilatation was first performed, then stents were placed to the lesion. Successful dilatation was obtained in 115 cases. The stenosis rate reduced to 2% post-stenting in ostial lesions and 16% in intracranial lesions. Transient neurological complications developed in 2 patients. Follow-up angiographies more than 6 months after stenting were performed in 94 patients with ostial lesions and all patients with intracranial lesions. Of these, 8 patients (9.5%) with ostial lesions and 4 patients (27%) with intracranial lesions developed restenosis. All patients with restenosis were treated successfully with PTA (percutaneous transluminal angioplasty). During the follow-up period, 3 patients developed recurrence of VBI (vertebro-basilar insufficiency) symptoms due to restenosis. One patient developed brain stem infarction due to in-stent occlusion 8 months after stenting. Conclusion. Stenting for vertebrobasilar artery stenoses is feasible and safe. Prevention of restenosis, especially in intracranial arteries, is the next problem to be solved.

Aged↗

[Beating heart surgery for ischemic mitral regurgitation: report of a case].

A 51-year-old man was admitted to our hospital because of dyspnea. Coronary angiography revealed triple vessel disease and echocardiography demonstrated severe mitral regurgitation with poor left ventricular function. Under a diagnosis of ischemic mitral regurgitation, on-pump beating mitral annuloplasty and coronary artery bypass grafting using the normothermic retrograde continuous coronary sinus perfusion of oxygenated blood was performed in order to prevent reperfusion injury. The patient was easily weaned from cardiopulmonary bypass and his postoperative course was uneventful. Because of the advantages of this procedure (e.g., no reperfusion injury, testing of the mitral valve repair is done in real physiologic conditions with beating tonus), on-pump beating heart surgery seems a good surgical option for ischemic mitral regurgitation with poor left ventricular function.

Heart-Lung Machine↗

[Mitral valve replacement for mitral regurgitation caused by papillary muscle head rupture complicating acute myocardial infarction: report of a case].

A 71-year-old female was admitted for acute posterolateral infarction. On the next day of the successful emergency perctaneous coronary intervention, she developed severe dyspnea and was intubated at intensive care unit. Massive mitral regurgitation was detected on color Doppler imaging and left ventricular cardiac failure was increasingly developed. The urgent operation was performed for papillary muscle rupture 18 days after first episode. Head rupture of the posterior papillary muscle was found during surgery and the mitral valve was replaced by a prosthetic valve (SJM # 25). The postoperative course was uneventful and she discharged on 52 days after surgery.

Aged↗

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.

Animals↗

[One-staged operation for mitral regurgitation and annuloaortic ectasia without aortic regurgitation with Marfan syndrome; report of a case].

A 32-year-old man with Marfan syndrome was admitted to our hospital for detail examination of congestive heart failure. Doppler echocardiography showed severe mitral regurgitation due to prolapse of posterior mitral leaflet. Annuloaortic ectasia without aortic regurgitation was also detected by aortography. Considering the future operative need for aortic root and ascending aorta, we performed mitral valve replacement with a mechanical valve and preventive concomitant aortic root replacement with a composite valve graft. His postoperative course was uneventful. Optimal surgical treatment of mitral regurgitation and annuloaortic ectasia in Marfan syndrome is controversial because the underlying connective tissue defect theoretically might compromise repair durability. Several surgical options for mitral regurgitation and annuloaortic ectasia in Marfan syndrome are discussed.

Adult↗

[In situ graft replacement for the thoracoabdominal aortic aneurysm with abscess around the aorta; report of a case].

A 58-year-old woman who complained of epigastralgia, back pain and pyrexia was admitted for further examination. A computed tomography (CT) scan revealed an abnormal mass between the descending aorta and esophagus. Exploratory thoracotomy was performed and brown purulent fluid was drained from the mass. Postoperatively, the white blood cell count normalized and the patient become afebrile. Eleven days postoperatively, circa 500 ml of blood discharged from a chest drain tube. A CT scan demonstrated enlargement of the thoracoabdominal aorta, necessitating an emergency operation. A pseudoaneurysm was found in the thoracoabdominal aorta, with inflammation in the aortic wall. On opening the aneurysmal sac, the intima of the aorta was found to have a partial defect. In situ graft replacement of the thoracoabdominal aorta and reconstruction of the intercostal artery were performed. Finally, a pedicled omental flap was used to cover the artificial graft. Two years postoperatively, the patient is doing well with no recurrence of infection.

Abscess↗

[Redo coronary artery bypass operation under beating heart via the left thoracotomy reusing patent grafts].

We report three cases of successful redo coronary artery bypass grafting (CABG) under beating heart via left thoracotomy with recycling of patent grafts previously implanted. Case 1 and 2: Anginal attack relapsed due to occlusion of the proximal portions of saphenous vein grafts (SVG) that had been sequentially anastomosed to the left coronary artery branches. In each case, the distal portion of the SVG was patent and functioned as coronary-coronary bypass. The left internal thoracic artery graft (ITAG) anastomosed to the left anterior descending coronary artery (LAD) was patent. Each patient underwent off-pump CABG through a left posterolateral thoracotomy. CABG was performed with the radial artery to the circumflex coronary artery (case 1) or the circumflex coronary artery and previous SVG (case 2). The proximal ends of radial artery grafts were anastomosed to the descending aorta. Case 3: Simultaneous reoperative CABG and the operation for the pseudoaneurysm that developed after the abdominal aortic graft replacement were performed. Bypass grafting between ITAG and LAD was performed with SVG via a left anterolateral thoracotomy because of severe anastomotic stricture of ITAG-LAD. The postoperative courses was uneventful for all patients.

Aged↗

Carotid artery intima-media thickness and brachial artery flow-mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes.

BACKGROUND: Epidemiological studies suggest that apolipoprotein E (apoE) polymorphism influences plasma lipoprotein levels and the development of cardiovascular disease. OBJECTIVE: To clarify the role of apoE polymorphism as a risk factor for early atherosclerosis. DESIGN: Using a high-resolution ultrasound method, we investigated the association between apoE phenotypes, carotid intima-media thickness (CCA-IMT), and flow-mediated dilation in the brachial artery (brachial-FMD) in 96 healthy asymptomatic Japanese men (mean +/- SD age, 50 +/- 8 years). RESULTS: Serum cholesterol and LDL-cholesterol levels in subjects with E3E4 were highest and those with E2E3 were lowest (P < 0.05 and P < 0.05, respectively). The CCA-IMT in E3E4 subjects (0.76 +/- 0.17 mm) was greater than that in E2E3 and E3E3 (0.61 +/- 0.15 and 0.64 +/- 0.14 mm, respectively; P < 0.01). In contrast, there was no difference between brachial-FMD and apoE phenotypes (P=0.15). By univariate analysis, CCA-IMT was positively correlated with age (r=0.51, P < 0.01), LDL-chol/HDL-chol ratio (r=0.37, P < 0.01), triglycerides (r=0.23, P < 0.05), and negatively correlated with HDL-cholesterol (r=-0.31, P < 0.01). An association between CCA-IMT and the presence of E4 allele was also found (P < 0.05). Logistic regression analysis revealed that the presence of E4 allele was a higher risk for increased IMT (relative risk of 4.4, 95% CI 1.5-12.5), even after adjustment for age, LDL-cholesterol, blood pressure and other known risk factors. A negative correlation between brachial-FMD and CCA-IMT was also found in all subjects (r=-0.21, P < 0.05), being most apparent in the E3E4 subjects (r=-0.53, P < 0.02). CONCLUSION: ApoE4 phenotype was independently associated with an increased risk of carotid atherosclerosis and elevated LDL-cholesterol levels in asymptomatic middle-aged Japanese men.

Adult↗

Cancer incidence and risk estimation among medical x-ray workers in China, 1950-1995.

Cancer incidence (1950-1995) among 27,011 medical diagnostic x-ray workers was compared by means of O/E system with that of 25,782 other medical specialists employed between 1950 and 1980 to provide evidence of human malignant tumors produced by protracted and fractionated exposure to ionizing radiation and to assess resultant cancer risk. Significant cancer risk was seen among diagnostic x-ray workers (RR = 1.2, 95% CI: 1.1-1.3). Significantly elevated risks were found for leukemia and cancers of skin, female breast, lung, liver, bladder, and esophagus; the RRs were 2.2, 4.1, 1.3, 1.2, 1.2, 1.8, and 2.7, respectively. The patterns of risk associated with years since beginning x-ray work and with age and calendar year of initial employment suggest that the excesses of leukemia, skin cancer, and female breast cancer-and possibly thyroid cancer-were related to occupational exposure to x rays. Because of a lack of individual dosimetry for Chinese medical x-ray workers (CMXW) before 1985, the dose was reconstructed by physical and biological retrospective dosimetry methods. The cancer risk of CMXW was estimated based on the reconstructed dose. The average cumulative dose for the earlier cohort (employed before 1970) was 551 mGy, and for the later cohort (employed from 1970 to 1980) it was 82 mGy. The RRs of leukemia and solid cancer were significantly high for the earlier cohort: 2.4 for leukemia, 1.2 for solid cancer. But no significant increase of RR was evident for the later cohort. The RR of leukemia was 1.7 and 1.1 for solid cancer. This means a significant cancer risk can be induced by long term fractionated exposure to ionizing radiation when the cumulative dose reaches a certain level.

Adult↗

Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design.

As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N'-pyridin-2-ylurea 15 (IC(50) = 0.10 microM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo-2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N'-pyridin-2-ylurea 26a (IC(50) = 0.042 microM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.

CDC2-CDC28 Kinases↗

ARR1, a transcription factor for genes immediately responsive to cytokinins.

Cytokinins are a class of phytohormones involved in various physiological events of plants. The Arabidopsis sensor histidine kinase CRE1 was recently reported to be a cytokinin receptor. We used a steroid-inducible system to show that the transcription factor-type response regulator ARR1 directs transcriptional activation of the ARR6 gene, which responds to cytokinins without de novo protein synthesis. This fact, together with characteristics of ARR1-overexpressing plants and arr1 mutant plants, indicates that the phosphorelay to ARR1, probably from CRE1, constitutes an intracellular signal transduction occurring immediately after cytokinin perception.

Adenine↗

Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes.

The purposes of the present study were to define precisely the ultrastructural features of apoptosis in cultured cardiomyocytes and to determine whether DNA fragmentation is essential for the apoptotic morphology. When cultured neonatal murine cardiomyocytes were incubated with an agonistic anti-Fas antibody in the presence of a non-toxic amount of actinomycin D or cycloheximide, approximately 70% of them had lost their viability after 24 h. The dead cardiomyocytes showed the typical ultrastructural changes of apoptosis on transmission and scanning electron microscopy, as well as by positive in situ nick end-labelling (TUNEL), positive Taq polymerase-based in situ ligation, a DNA ladder pattern on gel electrophoresis, and an increase in the active fragment of caspase-3. According to TUNEL at the electron microscopic level, apoptotic nuclear change, cytoplasmic shrinkage, and DNA fragmentation always occurred simultaneously in apoptotic cardiomyocytes. Other ultrastructural features of apoptosis were the appearance of abundant lipid-like structures in the cytoplasm of cardiomyocytes at the early phase, and a high incidence of plasma membrane rupture and formation of apoptotic bodies at the later phase. When zinc, an inhibitor of Ca2+/Mg2+-dependent endonuclease, was added to the present model, activation of caspase-3 and an apoptotic ultrastructure were still observed in spite of the lack of DNA fragmentation, indicating that this type of myocyte death is also apoptosis. In conclusion, the typical apoptotic ultrastructure and DNA fragmentation occur simultaneously in association with caspase-3 activation in Fas-stimulated cultured cardiomyocytes. Apoptotic morphology can, however, be observed even without DNA fragmentation.

Animals↗

Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process.

Dynamic process of apoptosis has not been elucidated in adult rat cardiomyocytes. Soluble Fas ligand (0.1 microg/ml) in the presence of actinomycin D (0.05 microg/ml) induced apoptosis in cultured adult rat cardiomyocytes, as documented by activated caspase-3, DNA fragmentation, and apoptotic ultrastructure. In the present model, we observed 60 adult cardiomyocytes with a normal rod shape under a real-time videomicroscope continuously for 48 hours. Seventeen cells (28%) were unchanged and 7 cells (12%) showed oncosis (so-called necrosis) in which no beating was evident. In the remaining 36 cells (apoptosis, 60%), a slow beating (17 +/- 3/min) was initiated 16 +/- 1 hours later. Approximately 1 hour later, the rod cells showed long-axial shortening as bone- or club-like, or square-shaped, accompanied with faster beating rates (35 +/- 7/min). In 29 cells (type A1 and A2), marked shrinkage occurred; the cellular shape became almost completely round with a smooth surface and the beating ceased 3.0 +/- 0.4 hours later. Then, smooth budding appeared 0.6 +/- 0.2 hours later. Apoptotic bodies were found in 8 cells 10 +/- 4 hours later (type A1, 13%) but not in 21 cells (type A2, 35%). In the other 7 cells (type A3, 12%), the cell surface became rough 8 +/- 3 hours later and the beating ceased. Maximal beating rate was greatest in type A1 (72 +/- 26/min) and greater in type A2 (29 +/- 5/min) than in type A3 (10 +/- 2/min). Electron microscopy confirmed apoptotic ultrastructure even in the cardiomyocytes with bone-, club-like, or square shapes, suggesting that type A3 as well as A1 and A2 is also under apoptotic process. A caspase inhibitor, zVAD.fmk, blocked beating, apoptotic morphology, and DNA fragmentation, indicating these depended on caspase activation. In the caspase-dependent apoptotic process of cultured adult cardiomyocytes, beating and the following deformity of the cellular edges were the initial signs and the rate of beating was related with the subsequent three different processes of apoptosis.

Animals↗