Biomedical subjects
Publications and source records attributed to T Misaki.
By affinity chromatography with Sepharose coupled to 2'-deoxy-1-beta-D-ribofuranosyl-N4-dodecanoylcytosine, deoxycytidine kinase and cytidine deaminase were purified 1,950- and 2,240-fold, respectively, from Ehrlich carcinoma cells, and their enzyme activities for several deoxycytidine analogs were investigated.
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Off-pump CABG was utilized on patients who had multivessel coronary artery disease and other organ diseases. A total of 79 patients who underwent off-pump CABG were evaluated. Of these, 66 suffered from OMI and AP, 4 form AP, 6 from u-AP, and 3 from AMI. LITA was used in 75 cases, RA in 48, GEA in 45, RITA in 13, IEA in 3, and SVG in 38. Revascularization was performed at # 2 in 3 cases, # 3 in 11, 4 PD in 37, 4 PL in # 7 or # 8 in 79, # 9 in 27, # 12 in 51, and # 14 in 17. A time of 10.3 min was spent on LAD revascularization, 9.8 min on D 1, 10.2 min on Cx, anf 11.5 on RCA. Seven patients were transferred to on-pump beating CABG because of hemodynamic instability. One patients suffered postoperative CVA, and 2 had wound infection. Complete revasculization was accomplished in 78 patients, and hospital death was not reported.
BACKGROUND: Intraarterial infusion of elastase has been used to create an experimental model of aortic aneurysm in rats. Unfortunately, the utility of this model is limited by a high mortality rate among experimental animals. This study examined the factors influencing mortality to help refine this model. MATERIALS AND METHODS: A total of 126 Wistar rats were divided into six groups. A 1.0-cm segment of infra-renal abdominal aorta was clamped (n = 21), clamped and cannulated via the femoral artery (n = 21), infused with saline (n = 21), or infused with solution containing 25 U of elastase from three different lots (each group, n = 21). Clamping or infusion was performed for 30 (n = 7), 60 (n = 7), and 120 min (n = 7). The mortality rates were calculated at 7 days. RESULTS: There were no deaths in the clamp group, but 29% of the rats that underwent cannulation with clamping or saline infusion for 2 h died. The mortality rate for a 30-min elastase infusion ranged from 0 to 71%. Mortality for a 60-min infusion ranged from 14 to 100%. Mortality for a 2-h infusion ranged from 43 to 100%. The mortality rate was dependent on the treatment time and the elastase lot number. CONCLUSIONS: Aortic cannulation, elastase infusion, and prolonged infusion times all increase the mortality rate in the elastase-induced rat aortic aneurysm model. Mortality is also dependent on the elastase lot number.
Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from our initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal.
Here, we report a case of a two-day-old neonate with total anomalous pulmonary venous connection to the innominate vein and a bronchogenic cyst arising from the trachea. Antenatal echocardiography had delineated both cardiac and extracardiac lesions, and a repeated examination on the day of birth disclosed progressive enlargement in the cyst in a manner so as to obstruct the innominate vein. On the second day of life, the patient underwent complete correction of the cardiac lesion and total excision of the cyst. The patient recovered uneventfully and was discharged on the thirteenth postoperative day.
This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model.
T cells are divided into two subsets, alphabeta and gammadelta, according to the T-cell receptor (TCR) expressed. Recent findings indicate that gammadelta T cells serve as the first defense against microbial pathogens, and represent a link between innate and acquired immunity. We conducted a study to investigate the changes in circulating TCR subsets after cardiac surgery in children. Blood samples from 24 children who underwent cardiac surgery with cardiopulmonary bypass (CPB) were collected serially to analyze TCR subsets by flow cytometry. The alphabeta T cells reached a nadir on postoperative day (POD) 1, but recovered to pre-CPB levels on POD 3. On the other hand, the gammadelta T cells decreased after CPB and did not recover to pre-CPB levels even after POD 7. The alphabeta/gammadelta T-cell ratio was increased after POD 3. In children, gammadelta T cells recover more slowly than alphabeta T cells after cardiac surgery. These changes in TCR subsets may contribute to postoperative immunosuppression.
Previous findings vary regarding the timing and cause of elastin fiber degeneration in the elastase-induced rat abdominal aortic aneurysm model. We examined the timing and cause of elastin fiber degeneration after elastase infusion using two different elastase infusion times. Twenty-four Sprague-Dawley rats were divided into two groups. The infrarenal abdominal aorta was infused with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n = 12, 30-min infusion group). In each group, three rats were killed immediately and 1, 3, and 7 days after infusion, and then the aortas were excised for a histologic examination. Elastin fibers did not stain, even immediately after elastase infusion, in the 30-min infusion group. The degeneration of elastin fibers did not progress in the 15-min infusion group during the period of observation. Inflammatory cells infiltrated mainly to the adventitia near regions where the degeneration of elastin fibers spread totally through the aortic media. Elastin fibers degenerate immediately after elastase infusion and thus seem to degenerate not due to endogenous proteinases that are produced by the infiltrating cells, but due to the exogenously infused elastase itself. Inflammatory cell infiltration was thus found to be a result of the degeneration of elastin fibers in this model.
Orthotopic implantation of a metastatic cell line of Lewis lung carcinoma (LLC-MLN), which was isolated by an in vivo selection method, resulted in greater metastatic growth in mediastinal lymph nodes as compared with that of the original LLC cells. LLC-MLN cells also had increased invasive ability and activator protein-1 (AP-1) transcriptional activity as compared with the original LLC cells. This is well consistent with the previously reported finding that overexpression of AP-1 is associated with lymphatic metastasis in lung cancer patients. Oral administration of curcumin, which downregulates AP-1 transcription, significantly inhibited the mediastinal lymph node metastasis of orthotopically implanted LLC cells in a dose-dependent manner, but did not affect the tumor growth at the implantation site. Combined treatment with curcumin and an anti-cancer drug, cis-diamine-dichloroplatinum (CDDP), resulted in a marked inhibition of tumor growth at the implanted site and of lymphatic metastasis, and a significant prolongation of the survival time. The downregulation of transcriptional AP-1 activity by curcumin as seen in the dual luciferase assay caused inhibition of LLC cell invasion through the repression of expression of the mRNAs for urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR). Inhibition of AP-1 transcriptional activity may offer improved therapeutic efficacy for lung cancer patients with lymphatic metastasis.
Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.
UNLABELLED: 131I therapy is a widely accepted treatment for metastatic differentiated thyroid cancer. To investigate the feasibility of 131I therapy for breast cancer, we established breast cancer cells stably expressing Na-/I- symporter (NIS) gene that can be modulated and studied in vitro and in vivo. METHODS: We transfected rat NIS genes into a human breast cancer cell line (MCF7) by electroporation. Iodide accumulation was evaluated under various extracellular concentrations of sodium and iodide, and iodide efflux was also assessed. Biodistribution and tumor imaging were studied using tumor-bearing mice. RESULTS: A novel cell line (MCF3B), stably expressing the NIS gene, was established from MCF7. MCF3B took up 44 times more radioiodide in vitro than MCF7 did. Iodide uptake was completely inhibited by 1 mmol/L perchlorate and was dependent on external sodium and iodide concentrations. Iodide efflux from MCF3B cells was slower (half-life [T 1/2] > 27 min) than from FRTL5 thyroid cells (T 1/2 = 4 min). In the biodistribution study using MCF3B-xenografted mice, high tumor uptake of 125I was shown (16.73%) at 1 h after injection, and tumor-to-normal tissue ratios were also high (4.84-21.28), except in the stomach (0.47). However, the iodide accumulation in the tumor lessened with time, reaching less than 1% at 24 h after injection. CONCLUSION: Our preliminary data indicate that NIS-based gene therapy may be applied by concentrating a lethal dose of radiation in tumor cells in vivo, but further investigation is necessary to determine a method of maintaining radioiodine in the cells to allow greater therapeutic effects.
Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.
Increased extracellular glutamate ([GLU]e), under the condition of cerebral ischemia, anoxia or hypoxia, has been recognized as being associated with neuronal cell damage and death. We performed real-time monitoring of [GLU]e dynamics in vivo in the rat striatum during systemic acute anoxia or hypoxia, as well as monitoring the direct current potential (DC) and cerebral blood flow (CBF). Adult Wistar rats were orotracheally intubated and artificially ventilated with room air. A microdialysis electrode, temperature sensor probe, DC microelectrode and laser Doppler probe were then implanted. The inspired gas was changed to 100% N(2) (anoxia), or to 3, 5 or 8% O(2) (remainder N(2)) (hypoxia). With 100% N(2), distinct biphasic [GLU]e elevations were observed. With 3% O(2), a transient [GLU]e increase was seen before anoxic depolarization (AD). With 5% O(2), however, the start of the transient [GLU]e increase was significantly delayed. Anoxia-induced depolarization started at about 100 s. The 3% O(2)-induced transient depolarization and AD began at nearly the same time as the transient and AD-induced increase in [GLU]e. Similarly, the responses to 5% O(2) showed significant delays in the transient depolarization and AD-induced increase in [GLU]e. CBF during 3 or 5% O(2) hypoxic insult was consistently maintained above the control level, i.e., prior to cardiac arrest. Our new dialysis electrode method employing both GOX and ferrocene-conjugated bovine serum albumin allowed evaluation of transient [GLU]e dynamics in the early phase of severe hypoxia in vivo.
BACKGROUND: Anthracycline drugs for cancer therapy often cause functional myocardial impairment even in relatively low doses. We investigated the left ventricular function in asymptomatic anthracycline-treated children by automatic border detection (ABD) to assess its clinical usefulness for unmasking latent anthracycline-induced myocardial damage. METHODS AND RESULTS: Thirty-four children (0.7 to 17.6 years old) during or after anthracycline chemotherapy (26 to 1100 mg/m2) for malignancy (Chemo group) were studied, and 40 children (2.8 to 15.6 years old) without cardiac involvement served as normal control subjects (Control group). All patients underwent complete echocardiographic examination, including M-mode, Doppler, and ABD. Conventional echocardiography disclosed no difference between groups with regard to ejection fraction and the ratio of early to late transmitral flow velocity. In marked contrast, an investigation using ABD revealed that the Chemo group appeared to have some anthracycline-induced myocardial damage. In the apical 4-chamber view, peak filling rate in the Chemo group [2.3+/-0.4 end-diastolic area (EDA)/s] was significantly lower than that in the Control group (3.1+/-0.5 EDA/s) (P<0.0001), and time to peak filling rate in the Chemo group (106+/-31 ms) was clearly prolonged compared with that in the Control group (74+/-22 ms) (P<0.0001). CONCLUSIONS: Echocardiographic ABD may be a sensitive and useful noninvasive approach for evaluating subclinical anthracycline cardiotoxicity.
OBJECTIVE: This study was performed to determine whether it would be possible to shorten the elastase infusion time in the elastase-induced rat aneurysm model. METHODS: The abdominal aortas of 76 male Sprague-Dawley rats were dissected and infused for 10, 20, 30, 60, or 120 min with a solution containing 14 U of elastase or for 30 min with saline solution (control). After infusion, the rats were evaluated every day for calculation of the mortality rate. On day 7, the surviving rats underwent laparotomy. The diameter of the aorta was measured, and the aortic tissue was excised for histologic examination. RESULTS: There were no deaths among the rats infused for 10, 20, or 30 min. The mortality rate was 64% in the 60-min and 90% in 120-min groups. There were no significant differences in the diameters of the 30-min saline-infused aortas and the 10- or 20-min elastase-infused aortas. The diameter of the 30-min elastase-infused aortas (6.2 +/- 2.1 mm) was significantly larger (P < 0.01) than the diameters of the 10- and 20-min elastase-infused aortas. There were no significant differences between the 30-min and the 60- and 120-min elastase-infused aortas. Microscopically, there was total or subtotal loss of elastic tissue and marked inflammatory cell infiltration of the aortic wall in the 30-, 60-, and 120-min elastase-infused aortas. CONCLUSIONS: It is possible to shorten the elastase infusion time from 120 to 30 min in the elastase-induced rat aneurysm model. This shortening of infusion time reduces the experimental time and mortality rate.
BACKGROUND: In several experimental studies, double cardiomyoplasty using both latissimus dorsi muscles did not provide sufficient assist to the failing heart and did not clearly show improvement compared with single cardiomyoplasty. This study demonstrated the superior efficacy of our method of double cardiomyoplasty compared with single cardiomyoplasty. METHODS: In 16 dogs, the two latissimus dorsi muscles were crossed in front of the heart and directly sutured to each other behind the heart. Control hemodynamic measurements were obtained, and acute heart failure was induced by intravenous administration of propranolol. After the hemodynamic changes with bilateral latissimus dorsi muscle assistance were measured, single cardiomyoplasty was done in the same dog, and the hemodynamic variables were measured. RESULTS: With our double cardiomyoplasty, aortic systolic pressure increased by 25% (p < 0.001); pulmonary artery systolic pressure, by 40% (p < 0.001); end-systolic elastance, by 155% (p < 0.001); and cardiac output, by 55% (p < 0.001). There were significant increases in aortic pressure, pulmonary artery pressure, end-systolic elastance, stroke volume, and cardiac output with our double cardiomyoplasty compared with single cardiomyoplasty. CONCLUSIONS: In this study, our double cardiomyoplasty provided significant hemodynamic improvement compared with single cardiomyoplasty.
BACKGROUND: Single-vessel coronary artery bypass grafting of the left internal mammary artery to the left anterior descending coronary artery using a minithoracotomy has been shown to produce excellent results with a very low mortality rate. However, this procedure cannot be used in patients with double- or triple-vessel disease. Our goal was to develop a minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass for total revascularization of the left ventricle using multiple arterial grafts. METHODS: Limited lateral thoracotomy was performed in the fourth or fifth intercostal spaces, exposing the left anterior descending coronary artery and left circumflex coronary artery. Two or three arterial grafts were harvested. Revascularization of the left anterior descending coronary artery and the left circumflex coronary artery were performed in 20 patients without cardiopulmonary bypass through the limited lateral thoracotomy using complex performed arterial grafts. In 4 patients, triple- and quadruple-vessel grafting was performed. RESULTS: The mean coronary cross-clamp time was 14.5+/-4.0 minutes for the left anterior descending coronary artery and 16.8+/-5.1 minutes for the left circumflex coronary artery. No early deaths or postoperative complications occurred. There were no late deaths or angina during the mean follow-up of 7.0 months (range, 2 to 22 months). Postoperative coronary angiography demonstrated widely patent grafts in all patients. CONCLUSIONS: Minimally invasive approach through a limited thoracotomy in multiple coronary artery bypass graftings are technically feasible and may be an alternative approach in the complete revascularization of the left ventricle. Mechanical immobilization of the coronary artery enhances early graft patency and is an essential part of this procedure.