Shunichi Takaya

Relationship between postoperative recurrence and expression of cyclin E, p27, and Ki-67 in non-small cell lung cancer without lymph node metastases

Abstract.Background: Cyclin E and p27 play pivotal roles in cancer development and progression. We investigated whether the prognosis in cases of non-small cell lung cancer without lymph node metastases that underwent complete resection could be associated with tissue expression of cyclin E, p27, and Ki-67.nMethods: Tumors from 62 patients at least 5 years after surgery were assessed by immunohistochemistry for expression of cyclin E, p27, and Ki-67. Disease-free survival (DFS) after surgery was used to evaluate disease prognosis. We also investigated the relationship between expression of these factors and postoperative recurrence.nResults: In non-small cell lung cancer, p27-negative expression and pT factor were significantly unfavorable prognostic factors in multivariate analysis. The DFS rate in cyclin E-positive expression was significantly lower than in cyclin E-negative expression. Similarly, p27-negative expression and high Ki-67 expression correlated with a shortened DFS rate. In combinations of expression of cyclin E and p27, the cyclin E-negative/p27-positive group had a significantly higher DFS rate than did the other groups. According to histological type, there were correlations between the risk of postoperative recurrence and expression of these three biological factors, especially in adenocarcinoma.nConclusion: By analyzing the expression of cyclin E, p27, and Ki-67 of tumor cells, it was possible to extract the patient group for whom closer follow-up and postoperative treatment is necessary to improve survival rate.

The Influence of Liver Dysfunction on Cyclosporine Pharmacokinetics —A Comparison between 70 per cent Hepatectomy and Complete Bile Duct Ligation in Dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects.

Restoration of sarcoplasmic reticulum protein level by thyroid hormone contributes to partial improvement of myocardial function, but not to glucose metabolism in an early failing heart

OBJECTIVEnIn heart failure, sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) activity is decreased, resulting in abnormal Ca(2+) handling and contractile dysfunction. We have previously reported that impaired glucose transporter (GLUT4) activity was an early indicator of progression of heart failure in pressure overload hypertrophied heart. This study was aimed to examine the contribution of both SERCA2 and glucose metabolism in pressure overload hypertrophied heart. Thyroid hormone, which is known to restore GLUT4 and/or SERCA2 function, was also tested.nnnMETHODSnHypertrophied rat heart was created by abdominal aortic banding for 16 and 26 weeks. Then 20-40 microg/kg of 3,5,3-triiodo-L-thyronine (T3) was administered subcutaneously daily for the last 4 weeks. Hypertrophied myocytes were created by the stimulation of H9c2(2-1) rat heart myoblasts with 2 micromol/L of isoproterenol for 3, 7 and 10 days. Left ventricle function of the hypertrophied rat hearts were measured in Langendorff perfusion. Myocardial protein levels of GLUT4 and SERCA2 in two models were analyzed by Western immunoblotting. Glucose and lactate concentration of cultured medium of myocytes were measured enzymatically to determine the efficacy of glycolysis.nnnRESULTSnDiastolic function (tau) was significantly deteriorated in 16-week heart with significantly lower SERCA2 protein (89.3%) than control. In 26-week heart, both systolic and diastolic function (+dP/dt max, -dP/dt max and tau) was significantly deteriorated. This was associated with significant decrease in both GLUT4 and SERCA2 protein (84.8 and 91.6%, respectively). In cultured hypertrophied myocytes, glycolysis was shifted from aerobic to anaerobic during progression of hypertrophy. GLUT4 protein was significantly decreased at day 7 (45.6% of control). This led to a down-regulation of SERCA2 protein at day 10 (51.8% of control). Although there was no impact of T3 treatment on GLUT4, SERCA2 protein level was almost reversed with partial improvement of myocardial function.nnnCONCLUSIONSnWe conclude that impairment of both glucose metabolism and SERCA2 function were seen in an early heart failure. Thyroid hormone partially improved myocardial function with successful improvement of SERCA2 protein but no impact on GLUT4 protein expression in hypertrophied rat heart. Restoration of glucose metabolism is a critical step to avoid further progression of heart failure.

Stent graft treatment for abdominal pseudoaneurysm near the celiac artery

pledget-supported suture. We did not use this method because of suspected infection and the severely damaged PA wall. The histologic findings also support our decision. However, the PA wall was extensively abnormal, and the suture line was disrupted. Resuturing incorporating the pulmonary valve annulus caused mild residual stenosis that could not be tolerated in the presence of severe right ventricular dysfunction. Pulmonary root replacement can be a method of choice in such patients. Therefore, we believe that a pulmonary allograft should also be made available whenever possible and should be implanted during the initial operation, if necessary. The last problem was the timing of the operation. Emergency intervention was required in most reported patients with aortopulmonary fistulae and in this patient also, although the history of the present illness was rather long, and his general condition was fair

Glomerular endothelial changes in cyclosporine A-treated rats: scanning and transmission electron microscopic studies.

This study focused on the glomerular structural changes observed after cyclosporine A (CsA)-induced nephrotoxicity. Renal structural changes were examined in rats treated with oral CsA, given as a daily dose of 50 mg/kg for periods of up to 49 days. By means of scanning electron microscopy and morphometry, we first demonstrated that the most conspicuous and reproducible ultrastructural changes could be detected in the endothelial cells of the glomerular capillaries. These changes included a reduction in the fenestral pore size and partial disappearance of endothelial fenestration, the appearance of microvilli-like projections on the endothelial surface, and flattening and widening of the cytoplasmic folds. We believe that the ultrastructural changes observed in this study are partially responsible for the alterations in renal function seen in the cyclosporine A-treated model, and that these alterations are caused by CsA-induced vasospasm.

Successfully repaired traumatic tracheal disruption and cardiac rupture with cardiopulmonary support.

A 19-year-old man suffering from dyspnea associated with tracheal and cardiac rupture from a traffic accident was found by bronchoscopy to have a 7.5 cm longitudinal tear in the membranous portion of the trachea. Right posterolateral thoracotomy was conducted and open ventilation through the left main bronchus initiated with standby cardiopulmonary bypass cannulation of the right femoral artery and vein. When oxygenation was poor, extracorporeal circulation was initiated through the cannulated artery and vein. Under the cardiopulmonary bypass, we safely repaired the tracheal laceration and cardiac rupture.

A Case Report of Double Aortic Arch, Vascular Ring Associated with Tracheal Stenosis.

重複大動脈弓,血管輪は先天性動脈奇形では比較的希な疾患であるが心内奇形を合併しない限り,循環動態に影響を及ぼすことはなくその予後は良好である.しかしながら初発症状が喘鳴,嚥下困難といった呼吸器や消化器症状であるため確定診断にいたるまで時間を要し予期せぬ合併症に見舞われることがある.われわれは喘鳴を初発症状としたEdwards IA型の血管輪を経験した.血管輪離断術を行ったが呼吸状態の改善を認めず,2回目の手術にて動脈管索離断術およびaortopexyを施行し,人工呼吸器より離脱できた.大動脈弓離断により,気管外からの圧迫は解除されたが気管チューブの刺激による気管内壁の肥厚が原因となって,気管内腔の狭小化をきたしたものと思われた.血管輪には気管軟化症に伴う気管狭窄が知られているが,その他の機序による気管狭窄も念頭に入れ早期診断と適切な治療法の選択が望まれる.