Nitric oxide confers cisplatin resistance in human lung cancer cells through upregulation of aldo-keto reductase 1B10 and proteasome.

In this study, we show that exposure of human lung cancer A549 cells to cisplatin (cis-diamminedichloroplatinum, CDDP) promotes production of nitric oxide (NO) through generation of reactive oxygen species (ROS) and resulting upregulation of inducible NO synthase (iNOS). The incubation of the cells with a NO donor, diethylenetriamine NONOate, not only reduced the CDDP-induced cell death and apoptotic alterations (induction of CCAAT-enhancer-binding protein homologous protein and caspase-3 activation), but also elevated proteolytic activity of 26S proteasome, suggesting that the activation of proteasome function contributes to the reduction of CDDP sensitivity by NO. Monitoring expression levels of six aldo-keto reductases (AKRs) (1A1, 1B1, 1B10, 1C1, 1C2, and 1C3) during the treatment with the NO donor and subsequent CDDP sensitivity test using the specific inhibitors also proposed that upregulation of AKR1B10 by NO is a key process for acquiring the CDDP resistance in A549 cells. Treatment with CDDP and NO increased amounts of nitrotyrosine protein adducts, indicative of peroxynitrite formation, and promoted the induction of AKR1B10, inferring a relationship between peroxynitrite formation and the enzyme upregulation in the cells. The treatment with CDDP or a ROS-related lipid aldehyde, 4-hydroxy-2-nonenal, facilitated the iNOS upregulation, which was restored by increasing the AKR1B10 expression. In contrast, the facilitation of NO production by CDDP treatment was hardly observed in AKR1B10-overexpressing A549 cells and established CDDP-resistant cancer cells (A549, LoVo, and PC3). Collectively, these results suggest the NO functions as a key regulator controlling AKR1B10 expression and 26S proteasome function leading to gain of the CDDP resistance.

[A surgical case of thoracic aortic aneurysm due to Takayasu's aortitis associated with ulcerative colitis].

We experienced a case of thoracic aortic aneurysm due to Takayasu's aortitis associated with ulcerative colitis. Steroid was medicated to control inflammation and operation was performed. The ascending aorta, aortic arch, brachiocephalic artery, and left carotid artery were replaced by artificial graft. We made elephant trunk type anastomosis at the distal side of the graft to provide for growth of the aneurysm after operation. This was a rare case considered autoimmune overlapping syndrome, and its background was complicated by HLA-Bw52 and parasitic Metagonimus Yokogawai. Relationship between steroid medication and progression of the disease is not certain yet. Postoperative course is uneventful, no recurrence of inflammation is seen and the aneurysm is not enlarged until now.

[Bloodless open heart surgery using membrane oxygenator--the efficacy of ultrafiltration].

The efficacy of ultrafiltration (UF) in the attempt of total bloodless open heart surgery using membrane oxygenator (MO) was investigated in two groups. Group I (GI) consisted of 6 ASD operations between Dec. 1983 and Feb. 1987, which cardiopulmonary bypass (CPB) were performed without UF and with non-hemic priming of Capiox II MO. (Age; 18 +/- 2 (SD) years old, Body Weight; 53 +/- 6 kg, CPB; 77 +/- 24 min.) Group II (GII) consisted of 11 cases (4ASD, 1VSD, 4MS/MR (2MVR), 2AR (2AVR] between Mar. 1987 and Sep. 1988, which CPB were performed with UF in 9 cases and with non-hemic priming of CML/VPCML MO. (Age; 34 +/- 20 yo, Body Weight; 52 +/- 12 kg, CPB; 112 +/- 54 min). Total bloodless surgery were successful in 9 cases (82%) of GII against in only one case (17%) of GI (p less than 0.05). The hematocrit values of successful 9 cases in GII were 40 +/- 2% before operations, more than 19 +/- 3% during CPB, 33 +/- 4% just after operations, and more than 29 +/- 3% through the postoperative course. Blood loss during operations were 1013 +/- 586 ml in GI, and 659 +/- 388 ml in GII (NS). Blood loss after operations were 696 +/- 283 ml in GI and 478 +/- 284 ml in GII (NS). In successful 9 cases of GII, blood loss after operations were 387 +/- 215 ml, significantly less than that in GI (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Intraoperative echocardiographic assessment of left ventricular muscle volume changes after intracardiac operation under cardiopulmonary bypass].

Cardiopulmonary bypass (CPB) and concomitant cardioplegic arrest (CA) may cause impairment of cardiac function with development of myocardial edema. There are few reports of intraoperative assessment of LV mass or muscle volume (MV) in patients, Fifteen patients (age; 0.5-68), 10 with congenital and 5 with valvular diseases, were studied by epicardial 2-dimensional and M-mode echocardiography. LVMV was obtained from M-mode study at pre- and post-CPB during surgery. Pre and post CPB LVMV-index (ml/m2) and percent change of LVMV were compared. CPB-time was 170 +/- 78 min (mean +/- SD), and CA time was 97 +/- 49 min. LVMV index increased significantly from 89 +/- 35 to 103 +/- 43 ml/m2 after CPB (p less than 0.01). Percent change ranging from -3 to +37% (14 +/- 12) correlated to CPB time (r = .81, p less than .01) and also to CA time (r = .62, p less than .05). These results indicated that CPB with CA caused acute increase in LVMV with a positive relation to its duration.

[Noninvasive and quantitative evaluation of pulmonary regurgitation by pulsed Doppler echocardiography--a study in patients with tetralogy of Fallot after corrective surgery].

A noninvasive and quantitative evaluation of pulmonary regurgitation (PR) using pulsed Doppler echocardiography (PDE) was performed in 25 patients with tetralogy of Fallot (TOF) after corrective surgery. Considering a possibility of the presence of the difference in regurgitant flow velocity in pulmonary artery, four sampling points for detecting the pulmonary regurgitant flow were designed as follows: point 0 was positioned at the right ventricular outflow tract; point 1, at the pulmonary annulus; point 2, at mid-portion of the pulmonary trunk; point 3, at bifurcation of the pulmonary artery. The values of maximum Doppler shift determined by analysing the sonograms recorded at point 1, 2 and 3 were examined in comparison with the grades of PR estimated by pulmonary arteriography and the results obtained were as follows. In a retrospective study in 18 patients with PR, the values of maximum Doppler shift were highest at point 1, and followed by point 2 and point 3 in order (p less than 0.005), indicating that the velocity gradient of regurgitant flow existed in the pulmonary artery. The values of maximum Doppler shift were highest in the group of PR grade III estimated by pulmonary arteriography, and followed by the group of PR grade II and grade I in order. At point 2, the group of grade III-PR showed significantly higher Doppler shift than the group of grade I-PR (p less than 0.05). Following above data, a new criteria for estimating the severity of PR by PDE according to the velocity gradient of regurgitant flow in the pulmonary artery was proposed. In a prospective study in a separate group of other 7 patients, the grade of PR estimated by PDE corresponded well with these of pulmonary arteriography, with a significant Spearman rank correlation coefficient (rs = 0.90, p less than 0.01). An experimental study using a dog with surgically induced PR of different grades confirmed the presence of higher Doppler shift in pulmonary artery corresponding to the grade of PR. These results indicated the usefulness of a newly proposed method evaluating PR by PDE applying a concept of Windkessel model for PR regurgitant flow.

Partially unroofed coronary sinus associated with tricuspid atresia. An important associated lesion in the Fontan operation.

A case of tricuspid atresia associated with partially unroofed coronary sinus following a Fontan operation is described. A 4-year-old boy with tricuspid atresia showed persistent arterial desaturation immediately after a modified Fontan operation. At reoperation on the next day, a partially unroofed coronary sinus was recognized and repaired through a left atriotomy. Although uncommon, this associated anomaly should be kept in mind even in the absence of a persistent left superior vena cava and should be suspected if arterial desaturation occurs after a modified Fontan operation.