Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Superoxide dismutase-like immunoreactivity in spheroids in Hallervorden-Spatz disease

Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS). Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage, we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS). Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative stress directly related to iron accumulation. Received: 15 March 1996 / Revised accepted: 15 July 1996     

Effects of gender on prognosis of patients with known or suspected coronary artery disease undergoing contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined. METHODS AND RESULTS: Follow-up (30+/-17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women. CONCLUSIONS: CE-DSE provides incremental information for predicting future cardiac events in both men and women.     

Use of an aortic connector system for vein grafting

OBJECTIVE: The aortic connector system was used to minimize cerebrovascular complications when performing the proximal anastomosis of vein grafts during coronary artery bypass grafting (CABG). The goal of this study was to investigate the intermediate outcomes of patients undergoing CABG with the aortic connector system. METHODS: The aortic connector was used on nine patients undergoing CABG between November 2002 and July 2003. Intermediate outcomes of the patients were examined, and the results of coronary angiography, which were performed before patient discharge and at least 6 months after discharge, were evaluated. RESULTS: There were no operative deaths or cerebrovascular accidents. One patient died 9 months after discharge, one patient had angina, and the remaining seven patients were asymptomatic. When evaluating the results of angiography performed before patient discharge, two of the 21 distal vein graft anastomoses were occluded (patency rate, 90.5%), but there was no stenosis or occlusion at the proximal anastomoses sites that were performed using the aortic connector. When evaluating the results of the second angiography performed after patient discharge, four of the eight proximal anastomoses were patent, one was completely occluded, two had 90% stenosis and one had 75% stenosis. Further, four of the 18 distal anastomoses were occluded (patency rate, 77.8%). There was no significant difference in graft flow or device size when comparing patients with patent vein grafts and those with stenotic or occluded vein grafts. CONCLUSION: Intermediate outcomes of vein grafting using the aortic connector were suboptimal. Long-term outcome data are forthcoming.     

The current role of preoperative and intraoperative autologous blood donation in pediatric open-heart surgery

Objective: We assessed the current role of preoperative and intraoperative autologous blood donation in pediatric open-heart surgery. Methods: Group 1 consisted of 51 patients between 5 and 10 years old who underwent preoperative autologous blood donation. Group 2 consisted of 50 age-matched patients without preoperative donation as controls. Intraoperative donation was conducted in both groups prior to cardiopulmonary bypass. We evaluated perioperative blood cell count, blood loss, and the need for homologous blood products. Results: No serious complications occurred in preoperative or intraoperative donation. Total preoperative donation storage was 17.5±3.4 mL/kg. Intraoperative donation was 21.7 ±6.1 mL/kg in Group 1 and 12.8±4.0 mL/kg in Group 2 (p<0.001). On admission, serum hemoglobin was lower in Group 1 (12.2±1.0 g/dL versus 13.6±1.6 g/dL, p<0.001) but returned postoperatively to the preoperative value. It hovered at a depressed level in Group 2 (12.2±1.4 versus 10.2±1.1 g/dL, p<0.001). The homologous blood requirement was significantly less in Group 1 than in Group 2 (0% versus 10%, p<0.05). Postoperative platelet counts showed similar curves, and blood loss was not statistically significantly different between groups. Conclusion: Preoperative and intraoperative donations are safe and continue to contribute uniquely to blood conservation, providing important options in comprehensive blood conservation programs in current pediatric open-heart surgery.     

Characteristic findings of hepatocellular carcinoma: an evaluation with comparative study of US, CT, and MRI.

The sensitivity, specificity, and accuracy of ultrasonography (US), dynamic incremented computed tomography (CT) with delayed phase imaging, and magnetic resonance imaging (MRI) with or without Gd-DTPA were studied for detecting the characteristic appearances of hepatocellular carcinomas (HCC): fibrous capsules, fibrous septa, and mosaic appearances. Results were prospectively evaluated in 30 patients who subsequently underwent hepatic lobectomies or segmentectomies. Pathologic evaluations of the resected liver specimens demonstrated fibrous capsules in 20 tumors (66.7%), fibrous septa in 13 tumors (43.3%), and mosaic appearances in 19 tumors (63.3%). The accuracies for fibrous capsules were 71.4% (20 of 28) for US, 81.5% (22 of 27) for CT, and 92.3% (24 of 26) for MRI. The accuracies for fibrous septa were 57.1% (16 of 28) for US, 59.3% (16 of 27) for CT, and 73.1% (19 of 26) for MRI. The accuracies for mosaic appearances were 71.4% (20 of 28) for US, 51.9% (14 of 27) for CT, and 69.2% (18 of 26) for MRI. Gd-DTPA administered MRI showed higher accuracies than did conventional MRI for all manifestations. In conclusion, the fibrous capsules of HCCs were readily detected by CT and MRI. Gd-DTPA administration demonstrated an advantage in clarifying fibrous capsules, as well as fibrous septa and mosaic appearances.     

Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.