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.     

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.     

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.     

Time course of superoxide generation by leukocytes—The MCLA chemiluminescence system

This study was performed to examine the pattern of Superoxide (O ₂ ^– ·) generation from leukocytes using the O ₂ ^– · specific chemiluminescence (CL) method.Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA) was used as a CL probe. The appropriate conditions of the MCLA method was first determined for the evaluation of the time course of O ₂ ^– · generation by leukocytes. The time course of O ₂ ^– · generation obtained by the MCLA-CL system was compared with that by the luminol-dependent CL, electron spin resonance (ESR)/spin trapping, and cytochromec systems. Following stimulation by three different stimulants (PMA, OZ, FMLP), leukocytes continuously generated O ₂ ^– · for up to 5 h in the MCLA-CL system, irrespective of the kind of stimulation. The curves obtained by generation ceased more rapidly in the luminol-CL, ESR/spin trapping, and cytochromec systems. A 50% activity of the initial value was observed at 70 min in the MCLA-CL system, but 30, 10 and 35 min in the other systems, respectively. The CL or O ₂ ^– · generation value decreased to less than 1% (possible termination) at 300, 90, 120 and 180 min, respectively. With the exception of ESR studies with OZ, the cell viability was not significantly affected in any of the trials. These results indicate that leukocytes can generate O ₂ ^– · much longer than previously estimated and that the MCLA-CL-system is the most suitable system for the measurement of the O ₂ ^– · generation by leukocytes.     

Hemobilia: Review of Recent Experience with a Worldwide Problem

Between 1981 and 1985, the reported incidence of hemobilia increased for two major reasons. First, a more sophisticated and better-trained medical community could entertain the diagnosis readily in certain settings and had broader access to diagnostic methods that precisely defined the source of bleeding into the biliary tract. Second, there was wider use of percutaneous techniques of diagnosis and treatment of biliary diseases. Once the diagnosis of hemobilia was made by endoscopic or arteriographic means, physicians and surgeons were quicker to institute proper therapeutic measures. For this reason, the mortality associated with hemobilia decreased compared with that reported earlier. The medical community must be aware that modern treatments are now the most common cause of this problem. Since invasive diagnostic methods are increasingly used by nonsurgeons, it is imperative that these patients are studied in the context of complete consultation with surgeons who can use definitive treatments when required.     

Comparison of flow capacities of arterial and venous grafts for coronary artery bypass grafting: evaluation with exercise thallium-201 single-photon emission tomography

Stress thallium-201 tomography was performed to compare the flow capacities of arterial and saphenous vein grafts in patients with coronary artery bypass grafting (CABG). One hundred and seven consecutive patients (95 male and 12 female; mean age 58±9.1 years) underwent exercise-redistribution ²⁰¹Tl myocardial single-photon emission tomography 4–5 weeks after CABG. When a reversible perfusion defect was present in the area covered by a patent bypass graft, the flow capacity of the graft was defined as insufficient. Of all 285 grafts, 211 were considered as complete bypass. Reversible perfusion defects were present in 29 (27%) of 108 myocardial areas supplied by patent arterial grafts but in only 5 (5%) of 103 myocardial areas supplied by patent saphenous vein grafts (P<0.0001). In the LAD area reversible defects were observed in 22 of 82 areas covered by arterial grafts, in contrast to only 1 of 29 areas covered by venous grafts (P<0.01); in the RCA area reversible defects were observed in 7 of 17 and 4 of 41 areas respectively (P<0.01). There was no difference between the native coronary artery stenosis bypassed by patent arterial and venous grafts (88%±12% vs 86%±14% respectively, P=0.27). In conclusion, flow capacities during peak myocardial demand were more frequently insufficient in arterial bypass grafts than in saphenous vein grafts. Received 23 May and in revised form 7 August 1997