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.     

Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy in rats

Ketogenic capacity of mitochondria from the remnant liver of 70% hepatectomized rats was studied in relation to mitochondrial phosphorylative activity. Ketogenic capacity increased to a maximum of 6.04 +/- 0.39 from 3.84 +/- 0.13 of control, with an enhancement of mitochondrial phosphorylative activity 6 hr after hepatectomy, and then decreased to normal levels within 24 hr. Adenylate energy charge, (ATP + 1/2ADP)/(ATP + ADP + AMP), of the remnant liver decreased to 0.825 +/- 0.006 as compared to 0.849 +/- 0.002 of control 6 hr after operation. At 12 hr, total ketone body concentrations of the arterial blood increased concomitant with a fall in ketone body ratio (acetoacetate/3-hydroxybutyrate) which reflects the decreased liver mitochondrial redox (NAD+/NADH) state. These findings suggest that an enhancement of mitochondrial fatty acid oxidation and ketogenesis occurs concomitant with an enhancement of mitochondrial phosphorylative activity in the remnant liver in response to a decreased energy charge after 70% hepatectomy.     

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.     

Thallium-201 SPECT depicts radiologically occult lung cancer.

A case of radiologically occult lung cancer is presented in which 201TI SPECT of the chest clearly delineated the involved area. A 66-yr-old man underwent chest screening examinations for asymptomatic smokers and presented a positive sputum cytology for lung cancer. Conventional chest x-ray, tomography of computed radiography, and a CT scan failed to locate the lesion in the lung. Thallium-201 SPECT, however, was successful in depicting the area of the involvement.     

Glucose consumption and rate constants for 18F-fluorodeoxyglucose in human gliomas.

To investigate the value of direct measurement of the rate constants by performing 18F-labeled fluorodeoxyglucose (FDG) studies of glucose consumption in human gliomas in vivo, a kinetic method with 3- and 4-parameter rate constant models for FDG uptake was used to analyze data from dynamic scans obtained by positron emission tomography after injection of FDG into 14 patients with glioma. The results were compared with those obtained by the autoradiographic method using 3- and 4-parameter rate constant models. There were no significant differences in the glucose consumption calculated by the four different methods both in the gliomas and in the contralateral intact cortex. It was found that the rate constant k4* could be neglected in calculation of glucose consumption in gliomas as well as in the contralateral intact cortex. The rate constant k3*, an index of hexokinase function, was higher in malignant gliomas than in benign gliomas and was close to that in the contralateral cortex. This study indicates that the 3-parameter autoradiographic method, which is the most common one used in clinical practice, is reliable for the calculation of glucose consumption in human gliomas. Furthermore, direct measurement of the regional rate constants for FDG by the kinetic method was found to be useful for evaluation of the biochemical and physiological characteristics of human gliomas in vivo.     

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.     

The results of an investigation of the various factors influencing the late patency ratio of coronary bypass grafting

The purpose of this communication was to find out the factors influencing the late patency ratio of coronary artery bypass grafts of 42 patients in our institution. The following results were obtained: 1. The size of the measured diameters of coronary arteries and the graft flow rates were correlated well to the late patency ratio (p less than 0.05). 2. The regular physical exercise trainings were significantly important to keep patent grafts (p less than 0.01). 3. In blood serum studies, serum uric acid levels were significantly lower (p less than 0.05), the average mean HDL cholesterol levels were much higher (p less than 0.001) and the ratio of total cholesterol to HDL cholesterol were significantly lower in the group with late patent grafts than with grafts occluded. Therefore, we found out the variables affecting graft patency ratio which were examined by a stepwise method were the diameter of the coronary artery, regular physical exercise training, the average of lower serum uric acid levels and higher HDL cholesterol levels. The multiple coefficient for these four variables was 0.562 (p less than 0.001) and the contribution was 31.6%. According to the base of this studies, we have concluded that postoperative regular physical exercise, low fat and restricted calorie intake were very important to keep the late patent grafts in long-term follow up period after coronary bypass surgery.