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.     

Enhancement of bradykinin-induced prostacyclin synthesis in porcine aortic endothelial cells by pertussis toxin Possible implication of lipocortin I

Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer. Although ADP-ribosylation of a protein with a molecular weight of 41–42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations. Furthermore, even if IAP was removed from the incubation medium at 3 hr, bradykinin-induced prostaglandin synthesis at 24 hr was still potentiated. Cycloheximide and actinomycin D enhanced bradykinin-induced prostacyclin synthesis and apparently blocked the effect of IAP. Since this result suggested the involvement of an inhibitor protein(s) of prostacyclin synthesis in the IAP effect, we studied the effect of IAP on the level of lipocortin I which is known to inhibit phospholipase A₂. Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I. These results suggest that the enhancement of bradykinin-induced prostacyclin synthesis by IAP is associated with a decrease in the level of lipocortin I.     

Biosynthesis of biotin-vitamers by family Enterobacteriaceae

The biosynthesis of biotin-vitamers from various carbon sources by the members of the Enterobacteriaceae as one of the groups of intestinal bacteria was investigated. The biotin-vitamers synthesized in each case included one or more of dethiobiotin (main product), 7-keto-8-aminopelargonic acid, and biotin. True biotin was shown to be synthesized under aerobic conditions but not under anaerobic conditions by each of several strains belonging to one of the genera, Erwinia, Escherichia, Proteus, and Serratia, and using culture media containing one of galactose, peptone, Polypepton, or casamino acid. In addition, a biotin precursor, pimelic acid, was also synthesized by several bacteria utilizing carbon sources such as maltose, mannose, galactose, peptone, or casamino acid.     

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.     

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.     

Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.