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.     

CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties

Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.     

Purification and characterization of aplysianin E, an antitumor factor from sea hare eggs

An antitumor factor, aplysianin E, inducing tumor lysis was purified to apparent homogeneity from the supernatant of a homogenate of eggs of the sea hare Aplysia kurodai. Purified aplysianin E was a 250-kDa glycoprotein containing three different subunits. This factor was half-maximally active at 2-114 ng protein/ml and lysed all the tumor cells tested but did not lyse normal white or red blood cells. Aplysianin E was labile on treatments with heat, low pH, urea, guanidine, sodium lauryl sulfate, and periodate, but not with proteases or organic solvents, Aplysianin E completely inhibited the syntheses of DNA, RNA, and protein by tumor cells within 2 h and caused their complete cytolysis within 15 h. Tumor lysis by aplysianin E was inhibited by N-acetylneuraminic acid, suggesting that recognition of the sugar moiety is a key step in cytolysis induced by aplysianin E. Aplysianin E also prolonged the survival of mice bearing syngeneic MM46 ascites or solid tumors. These results suggest that aplysianin E, found in an invertebrate, the sea hare, is a new antitumor factor.     

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.     

Clinical significance of selective middle hepatic venography

Selective middle hepatic venography was performed in 86 patients who had been scheduled to undergo liver resection because of hepatobiliary diseases. Special catheters were used of which tips were bended counterclockwise at an angle of 45 degrees. Successful middle hepatic venograms were obtained in 65 cases (76%). Abnormal findings were observed in 27 cases (42%), and it was difficult to diagnose them by ultrasonography or computed tomography. Selective middle hepatic venogram is very useful to understand surgical anatomy of the liver in each case preoperatively. In 5 cases of giant tumor, middle hepatic venography is necessary to identify the exact site of the tumor. Selective middle hepatic venography is considered to be one of the indispensable, examinations for liver resection.     

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.