Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.

Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.     

Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers

For the act of membrane fusion, there are two competing, mutually exclusive molecular models that differ in the structure of the initial pore, the pathway for ionic continuity between formerly separated volumes. Because biological “fusion pores” can be as small as ionic channels or gap junctions, one model posits a proteinaceous initial fusion pore. Because biological fusion pore conductance varies widely, another model proposes a lipidic initial pore. We have found pore opening and flickering during the fusion of protein-free phospholipid vesicles with planar phospholipid bilayers. Fusion pore formation appears to follow the coalescence of contacting monolayers to create a zone of hemifusion where continuity between the two adherent membranes is lipidic, but not aqueous. Hypotonic stress, causing tension in the vesicle membrane, promotes complete fusion. Pores closed soon after opening (flickering), and the distribution of fusion pore conductance appears similar to the distribution of initial fusion pores in biological fusion. Because small flickering pores can form in the absence of protein, the existence of small pores in biological fusion cannot be an argument in support of models based on proteinaceous pores. Rather, these results support the model of a lipidic fusion pore developing within a hemifused contact site.     

Mixed venous oxygen saturation in abdominal aortic surgery: intraoperative hypothermia and vasodilator therapy implications

This prospective study was designed to test the hypothesis that intraoperative hypothermia occurring during abdominal aortic surgery and vasodilator therapy used to avoid severe consequences of aortic clamping could both disturb the mixed venous oxygen saturation signal (SVO2). Twenty high risk surgical patients, ASA physical status II or III, were catheterized with the standard pulmonary artery catheter; SVO2 was determined by direct spectrophotometric measurements of oxygen haemoglobin concentration of serial samples. The relationships between SVO2, haemodynamic, metabolic variables and core temperature were analyzed. Haemodynamic values and oxygen transport were stable while inadequate tissue oxygenation occurred. A significant correlation was found between SVO2 and CI (r = 0.59, p less than 0.01), SVO2 and SVRI (r = -0.4, p less than 0.01), SVO2 and CT (r = -0.46, p less than 0.01), SVO2 and VO2 (r = -0.76, p less than 0.001). SVO2 and Qs/Qt (r = 0.83, p less than 0.001), SVO2 and EO2 (r = -0.75, p less than 0.001. No correlation was observed between SVO2 and lactacidemia (r = 0.04, p less than 0.05). Satisfactory haemodynamic stability and oxygen transport steady-state were the main conditions for a significant correlation between SVO2 and haemodynamic factors. However, there was no correlation between SVO2 and inadequate tissue oxygenation. SVO2 reflected only oxygen extraction. Intraoperative hypothermia provided an increased haemoglobin affinity for oxygen. Vasodilator therapy which allowed a decrease in systemic vascular resistance produced an increase in the left-right shunt and in venous oxygen admission. Thus hypothermia and vasodilator therapy could be both responsible for the elevated SVO2 occurring during infrarenal abdominal aortic surgery.     

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.