Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Ascorbic acid can recycle alpha-tocopherol from the tocopheroxyl free radical in lipid bilayers and in micelles, but such recycling has not been demonstrated to occur across cell membranes. In this work the ability of intracellular ascorbate to protect and to recycle alpha-tocopherol in intact human erythrocytes and erythrocyte ghosts was investigated. In erythrocytes that were 80% depleted of intracellular ascorbate by treatment with the nitroxide Tempol, both 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and ferricyanide oxidized alpha-tocopherol to a greater extent than in cells not depleted of ascorbate. In contrast, in erythrocytes in which the intracellular ascorbate concentration had been increased by loading with dehydroascorbate, loss of alpha-tocopherol was less with both oxidants than in control cells. Protection against AAPH-induced oxidation of alpha-tocopherol was not prevented by extracellular ascorbate oxidase, indicating that the protection was due to intracellular and not to extracellular ascorbate. Incubation of erythrocytes with lecithin liposomes also generated an oxidant stress, which caused lipid peroxidation in the liposomes and depleted erythrocyte alpha-tocopherol, leading to hemolysis. Ascorbate loading of the erythrocytes delayed liposome oxidation and decreased loss of alpha-tocopherol from both cells and from alpha-tocopherol-loaded liposomes. When erythrocyte ghosts were resealed to contain ascorbate and challenged with free radicals generated by AAPH outside the ghosts, intravesicular ascorbate was totally depleted over 1 h of incubation, whereas alpha-tocopherol decreased only after ascorbate was substantially oxidized. These results suggest that ascorbate within the erythrocyte protects alpha-tocopherol in the cell membrane by a direct recycling mechanism.     

Shedding of the soluble IL-6 receptor is triggered by Ca2+ mobilization, while basal release is predominantly the product of differential mRNA splicing in THP-1 cells

The soluble IL-6 receptor (sIL-6R) is generated through either proteolytic shedding of the cognate receptor (PC-sIL-6R), or released as the product of differential mRNA splicing (DS-sIL-6R). Using monocytic THP-1 cells, we demonstrate that both mechanisms are independently regulated, and that each process contributes to sIL-6R production. Shedding of the IL-6R was activated by the Ca2+ ionophore, ionomycin, and inhibited by the TNF-alpha protease inhibitor (TAPI). In contrast, basal sIL-6R release was unaffected by Ca2+ depletion and largely insensitive to TAPI. Moreover, although IL-6R shedding was inactivated by serum starvation, non-stimulated production remained intact. Basal sIL-6R production via differential mRNA splicing was shown through the inhibitory action of brefeldin A and an enzyme-linked immunosorbent assay specific for DS-sIL-6R. Release of this isoform was unaffected by ionomycin or TAPI, indicating that Ca2+ mobilization activates PC-sIL-6R generation, but not DS-sIL-6R. The divergent control of these sIL-6R isoforms indicates that they may independently influence the inflammatory response.     

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.     

Psychology and genetics: A happy marriage?

Presents a lecture delivered at the 1980 meeting of the Canadian Psychological Association. The present status of behavior genetics is reviewed. The nature-nurture issue is considered, and research on the genetic–environment interaction is advocated. Many hybrid sciences use reductionism to explain the phenomena of complex systems by the principles of the more basic sciences that deal with the component parts of these systems. A reductionistic view of behavior genetics is rejected; instead, the author prefers an approach that examines how biological factors directly influence behavior. Current trends in behavior genetics are identified. (French abstract) (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potential antitumor agents. 19. Multiply substituted 4'-(9-acridinylamino)methanesulfonanilides

A series of 42 multiply substituted 4'-(9-acridinylamino)methanesulfonanilides has been prepared and evaluated in the L1210 system. In addition to biologic activity changes resulting from altered agent lipophilic-hydrophilic balance variants containing both acridine 4-CH3 and 3-NH2, NHCOCH3 or NO2 substituents have reduced activity. Variants 3,6-disubstituted, using functions of differing electronic character, have depressed activity, suggesting that there is limited site bulk tolerance. Asymmetric 3,5-disubstitution should then be the preferred pattern; the 3-ND-5CH-3'-OCH variant is the most dose potent (optimum dose qd 1-5, 1.25 mg/kg/day) of the high activity agents of this series so far prepared.     

Hydroxyaliphatic acids in branched copolymers with acyl chloride-terminated long side chains: A new shrink-resist treatment for wool

Two synthetic routes were followed to prepare graft copolymers with long side chains containing acyl chloride terminal groups. In the first of these methods acryloxy aliphatic acyl chlorides were synthesized from ricinoleic acid, 12-hydroxystearic acid and 10-hydroxydecanoic acid and then polymerized with other acrylate ester comonomers. In the second procedure, a prepolymer was formed by copolymerizing acryloyl chloride with acrylate esters. The prepolymer then was treated with 12-hydroxystearic acid or 9(10)-hydroxymethylstearic acid to produce polymers with side chains having terminal carboxylic acid groups. These polymers were made more reactive by conversion to acid chlorides. The active polymers were applied to wool fabrics; the imparted shrink-resistance was durable under an accelerated wash test procedure. An added advantage of the treatment is a soft “hand” or feel resulting from internal plasticization of the polymer coating. No. Market. Nutr. Res. Div., ARS, USDA. W. Market, Nutr. Res. Div. ARS, USDA.     

Functional longevity of intraperioneal drains: an experimental evaluation

Various types of drains were inserted into the peritoneal cavity of twenty-eight dogs. After one to seven days, all drains failed to show the presence of 200 cc of colored fluid injected intraperitoneally. On autopsy, all tubes were surrounded and occluded by omentum.     

Effects of water and other dielectrics on crack growth

Effects of water and a variety of organic liquids on crack-growth rates in soda-lime-silica glass was investigated. When water is present in organic liquids, it is usually the principal agent that promotes subcritical crack growth in glass. In region I, subcritical crack growth is controlled primarily by the chemical potential of the water in the liquid; whereas in region II, crack growth is controlled by the concentration of water and the viscosity of the solution formed by the water and the organic liquid. In region III, where water does not affect crack growth, the slope of the crack-growth curves can be correlated with the dielectric constant of the liquid. It is suggested that these latter results can be explained by electrostatic interactions between the environment and charges that form during the rupture of Si-O bonds.