Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice.

Cerium oxide nanoparticles (CNPs) have a unique surface regenerative property and can efficiently control reactive oxygen/nitrogen species. To determine whether treatment with CNPs can mitigate the delayed effects of lung injury after acute radiation exposure, CBA/J mice were exposed to 15 Gy whole-thorax radiation. The animals were either treated with nanoparticles, CNP-18 and CNP-ME, delivered by intraperitoneal injection twice weekly for 4 weeks starting 2 h postirradiation or received radiation treatment alone. At the study's end point of 160 days, 90% of the irradiated mice treated with high-dose (10 µM) CNP-18 survived, compared to 10% of mice in the radiation-alone (P < 0.0001) and 30% in the low-dose (100 nM) CNP-18. Both low- and high-dose CNP-ME-treated irradiated mice showed increased survival rates of 40% compared to 10% in the radiation-alone group. Multiple lung functional parameters recorded by flow-ventilated whole-body plethysmography demonstrated that high-dose CNP-18 treatment had a significant radioprotective effect on lethal dose radiation-induced lung injury. Lung histology revealed a significant decrease (P < 0.0001) in structural damage and collagen deposition in mice treated with high-dose CNP-18 compared to the irradiated-alone mice. In addition, significant reductions in inflammatory response (P < 0.01) and vascular damage (P < 0.01) were observed in the high-dose CNP-18-treated group compared to irradiated-alone mice. Together, the findings from this preclinical efficacy study clearly demonstrate that CNPs have both clinically and histologically significant mitigating and protective effects on lethal dose radiation-induced lung injury.

Trinucleotide repeat expansion in the FRAXE locus is not common among institutionalized individuals with non-specific developmental disabilities.

Expansion of a polymorphic GCC-repeat at the FRAXE locus has been associated with expression of chromosome fragility at this site and cognitive impairment in some individuals previously testing negative for CGG-repeat expansion in the fragile X mental retardation-1 (FMR1) gene. To determine the frequency of FRAXE triplet repeat expansion among persons with developmental disability, 396 individuals from two institutions were studied, all of whom were negative for FMR1 repeat expansion. Clinically, there was a wide range of mental impairment, with the majority (61.1%) being severely to profoundly affected. The distribution of FRAXE GCC-repeat numbers in the study population was 5-38: 28 (5.6%) with 10-14 repeats; 366 (73.8%) with 15-19 repeats; 74 (14.9%) with 20-24 repeats; 20 (4.0%) with 25-29 repeats; and 5 (1.0%) with 30-38 repeats, with no individuals demonstrating repeat expansion. One profoundly retarded male was found to have a deletion of about 40 bp. Southern blots of HindIII-digested DNAs from individuals with > or = 26 repeats all showed normal patterns. These results suggest that FRAXE GCC-repeat expansion is not a common cause of developmental disability in institutionalized persons with mild to profound mental retardation.

Recovery of immunologically reactive antibodies and antigens from breast cancer immune complexes by preparative isoelectric focusing.

A new technique for the recovery of immunologically reactive antibodies and putative antigens from breast cancer-associated immune complexes was described. Soluble immune complexes were isolated from extracellular fluids by 2.5% polyethylene glycol fractionation and affinity chromatography on Protein A:Sepharose CL-4B. The immune complexes bound to immobilized Protein A were then subjected to preparative isoelectric focusing. The dissociated immunoglobulins and putative antigens were recovered from the appropriate pH regions of the preparative isoelectric focusing gel. G-type immunoglobulins recovered from immune complexes isolated from a breast cancer patient bound to the recovered putative antigen(s) and three breast cancer cell culture lines, but these immunoglobulins did not bind to carcinoembryonic antigen or other cancer cell culture lines originating in colon, pancreas, prostate, or lymphoblast. The recovered putative antigens had isoelectric points between pH 3.0 and 5.0 and molecular weights of 20,000 and 42,000.

Isoelectric focusing--a new approach to the study of immune complexes.

Isoelectric focusing was used to examine antigen-antibody complexes. BSA : anti-BSA complexes were dissociated and antigen was separated from antibody based upon differences in pI value by isoelectric focusing (pH gradient 3--10). The recovered proteins were homogeneous as determined by immunodiffusion and polyacrylamide gel electrophoresis analyses. The technique was capable of resolving 6.4 microgram of BSA : anti-BSA complexes. More than 90% of the complexes applied to isoelectric focusing gels were dissociated and entered the gels. It was further demonstrated, by the use of complexes containing enzymes (acid phosphatase or alkaline phosphatase), that the dissociated enzymes retained their native pI as well as enzymatic activities. The isoelectric focusing technique, therefore, represents a new and effective approach to the dissociation of antigen-antibody complexes.