The anabolic effects of parathyroid hormone on cortical bone mass, dimensions and strength--assessed in a sexually mature, ovariectomized rat model

We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.     

Platinum concentrations in urban road dust and soil, and in blood and urine in the United Kingdom

Increasing Pt concentrations from vehicle catalysts have been reported from a number of countries. Analysis of Pt and Pd in soils and road dusts taken from areas of high and low traffic flows in SE England show concentrations of Pt in the range < 0.30-40.1 ng g-1 and Pd in the range < 2.1-57.9 ng g-1. Higher concentrations of Pt are associated with high traffic densities. Samples taken from streets of lower traffic flows were found to contain the lower concentrations of the ranges. Pilot studies of Pt concentrations in blood and urine using ICP-MS have been carried out. Platinum concentrations in whole blood were: precious metal workers, 780-2170, mean 1263 pmol l-1 (0.152-0.423, mean 0.246 microgram l-1); motorway maintenance workers, 645-810, mean 744 pmol l-1 (0.126-0.158, mean 0.145 microgram l-1); Imperial College staff, 590-713, mean 660 pmol l-1 (0.115-0.139, mean 0.129 microgram l-1). Platinum concentrations in urine in pmol Pt per mmol creatinine were: precious metal workers, 122-682, mean 273 [0.21-1.18, mean 0.47 microgram Pt (g creatinine)-1]; motorway maintenance workers, 13-78, mean 33.7 [0.022-0.135, mean 0.058 microgram Pt (g creatinine)-1]; Imperial College staff, 28-130, mean 65.6 [0.048-0.224, mean 0.113 microgram Pt (g creatinine)-1]. Detection limits were 0.03 microgram l-1 for both blood and urine. The possible health effects of increasing Pt in the environment are discussed. Platinum provides an excellent example of the significance of speciation in metal toxicity. Platinum allergy is confined to a small group of charged compounds that contain reactive ligand systems, the most effective of which are chloride ligand systems. Metallic Pt is considered to be biologically inert and non allergenic and since the emitted Pt is probably in the metallic or oxide form, the sensitising potential is probably very low. Platinum from road dusts, however, can be solubilised, and enter waters, sediments, soils and the food chain. There is at present no evidence for any adverse health effects from Pt in the general environment, particularly allergic reactions.     

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent degradation are highly efficient inducers of cytolytic T lymphocytes

We generated plasmid expression vectors encoding ubiquitin and beta-galactosidase (beta-gal) with different intervening amino acids, allowing for the production of processed protein products that have either stabilizing or destabilizing residues at their N-termini. P815 cells transfected with plasmids encoding beta-gal with a destabilizing N-terminus did not have detectable expression beta-gal unless they were treated with inhibitors specific for the proteasome. Inhibitors of other proteolysis pathways had no such effect. Nevertheless, transfectants expressing beta-gal with different amino acid residues were equally sensitive to cytolysis by a CTL clone specific for a beta-gal peptide presented in the context of H-2Ld. In contrast to vectors encoding native beta-gal, plasmid vectors encoding beta-gal with a destabilizing residue did not induce detectable anti-beta-gal Abs when injected into skeletal muscle of BALB/c mice. However, such vectors were significantly more effective than vectors encoding native beta-gal or beta-gal with a stabilizing residue in stimulating CTL specific for P13.2, a lacZ transfectant of P815. We conclude that incorporation of strategies that enhance proteasome-dependent degradation may generate DNA vaccines that are more effective in inducing cellular immunity against targeted Ags.     

Die Langzeit-Korrosionsgeschwindigkeit des passiven Eisens in anaeroben alkalischen Lösungen

The long-term corrosion rate of passive iron in anaerobic alcaline solutions Gas generation is an important issue in safety assessments of low and intermediate level radioactive repositories. In this connection the hydrogen production from corrosion of passive iron in saturated calcium hydroxide, in dilute alkali hydroxide and cement porewater solutions has been determined. The measurements were performed manometrically using fusion sealed glass cells, the measurement periods being between 275 and 560 days. In 0.1 M and 0.04 M alkali hydroxide solutions the initial hydrogen generation rate was 12 mmol/m²yr corresponding to a linear corrosion rate of 64 nm/yr. The reaction rate decreases with time. The smallest value obtained after 330 days is 0.3 mmol/m²yr corresponding to 1.5 nm/yr. The influence on iron of the saturated calcium hydroxide solution and the calcic porewater solutions differs from that of the alkali hydroxide solutions. At pH 12.5 the hydrogen generation rate remains practically constant up to breaking off the experiment, the value being about 1 mmol/m²yr corresponding to 5 nm/yr.