Impact of human leukocyte antigen molecules E, F, and G on the outcome of transplantation.

BACKGROUND: HLA class I molecules are divided into classic (Ia) and nonclassic (Ib). Nonclassic HLA molecules (E, F, and G) have acquired relevance owing to their immunomodulatory properties and possible repercussions for induction of tolerance in organ transplantation. The objective of this study was to identify the impact of these molecules on transplant success or failure. METHODS: A systematic review of literature was performed with the use of MeSH terms in Pubmed. Clinical trials, randomized clinical trials, case-control studies, and reviews from the past 15 years were included. RESULTS: HLA-E*0103/E*0103 genotype is associated with lower risk of graft-versus-host disease, decreased mortality, and greater disease-free survival after bone marrow transplantation. There were no significant associations between HLA-F and clinical outcomes in any of the studies. Elevated serum levels of HLA-G were associated with a lower incidence of rejection in hepatic and renal transplantation during the 1st year and lower T-cell response after bone marrow, liver, and kidney transplantation. Detection of mRNA of HLA-G1 was also associated with less graft rejection. CONCLUSIONS: Current literature suggests that nonclassic HLA Ib molecules play an important role in immunotolerance in organ transplantation; however, more studies are required to predict outcomes related to specific genotypes.

External radiation assessment in a wet phosphoric acid production plant.

The factories dedicated to the production of phosphoric acid by the so-called wet acid method are usually considered typical NORM industries, because the phosphate rock used as raw material usually contains high concentrations of (238)U-series radionuclides. The magnitude and behaviour of the radionuclides involved in the production process revealed the need to determine its dosimetric impact on workers. This work aims to partially compensate this lack of knowledge through the determination of external effective dose rates at different zones in the process at a typical plant located in the southwest of Spain. To this end, two dosimetric sampling campaigns have been carried out at this phosphoric acid production plant. The first sampling was carried out when phosphate rocks originating in Morocco were processed, and the second one when phosphate rock processed came from the Kola Peninsula (Russia Federation). This differentiation was necessary because the activity concentrations are almost one order of magnitude higher in Moroccan phosphate rock than in Kola phosphate rock. The results obtained have reflected external dose rate enhancements as high as 1.4microSvh(-1) (i.e., up to thirty times the external exposition due to radionuclides in unperturbed soils) at several points in the facility, particularly where the digested rock (pulp) is filtered. However, the most problematic points are characterised by a small occupation factor. That means that the increment in the annual effective external gamma dose received by the most-exposed worker is clearly below 1mSv (European Commission limit for the general population) under normal production. Nevertheless, special care in the design and schedule of cleaning and maintaining work in the areas with high doses should be taken in order to avoid any possibility of exceeding the previously mentioned general population limit. In addition, the results of the dosimetric campaign showed no clear correlation between (226,228)Ra activity concentrations in the material fluxing during the process (the most important radionuclides from the dosimetric point of view) and the external dose rates. Furthermore, any general dependence of the origin of the rock (i.e., on their radioactive contents) on the external effective dose rate measured has not been observed. These latter findings could be a consequence of three effects: (1) a variable radiation shielding at the different points along the process, (2) a changing geometry of irradiation (from a rock pile up to a thin-layered pulp passing through a solid mass inside pipes and deposits), and (3) the existence of a "memory effect", or background contamination in the installation equipment due to the presence of radionuclide-enriched scales and sludges in pipes and deposits.

Enhancer dependence of polyomavirus persistence in mouse kidneys.

We previously showed that alterations in the enhancer sequence of polyomavirus DNA can alter both the level and the organ specificity of viral DNA replication during the acute phase of infection of newborn mice (R. Rochford, B. A. Campbell, and L. P. Villarreal, J. Virol. 64:476-485, 1990). In this study, we examined whether these enhancer sequence alterations can also affect polyomavirus replication during the persistent phase of infection in vivo. After infection of newborn mice with a mixture of three enhancer variants, the individual organs could select for enhancer-specific viral DNA replication during both the acute and the persistent phases of infection. Contrary to expectations, the ability of some variants to establish a high-level acute infection in some organs (e.g., the pancreas) did not necessarily lead to a persistent infection in those organs. Thus, enhancers can affect acute and persistent infections differently. In addition, some enhancer variants tended to establish a high-level persistent infection in the kidneys immediately following an acute infection; however, in all cases considerable histopathology was associated with these elevated long-term infections, and these mice were always runty. A persistent infection in the kidneys thus appears able to exist in two distinguishable states, a high-level pathological state and a low-level nonpathological state, which can be affected by the viral enhancer sequence.

Analysis of cellular DNA synthesis during polyoma virus infection of mice: acute infection fails to induce cellular DNA synthesis.

It is widely believed that infection with various DNA viruses stimulates quiescent host cells to divide in preparation for virus replication. To examine this issue, the effects of acute polyoma virus infection on cellular DNA synthesis are observed in newborn mice. Using [3H]thymidine incorporation and fluorography of whole mouse sagittal sections, we observed clear, high-resolution images of organ-specific patterns of cellular DNA synthesis in newborn animals. No alteration in these patterns was observed during acute polyoma virus infection. Other methods, including measurements of [3H]thymidine-labeled DNA-specific activities in various tissues and in situ autoradiography, also failed to detect virus-induced alterations in cellular DNA synthesis. These results indicate that newborn animals have high endogenous levels of DNA synthesis and imply that acute polyoma virus infection may not be associated with further induced levels of cellular DNA synthesis.