Activation-induced cytidine deaminase fails to induce a mutator phenotype in the human pre-B cell line Nalm-6

Activation-induced cytidine deaminase (AID) plays a key role in the induction of somatic hypermutation and class switching at the immunoglobulin loci of B lymphocytes. AID overexpression can induce a mutator phenotype in lymphoid and nonlymphoid cell lines, suggesting that AID by itself is sufficient to trigger hypermutation and class switching. AID expression in vivo is considered to be restricted to germinal center B lymphocytes, yet AID expression is also seen in many B cell lymphomas, hinting at a potential role for the development of these malignancies. We used a GFP-based reversion assay to efficiently evaluate the activation of mutator phenotypes. As expected, AID overexpression in the human Burkitt lymphoma cell line BL70 caused hypermutation. Surprisingly, AID overexpression in the human pre-B cell line Nalm-6 failed to induce a detectable mutator phenotype, indicating that Nalm-6 cells are probably lacking an essential factor(s) to confer AID-induced mutagenesis. This finding supports the concept that AID overexpression by itself must not automatically lead to the onset of a mutator phenotype. In addition, treating Nalm-6 transfectants with thymidine, a potential mutagenic drug, caused profound mutation rates on the GFP transgene. Thus, the GFP-based mutation assay might prove a powerful tool to study protein- and chemical-induced mutator phenotypes in cell lines.     

Traffic related pollutants in Europe and their effect on allergic disease

PURPOSE OF REVIEW: The prevalence and incidence of allergic diseases have increased in Europe during the last decades, as in most industrialized countries in other parts of the world. Persistent exposure to traffic related air pollution and especially particulate matter from motor vehicles has often been discussed as one of the factors responsible for this increase. This view seems to be supported by recent human and animal laboratory-based studies, which have shown that particulate pollutants, and in particular diesel exhaust particles, can enhance allergic inflammation and induce the development of allergic immune responses. However, the results from epidemiologic research provide a more complex picture. RECENT FINDINGS: It has been clearly shown in many studies that traffic related air pollution contributes to increased mortality risk; in particular in relation to cardiopulmonary causes. Traffic related air pollution also increases the risk of non-allergic respiratory symptoms and disease. However, for allergic symptoms and illnesses like asthma, allergic rhinitis, atopic dermatitis, wheeze, and allergic sensitization less consistent results have been found. This is the reason why the World Health Organisation concludes cautiously that traffic related air pollution may increase the risk of allergy development and may exacerbate symptoms in particular in susceptible subgroups. This review concentrates on recent epidemiologic studies on the long-term effects of exposure to traffic related air pollution on allergic disease in Europe. SUMMARY: In conclusion, the evidence for an increased risk for asthma and hay fever still is weak but seems to be strengthened a little. However, many questions are left open.     

Time trends of thyroid cancer incidence in Ukraine after the Chernobyl accident.

The rate of childhood thyroid cancer incidence observed in northern Ukraine during the period 1986-1998 is described as a function of time-since-exposure, age-at-exposure, and sex. Conclusions are drawn for the excess absolute risk per dose: after a minimal latency period of about three years it shows a linear increase with time-since-exposure for at least nine years. It is roughly constant in age-at-exposure, up to 15 years. For girls exposed very young it is about a factor 2 larger than for boys. For children exposed at age 16-18 this ratio increases to about 5. The thyroids of young children are not more sensitive to radiation dose than those of older ones in absolute risk in northern Ukraine in the currently used data set. As the background is increasing with age, a constant absolute risk gives a decreasing relative risk.     

Thermoluminescence dosimetric properties of a new thin beta detector (LiF:Mg, Cu, P; GR-200F) in comparison with highly sensitive Al2O3:C beta dosimeters.

There is an increasing need for efficient beta detectors to fulfil ICRU recommendations for new quantities especially in the field of medical physics and retrospective dosimetry. The thermoluminescence properties of thin LiF:Mg, Cu, P (GR-200F) tapes produced in 1998 by Sange Company, People's Republic of China, are investigated and compared with those of highly sensitive thin Al2O3:C beta detectors as regards their applicability in the detection of low energy photons and beta particles. The radiation dose response, minimum detectable dose, reproducibility of measurements and effect of residual signal at low dose are assessed for the possible low level beta dosimetry use. The radiation dose response and photon and beta detection efficiencies are tested underpractical laboratory conditions. The effects of indoor fluorescent light and residual signal after the first read-out are investigated with a view to optimising handling conditions such as post-irradiation and pre-heating treatments for routine dosimetry. The photon energy responses of the detectors are investigated using 150 keV filtered x-rays and 60Co gamma-rays.     

Induction and suppression of anti-antibodies to syngeneic T cell-binding antibodies in mice

Considerable effort is being invested in antibody gene technologies for production of species-adapted anti-T cell antibodies which can overcome formation of neutralizing anti-antibodies (anti-Ab). By establishing a mouse model for the generation of syngeneic anti-T cell MoAb, we addressed the question of whether ideally species-adapted T cell-binding antibodies can prime mice to produce anti-Ab. Two anti-Thy-1.2 MoAbs of IgG2a (MmTC) or IgM (MmTC-IgM) isotype were generated in congenic C57Bl/6-Thy-1.1 mice. Three injections of MmTC in C57Bl/6-Thy-1.2 or (C57Bl/6-Thy-1.2×C57Bl/6-Thy-1.1)F₁ hybrids where they act as syngeneic anti-T cell MoAbs induced low anti-Ab. When MmTC was injected as Igh-mismatched antibody in CBA/J mice, high titre anti-MmTC antibodies were measured and fully mismatched skin allografts rejected within 26 days. MmTC injected twice weekly in syngeneic C57Bl/6 mice induced low anti-MmTC and prolonged graft survival up to day 117. In contrast, retreatment induced anti-MmTC with graft rejection within 32 days. Thus, upon retreatment, the immunosuppressive effects of MmTC were inhibited to a similar extent as that seen after antibody treatment in Igh-mismatched mice. However, a recently analysed immunological principle to suppress anti-Ab against T cell binding allo- or xenoantibodies by preinjection of T cell-depleting antibody with species differences in heavy chains also suppressed syngeneic anti-Ab after MmTC retreatment. This effect was accompanied by prolonged graft survival. Thus, our data indicate that inhibitory anti-Ab must be considered in humans even when treated with fully species-adapted anti-T cell MoAb, but may be suppressed by preinjection of a Fc region-mismatched anti-T cell antibody.     

The 3rd international intercomparison on EPR tooth dosimetry: Part 1, general analysis.

The objective of the 3rd International Intercomparison on Electron Paramagnetic Resonance (EPR) Tooth Dosimetry was the evaluation of laboratories performing tooth enamel dosimetry below 300 mGy. Participants had to reconstruct the absorbed dose in tooth enamel from 11 molars, which were cut into two halves. One half of each tooth was irradiated in a 60Co beam to doses in the ranges of 30-100 mGy (5 samples), 100-300 mGy (5 samples), and 300-900 mGy (1 sample). Fourteen international laboratories participated in this intercomparison programme. A first analysis of the results and an overview of the essential features of methods applied in different laboratories are presented. The relative standard deviation of results of all methods was better than 27% for applied doses in the range of 79-704 mGy. In the analysis of the unirradiated tooth halves 8% of the samples were identified as outliers with additional absorbed dose above background dose.     

Estimation of patient dose from radiopharmaceuticals using voxel models

The aim of this study was to demonstrate the advantages of patient dosimetry using voxel models and to present sets of dose estimates for patients of different gender and size. These models offer greater realism with respect to organ shape and topology than the well-established Medical Internal Radiation Dose (MIRD)-type mathematical models. At the National Research Centre for Environment and Health (GSF), specific absorbed fractions have been previously calculated for 4 male and 3 female voxel models, representing different age and stature, for a wide range of source organs. For this study, estimates both for established and new radiopharmaceuticals were performed using biokinetic data from International Commission on Radiological Protection (ICRP). The above calculations allowed for comparison to the MIRD technique in relation to the resulting absorbed organ and effective doses. Furthermore, data sets representing a range of voxel phantoms were investigated. It was found that dose differences among the voxel models can amount up to a factor of 3.     

The big ban on bituminous coal sales revisited: serious epidemics and pronounced trends feign excess mortality previously attributed to heavy black-smoke exposure

The effect of banning bituminous coal sales on the black-smoke concentration and the mortality rates in Dublin, Ireland, has been analyzed recently. Based on the application of standard epidemiological procedures, the authors concluded that, as a result of the ban, the total nontrauma death rate was reduced strongly (-8.0% unadjusted, -5.7% adjusted). The purpose of this study was to reanalyze the original data with the aim of clarifying the three most important aspects of the study, (a) the effect of epidemics, (b) the trends in mortality rates due to advances in public health care, and (c) the correlation between mortality rates and black-smoke concentrations. Particular attention has been devoted to a detailed evaluation of the time dependence of mortality rates, stratified by season. Death rates were found to be strongly enhanced during three severe pre-ban winter-spring epidemics. The cardiovascular mortality rates exhibited a continuous decrease over the whole study period, in general accordance with trends in the rest of Ireland. These two effects can fully account for the previously identified apparent correlation between reduced mortality and the very pronounced ban-related lowering of the black-smoke concentration. The third important finding was that in nonepidemic pre-ban seasons even large changes in the concentration of black smoke had no detectable effect on mortality rates. The reanalysis suggests that epidemiological studies exploring the effect of ambient particulate matter on mortality require improved tools allowing proper adjustment for epidemics and trends. Aspects of harvesting and more recent results derived from a distributed lag model covering the effects of black smoke and temperature are also discussed.