Monitoring of Venus transgenic cell migration during pregnancy in non-transgenic rabbits.

Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system. Three different methods [fluorescence microscopy, flow cytometry and quantitative polymerase chain reaction (QPCR)] were employed to search for TG cells and gene products in blood and other tissues of non-TG rabbits. Venus positive peripheral blood mononuclear cells (PBMCs) were not detected in the blood of non-TG littermates or non-TG does by flow cytometry. Tissue samples (liver, kidney, skeletal and heart muscle) also proved to be Venus negative examined with fluorescence microscopy, while histology sections and PBMCs of TG rabbits showed robust Venus protein expression. In case of genomic DNA (gDNA) sourced from tissue samples of non-TG rabbits, CAGGS promoter-specific fragments could not be amplified by QPCR. Our data showed the lack of detectable cell transfer between TG and non-TG rabbits during gestation.

Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice.

Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non-specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.

Computerised Decision Support Systems for the management of freshwater radioecological emergencies: assessment of the state-of-the-art with respect to the experiences and needs of end-users.

Assessment of the environmental and radiological consequences of a nuclear accident requires the management of a great deal of data and information as well as the use of predictive models. Computerised Decision Support Systems (CDSS) are essential tools for this kind of complex assessment and for assisting experts with a rational decision process. The present work focuses on the assessment of the main features of selected state-of-the-art CDSS for off-site management of freshwater ecosystems contaminated by radionuclides. This study involved both developers and end-users of the assessed CDSS and was based on practical customisation exercises, installation and application of the decision systems. Potential end-users can benefit from the availability of several ready-to-use CDSS that allow one to run different kinds of models aimed at predicting the behaviour of radionuclides in aquatic ecosystems, evaluating doses to humans, assessing the effectiveness of different kinds of environmental management interventions and ranking these interventions, accounting for their social, economic and environmental impacts. As a result of the present assessment, the importance of CDSS "integration" became apparent: in many circumstances, different CDSS can be used as complementary tools for the decision-making process. The results of this assessment can also be useful for the future development and improvement of the CDSS.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: study of errors in dosimetry.

To provide direct estimates of cancer risk after low-dose protracted exposure to ionizing radiation, a large-scale epidemiological study of nuclear industry workers was conducted in 15 countries. As part of this study, identification and quantification of errors in historical recorded doses was conducted based on a review of dosimetric practices and technologies in participating facilities. The main sources of errors on doses from "high-energy" photons (100-3000 keV) were identified as the response of dosimeters in workplace exposure conditions and historical calibration practices. Errors related to dosimetry technology and radiation fields were quantified to derive period- and facility-specific estimates of bias and uncertainties in recorded doses. This was based on (1) an evaluation of predominant workplace radiation from measurement studies and dosimetry expert assessment and (2) an estimation of the energy and geometry response of dosimeters used historically in study facilities. Coefficients were derived to convert recorded doses to H(p) (10) and organ dose, taking into account different aspects of the calibration procedures. A parametric, lognormal error structure model was developed to describe errors in doses as a function of facility and time period. Doses from other radiation types, particularly neutrons and radionuclide intake, could not be adequately reconstructed in the framework of the 15-Country Study. Workers with substantial doses from these radiation types were therefore identified and excluded from analyses. Doses from "lower-energy" photons (<100 keV) and from "higher-energy" photons (>3 MeV) were estimated to be small.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

Individual monitoring for internal exposure of workers: regulation and practice in Hungary.

Decree of Ministry of Health for the enforcement of the Act on Atomic Energy has put special emphasis on the regulation of monitoring for internal exposure in Hungary. The necessarily general prescription of the Decree called for a guidance to assist the work of the competent authority. The Guide was elaborated on the basis of the IAEA Safety Guide No. RS-G-1.2. According to the IAEA Safety Guide the decision factor shall first be determined for the potential radionuclides and practice applied. For routine monitoring the required frequency, method and MDA values, moreover for special monitoring the method and MDA values were derived for over 50 radionuclides considering two basic assumptions: the activity remaining in or excreted from the body could be determined by the given measurement method and the possible underestimation of intake shall be less than a factor of 3 within the monitoring interval.

Preparation and investigation of thermoluminescence properties of CaSO4:Tm,Cu.

A new sort of thermoluminescent phosphor has been developed with the purpose of enlarging the range of linear dose-response. The thermoluminescence properties of CaSO(4):Tm,Cu, prepared according to our method, were studied in the dose range of 0.5 Gy-125.0 kGy. The results of the present work show that the CaSO(4):Tm,Cu is an excellent new dosimetric material due to its relatively simple glow curve, as a consequence of its simple trap system. Several applications are possible in dosimetry due to its wide range of linearity (2 x 10(-6) to 2 x 10(3) Gy), from environmental and space dosimetry to accidental and high-dose irradiation, e.g. gamma irradiation facilities, electron accelerators, nuclear power plants, radiotherapy, medical physics, and so on.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Demonstration of Trichomonas vaginalis in tracheal aspirates in infants with early respiratory failure.

Trichomonas vaginalis was isolated from the tracheal aspirates of two premature newborns with early respiratory failure who were delivered vaginally by mothers with T. vaginalis infection. The babies were treated successfully with antiparasitic drugs.

Neonatal pneumonia caused by Trichomonas vaginalis.

The authors present two cases of newborn babies infected by Trichomonas vaginalis (hereafter referred to as T. vaginalis) and suffering from severe congenital breathing difficulties and needing artificial respiration. Microscopic examination of the tracheal discharge revealed characteristically moving, flagellated, pear-shaped unicellular organisms. Cultures on CPLM medium proved the presence of T. vaginalis. During pregnancy the mothers' clinical status was negative and both of them mentioned leukorrhoea of changing intensity. They were regularly involved in antenatal care. The infection caused by T. vaginalis could be detected in the two mothers later by culture procedures.

Did NATO attacks in Yugoslavia cause a detectable environmental effect in Hungary?

Because of the intensive NATO bombardment of the neighboring region to Hungary, i.e., Vojvodina, North Yugoslavia, air monitoring for detection of depleted uranium particles supposed to be used as a component of bullets was extended to the Southern region of the country. Alpha spectrometry was applied as a sensitive analytical technique able to detect uranium. Though no depleted uranium was detected in air by the sensitive technique of alpha-spectrometry, the increased uranium content in natural ratio as a component of normal soil, natural gas, etc., is suggested to originate from well dispersed dust (2.5 microm size) emitted to the atmosphere by explosions during bombing. This observation is supported by the geographical distribution and the relatively rapid decrease of pollution after the bomb attacks ceased.

[Neonatal respiratory insufficiency caused by maternal infection with trichomonas vaginalis]. / Anyai Trichomonas vaginalis okozta (újszülöttkori) veleszületett légzészavar.

Authors presented cases of two premature newborns with severe respiratory insufficiency due to congenital maternal Trichomonas vaginalis infection requiring mechanical ventilation. They focused on this special perinatal problem and also on diagnostical and therapeutical modalities of this newly recognised syndrome in the early neonatal period.

The collagen-binding leech products rLAPP and calin prevent both von Willebrand factor and alpha2beta1(GPIa/IIa)-I-domain binding to collagen in a different manner.

Calin and rLAPP are two natural inhibitors that are able to inhibit the vWF-binding and platelet adhesion to collagen both under static and flow conditions. In this study we demonstrate that both rLAPP and Calin prevent alpha2I-domain binding to human collagen type I with an IC50 of 5 microg/ml. However, although both vWF and alpha2I-domain binding to collagen is prevented by rLAPP and Calin, the latter two do not bind to the same collagen site since Calin only partially could compete with rLAPP for binding to collagen. Also vWF and the alpha2I-domain were unable to compete completely with each other for the binding to collagen. So the following hypothesis can be made: the binding sites of vWF and of the alpha2I-domain on human collagen type I are different but close to each other since rLAPP could inhibit both interactions, and thus should bind to an overlapping epitope. The Calin preparation on the other hand may still contain two active principles, one interfering with vWF-binding, the other with the alpha2I-domain-binding to collagen.

[Evaluation of a complex trace element composition and bioutilization using isotope technics and total body measurement]. / Komplex nyomelem készítmény biológiai hasznosulásának tanulmányozása izotópos nyomjelzéstechnika és egésztest-mérés alkalmazásával.

Modified mineral and trace element solutions were prepared containing Zn-65, Co-57, Mn-54, Fe-59, Mo-99 and Ni-63 isotopes which were physico-chemically identical to the original solution. Bioutilization examinations were carried out on animals receiving their normal feeding, after p. os application of complex trace element composition (CTEC) namely whole-body retention studies, bioassays, scintigraphic and excretion examinations in altogether 180 Wistar rats, 6 Beagle and 2 mongrel dogs using whole body counter, gamma and beta counters, gamma camera and metabolic cages. Extremely high whole body retention was measured in case of iron (8-30%), high utilizations in case of zinc (4-5%), cobalt (4-6%), molybdenum (3-4%) and manganese (2-4%) and a lower value in case of nickel. Bioassay and scintigraphic evaluations showed marked liver-, kidney-, and muscle and moderated blood uptakes. The way of excretion was mainly (more than 90%) via the faeces in case of zinc, manganese, iron and nickel, although cobalt excreted in 8% and molybdenum in 52% via the urinary tract. Our results show, that isotope technique combined with whole body counting and excretion studies in an available method for trace element bioutilization studies.

Organometallic photonucleases: a novel class of DNA-cleaving agents.

The first demonstration of DNA cleavage by an organic radical generated via homolysis of a metal-alkyl bond in a Cp-metal complex is presented. Irradiation of CpW(CO)3CH3 (1.5 molecules/base pair) produced methyl radical, giving single-strand cleavage of pBR322 DNA. This process was inhibited by the general radical trap cysteine and by TEMPO, which traps carbon radicals but not oxygen-centered radicals.

Cancer consequences of the Chernobyl accident in Europe outside the former USSR: a review.

The accident which occurred during the night of April 25-26, 1986 in reactor 4 of the Chernobyl nuclear power plant in the Ukraine released considerable amounts of radioactive substances into the environment. Outside the former USSR, the highest levels of contamination were recorded in Bulgaria, Austria, Greece and Romania, followed by other countries of Central, Southeast and Northern Europe. Studies of the health consequences of the accident have been carried out in these countries, as well as in other countries in Europe. This report presents the results of a critical review of cancer studies of the exposed population in Europe, carried out on the occasion of the 10th anniversary of the Chernobyl accident. Overall, three is no evidence to date of a major public health impact of the Chernobyl accident in the field of cancer in countries of Europe outside the former USSR.

Pharmacokinetics of radiopharmaceuticals.

The pharmacokinetics of various radiopharmaceuticals following i.v. administration in mice and rats has been studied and compared. Before injection the radiochemical purity (RP) of the compounds were determined by HPLC and PAGE. In all cases RP-s were higher than 90%. The biodistribution of 99mTc labelled anti CEA IgG was studied in mice bearing human colon carcinoma xenografts. Animals with different tumour weights showed different blood kinetic and tumor uptake. The pilot clinical study of the 99mTc labelled anti melanoma Fab and 111-In-DTPA labelled anti melanoma F(ab')2 showed differences in the pharmacokinetic parameters. (99mTc labelled: comp.A. 84.6%; T1/2:0.6 h, 111-In-labelled: comp.A.: 46%, T1/2 1.5 h.) The various isonitrile derivatives synthetized in our laboratory were labelled with 99mTc and the biodistribution were tested in rats. The kinetic study showed that all the three molecules have different half lives in the heart and liver (T1/2 for heart ranged 5.1-18.6 h, for liver T1/2:1.2-2.5 h). Reversed phase HPLC study of the collected bile showed the 15-100% of injected compounds are metabolized during hepatic excretion. Literature data and our recent observations confirm that the knowledge of pharmacokinetics of radiolabelled compounds both in research, development and clinical practice is of basic importance.