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Chromosomal changes in somatic cells in seminoma patients after treatment with ionizing radiation or cytostatics.

Seminomas are sensitive to both ionizing radiation and cytostatic drugs. The study's objective was to find out the effects of cytostatics or ionizing radiation by comparing the results of genome testing before treatment and immediately afterwards. Repeat cytogenetic testing six months after completion of treatment was used to find out changes resulting from reparatory processes after various types of treatment and the degree of elimination of defective lymphocytes from circulation. Three cytogenetic tests were used in our study to find out structural changes in chromosomes (percentage of aberrations), sister chromatid exchanges (SCE) and the number of micronuclei in binuclear lymphocytes (MN). In patients treated with ionizing radiation, strong inhibition of the mitotic activity of lymphocytes occurred after irradiation of para-aortal and ipsilateral inguinal lymph nodes. However, it is difficult to make a connection between the mitotic activity of lymphocytes and their total number, which was found to be within a normal range throughout the study. There is, therefore, another possibility, i.e. that this process actually involves impairment of intracellular enzymes and blockage of the synthesis of macromolecules in lymphocytes which have suffered a large degree of genome damage. Six months after a completed course of irradiation, mitotic activity was found to be mostly normal; however, there was still a very high percentage of aberrations compared with group II (patients treated with a cytostatic, paraplatin) or with respect to the control group, in which the average percentage of aberrations was 1.42 (excluding dicentrics and rings, which are found in all irradiated patients). From the cytological-mutagenetic point of view, chemotherapy proved to be less aggressive to patients. The results of recovery were visible earlier and the elimination of damaged cells was quicker.

Adolescent↗

Combined effects modeling of ionizing radiation and biological agent exposures.

A simple two-species population model is used to simulate the interactions of a replicating pathogen and the immune system response. This deterministic model is flexible enough to reproduce the salient population-dynamic features, chiefly the tendency toward an equilibrium state in which the pathogen population is reduced to zero or a negligible level after some finite time. The specific immune system species that can be taken initially at zero increases to a finite equilibrium level that represents an immune system "memory" of a given pathogen. The coefficients in the model equations represent production, interaction, and loss rates. Their relative sizes determine the qualitative behavior of the solution in its phase space. The effect on the immune system of exposure to ionizing radiation is modeled by reducing the production rate coefficients; the reduction is proportional to the level of ionizing radiation. According to the model and based on historical hematopoietic data from retrospective accident studies, exposures to ionizing radiation can cause pathogen levels to rise an order of magnitude or more than the baseline (no radiation exposure) case and, for some simulated levels, escape from the bounded region of the phase space. A means is offered to link the deterministic model of time-varying pathogen level in an individual host to the corresponding probability of lethality (increasing with time) of an individual in a population.

Animals↗

Effect of the medium on the ionization constants of some triazole compounds.

The deprotonation and acid ionization constants of some triazole derivatives in various aqueous-organic solvent mixtures were determined potentiometrically at 20 degrees C. The organic solvents used were methanol, ethanol, DMF, DMSO, acetonitrile, acetone and dioxane. The high stabilization of both the non-protonated form by dispersion forces and of the proton by its interaction with the organic solvent are the main factors influencing the deprotonation constant in aqueous mixtures of methanol, ethanol, DMF or DMSO. On the other hand, the hydrogen bonding interactions and the solvent basicity, in addition to the electrostatic effect, contribute to the major effects in the deprotonation process (in solutions enriched with acetonitrile, acetone or dioxane) and the acid ionization process in different aqueous-organic solvent mixtures. Some thermodynamic parameters (delta H, delta G, delta S) of the ionization processes in a pure aqueous medium are also determined and discussed.

Acetone↗

[Plasma ionized magnesium concentration following cardiopulmonary bypass].

We performed a retrospective study to analyze plasma ionized magnesium concentration following cardiopulmonary bypass. Severe decrease of ionized magnesium concentration associated with frequent abnormal ECG sign was found in a patient with magnesium-free cardioplegia. Cardioplegia containing 16 mmol.l-1 of magnesium ion maintained ionized magnesium concentration within normal ranges without postoperative magnesium loading. Use of cardioplegia containing magnesium or adequate magnesium supplement is thought to be essential for patients receiving cardiopulmonary bypass.

Aged↗

Regulation of Ionizing Radiation-induced Apoptosis by MnSOD Gene Transfection.

Ionizing radiation induces the production of superoxide radicals (O(2)(-).) which play a role in apoptosis generation. Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme involved in scavenging O(2)(-). This study is designed to investigate the effect of MnSOD on ionizing radiation-induced apoptosis. The eukaryotic expressing vector, pHbetaAPr-3p-neo, containing sense and antisense human MnSOD cDNA have been introduced into Chinese hamster ovary (CHO) cells respectively by gene transfection method and the MnSOD overexpressing cell lines have been used in this study. It was found that the cell clone overexpressing sense MnSOD could effectively prevent 8 Gy X-ray-induced apoptosis in CHO cells, whereas the clone overexpressing antisense MnSOD increased their sensitivity. Further studies also demonstrated that alterations of mitochondrial membrane potential (deltapsi(m)) may play an important role in the regulatory mechanisms of MnSOD on ionizing radiation-induced apoptosis.

Journal Article↗

[Effects of artificial atmospheric ionization on thyroid gland in albino rat (author's transl)].

Artificial atmospheric ionization acts on rat thyroid gland, but results are depending on treatment polarity: After negative aero-ionization, thyroid gland shows signs of high activity (increased area of follicular epithelium, increased volume of epithelial cell nucleus, and resorption of follicular colloidal material). On the contrary, after positive aero-ionization, hypothyroidism symptoms may be observed, however these signs are less distinct and less homogeneous than signs of activity reported after negative treatment. The simultaneous modifications of serotonemia would be able to partially explain these results.

Animals↗

Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation.

Although it is well established that inheritance of mutations in the Brca1 gene significantly increases the chances of developing breast or ovarian cancers, the mechanisms underlying this specific tumor susceptibility remain to be clarified. It is clear that one of the roles of the Brca1 protein is to facilitate cellular responses to DNA damage. We recently reported that Brca1 function is required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. We also found that mutation of serine 1423 in Brca1, a target of Atm phosphorylation, abrogates the G2-M checkpoint but not the ionizing irradiation-induced S-phase checkpoint. Here we demonstrate that mutation of serine 1387 in Brca1, another target of Atm phosphorylation, conversely abrogates the radiation-induced S-phase arrest but does not affect the G2-M checkpoint. Thus, these two posttranslational modifications of Brca1 have two distinct functional roles in the protein. In addition, although mutation of this site abrogates the ionizing irradiation-induced S-phase arrest, it does not adversely affect cell survival after irradiation. This demonstrates that loss of this checkpoint function by itself does not affect cell survival and suggests that some other function of Brca1 alters cell survival after DNA damage.

Ataxia Telangiectasia Mutated Proteins↗

An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents.

Ku is a heterodimer of M(r) 70,000 and M(r) 86,000 subunits. It binds with strong affinity to DNA ends and is indispensable for nonhomologous DNA end joining (NHEJ) and V(D)J recombination. In this study, we investigated whether down-regulation of the Ku86 gene, by 2'-O-methoxyethyl/uniform phosphorothioate chimeric antisense oligonucleotides (ASOs), increases the sensitivity of the DNA-protein kinase catalytic subunit (PKcs)-proficient human glioma cell line (M059K), and its isogenic DNA-PKcs-deficient counterpart (M059J), to ionizing radiation and anticancer drugs. Transfection of these cell lines with 200 nM Ku86 antisense ASOs was associated with a specific decrease in Ku86 mRNA levels (IC(50) <25 nM; n = 3) and a concomitant rapid decrease (<10% of control) in Ku86 protein expression. Moreover, transfection of M059K cells with Ku86 antisense ASOs markedly increased cell death after treatment with ionizing radiation, bleomycin, and etoposide. However, no sensitization to the DNA cross-linking agents chlorambucil and cisplatin was observed after Ku86 antisense transfection. As expected, transfection of M059J cells with Ku86 antisense ASOs did not result in any sensitization to ionizing radiation, bleomycin, or DNA cross-linking agents, but there was a 2-fold increase in sensitivity to etoposide. Thus, our results indicate that antisense ASOs targeted against Ku86 may increase the efficacy of radiotherapy and DNA-damaging agents in tumor treatment. Furthermore, Ku86 antisense ASOs may be used to create a temporal knockout in different human cell lines to further investigate the biological roles of Ku86.

Antigens, Nuclear↗

Engagement of PI-3-kinase mediated protein kinase C zeta activation in protecting Friend cells from ionizing radiation-induced apoptosis.

Murine erythroleukemia cells (Friend) respond to ionizing radiation with the activation and nuclear translocation of p85alpha subunit of phosphatidylinositol-3-kinase (PI-3-kinase) which mediates the downstream activation and nuclear translocation of atypical Protein kinase C zeta (PKC zeta). This event occurs mainly upon high dose of ionizing radiation (15 Gy) and is concomitant to an increase in BrdU incorporation, which probably accounts for a predominant repair DNA synthesis. Following treatment with wortmannin, a relatively specific inhibitor of PI-3-kinase, both an increased number of apoptotic cells and the inhibition of protein kinase C zeta translocation were detected. Altogether the evidence suggests a potential role of the PI-3-kinase/PKC zeta pathway in protecting Friend cells from ionizing radiation-induced apoptosis offering PKC zeta for consideration as possible target of pharmacological treatments.

Apoptosis↗

Serum ionized calcium and parathyroid hormone in renal stone disease.

Serum ionized calcium was shown to be significantly elevated in a group of twenty-eight subjects with idiopathic hypercalciuria in whom the mean total serum calcium concentration was within normal limits. Measurement of parathyroid hormone levels confirmed that elevated values are suppressible by infusion of calcium. Ten subjects with simultaneous elevation of serum ionized calcium and parathormone levels above 3 S.D. of normal were referred for neck exploration, and a parathyroid adenoma was found and removed in nine. Significant decreases to normal values of serum ionized calcium and parathormone levels of urine and calcium excretion were documented some weeks following operation. The results conflict with both the alimentary calcium hyperabsorption theory and the renal calcium leak theory of the aetiology of idiopathic hypercalciuria, and support the possibility that idiopathic hypercalciuria in many cases represents an early or mild form of 'normocalcaemic' primary hyperparathyroidism.

Adenoma↗

[The multicolour three-photon resonant ionization spectrum studies in uranium atom].

The multicolour three-photon resonant ionization spectra of 238U were measured by using the pulsed dye lasers system synchronously pumped by a frequency doubled Nd:YAG-laser 532 nm output(operated at 10 Hz), a device for atomic beam of U, time-of-flight mass spectrometer and boxcar integrator. The dye laser pulses have a 6 ns duration. Beams from the dye lasers, which have the same polarization direction and are focused by lenses, entered an interaction chamber through opposite windows on a common axis and spatially overlapped the U atomic beam. The optical pulse from dye laser DL2 was delayed to arrive at the interaction region 8 ns after the pulse from dye laser DL1; in the same way, the pulse from DL3 was delayed 8 ns after from DL2. The atomic beam device was made from stainless steel. We generated the U vapor by heating solid U in a graphite crucible by e-type electron-field on first excited states were studied in uranium atom. The question how to determine single-colour, two-colour and three-colour three-photon resonant ionization peak in the three-colour three-photon resonant ionization spectra diagram were solved.

English Abstract↗

Differential and integral W-values for ionization in gaseous water under electron and proton irradiation: consistency of inelastic collision cross sections.

Differential and integral W-values for ionization in gaseous water for electron and proton irradiation have been analyzed from the theoretical point of view for consistency between ionization and total inelastic collision cross sections. For low-energy electrons, which are ubiquitous for all primary radiations, the experimental or compiled cross sections from different sources are sometimes not consistent with one another. A practical, self-consistent procedure is outlined in such cases. The high-energy asymptotic W-values for differential and integral ionization are calculated to be 33.7 and 34.7 eV, respectively, for electron irradiation and 34.6 and 32.5 eV, respectively, for proton irradiation. The computed variations of the W-values with energy are generally in good agreement with experiment. Integral primary W-values due only to the interactions between the incident particle and the water vapor are calculated to be 43.5 and 45.0 eV for electrons and protons, respectively, in the high-energy asymptotic limit.

Electrons↗

[Current epidemiological evidence regarding the health effects of low-dose ionizing radiation. Implications for radiation protection, public health and forensic medicine].

The health effects of low-dose ionizing radiation have been widely studied, but remain uncertain. Up-to-date knowledge about epidemiologic evidence for potential human health effects of low dose ionizing radiation is important for revising national radiation protection legislation. This review, conducted by a multidisciplinary research team of the Italian Institute of Social Medicine, evaluates epidemiologic studies published since July 2003. After careful selection, a total of 302 studies were reviewed. Greater emphasis was given to papers that analyzed data using standardized incidence and mortality ratios and to studies regarding occupational exposures in all workers, healthcare workers and aircrew members. Nevertheless, studies regarding A-bomb survivors of Hiroshima/Nagasaki, Chernobyl cleanup workers, patients exposed for medical reasons, and workers in nuclear plants were also included. Given the limitations of epidemiological studies and excluding the cosmic rays context, which requires further research, the authors conclude that harmful effects from exposures to ionizing radiation at doses lower than 100 mSv cannot be ruled out. Nevertheless, if any harmful health effects do exist, they are certainly very small. The implications for radiation protection, public health and forensic medicine are discussed.

Humans↗

Caspase-1 enhances the apoptotic response of prostate cancer cells to ionizing radiation.

BACKGROUND: The significance of caspase-1 in prostate cancer has recently been documented (Cancer Res 61: 1227-1232, 2001). In this study, we investigated the role of caspase-1 in radiation-induced apoptosis in order to identify the significance of this apoptotic initiator in radiation resistance. MATERIALS AND METHODS: Caspase-1 was over-expressed in DU-145 prostate cancer cells (which have weak endogenous expression of caspase-1), via transfection-mediated gene transfer. Stable transfectants were cloned and expression of caspase-1 was established at the mRNA and protein levels by RT-PCR and Western blot, respectively. Caspase-1 overexpressing clones were characterized for their apoptotic response to ionizing irradiation (0-9 Gy) on the basis of cell viability and Hoechst staining assays and profiling of expression of key apoptosis regulators, such as caspase -3 and -9. RESULTS: Caspase-1 transfectants exhibited a greater sensitivity in response to ionizing radiation than the neomycin control transfectants, as demonstrated by a dramatic loss in cell viability, that temporally correlated with apoptosis induction. Furthermore, caspase-1 overexpression resulted in a significant decrease in clonogenic survival following treatment with ionizing radiation, while the caspase-1 inhibitor, Z-YVAD.fmk, suppressed apoptosis induction in caspase-1 transfectants (p<0.008). The apoptotic effect was associated with increased expression of the pro-enzyme form of caspase-3 in both the caspase-1 transfectants and neo controls cells, with the activated caspase-3 being detected in caspase-1 transfectants only. While this activation of caspase-3 was paralleled by an elevated caspase-9 expression at 9 h post-irradiation, there was no major induction in Apaf-1 or cytochrome c release. CONCLUSION: The present study provides an initial mechanistic insight into the functional involvement of caspase-1 in changing the apoptotic threshold of prostate cancer cells to radiation. These findings will enhance the understanding of the molecular basis of prostate tumor radioresistance and may have significant clinical relevance in improving the therapeutic index of radiotherapy in prostate cancer patients.

Apoptosis↗

[Multiaberrant cell formation caused by exposure to internal densely-ionizing irradiation].

The origin of multiaberrant cells (MACs) was studied by comparing the structure and intensity of chromosome damage in peripheral blood lymphocytes of two groups of people: workers of Siberian Chemical Plant differing in the content of plutonium-239 in their bodies, and inhabitants of a non-polluted settlement (control group). Plutonium-239 is known to be a long-lived densely-ionizing source of alpha-radiation with high linear energy delivery; therefore, it has a stronger effect on cell hereditary structures than gamma-rays. In persons with the content of plutonium-239 higher than 13 nCu, the frequency of MAC was 0.105% which at least tenfold exceeds the spontaneous level. The chromosome-type aberrations that are usually induced by ionizing radiation predominated in MACs. Our results suggest that MAC formation may be caused by internal body irradiation with the incorporated sources of densely-ionizing radiation.

Adult↗

[The two-step three-photon resonant ionization of atom Cu].

This paper discusses the process of resonant laser ablation (RLA), where the two-step three-photon resonant ionization of copper is considered as the best scheme. The rate equations of resonant ionization of copper are calculated and the factors that affect the ionization efficiency are discussed. The results prove the potential advantages of RLA especially the low energy threshold.

English Abstract↗

[The ionized calcium in the blood of domestic chickens: dependence on the laying cycle].

In the present study the plasma concentration of both ionized and total calcium in arterial as well as in venous blood of Leghorn hens and its dependence on the ovulatory cycle were investigated. During the ovulatory cycle, the concentration of ionized calcium in blood of hens follows the course of a sine curve. Maximum calcium ion concentrations (1.58 mmol/l in venous blood and 1.48 mmol/l in arterial blood, respectively) were observed 3 to 6 hours after oviposition, and minimum concentrations (1.26 and 1.19 mmol/l, respectively) at 18 to 21 hours after oviposition. Changes in total and ionized calcium concentration went parallel. Six to 9 hours after oviposition maximum values (4.24 and 4.15 mmol/l respectively) and 21 to 24 hours after oviposition minimum values (3.25 and 2.99 mmol/l, respectively) were measured. The arterio-venous difference was -0.22 mmol/l on average.

Animals↗

Experimental evaluation of conversion factors, N(D,w)/N(X), for Roos-type and Advanced-Markus-type plane-parallel ionization chambers.

A Japanese code of practice for clinical dosimetry, titled "Standard Dosimetry of Absorbed Dose in External Beam Radiotherapy" was published by the Japan Society of Medical Physics (JSMP) in 2002. It mostly followed IAEA Technical Reports Series No. 398, which was based on N(D,w), i.e., the calibration factor in terms of absorbed dose to water for a dosimeter. The Japanese primary standard dosimetry laboratory, however, has not supplied N(D,w) but N(X), as the calibration factor in terms of exposure. The unique feature of the Japanese code was provision of a data table of calculated conversion factors, N(D,w) / N(X) values, for many types of ionization chambers, excluding new plane-parallel ionization chambers. This paper describes the experimental evaluation of the conversion factors for the new plane-parallel ionization chambers, such as the Roos-type and Advanced Markus chambers. The obtained N(D,w) / N(X) values for PTW 34001, Wellhöfer PPC 40 and PTW 34045 were 37.96 +/- 0.19, 37.85 +/- 0.36 and 37.90 +/- 0.26 (Gy/C kg(-1)), respectively. They agreed with estimations based on Monte Carlo calculations.

Calibration↗