Biomedical subjects

G Kraft

Publications and source records attributed to G Kraft.

At least 55 records · Page 3Linked to original sources

PubMed1998

Biological verification of heavy ion treatment planning.

Chinese hamster ovary (CHO) cells and thermoluminescent detectors (TLD-700) were used for physical and biological verification of heavy ion treatment planning. Experiments were performed in a cylindrical water phantom, in some cases with lung and bone equivalent material in front of the target volume. The results confirm the possibility of using thermoluminescent detectors for a quantitative verification of dose distributions. CHO cells can be used at least for qualitative dose verification.

Animals↗

PubMed1998

Induction of chromosomal damage in CHO-K1 cells and their repair-deficient mutant XRS5 by X-ray and particle irradiation.

The cytogenetic effects of X-rays and Au ions were investigated in repair-proficient CHO-K1 cells and their radiosensitive mutant strain xrs5, which shows a defect in the rejoining of DNA double-strand breaks. Both cell lines were synchronized by mitotic shake off, irradiated in G1-phase with either 250 kV X-rays or 780 MeV/u Au ions (LET: 1150 keV/micrometer) and chromosome aberrations were analyzed in first post-irradiation metaphases. Isoeffective doses of X-rays for the induction of aberrant cells and aberrations per cell were about 14 times lower for xrs5 than for CHO-K1 cells. After high LET radiation the difference in the cytogenetic response of both cell lines was drastically diminished. Furthermore, the analysis of the aberration types induced by sparsely and densely ionizing radiation showed for both cell lines specific changes in the spectrum of aberration types as LET increases. The experimental results are discussed with respect to the different types of lesions induced by sparsely and densely ionizing radiation.

Animals↗

PubMed1998

Analysis of chromosome damage based on the time course of aberrations.

PURPOSE: To describe a method for the analysis of radiation induced chromosome aberrations which will in particular be suitable for the comparison of different radiation qualities. The method is applied to previously published data. METHODS: The basic idea of the approach is to use the time-course of aberrations up to the time when all cells have passed through first mitosis. Instead of comparing data obtained at a single sampling time, the number of aberrant cells or aberrations is integrated over several sampling times. The integral represents a measure of the total fraction of cells showing aberrations and the total amount of aberrations induced in the irradiated cell population. In addition, a correction factor is applied which takes into account the dilution of heavily damaged cells at late sampling times by cell division of undamaged or less severely damaged cells. RESULTS AND CONCLUSIONS: Previously published data on the induction of chromosome aberrations by 4.6 MeV/u Ar ions and X-rays are re-analysed using the new approach. It is demonstrated that this method allows a better comparison of experiments using extremely different radiation qualities and consequently different cell cycle perturbations.

Animals↗

PubMed1998

Survival, differentiation and collagen secretion of human fibroblasts after irradiation with carbon ions and X-rays.

Human fibroblasts are a suitable model to investigate early and late radiation-induced damages because they are involved in most medical irradiation. Early damages of healthy tissue in the entrance channel of the beam and around the tumor are estimated on the basis of cell inactivation measurements (X-ray 250kV, 3.2 Gy/min.; carbon ions at 199 MeV/u, LET 16.2 keV/micrometer; carbon ions at 11MeV/u, LET 153.5 keV/micrometer). Late effects have been assessed by measuring premature differentiation and increased collagen secretion of fibroblasts. In the organism premature differentiation and increased collagen secretion are part of a fibrotic reaction due to a response of tissue cells (among fibroblasts) to primary parenchymal damage. 10 days after irradiation fibroblasts show a dose--and LET--dependent increased collagen secretion correlating with premature terminal differentiation.

Carbon↗

PubMed1997

Computation of cell survival in heavy ion beams for therapy. The model and its approximation.

A simplified method for the calculation of mammalian cell survival after charged particle irradiation is presented that is based on the track structure model of Scholz and Kraft [1, 2]. Utilizing a modified linear-quadratic relation for the x-ray survival curve, one finds that the model yields linear-quadratic relations also for heavy ion irradiation. If survival is calculated as a function of specific energy, z, in the cell nucleus--thus reducing the stochastic fluctuations of energy deposition--the increase in slope of the survival curve and therefore the coefficient beta z can be estimated with sufficient accuracy from the initial slope, alpha z. This permits the tabulation of the coefficients alpha z for the particle types and energies of interest, and subsequent fast calculations of survival levels at any point in a mixed particle beam. The complexity of the calculations can thereby be reduced in a wide range of applications, which permits the rapid calculations that are required for treatment planning in heavy ion therapy. The validity of the modified computations is assessed by the comparison with explicit calculations in terms of the original model and with experimental results for track-segment conditions. The model is then used to analyze the influence of beam fragmentation on the biological effect of charged particle beams penetrating to different depths in tissue. In addition, cell-survival rates after neuron irradiation are computed from the slowing-down spectra of secondary charged particles and are compared to experimental observations.

Animals↗

PubMed1997

Proteolipid protein is necessary in peripheral as well as central myelin.

Alternative products of the proteolipid protein gene (PLP), proteolipid protein (PLP) and DM20, are major components of compact myelin in the central nervous system, but quantitatively minor constituents of Schwann cells. A family with a null allele of PLP has a less severe CNS phenotype than those with other types of PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating peripheral neuropathy, not seen with other PLP mutations of humans or animals. Direct analysis of normal peripheral nerve demonstrates that PLP is localized to compact myelin. This and the clinical and pathologic observations of the PLP null phenotype indicate that PLP/DM20 is necessary for proper myelin function both in the central and peripheral nervous systems.

Adolescent↗

PubMed1997

Acute response of pig skin to irradiation with 12C-ions or 200 kV X-rays.

The acute response of pig skin to treatment with high energy carbon ions (plateau region) at the Gesellschaft für Schwerionenforschung (GSI, Darmstadt, Germany) was compared with changes after 200 kV x-irradiation. Carbon doses isoeffective to the x-ray doses were computed with a recently established model for calculation of the biological effect of heavy ions. Clinical changes and physiological symptoms (blood flow, erythema, trans-epidermal water loss, skin hydration) were scored. The parameters analyzed were maximum and mean values of each symptom during days 24 to 70 after irradiation, and the quantal endpoints for the establishment of dose effect curves were the median values of these. With exception of the maximum change in the red blood cell concentration (p < 0.02) no significant differences could be found in the response to x-rays and RBE-corrected heavy ions. These results indicate that the model is valid for the calculation of biological effects of 12C-ions (plateau region) and may at least for epidermis be applied to treatment planning.

Animals↗

PubMed1996

Measurement of intracellular dna double-strand break induction and rejoining along the track of carbon and neon particle beams in water.

PURPOSE: The study was aimed at the measurement of effect-depth distributions of intracellularly induced DNA damage in water as tissue equivalent after heavy ion irradiation with therapy particle beams. METHODS AND MATERIALS: An assay involving embedding of Chinese hamster ovary (CHO-K1) cells in large agarose plugs and electrophoretic elution of radiation induced DNA fragments by constant field gel electrophoresis was developed. Double-strand break production was quantified by densitometric analysis of DNA-fluorescence after staining with ethidium-bromide and determination of the fraction of DNA eluted out of the agarose plugs. Intracellular double-strand break induction and the effect of a 3 h rejoining incubation were investigated following irradiation with 250 kV x-rays and 109 MeV/u carbon- and 295 MeV/u neon-ions. RESULTS AND CONCLUSION: While the DNA damage induced by x-irradiation decreased continuously with penetration depth, a steady increase in the yield of double-strand breaks was observed for particle radiation, reaching distinct maxima at the position of the physical Bragg peaks. Beyond this, the extent of radiation damage dropped drastically. From comparison of DNA damage and calculated dose profiles, relative biological efficiencies (RBEs) for both double-strand break induction and unrejoined strand breaks after 3 h were determined. While RBE for the induction of DNA double-strand breaks decreased continuously with penetration depth, RBE maxima greater than unity were found with carbon- and neon-ions for double-strand break rejoining near the maximum range of the particles. The method presented here allows for a fast and accurate determination of depth profiles of relevant radiobiological effects for mixed particle fields in tissue equivalent.

Animals↗

PubMed1996

Nuclear fragmentation of high-energy heavy-ion beams in water.

As a part of the physical-technical program of the heavy-ion therapy project at GSI we have investigated the nuclear fragmentation of high-energy ion beams delivered by the heavy-ion synchrotron SIS, using water as a tissue-equivalent target. For a direct comparison of fragmentation properties, beams of 10B, 12C, 14N, and 16O were produced simultaneously as secondary beams from a primary 18O beam and separated in flight by magnetic beam analysis. The Z-distributions of beam fragments produced in the water target were measured via energy loss in a large ionisation chamber and a scintillator telescope. From these data we obtained both total and partial charge-changing cross sections. In addition we have performed Bragg measurements using two parallel-plate ionization chambers and a water target of variable length. The detailed shape of the measured Bragg curves and the measured cross sections are in good agreement with model calculations based on semi-empirical formulae.

Boron↗

PubMed1996

Track structure and the calculation of biological effects of heavy charged particles.

A new approach for the calculation of biological effects of heavy charged particles is discussed. In contrast to other models, the biological effect is determined locally as a function of the local dose deposited by the charged particle tracks. Based on measurable quantities like the X-ray survival curve, the radial dose profile within a track and a geometrical description of the cell nucleus, the model is able to predict several high LET specific properties of charge particle beams, like: (1) the relationship of inactivation cross sections vs. LET and vs. specific energy; (2) the RBE as a function of energy and atomic number of the particles, including the Z-dependent shift of RBE-maxima from 30 keV/micrometer for protons to 300 keV/micrometer for carbon ions; (3) the transition from exponential to shouldered survival curves, depending on the size of the biological object and the corresponding particle fluences.

Alpha Particles↗

PubMed1996

Induction and rejoining of DNA double-strand breaks in CHO cells after heavy ion irradiation.

DNA double-strand breaks (DSBs) are the crucial events ultimately leading to cell inactivation. Aimed at understanding the biological action of the charged particle component of cosmic radiation, the induction of DSBs and their repairability was evaluated in Chinese hamster ovary (CHO-K1) cells after exposure to accelerated particles. Irradiations were performed with various ion species including O, Ni and Ca, covering a LET range from 20 to 2000 keV/micrometer. DSBs were determined for plateau-phase cells using the electrophoretic elution of radiation-induced DNA fragments in a static electric field combined with fluorescence scanning of ethidium bromide stained gels. Assuming a DSB yield of 22 DSB per Gy per cell, as derived from X-irradiation, cross-sections for DSB production were calculated from the corresponding fluence-effect curves at a fraction of 0.7 of DNA retained. The same ordinate was used as a reference for the calculation of relative biological efficiency (RBE) for DSB induction. At low LETs (< or = 20 keV/micrometer) RBE values slightly above unity were obtained, but a decrease of RBE was observed with increasing LET. In the region of 100-200 keV/micrometer the RBE for initial DSB induction was clearly below unity. Rejoining of DSBs was assessed by measuring the fraction of DNA retained following post-irradiation incubation of cells under culture conditions. After exposure to Ca ions, DSB rejoining was considerably impaired compared to X-rays.

Animals↗

PubMed1996

Comparison of chromosomal damage induced by X-rays and Ar ions with an LET of 1840 keV/micrometer in G1 V79 cells.

Synchronous V79 Chinese hamster cells were exposed in G1 to either X-rays or 4.6 MeV/u Ar-ions (LET = 1840 keV/micrometer) and the induction of chromosomal damage was measured at five sampling times ranging from 14 to 30 h after treatment. To distinguish between cells in the first and second post-irradiation cycle the fluorescence-plus-Giemsa technique was applied. The experiment showed that the time-course of the appearance of damaged cells was markedly influenced by radiation-induced cell cycle delays and depended on both radiation quality and dose. The yield of aberrant metaphases and the number of aberrations per metaphase was found to increase with sampling time, but this increase was more pronounced for Ar ions. These differences in yield-time profiles of X-ray and Ar ion induced chromosomal damage are particularly important for an accurate determination of the RBE for particles. Our data clearly indicate that meaningful RBEs can only be obtained if chromosomal damage is analysed at several post-irradiation sampling times and the complete time-course of the expression of chromosomal damage is taken into account. Besides these quantitative differences, differences in the spectrum of chromosomal lesions were observed for X-rays and Ar ions. Following particle exposure more breaks and less exchange-type aberrations were formed compared with X-irradiation and, despite irradiation in G(1), a significant number of chromatid-type aberrations occurred in Ar-irradiated samples. The experimental results are interpreted on the basis of the different pattern of energy deposition by sparsely and densely ionizing radiation. In addition, a statistical analysis based on the Neyman type A distribution is performed, which takes into account the specific stochastic properties of particle irradiation.

Animals↗

PubMed1995

Autonomy for nursing home residents: the role of regulations.

The importance of autonomy and choice to nursing home residents' well-being has been well established. This paper examines the complex role of regulation as it affects the autonomy of nursing home residents. Nonstandardized interviews with residents, family members, nursing staff members, and administrators were conducted at three nursing homes in suburban Maryland. These anecdotal interviews identified the most problematic areas where regulations enforce barriers to autonomy and control. These areas include: scheduling of activities of daily living, food portions, physical environment, and documentation. Suggestions for possible improvements are discussed.

Adaptation, Psychological↗

PubMed1995

Detection of heavy-ion-induced DNA double-strand breaks using static-field gel electrophoresis.

Radiation-induced DNA double-strand breaks (DSBs) were measured in Chinese hamster ovary cells (CHO-K1) using an experimental protocol involving static-field gel electrophoresis following exposure to various accelerated ions. Dose-effect curves were set up, and relative biological efficiencies (RBEs) for DSB induction were determined for different radiation qualities. RBEs around 1 were obtained for low energy deuterons (6-7 keV/microns), while for high energy oxygen ions (20 keV/microns) an RBE value slightly greater than 1 was determined. Low energetic oxygen ions (LET approximately 250 keV/microns were found to show RBEs substantially below unity, and for higher LET particles (> or = 250 keV/microns) RBEs for DSB induction were generally found to be smaller than 1. The data presented here are in line with the generally accepted view that not induced DSBs, but rather misrepaired or unrepaired DNA lesions are related to cellular inactivation.

Animals↗

PubMed1995

Induction of DNA double-strand breaks in CHO-K1 cells by carbon ions.

Radiation-induced DNA double-strand breaks (dsbs) were measured in CHO-K1 cells by means of an experimental approach involving constant-field gel electrophoresis and densitometric scanning of ethidium bromide stained gels. For X-irradiation, an induction efficiency of 36 +/- 5 dsbs (Gy x cell)-1 was determined. With this set-up, the induction of dsbs was investigated in CHO-K1 cells after irradiation with accelerated carbon ions with specific energies ranging from 2.7 to 261 MeV/u. This set of particle beams covers the important linear energy transfer (LET) range between 17 and 400 keV/microns, where maximum efficiencies have been reported for other cellular endpoints like inactivation or mutation induction. For LETs up to 100 keV/microns, RBEs of approximately 1 have been determined, while efficiencies per unit dose decline for higher LETs. No RBE maximum > 1 was found. Data are compared with published results on dsb induction in mammalian cells by radiations of comparable LET.

Animals↗

PubMed1994

Heavy ion induced membrane damage: hemolysis of erythrocytes and changes in erythrocyte membrane fluidity.

Human erythrocytes were irradiated with heavy ions of energies between 4 and 18 MeV/u having linear energy transfer (LET) values between 92 and 14,000 keV/microns. Hemolysis has been studied as a macroscopic parameter for membrane damage and changes of the fluidity as a more microscopic parameter. The membrane fluidity changed in a characteristic dose-dependent manner as detected by electron spin resonance employing 12-doxylstearic acid methyl ester spin label (SL 12). Lysis cross sections and RBE values were determined from dose effect curves. The results demonstrate a high hemolytic efficiency of heavy ions compared to X rays. With increasing LET values the measured relative biological efficiency (RBE) values increase continuously. In the complete LET range the cross sections formed one common curve as function of LET and no saturation effects are observed. This is in direct contrast to other biological endpoints such as cell inactivation or DNA damage.

DNA Damage↗

PubMed1994

Calculations of heavy-ion track structure.

A Monte Carlo model is presented to study details of the energy deposition inside tracks of heavy charged particles in water vapor. The input data for most of the calculations based on the binary encounter approximation are double-differential cross sections for electron emission after heavy-ion impact. The paths of the liberated electrons are simulated, taking into account elastic scattering, ionization, and excitation. Each basic interaction of an electron or heavy ion is treated individually. Radial dose distributions and specific energy deposition are calculated for projectiles from protons to uranium in the energy range from one to several hundred mega-electron volts per unified atomic mass unit. Good agreement with measurements in tissue-equivalent gas and propane is obtained for light and medium-heavy projectiles, whereas for heavy projectiles such as uranium, deviations around a factor of 2-3 are observed.

Electron Transport↗

PubMed1994

Combination of static-field gel electrophoresis and densitometric scanning for the determination of radiation-induced DNA double-strand breaks in CHO cells.

An experimental setup using static-field gel electrophoresis (SFGE) was developed to determine radiation-induced DNA double-strand breaks (DSBs) in CHO-K1 cells after exposure to X-rays or heavy charged particles. The fraction of DNA eluted into the gel matrix depends on the quantity of DSBs introduced. In agreement with a recent report, SFGE and pulsed-field electrophoresis were found to be equally sensitive in DSB detection. With radiolabeled DNA from cell cultures, the absolute amount of DNA migrating out of agarose plugs into the gel was quantified by determining the radioactivity in the gel lane. Alternatively, relative measurements of the amount of DNA released into the gel were achieved with a standardized protocol for both SFGE and a subsequent densitometric scanning of photographic negatives from gels stained with ethidium bromide. After calibration with the radioactive method, the fractions of DNA retained could be calculated directly from the data obtained with the densitometric assay to set up classical dose-effect curves. This procedure was validated for its application with heavy ions using an 500 MeV/u lead beam.

Animals↗