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Biomedical subjects

G Kraft

Publications and source records attributed to G Kraft.

15 recordsLinked to original sources

Histologic evidence of myocardial damage in apparently healthy subjects with ventricular arrhythmias and myocardial dysfunction.

The association of ventricular arrhythmias and myocardial dysfunction could be considered an early step toward cardiomyopathy; therefore, we studied 28 patients in NYHA class I and II, characterized by complex ventricular arrhythmias (VA) on 24-h Holter monitoring and volumetric and/or contractile abnormalities on a standard two-dimensional echocardiogram (2-D echo). All patients underwent radioisotopic angiography, 20 patients complete hemodynamic study, and 15 patients endomyocardial biopsy. Ambulatory ECG monitoring showed the presence of frequent premature ventricular contractions in 14 patients (50%) and episodes of ventricular tachycardia in 16 patients (57%). 2-D echo showed mono- or biventricular enlargement and dyssynergies in 25 patients (89%) (left ventricle in 6, right ventricle in 11, both in 8). Two patients showed only left ventricle enlargement and one patient isolated left ventricular dyssynergies. Radioisotopic angiography showed mono- or biventricular ejection fraction reduction in 24 patients (85%) and regional dyssynergies in 24 patients (85%) in accordance with 2-D echo. Hemodynamic study showed in all patients normal coronary arteries, and right and left angiography confirmed enlargement and/or regional dyssynergies. Endomyocardial biopsy was abnormal in 11 of 15 patients: various degrees of hypertrophy, parcellar fibrosis, and adipogenic infiltration were found. Our preliminary data suggest that the simultaneous occurrence of ventricular arrhythmias and ventricular dyssynergies and/or enlargement in patients without apparent clinical heart disease may represent an early stage of dilated cardiomyopathy.

Adolescent

Irradiation increases proteolysis in erythrocyte ghosts: a spin label study.

X- and gamma-irradiation of human erythrocyte membranes (250-1000 Gy) was found to decrease the ratio of weakly to strongly immobilized signal height of membrane-bound maleimide spin label (Mal-6). Subsequent incubation of spin-labeled membranes at ambient temperature (21 degrees C) induced a progressive increase in this ratio, faster for membranes irradiated with low doses which was hampered by protease inhibitors. These results demonstrate that ionizing radiation stimulates proteolysis of erythrocyte membrane proteins by membrane-associated proteases.

Blood Proteins

LET, track structure and models. A review.

Swift heavy ions when penetrating through matter strip off those electrons having a smaller orbital velocity than the ion velocity. The remaining electrons screen the nuclear charge yielding an effective charge. The effective charge of the ions interacts predominantly with the target electrons causing excitation and ionizations of the target atoms. Using the Bethe Bloch formula for the energy loss combined with the Barkas formula for effective charge, the energy loss values as well as unrestricted and restricted linear transfer can be calculated within a few percent of accuracy. From the primary energy loss only a small fraction of 10% or less is transformed into excitation. The major part of the energy loss is used for the ionization of the target atoms and the emission of the corresponding electrons with a high kinetic energy. These electrons form the track around the trajectory of the primary ion in which two thirds of the primary energy is deposited by collisions of primary, secondary and later generations of electrons with the target molecules. In the electron diffusion process the energy is transported from the center of the track into the halo. The radial dose decreases with the square of the radial distance from the center. The diameter of the track is determined by the maximum range of the emitted electrons, i.e. by the maximum energy electrons. All ions having the same velocity i.e. the same specific energy produce electrons of the same energy and therefore tracks of the same diameters independent of the effective charge. But the dose inside the track increases with the square of the effective charge. Track structure models using this continuous dose distributions produce a better agreement with the experiment than models based on microdosimetry. The critical volume as used in microdosimetry is too large compared to the size of the DNA as critical structure inside the biological objects. Track structure models yield better results because the gross-structure of the track i.e. its lateral extension and the thin down toward the end of the track is included in these calculations. In a recent refinement the repair capacity of the cell has been included in a track structure model by using the complete shouldered x-ray survival curve as a template for the local damage produced by the particle tracks. This improved model yields presently the best agreement with the experiment.

Energy Transfer

When is a family not a family?

Recent molecular investigations of the small-subunit rRNA gene sequences have indicated that established taxonomic hierarchies can be clearly at odds with the degree of evolutionary divergence (as inferred from molecular divergence) between supposedly equivalent taxa at every rank (i.e., species through class), both within and across biological divisions. This is particularly true between the Rhodophyta and the Phaeophyta, whose higher-order taxa appear under- and overinflated, respectively. We present two plausible alternatives that algal taxonomists might adopt in order to invoke discussion on their relative merits.

Eukaryota

Fluidity alterations induced by chemical modification of erythrocyte membrane proteins.

Using EPR technique we have examined the effect of chemical agents on pig erythrocyte membranes. Treatment of the erythrocyte membranes with SH-oxidizing and denaturing or specific for amino groups reagents affects both the membrane proteins and lipids. These results suggest that modified proteins may perturb the interactions of the membrane components and lead to alterations of the membrane organization in the polar region.

Animals

Heavy-ion effects on bacteria spores: the impact parameter dependence of the inactivation.

The impact parameter dependence of the inactivation of Bacillus subtilis-spores has been measured using a heavy-ion minibeam facility, which permits single-ion exposure of individual spores with a spatial accuracy of about 1 micron. The apparatus consists basically of a collimator and a microscope used to position the biological objects directly behind the collimator. Measurements were obtained for nickel, tin, and uranium ions at 1.4 MeV/u. for central hits the results show an inactivation probability of less than one with a continuous decrease in inactivation with increasing distance. Long-ranging effects which extend beyond the range of the delta electrons could not be confirmed.

Bacillus subtilis

The formation of strand breaks in DNA after high-LET irradiation: a comparison of data from in vitro and cellular systems.

This paper presents a summary of our understanding to date of the formation of DNA strand breaks induced by highly energetic particle beams (high-LET radiation). We have compared our own recent data on the formation of strand breaks induced in DNA in an aqueous solution with our previous data and those of others available from the literature for similar lesions made in cellular DNA. When the strand break induction frequency, as number of breaks per Gy per unit DNA, is plotted against LET, a series of biological effect curves (one for each particle atomic number Z) is obtained. The frequency of the formation of single-strand breaks has an RBE of less than 1 for DNA in solution and for DNA in the cell; the frequency of the formation of double-strand breaks (dsb) also has an RBE of less than 1 for DNA in a solution containing low amounts of free radical scavenger(s), while the RBE can be greater than 1 in the 50-200 keV/microns range for cellular DNA. RBE values are with respect to X-rays or cobalt gamma-rays. In cells the level of unrejoined strand breaks is also highest in the 50-200 keV/microns range and may reach 25-35% of the initial break yield depending on particle energy and Z-value. These irreparable lesions include double-strand scissions and some form(s) of single-strand breaks. The data presented cover results obtained for helium to uranium particles, with an LET range of 16 to 160,000 keV/microns. When different biological end-points are compared a strong correlation is found between induction of dsb, chromosomal abnormalities and mutation induction.

DNA

The radiobiological and physical basis for radiotherapy with protons and heavier ions.

Heavy charged particles exhibit a superior dose distribution compared to all conventionally used beams. The small lateral and range straggling, combined with an increase of the dose deposition with increasing penetration depth enables the production of dose profiles shaped precisely to the contours of the treatment volume. In addition, heavy ion beams exhibit an elevated biological efficiency close to the end of the particle range. Therefore, beams of heavy ions deliver a high physical dose combined with a high biological efficiency to a tumor volume while the surrounding healthy tissue is maximally spared.

Cell Cycle

The medical heavy ion therapy project at the Gesellschaft für Schwerionenforschung facility in Darmstadt.

It could be demonstrated that local tumor control is considerably improved by radiation therapy with charged particles (protons or heavier ions). The advantages of heavy ion therapy compared to conventional photon therapy techniques are due to the better physical dose distributions achievable and the radiobiological characteristics of heavy ions. However, because of the expense and complexity of heavy ion therapy it is only carried out at a few facilities throughout the world. The Radiologische Universitätsklinik (Radiological University Hospital) and the Deutsches Krebsforschungszentrum (German Cancer Research Centre, DKFZ) in Heidelberg, in collaboration with the Gesellschaft für Schwerionenforschung (Laboratory for Heavy Ion, GSI) in Darmstadt, have developed a concept to use the new heavy ion synchrotron (Schwerionen-Synchroton SIS) in Darmstadt for medical-clinical irradiations. Due to the high flexibility of the SIS accelerator the medical program can be performed in addition to the planned physical experiments with minor interference only. The close geographical proximity of the three institutes involved and the accelerator which will be completed by the end of 1989 provide the unique opportunity to carry out relevant clinical, medical-physical, physical-technical, and radiobiological research in a relatively short time and, compared to similar projects in other countries, at low cost.

Costs and Cost Analysis

Heavy ion effects on yeast: inhibition of ribosomal RNA synthesis.

Diploid wild-type yeast cells were exposed to beams of heavy ions covering a wide range of linear energy transfer (LET) (43-13,700 keV/microns). Synthesis of ribosomal RNA (rRNA) was assessed as a functional measure of damage produced by particle radiation. An exponential decrease of relative rRNA synthesis with particle fluence was demonstrated in all cases. The inactivation cross sections derived were found to increase with LET over the entire range of LET studied. The corresponding values for relative biological effectiveness were slightly less than unity. Maximum cross sections measured were close to 1 micron 2, implying that some larger structure within the yeast nucleus (e.g., the nucleolus) might represent the target for an impairment of synthetic activity by very heavy ions rather than the genes coding for rRNA. Where tested, an oxygen effect for rRNA synthesis could not be demonstrated.

Energy Transfer

The formation of radiation-induced DNA breaks: the ratio of double-strand breaks to single-strand breaks.

Ionizing radiation causes the formation of strand breaks in cellular DNA, as well as other types of lesions in the chromatin of cells. Some of the earliest investigations of the molecular basis of radiation-induced damage and the implications of enzymatic repair were done by Dr. H. S. Kaplan. The induction frequency of DNA double-strand breaks is of special importance, and it is of interest to know the relative proportions of single-strand and double-strand breaks. This ratio changes noticeably with the radiation quality (ionization density). Because it is difficult to assay for DNA lesions in the large mammalian genome, we have developed a method of assaying for DNA double-strand breaks in the supercoiled nucleosome-complexed Simian virus 40 (SV40) genome, irradiated intracellularly. In this communication we present our measurements of the DNA double-strand breaks (DSBs) to single-strand breaks (SSBs) ratio obtained from the intracellularly irradiated SV40 genome. After cobalt gamma ray and X ray irradiations, this ratio is about 1/10. Our methods and results are compared with pertinent data in the literature. If the DSBs/SSBs ratio of 1/10 for cellular chromatin is correct, a substantial number of DNA double-strand breaks are formed in a mammalian cell after moderate doses (1 Gy) of radiation. The implications of different types of DNA double-strand breaks are discussed.

Cobalt Radioisotopes

[Lipid islands in the gastric mucosa].

Circumscribed lipoid deposition in the gastric mucosa ("lipid island") can macroscopically be mistaken for "early cancer" of the stomach. The aetiology of the lipid islands is not quite clear. Precise diagnosis is possible only with selective biopsy and special staining. Such lipid islands were found in five patients among 1 200 gastrocopies.

Biopsy