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J Rassow

Publications and source records attributed to J Rassow.

At least 73 records · Page 4Linked to original sources

Dosimetry and fluence measurements with a new irradiation arrangement for neutron capture therapy of tumours in mice.

Incorporation of 10B in human tumours treated with fast neutrons would increase the local dose in the tumour. In tissue the neutrons are thermalized mainly causing the neutron capture reaction 10B (n,a) 7Li. The dose enhancement can be calculated using the thermal neutron fluence measured by activation of gold foils in a phantom. At a phantom depth of 5 cm a dose enhancement of (0.056 +/- 0.0028)% for each microgram of 10B per gram of tissue was determined in the tumour. A therapeutic gain by this dose enhancement in fast neutron therapy should be examined for a solid tumour in a mouse. The feasibility for neutron capture therapy of tumours in mice depends on the distribution of the tumour dose and on the effective shielding of the bodies of the mice. Therefore, a special holding device for simultaneous irradiation of four tumours was developed. The dose distribution in the tumours and in the surrounding bodies of mice was measured with TLD-300 in a special mouse phantom.

Animals↗

Polypeptides traverse the mitochondrial envelope in an extended state.

Most mitochondrial proteins are synthesized as precursors in the cytosol and imported through contact sites between outer and inner mitochondrial membranes. The molecular mechanism of membrane translocation of precursor proteins is largely unclear. For this report, various hybrid proteins between portions of the precursor of cytochrome b2 and the entire dihydrofolate reductase (DHFR) were accumulated in mitochondrial contact sites. We unexpectedly found that about 50 amino acid residues of the polypeptide chain in transit were sufficient to span both membranes. This suggests a linear translocation of the polypeptide chain and presents evidence for a high degree of unfolding of polypeptides traversing the mitochondrial membranes.

Biological Transport↗

Energy requirements for unfolding and membrane translocation of precursor proteins during import into mitochondria.

ATP is involved in conferring transport competence to numerous mitochondrial precursor proteins in the cytosol. Unfolded precursor proteins were found not to require ATP for import into mitochondria, suggesting a role of ATP in the unfolding of precursors. Here we report the unexpected finding that a hybrid protein containing the tightly folded passenger protein dihydrofolate reductase becomes unfolded and specifically translocated across the mitochondrial membranes independently of added ATP. Moreover, interaction of the precursor with the mitochondrial receptor components does not require ATP. The results suggest that ATP is not involved in the actual process of unfolding during membrane translocation of precursors. ATP rather appears to be necessary for preventing the formation of improper structures of precursors in the cytosol and for folding of imported polypeptides on (and release from) chaperone-like molecules in the mitochondrial matrix.

Adenosine Triphosphate↗

Contact sites between inner and outer membranes: structure and role in protein translocation into the mitochondria.

Contact sites between both mitochondrial membranes play a predominant role in the transport of nuclear-coded precursor proteins into mitochondria. The characterization of contact sites was greatly advanced by the reversible accumulation of precursor proteins in transit (translocation intermediates). It was found that the sites are saturable, apparently contain proteinaceous components and mediate extensive unfolding of the polypeptide chain in translocation. Some components of mitochondrial contact sites are currently being identified.

Animals↗

Treatment planning for neutron therapy of high-grade astrocytomas and pencil gliomas.

If astrocytomas of grade III and IV and pencil gliomas of the spinal cord would be good indications for neutron therapy, high accuracy and homogeneity of the target absorbed dose and the planned spatial dose distribution would be pre-conditions for acceptable low complication rates. Therefore, results of treatment planning calculations have been compared with in vivo measurements and found to be in good agreement. Special care is necessary if the percentage of the gamma-ray component is spatially varying and additionally for fixation of the patient and combination of radiation fields in the case of pencil gliomas. Examples are given how to avoid overdosage and to hold the inhomogeneity even at the borderline of adjacent fields within 10%.

Brain Neoplasms↗

[Neutron flow measurements in the d(14) + Be neutron radiation field from the cyclotron in Essen].

It exists the possibility in the neutron therapy of specific tumours to increase the local energy dose in the tumour by treatment with fast neutrons under use of B-10. Thermal neutrons cause the neutron capture reaction B-10(n, alpha)Li-7 in tissue. A sufficiently high number of thermic neutrons is necessary combined with a possibly selective concentration of B-10 in the tumour as target volume for the clinical application. Gold foils were activated in a water phantom at several depths for the quantitative determination of the thermal neutron fluence. A result of this measurements is a maximal thermal neutron fluence of 1.44 X 10(10) cm-2 at depth of 5 cm with applied total energy dose of 0.8 Gy.

Fast Neutrons↗

[Neutron dosimetry in a model of the body's inhomogeneities using the TLD-300 detector].

The modification of the absorbed dose distribution due to the presence of inhomogeneities in the human body requires thorough research within the scope of radiation treatment planning for tumour therapy with fast neutrons. In this work the effect of air and lung cavities and the depth dose distribution in the near and distant vicinity of the inhomogeneity is studied. By means of thermoluminescence detectors TLD-300 the total absorbed dose is measured in mixed neutron-photon radiation fields in the used polystyrene phantom with embedded inhomogeneity. Lung tissue is simulated by cork. Differences in the concentration of hydrogen between inhomogeneity and surrounding soft tissue lead to new build-up effects. These cause an increase behind and a decrease of the total dose beside and in front of the inhomogeneity. In case of the cork inhomogeneity an absorbed dose increase of maximally 20% in comparison to the absorbed dose in the homogeneous phantom was found. With air as inhomogeneity the increase of absorbed dose reaches a maximum of 30% compared to the homogeneous phantom.

Air↗

Translocation arrest by reversible folding of a precursor protein imported into mitochondria. A means to quantitate translocation contact sites.

Passage of precursor proteins through translocation contact sites of mitochondria was investigated by studying the import of a fusion protein consisting of the NH2-terminal 167 amino acids of yeast cytochrome b2 precursor and the complete mouse dihydrofolate reductase. Isolated mitochondria of Neurospora crassa readily imported the fusion protein. In the presence of methotrexate import was halted and a stable intermediate spanning both mitochondrial membranes at translocation contact sites accumulated. The complete dihydrofolate reductase moiety in this intermediate was external to the outer membrane, and the 136 amino acid residues of the cytochrome b2 moiety remaining after cleavage by the matrix processing peptidase spanned both outer and inner membranes. Removal of methotrexate led to import of the intermediate retained at the contact site into the matrix. Thus unfolding at the surface of the outer mitochondrial membrane is a prerequisite for passage through translocation contact sites. The membrane-spanning intermediate was used to estimate the number of translocation sites. Saturation was reached at 70 pmol intermediate per milligram of mitochondrial protein. This amount of translocation intermediates was calculated to occupy approximately 1% of the total surface of the outer membrane. The morphometrically determined area of close contact between outer and inner membranes corresponded to approximately 7% of the total outer membrane surface. Accumulation of the intermediate inhibited the import of other precursor proteins suggesting that different precursor proteins are using common translocation contact sites. We conclude that the machinery for protein translocation into mitochondria is present at contact sites in limited number.

Amino Acid Sequence↗

Neutron therapy of low grade "pencil" gliomas of the spinal cord: a review of ten cases.

Between 1980 and 1986 ten patients (two males, eight females, median age: 35 years) with spongioblastomas and ependymomas grade I of the spinal cord were treated with fast neutrons from the d(14) + Be reaction after incomplete tumour surgery. Eight patients received three weekly fractions of 0.7 to 1.33 Gy and two patients four weekly fractions of 0.8 Gy to total doses of 7.4 to 10.4 Gy. Two complete and six partial remissions of ataxia and motor disturbances were observed. Bladder dysfunctions in five patients cleared up partially in three cases. In two patients the symptomatology remained unchanged. After a follow-up of eight to 88 months two initially complete and two out of six partial remission were maintained. No severe late effects of the skin have been determined. In summary it is concluded that for incompletely resected "pencil"-gliomas fast neutron therapy seems to be a feasible treatment modality.

Adult↗

Quality control of radiation therapy equipment.

A review is given dealing mainly with the quality control functional performance characteristics of medical electron accelerators as the leading case of all equipment for radiotherapy. The International Electrotechnical Commission (IEC) has prepared a standard and a report, which are now in print. The standard addresses the definition of functional performance characteristics, the specification of test methods and conditions and the obligation of the manufacturer to declare the actual performance values of his equipment in a standardized format. In Germany, a translation of this standard is published as draft standard DIN 6847 part 4. IEC has prepared for simplified test procedures a report with guidelines and a reduced volume of test conditions for periodic tests during the working life of the accelerator. In Germany a standard DIN 6847 part 5 is published on "constancy checks" which is slightly but characteristically different from the IEC Report. The differences are schematically listed and discussed.

Equipment Safety↗

Import pathways of precursor proteins into mitochondria: multiple receptor sites are followed by a common membrane insertion site.

The precursor of porin, a mitochondrial outer membrane protein, competes for the import of precursors destined for the three other mitochondrial compartments, including the Fe/S protein of the bc1-complex (intermembrane space), the ADP/ATP carrier (inner membrane), subunit 9 of the F0-ATPase (inner membrane), and subunit beta of the F1-ATPase (matrix). Competition occurs at the level of a common site at which precursors are inserted into the outer membrane. Protease-sensitive binding sites, which act before the common insertion site, appear to be responsible for the specificity and selectivity of mitochondrial protein uptake. We suggest that distinct receptor proteins on the mitochondrial surface specifically recognize precursor proteins and transfer them to a general insertion protein component (GIP) in the outer membrane. Beyond GIP, the import pathways diverge, either to the outer membrane or to translocation contact-sites, and then subsequently to the other mitochondrial compartments.

Binding Sites↗

Infrared and visible thermoluminescence signals of Tm-doped CaF2 measured by a semiconductor photodiode.

A silicon semiconductor photodiode was used to measure the TL-signal of TLD-300 (CaF2:Tm) detectors irradiated with 60Co gamma rays and 226Ra alpha particles. The applied dose values varied from 0.12 to 14.3 Gy for gamma rays and from about 50 to 300 Gy for alpha particles. Because of the infrared sensitivity of the photodiode the infrared emission of the planchet and the TLD-detector produced a high output signal above about 200 degrees C. In addition to this background signal an infrared emission from the TLD-300 detectors could be detected. This infrared TL-signal exhibited the same dose dependences as the visible signal, but the amplitude was higher than that of the visible TL-signal. For the applied photodiode the ratio of the infrared TL-signal to the visible TL-signal was about 24 for the 100 degrees C peak, about 15 for the 150 degrees C peak and 6 for the 240 degrees C peak.

Alpha Particles↗

Quality assurance procedures in radiotherapy--IEC specifications for equipment.

The International Electrotechnical Commission (IEC) worked out international standards for requirements and tests of electrical, mechanical and radiation safety as well as for definition and tests of functional performance characteristics of radiotherapy equipments (medical electron accelerators, gamma beam teletherapy and afterloading equipments, simulators and accessories) and for clinical dosimeters and terminology for medical radiology. A survey is given on the actual state of standardization projects. The problems of such standards are shown for the standard for functional performance characteristics of medical electron accelerators as example.

Humans↗

A neutron-photon treatment planning intercomparison.

In order to assess different treatment philosophies in different neutron therapy centres as well as to gauge the quality of neutron dose distributions relative to corresponding photon plans, a neutron-photon treatment planning intercomparison has been organized amongst the neutron therapy centres in Europe and the U.S.A. Treatment plans were compared for patients with a tumour in the floor of the mouth, a carcinoma of the base of the tongue and a large bladder carcinoma. A wide variety in treatment plans was received. This was mainly caused by the different assumptions on the treatment margin around the tumour and whether or not the lymph nodes should be irradiated electively. Within the same institute, however, similar types of plans were used for both the neutron and the photon irradiations. The homogeneity of the adsorbed dose over the target volume can be made almost the same for photon and neutron irradiations, although this may require a more complicated technique for neutron treatment. The relative absorbed dose to normal tissues was somewhat higher for the neutron treatment. There is an increased chance of the occurrence of a hot spot with the relatively low energy neutron beams compared to the photon beams.

Aged↗