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R Nolte

Publications and source records attributed to R Nolte.

At least 19 recordsLinked to original sources

RBE of quasi-monoenergetic 60 MeV neutron radiation for induction of dicentric chromosomes in human lymphocytes.

The production of dicentric chromosomes in human lymphocytes by high-energy neutron radiation was studied using a quasi-monoenergetic 60 MeV neutron beam. The average yield coefficient [see text] of the linear dose-response relationship for dicentric chromosomes was measured to be (0.146+/-0.016) Gy-1. This confirms our earlier observations that above 400 keV, the yield of dicentric chromosomes decreases with increasing neutron energy. Using the linear-quadratic dose-response relationship for dicentric chromosomes established in blood of the same donor for 60Co gamma-rays as a reference radiation, an average maximum low-dose RBE (RBEM) of 14+/-4 for 60 MeV quasi-monoenergetic neutrons with a dose-weighted average energy [see text] of 41.0 MeV is obtained. A correction procedure was applied, to account for the low-energy continuum of the quasi-monoenergetic spectral neutron distribution, and the yield coefficient alpha for 60 MeV neutrons was determined from the measured average yield coefficient [see text]. For alpha, a value of (0.115+/-0.026) Gy-1 was obtained corresponding to an RBEM of 11+/-4. The present experiments extend earlier investigations with monoenergetic neutrons to higher energies.

Cells, Cultured↗

Quasi-monoenergetic neutron reference fields in the energy range from thermal to 200 MeV.

Well-characterised neutron fields are a prerequisite for the investigation of neutron detectors. Partly in collaboration with external partners, the PTB neutron metrology group makes available for other users neutron reference fields covering the full energy range from thermal to 200 MeV. The specification of the neutron fluence in these beams is traceable to primary standard cross sections.

Algorithms↗

Measurement of neutron fluence spectra up to 150 MeV using a stacked scintillator neutron spectrometer.

A stacked scintillator neutron spectrometer (S3N) consisting of three slabs of liquid organic scintillator is described. A pulsed beam providing a broad spectrum of neutron energies is used to determine the detection efficiency of the spectrometer as a function of incident neutron energy and to measure the pulse height response matrix of the system. Neutron spectra can then be determined for beams with any kind of time structure by unfolding pulse height spectra measured by the S3N. Examples of fluence spectrum measurements in the energy range 20-150 MeV are presented.

Calibration↗

Spectral characteristics of light sources for S-cone stimulation.

PURPOSE: Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. METHODS: First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. RESULTS: Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). CONCLUSION: Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

Humans↗

Dosimetric measurements of electron and photon yields from solid targets irradiated with 30 fs pulses from a 14 TW laser

A 14 TW Ti:Sa laser furnishing pulses with a duration of 30 fs (full width at half maximum) at a repetition rate of 10 Hz was used to expose solid targets to intensities of up to 3x10(18) W/cm(2). Dosimetric techniques were employed to study the total x-ray yield, the spectral and angular distribution of the x-ray photons and the energy distribution of high-energy electrons injected into the solid target and emitted into the vacuum. Scans of laser pulse energy and duration were carried out to study the dependence of the x-ray generation efficiency on these parameters. The radiation transport processes in the target were modeled using the Monte Carlo method. The results of these calculations were used to interpret the measurement results and to critically discuss the applicability of dosimetric methods to the investigation of photon and electron emission from laser-produced plasmas.

Journal Article↗

A model for photon detection and dosimetry with superheated emulsions.

A model is presented for the analysis and prediction of the photon response of detectors based on superheated emulsions of light halocarbons in tissue equivalent gels. It is shown that on the basis of a nondimensional thermodynamic quantity, called reduced superheat, it is possible to identify the degree of superheat, or the operating temperature, corresponding to the photon sensitization of the emulsions. Moreover, on the basis of the mass energy absorption coefficients, it is possible to determine the energy dependence of the photon response. The vaporization energy necessary for bubble nucleation is estimated by means of the thermal spike theory developed for bubble chambers. The energy deposition requirements are consistent with the energy transferred by secondary electrons at the end of their range in the halocarbons. These findings provide design criteria for photon detectors based on superheated emulsions. It is shown that light halocarbons of low effective atomic numbers present the best dosimetric properties. In particular, by manufacturing superheated emulsions with octafluoropropane, or halocarbon R-218, photon sensitivity is achieved at room temperature along with a fairly constant air-kerma response.

Emulsions↗

Activation of the fifth component of human complement, C5, without cleavage, by methionine oxidizing agents.

Purified human C5 was incubated with chloramine T (Cl-T) or N-chloro-succinimide (N-Cl-S) in barbital buffer, pH 7.2. The treatment led to C5 activation: Cl-T- and N-Cl-S-treated C5 acquired a binding site for C6; upon incubation with C6 and subsequent addition of C7, C8 and C9 a membrane attack complex formed which lysed non-sensitized guinea pig red cells (reactive lysis). While the physiological activation of C5 follows its specific cleavage, the resulting fragment C5b representing the activated C5 and expressing the C6 binding site, the treatment with the mentioned chemicals does not lead to fragmentation of the C5 protein. So, functionally, the product of the chemical treatment is C5b-like, but chemically, it comprises the whole protein; no C5a is released. Cl-T and N-Cl-S are known to more or less selectively oxidize methionine residues in proteins, dependent on the conditions. Other sensitive amino acid residues are tryptophan and cysteine. Conditions were chosen for treatment of C5 with Cl-T which exclude attack on tryptophan, and we have ensured that human C5 does not contain free cysteine residues. Further, oxidation of about 60% of the methionine residues of C5 by Cl-T was demonstrated by amino acid analysis. So, all evidence points to methionine residue(s) as the site of attack of Cl-T and probably also of N-Cl-S. The oxidation product of methionine, its sulphoxide, may cause a change in structural conformation of C5 which involves expression of the C6 binding site. Earlier it was found that oxidation of C5 by hydroxyl radicals leads to its activation without cleavage. Since the properties of this C5b-like product resemble those of the product of treatment with Cl-T and N-Cl-S, it is suggested that the formerly found activation of human C5 by hydroxyl radicals is also mediated by oxidation of methionine residue(s) in the C5 protein.

Chloramines↗

[West syndrome].

West-Syndrome is an age-dependent early epileptic encephalopathy manifesting during the first year of life. It carries a high risk for an unfavourable longterm prognosis, especially for the prevailing group of patients with the symptomatic form. Etiologically associated factors are heterogeneous. Among them fetal developmental defects and perinatal hypoxic-ischemic complications predominate. Infantile spasms difficult to control and early manifesting defects in social and communicative capacities determine the poor outlook for longterm mental prognosis. Benefits and risks of currently used anticonvulsant medication are discussed. The need for systematic multimodal longterm care is stressed.

Adrenal Cortex Hormones↗

Behavioural and developmental aspects of primary generalized myoclonic-astatic epilepsy.

The evolution of psychomotor development and behaviour was studied in 15 children with primary generalized myoclonic-astatic epilepsy and with developmental status adequate for age at final examination at school age following a mean follow-up period of 8.5 years. Temporary arrest of mental and motor development in 4 children was related to high seizure frequency or, in 3, to non-convulsive status. Different types of behavioural abnormalities were documented frequently during the course of the disorder; they were significantly related to active seizure periods and to a lesser extent to anticonvulsant medication. Persistent behavioural abnormalities were noted in 5 children. Hyperkinesia, short attention span and emotional lability were the most frequent complaints. None of the children needed special care and those followed-up until school age were seizure-free, without medication and in classes appropriate for their age. At initial examination the high probability of a favourable prognosis may be anticipated in children with normal development before seizure onset, lack of gross brain pathology and with strong indications (family history and/or EEG criteria) for a genetic predisposition. Nevertheless, repeated systematic re-evaluation for early recognition of possible developmental and/or behavioural deviances throughout the course of illness are recommended.

Child Behavior Disorders↗

Binding of iron to the 5th component of human complement directs oxygen radical-mediated conversion to specific sites and causes nonenzymic activation.

It was earlier found that hydroxyl radicals (OH.) generated in a fluid phase system, convert human C5 to an activated, C5b-like form without cleavage. For the conversion catalytic amounts of divalent iron were necessary; upon their oxidation OH. are generated. In view of the extraordinary reactivity of OH. their specific effect on C5 was surprising. It has now turned out that C5 binds iron, about 13-15 Fe ions per molecule C5. C5 was fully bound to iron-loaded Chelating Sepharose and in this way removed form the medium. Only at the sites where iron is bound, is OH. generation possible. The half-life of OH. is extremely short and hence the radicals can act on C5 only in the immediate environment of the binding sites for iron. In this way the oxidative change of C5, induced by the radicals, is restricted to some sites on the molecule determined by the iron binding. The hydroxyl radical scavenger, dimethylsulfoxide (DMSO), is unable to interfere with the conversion of C5 by OH. generated on iron-Sepharose, it does not reach the site of reaction in that system. In fluid phase systems DMSO does inhibit the conversion of C5 to C5b-like C5.

Binding Sites↗

Non-enzymic activation of the fifth component of human complement, by oxygen radicals. Some properties of the activation product, C5b-like C5.

Purified human C5 was converted non-enzymically to an activated form as defined by its ability to participate in reactive lysis. This conversion occurred following exposure to systems that generate oxygen radicals, namely addition of H2O2 in the presence of ascorbic acid and iron or the addition of xanthine oxidase, acetaldehyde and iron. The conversion of C5 to a functionally active species was iron-dependent and inhibited by hydroxyl radical scavengers such as DMSO. The findings suggest that OH. is the active oxygen species that converts C5. The conversion product of C5, termed C5(H2O2), is C5b-like due to its ability to bind C6 and cause reactive lysis. C5(H2O2) is much more stable than C5b obtained by complement convertases. Although C5(H2O2) has lost the binding site of native C5 for C3b it can be cleaved by complement-derived convertases; the cleavage is, however, less efficient than in the case of native C5. The resulting cleavage product, which is C5a-like, is chemotactic although C5(H2O2) is not chemotactic. C5(H2O2) serves as a better substrate for plasma kallikrein than native C5, resulting in the generation of a C5a-like chemotactic product. These data indicate that oxygen radicals can bring about a conformational change in C5, causing it to behave as a functionally activated molecule of the complement system. This may have implications for the role of complement and its activation in the inflammatory response.

Complement Activation↗

Preliminary report of a multi-center study on the West syndrome.

During a 12-month period, 54 infants with the West syndrome (10 idiopathic, 44 symptomatic) referred to 10 major children's hospitals for initial treatment were evaluated to obtain comprehensive data on clinical findings and current treatment modalities. Prominent features included prevalence of prenatal and perinatal etiologies, severe neurological deficits and disturbed psychomotor development as well as patient-specific spectrum of seizure manifestations. Characteristic behavioural abnormalities before onset of spasms are an early indicator for the West syndrome. Therapeutic management varied considerably. Response to ACTH/steroid regiments was more favourable than to non-ACTH/steroid regimens. The most frequent serious adverse reactions during the initial treatment period were arterial hypertension and infections. Improved therapeutic strategies based on detailed initial patient assessment and systematic monitoring of beneficial effects and adverse reactions are necessary for future trials.

Female↗

Generation of an activated form of human C5 (C5b-like C5) by oxygen radicals.

Treatment of purified human C5 with hydrogen peroxide leads to a reduction of functional activity in the classical immune haemolysis assay. The effect of H2O2 is enhanced by traces of iron-EDTA, and becomes even stronger when ascorbic acid is present in addition. The enhancement by iron and protective effects of various radical scavengers indicate that the conversion of C5 is brought about by hydroxyl radicals mainly, generated from H2O2 during its decomposition. By the conversion C5 acquires a new functional property: it becomes capable of binding C6, and the resulting complex C56 lyses non-sensitized red cells in cooperation with the late components C7, C8, and C9 (reactive lysis). In this respect, H2O2-treated C5 resembles the activation fragment of C5, C5b. However, unlike C5b, C5(H2O2) is not fragmented but comprises the whole molecule, according to polyacrylamide gel electrophoresis. In accordance with the lack of cleavage, no chemotactic activity indicating formation of C5a, became apparent after H2O2 treatment of C5. In whole human serum, however, the H2O2 system induces additional processes leading to the generation of C5a activity and indicating C5 cleavage. The pathways to this reaction are as yet not clear. The effect of oxygen radicals on C5 may be the basis of the enhancing effect of stimulated leukocytes on C5 activation in body fluids. Activated leukocytes are known to produce H2O2 and oxygen radicals.

Complement Activation↗

Activation of the alternative pathway of human complement by sulfhydryl compounds of analytic and therapeutic use.

Thiol-containing drugs (dimercaprol, dimercaptopropanesulfonate, captopril, penicillamine, N-acetylcysteine) and the standard reducing agent beta-mercaptoethanol, activate the alternative pathway of complement as shown by in vitro experiments. Depending on the substance tested, at concentrations of 0.5-5 mM, cleavage products of C3 and factor B were demonstrable in serum by immunoelectrophoresis. The regulatory protein factor I proved to be very sensitive to thiols; this observation offers an explanation for the alternative pathway activating effect of these substances. At concentrations of thiols that initiate the alternative pathway, the classical pathway was not or only to a minor extent activated; however, the activity of C2, C5 and one or several of the components C6-9 was directly affected. Alkylation of the thiol group of the compounds tested, abrogated their effects on the complement system.

Alkylation↗

Activation of the alternative pathway of complement by DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (Mergetpa).

Incubation of normal human serum with 3-5 mM Mergetpa causes activation of the alternative pathway of complement as indicated by fragmentation of C3 and factor B, dependent on the presence of divalent cations. Mergetpa inhibits the regulatory protein factor I and, as a consequence, may allow initiation of the feedback cycle of the alternative pathway by deregulation. The classical pathway is not or only to a minor extent activated. A decrease in the hemolytic activity of C2, C5 and one or several of the components C6-9 in the presence of 5 mM Mergetpa may be explained by direct inactivation. The described effects are probably mediated by Mergetpa acting as a thiol.

3-Mercaptopropionic Acid↗