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J Kiefer

Publications and source records attributed to J Kiefer.

At least 19 recordsLinked to original sources
PubMed2002

[Test set for the evaluation of hearing and speech development after cochlear implantation in children].

BACKGROUND: Since autumn 1998 the multicenter interdisciplinary study group "Test Materials for CI Children" has been compiling a uniform examination tool for evaluation of speech and hearing development after cochlear implantation in childhood. METHODS USED: After studying the relevant literature, suitable materials were checked for practical applicability, modified and provided with criteria for execution and break-off. For data acquisition, observation forms for preparation of a PC-version were developed. RESULTS: The evaluation set contains forms for master data with supplements relating to postoperative processes. The hearing tests check supra-threshold hearing with loudness scaling for children, speech comprehension in silence (Mainz and Göttingen Test for Speech Comprehension in Childhood) and phonemic differentiation (Oldenburg Rhyme Test for Children), the central auditory processes of detection, discrimination, identification and recognition (modification of the "Frankfurt Functional Hearing Test for Children") and audiovisual speech perception (Open Paragraph Tracking, Kiel Speech Track Program). The materials for speech and language development comprise phonetics-phonology, lexicon and semantics (LOGO Pronunciation Test), syntax and morphology (analysis of spontaneous speech), language comprehension (Reynell Scales), communication and pragmatics (observation forms). The MAIS and MUSS modified questionnaires are integrated. CONCLUSIONS: The evaluation set serves quality assurance and permits factor analysis as well as controls for regularity through the multicenter comparison of long-term developmental trends after cochlear implantation.

Child↗
PubMed2002

DNA double strand break induction in yeast.

The induction of DNA double strand breaks (DSBs) by accelerated heavy ions was systematically measured in diploid yeast cells. Particles were provided by the accelerators at GSI, Darmstadt, and HMI, Berlin. DNA was separated using pulsed field gel electrophoresis and the intensity of the largest bands used to determine the loss of molecular weight. Since the DNA content of each chromosome is exactly known absolute values for DSB induction can be measured without calibration procedures. Ions used range from protons to uranium with LET values between 2 and about 15,000 keV.micron-1. Induction cross sections increase in the lower LET region approaching a plateau around 200 keV.micron-1. With higher LET values the dependence can no longer be described by a common curve with each ion showing a specific behaviour. With very heavy particles the influence of the penumbra becomes obvious: cross sections decrease with LET because of the reduced penumbra extensions. Classical target theory would predict cross sections to follow a simple saturation function which is not substantiated by the data. Track structure analysis as introduced by Butts and Katz in 1967 is also not able to predict the experimental results. A semi-empirical fit indicates a linear-quadratic dependence of induction cross sections on LET up to about 1000 keV.micron-1. RBE for DSB induction rises above unity reaching a maximum of about 2.5 around 200 keV.micron-1. This is different from many experiments in mammalian cells and is presumably due to differences in chromatin structure since yeast cells seem to lack a functional III histone.

DNA Damage↗
PubMed2001

Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy.

Analysis of 1,060 xenotransplants derived from cancer cell lines as wel as spontaneously occurring tumors from the larynx, pharynx, mammary gland, uterine cervix, and vulva revealed that tumor regression induced by treatment with monoclonal antibodies (EMD 55900 and EMD 72000 against the epidermal growth factor receptor (EGFR) could be enhanced by tumor necrosis factor alpha (TNF-alpha) treatment in vivo. Moreover, tumor that primarily do not respond to antibody treatment can be made suscep tible by additional TNF-alpha treatment. To investigate the in vivo effects of monoclonal antibodies, we treated tumors derived from cell lines (A431 and Detroit 562) as well as spontaneously occurring squamous cell carci nomas and adenocarcinomas (transplanted on NMRI-nu/nu mice) gener ally with EMD 55900 (40 microg/g mouse) and its humanized version EMD 72000 (40 microg/g mouse). When treated with EMD 55900 and EMD 72000 carcinomas with an EGFR concentration of > or = 70 fmol/mg protein showed significant reduction in tumor size compared with untreated controls. The degree of tumor regression correlated with the EGFR concentration of the tumor. In mice treated with TNF-alpha (0.5 microg/g mouse) and EMD 55900 72000 simultaneously, we observed enhanced antitumor effects up to complete tumor eradication. Carcinomas with an EGFR concentration <70 fmol/mg protein could be made susceptible to treatment with EMD 55900 and EMD 72000 by simultaneous treatment with TNF-alpha, resulting in a significant reduction in tumor size.

Adenocarcinoma↗
PubMed2001

Perimodiolar electrodes in cochlear implant surgery.

Perimodiolar-positioned cochlear implant electrodes have been developed in order to bring the electrode contacts as close as possible to the spiral ganglion cells, which are the target of electrostimulation. This results in lower electrical thresholds, higher dynamic ranges and less channel interaction when compared with normal implant electrodes which are usually located peripherally within the scala tympani. In this study we evaluated 4 different types of perimodiolar electrode: the Clarion Preformed electrode, the Clarion Preformed electrode with positioner, the Nucleus Contour electrode and the Med-El Perimodiolar Combi 40 electrode. These devices require different approaches to achieve a perimodiolar electrode position. The electrodes were inserted in fresh human temporal bones. After processing these bones with the electrodes in situ by employing a sawing, grinding and polishing technique, the inner ear structures as well as the electrode positions could be evaluated in detail. All electrode types studied had a more or less perimodiolar position; however, each type produced a certain amount of trauma to cochlear structures which is discussed in relation to mechanical properties. Further human temporal bone studies with improved perimodiolar cochlear implant electrodes are necessary in order to find an optimized type of electrode.

Cochlea↗
PubMed2001

Mutations in mammalian cells induced by heavy charged particles: an indicator for risk assessment in space.

Induction of mutations at the HPRT locus in V79 Chinese hamster cells by heavy charged particles is reviewed. A unique dependence of mutation induction cross sections on LET or any other physical parameter of the particles cannot be found. There is, however, a general trend showing an increase up to about 100 keV/microm and an indication of a saturation with higher LET. An empirical expression is given approximating the data which may be useful for practical purposes. On the basis of this expression, it is suggested that the formula used by the ICRP for the quality factor overestimates the risk for very heavy particles. This may have implications for the assessment of the risk of exposure to iron ions in space.

Aerospace Medicine↗
PubMed2001

Space radiation research in the new millenium--from where we come and where we go.

Space radiation research had a significant impact in the past. The physical interaction of heavy charged particles with living matter and the development of models, including microdosimetry, were stimulated by problems encountered in space. New phenomena were discovered. Advanced dosimetric techniques had to be developed and computational methods to describe the radiation field in space. The understanding of the radiobiology of heavy ions, necessary for a well-founded risk assessment and prompted by space radiation research, constitutes also the basis for heavy ion radiotherapy. So far unknown areas like the interaction of microgravity and radiation were opened. The space station will give even more opportunities. For the first time it will be possible to investigate animals for a longer time under the influence of both microgravity and radiation. Living systems can be exposed under well defined conditions with parallel physical measurements. Solar particle events are still an unsolved problem. Significant improvement in their predictability and quantitative description can be expected. All this will not only give exciting opportunities for research but will also translate into immediate benefit for human beings. This paper will attempt to give an overview of the past achievements and glance into the future.

Animals↗
PubMed2000

Optimized speech understanding with the continuous interleaved sampling speech coding strategy in patients with cochlear implants: effect of variations in stimulation rate and number of channels.

The purpose of this study was to investigate the effect of systematic variations in stimulation rate and number of channels on speech understanding in 13 patients with cochlear implants who used the continuous interleaved sampling speech coding strategy. Reducing the stimulation rate from 1,515 to 1,730 pulses per second per channel to 600 pulses per second per channel resulted in decreased overall performance; the understanding of monosyllables and consonants was more affected than the understanding of vowels. Reducing the number of active channels below 7 or 8 channels decreased speech understanding; the identification of vowels and monosyllables was most affected. We conclude that vowel recognition with the continuous interleaved sampling strategy relies on spectral cues more than on temporal cues, increasing with the number of active channels, whereas consonant recognition is more dependent on temporal cues and stimulation rate.

Cochlear Implantation↗
PubMed2000

Stochastic radial dose distributions and track structure theory.

Measured single-event distributions of the specific energy deposited in cylindrical volumes with simulated diameters down to 150 nm for (4)He and (12)C ions with energies of 25 MeV/nucleon and (16)O ions with 21 MeV/nucleon and radial distances up to 12 microm are presented. The mean specific energy per ion , the mean specific energy per target hit z(1)(r), and the relative frequency of target hits nu(r) as a function of radial distance are evaluated and compared with the corresponding quantities of the track structure model of Kiefer and Straaten (Phys. Med. Biol. 31, 1201-1209, 1986). Though there are some discrepancies in the absolute values, the radial dependence of , z(1)(r) and v(r) for (12)C and (16)O ions is reproduced satisfactorily. The model fails to describe the data for (4)He ions. A more detailed comparison of the radial shape of the mean specific energies calculated from the experimental data from the present work and data from the literature reveals a significant projectile charge dependence which is not included in track structure models.

Carbon↗
PubMed2000

Induction and repair of DNA double-strand breaks under irradiation and microgravity.

The influence of microgravity on induction and repair of double-strand breaks was studied in the yeast mutant rad54-3, which is temperature-conditional for the repair of DNA double-strand breaks. The experiment was performed on the shuttle Atlantis flight STS-84. Cell samples were kept at 0-4 degrees C until they reached orbit, where they were transferred to 22 (permissive temperature for repair) and 37 degrees C (restrictive temperature). They were exposed to graded doses of beta particles from an in-built (63)Ni source during the repair period. After 152 h in microgravity, the radiation exposure was stopped, and the samples were returned to low-temperature conditions, where they remained until final evaluation in the home laboratory. The amount of double-strand breaks remaining was estimated from the differences in survival after plating and incubation at the restrictive temperature. The results show that there is no significant difference for both the induction and the repair of double-strand breaks between microgravity and terrestrial conditions.

DNA Damage↗
PubMed1999

Mutation induction by different types of radiation at the Hprt locus.

Mutation induction at the Hprt locus in Chinese hamster cells was studied after exposure to ultraviolet light, X-rays and alpha particles. While mutant frequency as a function of dose or fluence followed a linear-quadratic relationship with UV and X-rays, it showed a linear dependence for alpha particles. If mutant frequency is plotted vs. the logarithm of surviving fraction, a linear relationship is found in all cases although with different slopes. These are about equal with the two types of ionising radiations but about 10 times larger for UV. They can be used as a measure of mutagenic potential and are termed mutagenicity. It is shown that this parameter is correlated with the maximum of mutant yield, i.e., the number of mutants per cell at risk. It is concluded from this analysis that the maximum mutant yield is always found at doses or fluences which lead to 37% survival irrespective of the kind of radiation. If mutation induction is measured in X-irradiated cells after pre-exposure to UV, mutant frequency is higher than expected on the basis of independent action of the two radiations. Deletion spectra were determined by using multiplex polymerase chain reaction. It was found that the background of spontaneous mutants varied considerably and showed frequently repetitive patterns, presumably because of clonal expansion of pre-formed mutants. UV-induced mutants did not contain any deletions, while those with both X-rays and alpha particles the majority displayed partial and total deletions. Based on a total number of 134 X-ray- and 192 alpha-induced mutants, it is concluded that the total fraction of mutant clones without deletions (partial or total) is about 40% for X-rays and only about 20% for alpha-particles.

Alpha Particles↗
PubMed1999

Space radiation effects and microgravity.

Humans in space are exposed both to space radiation and microgravity. The question whether radiation effects are modified by microgravity is an important aspect in risk estimation. No interaction is expected at the molecular level since the influence of gravity is much smaller than that of thermal motion. Influences might be expected, however, at the cellular and organ level. For example, changes in immune competence could modify the development of radiogenic cancers. There are no data so far in this area. The problem of whether intracellular repair of radiation-induced DNA lesions is changed under microgravity conditions was recently addressed in a number of space experiments. The results are reviewed; they show that repair processes are not modified by microgravity.

Beta Particles↗
PubMed1999

Radiation risk in manned space flights.

This paper addresses some of the pertinent questions relating to the assessment of radiation risk for humans in space; the paper is not intended as a comprehensive review. The radiation field is briefly summarised and doses to be expected are given based on recent on-board measurements. The problems in adapting terrestrial epidemiological data to the space situation are outlined. Apart from the intrinsic uncertainties in deriving risk factors the specific difficulties are mainly concerned with the effects of energetic charged particles for which no human data exist. The necessity for continuing ground-based research is stressed. Also discussed is whether the principles of radiation protection successfully applied on Earth are really suitable for the space situation or whether they should be replaced by a different approach.

Astronauts↗
PubMed1999

Repair of cellular radiation damage in space under microgravity conditions.

The influence of microgravity on the repair of x-ray-induced DNA double-strand breaks was studied in the temperature-conditional repair mutant rad54-3 of diploid yeast Saccharomyces cerevisiae. Cells were exposed on the ground and kept at a low temperature until microgravity conditions were achieved. In orbit, they were incubated at the permissive temperature to allow repair. Before re-entry they were again cooled down and kept at a low temperature until final analysis. The experiment, which was flown on the shuttle Atlantis on flight STS-76 (SMM-03), showed that repair of pre-formed DNA double-strand breaks in yeast is not impaired by microgravity.

Aerospace Medicine↗
PubMed1999

Conservation of intracellular Wnt signaling components in dorsal-ventral axis formation in zebrafish.

The mechanism of early dorso-ventral axis specification in zebrafish embryos is not well understood. While beta-catenin has been clearly implicated as a determinant of the axis, the factors upstream and downstream of beta-catenin in this system are not defined. Unlike in Xenopus, where a sperm-induced cortical rotation is used to localize beta-catenin on the future dorsal side of the embryo, zebrafish do not have an obviously similar morphogenetic movement. Recently, a GSK-3 (Glycogen Synthase Kinase-3) binding protein (GBP) was identified as a novel member of the Wnt pathway required for maternal dorsal axis formation in Xenopus. GBP stabilizes beta-catenin levels by inhibiting GSK-3 and potentially provides a link between cortical rotation and beta-catenin regulation. Since zebrafish may use a different mechanism for regulating beta-catenin, we asked whether zebrafish also express a maternal GBP. We report the isolation of the zebrafish GBP gene and show that it is maternally expressed and is present as mRNA ubiquitously throughout early embryonic development. Over-expression of zebrafish GBP in frogs and fish leads to hyper-dorsalized phenotypes, similar to the effects resulting from over-expression of beta-catenin, indicating that components upstream of beta-catenin are conserved between amphibians and teleosts. We also examined whether Tcf (T cell factor) functions in zebrafish embryos. As in frogs, ectopic expression of a dominant negative form of XTcf-3 ventralizes zebrafish embryos. In addition, ectopic beta-catenin expression activates the promoter of the Tcf-dependent gene siamois, indicating that the step immediately downstream of beta-catenin is also conserved between fish and frogs.

Amino Acid Sequence↗
PubMed1999

Eosinophilic cationic protein as a marker of nasal inflammation in patients with cystic fibrosis.

OBJECTIVES: Evaluation was made of eosinophilic cationic protein (ECP) in nasal secretion for measuring the degree of nasal inflammation and monitoring response to therapy in cystic fibrosis (CF) patients with chronic rhinosinusitis. Symptoms and findings in regard to ECP levels before and after treatment were described. STUDY DESIGN: Study was prospective, with 21 CF patients aged 4 to 19 years; 20 healthy volunteers served as controls. Collection of nasal secretion by a sponge was performed, and blood samples were obtained for serum. Cystic fibrosis (CF) patients were classified according to nasal symptoms and findings. METHODS: ECP was measured by fluoroimmunoassay. Age, sex, nasal symptoms, and endoscopic and histological findings were obtained, and examinations were conducted before and after treatment; recurrences were recorded. RESULTS: In CF patients with chronic nasal inflammation, increased nasal levels of ECP were detected when compared with asymptomatic CF patients or healthy nonatopic subjects. ECP concentrations were strongly related to the extent of nasal disease; patients with nasal polyps had higher levels than those without. Checked at 1 and 4 months after treatment, ECP levels declined with regression of symptoms, and in patients with exacerbation of nasal disease, ECP levels rose. CONCLUSIONS: According to our study, there is a relationship between levels of ECP in nasal secretions and the degrees of nasal inflammation. In addition, the measurement of ECP could be useful in monitoring nasal disease in CF patients.

Adolescent↗
PubMed1998

Deletion-pattern analysis of alpha-particle and X-ray induced mutations at the HPRT locus of V79 Chinese hamster cells.

To investigate the mutagenic mechanisms of low-energy alpha particles V79 Chinese hamster cells were irradiated with 241Am-alpha particles (mean LET of 112 keV/micron). Parallel experiments were performed using 300 kV X-rays. Cell inactivation and mutation induction cross sections were measured. At approximately 20%--survival level, DNA deletions were analysed at the HPRT locus by multiplex-PCR-analysis of all nine exons of 47 alpha-irradiated and 36 background mutants. 92 HPRT- mutants isolated after 300 kV-X-irradiation were analysed similarly for comparison, along with 15 corresponding background mutants. The resulting mutant deletion-pattern distributions were corrected for background mutations. alpha Particles induced a larger fraction of deletions than X-rays. Furthermore, non-contiguous partial deletions were present among the alpha-induced mutants, a type not found after X-irradiation.

Alpha Particles↗
PubMed1998

A review of dsb induction data for varying quality radiations.

PURPOSE: This short review summarizes the data obtained with various techniques for measuring the yields of double strand breaks (dsb) produced by particle radiations of differing linear energy transfer (LET) in order to obtain relative biological effectiveness (RBE) values. RESULTS AND CONCLUSIONS: Studies aimed at understanding the interactions of different types of radiation with cellular DNA have monitored the yields of DNA dsb versus radiation quality. Several techniques have been used to measure dsb yields in mammalian cells, and these include: neutral sedimentation gradients, filter elution and more recently pulsed field gel electrophoresis techniques (PFGE). Recent developments in PFGE have allowed the measurement of both the yields and the distribution of breaks within the genome, which go part of the way to explaining the RBE values close to 1.0 previously measured using other approaches with various radiation qualities. It is clear that future studies to determine the effectiveness of radiations of differing LET must use techniques that determine both yields and distributions of dsb, and assays need to be developed to allow these measurements at biologically relevant doses.

Alkalies↗