Search PubMed⌕ Search

Biomedical subjects

J Kiefer

Publications and source records attributed to J Kiefer.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Separation of PP2A core enzyme and holoenzyme with monoclonal antibodies against the regulatory A subunit: abundant expression of both forms in cells.

Protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit, C, and two regulatory subunits, A and B. The A subunit is rod shaped and consists of 15 nonidentical repeats. According to our previous model, the B subunit binds to repeats 1 through 10 and the C subunit binds to repeats 11 through 15 of the A subunit. Another form of PP2A, core enzyme, is composed only of subunits A and C. It is generally believed that core enzyme does not exist in cells but is an artifact of enzyme purification. To study the structure and relative abundance of different forms of PP2A, we generated monoclonal antibodies against the native A subunit. Two antibodies, 5H4 and 1A12, recognized epitopes in repeat 1 near the N terminus and immunoprecipitated free A subunit and core enzyme but not holoenzyme. Another antibody, 6G3, recognized an epitope in repeat 15 at the C terminus and precipitated only the free A subunit. Monoclonal antibodies against a peptide corresponding to the N-terminal 11 amino acids of the A alpha subunit (designated 6F9) precipitated free A subunit, core enzyme, and holoenzyme. 6F9, but not 5H4, recognized holoenzymes containing either B, B', or B" subunits. These results demonstrate that B subunits from three unrelated gene families all bind to repeat 1 of the A subunit, and the results confirm and extend our model of the holoenzyme. By sequential immunoprecipitations with 5H4 or 1A12 followed by 6F9, core enzyme and holoenzyme in cytoplasmic extracts from 10T1/2 cells were completely separated and they exhibited the expected specificities towards phosphorylase a and retinoblastoma peptide as substrates. Quantitative analysis showed that under conditions which minimized proteolysis and dissociation of holoenzyme, core enzyme represented at least one-third of the total PP2A. We conclude that core enzyme is an abundant form in cells rather than an artifact of isolation. The biological implications of this finding are discussed.

Animals↗
PubMed1997

Optimization of channel number and stimulation rate for the fast continuous interleaved sampling strategy in the COMBI 40+.

OBJECTIVE: To investigate the interrelation between number of channels and stimulation rate in the continuous interleaved sampling strategy (CIS). SUBJECTS AND METHODS: Three of the first recipients of the new COMBI 40+ cochlear implant participated in consonant, vowel, number, and sentence tests. Speech understanding was evaluated for different combinations of number of active channels from two to twelve and stimulation rate per channel between 1,515 and 9,090 pulses per second. RESULTS: The results indicate that the optimum number of active channels is not necessarily the maximum number of usable channels.

Adult↗
PubMed1996

A follow-up study of long-term results after cochlear implantation in children and adolescents.

The time course of speech development in children after cochlear implantation may extend over many years, thus making long-term studies necessary to evaluate any outcome. We report our long-term results after cochlear implantation in children and adolescents. Mean follow-up was 28 months, ranging from 1 to 5 years. After at least 1 year of experience all children were found to benefit from their cochlear implants. The majority of children scored above chance in speech identification tasks requiring closed set word and sentence understanding). At the 4-year interval, all children tested including prelingually deaf children had developed open set sentence understanding. The most relevant factor accounting for differences in the results was the duration of implant use in all groups. Even beyond 3 years the results continued to improve. Peri- or postlingually deafened children tended to have favorable results. For prelingually deaf children, duration of deafness and age at implantation were correlated negatively with the results.

Adolescent↗
PubMed1996

Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.

Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.

Adult↗
PubMed1996

HPRT mutations in V79 Chinese hamster cells induced by accelerated Ni, Au and Pb ions.

Mutation induction by accelerated heavy ions to 6-TG resistance (HPRT system) in V79 Chinese hamster cells was investigated with Ni (6-630 Me V/u), Au (2.2, 8.7 Me V/u) and Pb ions (11.6-980 Me V/u) corresponding to a LET range between 180 and 12895 ke V/microns. Most experiments could only be performed once due to technical limitations using accelerator beam times. Survival curves were exponential, mutation induction curves linear with fluence. From their slopes inactivation- and mutation-induction cross-sections were derived. If they are plotted versus LET, single, ion-specific curves are obtained. It is shown that other parameters like ion energy and effective charge play an important role. In the case of Au and Pb ions the cross-sections follow a common line, since these ions have nearly the same atomic weight, so that they should have similar spatial ionization patterns in matter at the same energies. Calculated RBEs were higher for mutation induction than for killing for all LETs.

Animals↗
PubMed1995

Oxygen radical production and thiol depletion are required for Ca(2+)-mediated endogenous endonuclease activation in apoptotic thymocytes.

Glucocorticoid hormones stimulate apoptosis in thymocytes via a mechanism that involves changes in intracellular Ca2+, and exogenous Ca2+ can also directly promote the nuclear alterations of apoptosis (lamin degradation and chromatin cleavage) in isolated nuclei. Here we report that glucocorticoid treatment resulted in the production of reactive oxygen species and the depletion of reduced glutathione. Separation of apoptotic cells on Percoll gradients demonstrated that both effects selectively occurred in thymocytes undergoing apoptosis. Moreover, glucocorticoid-induced endonuclease activation was partially blocked by the antioxidant N-acetyl-L-cysteine. Although abrogation of methylprednisolone-induced Ca2+ increases using the intracellular Ca2+ buffer 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid resulted in inhibition of endonuclease activation, it failed to prevent GSH depletion. However, N-acetyl-L-cysteine almost completely blocked methylprednisolone-induced elevations in cytosolic calcium levels, indicating that oxidative stress was playing a role in the Ca2+ response. Our results support the idea that oxidative stress is a key component of the apoptotic effector pathway in thymocytes, and that it interacts, at least in part, with the Ca2+ response.

Acetylcysteine↗
PubMed1995

[Factors influencing the prescribing of nootropic drugs. Results of a representative inquiry in Lower Saxony].

AIM OF INVESTIGATION: To discover (1) to what extent patients' wishes and the extent of any abnormality of brain performance influence the frequency with which "nootropic" drugs (those thought to affect brain activity, e.g. piracetam, pyritinol, or improve cerebral circulation, e.g. xanthine derivatives, Ginkgo biloba, secale alkaloids, calcium antagonists) are prescribed; (2) the medical practitioner's expectations of the effectiveness of such medications. METHOD: In a personal interview, 145 family doctors and 14 neurologists in private practice in the Göttingen area of Germany (participation rate: 83.2% of those asked to participate) were questioned about fictitious cases (case 1: mild memory problem with or without expressed wish for medication; case 2: moderate dementia, of Alzheimer or multi-infarct type). The previously arranged interviews, which took place in the doctors' practice rooms, consisted of standardized open questions to the written case reports. RESULTS: Regardless of the wish of the patient and the extent and type of the abnormal brain function about 70% of all participating doctors would prescribe those drugs, even though about 56% had doubts about their effectiveness. About 28% expected a positive effect on brain performance. A nearly equal proportion of doctors would continue an existing drug regimen as would prescribe one. CONCLUSION: The prescription of the named group of drugs is influenced less by medical criteria than by factors which concern doctor-patient relationship.

Adult↗
PubMed1995

Functional glucocorticoid receptor expression is required for cAMP-mediated apoptosis in a human leukemic T cell line.

The involvement of the glucocorticoid receptor (GR) in cAMP-induced apoptosis in a GR-deficient derivative of the CEM.C7 human T-ALL line was investigated. Incubation of the parental CEM.C7 cells with agents that elevate cAMP levels (dibutyryl cAMP and forskolin) resulted in DNA fragmentation characteristic of apoptotic cell death, whereas the GR-deficient ICR.27 cells were insensitive to the cytolytic effects of cAMP. Reconstitution of GR expression by transfection not only restored glucocorticoid sensitivity to the ICR.27 cells, but also promoted sensitivity to induction of apoptosis by cAMP. Thus, cAMP-induced apoptosis in T cells appears to occur via ligand-independent stimulation of at least some aspects of glucocorticoid receptor function.

Apoptosis↗