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Biomedical subjects

F Vogel

Publications and source records attributed to F Vogel.

At least 109 records · Page 6Linked to original sources

Induction of lymphomas by the hamster papovavirus correlates with massive replication of nonrandomly deleted extrachromosomal viral genomes.

The hamster papovavirus isolated from skin epithelioma can induce lymphomas and leukemias after subcutaneous inoculation into newborn hamsters. The lymphoma cells are virus free but contain large amounts of extrachromosomal hamster papovavirus DNA. We have cloned and partly sequenced some of these DNA molecules from independent tumors. These genomes displayed overlapping deletions consistently sharing a common end within the noncoding regulatory sequences; the other end was variable but always extended into the sequence coding for the N-terminal part of the viral capsid VP2. This unique in vivo interaction between a polyomavirus and its cellular host, the genesis of these variant molecules, and their role in the lymphoma formation are discussed.

Animals↗

Research strategies in human behaviour genetics.

Genetic variation influencing normal and abnormal human behaviour has been studied since Francis Galton's work in the second half of the 19th century. However, most of these studies have consisted of biometric analysis of complex phenotypes; the genotype has been treated as a 'black box'. The concepts and analytical tools of modern genetics have rarely been used. In this lecture, some examples are given of approaches combining tools from genetics, cytogenetics, and various fields of neurobiology which might help in the analysis of genetic mechanisms leading, in interaction with the environment, to individual differences in behaviour, mental performance, and susceptibility to mental diseases.

Genetics, Behavioral↗

No consistent relationships between oscillations and latencies of visually and auditory evoked EEG potentials and measures of mental performance.

In this study, the hypothesis was tested whether there is any relationship between measures of intelligence and working speed on the one hand, and characteristics of visually or auditory evoked EEG potentials, on the other. The study was performed on two samples: 1. In 236 University students selected for presence of four different, inherited EEG variants, product-moment correlations were computed between test scores for various aspects of mental performance on the one hand, and two measures of averaged visual and auditory evoked EEG potentials (VEPs and AEPs), on the other. The two EP measures were the average latency of all identifiable peaks between 70 and 600 ms after stimulation; and the "oscillation", a combined measure of amplitudes, comparable to Hendrickson's "string measure". Moreover, correlations were computed between two selected test scores (IQ and Raven) on the one sides, and the amplitudes and latencies of the components named P1, N1, and P2 by Buchsbaum on the other. 2. Twenty-four adults with mental retardation of unknown origin, inmates of an institution for the mentally retarded, were compared with 19 normal controls matched for age and sex - there were no consistent positive correlations between the characteristics of VEPs and AEPs and any of the performance measures studied. Hence, the hypothesis that there are consistent correlations between oscillation and latency of EPs and measures of mental performance was not confirmed. There is no convincing overall explanation for the discrepancies between various results reported in the literature but some of them may be explained either by individual differences in EEG maturation among children, or by additional sensoric input in some series, or by admixture of subjects with organic brain damage in some of the series, or by the individual characteristics of the resting EEG - a parameter that had been neglected in all previous studies.

Adult↗

[Nosocomial infection].

Sepsis is a systemic disease caused by pathogenic microorganisms and their toxic products in blood. Very often it is not possible to identify the pathogenic organisms before therapeutic treatment. Thus, diagnosis has to be made based on the patients' disposition as well as clinical symptoms. In septic patients clear alterations of plasma protein fractions are found. Depending on the clinical degree of severity, the low molecular proteins, detectable by column chromatography in plasma fraction III, are considerably increased. Population of implanted synthetic materials (such as catheters and cardiac valves) with facultative pathogenic microorganisms that may persist under antibiotic influence due to extracellular polymeric substances, is also of great importance. Therapy with antibiotic combinations is the most important therapeutic principle for sepsis and can be intensified by simultaneous administration of immunoglobulins.

Anti-Bacterial Agents↗

Mammalian aldolases are isomer-selective high-affinity inositol polyphosphate binders.

A search for target proteins of inositol polyphosphates in mammalian tissues revealed that fructose 1,6-bisphosphate aldolases are potent isomer-selective binders of inositol polyphosphates. Binding was measured by tryptophan fluorescence quenching, by difference spectroscopy, and, in aldolase A, by equilibrium dialysis. Among a series of inositol phosphates containing between one and six phosphates and varying in their positions, inositol 1,4,5-trisphosphate was found to be bound strongest both by aldolase A [( L]0.5 = 0.58 microM) and aldolase B [( L]0.5 = 0.83 microM). Aldolase A showed also a strong binding of inositol tetrakisphosphate [( L]0.5 = 0.83 microM), of inositol 2,4,5-trisphosphate [( L]0.5 = 1.4 microM) and of inositol 1,3,4,5,6-pentakisphosphate [( L]0.5 = 2.0 microM); in aldolase B but not in aldolase A inositol 4,5-bisphosphate was bound as strongly as inositol 1,4,5-trisphosphate [( L]0.5 = 0.95 microM) and also inositol 2,4,5-trisphosphate was tightly bound [( L]0.5 = 1.2 microM). Both in aldolase A and B, 4 mol inositol 1,4,5-trisphosphate were bound/mol tetramer, in aldolase A a total binding of 8 mol inositol 1,4-bisphosphate/mol tetramer was evaluated. Difference spectra revealed that the binding of inositol phosphates to both isoenzymes may be associated with conformational changes. The binding of all inositol phosphates led to an inhibition of the enzyme activity. In aldolase A the inhibition was purely competitive, in aldolase B a complex cooperative type of inhibition was evident with fructose 1,6-bisphosphate as a substrate whereas with fructose 1-phosphate the inhibition also was purely competitive. Model calculations based on the in vitro data indicated a significant potential of aldolase to bind preferentially inositol 1,4,5-trisphosphate also in the presence of excess fructose 1,6-bisphosphate.

Animals↗

The hamster papovavirus: evolutionary relationships with other polyomaviruses.

The hamster papovavirus (HaPV) is a polyoma virus with a restricted tumor spectrum. It is actively replicated in hair follicle tumors arising spontaneously in young Syrian hamsters. It can also induce lymphomas and leukemias in newborn hamsters. The complete nucleotide sequence of a cloned HaPV has been established recently. This report presents a comparison of this sequence with other polyomavirus genomes (polyoma, SV40, BKV, LPV) by matrix dot analysis and electron microscopy heteroduplex mapping. The results demonstrate a close relationship between the HaPV and the murine polyoma virus and designate the LPV as the closest relative among the primate polyomaviruses.

Animals↗

Complete structure of the hydrophilic domain in the porcine NADPH-cytochrome P-450 reductase.

The 622-residue amino acid sequence of the hydrophilic domain in the porcine NADPH-cytochrome P-450 reductase (EC 1.6.2.4) is reported. The structural data required to complete the sequences published previously [Vogel, Kaiser, Witt & Lumper (1985) Biol. Chem. Hoppe-Seyler 366, 577-587] and to establish the primary structure of the porcine hydrophilic domain have been obtained by sequencing proteolytic subfragments derived from CNBr fragments and by characterizing the overlapping S-[14C]methylmethionine-containing peptides isolated from tryptic digests of the [14C]methyl-labelled hydrophilic domain. The hydrophilic domain displays 91.8% positional identity with that of the corresponding domain in the rat NADPH-cytochrome P-450 reductase. The region Val528-Ser678 in the NADPH-cytochrome P-450 reductase shows a significant homology to the sequence Ile165-Tyr314 in the spinach ferredoxin-NADP+ oxidoreductase. A model for the secondary structure of the hydrophilic domain has been derived by computer-assisted analysis of the amino acid sequence. Cys472 and Cys566 are protected against chemical modification in the NADP+ complex of the NADPH-cytochrome P-450 reductase.

Amino Acid Sequence↗

The 4-5 cycles per second rhythm--changes in time.

The 4-5 cycles per second (c/s) rhythm is a relatively rare, individual EEG variant. Age distribution of subjects carrying this variant and longitudinal studies over many years have indicated that it may sometimes disappear during middle age. Observations on female monozygotic twins at 15, 23 and 45 years of age suggest that disappearance of this trait might also be under genetic control.

Adolescent↗

Dose effects of temazepam tablets on sleep.

The dose effects of temazepam tablets (15 and 30 mg) were studied at two sleep centres in 48 volunteers who had objective polysomnographic evidence of sleep onset insomnia. Volunteers slept in the laboratory, retiring at their usual bedtime after taking placebo or temazepam 30 min earlier, and were monitored for 8 h using standard polysomnographic techniques. Acute (nights 5-7) and short term (nights 11-13) temazepam, both 15 and 30 mg, improved the sleep of these volunteers by reducing sleep latency and increasing sleep time compared to the placebo baseline (nights 2-4). Dose differences were found primarily on the measurement of sleep staging, with 30 mg having a greater or more consistent effect than 15 mg. No residual effects were observed on the basis of questionnaires and objective tests of performance and no consistent evidence of disturbed sleep after discontinuing treatment was seen.

Adult↗

Characterization of the DNA of the hamster papovavirus: IV. Transcription mapping of calf-thymus DNA polymerase II.

Nascent RNA, synthesized by calf thymus RNA polymerase II on restriction endonuclease BamHI linearized hamster papovavirus (HaPV) DNA, was rehybridized to the template strand under conditions allowing transcription R-loop formation. Hybrids, visualized by electron microscopy, were plotted and mapped according to the physical map of HaPV. Two predominant regions of transcription could be localized at 0.10--0.40 and 0.50--0.82 m.u., respectively. For the start sites of transcription at map positions 0.67 and 0.75, respectively, on the HaPV genome a transcription in opposite direction were estimated. This genome region harbours the putative origin of replication of HaPV DNA. These results suggest a distinct relatedness of HaPV to the polyomavirus group.

Animals↗

Characterization of the DNA of the hamster papovavirus. III. Mapping of inverted repeated DNA sequences within the viral genome.

Sequences with 2-fold axis of symmetry (inverted repeated sequences) have been detected and mapped on the hamster papovavirus (HaPV) genome by their ability to form secondary structures like hairpins or stem-loops on single-stranded HaPV DNA. DNA regions with secondary structure were visualized by electron microscopy and mapped according to the physical map of HaPV. Eleven positions containing inverted repeats could be determined. The nucleotide sequence within all of these inverted repeats may be related since these regions can crosshybridize with each other. The possible functions of these sequences within the HaPV genome are discussed with respect to conditions found for genomes like those from SV40 and polyoma virus to get first indications for the localization of DNA regions representing the origin and termination of replication of HaPV DNA.

Animals↗

[Principles and significance of genetically-induced variability of the normal human EEG].

This review describes the following results of human genetic research on the "normal" human EEG: As shown by comprehensive studies on mono- and dizygotic twins, interindividual variability of the human EEG under "normal" conditions is largely genetically determined. This was mainly shown for the resting EEG, but holds true also for the sleeping EEG, the reaction to ethanol, and for visually and auditory evoked potentials. Some fairly common EEG variants have been described which follow simple Mendelian modes of inheritance. Hence, they must go back to correspondingly simply differences in certain genes and gene-determined proteins. These variants have been useful as model systems for a neurobiologically founded research strategy in behaviour genetics of man. Comparative studies using psychological, neurophysiological (visual and auditory evoked potentials) and biochemical methods revealed group difference especially between carriers of the low-voltage EEG, the EEG with monomorphic alpha-waves and an EEG variant containing, in addition to alpha-waves, numerous diffuse beta-waves. Utilizing concepts from basic research in neurophysiology, they could be explained by corresponding differences in central information processing. Individual differences of EEG reaction are also observed after a controlled ethanol load. They have a genetic basis, too. An especially clearcut reaction of the EEG to alcohol can be seen in individuals with irregular alpha-activity of low amplitude in the resting EEG. Moreover, these persons appear to be especially susceptible for "learning" to become alcohol addicts. Individual variability in maturation during childhood and youth of brain structures responsible for EEG production are also under genetic control. This EEG maturation influences intellectual and psychic maturation.

Alpha Rhythm↗

Visually and auditory evoked EEG potentials in carriers of four hereditary EEG variants.

Visually and auditory evoked EEG potentials were studied in 248 healthy university students, who were carriers of one of the following hereditary EEG variants: Monomorphic alpha-waves; low-voltage-EEG; EEG in which the alpha-rhythm was mixed diffusely with beta-waves; and EEG with fronto-precentral beta-groups. The study uncovered consistent and statistically significant group differences between the EEG-countertypes, monomorphic alpha-waves and the low-voltage EEG: subjects with monomorphic alpha-waves showed higher amplitudes and longer latencies of most peaks of the visually evoked potential (VEP), and higher amplitudes for most peaks of the auditory evoked potentials (AEP). Similar differences between EEG types were shown for two measures--overall amplitude (oscillation) and average latency--of all peaks for VEPs and AEPs. The results are consistent with a hypothesis discussed in an earlier paper in which differences between these two EEG types in processing of information in the CNS were assumed on the basis of psychological test results and neurophysiological theory. The two EEG types with beta-waves in addition to alpha-waves showed latencies of evoked potentials in-between those found in the EEG types with monomorphic alpha-waves, on the one hand, and the low-voltage EEG on the other. There was no significant difference in the frequency of VEP augmenters and reducers between EEG types.

Adult↗

Changes in aerobic faecal bacterial flora of severely ill patients during antibiotic treatment.

The stool of patients both undergoing and not undergoing antibiotic treatment was examined for aerobic faecal bacterial flora (quality and quantity) in an intensive care unit. The bacterial flora in the stool of patients not undergoing antibiotic treatment was generally normal. In patients undergoing antibiotic treatment the faecal bacterial flora showed changes as a result of the use of the antibiotic. Under cephalosporin treatment alone (cefotaxime, cefazolin) E. coli was still to be found. In patients being treated with a combination of two or three antibiotics the frequency of occurrence of E. coli was markedly reduced. Pseudomonas aeruginosa were however substantially more often detected showing increased resistance. The wider the antibiotic spectrum, the more facultative pathogenic microorganisms in the faeces increase, especially Pseudomonas aeruginosa, which can then become an important source for nosocomial infections.

Adult↗