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Biomedical subjects

F Vogel

Publications and source records attributed to F Vogel.

At least 127 records · Page 7Linked to original sources

Recurrent mutation pressure does not explain the prevalence of the marker (X) syndrome.

In order to test the hypothesis that the high prevalence of the mar(X) syndrome is caused by a high mutation rate in male germ cells only, the fraction of new mutants among mothers of probands in 112 informative families has been examined by segregation analysis among their brothers and sisters. The estimated fraction of new mutants among these mothers is much lower than expected if a stable equilibrium existed between an unusually high mutation rate and a selective disadvantage of mentally retarded, male and female mar(X) carriers. Hence, the above-mentioned hypothesis could not be confirmed.

Female↗

Eligibility requirements in hypnotic trials.

Forty-eight patients complaining of insomnia were studied at two sleep laboratories using an identical protocol to evaluate hypnotic efficacy. All met the screening requirement of a mean sleep latency of 30 min or greater on 3 laboratory nights following an adaptation night. Of these patients 34 still complaining of insomnia were screened a second time 2 to 6 months later. Sixteen of the 34 failed the second screen. Sleep parameters for the 34 on screen 1 compared with screen 2 were the same except for sleep latency (the eligibility criteria), which was significantly shorter. There was no evidence of a systematic difference between laboratories, a change in procedure from screen 1 to 2, or a systematic loss of patients from screen 1 to 2. The data show that the statistical phenomenon of regression toward the mean must be considered in designing hypnotic efficacy studies.

Adult↗

NADPH-cytochrome P-450 reductase (pig liver). Studies on the sequence of the cyanogen bromide peptides from the catalytic domain and on the reactivity of the thiol groups.

The reactivity of the cysteine residues in the non-denatured catalytic domain of the NADPH-cytochrome P-450 reductase (pig liver) was studied using the -SH reagent monobromobimane. Prerequisite was the characterization of the cysteine residues by their surrounding amino-acid sequences. In pursuit of these aims the CNBr fragments obtained from the catalytic domain were sequenced. The cysteine residues are distributed on six CNBr fragments of the catalytic domain [Vogel and Lumper (1984) Hoppe-Seyler's Z. Physiol. Chem. 365, 1074]. Only the 11-kDa CNBr peptides with the N-terminal sequences Val-Gly-Pro-Thr- and Ala-Ser-Ser-Ser-, respectively, contain two cysteine residues each. The cysteine residues of the catalytic domain accessible to monobromobimane were localized on three CNBr peptides with the N-terminal sequences Val-Gly-Pro-Thr-, Ala-Ser-Ser-Ser- and Ala-Arg-Asp-Val-, respectively. Inactivation of the trypsin-solubilized enzyme by -SH-directed reagents is caused by the modification of the accessible cysteine residue (which can be protected by NADPH) in the 11-kDa CNBr fragment (N-terminal sequence: Val-Gly-Pro-Thr-). The cosubstrate NADPH protected a second cysteine residue localized in the 11-kDa CNBr peptide with the N-terminal sequence Ala-Ser-Ser-Ser-, which is however modified at a distinctly slower rate than the critical cysteine residue characterized by the sequence -Gly-Glu-Thr-Leu-Leu-Tyr-Tyr-Gly-Cys-Arg-Arg. Five non-reacting thiol groups were localized on CNBr fragments with the N-terminal sequences Val-Gly-Pro-Thr-, Ala-Ser-Ser-Ser-, Ser-Leu-Asn-Asn-, Gly-Lys-Tyr-Val-Asp- and Ala-Ala-Asp-Pro-.

Amino Acid Sequence↗

Characterization of the DNA of the hamster papovavirus: II. A comparison of binding sites for Escherichia coli- and calf thymus RNA polymerase II on the hamster papovavirus genome.

Calf thymus (CT) RNA polymerase II bound to hamster papovavirus (HaPV) DNA was visualized by electron microscopy and compared to binding sites obtained after binding of Escherichia coli RNA polymerase to the HaPV genome. Thirteen binding sites were observed with CT polymerase II at map positions 0.04-0.07; 0.11; 0.18; 0.30; 0.37; 0.47; 0.57; 0.65; 0.78; 0.83; 0.90 and 0.94 using the unique BamHI cleavage site as zero point on the HaPV physical map. These binding sites correlate well with A + T rich sequences within the HaPV DNA as revealed by experiments using protein 32 coded for by phage T4. A comparison of binding of prokaryotic and eukaryotic RNA polymerase demonstrates a high degree of correspondence for most of the binding sites on the HaPV genome.

Animals↗

Phenotypic deviations in heterozygotes of phenylketonuria (PKU).

There are reports in the literature that suggest slightly impaired average intellectual ability, slightly increased signs of brain irritability, and possibly, a slightly increased susceptibility to late-onset schizophrenia with depressive signs, reproductive anomalies, and varicose veins in heterozygotes for phenylketonuria (PKU). The possible significance of such results for our understanding of genetic liabilities for common disease, or of genetic variability influencing mental performance in the normal range is discussed.

Adult↗

[Principles of the prevention of pneumonia by the intratracheal instillation of aminoglycoside antibiotics].

In long-term respiration the descension of the pharyngeal contents into the tracheobronchial system appears as unavoidable as the colonisation of the oropharynx with pathogens. On the other hand, elimination of the descended pathogens from the trachea and the bronchi by setting up an antibiotic barrier represented by the aminoglycoside antibiotics, can prevent colonisation of the lower respiratory passages. As a matter of fact, the aminoglycoside antibiotics exercise, first of all, rapid and bactericidal action, and secondly a spectrum of pathogens. Intratracheal application of 4 X 40 mg tobramycin daily, distributed over 24 hours, leads in the case of persons with healthy kidneys to serum levels between 0.4 and 0.7 micrograms/ml. Side effects are mainly seen in patients with restricted renal function in the form of cumulative serum concentrations. At present there are no alternative possibilities of prophylaxis against the sequels of descension.

Aminoglycosides↗

[Adhesion of mircroorganisms to respirator tubes].

Potentially pathogenic microorganisms may adhere to and persist on plastic surfaces by extracellular polymeric substances. Intubation tubes used between 30 minutes and 10 days in 14 ventilated patients of a medical intensive care unit were examined by scanning electron microscopy. All interior tube surfaces showed heavy colonisations which thus can persist over prolonged periods. The clinical relevance of these findings consists of the fact that, as on other plastic surfaces, microbial organisms may remain attached to ventilation tubes. Through formation of extracellular polymeric substances they are protected against effects of antibiotics and disinfectants. Aspiration of these microorganisms from the tubes may lead to pneumonias in ventilated patients.

Adhesiveness↗

Serum gentamicin concentrations during intratracheal administration.

In artificially ventilated patients, intratracheal aminoglycoside administration is used as a form of prophylaxis of broncho-pulmonary infections. In artificially ventilated patients with multiple organ failure, serum gentamicin concentrations were measured dependent on renal function after endotracheal administration. A standard commercial ampule of 40 mg gentamicin in a 1 ml solution was injected in undiluted form, intratracheally through the tubus , every 6 h. In the patients without renal failure, values over 1 microgram/ml were only found in certain individual cases and reached a maximum of 1.5 micrograms/ml. In patients with renal failure even after prolonged application, the average serum concentrations were between 2 and 3.5 micrograms/ml. In a very few cases, however, levels of up to 10.5 micrograms/ml were measured. The daily serum pattern revealed a distinct dependence on the administration; 1 h after administration there was an increase in the serum concentrations which decreased to the initial levels after 6 h. When patients with renal impairment are given an aminoglycoside intratracheally, serum levels of up to 10.5 micrograms/ml may be reached and thus additional systemic aminoglycoside therapy should be avoided.

Acute Kidney Injury↗

[The effect of air pollution on man].

During the last years, the human organism has been exposed to airborne pollutants to an increasing extend, among them the following most important: SO2, NOx , hydrocarbons, CO, photochemical smog, airborne particles containing the heavy metals lead and cadmium. The local effects on the lung and the bronchial mucous membrane are described including irritations of the mucous membrane and disturbances of the defence and elimination mechanisms. The main consequences are chronic bronchitis and bronchial carcinoma. The systemic effects of inhaled airborne pollutants are mutagenicity, cancerogenicity and toxicity. Disturbances of the immunological system may occur. Details as regard the effects of carbon monoxide, lead and cadmium, photochemical smog and SO2 are given.

Air Pollution↗

Sequence homology between polyoma virus, simian virus 40, and a papilloma-producing virus from a Syrian hamster: evidences for highly conserved sequences.

Sequence homology between the genomes of a hamster papovavirus (HaPV), polyoma virus (Py), and Simian virus 40 (SV40) has been studied by filter hybridization and electron microscopy under conditions of varying stringency. Hybrids between the HaPV and SV40 DNAs could be demonstrated only under nonstringent conditions. The region of highest homology was mapped in the early region of the SV40 genome. Extensive homology was detected between the genomes of HaPV and Py under stringent hybridization conditions, indicating at least 80% base matching in the regions of strongest sequence homology. These sequences were localized within both the early region and the late region of the Py genome. The homologous DNA segments mapped in the Py and the SV40 genomes are among the most strongly conserved regions in the polyoma (miopapova)-virus group.

Animals↗

Elimination of X-ray-induced chromosomal aberrations in the progeny of female mice.

Female NMRI mice were irradiated with various doses of X-rays and induced chromosome aberrations were scored in MII oocytes (Dosage: 0.222, 0.666, 2 and 6 Gy). After irradiation with 2 Gy, early zygotes were examined in the 2-cell stage; additional dominant lethals were counted and surviving embryos were examined after 13.5 days of pregnancy. 87.2% of the MII oocytes showed structural chromosomal aberrations after irradiation with 2 Gy. Surviving embryos, however, failed to show any increase in the aberration rate. This result points to (almost) complete elimination of genetically damaged oocytes and zygotes already before birth. In addition to the structural aberrations, aneuploidies were induced. Most of them, however, were hypoploidies. Hence, the study confirmed the well-known susceptibility of oocytes around the time of fertilization for induced chromosome loss. Induced hyperploidies, however, were very rare. Evidence for induction of meiotic non-disjunction was weak. In surviving embryos, no increase in numerical aberrations, either hypoploid or hyperploid was discovered. The significance of these data for the prediction of chromosomal damage due to to ionizing radiation in humans is discussed. Recent risk estimates of UNSCEAR and other agencies represent very cautious upper levels.

Animals↗

Mutation and selection in the marker (X) syndrome. A hypothesis.

Sherman et al. (1984) concluded from a cytogenetic and genetic analysis of families with the marker (X) syndrome that the rate of the mutation leading to this syndrome is extraordinarily high (7.2 X 10(-4) in male germ cells), and that these mutations occur exclusively in male germ cells. It is shown by some model calculations that the empirical evidence can be reconciled with more conventional assumptions on the mutation rate if a moderately increased fertility of clinically unaffected female and possibly male carriers in the past is assumed. Indirect evidence for such an increased fertility can be derived from old reports on higher reproduction of slightly subnormal individuals. On the other hand, complete compensation of gene loss in affected individuals by higher fertility of unaffected carriers appears to be rather unlikely. At present, a moderately high mutation rate--as found, for example, in Duchenne muscular dystrophy or haemophilia A--in combination with a moderately increased fertility of clinically unaffected carriers is the most likely alternative.

Female↗

Characterization of the DNA of the hamster papovavirus: I. Genom length and molecular cloning.

The complete genome of the hamster papovavirus (HaPV) which was isolated from virions found in multiple skin tumors of the Syrian hamsters was measured by electron microscopy and cloned in Escherichia coli using the certified plasmid vector pBR322. The cloned viral DNA were characterized by digestion of the recombinant DNA with various restriction enzymes followed by comparison of their electrophoretic mobilities in agarose gels with that of similarly digested uncloned DNA and by electron microscopy to determine the genome size of cloned HaPV DNA. The restriction enzyme analysis of the cloned HaPV DNA showed the same cleavage pattern as the corresponding fragments from the uncloned DNA. No major insertions or deletions could be detected by heteroduplex analysis between cloned HaPV DNA and the starting material. The estimated genome size of 5.52 kb for HaPV DNA is approx. 300 bases larger than those determined for other known papovaviruses as SV40 or polyoma.

Animals↗

Clinical consequences of heterozygosity for autosomal-recessive diseases.

Heterozygotes of autosomal-recessive diseases can often be recognized by special heterozygote tests, since enzyme activities are normally reduced in comparison with the normal homozygote state. In Drosophila, the majority of recessive lethal mutations shows a reduction of fitness in heterozygotes, whereas in a strong minority fitness of heterozygotes is increased. This review will be devoted to a consideration of the extent to which heterozygotes for a wide variety of nominally recessive diseases are subject either to an increased liability for common diseases or slight shifts of behavioral characteristics. The available evidence has been collected and will be discussed in three steps: Most studies are available for phenylketonuria. For this group of diseases, a slight reduction of average--especially verbal--I.Q. in heterozygotes has been reported together with signs of a slightly increased cerebral irritability, a possible slight increase of risk for mental disease, and an increase of blood phenylalanine levels in stress situations. The PKU example is used to discuss methodological problems involved in such studies. Other conditions for which relevant deviations in heterozygotes are possible or even likely include among others lipid storage diseases, microcephaly, myoclonus epilepsy, Wilson's disease, galaktokinase deficiency, homocystinuria, recessive myotonia and ataxia- teleangiectasia (increased cancer risk). Since heterozygotes for autosomal recessive diseases are common, it is possible that an appreciable fraction of "multifactorial" genetic liabilities for common, "constitutional" or mental disease might simply be due to heterozygosity for genes whose homozygous affects are already well known. By the same token, much of the "normal" genetic variability influencing cognitive performance (I.Q.)--especially in the lower range--and personality characteristics could also be caused by recessive genes in the heterozygous state.

Adolescent↗