[Not Available].
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History, 19th Century↗
Biomedical subjects
G Kaufmann
Publications and source records attributed to G Kaufmann.
[A case from practice (293). HIV-infection and histoplasmosis].
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AIDS-Related Opportunistic Infections↗
In vivo-effect of intraadrenal nicotine and substance P application on rat adrenal medullary catecholamine secretion.
The present study was conducted to characterize in vivo the intraadrenal catecholamine (CA) secretion in rats. This was possible by using a microdialysis system (MDS) which mimics some properties of an artificial capillary. One end of this system was connected to a peristaltic pump, from the other end fractions were sampled at 5 min intervals. Concentrations of epinephrine (E) and norepinephrine (NE) in adrenal dialysate fractions were determined by HPLC electrochemical detection. Through this MDS nicotine was administered directly into the adrenal medulla of freely moving rats and the response of catecholamine release was determined. In the second part of the study the effect of exogenous substance P (SP) on spontaneous as well as on nicotine-stimulated CA release was investigated. Like nicotine, SP was administered directly into the adrenal medulla. At a flow rate of 25 microliter/min the transfer rates of CA and nicotine were approximately 1% whereas SP passed at a rate of 01.-0.2%. Under resting conditions CA release remained constant. In response to 2 x 10(-7) M nicotine (which resulted in local concentration of 2 x 10(-7) M), E and NE secretion increased 2.9 and 5.4-fold, respectively. However, due to an increased E response this difference attenuated with a later onset of the first stimulus. The higher concentrations of 10(-4) M resulted in 8.1 and 10.8-fold increases for E and NE. This latter response is clearly supraphysiologic and therefore the 2 x 10(-5) M concentration was used for further experimentation. CA secretion was stimulated with nicotine four times at 30 min intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Glands↗
Maternal education and child survival: anthropological responses to demographic evidence.
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Anthropology↗
State v. Chabot: a euthanasia case from the Netherlands.
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Euthanasia, Active↗
Normal and stable transfected cancer cell lines: tools for a screening of progestogenic, antiprogestogenic and antiglucocorticoid substances.
Synthetic ligands for steroid receptors represent important drugs in the control of fertility and in the therapy of a large variety of endocrinological diseases. In the present study we describe the establishment of different biochemical and molecular biological screening methods. We developed a microtiter plate assay for the induction of the de novo synthesis of alkaline phosphatase in T47D cells as a suitable and fast system for the measurement of actions of progestogenic and antiprogestogenic compounds. We compared several progestogenic activities with relative molar binding affinities (RBA) to the progesterone receptor. The ED50 values for the induction of alkaline phosphatase are in good accordance with RBA to the progesterone receptor. Furthermore, glucocorticoid and antiglucocorticoid effects were measured in the stable transfected breast cancer cell line ZR75/-763AGP-CAT. The construct AGP-CAT contains the glucocorticoid responsible element of the rat alpha-1-acid glycoprotein (AGP) gene with the bacterial chloramphenicol acetyltransferase (CAT) gene. The rat hepatoma Reuber cell line H4-II-E with the tyrosine aminotransferase gene is a further suitable marker of glucocorticoid action and was used as a second model for glucocorticoid activity. Thus, we demonstrated in three cell systems the antiprogestogenic and antiglucocorticoid activities of the model compound mifepristone.
Alkaline Phosphatase↗
Functional expression and properties of the tRNA(Lys)-specific core anticodon nuclease encoded by Escherichia coli prrC.
Escherichia coli carrying the optional locus prr harbor a latent, tRNA(Lys)-specific anticodon nuclease, activated by the product of phage T4 stp. Anticodon nuclease latency is ascribed to the masking of prrC, implicated with the enzymatic activity, by flanking, type Ic DNA restriction modification genes (prrA, B&D-hsdM, S&R). Overexpression of plasmid-borne prrC elicited anticodon nuclease activity in uninfected E. coli. In vitro, the prr-C-coded core activity was indifferent to a synthetic Stp polypeptide, GTP, ATP, and endogenous DNA, effectors that synergistically activate the latent enzyme. Several facts suggested that PrrC is highly labile in the absence of the masking proteins. The core activity decayed with t1/2 below 1 min at 30 degrees C, and the PrrC portion of a fusion protein was unstable. Moreover, expression of prrC from its own promoter at low plasmid copy number did not allow detection of core activity. Yet, it sufficed for establishment of a latent, T4-inducible enzyme when complemented by the masking Hsd proteins, which were provided by another replicon. Interaction between the antagonistic components of latent anticodon nuclease was also demonstrated immunochemically. The coupling of anticodon nuclease with a DNA restriction modification system may serve to ward off its inadvertent toxicity and maintain it as an antiviral contingency.
Amino Acid Sequence↗
[The endocrinologic profile of metabolites of the progestin dienogest].
Two identified metabolites of the orally active progestin dienogest, the compounds STS 749 (17 alpha-cyanomethyl-11 beta,17 beta-dihydroxy-estra-4,9-dien-3-one) and STS 825 (17 alpha-cyanomethyl-estra-1,3,5(10),9(11)-tetraene-3,17 beta-diol), furthermore 4 microbially formed metabolites and 10 chemically prepared analoga of dienogest were characterized by endocrinological tests. The compounds were investigated for progesterone-receptor binding, progestational and antiprogestational, estrogenic and antigonadotropic activities, furthermore for inhibition of fertility. In no case an increased progestational activity of metabolites or analoga was found, compared to the parent substance. Therefore, it should be excluded, that dienogest acts as a prodrug. Additionally, the dosages necessary to produce the progestational effects are quite similar using oral or subcutaneous application. Therefore, a first-pass effect can be neglected. Regarding the low endocrine side effects of dienogest, the antiprogestational activity may be caused, at least in part, by metabolites.
Androgen Antagonists↗
HSD restriction-modification proteins partake in latent anticodon nuclease.
Phage T4-induced anticodon nuclease triggers cleavage-ligation of the host tRNA(Lys). The enzyme is encoded in latent form by the optional Escherichia coli locus prr and is activated by the product of the phage stp gene. Anticodon nuclease latency is attributed to the masking of the core function prrC by flanking elements homologous with type I restriction-modification genes (prrA-hsdM and prrD-hsdR). Activation of anticodon nuclease in extracts of uninfected prr+ cells required synthetic Stp, ATP and GTP and appeared to depend on endogenous DNA. Stp could be substituted by a small, heat-stable E. coli factor, hinting that anticodon nuclease may be mobilized in cellular situations other than T4 infection. Hsd antibodies recognized the anticodon nuclease holoenzyme but not the prrC-encoded core. Taken together, these data indicate that Hsd proteins partake in the latent ACNase complex where they mask the core factor PrrC. Presumably, this masking interaction is disrupted by Stp in conjunction with Hsd ligands. The Hsd-PrrC interaction may signify coupling and mutual enhancement of two prokaryotic restriction systems operating at the DNA and tRNA levels.
DNA Restriction-Modification Enzymes↗
The clastogenic potential in vitro of pyrrolizidine alkaloids employing hepatocyte metabolism.
Three pyrrolizidine alkaloids (PAs), monocrotaline, retrorsine and isatidine, were tested for their clastogenic activity under different conditions of metabolic activation in vitro. All three compounds exhibited a weak activity when V79 cells were treated at very high concentrations for 18 h in the absence of a metabolizing system. Short-term (2 h) treatment with rat liver S9 mix led to a strong and concentration-dependent increase in chromosomal aberrations for retrorsine. Isatidine was not mutagenic with S9 mix and monocrotaline was positive at high concentrations only. In contrast, a prolonged treatment (18 h) in vitro under activation conditions in the presence of primary hepatocytes led to clear concentration-dependent positive responses for all three PAs investigated. Particularly the results with isatidine demonstrate that in vitro tests using S9 mix for metabolization can generate misleading results. It is not clear whether the results could be attributed to a better activation of the test compounds by intact hepatocytes in comparison to S9 mix or if the fact that only hepatocytes allow a treatment for the whole culture period under activation conditions was more important. Owing to its strong cytotoxicity the exposure to S9 mix is generally limited to 2-4 h, limiting also the exposure of the target cells to a test chemical as well as its metabolites. The results presented show significant differences in mutagenic potency of PAs due to variations in the activation system. This underlines the usefulness of primary hepatocytes, e.g., for the detection of pre-mutagens. The PAs investigated are present in plants which are used for phytotherapeutic medicinal products. They do not contribute to their efficacy and are, therefore, not to be tolerated in amounts that may impose a risk for the user.
Animals↗
Steroid-1-dehydrogenase of Rhodococcus erythropolis: purification and N-terminal amino acid sequence.
The inducible steroid-1-dehydrogenase from the bacterium Rhodococcus erythropolis IMET 7030 was purified to homogeneity using affinity chromatographic, electrophoretic, and ion exchange techniques. The spectrum of the pure enzyme is characterized by the associated FAD. The M(r) of the enzyme is 56,000. The amino acid composition and the sequence of the 13 N-terminal amino acids are given.
Amino Acid Sequence↗
Assembly of simian virus 40 Okazaki pieces from DNA primers is reversibly arrested by ATP depletion.
We have previously proposed that DNA polymerase alpha-primase provides short RNA-DNA precursors below 40 nucleotides (DNA primers), several of which assemble into an Okazaki piece after intervening RNA has been removed and the gaps have been filled by DNA polymerase delta (or epsilon) (T. Nethanel, S. Reisfeld, G. Dinter-Gottlieb, and G. Kaufmann, J. Virol. 62:2867-2873, 1988; T. Nethanel and G. Kaufmann, J. Virol. 64:5912-5918, 1990). In this report, we confirm and extend these conclusions by studying the effects of deoxynucleoside triphosphate (dNTP) concentrations and the presence of ATP on the occurrence, dynamics, and configuration of DNA primers in simian virus 40 replicative intermediate DNA. We first show that these parameters are not significantly affected by a 10-fold increase in dNTP precursor concentrations. We then demonstrate that Okazaki piece synthesis can be arrested at the level of DNA primers by ATP depletion. The arrested DNA primers faced short gaps of 10 to 20 nucleotides at their 3' ends and were progressively chased into Okazaki pieces when ATP was restored. ATP could not be substituted in this process by adenosine-5'-O-(3-thiotriphosphate) or adenyl-imidodiphosphate. The chase was interrupted by aphidicolin but not by butylphenyl-dGTP. The results implicate an ATP-requiring factor in the switch between the two DNA polymerases engaged in Okazaki piece synthesis. They also suggest that the replication fork advances by small, DNA primer-size increments.
Adenosine Triphosphate↗
[The internist--a many-sided profession].
"Internal medicine" in the USA, and "general medicine" in the UK, are increasingly assuming the form of basic medical knowledge with a view to subsequent specialization. In Switzerland, three types of practising internists or physicians (in the strict sense) can be described: the internist as general practitioner, the general internist with a main centre of interest, and the subspecialist. Continuing medical education must take these manifold aspects of the profession into account. For practising physicians, joint meetings of internists of the second and third types are desirable, on the lines of those for physicians in the major hospitals.
Education, Medical, Graduate↗
[Hypercholesterolemia and hypertension--equivalent risk factors?].
Official recommendations for handling of hypercholesterolaemia are based on the comprehensive knowledge of serum cholesterol values in the healthy population as knowledge of blood pressure is desirable. To question this premise, both observational and interventional trials concerning the two risk factors are compared. Apparent similarities are produced by the fact that in hypertension trials control persons often are treated in the condition of normal care, whereas in lipid trials they are not. Early hypertension studies confirm beyond any doubt that the profit of hypotensive drugs is much higher than that of any cholesterol-lowering measure. The difference is most striking in the high-risk groups, comparing the treatment benefit in malignant hypertension with the hitherto poor results in familial hypercholesterolaemia. The author suggests a thorough analysis of all screening tests and interventional recommendations in medicine, aiming to allocate only a limited proportion of the normal population to regular medical supervision. There hypercholesterolaemia will have its modest place. Instead of intensified screening and drug treatment of healthy individuals, general advice for nutritional changes seems more reasonable.
Adult↗
Report of a comparative study of DNA damage and repair assays in primary rat hepatocytes with five coded chemicals.
We report the results of a collaborative study for the detection of chemical-induced DNA damage in primary cultures of rat hepatocytes. The methods include the detection of unscheduled DNA synthesis (UDS) with either autoradiography (5 laboratories) or liquid scintillation counting (2 laboratories) and the assessment of DNA single-strand breaks with the alkaline elution assay (1 laboratory). Interlaboratory standardization was omitted in order to prove the agreement of the assays under routine conditions. Five coded chemicals were tested. For 4 chemicals (2-acetylaminofluorene, thiourea, glycerine and potassium chloride) the UDS data were consistent in all laboratories, thus indicating a high consensus of the test systems applied in the different laboratories. Those 3 chemicals that were not expected to elicit genotoxic activity (thiourea, glycerine, and potassium chloride) yielded negative results in all laboratories. 2-Acetylaminofluorene, a known DNA-damaging agent in hepatocytes, gave strongly positive responses in all laboratories. In contrast, N-nitrosodiphenylamine led to equivocal responses.
2-Acetylaminofluorene↗
The optional E. coli prr locus encodes a latent form of phage T4-induced anticodon nuclease.
The optional Escherichia coli prr locus restricts phage T4 mutants lacking polynucleotide kinase or RNA ligase. Underlying this restriction is the specific manifestation of the T4-induced anticodon nuclease, an enzyme which triggers the cleavage-ligation of the host tRNALys. We report here the molecular cloning, nucleotide sequence and mutational analysis of prr-associated DNA. The results indicate that prr encodes a latent form of anticodon nuclease consisting of a core enzyme and cognate masking agents. They suggest that the T4-encoded factors of anticodon nuclease counteract the prr-encoded masking agents, thus activating the latent enzyme. The encoding of a tRNA cleavage-ligation pathway by two separate genetic systems which cohabitate E. coli may provide a clue to the evolution of RNA splicing mechanisms mediated by proteins.
Amino Acid Sequence↗
Steroid-1-dehydrogenases in nocardioform bacteria studied by electrophoresis and immuno blotting techniques.
Fifteen noncardioform bacteria strains, capable of transforming steroid compounds were investigated with regard to their range of inducible steroid-1-dehydrogenase (St1DH)1 activities. The St1DHs of these bacteria were compared due to their immuno reactivity in Western blot experiments with a rabbit antiserum raised against the purified St1DH of Rhodococcus rhodochrous 7030. Four strains exhibited a strong immuno reactivity, irrespective of differences in the electrophoretic mobility of the enzymes. Five strains revealed significantly diminished reactivities, and in five strains with a very low St1DH content, no reactivity was found. One strain, designated as Nocardiaspec. 7151, exhibited a high, inducible St1DH activity, but no immunoreaction was found. The absence of immuno reactivity is discussed in connection with the considerably diminished electrophoretic mobility of this enzyme.
Blotting, Western↗
Shifts in auditory brainstem response latencies following plasma-level-controlled aminoglycoside therapy.
The ototoxic effect of plasma-level-controlled netilmicin and tobramycin was monitored in 20 intensive care patients, using auditory brainstem responses (ABRs). ABRs were recorded at the onset and after 6 days of treatment. Significant shifts in the ABR wave V latency were observed independent of the type of medication received or whether the patients were intubated or not. Shifts were also observed in wave I latencies. These latter changes were only significant for the complete population, probably because this potential is more difficult to elicit and measure than is wave V. The I-V interlatency time was greater for netilmicin than for tobramycin. These results indicate that the cumulative effects of aminoglycoside ototoxicity may be different for the central and peripheral nervous systems, and therefore ABR measurements may be the most accurate way of controlling ototoxicity in intensive care patients.
Adult↗