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Biomedical subjects

R Ehrlich

Publications and source records attributed to R Ehrlich.

At least 289 records · Page 16Linked to original sources

[Analysis of the stability and local cooperativity of DNA: proposal of a molecular mechanism for the initiation of the transcription of gene A3 of bacteriophage T7 by the RNA polymerase from E. coli].

RNA polymerase (RNAP) complexed to the A3 promoter of bacteriophage T7 is known to unwind a DNA segment located downstream of the Pribnow box. This finding can be accounted for if it is assumed that the subunit sigma of RNAP unstabilizes three GC base pairs located just upstream of the transcription start. As a consequence, the rate of promoter utilisation might be related to the relative stability of the DNA between the "Pribnow box" and the transcription start.

Base Composition↗

[Analysis of the stability and local cooperativity of DNA : elements permitting the recognition of promoters by DNA-dependent RNA polymerase].

Analysis of the local stability of promoters processed by E. Coli RNA polymerase shows that they bear a characteristic stability profile: two segments of low stability are located around --35 and --8 bases ahead of the transcription start and are generally bordered by more stable segments. This key profile may act as a recognition signal for both attracting and positioning the RNA polymerase in the promoter site.

Base Sequence↗

Some characteristics of natural cytostatic mouse splenocytes.

Murine B16 melanoma cells and metastasis variants of this tumor are resistant to NK activity mediated by normal splenocytes. The B16 cells are, however, sensitive to splenocyte-mediated cytostasis. Cytostasis was measured by a [125I]UDR incorporation-inhibition [(125I]UDR I-I) assay. The main characteristics of the [125I[UDR I-I assay and of the cells mediating it are as follows: The activity is mediated by splenocytes but not by thymocytes, it is not syngeneically restricted and it does not decrease with age. The presence of effector cells is required as splenocyte supernatants or supernatants of effector-target cell mixtures do not cause [125I]UDR I-I. The activity is probably mediated by at least 2 populations of non-phagocytic splenocytes. The first population adheres to plastic surfaces and to Sephadex G-10 columns while the other does not. The sensitivity to [125I]UDR I-I of the high metastasis B16 variant was similar to that of the low metastasis variant.

Animals↗

Effects of exposure to ozone on susceptibility to experimental tuberculosis.

Exposure of mice to 1.96 mg/m3 ozone (O3) 3 h/day, 5 days/week, for up to 8 weeks beginning at 1 or 2 weeks after challenge with Mycobacterium tuberculosis R1Rv resulted in significant enhancement of bacterial titers in the lungs at 5 through 8 weeks after challenge when compared to mice exposed to filtered air. Exposure to lower concentrations of O3 did not produce any significant changes compared to controls. Exposure of guinea pigs to 2.9 mg/m3O3 for 3 h immediately after challenge with M. tuberculosis resulted in a suppression of the cutaneous delayed hypersensitivity response, without affecting the serum hemagglutination antibody titers. However, exposure of guinea pigs to 0.98 mg/m3 O3 3h/day for 5 days, initiated within 3 h after the infectious challenge, enhanced hemagglutination antibody titers initially, but the delayed hypersensitivity reaction did not differ from controls.

Animals↗

Effects of exposure to peroxyacetyl nitrate on susceptibility to acute and chronic bacterial infection.

A significant increase in mortality due to acute respiratory pneumonia caused by inhalation of Streptococcus pyogenes aerosol was seen after a single 3-h exposure of mice to 14.8-28.4 mg/m3 peroxyacetyl nitrate (PAN). The excess mortality ranged from 8 to 39% and the decrease in survival time from 2.4 to 7.9 d. A single exposure to 25.0 mg/m3 PAN resulted in a significant increase in total number of cells lavaged from the lungs but somewhat decreased levels of adenosine triphosphate (ATP) in alveolar macrophages. Exposure to 7.4 mg/m3 PAN for 3 h/d, 5 d/wk, for 2 wk resulted in a reduced total count of free pulmonary cells and a significant reduction of ATP levels in alveolar macrophages but had no effect on mortality or survival rate. Scanning electron microscopic observations of the respiratory tract after both single and multiple exposures to PAN showed raised and sloughing nonciliated cells in the nasal cavities and tracheas and presence of excess mucus. Six daily 3-h exposures to 25.0 mg/m3 PAN did not produce any marked changes in a chronic respiratory infection in mice as measured by Mycobacterium tuberculosis lung titers.

Acetates↗

Fluorimetric study of yeast tRNAPheCCF in the complex with phenylalanyl-tRNA synthetase. Evidence for a correlation between the structural adaptation of both macromolecules and the appearance of the acylation activity.

The fluorescence properties of yeast tRNAPheCCF (tRNAPhe in which the 3'-terminal adenosine has been replaced by formycin) and tRNAPheCCFoxi-red (tRNAPheCCF after periodate oxidation followed by borohydride reduction) were studied in the complex with the cognate aminoacyl-tRNA synthetase. In both cases a conformational change affecting the 3' end was observed in a magnesium concentration range close to 1 mM. The modification of formycin fluorescence could be ascribed simultaneously to the existence of a tautomeric equilibrium of the fluorescent probe and to a pH effect raising from a prototropic effect at the active site of phenylalanyl-tRNA synthetase, and to a partial destacking of the 3'-formycin from the adjacent C residue. The observed transconformation, which can be related to the structure modification of the anticodon loop previously reported [Ehrlich, Lefèvre, and Remy (1980) Eur. J. Biochem. 103, 145-153], takes place in the magnesium concentration range allowing the transfer of the activated amino acid from the adenylate to the tRNA. The interconnection between the anticodon loop and the accepting end was further supported by the observation that wybutine excision hinders the specific structure modification of 3'-formycin upon binding to the synthetase. The tRNAPhe transconformations occurring in the complex with the cognate synthetase probably reflect a reciprocal adaptation of both macromolecules which might lead to the optimal aminoacylation velocity and thus contribute to the specificity of aminoacylation, since it was previously established that this specificity relies more strongly on the kinetics of the reaction than on a discrimination of tRNAs according to different affinities.

Amino Acyl-tRNA Synthetases↗

Natural cellular reactivities mediated by splenocytes from mice bearing three types of primary tumor.

The ability of splenocytes from mice bearing three types of primary tumor to lyse YAC-I target cells (NK activity) and to inhibit [125I]dUrd incorporation ([125I]dUrd I-I = cytostasis) into B16-F10 target cells was compared to the ability of normal splenocytes to perform such activities. The tumor systems used were urethane-induced lung adenomas in BALB/c mice, dimethylbenzanthracene (DMBA)-induced tumors in hormonally-stimulated BALB/c mice and mammary tumors in force-bred C3HeB mice. The two types of natural cellular reactivity in lung adenoma-bearing mice were unaffected. The NK activity of mice bearing DMBA and forced-breeding-induced tumors was suppressed. The cytostatic ability of splenocytes from mice bearing DMBA-induced tumors was significantly elevated. The spleens of mice bearing primary DMBA-induced tumors contained cells able to suppress NK activity or to compete against target cells for NK cells.

Adenoma↗

[Use of the degeneracy of the genetic code by selective pressure to cut up genes of procaryote genomes].

The DNA sequences of three bacteriophages are analysed in order to localise those parts coding for a protein. A weak stability on the DNA molecule allows us to characterize the beginning and the end of genes. A survey of the codons used shows that the cause for this weak stability is the systematic use of A-T bases in third position, which is made possible by the degeneracy of the genetic code.

Bacteriophage phi X 174↗

Social perspectives in Huntington's chorea.

The social implications of Huntington's chorea are serious and far-reaching, affecting all members of the family and the community as a whole. The relativly common occurrence of suicide and of major and minor crimes are cause for concern. The disease imposes a significant economic burden on both the family and society. The minimum direct cost to the state of a single affected prson with Huntington's chorea in South Africa is estimated at R23 000.

Crime↗

Fluorimetric study of the complex between yeast phenylalanyl-tRNA synthetase and tRNA-Phe. 2. Evidence for an asymmetric behaviour of the enzyme.

The variations of several spectroscopic properties of yeast tRNA-Phe and phenylalanyl-tRNA synthetase upon complex formation, were used to study the stoichiometry of the complex in different experimental conditions. In all cases, for the tRNA-Phe-enzyme complex, in the absence of other ligands, the saturations of the different conformational changes monitored for both macromolecules, are achieved at a 2:1 tRNA/enzyme stoichiometry. Phenylalanine does not modify this saturation. In contrast, the presence of 1 mM ATP induces an asymmetric behaviour of the synthetase: two tRNAs are still bound per enzyme molecule but the conformational change of the latter is completed upon binding of a single tRNA molecule.

Amino Acyl-tRNA Synthetases↗

Interaction between environmental pollutants and respiratory infections.

The major aspects that must be considered in studies of the health effects of environmental pollutants are: the direct damage due to the exposure, the role of pre-existing disease, and effects of the exposure on the response to secondary stresses. In experimental studies at concentrations of air pollutants found in urban environments frank toxicological responses are rarely observed. However, exposure to a secondary stress, i.e. respiratory challenge with infectious bacteria, can exacerbate the response of the experimental host. Changes in the resistance to respiratory infections provide a highly sensitive experimental animal model system, which is increasingly used in studies of health effects of air pollutants. This model indicates the impairment of the basic defense mechanisms of the respiratory system by the combined exposure to low concentrations of pollutants and the superimposed bacterial infection. Changes in the resistance to respiratory infections were studied in various species of laboratory animals. S. pyogenes and K. pneumoniae are the bacteria of choice to induce the pulmonary infection. Included in the studies are short-term single and multiple exposures as well as long-term exposures to gaseous pollutants such as O3 and NO2 and particulate pollutants such as sulfates and nitrates. Changes in the resistance are measured as excess mortalities and reduced survival time as compared to those in infected animals not exposed to the pollutants. Other parameters measured ranged from changes in the immune response to changes in retention rates of bacteria in lungs.

Aerosols↗

Thermal perturbation differential spectra of ribonucleic acids. I. Hydration effects.

A relatively important change in UV absorption is observed upon thermal perturbation of nucleotide solutions. Comparison of these thermal perturbation spectra of nucleic acid residues with solvent perturbation spectra of the same compounds suggests that this spectral change can most probably be attributed to temperature induced hydration change of the bases. This conclusion is confirmed by the results obtained from acid-base perturbation spectra of these nucleotides as well as thermal perturbation spectra of nucleotides containing modified bases. It is shown that this temperature dependent change in UV absorption is also present in dinucleoside monophosphates. In that case, this effect is superimposed upon the well known change in absorbance due to the unstacking of the bases during heating.

Hydrogen-Ion Concentration↗

Thermal perturbation differential spectra of ribonucleic acids. II. Nearest neighbour interactions.

Dinucleoside monophosphates are used here as models for studying sequence dependence of the hypochromic effect correlated with base stacking. It was shown that once the contribution due to the temperature dependent hydration change of the bases is substracted from the thermal perturbation difference spectra of dinucleoside monophosphates, the absorbance change of the dimer only due to unstacking of the bases could be obtained. In order to be able to use these corrected thermal perturbation difference spectra as models for studying nearest neighbour interactions in nucleic acids, it was necessary to normalize them to 100% unstacking of the bases. To perform this normalization, apparent thermodynamic parameters were extracted from the corrected transition curves by means of the two-state model.

Chemical Phenomena↗

Ribosomal protein alterations in thiostrepton- and Micrococcin-resistant mutants of Bacillus subtilis.

Ribosomal proteins of parental thiostrepton- and micrococcin-sensitive Bacillus subtilis cysA14 and thiostrepton-and micrococcin-resistant mutants were compared. Several electrophoretic and immunochemical techniques showed unambiguously that BS-L11 was not present on 50 S ribosomal subunits from the six thiostrepton-resistant mutants. Protein BS-L11 reappeared in all six revertants from thiostrepton resistance to thiostrepton sensitivity. No definitive protein alteration could be ascribed to the mutation from micrococcin sensitivity to resistance. It was also demonstrated that B. subtilis protein BS-L11 is homologous to Escherichia coli ribosomal protein L11. The finding that ribosomes from thiostrepton-resistant mutants do not contain protein L11 suggests that L11 not only is involved in binding of thiostrepton, but also, when mutationally altered, confers resistance to this antibiotic. Although the ribosomes of these strains do not contain protein L11, all thiostrepton-resistant mutants showed the same viability as the parental strain. Thus protein L11 cannot be obligatory for the structure and function of the ribosome.

Anti-Bacterial Agents↗