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J Drews

Publications and source records attributed to J Drews.

At least 55 records · Page 3Linked to original sources
PubMed1977

Further evidence that elongation factor 1 remains bound to ribosomes during peptide chain elongation.

This paper describes three types of experiments which indicate that the binding sites for elongation factor 1 (EF-1) and elongation factor 2 (EF-2) on ascites cell ribosomes are not identical and perhaps not even overlapping. The experimental evidence presented includes direct competitive binding of labeled elongation factors to ribosomes as well as the influence of pokeweed antiviral protein and Escherichia coli anti L7/L12 proteins on the binding and function of the two factors. It is further shown that EF-1beta from Artemia salina does not function in displacing EF-1 from mouse ascites tumor cell ribosomes. These results also support our recently proposed model that EF-1 remains bound to the ribosome during the peptide chain elongation cycle.

Animals↗
PubMed1976

Functional identity of the monomeric and multiple forms of elongation-factor 1 from Krebs-II mouse ascites-tumor cells.

Highly purified 3H-labelled elongation factor 1 (EF-1) from Krebs II mouse ascites tumour cells was separated into biologically active monomeric and aggregate forms of the enzyme by either gradient centrifugation or gel filtration. When corrected for their content of inactive enzyme both forms of the factor were found to be equally active whether tested in the binding or synthesis reaction. The only form of the enzyme found bound to ribosomes was the monomer; it was therefore concluded that the aggregate form of the enzyme must first dissociate before it reacts with the ribosome. The stoichiometry of the aminoacyl-tRNA binding reaction to ribosomes in the presence of guanosine nucleotides was also studied. It was found that one molecule of aminoacyl-tRNA and of Guo-5'-P2-CH2-P is bound per molecule of EF-1 bound to the ribosome. Following interaction with a release from, the ribosomes, EF-1 was found to be predominantly monomeric.

Animals↗
PubMed1976

The binding of tritiated elongation-factors 1 and 2 to ribosomes from Krebs II mouse ascites-tumore cells. The influence of various antibiotics and toxins.

The effect of a number of different antibiotics and toxins on the capacity of Krebs II mouse ascites ribosomes to bind 3H-labelled elongation factors (EF-1 and EF-2) has been examined. It was found that abrin and ricin inhibit the binding of EF-2, while diphtheria toxin, sparsomycin, streptovitacin A, and cycloheximide had essentially no effect on its binding. Of the other compounds examined, sparsomycin was unique in its capacity, under some circumstances, to significantly affect the binding of aminoacyl-tRNA and EF-1 to ribosomes. Fusidic acid appears to nonspecifically enhance the binding of both EF-1 and EF-2.

Abrin↗
PubMed1976

Effect of active and passive immunizations with lipid A and salmonella minnesota Re 595 on gram-negative infections in mice.

The capacity of lipid A, a structure common to the lipopolysaccharide cores of all gram-negative bacteria, to serve as an active immunizing agent in mice and to protect these animals against gram-negative infections was investigated. Active immunization experiments were also performed with the Re mutant of Salmonella minnesota 595 which carries a lipopolysaccharide composed of lipid A and three residues of ketodeoxyoctonic acid. Single injections of lipid A complexed to acid-hydrolyzed bacteria as carriers failed to induce specific protection against subsequent challenge infections with E. coli O4 and S. breslau. Repeated injections of lipid A resulted in good protection against intraperitoneal challenge with S. breslau and partial protection against intravenous challenge with the same organism but did not alter the sensitivity of mice to challenge infections with E. coli or Pasteurella multocida. Whole antisera or serum fractions from rabbits in which high titers against lipid A had been attained by repeated intravenous injections of the antigen did not protect mice against challenge infections with E. coli O4. In contrast a single injection of the Re mutant of S. minnesota antigen in combination with incomplete Freund's adjuvant provided substantial protection against an otherwise lethal intraperitoneal infection with S. breslau over a period of at least 45 days. Repeated application of the Re antigen resulted in partial protection against experimental infections with E. coli O4, S. breslau and Pasteurella multocida. Injections of S. minnesota Re 595 antiserum provided better protection against an E. coli O4 infection than lipid A sera or antibodies of the IgG or IgM type directed against this antigen.

Animals↗
PubMed1976

Parameters of acquired resistance and their role in the evaluation of new chemotherapeutic drugs.

Acquired resistance can be defined as a qualitative alteration of the genetic material of a cell which is phenotypically correlated with a measurable decrease of the cell's sensitivity against one or several chemotherapeutic agents. There are two basic genetic mechanisms which can lead to the emergence of resistance: mutation and the acquisition of additional genetic material from another cell. Both forms of resistance play an important role in clinical situations: the emergence of resistance by mutation occurs in tumor cells and can also lead to therapeutic problems in antimicrobial chemotherapy. In bacteria, however, acquisition of resistance plasmids represents the dominating mechanism which is responsible for most therapeutic problems in the clinical environment. The different genetic mechanisms involved in the emergence of resistance are paralleled -- at least in bacteria -- by two principally different groups of biochemical mechanisms implementing resistance. Mutations lead to alterations of single cell constituents such as the cell membrane or cellular receptors necessary for the binding of the antimicrobial agent. This form of resistance is biochemically characterized by the inaccessibility of the cell interior for a particular compound or by the modification of an intracellular binding site which loses its affinity for the chemotherapeutic agent. Resistance plasmids on the other hand code for enzymes which inactivate the antibiotic (beta-lactamases, aminoglycosideinactivating enzymes, chloramphenicol-acetyltransferase); In some cases, they direct the synthesis of proteins which affect cell permeability (tetracycline) or isoenzymes which have a lower affinity for the inhibitor (trimethoprim). Resistance against antibiotics can be inducible; In these cases the regulatory mechanisms involved are stable genetical traits as resistance itself; Using chloramphenicol, beta-lactam-antibiotics and aminoglycosides as examples, it is demonstrated that resistance data gathered early in the development of a new drug are of little value in estimating the clinical potential of a new compound. Information on the rate at which resistance develops, on the pattern according to which it emerges ("single step" or "multi step") and on cross-resistance patterns is important in the characterization of a new drug but is often invalidated by later findings obtained in the clinical environment; The problem appears somewhat simpler if a new drug is a member of an already known class of compounds, e.g. a beta-lactam or an aminoglycoside. In such cases our knowledge of frequent enzymatic inactivation mechanisms provides a basis not only for the evaluation of an existing drug, but also for the synthesis of new derivatives.

Anti-Bacterial Agents↗
PubMed1976

A new concept of the function of elongation factor 1 in peptid chain elongation.

An entirely new model for the mechanism of elongation factor 1 (EF-1) function is presented. Experiments in which mixtures of [3H]EF-1, ribosomes from Drebs II ascites cells and various additional co-factors were analyzed by chromatography on Sepharose 6B, show that EF-1 binds to the ribosome early in the translation process and remains bound on the ribosome during translation. Optimal EF-1 binding occurs on polynucleotide-programmed ribosomes carrying a tRNA in their P-site. On the other hand it was clearly shown that EF-2 attached at each translocation event and was then released before a new Phe-tRNA could be bound.

Animals↗
PubMed1975

[Treatment of thyroid storm with plasmapheresis (author's transl)].

The conventional treatment of thyrotoxicosis is based on central and periphery therapeutic measures which respectively block the thyroid hormone production and subdue the hormone effect in the tissue. On account of long biological hal-life of thyroxine conventional methods of treatment fail to achieve a rapid reduction of the excessively high serumhormone level. As the overwhelming proportion of thyroid hormone is boud to serum proteins, plasmapheresis presents itself as a possibility of achieving this therapeutic aim. In the following a report is given on the successful practice of plasmapheresis in two cases of thyrotoxiicosis. In each of these, 1.4 and 1.2 litres of plasma respectively were re moved in all. Immediate combined use of plasmapheresis and conventional therapy appears to constitute a definite improvement in the treatment of thyrotoxicosis.

Adult↗
PubMed1975

The binding of tritiated elongation factors 1 and 2 to ribosomes from Krebs II mouse ascites tumor cells.

Tritiated elongation factors 1 and 2 (EF-1 and EF-2) were obtained from Krebs II ascites cells which had been grown in mice injected with radioactive amino acids. The highly purified factors were sufficiently radioactive to be used in a study of the interactions between ribosomes and elongation factors. The following results were obtained. 1. EF-1 binding to ribosomes requires the presence of a polynucleotide, an aminoacyl-tRNA specified by the latter and a guanosine nucleotide carrying three phosphate groups. The hydrolysis of the GTP molecule involved in the binding reaction leads to the immediate release of EF-1. If GTP is replaced by Guo-5'-P2-CH2-P the factor remains bound to the ribosome and can be detected by sucrose gradient centrifugation techniques. 2. Likewise EF-2 binding to ribosomes can only be detected in the presence of GUO-5'-P2-CH2-P. 3. The affinity of ribosomes for EF-2 appears to be higher than for EF-1: PREINCUBATION OF RIBOSOMES WITH EF-2 inhibits the subsequent attachment of EF-1 almost completely. EF-1 prebound to ribosomes in the presence of GUO-5'-P2-CH2-P, POLY(URIDYLIC ACID) AND Phe-tRNA-Phe is partially removed from the ribosomes together with Phe-tRNA during a second incubation with EF-2. 4. Although EF-2 binding to ribosomes precludes any stable association between ribosomes and EF-1 it does not prevent the insertion of aminoacyl-tRNA into the ribosomal A-site. The attachment of aminoacyl-tRNA under these conditions enhances the binding of EF-2 to the ribosome. 5. The antibiotic showdomycin strongly inhibits the attachment of EF-1 to ribosomes and to a lesser degree impairs the binding of EF-2. 6. A-site ribosomes display a strong preference for the attachment of EF-2 and bind EF-1 only very poorly. The reverse is true for P-site ribosomes which are good substrates for the binding of EF-1 and bind EF-2 less efficiently than A-site ribosomes. These results and a number of additional findings made in this and in previous studies are discussed in the general context of the structure and function of mammalian elongation factors 1 and 2.

Animals↗
PubMed1975

Antimicrobial activities of 81.723 hfu, a new pleuromutilin derivative.

The new pleuromutilin derivative 81.723 hfu is extremely active against gram-positive organisms such as streptococci, staphylococci, and against mycoplasmas. A number of Shigella, Klebsiella, and Escherichia coli strains were also found to be quite susceptible to this new agent, whereas other gram-negative organisms like Pseudomonas aeruginosa, Proteus species, and Alcaligenes faecalis proved to be naturally resistant to 81.723 hfu. The new compound acts bacteriostatically. Bactericidal effects have been observed only at concentrations which are 100-fold higher than the minimal inhibitory concentrations. The new antibiotic is well tolerated in all animal species tested so far and has been successfully used in the treatment of experimental infections with gram-positive organisms and with mycoplasmas in mice and rats. Resistance against this new compound arose gradually in all microorganisms investigated. It is noteworthy that the rate at which resistance against 81.723 hfu emerged in mycoplasmas (Mycoplasma gallisepticum and Mycoplasma hyorhinis) was significantly slower than the corresponding rate at which resistance against tylosin tartrate appeared. Mycoplasma strains which became insensitive to 81.723 hfu were also resistant to tylosin tartrate, whereas mycoplasmas which developed resistance against tylosin tartrate, although less sensitive to 81.723 hfu than wild-type strains, were still eliminated by this drug. In a strain of Klebsiella pneumoniae, complete cross-resistance was observed between the pleuromutilin derivative on one hand and lincomycin and erythromycin on the other. Modest degrees of cross-resistance were also observed with chloramphenicol. However, it appears unlikely that the latter phenomenon is sufficiently pronounced to affect treatment with either antibiotic.

Agaricales↗