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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 955 records · Page 53Linked to original sources
PubMed1975

Interaction of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein with DNAs of different base composition.

The changes in absorption spectra in the visible region observed on adding different naturally occurring and synthetic DNA duplexes to solutions of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein indicate that the mercurial reacts with polynucleotides of this type. The reaction is reversible as proved by adding excess of KCN which restores the original spectra of the free dye. The interaction is characterised also by quenching of the fluorescence of the dye and the induction of optical activity in it. The extent of these spectral effects depends strongly on the (A+T) content of the complexed DNA and decreased in the order: poly [d(A-T)], Clostridium perfringens DAN, Escherichia coli DNA, Micrococcus luteus DNA and poly(dC). From equilibrium-dialysis experiments the same order in affinity is obtained when these poly-nucleotides are at equilibrium with the same concentration of 4,5-dibromo-2,7-di-(acetatomercuri)-fluorescein. From the changes produced by different mercurials in the ORD spectra and viscosity of a DNA solution it has been concluded that 4,5-dibromo-2,7-di(acetatomercuri)-fluorescein does not cause any drastic alteration of the secondary structure of DNA.

Animals↗
PubMed1975

Interactions of heteroaromatic compounds with nucleic acids. 1. The influence of heteroatoms and polarizability on the base specificity of intercalating ligands.

We have examined the origins of base specificity in intercalating ligands by studying the interaction with DNA of a series of proflavine and acridine orange analogs differing in the heteroatoms present in the chromophore. Base specificity was determined by differential dialysis of the dye against DNA samples of differing G-C content. We find that G-C specificity increases as the visible absorbance band of the chromophore moves to longer wavelength, implying a relation between specificity and polarizability of the chromophore. This can be rationalized by recognizing that the G-C pair is more polar than A-T, and should therefore interact more favorably with an easily polarized ring system. We find in addition that dimethylation of the chromophore amino groups increases specificity which we discuss in terms of steric and coupled steric-electronic contributions. Our results also bear on the origin of G-C specificity in binding actinomycin to DNA. Some of the compounds studied are as G-C specific as actinomycin, yet they lack hydrogen-bonding functions as plausible determinants of specificity. This observation gives new life to the hypothesis that the specificity of actinomycin is determined primarily by preferential interaction of the chromophore with a G-C pair.

Acridines↗
PubMed1975

Interactions of heteroaromatic compounds with nucleic acids. 2. Influence of substituents on the base and sequence specificity of intercalating ligands.

This paper presents the results of a systematic study on the effects of substituents on the base and sequence specificity of tricyclic heteroaromatic compounds interacting with DNA by intercalation. All the compounds tested are derived from proflavine and acridine orange analogs with different heteroatoms in the middle ring. Their base and sequence specificities were determined by differential dialysis of the ligand against DNA samples of differing G-C content. The main results indicate that (a) the introduction of a phenyl substituent into one of the two available positions of the middle ring increases or decreases the G-C specificity of the ligand depending on the position where the substitution takes place; (b) compounds of the substitution type of neutral red (2-methyl-3-amino-7-dimethyl-amino-phenazine) show unexpectedly high G-C specificities and (c) DNA ligands of pronounced sequence specificity for adjacent G-C pairs can be constructed by combining the structural elements of neutral red with an additional phenyl residue in the same molecule. The further study of compounds related to the phenylated neutral red revealed that the G-C specificity can be improved or destroyed by additional substituents. The comparison of the G-C specificity and the DNA-affinity data of the compounds studied leads to the suggestion that the specificity arises mainly from electronic factors which are strongly controlled through steric constraints on possible ocmplex geometries. As a basis for the discussion a possible structure for the DNA complex of the phenylated neutral red is considered in which the extra phenyl ring at N-5 of the phenazinium system, protrudes into the large groove of the DNA helix while the tricyclic part of the ligand is inserted between the DNA base-pairs.

Acridines↗
PubMed1975

Interactions of heteroaromatic compounds with nucleic acids. A - T-specific non-intercalating DNA ligands.

In the present paper we report the results of a study on the base specificity and affinity of eight dyes potentially able to interact with DNA. These compounds include four triphenylmethane dyes used in histochemistry, auramine, "Hoechst 33258" and two acridines substituted with t-butyl groups. They were selected with regard to their inability to intercalate between the base pairs of helical polynucleotides due to structural limitations. Hydrodynamic studies performed with the DNA complexes of crystal violet and Hoechst 33258 confirmed our assumptions that compounds of this type bind to the outside of DNA. The main results from DNA binding studies indicate that the triphenylmethane dyes except p-fuchsin are bound with high preference to two adjacent A - T pairs while Hoechst 33258 seems to need three A - T pairs as the binding site. Model studies with synthetic polynucleotides revealed that not only a sequence of A - T pairs, but also their structural arrangement in a helix, is crucial for the high affinities observed for most of the ligands when interacting with natural DNA. Methyl green and Hoechst 33258 can be used for increasing the resolution power of cesium chloride density gradients for DNAs with different (A + T) content.

Acridines↗
PubMed1975

Histological study of effects of colloidal 90 yttrium on knee joint tissues of rabbits.

The administration of 0-2-0-4 mCi 90 yttrium (90Y) into a normal rabbit knee joint fails to induce medical synovectomy and results in the proliferation of the synovialis. The synovial mesothelium shows early radiation damage but subsequently follows a restitution of the whole. Later (within 4 to 16 weeks) an extensive fibrosis of the stratum synovialis develops, as well as an occlusion and sclerosis of smaller synovial vessels and capillaries. These changes explain the beneficial therapeutic effect of 90Y in a chronic inflammatory joint effusion. After irradiation that joint cartilage shows an increased cellular proliferation of the superficial tangential cells and in the vicinity of the cruciate ligaments small foci of degenerated cartilage are present. The overall pattern of a joint treated with intra-articular 90Y corresponds to the histological pattern encountered regularly in joints of older people. Changes of the cartilage after the 90Y radiation could represent a factor predisposing the treated joint to a subsequent development of osteoarthrosis.

Animals↗
PubMed1975

Treatment of chronic articular effusions with 90-yttrium (90Y).

In an open, controlled trial, radioactive 90Yttrium was injected in doses of 3-6 mCi into 40 joints with chronic effusions in patients suffering from rheumatoid arthritis and other rheumatoid diseases. The processing in a computer was carried out by the punch card method. Intra-articular administration of 90Y resulted in a significant improvement of five objective criteria. In our study we have paid particular attention to the clinical and statistical differentiation of the effects of systemic, and especially of basic therapy, from the effects of topical intra-articular therapy. At the time of the last check-up examination, 43% of the patients were free of any effusion. The treatment was well tolerated. Skin necrosis occurred in only one single case. Intra-articular treatment with radioactive 90Yttrium represents a valuable contribution to the therapeutic arsenal for the treatment of the chronic articular effusions when all other methods of treatment failed.

Adrenal Cortex Hormones↗
PubMed1975

[The diagnosis of condylar process fractures].

The detection of condylar process fractures by clinical examination and the interpretation of radiographs belong to the stomatologist's diagnostic tasks. On the contrary, the exact location of the fracture lines and the recognition of the types of proximal fragment displacement often present problems. Diagnostic errors may also occur, mainly resulting from radiological illusions. The comprehensive evaluation of the data from 3027 patients with injuries of the facial bones, involving 1050 condylar process fractures, and the verification of the relevant radiological findings permitted to determine the location of the fracture lines and the types of fragment displacement, to recognize misinterpretations and to give suggestions for establishing a definite diagnosis.

Child↗
PubMed1975

Experimental evidence for a significant impairment of host defense for gram-negative organisms by a specific cutaneous toxin produced by severe burn injuries.

Dry heat forms a specific burn toxin in mouse and human skin from a naturally occurring precursor by a polymerization process and not by producing breakdown products. Precursor and toxin are both macromolecular lipid-protein complexes with similar chemical composition and physical structure both occurring in mouse and human skin as well as in serum of burned patients. Specific toxicity resides only in the apoprotein of the polymeric toxic form which also has new specific artificially produced antigenic site or sites. This phenomenon makes it possible to jump the species from man to mouse, shown by the success of specific immunotherapy. Neutral apolar lipids of the coat are contributing in an unspecific but significant manner to the toxic effect. Bacteria are not involved in toxin production nor in toxin activity. The target systems of the toxin are the cell wall membranes of all parenchymal cells of paractically all organs. The toxin apparently causes severe damage of the membrane verified by an increased permeability for compounds which otherwise do not penetrate. This basic cell damage itself is able to kill the animal, depending on the ratio of intact to damaged cells. Sublethal doses of toxin, however, prepare the background upon which bacteremia in burn injuries leads to a lethal sepsis. Finally, the direct toxic action as well as the enhancement of the susceptibility for gram-negative organisms both leading to the lethal outcome can be counteracted by specific passive antitoxic immunotherapy.

Animals↗