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Biomedical subjects

G Löber

Publications and source records attributed to G Löber.

At least 37 records · Page 2Linked to original sources
PubMed1990

Ambazone as a membrane active antitumor drug.

Ambazone (1,4-benzoquinone guanylhydrazone thiosemicarbazone) was found to be active against various transplantable tumors in mice as well as rats. When administered orally for 4-9 days, the effective therapeutic dose ranged between 60 and 125 mg/kg. The antineoplastic effect of ambazone appeared to be mediated, at least in part, by the immune system. In order to characterize the drug, biophysical and biophysicochemical studies were carried out using thin-layer chromatography, absorption spectroscopy and polarographic measurements. The distribution of ambazone in an n-octanol/water system indicated low hydrophobicity, thereby excluding the possibility of a preferential contribution from hydrophobic forces to the mode of action of ambazone. Ambazone undergoes three protonation reactions with pK values at 10.69 (equilibrium between the negatively charged and neutral forms), 7.39 (equilibrium between the neutral and singly positively charged form) and 6.22 (equilibrium between the singly and doubly positively charge form). Interaction of the drug with model membrane system was monitored by spectrophotometric and fluorescence measurements. Using the fluorescence label 1-anilino-8-naphthalenesulfonic acid (ANS) as a probe pointed to the interaction of ambazone with the inner area of the phospholipid bilayer matrix of liposomes as being nonspecific. Ambazone induces an overall increase in the cellular cAMP content of leukemia cells and macrophages. So far, membrane interaction has provided a molecular basis for both immunological and antineoplastic activities of the drug. By performing DNA melting experiments, it was shown that neutral or singly positively charged ambazone species stabilize the secondary structure of DNA, while the doubly positively charged form binds more strongly and destabilizes the DNA. After oral administration to rats and mice, ambazone was found to be incompletely absorbed from the gastrointestinal tract, to an extent of about 35-50%. Absorbed ambazone binds only weakly to plasma proteins, whereas its binding to red blood cells is relatively strong. The mutagenic potential of ambazone shown in bacterial systems and human lymphocytes corresponds to its relatively weak interaction with DNA. The toxic action of ambazone on the intestine is believed to be due to inhibition by the drug of bacterial DNA, RNA and protein syntheses. It is assumed that the reported affinity of ambazone for different cellular targets, i.e., membranes, nucleic acids and proteins, contributes to the overall antibacterial effect. The weak antiviral activity of ambazone in the Sendai virus/chicken embryo fibroblast system is probably the result of the interaction with Sendai virus NH glycoprotein.

Animals↗
PubMed1986

Differential effects of treatment with UV-light (365 nm) and 8-methoxypsoralen on chromosomes of healthy persons and psoriatic patients.

The effect of 8-methoxypsoralen (8-MOP, 5 X 10(-5) M), near UV-light of 365 wavelength (UVA, 1.5 J/cm2) and the combination of both (PUVA treatment) were studied on lymphocytes in vitro taken from healthy persons and patients with psoriasis vulgaris and psoriasis arthritis (psoriasis arthropathica). Chromosomes isolated from cell nuclei were visualized by means of Giemsa staining technique and analyzed for induction of chromosomal defects, i.e. premature centromere division (PCD), major coiling (MC), and formation of gaps and fragile sites. Exposure of nonpsoriatic lymphocytes to 8-MOP, UVA or PUVA increased the rate of PCD or MC generation. In experiments with psoriatic lymphocytes a much weaker effect was found, with a moderate increase of PCD and MC after UVA or PUVA treatment in the case of psoriasis vulgaris, and of MC after UVA treatment of psoriasis arthritis. On the average the number of chromosomes per metaphase plate displaying PCD did not exceed 10. No indication was obtained for the preference of certain chromosome groups or the appearance of "fragile sites". Under all experimental conditions the number of chromosome gaps ranged in the order of their spontaneous induction. Our findings suggest PCD and MC investigations as possible sensitive tools for diagnosing latent psoriasis and for refined analysis of psoriatic cells or chromosomes. However, more experiments along this line are needed.

Chromosomes, Human↗
PubMed1982

[Studies on the effect of low concentrations of thiocyanate on the protein human serum albumin].

By means of fluorescence and absorption measurements the authors studied the interaction of the protein human serum albumin with relatively low concentrations (up to 5 mmol/l at the most) of thiocyanate ions. Such concentrations lead to a slight quenching of the tryptophan fluorescence in human serum albumin. The effect of thiocyanate is not due to an overall action on the protein (as sometimes observed with higher thiocyanate concentrations), but to a local interaction of the fluorophore tryptophan with the neighbouring anion-binding site which is occupied by thiocyanate.

Binding Sites↗
PubMed1979

Interaction of phenosafranine with nucleic acids and model polyphosphates. III. Heterogeneity in phenosafranine interactions with DNA base pairs.

Fluorescence and circular dichroism spectral measurements, thermal denaturation studies and binding competition experiments with netropsin and actinomycin D were carried out in systems containing phenosafranine bound to DNA's differing in base composition. The investigated properties exhibit a heterogeneity related to the content of A.T and G.C pairs in DNA and to the nature of phenosafranine binding modes. At low level of saturation of binding sites (r less than 0.1) phenosafranine does not show strong preference for any of the DNA base pairs in the overall binding. However, the strong monomer non-cooperative binding outside the helix (mode I1) occurs predominantly, even though not exclusively in G.C rich regions. The strong binding modes involving intercalated dye molecules (mode I2 and eventually mode II1) prevail in A.T rich regions. These binding modes become the principal types of strong phenosafranine interaction with DNA when the level of saturation of binding sites increases, i.e. at r greater than 0.1.20

Bacillus cereus↗
PubMed1978

Photochemistry and photobiology of 5-azacytidine: effect of repair on photostabilization of Escherichia coli.

The photochemical stability of the anomalous nucleic acid base 5-azacytidine (z5Cyd) on irradiation at 254 nm is by about one order of magnitude less than that of cytidine (Cyd). Contrary to the photochemical behaviour, incorporation of z5Cyd into the nucleic acids of E. coli strains SR 20 (uvr+ rec+), SR 74 (uvr+ rec-) and SR 22 (uvr- rec+) produced a higher resistance to UV light. Only the SR 73 (uvr- rec-) strain was shown to have an increased UV sensitivity. This latter finding is in accord with the photochemical properties of z5Cyd. The results led to the conclusion that excision and recombination repair processes contribute to the observable protective effect. The fact that inhibition of excission repair by caffeine or proflavine of the mutant uvr+ rec- changes protection into sensitization supports this idea.

Acriflavine↗
PubMed1978

Interaction of phenosafranine with nucleic acids and model polyphosphates. I. Self-aggregation and complex formation with inorganic polyphosphates.

Aggregation or phenosafranine in concentrated aqueous solutions and its interaction with polyphosphates was Studied by absorption and fluorescence spectroscopy. At concentrations > 10(-3) M phenosafranine forms dimers (Kd = 3.8 x 10(2) l.mole(-1)), which are characterized by a hypsochromic shift of the visible and near ultraviolet absorption maxima accompanied by a hypochromic effect. No fluorescence could be detected from phenosafranine dimers. Analogous spectral changes were observed when a polyphosphate was titrated with phenusafranine, which indicated that with increasing saturation of the polyphosphate binding sites phenosafranine gradually became bound in the aggregated form. Full saturation of the polyphosphate binding sites with phenosafranine was reached only when an excess of free dye was present. The cooperative binding of phenosafranine to a polyphosphate could be evaluated by means of a theory proposed by Schwarz et al. At the zero ionic strength and at 25 degrees C the binding was characterized by cooperative binding constant K = 6.2 x 10(5) l.mole(-1), number of binding sites per monomeric phosphate residue g = 0.4, and cooperativity parameter q reverse similar 30. Spectroscopic properties of phenosafranine in the aggregated and poly phosphate-bound stotes were compared with those of ethidium bromide.

Journal Article↗
PubMed1978

Antiviral pyrimidine derivatives: binding with biopolymers and photosensitization.

Two antiviral pyrimidine derivatives, known to partially inhibit RNA dependent RNA polymerase of Mengo virus in a cell-free system, were found to bind with biopolymers. The antiviral compounds, at concentration of 100 and 50 muM and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. Both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of UV light of the wavelength of 366 nm. The fluorescence intensity increased upon addition of aqueous solutions of DNA, RNA and human serum albumin. This indicates that both compounds are capable of binding with nucleic acids and proteins. Based on the binding experiments alone it cannot be decided whether interference with nucleic acid template activity, enzyme function, or both are responsible for the virostatic action. Irradiation with violet light considerably enhances the virostatic activity, a fact that may be caused by photodynamic processes.

Antiviral Agents↗
PubMed1977

[Effect of ultraviolet and visible light on nucleic acids and proteins].

Three possible photochemical reaction mechanisms have been discussed which might cause changes in biological materials: 1. Photoreactions induced in that constituents of cell substrates absorb UV-light by themselves, i. e. heteroaromatic moieties of nucleic acids and proteins. 2. Photoreactions induced in that constituents not belonging to the natural biological system absorb UV-light, i. e. furocoumarins or cancer producing hydrocarbons. 3. Photoreactions induced in that proper sensitizer molecules absorb UV-light or visible light. The latter type of photoreactions consumes molecular oxygen but does not consume sensitizer molecules (photodynamic action). Examples have been given for the three possibilities concerning photochemistry of nucleic acids and proteins. Damages of biopolymers were discussed with respect to their biological consequences. Photodynamic changes in the blood system might be caused either after addition of sensitizers to blood or by sensitizers which are constituents of blood itself, i. e. porphytines.

Amino Acids↗
PubMed1976

Interaction of DNA and deoxyribonucleoprotein with methylene blue after the treatment with fixation solutions used in chromosome G-banding techniques.

Maximum binding capacity of calf thymus DNA and deoxyribonucleoprotein for methylene blue was investigated. The binding capacity of native and heat-denatured solutions of the biopolymers was compared with that of the solutions incubated with fixatives used in cytology, viz. 4% formaldehyde and methanol-acetic acid (3 : 1) mixture. The binding capacity of DNA and DNP is strongly reduced after the treatment with both fixation agents. Thermal denaturation leads to a small decrease in the binding capacity of DNA, but does not influence that of DNP. These results were compared with microphotometric determination of nuclear methylene blue content in thymocyte spreads. Fixation with MeAc increased the dye content as compared with air-dried thymocytes, whereas 4% formaldehyde exhibited practically no influence. The mechanisms connected with the different staining properties after incubating with fixation agents DNA and DNP solutions on the one hand and the nuclear material of thymocyte spreads on the other hand are discussed.

Binding Sites↗
PubMed1975

Photobiological behaviour of bacteria and phages supplemented with aza-analogoues of nucleic acid bases.

The photochemical stability of anomalous nucleic acid bases of the azatype, 5-azacytosine (I), 5-azacytidine (II), 6-azacytosine (III), 6-azacytidine (IV), 6-azathymine (V), 6-azauracil (VI), and 8-aza-adenine (VII) to U. V. light of the wavelength 254 nm differs from the U. V. stability of the normal constituents. Changes of the U.V. inactivation of Escherichia coli K12 C600, E. coli B, Bacillus cereus, as well as E. coli phages gamma cb2 and gamma b2b5 supplemented with azaderivatives prior to irradiation were investigated. It was found that I, II, III, IV, and VII are more, V and VI less sensitive to U. V. light compared with corresponding natural nucleic acid bases. Their changed U. V. sensitivities are reflected in the survival curves after U. V. -irradiation in as far as azabases are incorporated into the nucleic acids in vivo. This explains the increase in U.V. sensitivity of E. coli K12 C600, E. coli B, and B. cereus supplemented with I, II, III, IV, and VII and the decrease in U.V. sensitivity of Streptococcus faecalis supplemented with V (the latter information was taken from Gunther and Prusoff 1967). The lack of any significant influence on inactivation curves of E. coli K12 C600 by V and VI, and on E. coli phages gamma cb2 and gamma c2b5 by II, is discussed in terms of too small incorporation rates. No discrimination was put forward with respect to DNA and RNA incorporation.

Adenine↗
PubMed1975

Effects of the antibiotic resistomycin on the synthesis of macromolecules.

Resistomycin preferentially inhibits RNA synthesis in comparison to DNA and protein synthesis in intact bacterial cells. Studies with cell-free systems have shown that the antibiotic interferes with DNA and RNA synthesis, while protein synthesis is inhibited to a much lesser extent. Detailed studies in cell-free systems indicate an interaction of resistomycin with DNA- and RNA polymerase. In the case of RNA polymerase this was proved by CD measurements, whereas no interaction of the antibiotic with DNA, RNA, and homopolynucleotides could be found. One can conclude that the binding of the antibiotic to RNA polymerase is the basis for its interference with RNA synthesis.

Anti-Bacterial Agents↗