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Biomedical subjects

L Kittler

Publications and source records attributed to L Kittler.

At least 37 records · Page 2Linked to original sources
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

Photobiology of furocoumarins. Various types of crosslinking with DNA and their interference with the development of lambda phage.

It was shown that the multiplication of phage lambda was strongly suppressed by furocoumarins after irradiation with near ultraviolet light of 365 nm wavelength. Using xanthotoxin or angelicin there was a marked inhibition of the phage DNA injection and replication but adsorption was unaffected. This inhibition was attributed to various types of DNA crosslinking produced in the phage heads. Type I crosslink corresponded to covalent binding between adjacent sites in opposite strands of the double helix. Crosslink type II (hairpin crosslink) required a highly condensed DNA and corresponded to covalent binding between adjacent sites on double-helical segments of a folded DNA molecule. The relationships of the type I crosslinks to the DNA replication and of the type II crosslinks to DNA injection are being discussed. Like type II crosslinks, the nucleic acid--protein crosslinks hinder injection.

Adsorption↗
PubMed1981

Interaction of bacteriophage O2 with strains of the genus Oerskovia.

Bacteriophage O2 multiplies normally on Oerskovia turbata IMET 47 153. It has a burst size of about 100 p.f.u. per infected cell and a latent period of 100 min at 30 degrees C. On Oerskovia xanthineolytica IMET 47 383 clear spots were formed after addition of high phage concentrations onto agar top layers. By phase contrast observation, and measurement of the optical density of infected cultures, it was found that the clearing effect on strain IMET 47 383 was due to lysis-from-without. Phage O2 adsorbs and injects its DNA into cells of strain IMET 47 383 but phage multiplication does not occur, and the phage DNA becomes degraded. Inhibition of phage DNA injection by the combined action of xanthotoxin -- u.v. irradiation abolished the clearing activity of phage lysates. Therefore, both adsorption and DNA injection seem to be prerequisites for the release of a lytic activity out of the phage particle, which is responsible for the clearing effect on strain IMET 47 383.

Adsorption↗
PubMed1980

Cross-link formation of phage lambda DNA in situ photochemically induced by the furocoumarin derivative angelicin.

The combined action of 365 nm ultraviolet light and xanthotoxin or angelicin inhibits the injection of phage lambda into the host. For both furocoumarin derivatives the inhibition of injection is discussed in terms of photochemically induced cross-linking of the DNA inside the phage heads; Cross-linking of DNA has previously been described for xanthotoxin (Musajo, L. and Rodighiero, G. (1972) in Photophysiology (Giese, A.C., ed.), Vol. VII, pp. 115-147, Academic Press, New York and Scott, B.R., Pathak, M.A. and Mohn, G.R. (1976) Mutation Res. 39, 30-74) but not for angelicin. The electronic structures in the first excited states calculated by means of quantum chemistry according to the Pariser-Parr-Pople method are very similar for xanthotoxin, psoralen and angelicin. Hence angelicin should be capable of acting bifunctionally like xanthotoxin, but for sterical reasons such reaction should be possible only for the folded DNA, as in phage heads, but not for diluted aqueous solution of DNA.

Bacteriophage lambda↗
PubMed1979

Enhancement of the antiviral activity of pyrimidine derivatives against mengovirus by visible light.

Eleven pyrimido-pyrimidine derivatives, seven with significant antiviral activity against Mengovirus, five against Coxsackie B1 virus and four antiviral negative compounds were tested for their photosensitizing ability. All seven compounds with antiviral activity in vitro showed an enhanced antiviral action against Mengovirus under irradiation with visible light, a fact that may be caused by photodynamic processes. It was tried to correlate the oxidation potentials of sensitizers with their photodynamic activity. By means of mass-spectrometric investigations, molecular fragmentation was examined following thin layer chromatography (TCL) before and after irradiation. Furthermore, binding affinity to biopolymers (BSA and RNA) was investigated to reveal conformity in differences of antiviral activity. The main results are the following: 1. Generally, strong antiviral activity can be correlated with strong binding affinity. 2. No significant correlation could be detected between oxidation potentials of antiviral compounds and their enhanced antiviral activity under irradiation conditions, although in some cases sensitizer with higher oxidation potentials are more effective than those with lower ones. 3. The lower the photostability of the compounds the higher was the light-induced antiviral activity. 4. No alteration of the molecular ion peak and fragmentation pattern before and after irradiation was indicated by means of mass-spectrometry and TLC using fairly comparable conditions.

Amnion↗
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↗
PubMed1976

[The molecular mechanism of the photochemical reaction of furocoumarins with nucleic acids].

1. The photoreaction of furocoumarins with cell substrates of high molecular weight are limited on nucleic acids. Both molecules are jointed together via a cyclobutane ring system. The 5.6 double bonds of thydine or uracil and the 3.4 and/or 4',5' positions of furocoumarins act as binding sites. Proteins, polysaccharides, and lipides behave quite inert. 2. The photoreactions of cancerogenic hydrocarbons with nucleic acids are similar to those of furocoumarins. 3. Photochemically induced cross-links of DNA strands by furocoumarins are to a high degree dependent on the secondary structure of nucleic acids. Double stranded DNA is much more favoured to bind furocoumarins than single stranded DNA or RNA. 4. Lethal and mutagenic effects in cells caused by photoreactions between furocoumarins and DNA are well explainable on molecular level. It consists a satisfactory correlation between skin sensitization and binding tendency of furocoumarins to DNA. Possibilities of repair of furocoumarine induced DNA damages are discussed.

Animals↗
PubMed1976

Conformational changes of nucleic acids and poly (d(A-T)-d(A-T)) caused by photoaddition of furocoumarins.

DNA's of various AT content, poly[d(A-T)-d(A-T)], and double-stranded RNA were irradiated with UV light at 365 nm in the presence of linear (xanthotoxin) or angular (angelicin) furocoumarins. The covalent photobinding is strongly dependent on the spatial arrangement of furocoumarin molecules at the polymer conformation. CD measurements demonstrate that the bifunctional photochemical binding of xanthotoxin with double-stranded DNA's and poly[d(A-T)-d(A-T)] is accompanied by conformational changes which involve probably decreasing helical twisting of the double helix. This effect is greatly enhanced with increasing AT content. The formation of A-like structures is very unlikely since the B leads to A transition induced by ethanol addition was found to be strongly suppressed in xanthotoxin photoreacted DNA. The B-type helix appears to be the most sensitive conformation with minor restriction to produce photochemically induced cross-links.

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↗
PubMedDate not supplied

DNA binding properties of minor groove binders and their influence on the topoisomerase II cleavage reaction.

We present titrations of the human delta beta-globin gene region with DNA minor groove binders netropsin, bisnetropsin, distamycin, chromomycin and four bis-quaternary ammonium compounds in the presence of calf thymus topoisomerase II and DNase I. With increasing ligand concentration, stimulation and inhibition of enzyme activity were detected and quantitatively evaluated. Additionally we show a second type of stimulation, the appearance of strong new topoisomerase II cleavage sites at high ligand concentrations. The specific binding sites of the minor groove binders of the DNA sequence and their microscopic binding constants were determined from DNase I footprints. A binding mechanism for minor groove binders is proposed in order to explain these results especially when ligand concentration is increased.

Animals↗