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Biomedical subjects

G Bischoff

Publications and source records attributed to G Bischoff.

13 recordsLinked to original sources
PubMed2002

DNA-phospholipid recognition: modulation by metal ion and lipid nature. Complexes structure and stability calculated by molecular mechanics.

The structures and formation energies of nucleic acid-phospholipid complexes both in the absence and in the presence of Mg(2+) ions were calculated taking double-stranded trinucleoside diphosphates NpNpN or heptanucleotides ApAp(NpNpN)pApA, composed of 64 possible combinations of genetic code, and phosphatidylcholine (PC) and sphingomyelin (SM) as model compounds. The dependence of intramolecular interactions on the primary structure of nucleic acid molecules and on the presence of a cationic bridge was revealed. The formation energies and structure of oligonucleotides were found by molecular mechanics calculations with the AMBER force field. The structures of phospholipid and MgCl(2) molecules were calculated by the semiempirical PM3 method, while the energies of phospholipid-oligonucleotide complexes were calculated by the molecular mechanics method. Calculations of complexes were carried out with consideration of solvation effects. Considerable gain in the formation energy of triple complexes is achieved due to the presence of the electroneutral metal bridge. A tendency toward increasing the stability of "triple" PC complexes (but not SM ones), containing guanosine- and cytidine-enriched triplets was revealed. Depending on the structure of NpNpN trinucleotides, the formation energy values of NpNpN-MgCl(2)-PC and ApAp(NpNpN)pApA-MgCl(2)-PC complexes differ by 1.7-2.6 kcal mol(-1), which can be considered as the atomic-scale manifestation of the recognition phenomenon. Presence of metal (II) ion bridge results in a greater stabilization of the phospholipid-nucleic acid complexes for SM in comparison to PC (the total energy difference equals to 4-16 kcal mol(-1)). Depending on the structure of NpNpN trinucleotides, the formation energies of NpNpN-MgCl(2)-SM and ApAp(NpNpN)pApA-MgCl(2)-SM complexes differ by 1.7-2.1 kcal.mol(-1), which is essential at physiological conditions and can also be considered as the recognition effect.

Base Sequence↗
PubMed2002

A spectroscopic and surface plasmon resonance study of oleic acid/DNA complexes.

The interaction of synthetic polynucleotide double strands with a natural lipid, oleic acid, was examined in diluted aqueous solutions by circular dichroism spectra, UV-absorption measurements, and surface plasmon resonance biosensor investigations. The investigations were performed with defined double and triple stranded oligo- and polydeoxyribonucleotides. Whereas duplexes are influenced by oleic acid ligandation, which could not be removed by ethanol dialysis procedure, no binding occurs to triple stranded DNA. The spectroscopic results indicate that oleic acid shows molecular recognition to AT b.p. motifs by groove binding. GC tracts - in particular alternating d[G-C] motifs - are strongly influenced by ligand interaction up to a ratio of one molecule per two base pairs. Likewise, the spectroscopic and morphologic changes in the supramolecular association of the complexes after treatment occur even after dialysis procedure. This was monitored with scanning force microscopy (SFM) as well. Additionally, monolayers of biotinylated DNA duplexes were immobilized on a streptavidin sensor-layer for surface plasmon resonance (SPR) observations. Small portions of the ligand were injected in continuous flow. Loosely bound molecules were removed by washing procedure. Injections of sodium hydroxide denature the DNA, releasing the tightly bound effectors. The amount of tightly bound oleic acid molecules was determined at one molecule per 2-3 base pairs. As consequence, a new mechanism of regulation of gene expression at nuclear membrane or by lipids inside DNA double helix has to be discussed.

Base Pairing↗
PubMed2002

DNA-binding of drugs used in medicinal therapies.

The interactions of various low-molecular weight substances with DNA are naturally relevant mechanisms in the cellular cycle and so also used in medicinal treatment. Depending on the particular drug structure, DNA-binding modes like groove-binding, intercalating and/or stacking, give rise to supramolecular assemblies of the polynucleotides, as well as influence the DNA-protein binding. In this review, we compare the underlying molecular structures, including general aspects of DNA sequences, with the benefit in medicinal treatment. While so far interest in this field had mainly been devoted to isolated nucleic acid/drug interactions, the present paper will focus on drug efficiencies generating and influencing supramolecular organizations and their complex sequence-dependent structure-activity codes. In particular, the attention will be directed to stereoelectronic relationships. Spatial enantioselective properties are discussed in details. As examples, the drug self-assemblies, as well as the influence of drugs on supramolecular DNA formations are described. A hypothetical connection between drug-influenced DNA-toroids and the formation of micronuclei in tissues will be interpreted.

Binding, Competitive↗
PubMed2001

[Correlation of 55 samples of contact lens fluid and direct swabbings of the eye surface of symptomatic wearers of contact lenses].

BACKGROUND: The microbiological examination of contact lens storage solutions may reveal the etiological organisms responsible for keratitis and additionally harbour environmental contaminants. PATIENTS AND METHODS: From 1995 to 1998, conjunctival and corneal smears and scrapes, as well as the storage solutions of 55 soft contact lens wearers were examined microbiologically in a prospective non-randomised cohort study involving 53x unilateral and 2x bilateral cases of keraitis. RESULTS: In 42 of the in-use contact lens storage solutions, the following organisms were found: 8x Bacillus sp., 7x P. aeruginosa and 8x other pseudomonads, 6x Alcaligenes xylosans, 4x Serratia liquefaciens, 4x Enterobacter sp., 4x coagulase negative staphylococci, 3x Serratia marcescens, 3x S. aureus, 2x Streptococcus faecalis, 1x Klebsiella oxytoca and 5x Acanthameba. A significant correlation of ocular cultures was found for Pseudomonas, Enterobacter, Serratia, S. aureus, S. faecalis and Acanthameba, but not for Bacillus, Alcaligenes, and coagulase negative staphylococci. Fungi were not found. The more pronounced the clinical picture, the more Gram-negative bacteria were isolated. CONCLUSIONS: The microbiological examination of soft contact lens storage solutions of 55 keratitis patients confirmed that the microbes responsible were to be found in the fluid, in addition to environmental contaminants.

Acanthamoeba Keratitis↗
PubMed2001

Scanning force microscopy observation of tumor cells treated with hematoporphyrin IX derivatives.

Cells from human head-neck squamous cell carcinoma (hypopharynx, UMSCC11, and UMSCC22) and lung tumor (alveolus, UMSCC7) were investigated by light and scanning force microscopy (SFM) observation. In the present study a less-invasive contact mode was used to scan living cells in air covered with a thin fluid layer. The investigations were done without any pretreatment of the specimens for such observations as chemical fixation, or staining. Untreated tumor cells, and those treated with the antitumor drug hematoporphyrin IX derivative (HpD) were studied without photosensitizing. Additionally, the temperature influence on cell proliferation was studied. Three-dimensional topographic images and their magnifications offer highly informative insights into the untreated cell surface. In the present study, the cell structure destruction and cell death could partly be visualized by observing the head-neck tumor cells incubated with HpD. Most of the drug-treated head-neck tumor cells died (only 2%-5% of survivors). However, HpD could not affect cells of the lung tumor cell type. They, well known as more resistant against oxidation processes, survived to a great extent. Also, no distortion of the membrane under drug treatment could be observed. The possibilities and limits in the use of SFM for studying the topography of cell surfaces are presented in many details.

Antineoplastic Agents↗
PubMed2000

A structure-function study of nucleic acid-fluorenone complexes.

Several 2.7-bis-[(dialkylamino)-acetylamino]-fluoren-9-one derivatives (fluoramides) were synthesized as analogues of the DNA binding compound tilorone (2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one). Previous studies showed the drugs to induce cytokines and inhibit reverse transcription. Here, their binding to DNA was evaluated using UV and circular dichroism studies. Like tilorone, the fluoramides derivatives also intercalate resulting in increased Tm values and new CD signatures. A preference to alternating A-T and G-C sequences was detected; only minor interaction to homologous sequences was observed. Moreover, no upper limit in the drug/DNA ratio was found, testing limit being the precipitation of the drug. However, surface plasmon resonance (SPR) studies of tilorone and 2,7-bis-[(dipropylamino)-acetyl-amino]-fluoren-9-one, indicate an astonishing drug/base pair ratio (r > 1), which point to a multitude of interactions under SPR conditions. Molecular modeling calculations, where the geometries of the complexes optimized under the assumption of intercalative and multitude of suprahelical arrangements, rationalize the observations. Based on the thermodynamic and biological studies, a structure-function model is proposed.

Animals↗
PubMed2000

Biomesogenic matrix systems.

The bifunctionally reactive nucleoside and distant nucleoside analogs adenosine (Ado), S-[(adenine-9-yl)methoxyethyl]-L-cysteine (Na-salt) (cysA) and 9-vinyladenine (vA) in aqueous solutions assemble on complementary polyuridylic acid templates to form complex lyomesophases. The systems are investigated by polarizing microscopy, differential scanning calorimetry (DSC) and 1H- and 31P-nmr spectroscopies, assisted by molecular modeling studies. The results indicate the importance of biomesogenic (pre)ordering in nucleic acid native and artificial matrix reactions.

Adenine↗
PubMed2000

Self-assembly and lyomesophases formed by long-chain alkoxymethyl-nucleobase derivatives.

Amphiphilic complementary nucleobase derivatives, containing n-octadecyloxymethyl substituents at the N1 position of pyrimidine and N9 of purine, dissolved in chloroform form non-specific lyotropic mesophases, which were analyzed by optical polarizing microscopy. Molecular modeling studies visualize hypothetical horizontal and vertical nucleobase hydrogen-bonding and stacking arrangements, as well as aliphatic long-chain interstrand interaction.

Chloroform↗
PubMed1999

A spectroscopic and thermodynamic study of Taxol nucleic acid complexes.

The interactions of natural and synthetic polynucleotide double strands with the antitumor agent paclitaxel and the oncological product "Taxol for Injection Concentrate" (abbreviated as taxol) were examined in diluted aqueous solutions by thermal denaturation profiles (Tm), CD spectra and UV-absorption measurements. Furthermore, DNA-paclitaxel and -taxol complexes in condensed nucleic acid solutions were studied by differential scanning calorimetry. As polynucleotides alternating and homologous poly[d(AT)] and poly[d(GC)] and calf thymus DNA were used. The results point to stabilizing interactions of paclitaxel to AT nucleotides, whereas in the presence of GC base pairings no interaction took place. Thereby the interaction to homologous (dA).(dT)-tracts seems to be preferred.

Calorimetry, Differential Scanning↗
PubMed1998

DNA-drug interaction measurements using surface plasmon resonance.

The interactions of the drugs 2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one dihydrochloride (Tilorone), 2,7-bis[(dipropylamino)-acetamido]-fluoren-9-one dihydrochloride (FA-2), 2'-(4-hydroxyphenyl)-5-(4-methyl-1-piperazinyl)-2,5'-bi-1H-benzimidazole trihydrochloride (Hoechst 33258), and hematoporphyrin IX derivative (HPD) with synthetic self-complementary DNA (36-b.p.; 5'-biotin-spacer-[d(CGCTATATAGCG)]3-3') were studied by SPR (Surface Plasmon Resonance). Monolayers of biotinylated DNA were immobilized on a streptavidin-dextran-gold triple-layer. Small portions of the drugs (approximately 30 pmol/ml) were injected in continuous flow. The mass corresponded to the amount of the bound molecules. Injections of 50 mM sodium hydroxide pulses separated the DNA double strands, releasing the effector molecules. Subsequent treatments with the effectors gave reproducible results. The maximum interaction between drug and DNA was observed in the case of Tilorone. 41 molecules could bind to the 36-b.p. DNA duplex. To investigate the microscopic behavior in condensed nucleic acid phases, SFM (Scanning Force Microscopy)-imaging and polarizing microscopic observations of DNA-effector complexes were carried out. Supplementary UV-absorption thermal denaturation curves of DNA with the above-mentioned effectors in dilute solutions were measured. As an additional aid to understand the geometries of DNA-drug interactions, computer simulations were performed and compared with the experimental data.

Bisbenzimidazole↗
PubMed1983

[Bufuralol: do beta blockers reduce blood circulation in the kidneys?].

In 8 ambulatory patients with stable essential hypertension (WHO grade I and II) the effects of a new beta-blocker with marked sympathomimetic activity on arterial blood pressure, creatinin clearance and renal plasma flow, as measured by total PAH clearance (constant infusion technique), were studied. In contrast to previous findings no significant reduction in creatinin clearance or renal blood flow was observed during a 3-5 weeks' observation period. The small reduction in calculated renal vascular resistance was not statistically significant. In addition to its postulated peripheral vasodilatory effect, bufuralol appears to interfere less than propranolol with renal hemodynamics and renal excretory function.

Adrenergic beta-Antagonists↗