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Biomedical subjects

K R Fox

Publications and source records attributed to K R Fox.

At least 127 records · Page 7Linked to original sources
PubMed1990

Footprinting studies on the effect of echinomycin on the structure of a bent DNA fragment.

The interaction of echinomycin with a kinetoplast DNA fragment which contains phased runs of adenine residues has been examined by various footprinting techniques. DNAase I footprinting confirms that all drug-binding sites contain the dinucleotide CpG. However, not all such sequences are protected. Three sites, each of which is located between two adenine tracks in the sequence GCGA, are not protected from DNAase I attack. Enhanced cleavage by DNAase I, DNAase II and micrococcal nuclease is observed in regions surrounding drug-binding sites. The results suggest that echinomycin alters the conformation of the AT tracks, making them more like an average DNA structure. Echinomycin renders adenine residues in the sequence CGA hyper-reactive to diethyl pyrocarbonate.

Adenine↗
PubMed1990

Footprinting studies on the sequence-selective binding of pentamidine to DNA.

The sequence-selective binding of pentamidine, an antimicrobial aromatic diamidine, has been investigated by footprinting studies on two different DNA fragments using DNase I, micrococcal nuclease and hydroxyl radical as probes. Each probe reveals drug-induced protection from cleavage in AT-rich regions. The best binding sites consist of at least 5 consecutive AT base pairs. Three or less AT pairs do not constitute a pentamidine binding site.

Base Sequence↗
PubMed1990

The GC-selective ligand mithramycin alters the structure of (AT)n sequences flanking its binding sites.

DNA fragments containing (AT)n inserts cloned adjacent to putative mithramycin binding sites have been examined by footprinting experiments using a variety of nucleases in the presence of the drug. The results demonstrate that mithramycin induces a DNA structural change which renders adjacent (AT)n sequences sensitive to attack by DNase II. Significant changes are also revealed with DNase I and micrococcal nuclease. The results are consistent with a model in which mithramycin opens the DNA minor groove changing it to a structure which is locally more like A-DNA.

Adenine↗
PubMed1990

Echinomycin binding to the sequence CG(AT)nCG alters the structure of the central AT region.

DNA fragments containing the sequence CG(AT)nCG have been used in footprinting experiments to assess the effect of echinomycin, which binds to CG steps, on the structure of the central AT region. DNAase I normally cuts ApT much better than TpA; in the presence of the drug this preference is retained but cleavage at TpA is enhanced. Changes in cleavage by micrococcal nuclease have also been observed. Echinomycin renders alternate adenines hyperreactive to diethylpyrocarbonate. The results suggest that echinomycin induces structural changes in regions surrounding its binding site and that these can be cooperatively propagated over several turns of the DNA helix.

Base Sequence↗
PubMed1990

The strong binding of luzopeptin to DNA.

The effect of luzopeptin on the mobility of DNA in polyacrylamide gels has been determined. Experiments on a mixture of DNA fragments of various lengths have shown that the drug does not form intermolecular cross-links. Gel analysis of complexes of the drug with short DNA fragments (15-35 base pairs) reveals a ladder of discrete bands in which each band appears to correspond to the addition of a further drug molecule. The results suggest that luzopeptin binds very strongly to DNA, occupying about four base pairs and displays little or no sequence selectivity. Luzopeptin renders certain adenine residues hyperreactive to diethylpyrocarbonate, these occur in different positions to those affected by echinomycin.

Antibiotics, Antineoplastic↗
PubMed1990

Footprinting studies of the interaction of quinomycin antibiotic UK63052 with DNA: comparison with echinomycin.

The interaction between UK63052, a novel derivative of the quinomycin group of bifunctional intercalating antibiotics, with DNA has been investigated by footprinting techniques and the results compared with echinomycin. UK63052 binds strongly but reversibly to DNA and decreases the gel mobility of most DNA fragments, although the mobility of bent kinetoplast DNA is increased. The drug binds selectively to the dinucleotide CpG though not all such sequences present good binding sites. Binding is best when CG is surrounded by AT base pairs. UK63052 and echinomycin have different effects on DNA structure as assessed by changes in the sensitivity to modification by diethylpyrocarbonate. The results are interpreted by suggesting that substitutions on the chromophores affect the precise details of DNA recognition.

Anti-Bacterial Agents↗
PubMed1990

DNA sequence recognition by bleomycin.

The ability of bleomycin to cleave DNA fragments containing (TA)n and (GA)n/(CT)n inserts has been investigated. Bleomycin cuts efficiently after AT and GA though not at TA, AG and CT or TC. In the presence of ligands which modify DNA structure new cleavage products appear. It seems that the ability of bleomycin to discriminate between various sequences arises from their structural characteristics rather than merely from base-specific hydrogen bond contacts.

Base Composition↗
PubMed1990

Effect of actinomycin on a (TA)6 plasmid insert.

The effect of actinomycin on DNA structure has been studied by nuclease digestion of a DNA fragment containing the sequence AAGCT(TA)6AGCTT. The drug enhances DNase I cleavage at ApT and TpA bonds closest to the drug binding site (GC). Large changes in the relative susceptibility of bonds to cleavage by micrococcal nuclease and DNase II are also observed. The changes suggest that actinomycin alters DNA structure around its binding site, facilitating the formation of an alternating DNA structure. When a similar TA sequence was inserted further from the actinomycin binding site no changes in nuclease susceptibility were observed.

Autoradiography↗
PubMed1990

Footprinting studies of sequence recognition by mithramycin.

The binding of mithramycin to DNA has been investigated using a variety of chemical and enzymic footprinting probes. Mithramycin failed to affect DNA modification by several chemical agents which react in the DNA major groove, suggesting that the drug binds via the minor groove. The pattern of reaction with diethylpyrocarbonate was modified by the antibiotic at the binding site and in surrounding regions, consistent with drug-induced structural changes. Hydroxyl radical and DNase I footprinting confirms that the drug binds best to GpG, especially when this is located within a GC-rich environment. Cleavage by DNase II and micrococcal nuclease is inhibited around drug binding sites and suggests a local stabilization of the DNA helix.

Base Composition↗
PubMed1989

High resolution hydroxyl radical footprinting of the binding of mithramycin and related antibiotics to DNA.

The preferred binding sites for mithramycin on three different DNA fragments have been determined by hydroxyl radical footprinting. Sequences which appear as one long protected region using DNAase I as a footprinting probe are resolved into several discrete binding domains. Each drug molecule protects three bases from radical attack, though adjacent regions show attenuated cleavage. Mithramycin and the other related compounds induce similar footprinting patterns and appear to recognise GC rich regions with a preference for those containing the dinucleotide step GpG. The ability of each such site to bind the drug depends on the sequence environment in which it is located. The data are consistent with mithramycin binding to the DNA minor groove.

Antibiotics, Antineoplastic↗
PubMed1989

Sequence selective binding of ditrisarubicin B to DNA: comparison with daunomycin.

DNase I footprinting has been used to examine the sequence selective binding of ditrisarubicin B, a novel anthracycline antibiotic, to DNA. At 37 degrees C no footprinting pattern is observed, the drug protects all sites from enzymic cleavage with equal efficiency. At 4 degrees C a footprinting pattern is induced with low drug concentrations which is different from that produced by daunomycin. The best binding sites contain the dinucleotide step GpT (ApC) and are located in regions of alternating purines and pyrimidines.

Anthracyclines↗
PubMed1989

Interaction of mithramycin with metal ions and DNA.

The interaction of mithramycin with metal ions has been studied by absorbance and fluorescence spectroscopy. Magnesium shifts the drug absorbance spectrum to longer wavelengths and displays a weak binding constant (Kd = 1mM); no interaction with calcium was detected. The drug requires magnesium for binding to DNA and this is characterised by small additional hypochromic and bathochromic changes. Mithramycin does not bind to DNA in the presence of calcium. With 10mM magnesium the drug binds to DNA with an association constant of 9.2 x 10(4) M-1. The inability of calcium to substitute for magnesium has been confirmed by 'footprinting' experiments using both DNase I and hydroxyl radicals.

Base Sequence↗
PubMed1989

Exercise and health psychology: emerging relationships.

The increasing prominence of health psychology has been paralleled by developments in the study of the psychology of health-related exercise. Evidence has been amassed which supports the efficacy of regular physical activity in reducing the risks of some debilitating health conditions such as coronary heart disease and obesity, as well as the promotion of physical function and mental well-being. The significance of exercise as a health-related behaviour has brought to the fore the need to address motivational problems associated with its adoption and maintenance. In this respect, exercise psychology research would appear to provide potential for guiding significant public health initiatives. This paper addresses the issues of exercise and mental health and exercise motivation with a view to highlighting key sections of the exercise psychology literature for health and medical psychologists.

Exercise↗
PubMed1989

Left ventricular thrombus in the absence of detectable heart disease.

A woman presented with acute left leg pain requiring urgent left femoral embolectomy. Echocardiography showed a large, pedunculated left ventricular mass, but no additional cardiac abnormality. Clinical evaluation including cardiac catheterization and open heart surgery demonstrated no cardiac pathologic findings. At surgery, a large thrombus was removed from the left ventricle. We suggest that all patients with arterial embolic disease have echocardiography, even if heart disease is not suspected.

Adult↗
PubMed1989

Pulmonary edema as a complication of interleukin-2 therapy.

Eight patients underwent IV bolus therapy with recombinant interleukin-2 (Cetus Corporation, Emeryville, CA) for treatment of metastatic melanoma or renal cell carcinoma. The patients were randomized to receive interleukin-2 alone or interleukin-2 in combination with lymphokine-activated killer cells. Radiographs showed pulmonary edema in five of the eight patients. The changes ranged from mild interstitial edema (two patients) to frank pulmonary edema (three patients). The edema generally resolved within 4 days after the termination of therapy (four patients), however, one patient developed edema and arrhythmias approximately 7 days after interleukin-2 therapy ended. Seven of the eight patients had either cardiac arrythmias or angina. The mechanisms that contribute to the pathogenesis of these cardiac complications with interleukin-2 therapy remain unclear. The development of pulmonary edema is thought to be caused by capillary leakage and cardiac pulmonary edema due to cardiac toxicity of the drug. The radiologic appearances of these types of pulmonary edema were indistinguishable from one another and from other causes of pulmonary edema. Our study shows that interleukin-2 can cause pulmonary edema, cardiac arrhythmias, and unstable angina. The severity of these conditions is unrelated to dose.

Adult↗
PubMed1989

Effects of pulsed argon laser energy on bone.

Several investigators have reported that the presence of calcium may totally preclude resection of plaque material from the lumen of an occluded vessel. Because the authors did not support these findings, they tested the hypothesis and studied the effects of pulsed argon ion laser energy on other non-plaque but dense calcified tissue, such as cortical bone, and found that bone can be cut with ease and safety. Fresh bovine specimens were irradiated with a Spectra Physics model 170 argon ion laser, and the irradiated areas were examined, measured, and photographed.

Animals↗