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C A Reynolds

Publications and source records attributed to C A Reynolds.

54 records · Page 3Linked to original sources
PubMed1989

Identifying targets for bioreductive agents: using GRID to predict selective binding regions of proteins.

A computational procedure is described for investigating potential binding sites of a target macromolecule for their ability to bind both a reduced probe molecule and an oxidized probe molecule. The interaction energies are obtained using a molecular mechanics method and can be displayed as three-dimensional (3D) energy contours, indicating regions of the target molecule that may have favorable interactions with the probe molecule. Differences in the interaction energies of the oxidized and reduced probe with the target can also be plotted as contours, indicating regions that are selective for the reduced probe. These selectivity contours can be used to show whether the macromolecule is a potential target for bioreductive agents. The method has been applied to the chicken liver dihydrofolate reductase enzyme and has indicated new binding regions that may be suitable binding sites for bioreductive agents.

Binding Sites↗
PubMed1989

Solvation effects.

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Computer Simulation↗
PubMed1989

The binding of nonintercalative drugs to alternating DNA sequences.

Molecular mechanics methods have been applied to suggest possible models for netropsin and related compounds binding to two different sequences of DNA, namely poly[d(AT)].poly[d(AT)] and poly[d(GC)].poly[d(GC)], and to evaluate the different contributions to the binding affinities of these compounds in the ethidium displacement assay. The geometries found after energy refinement suggest that one of the reasons for the selectivity of binding of these agents to A + T-rich DNA regions could be the different widths of the minor groove of the double strand of DNA found in the complexes of these drugs with both DNA sequences.

Base Sequence↗
PubMed1988

Computed redox potentials and the design of bioreductive agents.

Anti-cancer agents that have been made selective for tumour cells by exploiting the known differences in the availability of oxygen between normal and transformed cells are a promising development in cancer chemotherapy. We have recently suggested a new type of bioreductive activity which would depend on a two-electron reduction. For rational design of such compounds, it is essential to be able to predict the redox potentials and the chemical modifications needed to produce the optimum redox value. Calculating redox potentials is a daunting task for the theoretician, however, as the effect of water solvation is clearly of major significance. Recent successful calculations of differences in the free energies of biologically important molecules in aqueous solution using the free-energy perturbation method prompted us to apply the technique to the computation of two-electron redox potentials. The results are accurate to within 20 mV, suggesting that we should be able to manipulate redox potentials by successfully predicting structures with the appropriate value.

Antineoplastic Agents↗
PubMed1988

The self-splicing intron in the Neurospora apocytochrome b gene contains a long reading frame in frame with the upstream exon.

We have determined the DNA sequence of intron 1 and flanking exons in the mitochondrial apocytochrome b gene of the Neurospora laboratory strain 74A and the natural isolate North Africa. In contrast to a previous report, we find that this intron contains an open reading frame (ORF) of 951 bases in frame with the upstream exon. The putative intron-encoded protein resembles those of other intron ORFs with respect to length, calculated isoelectric point, and proportion of basic, acidic, polar, and non-polar amino acids; however, no amino acid sequences resembling the "decapeptides" characteristic of maturase-like ORFs were found. Coupled with the previous finding that this intron is capable of self-splicing in vitro in the absence of proteins, the observations discussed here raise the possibility that other introns with long, in-frame ORFs may also be capable of RNA-catalyzed splicing in vitro.

Amino Acid Sequence↗
PubMed1971

Hemoglobin Savannah (B6(24) beta-glycine is greater than valine): an unstable variant causing anemia with inclusion bodies.

An abnormal hemoglobin, termed Hb Savannah, was found in red cell hemolysate of a young Caucasian girl with severe hemolytic anemia. The presence of this unstable variant became evident when inclusion bodies appeared rapidly upon exposure of red cells to redox dyes and a large percentage of hemoglobin in hemolysate precipitated on warming to 65 degrees C. Treatment of the hemoglobin with p-hydroxymercuribenzoate (PMB) caused a rapid dissociation into monomers; starch-gel electrophoresis of PMB-treated hemoglobin showed the presence of abnormal beta-chains. Data from structural studies of isolated beta-chains indicated substitution of a valyl residue for the normally occurring glycyl residue at position 24, which corresponds to helical residue B6. A similar substitution but with an arginine replacing the glycyl residue has been observed in Hb Riverdale-Bronx. The glycine to valine substitution will change the relationship of the B and the E helices which results in extensive conformational changes in the beta-chain. This change presumably causes an increased dissociation of the hemoglobin molecule into dimers and probably monomers, and a decreased stability of the alphabeta-dimers. The hemoglobin abnormality may be the result of a fresh mutation because the abnormality is not present in the parents nor in any of the seven siblings.

Amino Acid Sequence↗
PubMed1971

Hemoglobin Louisville (beta-42 (CD1) phe-leu): an unstable variant causing mild hemolytic anemia.

An unstable hemoglobin variant termed Hb Louisville, was found in four members of a Caucasian family, who were suffering from a mild hemolytic anemia. The variant showed a decreased stability upon warming at 65 degrees C and an increased tendency to dissociate in the presence of sulfhydryl group-blocking agents. The structural abnormality was identified as a replacement of phenylalanyl residue in position 42 (CD1) by a leucyl residue. Substitution of this phenylalanyl residue, which participates in the contact with heme, by a nonpolar leucyl residue has apparently less severe consequences than a replacement of the same residue by a polar seryl residue as in Hb Hammersmith. Oxygen equilibrium studies of total hemolysate from one Hb Louisville heterozygote indicated a decreased oxygen affinity, a marked decrease in heme-heme interaction, and a normal Bohr effect. Studies with isolated Hb Louisville were not made because it was not possible to separate the variant from normal Hb A.

Amino Acid Sequence↗
PubMedDate not supplied

The effect of anxiety and hostility in silent mentation on localized cerebral glucose metabolism.

Ten normal, wakeful, young (average age, 25.3 +/- 6.6 years) male subjects received positron emission tomographic (PET) scans 45 to 120 minutes after an infusion of D-[18 F]deoxyglucose in order to assess localized cerebral glucose metabolic rates during silent visual and other sensory imagery and cognitive mentation. The typescripts of the verbal reports, limited to 5 minutes, of this type of mentation (including free-associations to all the silent mental events), were blindly content-analyzed to provide objective measures of various kinds of anxiety and hostility. Many significant positive and negative correlations were found in medial cortical, lateral cortical, and subcortical gray matter, and white matter areas between the magnitude of the anxiety and hostility aroused in the silent mental processes and localized cerebral glucose metabolic rates. Clearly, energy consumption in the brain, as judged from localized glucose metabolic rates, is highly influenced by the quality and quantity of emotionally tinged private reveries and mental events occurring spontaneously within human subjects. Brain areas involved with the processing of language, sensation, cognition, memory, and emotional reactions appear to be involved especially in these significant correlations. The implications of such findings in the neurosciences and behavioral sciences are discussed.

Adult↗
PubMedDate not supplied

Correlation of lesion appearance and histologic findings for the nodes of a breast MR imaging interpretation model.

An interpretation model for evaluating magnetic resonance (MR) images of the breast was constructed that allowed differentiation of benign from malignant palpable or mammographically visible abnormalities. Architectural features define each node of the model. Investigation was subsequently made of the histologic findings in individuals within each node and of the frequency with which each histologic finding manifested as a particular architectural feature to determine whether nodal location and specific histologic findings are mutually predictive. The strongest associations were found between fibrocystic change and smooth masses, fibroadenoma and lobulated masses with nonenhancing internal septations, invasive ductal carcinoma (with or without ductal carcinoma in situ [DCIS]) and enhancing irregular or spiculated masses, invasive tubular carcinoma or radial scar and spiculated masses, medullary or colloid carcinoma and enhancing lobulated masses, invasive lobular carcinoma and the absence of a focal mass, DCIS and ductal enhancement, and DCIS (with or without invasive ductal carcinoma) and regional enhancement. Nodal location and histologic findings proved to be mutually predictive within the model; that is, the nodal location of MR imaging features within the model can be used to predict histologic findings and vice versa.

Biopsy↗