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Biomedical subjects

A W Payne

Publications and source records attributed to A W Payne.

16 recordsLinked to original sources
PubMed1998

CINEMA--a novel colour INteractive editor for multiple alignments.

CINEMA is a new editor for manipulating and generating multiple sequence alignments. The program provides both an interface to existing databases of alignments on the Internet and a tool for constructing and modifying alignments locally. It is written in Java, so executable code will run on most major desktop platforms without modification. The implementation is highly flexible, so the applet can be easily customised with additional functions; and the object classes are reusable, promoting rapid development of program extensions. Formerly, such extended functionality might have been provided via browser plug-ins, which have to be downloaded and installed on every client before loading data. Now, for the first time, an applet is available that allows interactive client-side processing of an alignment, which can then be stored or processed automatically on the server. The program is embedded in a comprehensive help file and is accessible both as a stand-alone tool on UCL's Bioinformatics Server; http:/(/)www.biochem.ucl.ac.uk/bsm/dbbrowser+ ++/CINEMA2.02/, and as an integral part of the PRINTS protein fingerprint database. Exploitation of such novel technologies revolutionises the way users may interact with public databases in the future: bioinformatics centres need not simply provide data, but are now able to offer the means by which information is visualised and manipulated, without the requirement for users to install software.

Color Perception↗
PubMed1995

A genetic algorithm for the automated generation of molecules within constraints.

A genetic algorithm has been designed which generates molecular structures within constraints. The constraints may be any useful function, for example an enzyme active site, a pharmacophore or molecular properties from pattern recognition or rule-induction analyses. The starting point may be random or may utilise known molecules. These are modified to 'grow' into families of structures which, using the evolutionary operators of selection, crossover and mutation evolve to better fit the constraints. The basis of the algorithm is described together with some applications in lead generation, 3D database construction and drug design. Genetic algorithms of this type may have wider applications in chemistry, for example in the design and optimisation of new polymers, materials (e.g. superconducting materials) or synthetic enzymes.

Algorithms↗
PubMed1994

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics.

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-mercaptobenzoate-arginine-glycine-aspartate-2-mer captoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular dichroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.

Amides↗
PubMed1993

Molecular recognition using a binary genetic search algorithm.

A genetic algorithm has been devised and applied to the problems of molecular similarity, pharmacophore elucidation, and determination of molecular conformation. The algorithm is based on a binary representation of molecular position and conformation. Using the genetic operators, crossover, mutation, and selection near optimum conformations and orientations of molecules may be determined which best-fit defined constraints. The constraints may be any useful function for example, intermolecular or intramolecular distances, electrostatic potential on a surface, or volume overlap. Problems with up to 30 degrees of freedom have been tackled successfully.

Algorithms↗
PubMed1987

Improved program for the analysis of DNA histograms.

We describe a computer program which will rapidly analyze a set of DNA histograms without further operator intervention after the initial input. The algorithm used was modified from that of Watson et al. (Cytometry 8:1-8, 1987). The program, coded in Pascal, has been implemented on two different systems. It has been tested by using simulated data and experimental data from cells labelled with bromodeoxyuridine. The program has been in use in this and other laboratories for over two years and has proved to be robust and fast and to give a reasonable approximation to the experimental data. It is particularly useful when dealing with badly perturbed DNA histograms.

Algorithms↗
PubMed1986

Comparative studies of total cross-linking, cell survival and cell cycle perturbations in Chinese hamster cells treated with alkylating agents in vitro.

The toxicities of 4-hydroperoxycyclophosphamide (4-OOH CY), phosphoramide mustard (PM), melphalan (MEL) and busulphan (BU) have been compared in Chinese hamster cells, V-79-753B. The initial total amount of cross-linking was a determining factor for the clonogenic survival of cells treated with MEL or PM. Although 4-OOH CY generated cross-links in this cell line, this damage did not account for the toxicity of the compound. There was no evidence for cross-link formation in cells treated with BU, even at a dose of the drug (1000 micrograms/ml) that was too toxic to measure clonogenic survival. Comparison for the four compounds at equitoxic doses showed that both PM and MEL caused the arrest of the cell cycle at G2 which persisted after drug removal. This was accompanied by a decline in the population growth rate and a decrease in total cell count. In contrast, both BU and 4-OOH CY caused a temporary arrest of the cell cycle G2, 24 hr after drug removal. However, the cell cycle distribution returned the control values within 3-4 days after treatment. Both BU and 4-OOH CY showed little effect on the initial growth rate of the cells. It is concluded that the initial amount of cross-links contributes to the toxicity of PM and MEL. However, it is unlikely that the generation of cross-links is of major importance for the toxicity of either 4-OOH CY or BU.

Alkylating Agents↗
PubMed1985

Antigenic heterogeneity of breast cell lines detected by monoclonal antibodies and its relationship with the cell cycle.

Established cell lines were stained by immunofluorescence with four monoclonal antibodies to study the phenomenon of antigenic heterogeneity and its possible relation to the cell cycle. Five cell lines thought to be of breast origin, MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL-100, were stained with three monoclonal antibodies (LICR-LON-M8, LICR-LON-M18, LICR-LON-M24) that each stain a distinct subset of normal breast epithelial cells, i.e. demonstrate antigenic heterogeneity in normal breast epithelial cells. Contrasting monoclonal antibodies LICR-LON-FIB75 and LICR-LON-FIB86 to homogeneously expressed antigens were also used. For the antibodies demonstrating heterogeneity distinct positive and negative fractions were not seen by flow cytometry; the intensity of fluorescence varied continuously from background to a hundred times stronger than background. Fluorescent DNA staining showed no obvious relation between antigen expression and the cell cycle. The essentially constant proportion of cells of a given antigenic phenotype in the various phases suggests that these antibodies do not distinguish a phenotype associated with a distinct proliferating population of cells.

Antibodies, Monoclonal↗
PubMed1982

IgA in dermatitis-herpetiformis skin is dimeric.

Skin-biopsy specimens from six patients with dermatitis herpetiformis (DH) were examined by means of indirect immunofluorescence with specific rabbit antisera for the presence of in-vivo J chain and secretory component in IgA deposits. The ability of IgA to bind purified secretory component was studied by means of indirect immunofluorescence with antisera to secretory component. Positive J-chain staining associated with IgA deposits was seen in cryostat sections of all seven DH skin-biopsy specimens. In-vivo secretory component was not detected, but on treatment of sections with a solution of purified secretory component, binding of the latter in the region of the IgA deposits was demonstrated in six of the seven DH skin-biopsy specimens. With double fluorochrome staining binding of secretory component was shown to be essentially coextensive with the IgA deposits. These findings suggest that the IgA deposited in DH skin originates from plasma cells in the small intestine.

Binding Sites, Antibody↗
PubMed1982

Diffusion in the vicinity of standard-design nuclear power plants--I. Wind-tunnel evaluation of diffusive characteristics of a simulated suburban neutral atmospheric boundary layer.

A large meteorological wind tunnel was used to simulate a suburban atmospheric boundary layer. The model-prototype scale was 1:300 and the roughness length was approximately 1.0 m full scale. The model boundary layer simulated full scale dispersion from ground-level and elevated release points over surfaces of comparable roughness length. This information should prove useful in a variety of transport and diffusion studies over short to moderate downwind distances. It will be used in Part II as the baseline data set with which to compare diffusion downwind of standard-design nuclear power plants.

Air Pollution, Radioactive↗
PubMed1982

Diffusion in the vicinity of standard-design nuclear power plants--II. Wind-tunnel evaluation of building-wake characteristics.

Laboratory experiments were conducted to simulate radiopollutant effluents released to the atmosphere from two standard-design nuclear power plants. The main objective of the study was to compare the dispersion in the wakes of the plants with that in a simulated atmospheric boundary layer. Dispersion functions are determined that describe the spread of the effluent plume in the wake of each plant. These dispersion functions are described by power laws. They are determined for three incident wind angles and the number of stacks associated with each plant. Lateral plume spread was directly related to the silhouette area of the plants. A graphical technique is presented relating the lateral dispersion to the associated silhouette area of the building or building complex.

Air Pollution, Radioactive↗
PubMed1982

Elimination into bile of circulating antigen by endogenous IgA antibody in rats.

Rats injected once into their Peyer's patches with insoluble precipitates of chicken antibody and antigen produced antibodies to chicken IgG (CGG) of the IgM and IgA classes which rose steeply between days 3 and 5 after injection; IgG antibody was detected later and rose more slowly. The IgA antibody was almost entirely in the bile whilst IgM and IgG were found predominantly in serum. In immunized rats with cannulated bile ducts injected intravenously with radiolabelled CGG on day 5 up to 22% of the injected dose was recovered in the bile in 24 hr; in control rats the maximum recovery was 0.4%. Although the complexes were unstable, intact 125I-CGG (some of it bound to rat IgA and secretory component) was demonstrated in bile collected from immunized rats between 1.5 and 3 hr after injection.

Animals↗
PubMed1981

The origin of IgA in chicken bile: its rapid active transport from blood.

In the chicken, there are two bile ducts, one draining the left lobe of the liver directly into the duodenum and the other draining the right lobe via the gall bladder. Cannulation of these ducts enabled us to collect bile in unanesthetized birds and to compare the IgA concentrations of the hepatic bile, gall bladder bile and blood serum. Bile from the cystic and hepatic ducts of the same bird contained similar amounts of IgA (1.7 mg/ml), roughly 10 times as much as in serum, but considerably less than that found in the concentrated bile collected by aspiration from the gall bladder (8 mg/ml). Ligation of the two bile ducts resulted in a three to fourfold increase in the concentration of IgA in serum suggesting that IgA is normally removed from serum by the biliary route. This was confirmed by a substantial recovery of i.v. injected, radiolabeled monoclonal dimeric human IgA in the bile corresponding to a rapid active clearance from the blood circulation; negligible amounts of monomeric human IgA, similarly injected, were recovered from the bile.

Animals↗
PubMed1981

The elimination of circulating complexes containing polymeric IgA by excretion in the bile.

Radiolabelled human dimeric IgA injected intravenously into rats behaved like oligomeric rat IgA in that 40% of the injected dose was recovered in the bile within 6 h. Monomeric IgA was not transported into bile. In addition, dimeric IgA was able to carry with it macromolecular material in the form of a complex that also included rat SC. This was demonstrated in rats which had received an intravenous injection of specifically purified radiolabelled rabbit antibody tao the idiotype of a human IgA myeloma: when a later injection of unlabelled IgA dimer with the corresponding idiotype was given up to 18% of the rabbit antibody when the monomeric form of the same IgA was injected. This mechanism for clearing complexes containing polymeric IgA is mediated by hepatocytes and is distinct from the phagocyte-mediated mechanisms which clear conventional complexes.

Animals↗
PubMed1980

Comparative aspects of the transport of immunoglobulin A from blood to bile.

Polymeric and monomeric human IgA were isolated from the sera of patients with IgA myeloma; rat IgA polymer, monomer and IgG2 were isolated from the ascitic fluid or sera of Lou/Wsl rats bearing appropriate myelomata. The purified Ig preparations were labelled with 125I and injected intravenously into rats, rabbits, guinea-pigs or sheep that had had a cannula inserted into the common bile duct so that their bile could be collected quantitatively. Rats and rabbits transported 30% of the injected dose of both IgA polymers, but no other type of immunoglobulin, from blood to bile within 5--7 h. Sheep and guinea-pigs were unable to transport any of the immunoglobulin preparations from blood to bile, even though the injected material remained circulating in the blood.

Animals↗