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Biomedical subjects

W D Wilson

Publications and source records attributed to W D Wilson.

At least 217 records · Page 12Linked to original sources

Organ culture model for the study of HVH-II infections in carcinoma of the cervix.

An experimental model is described whereby human and monkey cervical tissues may be maintained as organ cultures for 21 and 40 days, respectively. Inclusion of sodium carboxymethyl cellulose in the culture medium prolongs the survival time of tissues considerably. The sequential cytologic changes associated with herpesvirus hominis type II (HVH-II) infection are reported. These changes are considered in relation to the possible causal role of HVH-II infection in cervical carcinogenesis.

Animals↗

Ascending infection following cervicovaginal exposure to herpesvirus hominis type II.

An animal model is presented that demonstrates that following cervicovaginal inoculation, infective doses of herpesvirus hominis type II induce a form of herpetic encephalitis. Immunofluorescent results indicate that there is both neural and hematogenous spread of the herpes infection. The possible role of a latent viral infection in the genesis of an acute disease of the central nervous system is investigated in this experimental system.

Animals↗

Relation of herpesvirus hominis type II to carcinoma of the cervix. An animal model for the induction of long-term latency of herpesvirus hominis type II.

Proof of latency of herpesvirus hominis type II (HVH-II) following acute vaginocervical infection must be validated if it is to be considered an etiologic factor in carcinoma of the cervix. An animal model is presented which demonstrates acute HVH-II vaginocervical infection. Following the primary acute infection, animals maintained for an equivalent of 60 human years display persistance of the herpesvirus in the pelvic sensory ganglia. Evidence of the specificity of HVH-II as the infectious agent is presented.

Acute Disease↗

The interaction of propidium diiodide with self-complementary dinucleoside monophosphates.

The interactions of a quinacrine derivative, methylated at both the aromatic and aliphatic nitrogens, and propidium diiodide with the dinucleoside monophosphates CpG, GpC, UpA and ApU have been investigated using 13C-NMR (for the quinacrine derivative prepared with [13C]methyl substituents and 1H-NMR and ultraviolet-visible spectroscopy. The quinacrine derivative displayed negligible interaction with the dinucleosides at concentrations up to 5 - 10(-4) M. Propidium did form complexes with dinucleosides even at concentrations as low as 10(-4) M. Propidium displayed a pyrimidine-purine binding preference and gave especially large changes in ultraviolet-visible and 1H-NMR spectra in the presence of CpG. This suggests that propidium forms an intercalated complex with a Watson-Crick hydrogen-bonded CpG dimer. At higher concentrations UpA and GpC gave similar spectral changes indicating that they could also form significant amounts of an intercalated complex with propidium under appropriate conditions. The changes caused by ApU were small under all conditions and were more similar to the effects caused by mononucleotides. These results indicate that, at least for phenanthridines, cationic side chains do not greatly inhibit complex formation with dinucleoside monophosphates, and suggest that the weak interaction of the quinacrine derivative with dinucleosides is due to weaker interactions of the acridine ring system with nucleoside bases relative to the phenanthridine ring system.

Chemical Phenomena↗

The interaction of plant alkaloids with DNA. II. Berberinium chloride.

The interaction of berberinium chloride with DNA has been investigated using spectrophotometry, viscometric titrations with sonicated and closed circular superhelical DNA, and flow polarized fluorescence. The binding results for berberinium were found to fit the neighbor exclusion model. The two viscometric titrations and flow polarized fluorescence results exclusion model. The two viscometric titrations and flow polarized fluorescence results also indicated that berberinium binds to DNA by intercalation. Titration of sonicated DNA with berberinium produced viscosity increases which were less than those obtained with quinacrine and the titration of superhelical DNA indicated a significantly smaller unwinding angle for intercalation of berberinium than for quinacrine. These results can be interpreted in terms of a model in which (i) berberinium is partially intercalated into the double helix, or (ii) the alkaloid is more completely intercalated into the double helix, but causes bending of the helix due to the slight nonplanarity of the berberinium ring system, or (iii) a combination of (i) and (22).

Berberine↗

Interaction specificity of the anthracyclines with deoxyribonucleic acid.

The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.

Animals↗

Stereospecific binding of diastereomeric peptides to salmon sperm DNA.

Studies of the interaction specificities of L-lysyl-L-phenylalaninamide (1) and the diastereomeric dipeptide amide, L-lysyl-D-phenylalaninamide (2), with salmon sperm DNA reveal distinct differences in the binding site of the aromatic ring of the phenylalanine residue. The results of 1H nuclear magnetic resonance (NMR), spin-lattice relaxation rates, viscometric, and flow dichroism studies indicate the aromatic ring of 1 is "partially" inserted between base pairs of DNA whereas the aromatic ring of 2 points outward toward the solution. The terminal L-lysyl residue presumably interacts stereospecifically with DNA helix thus dictating the positioning of the aromatic ring of the C-terminal phenylalanine residue. In the accompanying paper (E. J. Gabbay et al. (1976), Biochemistry, following paper in this issue), the interaction of several oligopeptide amides (containing the N-terminal L-Lys-L-Phe residue) with DNA is examined. The results are found to be consistent with stereospecific binding of the terminal L-lysyl residue, and in addition, the evidence suggests that oligopeptides may bind to DNA via a modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).

Amides↗

The interaction specificity of peptides with DNA. Evidence for peptide beta-sheet-DNA binding.

Proton magnetic resonance studies (1H NMR) of the interaction of oligopeptide amides of defined sequence (and containing the amino acid, phenylalanine) with salmon sperm DNA are reported. The extent of upfield chemical shifts, deltasigma, and signal line broadening of the aromatic protons (in the presence of excess DNA) are found to depend on the primary sequence and stereochemistry of alpha carbons of the amino acids in the oligopeptide amides. The results obtained with 21 different di-, tri-, tetra-, penta- and hexapeptide amides are found to be consistent with a model whereby the peptide assumes a slightly modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).

Amides↗

Complex formation between naphthothiopheneethanolamines and deoxyribonucleic acids.

Reduced viscosities, viscometric titrations, fluorescence, and flow dichroism measurements indicate that the aromatic ring system of naphthothiopheneethanolamines (NA) is intercalated on binding to DNA. No marked change in binding was found on substituting a dibutylamino group for a piperidyl ring on the side chain. Ionic strength studies, however, did indicate that the positive charge on the side chain is quite important for binding. Both the binding equilibrium constant and the number of binding sites, as determined from a Scatchard plot of spectrophotometric results, decreased on increasing the sodium chloride concentration. The increase in Tm for several DNA samples, caused by adding NA to DNA at a fixed ratio, showed a marked dependence on the percentage of AT base pairs. The conclusion drawn from these data is that the DNA-NA complex involves high specificity of the NA for AT base pairs, intercalation of the aromatic ring system, and binding of the NA side chain in the DNA minor groove with strong interaction between the positively charged side chain and the DNA phosphate groups.

Antimalarials↗