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Biomedical subjects

R T Walker

Publications and source records attributed to R T Walker.

156 records · Page 9Linked to original sources

The use of fluorine-containing carboxylic acids for the large-scale isolation of highly polymerized deoxyribonucleic acids.

1. The precipitation of the proteins of calf-thymus nucleohistone and herringsperm nucleoprotamine with the salts of fluorine-containing carboxylic acids has been studied. Pentadecafluoro-octanoate gave a precipitate that could be sedimented almost completely by centrifuging at 2350g for 20min. omega-H-Hexadecafluorononanoate, omega-H-eicosafluoro-undecanoate and dodecyl sulphate gave precipitates that could only be partly sedimented under these conditions. 2. A method has been developed for the isolation of highly polymerized DNA on a large scale from calf thymus and herring sperm by the use of pentadecafluorooctanoate. This is more convenient and less tedious than existing methods.

Acids↗

Efficient syntheses of (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine; a nucleoside analogue with potent biological activity.

(E)-5-(2-Bromovinyl)-2'-deoxy-4'-thiouridine (S-BVDU) is a potent antiherpesvirus agent and its use in gene therapy as an anticancer agent has recently been described. We here outline 2 efficient methods for the synthesis of S-BVDU. The decision as to which method is to be used depends upon the starting materials available but starting from BVU, an overall yield of beta-nucleoside of 35% can be expected. From 5-ethyl-2'-deoxy-4'-thiouridine, radical bromination using bromine will give a quantitative conversion to S-BVDU if unreacted starting material is recycled (50%) or using N-bromosuccinimide, a one step yield in excess of 80% can be obtained.

Antineoplastic Agents↗

Some 6-aza-5-substituted-2'-deoxyuridines show potent and selective inhibition of herpes simplex virus type 1 thymidine kinase.

The synthesis and X-ray crystal structures of a series of 5-substituted-6-aza-2'-deoxyuridines is reported. These nucleoside analogues inhibit the phosphorylation of thymidine by HSV-1 TK but have no effect on the corresponding human enzyme. Detailed examination of one analogue proves it to be a competitive inhibitor of thymidine with a Ki of 0.34 microM and is a very poor substrate. The analogues are not substrates for the enzyme and also do not inhibit the degradation of thymidine by thymidine phosphorylase. Molecular modelling showed that the inhibitors fit well in the active site of HSV-1 TK, provided the conformation of the sugar moiety is the same for thymidine in the complex.

Antiviral Agents↗

Venous claudication. A report of 15 cases and a review of the literature.

The symptom of intermittent claudication is not invariably due to arterial disease. Exercise-related pain resulting from venous insufficiency is poorly defined, but has been described by a number of authors in the past. Fifteen patients with symptoms suggestive of venous claudication are reported. The history and clinical findings are described. The further investigation of these patients is outlined, starting with the non-invasive methods of Doppler ultrasonography and strain gauge plethysmography. Ascending phlebography was performed on all affected limbs (n. 19) and descending phlebography was performed on those shown to have a patent deep venous system. These investigations demonstrated deep venous abnormalities associated with the distinct symptom complex. Venous claudication is defined and the literature reviewed. It is hoped that a clearer understanding of the condition will result in more frequent and accurate diagnosis with subsequent benefit to the patient.

Adult↗

Mycoplasma evolution: a review of the use of ribosomal and transfer RNA nucleotide sequences in the determination of phylogenetic relationships.

Comparison of the nucleotide sequences of "structural" RNAs (ribosomal and transfer RNA) has enabled the construction of phylogenetic trees to be achieved. Data from 16S rRNA, 5S rRNA, and tRNA from a total of eight Mollicutes (excluding T. acidophilum) including representatives of the families Mycoplasmataceae, Spiroplasmataceae, and Acholeplasmataceae, show that these families share a close relationship and a common ancestor with the gram-positive eubacteria. Thermoplasma acidophilum is a member of the kingdom Archaebacteriae and has no relationship to the other Mollicutes.

Base Sequence↗