Biomedical subjects
Publications and source records attributed to Peter Thomson.
We report a case of airway fire during surgical tracheotomy using diathermy for the incision into the trachea. A literature review of airway fire during tracheotomy was carried out, and the management of airway fire is discussed. Recommendations are made to prevent this adverse outcome.
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Nitrothienylprop-2-yl ether formation on the 3'-phenolic position of combretastatin A-4 (1) abolishes the cytotoxicity and tubulin polymerization-inhibitory effects of the drug. 5-Nitrothiophene derivatives of 1 were synthesized following model kinetic studies with analogous coumarin derivatives, and of these, compound 13 represents a promising new lead in bioreductively targeted cytotoxic anticancer therapies. In this compound, optimized gem-dimethyl alpha-carbon substitution enhances both the aerobic metabolic stability and the efficiency of hypoxia-mediated drug release. Only the gem-substituted derivative 13 released 1 under anoxia in either in vitro whole-cell experiments or supersomal suspensions. The rate of release of 1 from the radical anions of these prodrugs is enhanced by greater methyl substitution on the alpha-carbon. Cellular and supersomal studies showed that this alpha-substitution pattern controls the useful range of oxygen concentrations over which 1 can be effectively released by the prodrug.
PURPOSE: This study investigates the enhancement of the vascular targeting activity of the tubulin-binding agent combretastatin A4 phosphate (CA4P) by various inhibitors of nitric oxide synthases. METHODS AND MATERIALS: The syngeneic tumors CaNT and SaS growing in CBA mice were used for this study. Reduction in perfused vascular volume was measured by injection of Hoechst 33342 24 h after drug administration. Necrosis (hematoxylin and eosin stain) was assessed also at 24 h after treatment. Combretastatin A4 phosphate was synthesized by a modification of the published procedure and the nitric oxide synthase inhibitors L-NNA, L-NMMA, L-NIO, L-NIL, S-MTC, S-EIT, AMP, AMT, and L-TC, obtained from commercial sources. RESULTS: A statistically significant augmentation of the reduction in perfused vascular volume by CA4P in the CaNT tumor was observed with L-NNA, AMP, and AMT. An increase in CA4P-induced necrosis in the same tumor achieved significance with L-NNA, L-NMMA, L-NIL, and AMT. CA4P induced little necrosis in the SaS tumor, but combination with the inhibitors L-NNA, L-NMMA, L-NIO, S-EIT, and L-TC was effective. CONCLUSIONS: Augmentation of CA4P activity by nitric oxide synthase inhibitors of different structural classes supports a nitric oxide-related mechanism for this effect. L-NNA was the most effective inhibitor studied.
The novel gene encoding Clone 4, previously isolated through the Serological screening of recombinant expression cDNA library (SEREX) in chronic myeloid leukaemia (CML), was characterized. It is localized to chromosome 7 at q22, occupies approximately 4.5 kb of DNA and comprises 4 exons. Three single nucleotide polymorphisms and a 13 base deletion/insertion polymorphism have been identified. The mRNA transcript was approximately 2.4 kb and contained a long 5'-untranslated region of almost 1 kb before the candidate open reading frame. Northern blot analysis and multiple tissue expression array indicated a restricted normal tissue distribution. Our findings provide a platform for future investigations into the role of the gene product in CML.