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Biomedical subjects

A L Russell

Publications and source records attributed to A L Russell.

At least 37 records · Page 2Linked to original sources

Mitochondrial RNA editing of cytochrome c oxidase subunit II (coxII) in the primitive vascular plant Psilotum nudum.

A 634-nucleotide tract, including primers, was amplified via the polymerase chain reaction within a mitochondrial coxII gene of the primitive vascular plant Psilotum nudum and sequenced. Alignment with homologous coxII gene sequences from diverse plant species having known RNA editing sites which restore amino acid sequence consensus was used to infer eight sites of C-to-U transitions in Psilotum. In every case, the predicted editing event would confer the selective advantage of conserving the amino acid residue at a site where amino acid sequence divergence has not been observed in other plant species. The plant mitochondrial editing machinery is shown for the first time to extend to one of the deepest branches of vascular plant phylogeny.

Amino Acid Sequence↗

cDNA sequence, deduced amino acid sequence, predicted gene structure and chemical regulation of mouse Cyp2e1.

The cDNA encoding the mouse Cyp2e1 protein has been isolated and sequenced, and shown to share 92%, 79%, 80% and 79% sequence similarity over the coding region with rat, human, rabbit 1 and rabbit 2 CYP2E1 cDNA sequences respectively. The predicted Cyp2e1 protein contains 493 amino acids, with a molecular mass of 56781 Da. The protein contains many features common to other cytochrome P450s, including a potentially phosphorylatable serine residue at position 129 within a canonical cyclic AMP-dependent protein kinase site. Southern blot analysis of genomic DNA prepared from C57BL/6 and DBA/2N mice suggests the presence of only a single Cyp2e1 gene. The Cyp2e1 gene was isolated and its organization was established by PCR using oligonucleotides to its predicted intron/exon boundaries. These results showed that the mouse Cyp2e1 gene is approx. 11,000 bp in length and has a similar structure to the human and rat CYP2E1 genes. Cyp2e1 protein expression was studied in a variety of tissues and a sexual dimorphism in its levels in some tissues was noted. Acetone treatment induced the Cyp2e1 protein in all of the tissues studied in both sexes, but this Cyp2e1 protein induction was not accompanied by an increase in Cyp2e1 mRNA levels. Indeed, mRNA levels were seen to be decreased on treatment, suggesting that acetone administration affects either mRNA translation efficiency or protein stability. Of a wide range of drugs known to modify other cytochrome P450 levels only diethylnitrosamine had a significant effect on Cyp2e1, causing a decrease in protein levels.

Amino Acid Sequence↗

Sexual differentiation and regulation of cytochrome P-450 CYP2C7.

The multigene family of proteins known as the cytochrome P-450-dependent monooxygenases play a central role in the metabolism of hormones and foreign compounds. As part of our studies into the function and regulation of these proteins we have isolated a little studied constitutively expressed isozyme CYP2C7 and have investigated its substrate specificity and mode of regulation. Interestingly the haem of this enzyme in its isolated form is almost 100% in the high spin state. The enzyme was active in the metabolism of a range of model resorufin substrates, but exhibits highest activity towards benzyloxyresorufin. Indeed, this isozyme appears to play a significant role in the metabolism of this substrate in microsomal samples from untreated male rats. Tissue distribution studies indicated that CYP2C7 was expressed in liver, kidney and possibly muscle tissue. Cytochrome P-450 CYP2C7 could not be significantly induced by any of a wide range of known modulators of cytochrome P-450 expression at the mRNA level, however some significant changes in protein expression were observed. Some of the agents used (e.g., diethylnitrosamine and carbon tetrachloride) caused a significant reduction in the expression of this protein. In agreement with other reports where mRNA levels were measured we found that the level of CYP2C7 protein expression was sexually differentiated. Female rats express two to three times the level found in males, the sex difference being reversible by hypophysectomy.

Animals↗

Piroxicam 0.5% topical gel compared to placebo in the treatment of acute soft tissue injuries: a double-blind study comparing efficacy and safety.

Piroxicam 0.5% gel, administered as 5 mg q.i.d. was compared to placebo gel in a double-blind study of the treatment of selected acute soft tissue injuries (ankle or acromioclavicular sprains, supraspinatus, or achilles tendinitis). A total of 200 patients (100 per treatment) were evaluated. Six patients (6%) in the piroxicam group discontinued treatment due to inefficacy, compared to 42/100 in the placebo group (p less than 0.001). Significantly greater reduction in pain (spontaneous and on movement), degree of joint restriction, pressure threshold and tenderness of the affected site were observed with piroxicam gel compared to placebo gel. The time to improvement was significantly less with the piroxicam gel. The overall evaluation of efficacy and of benefit to injury favoured piroxicam over placebo (p less than 0.0001). Both piroxicam and placebo gels were well tolerated, with 7 piroxicam and 15 placebo patients reporting primarily skin-related adverse effects. This study indicates that piroxicam 0.5% gel, administered as 5 mg q.i.d. is an effective treatment of musculoskeletal injuries (sprains and tendinitis), is significantly more effective than placebo, and is well tolerated.

Administration, Cutaneous↗

The Periodontal Index.

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Analysis of Variance↗