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Biomedical subjects

J M Cook

Publications and source records attributed to J M Cook.

118 records · Page 7Linked to original sources
PubMed1969

The inhibition of nucleic acid synthesis by mycophenolic acid.

1. Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro. 2. The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [(14)C]thymidine. 3. The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine. 4. The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine. 5. Mycophenolic acid does not inhibit the incorporation of [(14)C]thymidine into DNA in suspensions of Landschütz and Yoshida ascites cells in vitro. 6. Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschütz and Yoshida ascites cells and also in L cells in vitro. There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic. 7. Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschütz cells capable of converting hypoxanthine into IMP, XMP and GMP. 8. Preparations of IMP dehydrogenase from Landschütz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid. The inhibition showed mixed type kinetics with K(i) values of between 3.03x10(-8) and 4.5x10(-8)m. 9. Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschütz and Yoshida ascites cells and L cells in vitro.

Adenine↗
PubMedDate not supplied

Ventricular remodeling: insights from pharmacologic interventions with angiotensin-converting enzyme inhibitors.

Structural remodeling of the left ventricular (LV) myocardium develops in a time-dependent fashion following acute myocardial infarction and may be an integral component in the transition toward overt heart failure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular level, the remodeling process is associated with myocyte slippage, hypertrophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monotherapy with the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the progression of LV remodeling in dogs with LV dysfunction (ejection fractions 30-40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with enalapril (n = 7) or to no treatment (n = 7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and chamber sphericity increased significantly during the 3 months follow-up period. In contrast, in dogs treated with enalapril ESVI, EDVI and chamber sphericity remained essentially unchanged. Treatment with enalapril attenuated myocyte hypertrophy and the accumulation of interstitial collagen in comparison to untreated dogs. These data indicate that early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibition of direct action of angiotensin-II and possibly the decrease in bradykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Characterization of aminosaccharins in commercial sodium saccharin produced by the Maumee process.

The most abundant polar impurities detected by ion-pair high-pressure liquid chromatography of sodium saccharin produced by the Maumee process were identified as 5- and 6-aminosaccharin. The combined levels of these compounds in the samples analysed ranged from 99 to 152 mg/kg. Other less abundant polar impurities identified in Maumee process sodium saccharin were 7-aminosaccharin and o-sulphamoylbenzoic acid. Mutagenicity assays of 5-aminosaccharin, 6-aminosaccharin and a polar impurity fraction isolated from Maumee saccharin, gave negative results.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

The isolation and characterization of a new tetrahydroprotoberberine alkaloid from Corydalis clarkei.

The MeOH extract of Corydalis clarkei Prain yielded two tetrahydroprotoberberine alkaloids that bear the unusual 1,2- and 9, 10-tetraoxygenated substitution pattern observed previously only in caseanidine . The alkaloids have been identified as caseanidine (1) and the new alkaloid, clarkeanidine (2). The 1H- and 13C-nmr shifts of both alkaloids have been assigned unambiguously using 2-D nmr. The elucidation of the structure of 2 was achieved by comparison of the 1H- and 13C-nmr spectra of 2 with those of caseanidine coupled with additional spectroscopic evidence.

Alkaloids↗
PubMedDate not supplied

Synthesis of 10,11-dihydroxydihydroquinidine N-oxide, a new metabolite of quinidine. Preparation and 1H-nmr spectroscopy of the metabolites of quinine and quinidine and conformational analysis via 2D COSY nmr spectroscopy.

The first synthesis of 10,11-dihydroxydihydroquinidine N-oxide [7b], a recently isolated metabolite of quinidine, was accomplished in three steps from 1b. The related congener 7a in the quinine series was also prepared, as well as two other analogues 3a and 4a. In addition, the previously reported human metabolites 2a, 5a, and 6a of quinine [1a] and those 2b, 3b, 4b, 5b, and 6b of quinidine [1b] were synthesized. The chemical shift and coupling constants for all of the metabolites of quinine and quinidine were assigned via 2D COSY 1H-nmr spectroscopy. Moreover, the conformations of these metabolites in solution were found to parallel those of the parent alkaloids, quinine [1a] and quinidine [1b], respectively.

Molecular Conformation↗