The summary retrospective assessment of anticoagulants in myocardial infarction.
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Biomedical subjects
Publications and source records attributed to D L Smith.
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Painful shoulder conditions are common primary care problems. Providers should learn the topographical landmarks about the shoulder and understand shoulder mechanics. A careful clinical evaluation will usually provide a likely diagnosis. In unclear cases with marked pain, weakness, and reduced mobility, or with a suspected rotator cuff tear or rupture, arthrography or MRI will usually establish a diagnosis. Therapy of bursitis/tendinitis consists of a steroid injection into the inflamed subacromial area or a 14-day trial of an NSAID. Therapy of bicipital tendinitis, largely empiric because definitive studies are unavailable for any specific treatment, includes judicious peritendinous steroid injections and avoiding aggravating activities. In the management of patients with suspected tendon tears or rupture, primary care practitioners can confirm the diagnosis by ordering MRI or arthrography before referring these patients to an orthopedist for definitive surgical therapy. Optimal management of adhesive capsulitis remains unclear, but an intraarticular steroid injection appears beneficial at least in temporarily diminishing pain. Pendular motion exercising is also an integral part of therapy. Deleterious effects of peribursal or intraarticular steroid infiltration appear minimal; but injections into the tendon or frequent, repetitive injections are contraindicated. Each shoulder condition has a variable course, depending on the structure(s) and extent of involvement.
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Microsomal preparations derived from bovine placenta cotyledons, previously investigated as a convenient source of fatty acyl coenzyme A: estradiol-17 beta-acyl transferase, have been shown to acylate other steroids bearing 3 beta- or 17 beta-hydroxyl groups. In the presence of 0.1 mM oleoyl CoA, the apparent Km values for dehydroepiandrosterone, testosterone, and 5-androstene-3 beta,17 beta-diol (delta 5-DIOL) were 45, 67, and 20 microM, respectively. Acylation of delta 5-DIOL occurred at either the 3 beta- or 17 beta-positions to give monoesters. Testosterone, estradiol-17 beta, and delta 5-DIOL acted as competitive inhibitors for the acylation of the 3 beta-hydroxyl group of dehydroepiandrosterone (Ki values 71, 75, and 41 microM, respectively). Such data indicate that a single enzyme of wide substrate specificity may be involved in these acylation reactions. When estrogen receptor (ER) positive and negative human mammary cancer cell lines were incubated with 10 nM [3H]delta 5-DIOL, intracellular accumulation of delta 5-DIOL long-chain fatty acid esters occurred; rates being higher (p less than 0.001) in ER negative cells (MDA-MB-231 and MDA-MB-330) compared to MCF-7 cells (ER positive), and higher (P less than 0.005) in MDA-MB-231 cells compared to ZR-75-1 cells (ER positive). After exposure to 10 nM [3H]delta 5-DIOL for 16 h, the total labeled steroid fatty acid fraction was composed predominantly of delta 5-DIOL-3 beta- and 17 beta-monoesters (approximately 85%), the remainder containing approximately equal amounts of delta 5-DIOL-diesters and dehydroepiandrosterone-3 beta-esters. Subsequent transfer to medium lacking delta 5-DIOL was accompanied by a breakdown of the labeled esters, which was more rapid in the ER positive cell lines. During this period, intracellular free delta 5-DIOL levels rapidly declined in MDA-MB-330 cells but were maintained in MCF-7 cells, presumably by binding to ER. This behavior parallels that of estradiol-17 beta previously observed in these cell lines and further emphasizes the potential importance of the adrenal-derived estrogen delta 5-DIOL in consideration of a hormone-based etiology of human breast cancer.
Screening of crude extracts of the bark of Annona bullata showed cytotoxic and pesticidal activities. By monitoring with brine-shrimp lethality, two novel, extremely potent acetogenins, bullatacin [1] and bullatacinone [2], were isolated. Spectral and chemical methods identified bullatacin as a diastereomer of asimicin. Bullatacinone represents bullatacin with the lactone cleaved and reformed at the 4-OH. Compounds 1 and 2 show selective cytotoxicities in human tumor cell lines, and certain susceptible cells give ED50 values as low as 10(-12)-10(-15) micrograms/ml. Bullatacin was pesticidal at concentrations as low as 1 ppm, but bullatacinone lacked pesticidal activities. The known compounds liriodenine and (-)-kaur-16-en-19-oic acid were also isolated and were lethal to brine shrimp but were not significantly cytotoxic.
From the EtOH extract of the bark of Persea major, two bioactive compounds, majorynolide [1] and majorenolide [2], were isolated by activity-directed fractionation using brine shrimp. Their structures have been elucidated on the basis of spectral data as a pair of new alkene-alkyne delta-lactones, each with an exocyclic alkylidene methine carbon. Both 1 and 2 are moderately cytotoxic, and 2 is selectively pesticidal.
Activity-directed fractionation of the stem bark of Annona squamosa, monitoring with brine shrimp lethality, led to the isolation of the highly bioactive acetogenins bullatacin [1] and bullatacinone [2], thus demonstrating a new abundant plant source for these potent compounds. A new keto-monotetrahydrofuran acetogenin with a ketolactone terminus, as first seen in bullatacinone [2], was also isolated, characterized by spectral analyses, and named squamone [3]. The cytotoxicities of 3 were increased significantly by reduction of the two keto groups to hydroxyls, and the tetrahydrosquamone [7] and bullatacinone [2] both showed selective cytotoxicities to MCF-7 human breast carcinoma. Liriodenine and (-)-kaur-16-en-19-oic acid were also isolated.