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Biomedical subjects

C Sanders

Publications and source records attributed to C Sanders.

At least 91 records · Page 5Linked to original sources

Phase II study of carminomycin in a human tumor cloning assay.

The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin.

Breast Neoplasms↗

Chicken gizzard tropomyosin: head-to-tail assembly and interaction with F-actin and troponin.

Chicken gizzard and rabbit striated muscle tropomyosins have been compared with respect to their abilities to polymerize head-to-tail and to interact with rabbit skeletal F-actin and troponin. By both viscosity and sedimentation equilibrium measurements, the smooth muscle protein was shown to aggregate more extensively than the cardiac (skeletal) tropomyosin. The stoichiometry and cooperativity of binding of gizzard tropomyosin to F-actin were shown to be similar to the striated muscle protein, as were also the effects of MgCl2 and KCl concentration. Although the gizzard protein was found to interact with rabbit striated troponin as indicated by sedimentation velocity measurements, it was eluted at a lower KCl concentration from a column of immobilized troponin than the cardiac (skeletal) protein. The absence of a significant increase in viscosity upon addition of troponin to gizzard tropomyosin is consistent with a minimal influence on its head-to-tail aggregation. Thus while gizzard tropomyosin resembles rabbit cardiac (skeletal) tropomyosin in its propensity for head-to-tail polymerization and in its F-actin binding properties, it is similar to the nonmuscle tropomyosin from platelets in its interactions with skeletal muscle troponin. These observations suggest that the gizzard protein shares structural features with both striated muscle and platelet tropomyosins.

Actins↗

The inotropic actions of adrenaline on frog ventricular muscle: relaxing versus potentiating effects.

1. In frog ventricle, adrenaline increases the size of the action potential, potentiates twitch tension, and enhances relaxation. Because tension development is directly controlled by membrane potential in frog ventricle, experiments were designed to separate the effects of adrenaline on the action potential from its effects on the development of tension.2. Comparison of the tension-voltage relations in the presence and absence of adrenaline showed that during the initial portion of the voltage clamp step, adrenaline potentiated tension, but beyond 1 sec into the clamp pulse tension was depressed.3. The time and voltage dependence of the positive inotropic effect of adrenaline during voltage clamp pulses were compatible with the kinetics of the slow inward current, which is known to be augmented by adrenaline in frog and mammalian ventricle.4. Ni(2+), which has been shown to block the slow inward current in frog ventricle, also inhibited the positive inotropic effect of adrenaline.5. The relaxant effect of adrenaline was demonstrated to be present at least as early as 600 msec after the onset of membrane depolarization. However, generally 1 sec or more of membrane depolarization was required before the relaxant effect of adrenaline predominated over its positive inotropic effect.6. In catecholamine depleted strips, the augmentation of the action potential and twitch tension in the presence of adrenaline was found to occur at a sixty-fold lower concentration than the relaxant effect as judged by suppression of KCl-induced contractures.7. Pure beta-receptor agonists reproduced completely the electromechanical effects of adrenaline on the frog ventricle. alpha-receptor agonists or antagonists had no effect on action potential or development of tension.8. Cyclic AMP and dibutyryl cyclic AMP were found to augment the frog ventricular action potential and potentiate twitch tension in reserpinized or beta-blocked frog ventricular strips. However, none of the relaxant effects of catecholamines could be reproduced by these agents alone.9. Theophylline produced changes in the action potential similar to those induced by adrenaline and mimicked both the positive inotropic and relaxant effects of the drug.10. The results suggest that the positive inotropic effects of adrenaline results mainly from changes induced in the action potential plateau. The changes are both time and voltage dependent, and if inhibited, leave the relaxant effect of adrenaline unopposed.11. The findings are consistent with a cyclic AMP-mediated mechanism of the positive inotropic effect of adrenaline. However, the role of cyclic AMP in mediating the relaxant effects of adrenaline is less clear.

Animals↗

In vitro studies with cefaclor, a new oral cephalosporin.

In vitro studies were performed to evaluate the activity of cefaclor in comparison with cephalexin against 180 clinical isolates. Broth dilution susceptibility tests showed cefaclor to be 4- to 16-fold more active than cephalexin against Streptococcus pneumoniae, Haemophilus influenzae, and cephalothin-susceptible Enterobacteriaceae. Neither drug was highly active against cephalothin-resistant Enterobacteriaceae or methicillin-resistant Staphylococcus aureus. Cefaclor zones with 30-mug disks were generally larger than cephalexin zones, 4 mm larger than cephalothin zones against Enterobacteriaceae, and 6 mm smaller than cephalothin zones against S. aureus. Quantitative kill curves indicated that killing by both cefaclor and cephalexin was slow and often incomplete over a 24-h period. Cefaclor-induced filamentation of gram-negative bacilli was not as extensive as that produced by cephalexin, and some spherule formation did occur. However, cefaclor was significantly more unstable in solution than cephalexin, with a half-life of less than 6 h at 37 degrees C. Thus, results obtained in tests after prolonged incubation may not provide an accurate measure of cefaclor's activity.

Bacteria↗

Autopsy report.

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Adolescent↗