Effective salvage therapy for refractory disseminated breast cancer with 5-fluorouracil and high-dose continuous infusion folinic acid.
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Biomedical subjects
Publications and source records attributed to B Flanagan.
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Labeled proline from incubation media has been shown to be incorporated into living bone matrix collagen in vitro. Hydroxyproline is released from fresh bone slices in similar systems in a characteristic curve against time. This hydroxyproline is derived from three distinct sources, each of which may be separately quantitated. Part of the total represents passive solubilization of matrix collagen, part is derived from new synthesis of soluble collagen occurring in vitro, and the remainder is released by cell-mediated resorptive action. The latter two processes are linear with time up to 8 hr; the former decays to zero at about 2 hr. Consequently, rates of collagen synthesis and of new collagen deposition and resorption can be quantitated simultaneously in the same system. The ability to measure these parameters of bone collagen metabolism provides methods both for the accurate evaluation of organic matrix resorption in vitro and for the accurate measurement of rates of collagen synthesis and collagen deposition. The application of the method is illustrated using parathyroid hormone and thyrocalcitonin. Parathyroid hormone diminishes collagen synthesis and stimulates collagen resorption. It reduces slightly the deposition of newly formed collagen in stable matrix. The net effect of these changes is to produce a marked negative balance. It does not significantly affect the solubility of matrix collagen.Thyrocalcitonin does not affect collagen synthesis or its deposition. It causes a marked fall in resorption rate. It has no effect on matrix collagen solubility. The net effect is to produce a marked positive balance of matrix collagen.
The rates of both formation and resorption of bone collagen may be accurately quantitated by kinetic analysis of hydroxyproline metabolism in vitro. Using this approach we have studied the changes in bone collagen turnover with age in the rat. The rates of synthesis and resorption of collagen decline with age although the resorptive activity per cell increases up to 6 months of age. The solubility of collagen declines with age. The fraction of the newly synthesized collagen which is deposited as matrix declines dramatically with age revealing a new and hitherto unsuspected aspect of the osteoporotic process. The collagen balance becomes progressively more negative over the 1st 6 months of life. These results indicate that even in an animal who is not subject to clinical osteoporosis, biochemical measurement reveals that such a trend exists. The application of this approach to human subjects is feasible and has important implications.
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Macaques were immunised with lentil lectin purified recombinant SIVmac (BK28) derived gp160 (rgp160) with or without live vaccinia (vac)-env (BK28) priming, followed by a final boost with solid matrix antibody antigen (SMAA)-gp160 (J5) complexes and challenged with the SIVmac molecularly cloned virus J5M. Rgp160 and vac-env plus gp160 induced strong Ab responses against the homologous virus. Live vac-env did not enhance or prolong the antibody response, however, T cell responses were stronger. Analysis of the specificity of the immune response demonstrated that sequence variation within SIVmac viruses can affect antibody and T cell recognition. A single booster immunisation with the heterologous SIVmac J5 env recombinant protein was not sufficient to protect against the molecularly cloned virus J5M. These findings further illustrate the difficulty of generating protective immunity with immunogens based on single sequence recombinants.