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The contribution of pfcrt polymorphisms to drug efflux phenotype by investigating a series of Plasmodium falciparum clones differing only in their pfcrt allele is assessed. Allelic exchange mutants of pfmdr1, encoding a homologue of the human multidrug resistance efflux pump, are investigated.

Mutational analysis for elucidating the role of P-glycoprotein to confer multidrug resistance in cancer therapy and drug-induced conformational changes in the protein reveal that mutations alter drug transport by the protein as well as the affinity and number of the drug-binding sites of the protein.

Results reveal that the conformational changes in the P-glycoprotein are caused by binding and debinding of nucleotides as shown by the use of the conformation-sensitive monoclonal antibody UIC2. The data are interpreted using a conventional E1/E2 model.

Results reveal that colchicine enhances the monoclonal antibody UIC2 reactivity in some P-glycoprotein expressing cell lines, which correlates with UIC2 transport by the glycoprotein. Data further indicate that glycoprotein meidated ATP hydrolysis counteract cochicine induced protein conformation.

I. INTRODUCTION Most cancer deaths result from the cancer's either being intrinsically resistant to chemotherapeutic drugs or becoming resistant after being initially sensitive (127). Often, in cells grown in cell [...]

This article proposes a novel model of calcium homeostasis, based on the concept of a series of bone calcium-binding sites of varying calcium affinities. When an i.v. Ca load is administered to mammals, it is rapidly ([t.sub.1/2] < 1 min) dispersed into a volume equivalent to the extracellular fluid. Thereafter the calcium concentration drops monoexponentially with a [t.sub.1/2] of tens of minutes. When a negative Ca load is administered, as by EDTA injection, the return to the preinjection plasma Ca level, [[Ca.sub.s]], occurs also monoexponentially at the same rate as restoration after a positive load. The numerical value of the rate can be arrived at by taking into account the fraction of cardiac output (5%) that is directed to the skeleton. Acute regulation is brought about by controlling access to subpopulations of the Ca binding sites, whose average [K.sub.m] determines [[Ca.sub.s]]. Osteoblasts, when active and extended, block low-affinity binding sites; osteoclasts, when active and extended, block high-affinity sites. Exposure of sites is brought about when bone cells respond by rapid shape changes, osteoblasts rounding up in response to parathyroid hormone (PTH) or vitamin D, osteoclasts rounding up in response to calcitonin. These shape changes are the first steps in the cascade of events that lead to bone formation and resorption, but acute regulation need not involve the latter steps of a cascade. The model accounts for the changes in the response times to Ca loads that have been observed in older animals or those deprived of PTH, calcitonin or vitamin D. INDEXING KEY WORDS: osteoblasts; osteoclasts; parathyroid hormone; calcitonin; vitamin D

The function of calbindin, a calcium-binding protein, in the transportation of calcium across the intestinal mucosa is investigated. Evidence indicates that calcium absorption across the brush border of the intestinal epithelium is possible only in the presence of calbindin. The transfer of calcium from the luminal pole to the basolateral pole of the intestinal cell is likewise affected by the amount of calbindin present and the dissociation constant of the calcium-calbindin conjugate. Similarly it is proposed that an acidity gradient will facilitate calcium transport.