No abstract

Corticosterone production by isolated adrenal cells in response to adrenocorticotropic hormone is reduced when the cells are incubated in a medium that contains no calcium. This reduction is associated with an equal reduction of accumulation of cyclic adenosine monophosphate. Production of corticosterone and accumulation of cyclic adenosine monophosphate are increased when the calcium concentration in the medium is increased (from zero to 7.65 millimolar). This is in contrast to the situation in "subcellular membrane fragments" of adrenal tissue where high calcium in the medium (> 1.0 millimolar) inhibits cyclic adenosine monophosphate accumulation. We propose that adenyl cyclase in the intact plasma membrane is located in a compartment wherein calcium concentration is low and remains unaffected by the concentration of calcium in the extracellular space. It is proposed that, as the concentration of calcium in the incubation medium is increased from zero to 7.65 millimolar, the strength of the signal generated by the interaction of adrenocorticotropic hormone with its receptor and transmitted to the adenyl cyclase compartment is proportionately increased.

No abstract

Therapeutics development for cystic fibrosis (CF) involves a coordinated effort among many groups, including individuals with CF and their caregivers, clinical research teams, and those in academia and industry who have discovered and developed the therapeutic strategies. In the United States, the Cystic Fibrosis Foundation (CFF) has devoted over $875 million to facilitate and coordinate this process since 1986, resulting in the clinical development and/or assessment of ~50 drug candidates during that time. The more than 30 compounds currently in the pipeline of Foundation-funded therapeutics are used as a platform to discuss why and how therapeutic strategies are brought into clinical development. Consideration is also given to the funding, management, and infrastructure necessary and practical to support the progression of drug candidates and the availability of therapeutics for use by individuals with CF. The importance of the clinical trial process and relevant outcome measures to assess the efficacy of drug candidates is also discussed. Finally, the potential impact of the pipeline for individuals with CF is summarized.

No abstract