Cooperative interaction as the physical basis of the negative stiffness in hair cell stereocilia.

A recent report confirmed that stiffness of the stereocilia can be negative, as predicted by the Howard-Hudspeth model. According to this model, the mechanotransducer channel's gating not only reduces the stereociliary stiffness, but can alter its sign as well. The basic assumptions of this model do not include cooperativity in channel gating.

A positive-feedback model for the loss of acetylcholine in Alzheimer's disease.

We describe a two-component positive-feedback system that could account for the large reduction of acetylcholine that is characteristic of patients with Alzheimer's disease (AD). One component is beta-amyloid-induced apoptosis of cholinergic cells, leading to a decrease in acetylcholine. The other component is an increase in the concentration of beta-amyloid in response to a decrease in acetylcholine.

The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease.

We present a hypothesis for the loss of acetylcholine in Alzheimer's disease that is based on two recent experimental results: that beta-amyloid causes leakage of choline across cell membranes and that decreased production of acetylcholine increases the production of beta-amyloid. According to the hypothesis, an increase in beta-amyloid concentration caused by proteolysis of the amyloid precursor protein results in an increase in the leakage of choline out of cells. This leads to a reduction in intracellular choline concentration and hence a reduction in acetylcholine production.

Anomalous effects of hormone fragments on the measurement of parathyroid hormone by radioimmunoassay.

One of the basic assumptions underlying the use of radioimmunoassay and other competitive protein-binding assays is the homogeneity of the antigen or ligand. This assumption is not valid for the measurement of parathormone (PTH) because of the presence of fragments. Hence, there is a potential for errors and high variability in the measurement of parathyroid hormone (PTH) by radioimmunoassay.

Role of calcium channels in parathyroid hormone secretion.

Experimental evidence exists for the presence of parathyroid cell membrane calcium channels that respond to plasma calcium. In previous reports, the effects of various calcium channel agents on PTH secretion have revealed conflicting results. To resolve some of these inconsistencies, we have compared the pure calcium channel agonist, (+)202-791, and its antagonistic enantiomer (-)202-791 with other calcium channel agents--verapamil, nifedipine, and (+)Bay-K-8644.