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We describe a patient who had the recent onset of both primary hyperparathyroidism and parkinsonism. Surgical removal of a parathyroid adenoma was followed by spontaneous resolution of the parkinsonism. Hypoparathyroidism and other disorders of calcium metabolism are recognized causes of secondary parkinsonism, while hyperparathyroidism is not. We review the relevant literature, which supports the hypothesis that hypercalcemia may have induced cytotoxic changes in the basal ganglia of this patient. (Arch Intern. Med. 1993; 153:1134-1136)

We have investigated the formation of the prestalk-prespore pattern in Dictyostelium discoideum. Pattern formation occurs in clumps of Dictyostelium cells embedded in agar under a 100% oxygen atmosphere. Agar embedding allows us to control spatially the environment surrounding the cell clumps. Our results suggest that the ambient oxygen concentration plays a role in controlling the size of the multicellular mass. Further, oxygen gradients established across clumps embedded in agar or held in holes in a plastic barrier cause orientation of the prestalk-prespore pattern such that the anterior prestalk region forms at the highest end of the gradient. The results also indicate that developing cells have the ability to migrate up a gradient of oxygen.

Interstitial stem cells in Hydra are rapidly proliferating multipotent stem cells which continuously give rise to precursors for nerve and nematocyte differentiation. Growth of the stem cell population is controlled by the cell cycle time of the stem cells and the self-renewal probability, Ps (the fraction of stem cells in each generation which divide to yield more stem cells). In normal Hydra the stem cell generation time is 24 h and Ps = 0.6; under these conditions the stem cell population doubles in 3.5 days. In the present experiments we have systematically investigated the dependence of Ps on stem cell density. We culture stem cells in a feeder layer system consisting of aggregates of nitrogen-mustard (NM)-inactivated Hydra cells. In this system stem cell density can be varied over a wide range by changing the number of clone-forming units (CFU) added to the aggregates. We have measured the growth rate of the stem cell population and the cell cycle of stem cells in NM aggregates after 4–7 days of culture. From these data we calculate the value of Ps. The results indicate that the growth rate decreases 4-fold as the number of CFU seeded per aggregate increases from 10 to 400. Under these same conditions the cell cycle remains constant. The values of Ps calculated from these results indicate the Ps decreases from 0.75 in aggregates seeded with 10–30 CFU to 0.55 in aggregates seeded with 200–400 CFU. These results support a model in which Ps is controlled by negative feedback from neighbouring stem cells. In addition, our experiments indicate that Ps decreases during the growth of stem cell clones. When only a few stem cells are seeded in aggregates, they give rise to isolated clones distributed throughout the aggregate. Ps decreases markedly within such clones as they grow in size presumably due to increasing stem cell content of the clones. Since Ps in such isolated clones declines with growth, we infer that the local stem cell concentration is what controls Ps and that the spatial range of the negative feedback signal is short compared to the dimensions of NM aggregates.

The differentiation of nerve cells and nematocytes from interstitial stem cells in Hydra has been investigated under conditions of changing stem cell density. Interstitial stem cells were cultured in a feeder layer system consisting of aggregates of nitrogen mustard-inactivated tissue. The aggregates were seeded with varying numbers of stem cells from 10 to 400 per aggregate; between 4 and 7 days later the rates of nerve and nematocyte differentiation were measured. Nerve differentiation was scored by labelling the stem cell population with [3H]-thymidine and counting nests of 4 proliferating nematoblasts. In both cases the numbers of differentiating cells were normalized to the size of the stem cell population. The results indicate that the rate of nematocyte differentiation increases as the concentration of stem cells increases in aggregates; under the same conditions the rate of nerve differentiation remains essentially constant. To calculate the numbers of stem cells entering each pathway per generation, a computer was programmed to simulate the growth and differentiation of interstitial stem cells. Standard curves were prepared from the simulations relating the rates of nerve and nematocyte differentiation to the fraction of stem cells committed to each pathway per generation. The rates of nerve and nematocyte commitment were then estimated from the experimentally observed rates of differentiation using the standard curves. The results indicate that nerve commitment remains constant at about 0.13 stem cells per generation over a wide range of stem cell concentration. Nematocyte commitment, by comparison, increases from 0.15 to 0.21 stem cells per generation as stem cell concentration increases in aggregates. The fact that the ratio of nerve to nematocyte commitment changes under our conditions suggests that stem cell commitment is not a stochastic process but subject to control by environmental stimuli.

Differentiation of Dictyostelium amoebae can occur in submerged clumps of cells; under an oxygen atmosphere mature stalk cells and spores form, as has been shown in previous work. This report shows that at least 2 factors are released by the cells under these conditions, and that both, together, are required for differentiation of stalk cells and spores. One of the factors is ammonia (NH3 + NH4+). The other factor(s) is heat stable and dialysable but has not yet been further characterized. The factors can be collected in conditioned medium and, when added to cells, stimulate differentiation. Conditioned medium loses its biological activity upon the removal of the NH3 + NH4+. When NH3 + NH4+ is added back, activity is restored. Because NH3 + NH4+, alone, has no activity, a second factor(s) in the conditioned medium must be required for differentiation. It is also shown that calcium inhibits differentiation in submerged clumps and that in calcium-free medium the timing of differentiation is essentially the same as under aerial conditions.