Pattern Formation in the Longevity-Related Expression of Heat Shock Protein-16.2 in Caenorhabditis elegans.

Aging in Caenorhabditis elegans is controlled, in part, by the insulin-like signaling and heat shock response pathways. Following thermal stress, expression levels of small heat shock protein-16.2 show a spatial patterning across the 20 intestinal cells that reside along the length of the worm. Here, we present a hypothesized mechanism that could lead to this patterned response and develop a mathematical model of this system to test our hypothesis. We propose that the patterned expression of heat shock protein is caused by a diffusion-driven instability within the pseudocoelom, or fluid-filled cavity, that borders the intestinal cells in C. elegans. This instability is due to the interactions between two classes of insulin-like peptides that serve antagonistic roles. We examine output from the developed model and compare it to experimental data on heat shock protein expression. Given biologically bounded parameters, the model presented is capable of producing patterns similar to what is observed experimentally and provides a first step in mathematically modeling aging-related mechanisms in C. elegans.

Mathematical model of radiation effects on thrombopoiesis in rhesus macaques and humans.

A mathematical model that describes the effects of acute radiation exposure on thrombopoiesis in primates and humans is presented. Thrombopoiesis is a complex multistage dynamic process with potential differences between species. Due to known differences in cellular radiosensitivities, nadir times, and cytopenia durations, direct extrapolation from rhesus to human platelet dynamics is unrealistic. Developing mathematical models of thrombopoiesis for both humans and primates allows for the comparison of the system's response across species. Thus, data obtained in primate experiments can be extrapolated to predictions in humans. Parameter values for rhesus macaques and humans were obtained either from direct experimental measurements or through optimization procedures using dynamic data on platelet counts following radiation exposure. Model simulations accurately predict trends observed in platelet dynamics: at low radiation doses platelet counts decline after a time lag, and nadir depth is dose dependent. The models were validated using data that was not used during the parameterization process. In particular, additional experimental data was used for rhesus, and accident and platelet donor data was used for humans. The model aims to simulate the average response in rhesus and humans following irradiation. Variation in platelet dynamics due to individual variability can be modeled using Monte Carlo simulations in which parameter values are sampled from distributions. This model provides insight into the time course of the physiological effects of radiation exposure, information which could be valuable for disaster planning and survivability analysis and help in drug development of radiation medical countermeasures.

[Precocious puberty and laugh attacks]. / Pubertas praecox und Lachanfälle.

A 7 year old girl presented with precocious puberty and ictal laughter. Brief, repetitive, stereotyped attacks of laughter were the first manifestation of the epileptic syndrome. Stages of puberty were noted as B III-IV and PH II according to Tanner. X-rays showed a bone age of 11 years and the weight increased from the 50th beyond 97th percentile. Plasma concentrations of LH, FSH, testosterone and Ostradiol were elevated. The CT scan was normal and a magnetic resonance imaging showed an hypothalamic hamartoma. The control of the seizures control and social adjustment were poor. MR scanning 3 years later showed no change in the size of the lesion.

Incidence of malignant neoplasms of all types of patients with Graves' disease.

The incidence of malignancy among patients with Graves' disease who were residents of one Minnesota county was examined in 342 patients between 1935 and 1967. During 4,736 person-years of observation, 32 malignancies were diagnosed; 24 cases were expected and the difference is not significant. Four cases of breast carcinoma were found vs five expected. Other tumor sites were cervix (five), uterus (two), rectosigmoid colon (three), stomach (two), larynx (two), and lung (two). There were three cases of leukemia, and in nine other sites one cancer each was recorded. There was a slightly higher than expected incidence of malignancy in patients who had received 131I therapy; this finding requires further study in a larger patient population. Among patients who received thyroid hormone, the observed incidence of breast cancer was not significantly different from the expected incidence in our population.