Calpain mediates caspase-dependent apoptosis initiated by hydrogen peroxide in pancreatic acinar AR42J cells.

Several studies have shown that oxidative stress induces apoptosis in many cellular systems including pancreatic acinar cells. However, the exact molecular mechanisms leading to apoptosis remain partially understood. This study aimed to investigate the role of the cytosolic cysteine protease calpain in H2O2-induced apoptosis in pancreatic AR42J cells. Apoptosis was evaluated using flow cytometric analysis of sub-G1 DNA populations, electron-microscopic analysis, caspase-3-specific αII-spectrin breakdown, and measuring the proteolytic activities of the initiator caspase-12 and caspase-8, and the executioner caspase-3. H2O2 induced an increase in the calpain proteolytic activity immediately after starting the experiments that tended to return to a nearly normal level after 8 h and could be attributed to m-calpain. Whereas no caspase-12, caspase-8 and caspase-3 activations could be detected within the first 0.5 h, significantly increased proteolytic activities were observed after 8 h compared with the control. At the same time, the cells showed first ultrastructural hallmarks of apoptosis and a decreased viability. In addition, αII-spectrin fragmentation was identified using immunoblotting that could be attributed to both calpain and caspase-3. Calpain inhibition reduced the activities of caspase-12, caspase-8, and caspase-3 leading to a decrease in the number of apoptotic cells. Immunoblotting analyses of caspase-12 and caspase-8 indicate that calpain may be involved in the activation process of both proteases. The results suggest that H2O2-induced apoptosis of AR42J cells requires activation of m-calpain initiating the endoplasmic reticulum stress-induced caspase-12 pathway and a caspase-8-dependent pathway. The findings also suggest that calpain may be involved in the execution phase of apoptosis.

Explaining human movements and actions: children's understanding of the limits of psychological explanation.

Human actions and movements can be caused by psychological states (e.g. beliefs and desires), physical forces (e.g. gravity) and biological processes (e.g. reflexes). In three studies we explored young children's understanding of the causes of human movements in order to examine their ability to differentiate and coordinate psychological, physical and biological reasoning to account for the activities of one single entity--a human being. In Study 1, 4-year-olds explained characters' voluntary actions, mistakes, physically-caused and biologically-caused behaviors and movements. Children gave psychological explanations for the intended actions and mistakes, but biological and physical explanations for the biologically-caused and physically-caused movements. Studies 2 and 3 extended the investigation to younger children (3-year-olds), encompassed a greater variety of items, and used several converging methods in order to examine children's judgments and explanations. Consistently, 3- and 4-year-olds gave appropriately different responses and explanations to the different item types. These findings show that far from viewing people in strictly psychological terms, young children evidence multiple causal-explanatory construals of human behavior. We discuss the implications of these findings for children's everyday psychological, physical, and biological theories. One implication of the findings is that young children do not assume a match between entities and theories (persons-psychology, objects-physics). If they do not, this raises the question of what information they use to decide which explanatory system fits which events.

Young children's understanding of thought bubbles and of thoughts.

In a series of 4 studies, we explored preschoolers' understanding of thought bubbles. Very few 3-year-olds or 4-year-olds we tested knew what a thought-bubble depiction was without instruction. But, if simply told that the thought bubble "shows what someone is thinking," the vast majority of 3-year-olds and 4-year-olds easily understood the devices as depicting thoughts generally and individual thought contents specifically. In total, these children used thought-bubble depictions to ascertain the contents of characters' thoughts in a variety of situations; appropriately distinguished such depictions from mere associated actions or objects; described thought bubbles in the language of mental states; judged that persons' thoughts in these depictions were subjective in the sense of person-specific (and hence 2 people can have different thoughts about the same state of affairs); and judged that thought-bubble thoughts (a) were representational in the sense of depicting or showing some other state of affairs, (b) were mental and thus showed intangible, private, internal thoughts unlike real pictures or photographs, and (c) can be false, that is, can depict a person's misrepresentation of some state of affairs. We discuss the implications of these findings for young children's understanding of thoughts and thought bubbles, for their learning and comprehension of pictorial conventions, and for the use of thought bubbles to assess children's early understanding of mind.

[Side effects of BCG immune therapy in 511 patients with malignant melanoma]. / Nebenwirkungen der BCG-Immuntherapie bei 511 Patienten mit malignem Melanom.

The main side-effects of BCG vaccination by scarification in 511 patients with malignant melanoma since 1974 have been fatigue and exhaustion, swelling of the lymph-nodes, influenza-like symptoms, nausea and dizziness. Only in 8 patients were the side-effects more severe, requiring the cessation of treatment in some of them. One patient developed granulomatous hepatitis, another experienced a reactivation of pulmonary tuberculosis. Allergic reactions occurred in two patients. A further patient developed recurrent erysipelas in the draining areas of the scarification. In two patients we observed continuous severe joint troubles, which were not due to metastatic disease. The eighth patient developed keloids at the vaccination sites on the upper arms. One third of the patients had no side-effects. Altogether vaccinations were tolerated well by most of the patients. Nearly all of them were able to work normally.