ABSTRACT
Activation of hormone receptors was recently found to evoke oscillations of the cAMP concentration ([cAMP]) beneath the plasma membrane of insulin-secreting cells. Here we investigate how different time courses of cAMP signals influence the generation of cytoplasmic Ca(2+) signals and nuclear translocation of the PKA (protein kinase A) catalytic subunit in individual INS-1 beta-cells. [cAMP] was measured with a fluorescent translocation biosensor and ratiometric evanescent wave microscopy. Analysis of PKA nuclear translocation was performed with epifluorescence microscopy and FlAsH (fluorescein arsenical helix binder) labelling of tetracysteine-tagged PKA-Calpha subunit. Both oscillatory and stable elevations of [cAMP] induced by intermittent or constant inhibition of phosphodiesterases with isobutylmethylxanthine evoked Ca(2+) spiking. During [cAMP] oscillations, the Ca(2+) spiking was restricted to the periods of elevated [cAMP]. In contrast, only stable [cAMP] elevation induced nuclear entry of FlAsH-labelled PKA-Calpha. These results indicate that oscillations of [cAMP] lead to selective target activation by restricting the spatial redistribution of PKA.
Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Insulin-Secreting Cells/metabolism , Active Transport, Cell Nucleus , Animals , Calcium/metabolism , Catalytic Domain , Cell Line, Tumor , RatsABSTRACT
Embolization using poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel particles, of cylindrical spherical form, was successfully achieved in 42 children treated for non-operable haemangiomas of the liver, and angiodysplasias. Spherical PHEMA hydrogels appeared to be the only possibility for the treatment of 26 children suffering from extensive cavernous haemangiomas of face and neck. Particles were able to cover the tumour, stop its growth and allow the use of local hyperthermia with the electromagnetic field. A partial two-stage embolization using beaded PHEMA was also used as part of the multistage treatment for curing the spleen in 28 children suffering from haemolytic spherocytic anaemia, thrombocytopenic purpura and portal hypertension.
Subject(s)
Angiodysplasia/therapy , Chemoembolization, Therapeutic , Head and Neck Neoplasms/therapy , Hemangioma/therapy , Liver Neoplasms/therapy , Polyhydroxyethyl Methacrylate/administration & dosage , Adolescent , Anemia, Hemolytic/therapy , Chemoembolization, Therapeutic/methods , Child , Child, Preschool , Combined Modality Therapy , Cryosurgery/methods , Humans , Hypertension, Portal/therapy , Hyperthermia, Induced/methods , Infant , Purpura, Thrombocytopenic/therapy , SpleenABSTRACT
Effects of metabolites of testosterone and of anabolic androgens on bone marrow and thymus of ovariectomized mice were studied. Steroids contained in capsules made of silastic tubing were implanted on the day of castration or were injected at the day of castration (Noralone and T.P.), lymphatic organs were examined two weeks later. It was found that testosterone, 5 alpha-DHT, 3 alpha-diol, Dianabole, T.P., and Noralone caused increases in the relative number of large cells and in activity of 20 alpha SDH in bone marrow. Concomitantly, these steroids caused a marked reduction in thymus cell number and an increase in the responsiveness of the thymus cells to Con A and PHA. The steroid 3 beta-diol increased marrow cell 20 alpha SDH activity but did not affect the thymus cell number. Other steroids tested, Ad-dione 3 alpha or 3 beta-androsterone, 5 beta-DHT, epitestosterone, and progesterone had no effect on thymus or bone marrow.
