Freeze-fracture study of the crayfish stretch receptor

The crayfish slow-adapting stretch receptor was fixed under relaxed or stretched conditions (twice the relaxed length) and then processed for freeze-fracture study. The sensory neuron membrane had evenly distributed intramembrane particles mostly on its P face. The density of these particles was higher in the cell body than in the dendritic tips, which are the terminal portions of the dendrites. The dendritic tips were cylindrical under the relaxed condition and showed deformations with stretch stimuli. When they were fixed under the stretched condition with 1.6% glutaraldehyde in 0.12 M phosphate buffer (the total osmolarity of this fixative is isosmotic with the physiological solution), the dendritic tips showed regional swelling and shrinkage. The intramembrane particle density of the swollen parts decreased and there were particle-free patches of membrane, whereas the particle density of the shrunken parts increased. On the other hand, when the receptor was fixed with 1.6% glutaraldehyde in 0.2 M phosphate buffer (the total osmolarity is hyperosmotic but buffer osmolarity is isosmotic), the diameter of the dendritic tips became smaller, and their membrane particle densities were almost the same as that under the relaxed condition. The sheath cells covering the sensory neuron were characterized by their sheet-like profiles, gap junctions, and crater-like protrusions. The receptor muscle membrane had longitudinal foldings, occasional invaginations, peripheral couplings, stringshaped particle aggregates, and band-shaped particle aggregates.     

Coronary thrombosis in pathogenesis of acute myocardial infarction. Histopathological study of coronary arteries in 108 necropsied cases using serial section

An extensive histopathological study was carried out on the hearts of 108 patients with electrocardiographically proven acute myocardial infarction dying after admission to a coronary care unit. The occluded or the narrowest segments of the coronary arteries were examined at intervals of 100 mu using serial sections. Serial sectioning is important in such a study because the pathology of the lumen can vary considerably within a 2 to 3 mm segment. A high incidence (80.3%) of thrombus formation corresponding to the site of infarction was observed. These thrombi occluded the vessel lumen, were usually found proximally in the coronary arteries, and were associated with a ruptured atheromatous plaque in 90.8 per cent of cases. It is postulated that an increase of intraplaque pressure resulting from a honeycomb-like accumulation of foam cells, cholesterol clefts, and blood infiltration through the injured endothelial cells is the cause of rupture of the atheromatous plaque. This rupture into the vessel lumen may precede, and be responsible for, formation of thrombus and the onset of acute myocardial infarction.     

Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia

Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.