Coronary vascular endothelial cells release substances into the coronary circulation that modify the contractile system of cardiac myocytes, and cardiac myocytes may release factors that modulate the secretion of cardioregulatory substances by endothelial cells. This regulatory loop is sensitive to the rate of coronary flow and tissue oxygen tension. In the present study, coronary venous effluent from isolated perfused hearts and the contents of the coronary vascular endothelial cells have been collected, the latter by disrupting the cells with coronary perfusion at high pressure. The relative amounts of upregulating and downregulating factors in both collections have been estimated by assaying their effects on the contractility of isolated cardiac trabeculas. The amount of upregulating factor stored in the endothelial cells is sensitive to the rate of coronary flow just before disruption of the cells. The quantity of endothelin in the coronary venous effluent and in the vascular endothelial cell contents was measured by radioimmunoassay and compared with the degree of upregulation of contractility produced by the two types of solutions. Upregulation was never produced in the absence of endothelin. The extent of the increase in contractility that was observed with endothelial cell contents correlated with the concentration of endothelin and was approximately the same as the increase in contractility from similar concentrations of endothelin added to standard Krebs' solution. The amount of the increase in contractility from coronary effluent could be accounted for by the concentration of endothelin in the effluent with the additional presence of some downregulating factor as well. The endothelin antagonist BQ123 inhibited the upregulation from coronary perfusate. It appears that endothelin alone can account for all of the upregulation of contractility produced by the vascular endothelial cells. Coronary flow, probably through shear forces, seems to regulate the production of endothelin possibly from an inactive precursor. Tissue oxygen tension appears to modulate the rate of release of the endothelin from endothelial cells though substances released by cardiac myocytes or other cells in the tissue. The downregulating factor is stored to a much smaller extent.
Brief reports 2 8 7 plasma cells. The abundant free eosinophilic material also stained for kappa light chain. It was concluded that the nodules represented a plasmacytoma, producing abundant extracellular immunoglobulin which was being ingested by macrophages in particular, but also by alveolar and bronchiolar epithelial cells. Nine years later the patient is well and has no evidence of recurrence or of myelomatosis: he has no abnormal serum or urine immunoglobulin and no skeletal abnormalities: total serum protein is 79.8 g/1 and there are no abnormal fractions. DiscussionCrystalline cytoplasmic inclusions have been described in both normal and neoplastic plasma cells, in macrophages in both myelomatosis and solitary plasmacytomas and in renal epithelium in myelomat~sis~-~. The uptake of immunoglobulin by airway epithelial cells, demonstrated in this case, is unusual but not surprising as some of these cells normally process immunoglobulin A, adding secretory piece as this immunoglobulin crosses the epitheliumb. What defeated the initial diagnostic attempts in this case was the sparsity of plasma cells and the marked local deposition of their secretory product. Electronmicroscopy suggested the correct diagnosis which was confirmed by immunocytochemistry. Addis BJ. Lymphoproliferative disease. In Corrin B ed. The Lungs. Edinburgh: Churchill Livingston. 1990: 328. Addis BJ. Isaacson P. Billings JA. Plasmacytoma of lymph nodes. Cancer 1980: 46; 340-346. Mullen B, Chalvardjian A. Crystalline tissue deposits in a case of multiple myeloma. Arch. Pathol. Lab. Med. 1981: 105; 94-97. Chejfec G. Natarelli J, Gould VE. 'Myeloma lung'--a previously unreported complication of multiple myeloma. Hum. Pathol. 1983: Yamamoto T, Hishida A. Honda N. Ito I, Shirasawa H. Nagase M. Crystal-storing histiocytosis and crystalline tissue deposition in multiple myeloma. Arch. Pathol. Lab. Med. 1991: 115: 351-354. Goodman JR, Link DW. Brown WR. Nakane PK. Ultrastructural evidence of transport of secretory IgA across bronchial epithelium. Am. Rev. Resp. Dis.
The aim of this study was to determine if endothelial cells in the heart release substances into the coronary perfusion medium that modify the contractility of myocardial cells. To assay the effects on the contractility of cardiac muscle of fluid that has passed through the coronary vasculature, a new method has been developed based on the cascade principle used to study vascular smooth muscle function. The coronary venous effluent from an isolated perfused working heart was collected periodically, and after reoxygenation it was used as the bathing medium for trabeculae isolated from the endocardial surface of another heart. The coronary venous effluent changed the contraction of the isolated trabeculae. The amplitude and the direction of the change depended on the degree of oxygen saturation of the coronary effluent before it was reoxygenated and the rate of coronary flow at the time the effluent was collected. The response of the trabecula to the coronary effluent was substantially altered by damaging the endocardial endothelium with a 1-second exposure to 0.5% Triton X-100 in Krebs' solution. It was completely eliminated by damaging endothelial cells in both the perfused heart producing the effluent and the trabecula on which the effluent was assayed. Therefore, endothelial cells are required for the presence of cardioactive substances in the coronary effluent. The production of a labile endothelium-derived upregulating (positively inotropic) factor and a more stable endothelium-derived downregulating (negatively inotropic) factor has been demonstrated and appears to account for all of the changes in myocardial contractility produced by the coronary effluent. Neither of the endothelium-derived substances demonstrated in the isolated perfused heart is nitric oxide or endothelin. The concentration of the endothelium-derived upregulating factor is sensitive to oxygen tension, whereas the concentration of the endothelium-derived downregulating factor is sensitive to the rate of coronary flow but not oxygen tension. The coronary effluent appears to contain substances that stimulate secretion by the endothelial cells (preendothelial factors) as well as substances that have been produced by the endothelial cells (endothelial factors). The results indicate that during the passage of perfusion medium through the coronary vasculature upregulating and downregulating factors are added to the perfusate in relative concentrations that depend at least in part on local tissue PO2 and the rate of coronary flow. In the intact heart, this mechanism could operate to maintain balance between energy supply and work performed.
Carcinosarcoma of the salivary glands are rare tumours, often associated with a history of pleomorphic adenoma. A case of carcinosarcoma of the parotid arising following irradiation to the resection site of a pleomorphic adenoma is presented. The clinical and histological features are discussed and the literature reviewed.
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