2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Specific binding of acidic isoferritins to erythroleukemia K562 cells

An investigation of ferritin binding by human erythroleukemia K562 cells was prompted by recent studies suggesting that acidic isoferritins may act as regulators of granulopoiesis and hemopoiesis. Purified human heart and liver ferritins were labeled with iodine 125 and incubated with K562 cells at 37 degrees C. Specific uptake was calculated from the reduction in labeled ferritin binding in the presence of a 1000-fold excess of unlabeled ferritin. Specific uptake of 125I-labeled heart ferritin increased progressively, reaching a maximum after 2 to 3 hours' incubation, although nonspecific binding was too high to derive an affinity constant. There was no specific binding with 125I-labeled liver ferritin, and K562 cells bound neither 125I-labeled human serum albumin nor free 125I. Uptake of heart ferritin was negligible at 4 degrees C and was sharply reduced in the presence of 10% human plasma or fetal calf serum. There was no apparent relationship between the number of days of subculture and the level of uptake of acidic isoferritins by whole cells. These studies demonstrate a selective binding mechanism for acidic isoferritins on erythroleukemia cells and imply that these isoferritins have additional functions besides the storage of iron.     

Wheat germ agglutinin conjugated to TRITC: a novel approach for labeling primary projection neurons of peripheral afferent nerves

Wheat germ agglutinin conjugated to tetramethylrhodamine isothiocyanate-dextran (WGA-TRITC) was studied as a novel tracer of primary projection neurons of pharyngeal (PhN) and superior laryngeal (SLN) branches of the vagus nerve. The SLN and PhN were dissected from rat cervical tissues and the proximal end of the nerves were bathed in tracer for 60-90 min. The animals were sacrificed 42-72 h later. The tissue was fixed, sliced, mounted on slides and viewed under epifluorescence. The clarity of the fluorescent label in projection neurons was confounded in some regions of the brainstem by autofluorescence. A computer image analysis method was developed to quantify fluorescence intensity for definitive identification of labeled neurons. Brainstem neurons labeled by afferent projections of the SLN and PhN were localized to the nucleus tractus solitarius. Efferents were identified in the nucleus ambiguus. WGA-TRITC labeled cells were observed in the ipsilateral brainstem at intensities significantly different from the fluorescence observed in controls (P<0.01). The distribution and density of labeling is in agreement with results of previous investigations, suggesting that WGA-TRITC is a useful alternative for tracing SLN and PhN projections to brainstem nuclei.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog

Intramyocardial hemorrhage often occurs with reperfusion in experimental acute myocardial infarction and is thought to be associated with extension of necrosis. To determine if hemorrhage was associated with extension of necrosis, 20 anesthetized dogs were reperfused after 6 hours of circumflex coronary artery occlusion and 10 others had control occlusion with no reperfusion. Fifteen of the 20 reperfused dogs had gross hemorrhage and none of the control dogs did. In 12 reperfused and 10 control dogs, radioactive microspheres were injected after coronary occlusion to quantitate collateral flow and in the reperfusion group microspheres were injected to quantitative reflow. Complete flow data were available in eight reperfused and 10 control dogs. Twenty-four hours after coronary occlusion, 1-g segments of infarct and control regions were analyzed for hemorrhage, collateral flow and creatine kinase activity. Serial microscopic examination was performed in eight additional dogs reperfused after 6 hours to determine if hemorrhage occurs into otherwise microscopically normal myocardium. Pathologic examination indicated that hemorrhage did not occur into otherwise microscopically normal myocardium. In dogs with hemorrhage, the extent of hemorrhage was inversely related to myocardial creatine kinase concentration and collateral flow. Mean collateral flow in 47 hemorrhagic segments was 4.5 ml/100 g (4.2% of control). Mean creatine kinase in 36 hemorrhagic segments was 233 mIU/g (21% of control). No hemorrhage was found in areas with collateral flow more than 21% of control or creatine kinase more than 37% of control. Mean reflow in hemorrhagic segments was 78.5% of control flow. These studies indicate that hemorrhage on reperfusion is associated with severe myocardial necrosis and markedly depressed flow before reperfusion and thus occurs only into myocardium already markedly compromised at the time of reperfusion. There is no evidence for hemorrhage into areas that had normal or even moderately depressed flows before reperfusion.