Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the kallikrein-kinin and anticoagulation blood systems was studied in dogs with experimental myocardial infarction. Changes were revealed in the kallikrein-kinin system which create conditions for uncontrolled production of kinins in the first 24 hours of the disease. A direct correlation was detected between the activity of kallikrein and plasmin in the first three days of experimental myocardial infarction, which the authors claim to be a pathophysiological reaction of the body because it is conductive to the uncontrolled production of kinins. It is also noted that in this pathological process the depression of the anticoagulation system in the first two days is mainly due to reduced activity of nonenzymatic fibrinolysis, while, beginning with the third day, it is caused by reduced activity of enzymatic fibrinolysis, increased antiplasmin activity in particular.
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PMID:[Interrelation of the blood kallikrein-kinin and anticoagulation systems in experimental myocardial infarct]. 691 43

Previous research has shown that disseminated intravascular coagulation causes a depression in RE function. Fibronectin, a high-molecular-weight surface-binding glycoprotein, is known to modulate RE function by facilitating opsonic activity and is sensitive to proteolytic cleavage by plasmin, yielding FNDP. The present investigation suggests that isolated FNDP, generated in vitro by incubation with plasmin, can depress phagocytosis in vivo as well as in vitro. Phagocytosis in rats was determined by a clearance technique employing CR51-RBCs and in vitro by employing a monolayer of peritoneal exudate macrophages. The in vivo studies demonstrated significantly reduced hepatic phagocytosis after the injection of FNDP an delayed clearance of injected test particles. Macrophage uptake in vitro, supported by either normal rat serum or purified fibronectin, was significantly reduced when incubated with FNDP. These results suggest that depression of the RE system and phagocytosis during intravascular coagulation may be mediated in part by the formation of plasmin degradation products of plasma fibronectin.
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PMID:Depression of phagocytosis by plasmin degradation products of plasma fibronectin. 725 34

To assess the blood coagulative and fibrinolytic responses during cemented femoral neck replacement, we measured these parameters in 9 patients, including anti-thrombin III (AT-III), prothrombin time (PT) and activated partial thromboplastin time (APTT) before surgery, just before packing bone cement and after the insertion of the prosthesis. We also measured thrombin-anti-thrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC), and D-dimer. A significant increase in APTT, and decrease in AT-III and PT were observed before the insertion of bone cement and prosthesis. The value of TAT and D-dimer increased significantly after the insertion of the prosthesis, but there were no significant changes in PIC. The data suggest that blood coagulation is activated after the insertion of bone cement and prosthesis into the femoral shaft, and in addition, the fibrinolysis is also accelerated secondary to the activation of the coagulation. Further investigations are needed to establish whether the activation of the coagulation induced by the cemented replacement exerts a great influence on the appearance of pulmonary thrombosis or circulatory depression.
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PMID:Blood coagulation and fibrinolytic activity during femoral neck prosthetic replacement using bone cement. 760 97

Faster growth is observed in cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to cells from normotensive Wistar Kyoto (WKY) rats. It has been reported that transforming growth factor-beta (TGF beta), a bifunctional growth factor, shows higher mRNA accumulation in VSMC from SHR. Antisense oligodeoxynucleotide (ODN) complementary to TGF beta 1 mRNA significantly suppressed DNA synthesis of VSMC from SHR at high cell density in a dose-dependent manner, but elicited little inhibition of VSMC from WKY rats. Antisense ODN resulted in a depression of the cell number increase in SHR VSMC only. While DNA synthesis of VSMC was inhibited by antisense ODN at high cell density, it was stimulated at low cell density in both strains. In the presence of antisense ODN, plasmin, an activator of TGF beta, was unable to stimulate DNA synthesis of VSMC. These findings implicate a role of endogenous TGF beta in the exaggerated growth of VSMC from SHR.
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PMID:[Suppression of the exaggerated growth of vascular smooth muscle cells from SHR by antisense oligodeoxynucleotide to TGF beta]. 832 Aug 46

Fibrinolysis components were studied in 32 patients with slight and 38 ones with grave craniocerebral injuries on days 1, 3, 5, and 7 after the injury. No expressed disorders of blood fibrinolytic activity were revealed in patients with slight injuries. Grave craniocerebral injuries were associated with disorders of the plasmin system. Depression of the external and internal mechanisms of fibrinolysis were the most manifest starting from day 3 and caused by a number of factors characteristic of the developing disseminated intravascular blood coagulation syndrome and, possibly, by impaired regulation of the plasmin system by the central nervous system.
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PMID:[The possible mechanisms of a fibrinolytic disorder in patients with severe craniocerebral trauma]. 868 39

Respiratory distress syndrome (RDS) is characterized by the presence of fibrin-rich exudates in the alveoli. Fibrin and its degradation products may play an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). The purpose of this study was to test the hypothesis that preterm neonates with RDS have depressed alveolar fibrinolytic activity and that those with RDS progressing to BPD have an even greater impairment in alveolar fibrinolysis. Serial tracheal aspirate (TA) samples from intubated neonates--9 control and 46 with RDS--were analyzed for fibrinolytic activity. In neonates with RDS, 26 resolved, 18 progressed to BPD, and 2 died before 28 d. Plasminogen activator (PA) and its inhibitor (PAI) were identified in TA by reverse fibrin autography and immunoblotting. Net PA/plasmin activity in TA was significantly depressed on d 1 of life in patients with self-resolved RDS (median = 20.85 ng/mL, p < 0.05) and RDS progressing to BPD (median = 4.97 ng/mL, p < 0.001) compared with control patients (median = 87.1 ng/mL). In addition, neonates progressing to BPD had significantly lower PA/plasmin activity on day one of life compared with neonates with self-resolved RDS (p < 0.001). ELISA for specific PA and PAI were not significantly different. We speculate that depressed fibrinolytic activity may place preterm neonates at risk for RDS and that the degree of this depression may predict the progression to BPD. In infants < or = 30 wk of gestation at birth with RDS, a PA/plasmin activity < or = 10.0 ng/mL on the 1st d of life had a positive predictive value of 80% (12/15) and a negative predictive value of 82% (9/11) for the progression to BPD.
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PMID:Plasminogen activator activity in preterm infants with respiratory distress syndrome: relationship to the development of bronchopulmonary dysplasia. 882 92

Insulin-like growth factor-binding proteins (IGFBPs) modulate IGF action at cellular level, through either inhibition or potentiation, and they also have intrinsic activity that is independent of their binding to IGFs. In prostate carcinoma (PC-3) cells, which are capable of growth for several days in serum-free medium, non-glycosylated recombinant human IGFBP-3 (rhIGFBP-3) had a biphasic mitogenic effect, stimulation being dose-dependent up to 20 ng/ml, followed by progressive depression down to zero stimulation at 150-200 ng/ml. This mitogenic effect was not intrinsic activity, but involved IGF-II secreted by the cells, since stimulation was abolished in the presence of anti-type 1 IGF receptor antibody (alpha IR-3). Western ligand- and immunoblot analysis of the culture media revealed several IGFBP species, in particular IGFBP-3 which exhibited an electrophoretic profile characteristic of limited proteolysis. The amounts of the proteolytic fragments increased in parallel with the concentrations of added rhIGFBP-3, but a large amount of intact protein remained at the highest concentrations added. When a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulphonyl fluoride (Pefabloc SC), was added at concentrations demonstrated to be non-toxic to the cells, IGFBP-3 proteolysis was diminished and rhIGFBP-3-induced stimulation of proliferation was suppressed. Conversely, in the presence of plasminogen transformed to plasmin by urokinase secreted by the cells, proliferation stimulated by rhIGFBP-3 and its proteolysis were enhanced. Our results suggest that the biphasic mitogenic effect of rhIGFBP-3 on PC-3 cells reflects changes in the availability to the cells of the IGF-II they secrete. This availability depends on the extent of IGFBP-3 proteolysis (which promotes release of bound IGF-II) and on the proportion of intact forms (which sequestrate secreted IGF-II).
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PMID:Recombinant human insulin-like growth factor (IGF) binding protein-3 stimulates prostate carcinoma cell proliferation via an IGF-dependent mechanism. Role of serine proteases. 889 45

Elevated plasma levels of lipoprotein(a) [LP(a)] are associated with increased an risk of developing atherosclerosis. This increased risk may be due to an Lp(a)-mediated depression of fibrinolytic activity. Lp(a) regulates fibrinolysis by controlling the activity of plasminogen activators. Lp(a) is a low density lipoprotein with an apoprotein(a) subunit which has a high degree of homology with the fibrinolytic zymogen plasminogen. The apoprotein(a) subunit contains up to thirty seven copies of a domain homologous to the plasminogen kringle 4 domain, which enables Lp(a) to bind to fibrin. The subunit also has a zymogen domain, but it is not activated by plasminogen activators. Lp(a) inhibits plasminogen activation by competing with plasminogen for access to plasminogen activators bound to vascular surfaces. Lp(a) also competes with the irreversible inhibitor of plasminogen activators, plasminogen activator inhibitor-1. Therefore increases in Lp(a) concentration may decrease fibrinolytic activity by preventing activation of plasminogen, but Lp(a) may also prolong plasminogen activation by preventing the irreversible inhibition of the activators. At elevated levels of Lp(a) the decreased rate of plasmin generation may not be offset by the prolongation in plasminogen activation, and fibrinolysis will be inhibited.
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PMID:Lipoprotein (a) in the regulation of fibrinolysis. 922 22

Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-alpha). IFN-alpha therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-alpha occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, measenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-alpha. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-alpha included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-alpha was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.
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PMID:Response of severe systemic mastocytosis to interferon alpha. 958 Aug 6

In a previous study, the biphasic effect of increasing dosages of recombinant human insulin-like growth factor binding protein-3 (rhIGFBP-3) on proliferation in the prostate carcinoma PC-3 cell line (stimulation followed by depression) was shown to reflect changes in the bioavailability of IGF-II secreted by the cells, IGF-II being the major factor responsible for their autocrine growth. These changes depend on the extent of IGFBP-3 proteolysis induced by serine proteases, in particular, plasmin. In order to examine the mechanism of action of IGFBP-3, we investigated the effects of its two major fragments isolated by HPLC following limited proteolysis by plasmin in vitro. The predominant fragment with an apparent molecular mass of 22-25 kDa in SDS-PAGE (under non-reducing conditions) had previously been shown to retain weak affinity for IGFs, whereas the other fragment of 16 kDa lost all such affinity. From their recently determined amino acid sequences, these fragments correspond to the first 160 and 95 residues, respectively, of IGFBP-3. 0.5-5 nM intact rhIGFBP-3(1-264), when pre-incubated with 5 nM rhIGF-II, dose-dependently inhibited (up to 100%) its mitogenic effect, via sequestration owing to its strong affinity for IGF-II. The same concentrations of the larger fragment (IGFBP-3(1-160)) elicited only weak inhibition (up to 30%), coherent with its weak affinity. The smaller fragment (IGFBP-3(1-95)) provoked total inhibition despite its lack of affinity for IGFs and therefore by an IGF-independent mechanism. PC-3 cells in serum-free medium were weakly stimulated by 5 nM intact IGFBP-3. This had previously been shown to be related to its proteolysis and the ratio of proteolysed to intact IGFBP-3. At the same concentration, IGFBP-3(1-160) stimulated this proliferation by a factor of 5-7, whereas IGFBP-3(1-95) totally suppressed it. 5 nM IGFBP-3(1-95) inhibited the mitogenic action of 1% fetal calf serum by 80%, but by only 25% in the presence of an antibody blocking the type 1 IGF receptor. Its inhibition is therefore exerted principally, but not exclusively, via the IGF signalling pathway. Our data indicate that the IGFBP-3 fragments composed of residues 1-160 and 1-95 are biologically active on PC-3 cells and that their opposite actions may account for the events observed when IGFBP-3 is proteolysed in the cell environment. These proteolytic fragments may therefore play a role in the development of prostate adenocarcinomas in vivo.
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PMID:Prostate carcinoma (PC-3) cell proliferation is stimulated by the 22-25-kDa proteolytic fragment (1-160) and inhibited by the 16-kDa fragment (1-95) of recombinant human insulin-like growth factor binding protein-3. 1099 Apr 47


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