Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the precise etiologic incitant of the minimal lesion idiopathic nephrotic syndrome of childhood is not known, it is likely that a host mechanism mediates the permeability alterations of the glomerular capillary wall resulting in massive proteinuria. As a first step in examining the possibility that local kinin release may account for the proteinuria in this disorder, two parameters of the plasma kinin-generating system, plasma prekallikrein and kallikrein inhibitor, were assayed during 27 nephrotic episodes in 21 corticosteroid-responsive children. Plasma kallikrein was assayed by means of its esterase activity on a synthetic arginine ester substrate, N-alpha-tosyl-L-arginine methyl ester (TAMe), after activation of Hageman factor by kaolin. This activity, after subtraction of spontaneous arginine esterase activity (i.e., TAMe esterase activity measured in plasma not exposed to kaolin) is derived from prekallikrein. Plasma prekallikrein activity in 11 normal children was 99.6 +/- 2.9 mumol TAMe hydrolyzed/ml plasma/hr (mean +/- SEM). Kallikrein inhibitor was quantified in arbitrary units. Kallifrein inhibitor activity in 11 normal children was 0.94 +/- 0.04 units. During the overt nephrotic syndrome, before initiation of intensive daily corticosteroid treatment, mean values were: prekallikrein, 58.5 +/- 7.24 mumol/ml/hr; and kallikrein inhibitor, 0.35 +/- 0.06 units. After corticosteroid-induced remission occurred, mean values were: plasma prekallikrein, 118.6 +/- 3.2 mumol/ml/hr; and kallikrein inhitor, 0.78 +/- 0.03 mumol/ml/hr. Both parameters were again assayed in 14 of the 21 children after complete cessation of corticosteroid treatment. Plasma prekallikrein was normal, 99.6 +/- 4.8 mumol/ml/hr; but kallikrein inhibitor was still somewhat depressed, 0.84 +/- 0.03 units. A subset of 9 patients had marked depression of plasma prekallikrein to levels less than 20 mumol/ml/hr and essentially undetectable inhibitor activity. Serum alpha-2 macroglobulin was elevated in nephrotic patients: mean value during relapse, 862 +/- 29 mg/100 ml; during corticosteroid-maintaining remission, 615 +/- 29 mg/100 ml. After cessation of corticosteroids, mean serum level was 481 +/- 20 mg/100 ml. The proportional reduction of plasma prekallikrein and kallikrein inhibitor suggested that an enzyme-inhibitor complex formed in vivo, perhaps at a local site of activation in proximity to the glomerular basement membrane. These data suggest that the plasma kinin-generating system may be the host effector mechanism subserving the increased glomerular capillary permeability in the minimal lesion nephrotic syndrome of childhood.
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PMID:A study of the plasma kinin-generating system in children with the minimal lesion, idiopathic nephrotic syndrome. 5 8

The dextran sulfate (DS) cellulose column usually used for low-density lipoprotein (LDL) apheresis, is an activator of the contact phase of intrinsic coagulation pathway. Hageman factor (factor XII), high-molecular-weight kininogen (HMWK) and prekallikrein (PK) form a complex on the surface of this activator, and bradykinin is released from HMWK by the action of kallikrein converted from PK. Heparin, a frequently used anticoagulant, has no effect on this process, whereas a protease inhibitor, nafamostat mesilate (FUT-175) is thought to inhibit the process. Five patients with severe hypercholesterolemia were treated with LDL apheresis using heparin or FUT-175, each on a different day. During treatment with heparin, factor XII, HMWK, and PK were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing through the DS column, which led to an increase of blood bradykinin levels from 12.5 +/- 5.3(Mean +/- SEM) pg/ml to 127.3 +/- 67.1 pg/ml after 1000 ml plasma treatment. FUT-175 almost completely suppressed this bradykinin generation. Because bradykinin generated during LDL apheresis seems to have some vasodilative effect, FUT-175 might be preferred in cases with unstable hemodynamics, although this presumption remains to be demonstrated.
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PMID:Effect of nafamostat mesilate on bradykinin generation during low-density lipoprotein apheresis using a dextran sulfate cellulose column. 176 3

C1 inhibitor (C1 INH) is the major protease inhibitor of the first components of the classic complement system and of the proteases of the Hageman factor pathways. Since C1 INH may modulate inflammatory reactions associated with complement and contact system activation, we sought to determine if the cytokine gamma interferon (IFN-gamma) could modulate C1 INH production. Initial studies investigated the effect of IFN-gamma on the molecular and protein expression of C1 INH in human erythroleukemia (HEL) cells. HEL cells constitutively expressed the 2.1 kb mRNA for C1 INH. IFN-gamma (50 to 1,000 U/mL), but not interferon alpha or beta, increased twofold the amount of C1 INH mRNA expressed within HEL cells. Similarly, this cytokine increased HEL cell C1 INH synthesis of a 105 Kd protein 10-fold, from 1.9 +/- 0.5 microgram C1 INH antigen per 10(8) cells (mean +/- SEM) to 19 +/- 8 micrograms/10(8) cells in 8 days. C1 INH produced by HEL cells after IFN-gamma stimulation had fully intact kallikrein neutralizing activity. Moreover, conditioned media of IFN-gamma-treated HEL cells accumulated more secreted C1 INH in 8 days (6.7 micrograms/mL/10(8) cells) than untreated cells (0.6 microgram/mL/10(8) cells). Additional studies were done on plasma specimens from 22 patients with metastatic colorectal carcinoma who received IFN-gamma daily for 4 days by intravenous infusion. Before treatment, the mean +/- SEM C1 INH levels in these patients was 438 +/- 16 micrograms/mL. At day 10 from the start of the infusion, the plasma C1 INH in these patients increased to 586 +/- 32 micrograms/mL (P less than .0001). The extent of rise of plasma C1 INH after IFN-gamma treatment was independent of dose from 0.01 to 40 U/m2. After 30 days, the mean plasma C1 INH levels decreased to 502 +/- 27 micrograms/mL. These combined studies indicate that IFN-gamma can increase C1 INH protein expression in vitro and in vivo.
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PMID:Interferon gamma increases in vitro and in vivo expression of C1 inhibitor. 211 12

Although the biological function of histidine-rich glycoprotein (HRG) is unknown, it may serve as an antifibrinolytic agent by interfering with the binding of plasminogen to fibrin. To define the role of HRG, plasma titers were measured by single radial immunodiffusion in eleven patients with thromboembolism before and after streptokinase (SK) therapy and were found unchanged (84.7 +/- 6.2%, M +/- SEM before, and 99.5 +/- 6.3% after 12 hr of SK therapy). The HRG peaks on crossed immunoelectrophoresis before and after SK infusion were also unchanged. Alpha 2-plasmin inhibitor fell during SK infusion as measured immunologically (102.0 +/- 15.0% before and 28.0 +/- 1.6% after 12 hr of therapy) and fibrinogen-fibrin degradative products appeared (mean titer of 1:2,048 after 12 hr of therapy), indicating that the infused SK was biologically active. Plasminogen levels before therapy were normal, as measured functionally and immunologically (105.4 +/- 4.9% and 96.0 +/- 5.6%, respectively), and both decreased after 12 hr of SK therapy (15.2 +/- 5.6% and 50.8 +/- 4.3%). No changes in functional antithrombin III titer, Hageman factor antigen level, or fibrinogen concentration, as measured turbidimetrically, were observed. Thus, although these data do not allow one to make any firm conclusions regarding the physiologic role of this protein in fibrinolysis, they do not exclude its increased catabolism, compensated by increased production, in patients undergoing fibrinolytic therapy.
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PMID:Histidine-rich glycoprotein and changes in the components of the fibrinolytic system after streptokinase therapy in patients with pulmonary thromboembolism. 401 25

Prolonged extracorporeal circulation (ECC) using heparin as anticoagulant may be associated with pronounced thrombocytopenia and excessive bleeding. We, therefore, tested the hypothesis that reversible inhibition of platelet function, in lieu of heparinization, might preserve platelets and prevent coagulation in a perfusion circuit. When 500 ml of fresh heparinized (one U/ml) human blood was recirculated in a perfusion circuit constructed of standard silicone rubber components and a membrane oxygenator (0.95 M2), platelet counts declined to 9 +/- 2 (SEM) % of initial levels within 15 mins; plasma levels of the platelet specific protein LA-PF4 rose to 15 +/- 2 micrograms/ml within one hour indicating extensive release of platelet granule contents, and leukocyte counts declined to 91 +/- 4% within 15 mins. Prostacyclin (PGI2, greater than or equal to 25 eta M) or prostaglandin E1 (20 microM) and theophylline (12 mM) prevented platelet loss and release of granule contents. When heparin was reversed with protamine, however, immediate coagulation ensured. This occurred despite the absence of detectable activation of Hageman factor as evidenced by stability of plasma concentrations of prekallikrein in systems anticoagulated with heparin or citrate and despite our inability to detect thromboplastin-like properties in isolated leukocytes. Thus, coagulation in the presence of platelet inhibition suggests that alternative pathways, independent of platelet activation may exist. Platelet inhibition does preserve platelets preventing contact initiated release, but cannot serve by itself for anticoagulation.
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PMID:Prostacyclin in lieu of anticoagulation with heparin for extracorporeal circulation. 703