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

We have established a simplified assay system for the measurement of urinary kallikrein activity by utilizing the sensitive and specific radioimmunoassay system of kinins previously reported from our laboratory. Kinins were generated by incubating urine samples (50 microliter) with kininogen (1500 ng) in the presence of kininase inhibitors, and the generated kinins were measured by radioimmunoassay. Since the cross reactivity of kininogen in the kinin radioimmunoassay system was not recognized at dose up to 1.0 microgram, the amount of untreated kininogen in the radioimmunoassay samples did not interfere with the measurement of kinins. This eliminated the necessity for a kininogen extraction procedure. A good linear correlation (r = 0.939, p less than 0.001) was observed between the urinary kallikrein activity determined by this assay system (kininogenase activity) and that by esterolytic acitvity. Urinary kallikrein activity was 3.3 +/- 0.9 microgram/min/24 hour urine (mean +/- SEM), 1.4 +/- 0.4 microgram/min/24 hour urine and 0.25 +/- 0.06 microgram/min/24 hour urine in 6 normal subjects, 7 patients with non-complicated essential hypertension and 4 patients with chronic renal failure, respectively. Thus, urinary kallikrein activity was significantly lower in the patients with essential hypertension (p less than 0.05) and the patients with chronic renal failure (p less than 0.01) than in the normal subjects.
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PMID:Measurement of urinary kallikrein acitvity by kinin radioimmunoassay. 10 45

The possibility that bradykinin, a potent vasodilator, might be a physiological antagonist of the renin-angiotensin system was investigated. 11 norman subjects, ranging in age from 21 to 33 yr were studied. Seven of the subjects were given a 10 meq sodium, 100 meq potassium, 2500 ml isocaloric diet. After metabolic balance was achieved, they were infused with either 1 liter of 5 per cent glucose over 2 h or 2 liters of 0.9 per cent saline over 4 h. During the infusions, plasma renin activity (PRA), angiotensin II (A II), prekallikrein, bradykinin, and aldosterone levels were frequently determined. Plasma prekallikrein and kallikrein inhibitor did not change during the infusion of either glucose or saline. In subjects receiving saline, plasma bradykinin fell from 3.9 plus or minus 1.5 (SEM) ng/ml at 0 min to 0.93 plus or minus 0.2 at 30 min and 0.95 plus or minus 0.3 at 120 min. These changes paralleled the decrease in PRA over the same period (7.9 plus or minus 1.3 ng/ml/h to 5.6 plus or minus 0.8 at 30 min and 3.5 plus or minus 0.7 at 120 min). Similarly, A II fell from 113 plus or minus 12 pg/ml to 62 plus or minus 10 and 48 plus or minus 5, respectively, at 30 and 120 min. In contrast, the control group infused with glucose showed no change in bradykinin, A II, or PRA. Another four subjects were given a constant 200 meq sodium/100 meq potassium isocaloric diet. After metabolic balance was achieved, they were kept supine and fasting overnight. At 9 a.m. they assumed an upright position and began walking a fixed distance (200 ft) at a normal rate (3-4 ft/s). Plasma prekallikrein and kallikrein inhibitor did not change during the posture study. The plasma bradykinin rose from a base line of 0.54 plus or minus 0.01 (SEM) ng/ml to 0.96 plus or minus 0.13 at 20 min. 0.77 plus or minus 0.18 at 60 min, and 0.96 plus or minus 0.07 at 120 min. These changes parallel the increase in PRA over the same period (1.65 plus or minus 3.3 ng/ml/h to 3.6 plus or minus 0.85 at 20 min, 5.3 plus or minus 0.9 at 60 min, and 5.35 plus or minus 0.55 at 120 min). Likewise, the A II rose from 32.5 plus or minus 1.82 pg/ml to 50.8 plus or minus 3.6 at 20 min, 54.3 plus or minus 3.2 at 60 min, and 61.3 plus or minus 5.9 at 120 min. Thus, in sodium-depleted individuals, saline infusion produces a rapid fall of plasma bradykinin at a rate similar to that observed for a II and PRA. Conversely, in sodium-loaded individuals, assumption of upright posture leads to a parallel rise in A II, TPRA, and bradykinin. These studies indicate that there is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated.
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PMID:Response of the kallikrein-kinin and renin-angiotensin systems to saline infusion and upright posture. 23 59

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

Tumor necrosis factor has been implicated in the activation of blood coagulation in septicemia, a condition commonly associated with intravascular coagulation and disturbances of hemostasis. To evaluate the early dynamics and the route of the in vivo coagulative response to tumor necrosis factor, we performed a controlled study in six healthy men, monitoring the activation of the common and intrinsic pathways of coagulation with highly sensitive and specific radioimmunoassays. Recombinant human tumor necrosis factor, administered as an intravenous bolus injection (50 micrograms per square meter of body-surface area), induced an early and short-lived rise in circulating levels of the activation peptide of factor X, reaching maximal values after 30 to 45 minutes (mean +/- SEM increase after 45 minutes, 34.2 +/- 18.2 percent; tumor necrosis factor vs. saline, P = 0.015). This was followed by a gradual and prolonged increase in the plasma concentration of the prothrombin fragment F1+2, peaking after four to five hours (mean increase after five hours, 348.0 +/- 144.8 percent; tumor necrosis factor vs. saline, P less than 0.0001). These findings signify the formation of factor Xa (activated factor X) and the activation of prothrombin. Activation of the intrinsic pathway could not be detected by a series of measurements of the plasma levels of factor XII, prekallikrein, factor XIIa-C1 inhibitor complexes, kallikrein-C1 inhibitor complexes, and the activation peptide of factor IX. The delay between the maximal activation of factor X and that of prothrombin amounted to several hours, indicating that neutralization of factor Xa activity was slow. We conclude that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation, probably induced through the extrinsic route. Our results suggest that tumor necrosis factor could play an important part in the early activation of the hemostatic mechanism in septicemia.
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PMID:Activation of coagulation after administration of tumor necrosis factor to normal subjects. 221 25

The vascular smooth muscle cells belong to the category of "bidirectionally controlled cells", which can be activated (leading to contraction) by some first-messengers (such as Catecholamine-alpha 1, or Angiotensin II) in connection with a recently discovered intracellular second-messenger system-C (sms-C), namely, Diacylglycerol-dependent Protein Kinase-C + Calcium mobilization. On the other hand, these cells can be inhibited (leading to relaxation) by other first-messengers (such as Catecholamine-beta or PGI2) related to the classical "second-messenger system-A" (sms-A), namely: Ns--Adenylate Cyclase--cAMP--Protein Kinase-A. It is also known that kallikrein (via kinins) can stimulate PGI2 synthesis, and implicitly sms-A, relaxing the vascular tone by counteracting the opposite pressor effect of sms-C. In the four h samples of urine, collected before and after administration of kallikrein (i.m., 40 IU) to six hypertensive patients, we measured (RIA): 6-keto-PGF1 alpha, the stable metabolite of PGI2. The results 5.86 +/- 1.25 vs 9.94 +/- 0.6 pg/mL +/- SEM (p less than 0.05) indicate a rise in PGI2 synthesis. However, no such effect was obtained when the same patients were given aspirin (4 g in divided doses) one day before repeating the above test: 5.59 +/- 1.97 vs 6.85 +/- 1.28 (NS). We may conclude that administration of kallikrein can stimulate PGI2 synthesis, which, in turn, can be blocked by relatively high (= nocive) doses of aspirin. Some new aspects of chemical physiology, pathogeny and systematization of the two major messenger systems, MS-A and MS-C, are discussed.
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PMID:Inhibition by aspirin of the stimulated PGI2 synthesis after administration of kallikrein to hypertensive patients (new aspects of chemical pathogeny concerning the messenger systems: A and C). 282 18

The effect of cyclosporine (6 to 8 mg/kg/day) on urinary kallikrein excretion was examined in 10 patients with rheumatoid arthritis by using a radioimmunoassay for kallikrein, a product of renal tubular biosynthesis. All patients had baseline values of serum creatinine and blood urea nitrogen (BUN) within the normal range. The group had a mean baseline kallikrein excretion of 98.30 +/- 29.98 micrograms/24 hours (mean +/- SEM), and 3 and 6 months after therapy was initiated, kallikrein excretion was 44% and 46% of baseline, respectively (p less than 0.01). The five patients who had a normal mean baseline kallikrein excretion rate (106.60 +/- 15.21 micrograms/24 hr) excreted significantly less (p less than 0.05) kallikrein 3 and 6 months after therapy was initiated (56.60 +/- 3.98 micrograms/24 hr and 34.50 +/- 11.02 micrograms/24 hr, respectively), as did one patient with an elevated baseline kallikrein. All six of these individuals completed the protocol. In a subgroup of four patients with low baseline levels (28.25 +/- 5.06 micrograms/24 hr), two individuals experienced elevations of BUN such that cyclosporine was discontinued; in the two who completed the protocol, there was some further decrement in kallikrein excretion. Kallikrein excretion increased in all patients after a 3-month washout period. During a low-dose (3 mg/kg/day) open extension study that followed the initial trial, kallikrein excretion was determined monthly. Seven episodes in which kallikrein excretion decreased in six patients by 44% +/- 18% over a 1-month interval preceded any increase in serum creatinine by 1 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of cyclosporine on urinary kallikrein excretion in patients with rheumatoid arthritis. 341 Nov 94

The mechanisms causing high blood pressure in patients with Cushing's syndrome were investigated by measurements of humoral factors and pharmacological maneuvers. Twelve patients with adrenal adenomas were studied. The mean systolic and diastolic pressures of the patients were 171 +/- 28 and 109 +/- 15 mm Hg (+/- SEM), respectively, which were significantly higher than those of normal subjects. PRA, plasma renin concentration, plasma renin substrate, plasma cortisol, plasma aldosterone, urinary kallikrein, and urinary prostaglandin E2 were measured as the humoral factors. PC values were markedly elevated in patients with Cushing's syndrome. Among the components of the renin-angiotensin system, only plasma renin substrate was increased. Urinary kallikrein and prostaglandin E2 were decreased in patients with Cushing's syndrome. Oral administration of captopril lowered blood pressure, but infusion of an angiotensin II analog did not. Furthermore, the pressor responses to infusion of both norepinephrine and angiotensin II were increased. We conclude that blood pressure is elevated in patients with Cushing's syndrome because they have enhanced pressor responses to vasoactive substances, suppression of depressor systems, and some abnormalities of the renin-angiotensin system.
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PMID:Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome. 351 Feb 23

The rate of tissue kallikrein (EC 3.4.21.35) excretion into the urine has been examined with an active site-specific radioimmunoassay for kallikrein in renal transplant recipients, in post-uninephrectomy kidney donors, and in a normal control population. Normal individuals on uncontrolled diets excreted 96.88 +/- 7.00 (SEM) micrograms of active kallikrein/24 hr and 113.68 +/- 8.39 micrograms of total kallikrein/24 hr, as determined after trypsin treatment of urine samples. Uninephrectomized donors secreted significantly less (P less than 0.05) active (44.99 +/- 6.39 micrograms/24 hr) and total (73.59 +/- 11.95 micrograms/24 hr) kallikrein than either the entire normal population or an age-matched subpopulation. Recipients with good renal function who had received kidneys 2 to 13 years prior to kallikrein assay excreted less (P less than 0.05) active (13.21 +/- 2.50 micrograms/24 hr) and total (18.69 +/- 3.65 micrograms/24 hr) kallikrein than either normal or uninephrectomized populations. Similar values for active (11.05 +/- 1.56 micrograms/24 hr) and total (17.60 +/- 1.96 micrograms/24 hr) kallikrein were seen in patients who had received kidneys within 6 months of assay. Thus, kallikrein excretion in kidney recipients remains significantly lower than in uninephrectomized donors. As compared to normal individuals, the reduced kallikrein excretion in post-uninephrectomized kidney donors and in renal allograft recipients suggests that renal kallikrein excretion may reflect functional distal tubular mass.
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PMID:Kallikrein excretion in renal transplant recipients and in uninephrectomized donors. 390 May 31


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