Biomedical subjects

H T Johansen

Publications and source records attributed to H T Johansen.

At least 37 records · Page 2Linked to original sources

PubMed1994

[Angioedema associated with ACE inhibitors].

Angio-oedema as an adverse effect of angiotensin converting enzyme-inhibitors (ACE-inhibitors) is reported to occur in one to two of 1,000 treated patients per year. This estimate may be too low, since the swelling of face, lips, tongue and throat is very often attributed to food allergy. Furthermore, attacks of oedema may occur after months or even years of ACE-inhibitor treatment, thereby obscuring the link to the medication. This adverse effect is non-immunogenic. The oedema is explained by local enhancement of bradykinin, which under normal circumstances is broken down by angiotensin converting enzyme. The question of what makes some people vulnerable is still unsolved. The oedema can develop quickly and may lead to suffocation. In many cases, conventional antiallergic treatment in the form of steroids, antihistamines and epinephrine has inadequate effect. Intubation of the larynx may be necessary, but can be extremely difficult in the case of massive glassy oedema. Involvement of the neck can sometimes hinder tracheotomy, making early intervention essential. The authors describe two patients with moderate swellings, and discuss a potential, yet experimental, use of C1-inhibitor concentrate in the treatment of ACE-inhibitor provoked angioedema.

Angioedema↗

PubMed1994

C1 inhibitor and diagnosis of hereditary angioedema in newborns.

Symptoms of hereditary angioedema may present during the child's first years. Attacks may be a particular threat to the narrower airway of the child. An early diagnosis is most valuable because effective C1 inhibitor (C1 INH) concentrate is available. We present a reference area for the antigenic and functional determination of C1 INH by using uncontaminated umbilical cord blood from 80 normal newborns collected by puncturing vessels in the newly delivered placenta. We examined two full-term babies (1 and 2) from mothers with hereditary angioedema type I the same way. The concentration of C1 INH antigen was determined by radial immunodiffusion. The C1 INH functional assay was based on the addition of a known quantity of C1s, which enzymatically splits a chromogenic substrate. The test was performed in the presence of methylamine and heparin in a kinetic microtiter plate assay. Citrated plasma was used in both assays. The data obtained in the 80 cord blood samples (2.5-97.5 percentile) were 0.11-0.22 g/L for C1 INH antigen (adults, 0.15-0.33 g/L) and 47.2-85.9% for C1 INH function (percentage of adults). In cord blood, baby 1 had an antigenic value of 0.12 g/L (7.5 percentile) and C1 INH function of 61.8% (42 percentile). The corresponding values for baby 2 in cord blood were less than 0.05 g/L (0.106 g/L < 2.5 percentile) and 34.3% (12.9% < 2.5 percentile). Baby 2 had markedly lower C4 values yet much higher C4 activation products than baby 1. At 4 mo, baby 1 had an antigenic C1 INH value of 0.24 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioedema↗

PubMed1993

Location of plasminogen activator (PA) and PA inhibitor in human colorectal adenocarcinomas.

Both the coagulation and fibrinolytic cascades generate proteolytic enzymes which appear to be essential for tumor invasion. In the present investigation adenocarcinomas and normal colon from 14 patients with colorectal cancer were studied by immunohistochemistry. The most striking observation was an enrichment of plasminogen activator inhibitor in the tumor tissue, whereas no such immunoreactivity was detected in the biopsies of normal colon. The tumor-host interface was characterized by a massive accumulation of inflammatory cells, macrophages and T lymphocytes. In this area fibrin(ogen) immunoreactivity as a sign of local activation of the coagulation cascade was also seen. The transition zone between the tumor and normal tissue was furthermore characterized by a marked enrichment of urokinase plasminogen activator immunoreactivity. The study strongly indicates that proteases and inhibitors of the fibrinolytic system may be of great importance in tumor invasion.

Adenocarcinoma↗

PubMed1993

The contact system in human malignant and benign ascites.

The plasma contact system was studied in ascites and plasma from patients with gastrointestinal cancer and patients with liver failure. Our study demonstrates the presence of factor XII, factor XI, and prekallikrein and their main inhibitors in ascites and plasma from both patient groups. Both factor XII-like and plasma kallikrein-like activities were detected in the malignant ascites. The kallikrein-like activity in malignant ascites was found in complex with alpha 2-macroglobulin. In plasma samples from the patients functional values of factor XII and prekallikrein were decreased compared to controls. In benign ascites the proenzyme levels were significantly lower than in malignant ascites. Functional inhibition values in ascites and plasma from patients were unexpectedly high. Our findings indicate that the plasma contact system is activated in the ascites from cancer patients. Activation of the contact system generates vasoactive mediators, which may play a role in the accumulation of malignant ascites.

Aged↗

PubMed1993

Differential diagnosis of human ascites: inhibitors of the contact system and total proteins.

To assess their accuracies as markers for malignancy, we assayed alpha 2-macroglobulin, C1-inhibitor, alpha 1-protease inhibitor, and total proteins in ascites and plasma from patients with gastrointestinal cancer (n = 15) and non-malignant liver disease (n = 13), using functional and immunologic assays. For all inhibitors and total proteins determined in ascites, the values in the cancer group were significantly higher than the corresponding values in the group with non-malignant liver disease. The diagnostic accuracy for differentiating malignancy-related from non-malignant ascites was 93% for a alpha 1-protease inhibitor value > or = 50% of the pool plasma value and 90% for alpha 2-macroglobulin > or = 16%, C1-inhibitor > or = 40% (all functional assays), and total proteins > or = 20 g/l (biuret). In conclusion, functional assays for alpha 2-macroglobulin, C1-inhibitor, and alpha 1-protease inhibitor and determination of total proteins in ascites appeared to be very informative tests for the differential diagnosis of ascites. The test for alpha 1-protease inhibitor gave higher specificity (92% versus 77%) and likelihood ratio for a positive test (12 versus 4) compared with the other tests.

Adult↗

PubMed1992

Hemodynamic and proteolytic effects of intravenous injection of purified human plasma kallikrein.

To investigate the precise hemodynamic effects of purified human plasma kallikrein, small doses (0.3 U/kg) of this proteolytic enzyme were infused over 10 s in five pigs. Hemodynamic performance was evaluated by means of a Swan-Ganz catheter, and parameters of the plasma kallikrein-kinin, coagulation, and fibrinolytic systems were determined by means of chromogenic peptide substrate assays. The infusions of plasma kallikrein were followed by rapid decreases in mean arterial pressure (to 43 +/- 2% of baseline values) and increases in cardiac output (to 145 +/- 6% of baseline values), accounting for marked decreases in systemic vascular resistance, to 28 +/- 1% of initial values. Heart rate, mean pulmonary arterial, central venous, and pulmonary capillary wedge pressures did not change after the injection. Pulmonary vascular resistance decreased to 69 +/- 3% of baseline values. The hemodynamic changes gradually normalized during the following 10 min. Functional levels of prekallikrein, kallikrein, kallikrein inhibition, prothrombin, antithrombin III, plasmin, and antiplasmin were not affected by the injection or the resulting hemodynamic changes; the hematocrit and the number of circulating leukocytes or platelets were also unaffected.

Animals↗

PubMed1992

Activation of the plasma kallikrein-kinin system in respiratory distress syndrome.

Components of the plasma kallikrein-kinin and fibrinolytic systems together with antithrombin III were measured the first days postpartum in 13 premature babies with severe respiratory distress syndrome (RDS). Seven of the patients received a single dose of porcine surfactant (Curosurf) as rescue treatment. Nine premature babies without lung disease or any other complicating disease served as controls. There were no differences in prekallikrein values between surfactant treated and non-treated RDS babies during the first 4 d postpartum. The controls had, however, significantly higher prekallikrein values than the RDS babies already at the first day of age (mean +/- SD 32 +/- 8% in controls versus 22 +/- 6 and 21.5 +/- 5% in the treated and nontreated RDS groups, respectively). Plasma kallikrein activities did not differ between RDS and control patients. Plasma kallikrein inhibition values, which increased steadily in all groups, were lower in the RDS babies treated with surfactant than in controls at d 2 and 4. The degree of degradation of plasma high molecular weight kininogen was measured in RDS patients treated with surfactant and was significantly higher when compared with controls at d 1, demonstrating an increased proteolysis of kininogen to kinin early in RDS. There were no differences in plasminogen and plasmin values between RDS and control babies. This study shows that the plasma kallikrein-kinin system is activated in RDS. This system as well as the fibrinolytic system does not seem to be influenced by rescue instillation of a single dose of porcine surfactant into the lungs of premature babies with RDS.

Antithrombin III↗

PubMed1992

Activation of the contact system in ascites from patients with gastrointestinal cancer.

Our observations indicates that the plasma contact system is activated in ascites from patients with gastrointestinal cancer: Factor XII is activated, plasma kallikrein is present in complex with the protease inhibitor alpha 2-macroglobulin, and the plasma kallikrein substrate high molecular weight kininogen, is highly degraded. Contact activation seems to take place in spite of a high level of inhibition. Activation of the contact system generates mediators, which may play a role in the accumulation of ascites.

Adult↗

PubMed1991

Characterization of kininogens in human malignant ascites.

Ascites from seven patients with advanced cancer were studied to characterize the kininogens. Immunological quantification of low molecular weight kininogen (L-kininogen) and high molecular weight kininogen (H-kininogen) by rocket immunoelectrophoresis showed values of 42% and 39%, respectively, compared to control plasma. Release of kinin from the ascites samples was assayed on an isolated rat uterus. The total kinin released from the kininogens was 39% of the value in control plasma, while release selectively from H-kininogen amounted to 25% of plasma. This indicates about 30% of the bradykinin in H-kininogen to be released in vivo in ascites, and points to kinins as possible mediators of the increased vascular permeability causing accumulation of ascites. The function of kininogens as cysteine protease inhibitors (CPIs) was assayed as well, indicating that both L- and H-kininogen function as cysteine protease inhibitors in human ascitic fluid. The proteolytic cleavage of H-kininogen in ascites was studied by polyacrylamide gel electrophoresis and subsequent immunoblotting. H-kininogen was extensively cleaved in ascites compared to control plasma, with large amounts present of a degraded form with Mr of 99 kDa. The bands observed compared well with those described in plasma, and are consistent with contact activation taking place in ascites.

Ascitic Fluid↗

PubMed1991

Evaluation of a microassay for human kininogens as cysteine protease inhibitors.

Several methods have been described for the identification and quantification of kininogens based on both immunochemical and functional characteristics. This article presents a rapid, cheap and simple microplate assay of kininogens based on their ability to inhibit cysteine proteases. The target enzyme papain is activated by cysteine HCl and the activated enzyme will be inhibited by added kininogens. The residual enzyme activity that is not inhibited in this reaction subsequently hydrolyzes the added substrate, S-2302, generating a yellow color that is read in a microplate reader at 405 nm. This method is very sensitive, the smallest amount of kininogen that causes significant inhibition of papain is established to be 0.01 micrograms. As a quantitative method, the assay performs accurately when approximately 0.1 micrograms of low molecular weight kininogen or high molecular weight kininogen is added to the test system. The within-run coefficient of variation (%) of the method was 1.7% when the inhibition of papain was in the range 45-70% and the day to day variation as low as 2.3% when performed with a papain inhibition of 80%. Applications of the method are presented, studying chromatographic separated kininogens in plasma, ascites, and urine.

Ascites↗

PubMed1990

A new case of total kininogen deficiency.

Six families with total kininogen deficiency have been described in the literature. We report herein an additional case in a Pakistanese woman. The defect was discovered accidentally due to lack of normal clot formation in a preoperative routine blood sample. She had a borderline prolonged bleeding time, and reported occasional hematuria, but was otherwise without symptoms. Absence of both kininogen species was proven by functional and immunological methods, and by lack of kinin formation both by plasma kallikrein and hog pancreas kallikrein. Prekallikrein was reduced, probably because the main part circulates complexed to high molecular kininogen. Activation of intrinsic fibrinolysis was grossly hampered, and cold activation of coagulation absent with epsilonaminocaproic acid and greatly retarded by dextran sulfate, kaolin and ellagic acid. Together with other evidence the findings indicate the following order of importance for contact activation in plasma--F.XII, high molecular weight kininogen, prekallikrein.

Adult↗

PubMed1990

[The role of proteases in the growth, invasion and spread of cancer cells].

Cancer cells show a greater capability than normal cells do to break down proteins in the surrounding tissue. This tissue destruction involving proteolytic enzymes is probably essential for the invasion and metastatic spread of malignant cells. The process takes place through an interplay of proteolytic enzyme systems where plasmin-mediated proteolysis plays an important role. Plasminogen activator activity and receptors for plasminogen activators have been discovered in tumors, mainly in areas with invasive growth and tissue degradation. Patients with malignant diseases often demonstrate abnormalities in their blood coagulation, including hyperaggregability of platelets. Experimental research has shown that therapy with antiplatelet drugs, and prophylaxis with protease inhibitors, can limit spread of tumors.

Animals↗

PubMed1989

Rocket immunoassay of high and low molecular weight kininogens in human plasma.

High molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK) in human plasma could be rapidly (36 min.) separated on a DEAE-Sepharose Fast Flow column (1.0 x 5 cm and 0.50 ml plasma) by applying a NaCl step gradient. Quantification was then carried out by the Laurell rocket method with an antiserum raised against HMWK. Standard preparations for the assays were (I) crude HMWK and (II) crude LMWK prepared by the one-step procedure mentioned. In disc PAGE (8% with 0.1% SDS) immunoblot showed two main bands in I, migrating to apparent mol.wts. of 180,000 and 120,000. The 180,000 band predominated in native plasma. Purified HMWK (spec.act. 14 micrograms bradykinin/A 280) yielded in addition a band corresponding to a mol.wt. of 100,000. Immunoblot of II showed one broad zone over the mol.wt. range 65-70,000. The average assay values obtained in human plasma specimens from 10 males were 85 micrograms/ml for HMWK (range 65-130) and 174 micrograms/ml for LMWK (range 164-183). HMWK occasionally lost immunoreactivity during purification without a corresponding loss of kinin. Such a loss of immunoreactivity seemed to run parallel with a reduced release of kinin induced by hog pancreas kallikrein.

Humans↗

PubMed1986

Reduced or unchanged cofactor function of human high molecular weight kininogen induced by human plasma kallikrein.

Plasma kallikrein activated spontaneously during the purification of prekallikrein (I) and acetone-activated plasma kallikrein (II) were at pH 7.4 both capable of reducing the capacity of purified human high molecular weight kininogen (HMrK) to function as cofactor in the contact phase activation of factor XII in a crude plasma preparation. At pH 6.8 only I had such an effect. SDS polyacrylamide gel electrophoresis with reduction indicated that both I and II contained kallikrein as a cleaved 'three-chain molecule. I contained in addition a Mr 49,000 fraction reflecting possibly uncleaved heavy chain. The registration of reduced cofactor function of HMrK induced by plasma kallikrein is discussed in view of the assay procedure used.

Enzyme Activation↗

PubMed1986

Assay of kallikrein inhibitors and levels of acetone-activated kallikrein in plasma specimens from reactors to dextran or to contrast media.

The average level of kallikrein assayed as acetone-activated plasminogen activator (PGA) in plasma specimens from 10 reactors to clinical dextran or to radiographic contrast media did not differ from the level in 16 controls. This result was obtained in plasminogen-free citrated plasma stabilized with benzamidine. In the absence of benzamidine a significant reduction of PGA activity was registered in the reactor plasma, but not of activity against the tripeptide substrate S-2302 or the ester substrate BAEe. After storage of the plasma specimens for 12 to 18 months at -70 degrees, the PGA activity obtainable in reactor plasma had increased to the level registered in control plasma. Known inhibitors of plasma kallikrein and of histidine-rich glycoprotein (HRG) were assayed by radial immunodiffusion. The levels of alpha 2-macroglobulin, antithrombin-III and HRG were within the normal range in plasma from reactors, the level of C1-esterase inhibitor was slightly increased (116%), and the level of alpha 1-antitrypsin was higher than normal (124%). Evidence is provided that the loss of PGA activity taking place during acetone activation of fresh reactor plasma could not be due to a transition of native alpha-kallikrein to 3-chain beta-kallikrein. It is concluded that a plasma constituent unstable during storage is responsible for the selective and partial loss of PGA activity registered in reactor plasma.

Acetone↗

PubMed1984

Reduced cofactor function of human high molecular weight kininogen induced by human plasma kallikrein.

Most reports in the literature state that human plasma kallikrein does not destroy the capacity of human high molecular weight kininogen (HMrK) to function as a cofactor in the contact phase activation of factor XII. In the present work preparations of highly purified human plasma kallikrein that showed high plasminogen activator (PGA) activities rapidly reduced the cofactor function of human HMrK. Gel electrophoresis with SDS without reduction showed that all kallikrein preparations tested contained two protein bands, one major band with a Mr of about 83,000, and one weak band with a Mr of 80,000. The main band is probably identical with kallikrein I, which Levison & Tomalin (1982b), using Ac-Pro-Phe-Arg-OMe-HCl as substrate, found to be ten times more active (in terms of kcat/Km) than kallikrein II with Mr 3000 daltons lower. The rate of HMrK destruction in our experiments varied with the kallikrein preparation used, but assays of their hydrolytic activities against benzoyl arginine ethylester (BAEe) or the plasma kallikrein selective tripeptide substrate H-D-Pro-Phe-Arg-pNA (S-2302) did not discriminate between enzyme preparations with different HMrK-destroying capacities. Assay of PGA activities demonstrated a correlation between the level of PGA measured, and the HMrK-destroying capacity.

Carboxylic Ester Hydrolases↗

PubMed1984

Assay of prekallikrein as plasminogen proactivator in plasma specimens from reactors to dextran or to contrast media.

In a previous study of plasma specimens from reactors to clinical dextran, it was concluded that a factor activated by acetone converted the high-molecular-weight kininogen (HMrK) into a non-functional state. We recently identified the HMrK-destroying factor as a plasma kallikrein modification with high plasminogen activator (PGA) activity. The aim of the present work was to investigate whether the level of plasma kallikrein, assayed as PGA on fibrin plates, was higher than normal in plasma from patients reacting to dextran or radiographic contrast media. Plasma specimens from 10 reactors and 16 controls were examined. No difference in PGA level could be detected between reactors and controls in citrated plasma stabilized with benzamidine 9 mM, whereas a significant loss of PGA activity took place in citrated reactor plasma during the acetone activation procedure. The loss of PGA activity could not be due to known inhibitors of plasma kallikrein. It was only partial, and did not influence the amidase effect against the tripeptide substrate H-D-Pro-Phe-Arg-pNA. The results might indicate the presence in plasma of different amounts of an unknown constituent important for the obtainable level of plasma kallikrein with high PGA activity. The significant loss of PGA activity in reactor plasma might indicate an abnormally high level of the unknown plasma factor.

Acetone↗

PubMed1983

Separation of plasma kallikrein and a kallikrein-like plasminogen activator generated by acetone in rat plasma.

Plasminogen activator (PGA), kininogenase (Kase) and benzoyl arginine ethyl ester (BAEe) activities generated in plasminogen-free rat plasma by incubation with acetone (23% v/v) at 22 degrees were purified. The activities passed unadsorbed through columns of DEAE-Sephadex A-50 (pH 7.8) and arginine methylester-Sepharose 4B (pH 8.5). Part of the activities (rat plasma kallikrein) was adsorbed onto a soybean trypsin inhibitor (SBTI)-Sepharose 4B column at pH 8.5. At pH 7.0 a fraction with higher ratios PGA/BAEe esterase and Kase/BAEe esterase was also adsorbed. Both fractions could be eluted with 5 mM sodium hydroxide. The fraction not adsorbed at pH 8.5, but adsorbed at pH 7.0 was designated low molecular weight plasminogen activator (LMr-PGA), a plasminogen activator fraction with higher molecular weight, but without esterase activity being also present (Berstad & Briseid 1982). LMr-PGA was strongly inhibited by tranexamic acid (AMCA) 0.10 mM, whereas the fraction designated rat plasma kallikrein was not. By polyacrylamide gel electrophoresis Mr-values in the range 120,000 to 130,000 were established for native samples of both rat plasma kallikrein and LMr-PGA, whereas Mr-values of 78,000 to 80,000 were established after treatment with SDS.

Acetone↗