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Biomedical subjects

M Jochum

Publications and source records attributed to M Jochum.

At least 127 records · Page 7Linked to original sources
PubMed1986

Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents.

Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.

Animals↗
PubMed1986

Granulocyte proteinases as mediators of unspecific proteolysis in inflammation: a review.

In severe inflammatory response, various blood and tissue cells, including polymorphonuclear granulocytes, release lysosomal proteinases, extracellularly and into the circulation. Such enzymes, as well as normally intracellular oxidizing agents produced during phagocytosis, enhance the inflammatory response by degrading connective tissue structures, membrane constituents and soluble proteins by proteolysis or oxidation. We first used polymorphonuclear elastase (E) as a marker of such release reactions. The liberated proteinase competes with susceptible substrates, including alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin, and is eliminated finally as inactive enzyme-inhibitor complexes by the reticulo-endothelial system. Using an enzyme-linked immunosorbent assay, we determined the plasma levels of E-alpha 1PI following major abdominal surgery, multiple trauma and pancreatogenic shock. Whereas the operative trauma was followed by up to 3-fold increase of the E-alpha 1-PI, postoperative septicemia was associated with a 10 to 20 fold increase. The increase of E-alpha 1-PI and a concomitant decrease of plasma factors, such as antithrombin III, clotting factor XIII and alpha 2-macroglobulin, were correlated. Multiple trauma causes a substantial increase of E-alpha 1-PI up to 14 hours after accident. The released elastase seems to correlate with severity of injury, but assessing the relationship to consumption of plasma factors is complicated by concomitant transfusions. In acute pancreatitis, peaks, of E-alpha 1-PI coincide with a massive consumption of antithrombin III and alpha 2-macroglobulin during shock.

Blood Proteins↗
PubMed1985

The concentration of leukocyte elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy human subjects.

Although alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is widely thought to protect lung elastin against the elastolytic action of leukocyte elastase, there is only circumstantial evidence for such a protective role. We have demonstrated and quantified elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy smokers and nonsmokers using a new enzyme-linked immunosorbent assay. The relative concentration of complex is 0.36 +/- 0.48 mmol/mol albumin in nonsmokers and 0.33 +/- 0.29 mmol/mol albumin in smokers. Less than 1% of lavage fluid alpha 1-proteinase inhibitor is complexed with elastase (0.31% in nonsmokers and 0.34% in smokers). This proportion is, however, much higher than in normal plasma where only approximately 0.006% of inhibitor is bound to elastase. Our data confirm that alpha 1-proteinase inhibitor efficiently acts as an antielastase barrier in the lower respiratory tract.

Bronchi↗
PubMed1985

Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery.

To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.

Abdomen↗
PubMed1985

[The PMN elastase plasma level, a biochemical parameter of the severity of trauma].

Polytrauma patients with defined severity of trauma showed a significant release of lysosomal enzymes as measured by PMN leucocyte elastase-alpha 1 proteinase inhibitor complex in plasma. A positive correlation was found between the amount of liberated elastase and the severity of trauma (- indicated by means of extent of tissue trauma and blood loss). The concentration of elastase complexed with alpha 1 proteinase inhibitor may serve as an indicator for the severity of trauma and as an objective parameter supplementing the scales and scores used until now, which all are based upon subjective judgement.

Adolescent↗
PubMed1985

Isolation and characterization of porcine leukocyte elastase. Leukocyte elastase-inhibitor complexes in porcine blood, II.

Porcine leukocyte elastase was purified from granulocytes by chelating chromatography on copper chelate Sepharose and by ion exchange chromatography on CM-Sepharose. Thus an enzyme preparation with a specific activity (substrate: MeOSuc(Ala)2ProValNan) of 89.3 U/mg protein was obtained. Dodecyl sulphate gel electrophoresis revealed one protein band corresponding to a molecular mass of 27 kDa. The amino acid composition was determined and isoleucine was identified as the only N-terminal amino acid residue. The bimolecular velocity constant for the inhibition by diisopropyl fluorophosphate was determined as 2000 1 . mol-1 . min-1. The dissociation constants, Ki, of the complexes of porcine leukocyte elastase with various inhibitors were calculated. The kinetic constants for the elastase-catalysed hydrolysis of MeOSuc(Ala)2ProValNan, Suc(Ala)2ValNan and Suc(Ala)3Nan were determined, as well as the kinetic constants of the inactivation of leukocyte elastase by active site mapping reagents. Detergents such as Triton X-100, Tween 20 and Brij 35, as well as porcine serum albumin, activated the porcine leukocyte elastase preparation.

Animals↗
PubMed1984

Proteolytic activity in patients with hypercatabolic renal failure.

Proteolytic enzymes exist in ultrafiltrated plasma, concentrated dialysates and urine fractions of patients with posttraumatic renal failure. Differences in digestion pattern of phosphorylase kinase suggest the existence of different proteases in patients with hypercatabolic renal failure. Trypsin binding capacity is reduced in RDT patients and markedly lower in patients with posttraumatic ARF. Protein catabolism is inhibited in vitro by alpha 2-macroglobulin. From our in vitro studies we favour the application of fresh frozen plasma instead of the available plasma protein solutions to hypercatabolic patients. Hemodialysis may enhance proteinase inhibitory capacity of the plasma. Hemodialysis therapy induces the increase of plasma E-X1 PI. The continuous release of granulocyte elastase during hemodialysis therapy may enhance the risk for the development of destructive lung disease.

Acute Kidney Injury↗
PubMed1984

Plasma levels of human granulocytic elastase alpha 1-proteinase inhibitor complex (E-alpha 1-PI) in leukemia.

There is evidence that polymorphonuclear granulocytes release neutral proteinases such as elastase (E) and cathepsin G in the course of acute leukemia. These proteinases may inactivate clotting factors by unspecific degradation before they are eliminated via complex formation with endogenous inhibitors, e.g. the alpha 1-proteinase inhibitor (alpha 1-PI). In this study it was attempted to correlate plasma levels of the E-alpha 1-PI complex with factor XIII and antithrombin III in acute leukemia. Using a newly developed, sensitive enzyme-linked immunoassay the concentration of E-alpha 1-PI in patients with various types of leukemia, malignant lymphoma or multiple myeloma was determined. Only patients with acute myelocytic or promyelocytic leukemia (AML, APL) and chronic myelocytic leukemia with and without blastic transformation (CML) showed moderate to high levels of E-alpha 1-PI (2- to 20-fold of normal). However, coagulation factor concentration observed in the different types of leukemia seemed to be independent of elastase liberation. Most of the AML-patients with elevated E-alpha 1-PI levels showed peroxidase positive blood cell smears.

Acute Disease↗
PubMed1983

Inter-alpha-trypsin inhibitor of human serum: an inhibitor of polymorphonuclear granulocyte elastase.

Inter-alpha-trypsin inhibitor (ITI) was separated from human serum in a single step using ion-exchange chromatography via the fast protein liquid chromatographic system. The inhibitor preparation, identified as ITI by specific immunological assays, inhibited human polymorphonuclear granulocytic elastase besides bovine trypsin. Hence, ITI is the third candidate of the plasma proteinase inhibitors (in addition to alpha 1-proteinase inhibitor and alpha 2-macroglobulin) capable of inhibiting lysosomal granulocytic elastase.

Alpha-Globulins↗
PubMed1982

Disturbances of selected plasma proteins in hyperdynamic septic shock.

This study was performed on patients (n = 18) suffering from strictly defined hyperdynamic septic shock. Plasma factors (C-reactive protein, acid alpha 1-glycoprotein, fibrinogen, fibrinopeptide A, fibrinogen-fibrin split products, factor XIII, antithrombin III, complement factors C3 and C4, inter-alpha-trypsin-inhibitor and alpha 2-macroglobulin) measured during hyperdynamic septic shock were highly abnormal. The activation and consumption of clotting, fibrinolytic and complement factors due to system-specific proteinases (such as thrombokinase or plasminogen activators) seemed to be intensified by the nonspecific proteolytic activity of granulocytic proteinases probably released by the action of endotoxins. Possible therapeutic measures to maintain the endogeneous defence mechanism against enhanced proteolysis during septic shock are discussed.

Alpha-Globulins↗
PubMed1981

Clotting and other plasma factors in experimental endotoxemia: inhibition of degradation by exogenous proteinase inhibitors.

Endotoxemia in dogs was induced by a slow intravenous infusion of E. coli endotoxin for 2 h. Thereby, a significant decrease was observed in the plasma levels of several clotting, fibrinolysis and complement factors. The changes were studied over an experimental period of 14 h and checked for statistical significance by three-way analysis of variance. Application of the broad-spectrum proteinase inhibitor aprotinin (Trasylol) from bovine organs clearly lowered the endotoxin-induced decline of the plasma proteins studied. By intravenous application of a specific granulocytic proteinase inhibitor (Bowman-Birk inhibitor from soybeans), the endotoxin-induced reduction of the plasma proteins was prevented in a similar manner. It can be concluded that at least some of the pathobiochemical mechanisms observed in clotting, fibrinolysis and complement systems during endotoxemia are not only caused by a severe consumption reaction but also by unspecific proteolytic degradation due to neutral granulocytic proteinases.

Animals↗