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Biomedical subjects

K Ohlsson

Publications and source records attributed to K Ohlsson.

At least 163 records · Page 9Linked to original sources
PubMed1985

The mucosal defence capacity against proteolytic leukocyte enzymes.

Proteolytic enzymes are released from granulocytes in connection with normal turnover and phagocytosis. Interest has been focused on granulocyte elastase as it has been shown to be associated with the development of lung emphysema. Elastase is present in purulent bronchial secretions where it is the dominating cause of elastolytic activity. The dominating inhibitors of elastase in the respiratory tract are alpha 1-antitrypsin and antileukoprotease. Antileukoprotease, which seems to be locally produced, is a potent inhibitor of elastase and accounts for about 90% of the inhibiting capacity against elastase. A local protective function of antileukoprotease is suggested by the finding that antileukoprotease was bound to granulocyte elastase in purulent bronchial secretions. The function of alpha 1-antitrypsin and antileukoprotease is reduced by the addition of smoke condensate in a dose- and time-dependent way. Smoke condensate was also found to depress the enzymatic activity of granulocyte elastase. Further studies of the protease-antiprotease balance in bronchial secretions from smokers with and without airway disease are necessary before any conclusions can be drawn regarding the pathophysiological significance of these results.

Bronchi↗
PubMed1985

Experience of surgical treatment for chronic pancreatitis during a 10-year period.

Surgical treatment for chronic pancreatitis is performed usually because of severe pain and in case of complications like pseudocysts or obstruction of common bile duct or duodenum. Operative treatment is either ductal drainage or resection. The preoperative evaluation must include determination of operative strategy and ERCP seems to give the best information. In the present study the results of surgical treatment in 50 patients during a 10-year period were studied with a follow-up period with a mean of 76 months (range 6-120 months). Alcoholic abuse was the cause of disease in 30 of the 50 operated patients. In 22 patients ductal drainage was performed and in our experience a better result was achieved with a longitudinal than a distal pancreaticojejunostomy. The best results with resectional procedures were achieved when about 80% of the gland was resected. Pseudocysts were drained internally with good results. Poor results were noted especially in cases with continued alcoholic abuse.

Adult↗
PubMed1984

Changes in the kallikrein kinin system during acute pancreatitis in man.

Changes in the kallikrein-kinin system were analysed in 19 attacks of acute pancreatitis in man and correlated to the severity and clinical course of the disease. Prekallikrein, kininogen and kallikrein inhibition were significantly lower in blood in severe attacks than in moderate or mild attacks. These changes were even more pronounced in peritoneal fluid, where kallikrein activity was above normal, while kininogen and kallikrein inhibition were nil in severe attacks. Both high and low molecular weight kininogen were decreased, denoting an activation also by kininogenases other than plasma kallikrein. These changes indicate an activation of the kallikreinkinin system in acute severe pancreatitis in man, especially in the abdominal cavity. Although there is a great deal of evidence for activation of the kinin system in experimental shock states in animals (1-4), there are to date rather few studies showing that such an activation takes place in human acute pancreatitis. This lack of clinical studies is mainly explained by the difficulty in measuring activated components of the system, especially since these components are rapidly inactivated in different ways in vivo (5).

Acute Disease↗
PubMed1984

Interaction of granulocyte proteases with inhibitors in pulmonary diseases.

The elastase-antielastase hypothesis of lung tissue destruction has focused our interest on the two main inhibitors of granulocyte elastase in the lung, alpha 1-antitrypsin dominating blood, interstitial tissue and alveolar fluid lining and antileukoprotease dominating the respiratory tract mucosa. Antileukoprotease as well as elastase and alpha 1-antitrypsin show increased serum levels during bronchitis and bronchopneumonia, alpha 1-antitrypsin because it is an acute phase reactant, elastase and antileukoprotease because of influx from the inflamed tissues. Elastase is identified in the bronchial expectorates, mainly in complex with antileukoprotease, but often also in a free, active form. The granulocyte elastase in serum from these patients is, however, only found in complex with alpha 1-antitrypsin. The increased amounts of antileukoprotease in serum are always in a free and largely active form. The explanation for the absence of elastase-antileukoprotease complexes in serum is offered by some of our recent results. The elastase-antileukoprotease complexes are rapidly dissociated when mixed with serum in vitro, although the equilibrium dissociation constant Ki of the complex is 1.2 X 10(-11) M. Furthermore, in a pure in vitro system, alpha 1-antitrypsin is able to dissociate a leukocyte elastase-antileukoprotease complex with the rate constant of 1.3 X 10(-4) X S-1. A small part of the antileukoprotease released from the elastase-antileukoprotease complex on mixture with serum is recovered bound by elastase-alpha 2-macroglobulin complexes. Antileukoprotease inhibits the enzymatic activity of elastase-alpha 2-macroglobulin complex relatively slowly. 1:1 elastase-alpha 2-macroglobulin complexes are, however, inhibited more readily than 2:1 saturated complexes.

Bronchitis↗
PubMed1984

On the potential role of trypsin and trypsin inhibitors in acute pancreatitis.

The protective role of alpha 2-macroglobulin, alpha 1-antitrypsin and Aprotinin against trypsin-induced effects on C3 and kininogen was studied in a human in vitro model. When human cationic trypsin was added to human serum or plasma, there was a gradual saturation of alpha 2-macroglobulin and later of alpha 1-antitrypsin. When alpha 2-macroglobulin was 70% saturated, there was a prompt cleavage of both C3 and kininogen, in spite of 80% free and active alpha 1-antitrypsin. These biochemical changes and antiprotease levels are identical to our findings in patients with acute pancreatitis, especially in their peritoneal exudate. Very high concentrations of Aprotinin, 5-15 times higher than ever used clinically, blocked the cleavage of both C3 and kininogen, while doses commonly used clinically were without significant effect. The clinical implications are: A trypsin-induced activation of both the complement and kinin system with clinical consequence is possible in patients with acute pancreatitis because of very low alpha 2-macroglobulin levels. Aprotinin in adequate doses, 5-15 times higher than ever used clinically, seems to protect against activation of two systems.

Acute Disease↗
PubMed1984

Quantitation of some pancreatic juice exocrine proteins in the presence of radiocontrast medium used in endoscopic retrograde pancreatography (ERP).

The endoscopic collection of human pancreatic juice for chemical analysis is facilitated by the use of radiocontrast media. However, the effects of this material on pancreatic juice and the techniques used to analyze its proteins are unknown. This study has demonstrated no detrimental effects of a commonly used contrast medium on the pancreatic juice itself or on the analytic technique of radioimmunoassay and radial immunodiffusion. Likewise, the Phadebas enzymatic technique for amylase was not affected by this material. We conclude that techniques for the collection of pure pancreatic juice using radiocontrast material do not interfere with the analysis of pancreatic juice proteins using the techniques described.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1984

Fate of intravenously injected trypsin in dog with special reference to the existence of an enteropancreatic circulation.

In 3 mongrel dogs the pancreatic duct and bile duct were cannulated. After intravenous injection of 125I-labelled anionic dog trypsin bile, pancreatic juice and blood samples were collected during 3 h. 125I-trypsin is eliminated from the circulation in dogs with a half time of 15 min. Only 0.15% of the radioactivity is secreted in the pancreatic juice and 0.75% in the bile during 3 h. 10% of the radioactivity in pancreatic juice is protein bound and 45% in the bile is protein bound. The results argue against biologically significant enteropancreatic circulation of trypsin in dogs.

Animals↗
PubMed1984

Trypsin-like immunoreactivity in human Paneth cells.

Human intestinal Paneth cells characterized by their content of lysozyme were shown to contain cationic trypsin immunoreactivity. This trypsin-like immunoreactivity was shown in the Paneth cells at their normal localization at the basis of the crypts of Lieberkühn and also in Paneth cells of metaplastic areas in gastric mucosa. This original finding is a further indication of a resemblance between Paneth and acinar pancreatic cells.

Duodenum↗
PubMed1984

Interactions of the complex between human urinary trypsin inhibitor and human leukocyte elastase with alpha 1-proteinase inhibitor and alpha 2-macroglobulin.

The urinary trypsin inhibitor was recently shown to inhibit human leukocyte elastase. Complexes of human urinary trypsin inhibitor with human leukocyte elastase or human trypsin were produced and subjected to gel filtration. The complexes were found to be sufficiently stable up to 24 h incubation (at least 70% recovery). When human serum was added, elastase and trypsin dissociated from the urinary trypsin inhibitor and associated with alpha 1-proteinase inhibitor or alpha 2-macroglobulin. The addition of alpha 1-proteinase inhibitor to a complex of urinary trypsin inhibitor and leukocyte elastase caused a rapid dissociation of the complex (kdiss = 3.2 X 10(-2) s-1).

Autoradiography↗
PubMed1984

Gabexate mesilate (FOY) and aprotinin. A comparative study of the effects on trypsin-induced activation of the kinin and complement systems in vivo and in vitro.

The effect of gabexate mesilate (FOY) was studied in vitro in human and canine serum upon the addition of trypsin, and in vivo in dogs during intravenous trypsin infusion. The effect of FOY was compared with the effect of aprotinin. FOY did not show any protection against trypsin-induced activation of the complement and kinin systems in vitro or in vivo, while aprotinin did. All dogs exhibited signs of circulatory shock together with a consumption of the two main proteinase inhibitors, alpha-macroglobulin and alpha 1-proteinase inhibitor, when intravenous infusions of FOY and trypsin were performed simultaneously. However, all dogs survived without signs of shock if aprotinin was given instead of FOY. The ineffectiveness of FOY in serum is explained by the complete dissociation of FOY trypsin complexes together with a rapid degradation of FOY to inactive metabolites. Although FOY is an effective proteinase inhibitor in defined buffer systems in vitro, the results of the present study indicate that it is not an effective proteinase inhibitor in vivo. Aprotinin protects against trypsin-induced activation reactions, although much higher concentrations are needed in human than in canine serum.

Animals↗
PubMed1984

Aprotinin turn-over studies in dog and in man with severe acute pancreatitis.

The elimination of aprotinin after intravenous infusion was exponential until 95% of the dose was cleared from the plasma after 1 h in dogs with bile-induced pancreatitis. The half-life of this part of the elimination was 10 min. The concentration of aprotinin in the peritoneal fluid reached a maximum plateau after 1 h. Direct intra-abdominal infusion of aprotinin was followed by a relatively slow elimination of the inhibitor from the cavity. One hour after the infusion the concentration of aprotinin in the peritoneal exudate was about 50% of the initial value. Four hours later the concentration of inhibitor with unchanged immunoreactivity and inhibiting capacity was still about 25% of the initial value. Based on the results of this experimental study an intraperitoneal dosage schedule for aprotinin was tested in three patients with haemorrhagic pancreatitis. A total amount of 14 X 10(6) KIU was given in repeated dosages during 18 h. This resulted in a minimum level of aprotinin in the peritoneal exudate of about 10 mumol/l. According to our earlier published data this level should largely block trypsin-induced effects relevant in pancreatitis. In conclusion; due to the rapid elimination of aprotinin from plasma, after i.v. application a therapeutically useful concentration is never reached in the peritoneum, while the elimination from the peritoneum is relatively slow, thus providing therapeutically useful concentrations which can be maintained for some time after i.p. application.

Acute Disease↗
PubMed1984

On the role of the pancreatic secretory trypsin inhibitor as an inactivator of trypsin-alpha 2-macroglobulin complexes in acute pancreatitis.

High levels of immunoreactive pancreatic secretory trypsin inhibitor (PSTI) were demonstrated in the serum and peritoneal exudates of patients suffering from acute pancreatitis. Trypsin-like immunoreactivity in these fluids was found in complex with alpha 1-antitrypsin and in complex with alpha 2-macroglobulin and also as a free peak correlating to free trypsin(ogen). No trypsin-PSTI complexes or PSTI were demonstrated in the macroglobulin fraction of the peritoneal exudates. Saturated and partially saturated trypsin-alpha 2-macroglobulin complexes were prepared in vitro. PSTI was able to partially inhibit the BzArgNan-cleaving activity of both types of complexes in a slow dose-dependent non-linear reaction. Equilibrium was reached in each case within 1 h, but total inhibition was not reached even with large amounts of PSTI. Partially saturated trypsin-alpha 2-macroglobulin complexes were inhibited more readily than saturated complexes. The results support the concept of PSTI acting as a strictly local inhibitor of trypsin in compartments lacking plasma protease inhibitors.

Acute Disease↗
PubMed1984

A method for determination of immunoreactive trypsin in complex with alpha 1-antitrypsin in human sera.

A double antibody solid phase radioimmunoassay for the determination of cationic trypsin in complex with alpha 1-antitrypsin in human sera is described. No immunoreactive trypsin in complex with alpha 1-antitrypsin can be detected in normal sera. In sera from 8 patients with acute pancreatitis levels between 100 and 1000 micrograms/l are seen. The amount of trypsin in complex with alpha 1-antitrypsin in serum in acute pancreatitis equals or exceeds the amount of trypsinogen. Serum levels of trypsin in complex with alpha 1-antitrypsin also remain elevated longer than the trypsinogen levels in acute pancreatitis.

Acute Disease↗
PubMed1984

Protease inhibitors in acute human pancreatitis. Correlation between biochemical changes and clinical course.

A clinical and biochemical analysis of 27 attacks of acute pancreatitis was made throughout the course of the disease. In severe attacks alpha 2-macroglobulin (alpha 2-M) decreased during the first days, reaching values in blood below 40% of the normal value. In addition, this remaining alpha 2-M had a decreased trypsin-binding capacity, indicating circulating alpha 2-M protease complexes. The inter-alpha-trypsin inhibitor concentration was also decreased, whereas alpha 1-proteinase inhibitor, antichymotrypsin, and pancreatic secretory trypsin inhibitor increased. All changes were most pronounced in the peritoneal fluid and were also closely correlated to the severity of the disease, assessed by both Ranson's and McMahon's classification systems. All patients with clinical complications had profound biochemical changes. In accordance with earlier findings, activation of both the complement and kinin systems seems possible in both blood and peritoneal fluid at the low alpha 2-M concentrations found in severe attacks.

Acute Disease↗
PubMed1984

Studies on the role of antileukoprotease in respiratory tract diseases.

Antileukoprotease, an inhibitor of granulocyte elastase, was studied in paired sera from 19 patients with pneumonia and from 9 patients with cholecystolithiasis. The circulating level of antileukoprotease was significantly higher in patients with pneumonia compared with patients with cholecystolithiasis. In the latter group, surgery raised the level of general acute phase reactants, but did not affect the level of antileukoprotease. In sera from patients with pneumonia, antileukoprotease was recovered in a free and active form, as shown by gel-filtration of sera before and after the addition of leukocyte elastase. A local protective function of antileukoprotease is suggested by the finding that antileukoprotease was bound to granulocyte elastase in purulent bronchial secretions.

Acute-Phase Proteins↗
PubMed1984

Peritoneal lavage in severe acute pancreatitis.

An analysis is presented of 73 attacks of acute pancreatitis treated with non-operative peritoneal lavage, classified according to Ranson's 11 signs and followed up for on average four years. None of the 21 moderate attacks was associated with complications or mortality. In the 52 severe attacks, four patients (7.7%) died, new pseudocyst developed in five patients (9.6%) and abscess in four (7.7%), and diabetes was found in 12 patients (23%) at follow-up. In all these respects the severe attacks showed statistically significant difference from the moderate attacks, as did the need for assisted ventilation, the volume of gastric retention and the length of hospital stay. The authors conclude that non-operative peritoneal lavage is beneficial, probably by removing toxic substances from the peritoneal cavity.

Acute Disease↗
PubMed1984

Immunocytochemical distribution of trypsinogen and pancreatic secretory trypsin inhibitor in normal and neoplastic tissues in man.

Immunoreactive trypsinogen and pancreatic secretory trypsin inhibitor (PSTI) were demonstrated in pancreas by means of an immunoperoxidase technique. They had the same distribution in acinar cells of 'normal' human exocrine pancreas tissues. Ductal adenocarcinoma tissue and pancreatic undifferentiated carcinoma contained neither antigen. Scattered 'normal'-looking cells in the border area between normal and neoplastic tissue of both types of tumor stained positively for trypsinogen and for PSTI.

Adenocarcinoma↗