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Biomedical subjects

K Ohlsson

Publications and source records attributed to K Ohlsson.

At least 199 records · Page 11Linked to original sources
PubMed1982

Protease inhibitors and their relation to protease activity in human milk.

Protease inhibitors and protease (caseinolytic, elastinolytic and esterolytic) activity were analysed in 190 milk samples from 94 mothers from day 1 to day 160 after delivery. The main protease inhibitors in human milk are alpha 1-antichymotrypsin and alpha 1-antitrypsin. As measured by electroimmunoassay, the level of alpha 1-antichymotrypsin in day 1 colostrum was higher than that in normal serum. Trace amounts of inter-alpha-trypsin inhibitor, alpha 2-antiplasmin, alpha 2-macroglobulin, antithrombin III, or antileukoprotease could be demonstrated. According to their protease inhibiting activity, the 53 milk samples from day 1-3 could be divided into two groups. (1) Presence of protease inhibiting activity (n = 35). Both alpha 1-antitrypsin and alpha 1-antichymotrypsin appeared intact and were able to form complexes with added trypsin or chymotrypsin although the major part of alpha 1-antichymotrypsin showed a retarded electrophoretic mobility. The proteolytic inhibiting activity, in spite of the presence of immunoreactive inhibitors (n = 18). alpha 1-antichymotrypsin had a precipitate pattern similar to group 1, whereas alpha 1-antitrypsin had a major fraction with slightly retarded mobility and two minor peaks in the alpha 1-and beta-regions. These precipitate patterns were unchanged on addition of human trypsin or chymotrypsin compatible with the presence of nonreactive inhibitor only. These samples had a caseinolytic and esterolytic activity with an electrophoretic mobility in the beta-region. All samples from day 4 and later had a demonstrable protease inhibiting activity.

Chymotrypsin↗
PubMed1982

Glutaminyl-peptide gamma-glutamyltransferase dependence of the uptake of trypsin-alpha-macroglobulin complexes by macrophages.

The canine alpha-macroglobulin 125I-trypsin complexes were prepared and exposed to canine alveolar macrophages. The binding of the complexes to cells was time- and dose-dependent. A rapid uptake and degradation of the bound complexes was evidenced by the finding of less than 20% cell-bound radioactivity after a 4 h incubation at 20 degrees C. The canine alveolar macrophages contain a glutaminyl-peptide gamma-glutamyltransferase which shows slightly retarded agarose gel electrophoretic mobility as compared to the respective enzymes from tissues of other species, such as guinea pig and man. Evidence is presented that the binding and degradation of trypsin alpha-macroglobulin complexes by macrophages is dependent on this gamma-glutamyltransferase. Monodansylthiacadaverine, a strong inhibitor of this enzyme, blocks the binding of trypsin-alpha-macroglobulin complexes to macrophages and (probably as a consequence of this) degradation of the complexes. Furthermore, this gamma-glutamyltransferase is a calcium-dependent enzyme and the process of binding trypsin-alpha-macroglobulin complexes to the macrophages was likewise found to be calcium-dependent.

Acyltransferases↗
PubMed1982

Human granulocyte elastase is inhibited by the urinary trypsin inhibitor.

Two forms of urinary trypsin inhibitor, A and B, were purified from the urine of pregnant women. Form A was the only inhibitor present in fresh urine and inhibitor B arose from degradation of A upon storage of urine. The molecular masses of A and B were about 44 and 20 kDa, respectively, as judged from dodecyl-sulfate polyacrylamide gel electrophoresis, but about 60 kDa and 30 kDa, respectively, as judged from gel filtration analysis. The discrepancy can perhaps be explained by the carbohydrate content amounting to about 10% of each inhibitor. After reduction with mercaptoethanol, inhibitor A and inhibitor B had identical apparent molecular masses of about 20 kDa on dodecyl-sulfate gel electrophoresis. These results and the results of amino acid analysis suggest that one molecule of inhibitor A yields two molecules of inhibitor B. On agarose gel electrophoresis inhibitor A migrated as a rather broad band in the prealbumin region and inhibitor B as 3 well defined bands in the beta-region. Specific antisera were raised against inhibitor A and B. The two inhibitors showed the immunologic reaction of identity with each other and with the plasma inter-alpha-trypsin inhibitor, when using either antiserum. The inhibitors both gave quantitative inhibition of bovine trypsin, the results indicating a 4/1 trypsin/inhibitor molar ratio for A and a 2/1 ratio for B. The two substances also effectively inhibited granulocyte elastase. No inhibition of porcine pancreatic elastase was demonstrable.

Amino Acids↗
PubMed1982

The elimination of alpha 2-macroglobulin complexes from the arthritic joint. An experimental study in dogs.

The polyvalent protease inhibitor, alpha 2-macroglobulin, may counteract a protease-mediated rheumatoid joint destruction. The elimination of the complexed inhibitor from joints was analysed in inflamed and noninflamed conditions of the knee joints in dogs. The arthritis was immunologically induced. The fate of intra-articularly injected radioactive alpha 2-macroglobulin complexes was studied by external measurements, analyses of blood, lymph and urine, and by autoradiographic and immunohistologic methods. The results indicate that the elimination of complexes was accelerated by inflammation and joint movements with a half-life shorter than 2 hours in acute arthritis. In addition to absorption into the synovial membrane and degradation in macrophage-like cells, the process of clearance included elimination of complexes via the blood and the lymph capillaries of the joint and subsequent degradation in cells belonging to the reticuloendothelial system in the lymph nodes and the liver. The degradation products were excreted in increasing amounts in the urine. Referring to the earlier recognized high degree of saturation of synovial fluid alpha 2-macroglobulin in rheumatoid arthritis, the finding of a rapid articular clearance of alpha 2-macroglobulin complexes suggests a pronounced release of endoproteases under clinical conditions.

Animals↗
PubMed1982

Immunoreactive granulocyte elastase in rheumatoid synovial fluid and membrane.

A specific radioimmunoassay (RIA) was utilized to determine granulocyte elastase in the synovial fluid of a series of 45 rheumatoid joints in 39 patients. The average concentration was approximately 340 micrograms/l, exceeding that of the paired serum sample in all but 6 cases. No correlation was noted in synovial fluid between its content of granulocyte elastase and the total number of white blood cells. The concentrations in sera from rheumatoid patients with non-steroidal anti-inflammatory agents and controls were equivalent. Non-inflammatory exudates contained low concentrations of elastase. The immunoreactive granulocyte elastase in rheumatoid synovial fluid was bound to alpha 1-antitrypsin suggesting release of the enzyme in its active form. An uptake of elastase-containing complexes by macrophage-like cells in the synovial membrane was demonstrated by immunohistochemical staining of tissue using antiserum against granulocyte elastase. The concentrations of immunoreactive granulocyte elastase in the free synovial fluid of rheumatoid arthritic joints presumably only faintly reflect the situation concerning the target substrates.

Adolescent↗
PubMed1982

Immunoreactive alpha 2-macroglobulin in rheumatoid synovial membrane.

alpha 2-Macroglobulin was demonstrated immunohistochemically in macrophage-like cells of rheumatoid arthritic synovial tissue. It is concluded that these intracellular deposits probably represent phagocytosed protease-alpha 2-macroglobulin complexes. A contributing local production of alpha 2-macroglobulin is, however, not excluded by the present findings.

Adult↗
PubMed1982

The elimination of alpha 2-macroglobulin complexes from the arthritic joint. A clinical study in rheumatoid arthritis.

A phagocytic uptake of labeled elastase-alpha 2-macroglobulin complexes by macrophage-like synovial lining cells was demonstrated in rheumatoid arthritics. The appearance and distribution of these phagocytically active cells were similar to those containing immunoreactive alpha 2-macroglobulin. It was concluded that these deposits represented phagocytosed alpha 2-macroglobulin complexes and that the elimination of complexes from the arthritic joint at least partly was effected via local phagocytosis.

Aged↗
PubMed1981

Cyclic variation of proteinase inhibitors in human uterine fluid and influence of an IUD.

The occurrence of the serum proteinase inhibitors in uterine fluid has been evaluated using a quantitative immunoelectrophoretic method. Low concentration of inhibitors were found in the proliferative phase and at midcycle, and high concentrations in the luteal phase. In the presence of an IUD, increased concentrations of inhibitors were found in the proliferative phase and at midcycle. This may result from an increased transudation associated with local inflammation of the endometrium. Plasma proteinase inhibitors in the uterine fluid may help to balance proteinases associated with the intrauterine stages of reproduction. Increased amounts of native inhibitors in the presence of an IUD may disturb this normal balance.

Adolescent↗
PubMed1981

A radioimmunoassay for measurement and characterization of human antileukoprotease in serum.

This report describes a radioimmunological method for the measurement of the protease inhibitor antileukoprotease in nanogram quantities. Antileukoprotease, previously found in bronchial secretions, has now also been found in serum using this radioimmunologic technique. In healthy blood donors the serum level was 126 micrograms/l. The serum immunoreactive antileukoprotease was found in a free form and did not show any antigenic cross reaction with the normal plasma protease inhibitors. Further, it was also found to be active and to form a complex with active human granulocyte elastase.

Humans↗
PubMed1981

Localization and quantitation of a low molecular weight proteinase inhibitor, antileukoprotease, in the human uterus.

Antileukoprotease was demonstrated in the cervical mucosa, but was absent in the endometrium. It was shown immunohistologically to predominate in the epithelial lining of the cervical crypts. High concentrations were found in the cervical mucus. Although antileukoprotease was not present in the endometrium, low concentrations were found in the uterine fluid, probably secondary to diffusion from the cervical mucus. The concentration of antileukoprotease in cervical mucus varied greatly during the menstrual cycle, but no midcycle minimum was found. Increased concentrations were found in samples obtained during the week preceding onset of the menstruation in most women. Antileukoprotease was present in uterine fluid from intra uterine device (IUD) non-users in its free form. In fluid from IUD users it was partly in its free form, and partly in a complexed form. The major part of the non-complexed portion was biologically active. The complex consisted, at least partly, of elastase bound to antileukoprotease. Antileukoprotease may thus contribute to the neutralization of granulocyte elastase in the uterine fluid of IUD users.

Female↗
PubMed1981

Studies on the role of the plasma protease inhibitors on in vitro C3 activation and in acute pancreatitis.

Plasma samples from 32 patients with severe acute pancreatitis contained cleavage products of C3, and the C3 levels were significantly lower than those of control subjects. Peritoneal exudate from all patients showed complete degradation of C3 on crossed immunoelectrophoresis. Alpha 1-Antitrypsin and alpha 2-macroglobulin showed no signs of complex formation in plasma. However, in the peritoneal exudate, 5%-25% of the alpha 1-antitrypsin and 45%-100% of the alpha 2-macroglobulin were in complex. Trypsin-alpha 1-antitrypsin complexes were demonstrated in all peritoneal exudates. All patients showed significantly decreased levels of alpha 2-macroglobulin in their plasma. Alpha 1-Antitrypsin levels varied greatly, but the mean value was not significantly increased compared with those of normal controls. Orosomucoid, another acute-phase reactant, was present in increased concentration in the plasma of all patients. The addition of increasing amounts of human trypsin to serum in vitro resulted in the appearance of cleavage products of C3 upon saturation of alpha 2-macroglobulin, when the alpha 1-antitrypsin was found to be only about 40% saturated. Taken together, these data are evidence of complement catabolism in acute pancreatitis and suggest that this process takes place mainly in the abdominal cavity as a result of a protease-antiprotease imbalance. Alpha 2-Macroglobulin, but not alpha 1-antitrypsin, can protect against C3 degradation caused by trypsin in vitro.

Acute Disease↗
PubMed1981

Studies on the interaction of Trasylol (aprotinin) with trypsin-pancreatic secretory trypsin inhibitor (PSTI) complexes and with alpha 2-macroglobulin-trypsin-PSTI-complexes.

An investigation was performed to study the interaction of Trasylol with both trypsin-pancreatic secretory trypsin inhibitor (PSTI) and alpha 2-macroglobulin (alpha 2-M)-trypsin-PSTI complexes. Trasylol was readily able to displace immunogenic PSTI from a complex with trypsin in vitro. A similar scale of displacement of PSTI by Trasylol from alpha 2-M-trypsin-PSTI complexes could not be demonstrated. Using complexes manufactured in vitro with 125I-labelled PSTI, we found that only a small percentage of the PSTI label could be liberated, even when presented with amounts of Trasylol in a 10-molar excess to the PSTI.

Aprotinin↗
PubMed1981

Cyclic variation of plasminogen activation in human uterine fluid and the influence of an intrauterine device.

Activation of plasminogen to plasmin in uterine fluid results in the formation of plasmin-alpha 2-antiplasmin complexes. The degree of plasminogen activation was studied during the menstrual cycle in IUD-users and nonusers. The absence of free plasminogen in the presence of plasmin complexes indicated complete activation of the zymogen. The simultaneous occurrence of free plasminogen and plasmin complexes were interpreted to represent incomplete activation. Results were correlated with the concentration of alpha 2-antiplasmin, a major inhibitor of urokinase and plasmin. In the midcycle phase of IUD-non-users, plasminogen activation was complete and the concentration of alpha 2-antiplasmin was low. In the luteal phase of the same population the concentration of alpha 2-antiplasmin was high and there was no plasminogen activation. In contrast, IUD-users generally had an incomplete activation of plasminogen throughout the menstrual cycle. Also, their concentrations of alpha 2-antiplasmin were increased in the proliferative and midcycle phases.

Adolescent↗
PubMed1981

Alpha 1-antitrypsin--complexation and inactivation in the uterine fluid of IUD-users.

Electrophoretic homogeneity of alpha 1-antitrypsin (alpha 1-AT) was studied in the uterine fluid from two groups of normal women; one group was comprised of IUD-users, the other non-users. Alpha 1-AT was found in its free and active form in non-users. In IUD-users, one fraction was complexed by granulocyte elastase and neutral proteinase. The other fraction had the same electrophoretic mobility as the native inhibitor, but was inactive, as determined from trypsin inhibition studies. This may explain the finding of elastase activity together with non-complexed alpha 1-AT in some samples from IUD-users. It is concluded that uterine fluid in IUD-users possess a minimal, if any, proteinase inhibiting potential. Non-inhibited activity of granulocyte proteinases in the uterine cavity may influence hemostasis of the endometrium.

Adolescent↗
PubMed1981

Studies on the influence of heparin on trypsin-induced shock in dog.

Intravenous infusion of bovine trypsin in dogs can induce intravascular coagulation, which is claimed to be one of the causes of the shock accompanying such infusions. Treatment with heparin prior to trypsin administration prevents the usual decrease of fibrinogen but apparently does not influence the trypsin-induced shock seen upon trypsin saturation of alpha 2-macroglobulin. The prompt appearance of fibrinogen fragments following trypsin saturation of alpha 2-macroglobulin is probably a consequence of plasminogen activation. Under similar conditions alpha 1-antitrypsin (alpha 1-protease inhibitor) seems to be acting as plasma inhibitor in the absence of free alpha 2-macroglobulin and the fast reacting plasmin inhibitor, antiplasmin. Thus, trypsin-induced shock in dogs is apparently not caused by intravascular coagulation to any significant degree.

Animals↗