Biomedical subjects
Publications and source records attributed to A Borgström.
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.
High concentrations of immunoreactive trypsin (IRT) in the blood, and low concentrations of trypsin activity in fecal specimens have been found in newborn infants with cystic fibrosis (CF). The amniotic fluid concentrations of IRT and of IRT in complex with alpha 1-antitrypsin (alpha 1AT) were studied in 39 samples taken in about the 17th gestational week, and in 7 samples taken because the mothers had previously given birth to children with CF. The midtrimester samples contained trypsin in complex with alpha 1AT in a concentration of 30-200 micrograms/liter, and small amounts of trypsinogen, 0-50 micrograms/liter. Three of four amniotic fluid samples from CF fetuses had very low concentrations of trypsin in complex with alpha 1AT (less than 10 micrograms/liter), and only small amounts of trypsinogen (less than 10 micrograms/liter). Further prospective studies are needed to ascertain whether the determination of IRT in amniotic fluid may be of use in prenatal diagnosis of CF.
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.
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.
The levels of amylase, trypsinogen, and trypsin-alpha 1-protease inhibitor complexes, both in serum and in peritoneal fluid, were correlated to the severity and clinical course in 27 attacks of acute pancreatitis. Serum levels of trypsin-alpha 1-protease inhibitor complexes on admission correlated well with the severity and clinical course of the disease, whereas serum levels of amylase and trypsinogen did not. This may be of clinical importance in differentiating severe acute pancreatitis from milder and self-limiting forms of the disease.
The concentrations of pancreatic amylase, immunoreactive trypsin, and immunoreactive pancreatic specific trypsin inhibitor have been studied in serum drawn from 258 patients before an endoscopic retrograde cholangiopancreatography (ERCP) examination, in which both ducts were successfully filled. The results are correlated to the morphology of the ducts and the diagnosis given at the ERCP examination. One third of the patients with normal morphology of both ducts showed an abnormal concentration of at least one of the measured specific pancreatic proteins. Sixteen out of 38 patients with changes suggestive of chronic pancreatitis and 6 out of 23 patients with changes suggestive of pancreatic cancer showed normal levels of all variables measured. The sensitivity and specificity for pancreatic disease evident by ERCP were around 0.40 and 0.80, respectively, for all three proteins.
Fifty-five patients with severe acute pancreatitis were treated with peritoneal lavage at the Dept. of Surgery at Malmö General Hospital. In a randomized study 26 of the 55 patients received in addition 500,000 KIU aprotinin in the lavage fluid every 2 h. There were no significant differences between the aprotinin- and non-aprotinin-treated groups as to mortality and clinical results. The initial concentration of alpha 1-antitrypsin in plasma was mainly within normal range with increasing values during the treatment. No differences were seen between the two groups. The initial mean level of alpha 2-macroglobulin in plasma was slightly decreased, but 17 patients showed values below normal range. The alpha 2-macroglobulin level during the lavage showed a similar course in the two groups. alpha 1-Antitrypsin and alpha 2-macroglobulin in the lavage fluids showed signs of complexation but in plasma these inhibitors did not show any signs of complexation. On admission to the hospital the mean levels of C3 and kininogen in the plasma were slightly below normal. During the lavage treatment no differences were seen between the two groups. Degradation products of C3 and kininogen were seen in both serum and peritoneal fluids. The electrophoretic patterns of C3 and kininogen normalized in serum as well as in lavage fluids during the lavage treatment without any significant differences in the two groups. High levels of immunoreactive trypsin, pancreatic elastase, PSTI, and leukocyte elastase in serum were seen equally in both groups of patients.
The total daily amount of extractable cationic trypsin, chymotrypsin, and pancreatic elastase 2 in feces and ileostomy fluids has been studied in normal individuals and healthy colectomized subjects. Quantitation was performed using immunological assays with polyethylene glycol as a fecal marker. The extractable amount of each of these enzymes in the feces of normal individuals was less than 1 mg/24 h. However, in fecal extracts from antibiotic-treated normal individuals a 100-fold increase in immunoreactive cationic trypsin was observed, while chymotrypsin and elastase 2 were only 2- to 3-fold higher. In extracts from ileostomy fluids cationic trypsin, elastase, and chymotrypsin all showed mean values in the order of 50-200 mg/24 h. The characterization of the immunoreactivity of pancreatic proteases showed no qualitative differences when measured in duodenal juice or fecal and ileostomy extracts.
Immunoreactive cationic trypsin (irCT) was measured in 22 cystic fibrosis (CF) and 132 control infants. IrCT was analysed with radioimmunoassay of dried blood samples collected for PKU screening around the 5th day of life and stored on filter paper. The mean +/- 1 SD level of irCT for the control infants was 42 +/- 19 micrograms/1. Sixteen of the 22 CF children had an irCT level above 100 micrograms/1 (mean + 3 SD) while 6 had a level at or below this cut-off limit. A specificity of 99%, which gives a sensitivity of 73%, and an approximative noise: signal ratio of 30:1, suggests that the irCT test may be unsatisfactory as a neonatal screening method for CF.
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After intravenous injection of autologous purified and radiolabeled anionic and cationic trypsinogens in the dog, there is a multiexponential elimination from serum of the trypsinogens without activation to active trypsins. The results are in agreement with an elimination of the trypsinogens iva glomerular filtration, a variable tubular uptake of anionic trypsinogen, and a complete tubular uptake of cationic trypsinogen. Fractional catabolic rates for anionic trypsinogen were 0.35-0.92 h-1 and for cationic trypsinogen 0.38-1.05 h-1. The total amount of anionic trypsinogen turned over in the circulation is estimated at approximately 0.55 mg every 24 h, and the corresponding figure for cationic trypsinogen is 0.35 mg/24 h.
The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.
Radioimmunoassays for anionic and cationic dog trypsins are described. Characterization of the immunoreactivities in sera from fasting dogs demonstrated the presence of the two proenzymes only. Fasting sera from 10 dogs contained anionic and cationic trypsinogen in concentrations between 17-110 micrograms/l and 7-19 micrograms/l, respectively. Induction of experimental pancreatitis in dogs was accompanied by a large increase of immunoreactive anionic and cationic trypsins in the circulation. During the progress of the pancreatitis, immunoreactive trypsin with larger molecular weight than trypsinogen appeared. This high molecular weight immunoreactive trypsin was not seen in serum after intravenous injection of pancreatic juice in dogs. The high molecular weight immunoreactive trypsin probably consists of trypsin in complex with protease inhibitors. In vitro studies showed that the immunoreactivity of trypsin decreased considerably after binding to alpha 1-antitrypsin or alpha-macroglobulins.
A radioimmunoassay for human pancreatic elastase 2 is described. DFP-Inactivated pancreatic elastase 2 is used both as standard and tracer. The concentration in normal human plasma is approximately 60 micrograms immunoreactive pancreatic elastase 2, which rises in acute pancreatitis. Pancreatic elastase 2 appears in plasma in a form with a molecular size exceeding that of the proenzyme. In vitro studies demonstrate that a complex between pancreatic elastase 2 and alpha 1-antitrypsin arises after incubation of a mixture of pancreatic juice and plasma. The results presented support the conclusion that proelastase is bound by alpha 1-antitrypsin after the discharge from the pancreatic gland to the extracellular tissue fluids around the gland.
The activation of canine anionic and cationic trypsinogen by enterokinase, trypsin, thrombin, plasmin and extracts from canine granulocytes were studied in vitro. Enterokinase activates both trypsinogens about 1000 times faster than trypsin. The enterokinase-catalyzed activation is not inhibited by the main serum protease inhibitors, alpha-macroglobulin and alpha 1-antitrypsin. alpha-Macroglobulin cannot inhibit the activation of the trypsinogens by trypsin but this reaction is completely inhibited by alpha 1-antitrypsin. The results are discussed in relation to the pathogenesis of acute pancreatitis.
Anionic and cationic canine trypsinogens were purified from pancreatic juice by affinity chromatography with Trasylol coupled to Sepharose 4B followed by ion exchange chromatography with SP-Sephadex C-50. Automatic N-terminal amino acid sequence determination showed the following structures for the activation peptides: Thr-Pro-Thr-Asp-Asp-Asp-Asp-Lys for anionic trypsinogen, and Phe-Pro-Ile-Asp-Asp-Asp-Asp-Lys for cationic trypsinogen.
The concentration in serum of cathodal trypsinogen has been studied in certain clinical and experimental situations. The concentration correlated with pancreatic amylase activity. Low levels were found in patients with malabsorption due to exocrine pancreatic insufficiency. The concentration rose after endoscopic retrograde cholangiopancreatographic examinations (ERCP). After ERCP, however, no trypsin was detected complexed with protease inhibitors, as is generally found in acute pancreatitis. The trypsinogen concentration in serum also rose in renal failure indicating a renal elimination route for the endogenous trypsinogen.