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Biomedical subjects

K Ohlsson

Publications and source records attributed to K Ohlsson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa.

Specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor (PSTI). In normal colonic mucosa PSTI was found in the goblet cells in the basal parts of the crypts. In adenomas of tubular, villous, and tubulo-villous types PSTI was also found in the upper parts of the polyps, usually occurring in the regeneration zone. There was a more intense staining reaction in polyps with increased atypia. Carcinomas of different types and of various grades of differentiation and of in situ type did not contain PSTI. These findings indicate that PSTI could be a marker for adenomatous rather than carcinomatous epithelium in the colon. Furthermore, the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition.

Adenoma↗
PubMed1990

Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme.

Four stable hybridoma cell lines producing monoclonal antibodies specific for neutrophil proteinase 4 (NP4) were established and one monoclonal antibody was chosen to produce an immunoaffinity-resin for the purification of NP4. In a precipitation assay system these antibodies bound NP4 in a dose-dependent manner, but did so neither with neutrophil elastase nor with cathepsin G. NP4 was purified and electrophoresis of the affinity-purified enzyme in sodium dodecyl sulfate polyacrylamide gels resulted in a single Mr = 30,000 polypeptide. The purified enzyme digested fibrin but not elastin and it cleaved Boc-Ala-ONp readily (Km = 0.47mM) at neutral pH, but had no effect on Suc-[Ala]3 Nan and N-Suc-[Ala]2-Pro-Phe-pNA. The proteolytic activity was inhibited by DFP, alpha 1 PI and alpha 2 M with a Ki of 10(-9)M for the NP4-alpha 1 PI complex. The NH2-terminal sequence and the amino-acid composition of NP4 were distinct from those of elastase and cathepsin G. Neutrophils contain large amounts of NP4 as judged by the comparable amounts of elastase- and NP4-alpha 1 PI complexes present in inflammatory exudates.

Amino Acid Sequence↗
PubMed1990

Purification and N-terminal amino-acid sequence analysis of rat polymorphonuclear leukocyte cathepsin G.

Cathepsin G was purified by single-step cation-exchange chromatography from rat polymorphonuclear leukocytes, obtained from the peritoneal cavity after induction of a mild peritonitis. The 26 N-terminal amino acids were determined and showed 73% identity to those of human cathepsin G. Total amino-acid composition demonstrated a high degree of basic amino acids in accordance with its high affinity for the cationic-exchange gel medium. The protein was found to be a glycoprotein with a glucosamine content of 7.4% of the calculated Mr28,900. On SDS/polyacrylamide-gel electrophoresis the protein showed a Mr of 28,400. It migrated as two bands in a gradient SDS/polyacrylamide-gel indicating isoforms. The pH optimum for the proteinase was determined to be 8.0-8.5 using Suc-Ala-Ala-Pro-Phe-Nan as substrate (Suc = 3-carboxypropionyl; Nan = 4-nitroanilide). Km and Kcat/Km values for Suc-Ala-Ala-Pro-Phe-Nan were 0.86mM and 280M-1S-1 and for Suc-Phe-Leu-Phe-Nan 0.24mM and 3600M-1S-1, respectively.

Amino Acid Sequence↗
PubMed1989

Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity.

Cigarette smoking results in variable degrees of inflammation in the lower respiratory tract. Furthermore, smoking produces oxidant-mediated changes in the lung, important to the pathogenesis of emphysema. Since glutathione can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant and inflammatory injury. In the present study, broncholaveolar lavage (BAL) was performed in 27 smokers, and the concentrations of total glutathione as well as the cellular and humoral markers of inflammatory activity were studied. There were significant correlations between total glutathione and neutrophils; two neutrophil granule components, myeloperoxidase and elastase; and chemotactic activity for neutrophils. Moreover, the total glutathione correlated with the eosinophil cationic protein (ECP), a granule constituent of the eosinophil, with two locally produced antiproteases, secretory leukocyte protease inhibitor (SLPI) and antichymotrypsin (ACHY), but not with an alpha 1-protease inhibitor and albumin. These data suggest that the total glutathione levels in BAL fluid may reflect a degree of oxidative and inflammatory stress caused by cigarette smoke, and they are therefore likely to contribute to the protection against this stress.

Biomarkers↗
PubMed1989

The concentration of collagen and the collagenolytic activity in the amnion and the chorion.

Fetal membranes obtained from second-trimester abortions, elective Caesarean sections and after normal deliveries were studied. The hydrolytic activity against a DNP-peptide expressing the collagen turn-over was found to be very high in the second trimester and relatively high at term of pregnancy. The activity in the chorion was twice that in the amnion. The concentration of another collagen-degrading enzyme, leukocyte elastase, which is present during inflammatory reactions was high at the site of rupture. The collagen concentration given as micrograms hydroxyproline per mg dry weight was unchanged throughout pregnancy and labour in both fetal membranes. The concentration in amnion was twice that in the chorion. After delivery, the collagen content given as microgram/cm2 in the chorion was decreased at the rupture line. This was due to decreased thickness of the membrane, whereas the hydroxyproline concentration (microgram/mg dry weight) was unchanged. The amnion was thinner than the chorion, but the decreasing collagen content (micrograms/cm2) at the rupture line was less pronounced. The thinning of especially the chorionic membrane might be secondary to the mechanical stress of pregnancy and labour and/or, as our results suggest, due to enhanced catabolism.

Amnion↗
PubMed1989

Pancreatic pseudocyst fluid--a mixture of plasma proteins and pancreatic juice possessing a high proteolytic activity.

Pancreatic pseudocyst fluid from eight patients was examined biochemically. The fluid was found to be a mixture of plasma proteins and pancreatic juice, possessing a high proteolytic activity against high- as well as low-molecular-weight proteins. The proteolytic activity was found to be trypsin-, kallikrein- and plasmin-like. Gel filtration studies showed proteolytic activity to be present corresponding to alpha-2-macroglobulin-bound proteases and also to free proteases. Quantitative immunochemical levels were about 30-100% of normal plasma levels for alpha-2-macroglobulin, C1 inhibitor, antithrombin III and alpha-2-antiplasmin. However, there was practically no functional inhibitory capacity left in the pseudocyst fluid, except for alpha-1-protease inhibitor, which retained its inhibitory capacity. Neither native kininogen nor complement factor C3 was found: this was probably a result of the proteolytic activity. It is concluded, that a continuing proteolytic activity within the pseudocyst, although decreasing with aging of the cyst, could explain symptoms and complications caused by the pseudocyst.

Adult↗
PubMed1989

Abnormal proteolysis (DIC)--successful treatment with antithrombin III concentrate and a concentrate containing F XIII and native von Willebrand factor.

Two patients with life-threatening disseminated intravascular coagulation (DIC) syndrome, one caused by Gram-negative bacteria and one by premature separation of the placenta, are described. Specific substitution was given by antithrombin III concentrate and AHF-Kabi, a low purity factor VIII concentrate containing native von Willebrand factor and factor XIII. The treatment quickly returned the extremely low levels of antithrombin III, factor VIII:C, fibrinogen and factor XIII, initially found, to normal, and also returned the multimeric pattern of von Willebrand factor to normal. This resulted in diminished bleeding, enabling surgical treatment of the underlying disease.

Adult↗
PubMed1989

The inhibition of granulocyte phagocytosis by various components of nasal drops.

The effect of two decongestive substances and two preservatives used in nasal drops on phagocytosis by human granulocytes was studied. The vasoactive substances oxymetazoline chloride and zylometazoline chloride incubated with human granulocytes during 20 min. gave a reduction of phagocytosis to almost zero when using concentrations found in commercially used nasal drops (500 mg/l respectively 1000 mg/l). However, a dilution of 1:100 was consistent with an almost normal phagocytic function. The preservatives benzalkonium chloride and thiomersal gave a dose related reduction of phagocytosis down to zero. A dilution of 1:100 of the benzalkonium chloride solution used commercially (200 mg/l) and a dilution of 1:10 of the thiomersal solution used commercially (24 mg/l) were needed to get an almost normal phagocytic function. These results together with previous studies indicate that the addition of preservatives in nasal drops should be questioned, excluded or replaced with other less harmful substances.

Administration, Intranasal↗
PubMed1989

Early diagnosis and classification in acute pancreatitis. A comparison of clinical outcome with findings at computed tomography and Ranson's prognostic signs.

The clinical outcome in 52 consecutive episodes of suspected acute pancreatitis was compared with Ranson's prognostic signs and findings on noncontrast and contrast-enhanced computed tomography (CT) scans performed within 24 h of patient admission. The predictive value of CT scan for diagnosis was 95% for positive results and 53% for negative results. In providing an accurate prognosis of a single attack, scoring of extrapancreatic signs was as good as that of Ranson's prognostic signs. CT with contrast medium revealed pancreatic ischaemia in 3 cases of 4 with clinically severe disease. The risk of developing severe pancreatitis was 23% in first attacks and 6% in relapses. Early CT scan is recommended in most patients with suspected pancreatitis to confirm diagnosis and to predict the severity of an attack.

Acute Disease↗
PubMed1989

Pathobiochemistry and early CT findings in acute pancreatitis.

Extrapancreatic findings at computed tomography (CT), performed within 24 h in 42 consecutive episodes of acute pancreatitis, were classified according to a scoring system (EP score) and were correlated to Ranson's prognostic signs, to duration of hospital stay, biochemical changes in plasma and pancreatic ischaemia found at CT with contrast enhancement. Increasing EP score was found to be related to increasing number of positive Ranson's signs, longer hospital stay and pancreatic ischaemia. Plasma levels of immunoreactive cationic trypsin and amylase were not proportional to EP score. alpha 1-protease inhibitor, antichymotrypsin but not immunoreactive pancreatic secretory trypsin inhibitor increased proportionally to EP score. No changes related to EP score were seen in alpha 2-macroglobulin levels. Serum levels of trypsin-alpha 1-protease inhibitor complex were maximal after 3 days and most pronounced in cases with high EP scores. Plasma levels of factor X, alpha 2-antiplasmin and C1-esterase inhibitor were found to be inversely proportional to EP score.

Acute Disease↗
PubMed1989

Radioimmunological quantitation of the urinary trypsin inhibitor in normal blood and urine.

A radioimmunoassay for measurement of the urinary trypsin inhibitor in human serum and urine is described. Because of the immunological cross-reactivity between the inter-alpha-trypsin inhibitor and the urinary trypsin inhibitor the plasma and serum were treated with perchloric acid to precipitate the inter-alpha-trypsin inhibitor. Gel filtration of serum before and after acid treatment showed identical peaks corresponding to the urinary trypsin inhibitor. The normal level of the urinary trypsin inhibitor in fresh plasma from 30 blood donors was 6.38 +/- 0.33 mg/l (SEM), and in sera from 24 healthy volunteers 7.14 +/- 0.27 mg/l (SEM). In urine from 23 healthy volunteers the normal excretion was 8.17 +/- 1.18 mg/24 h (SEM).

Adolescent↗
PubMed1989

Patterns of immunoreactive trypsin in serum from patients with acute abdominal disorders.

Immunoreactive trypsin in serum can be divided into trypsinogen and trypsin-alpha 1-proteinase inhibitor (alpha 1PI) complexes. These were studied separately in serum from 204 patients with acute gastro-intestinal symptoms. Elevated levels of both trypsinogen and trypsin-alpha 1PI complexes were seen in patients with acute pancreatitis. Elevated levels of trypsinogen and normal or slightly elevated levels of trypsin-alpha 1PI complexes were seen in patients with biliary tract diseases. An isolated increase in the concentration of trypsin-alpha 1PI complexes with normal trypsinogen and amylase levels were seen in patients with perforated ulcer. This third cluster may result from an absorption of active trypsin from the peritoneal cavity. Small amounts of trypsin-alpha 1PI complexes were present also in serum from patients free from pancreatic disease. The results in this study show that high levels of trypsin-alpha 1PI complexes in serum are seen mainly in patients with acute pancreatitis. However, elevated levels are also seen in other pathological conditions in the upper gastrointestinal tract; therefore an assay for these complexes is not a specific diagnostic test for acute pancreatitis.

Abdomen, Acute↗
PubMed1989

Local administration of human pancreatic secretory trypsin inhibitor prevents the development of experimental acute pancreatitis in rats and dogs.

The objective of this investigation was to test the capacity of recombinant human pancreatic secretory trypsin inhibitor (rhPSTI) to provide prophylaxis against experimental pancreatitis. Acute hemorrhagic pancreatitis was induced by intraductal injection of sodium taurocholate in rats and by intraductal injection of bile in dogs. In one treatment group of rats the injection of taurocholate was preceded by injection of rhPSTI. In a second group of rats the rhPSTI was given intraperitoneally starting 15 min after the induction of acute pancreatitis. The survival rate in a control group of rats was 13%. In contrast, the survival rate in groups receiving rhPSTI intraductally or intraperitoneally was 80% and 63%, respectively. The survival rate in a control group of dogs was 40% at 24 h and 0% at 48 h. In contrast, all the dogs receiving a single intraductal dose of rhPSTI, either immediately before the bile injection or mixed with the bile, survived for up to 6 weeks. Detailed biochemical and immunohistologic studies in the dog indicate that, whereas rhPSTI cannot prevent the initial bile-induced injury, it does prevent the subsequent development of that injury to the point where there is massive damage to the pancreas and the surrounding tissues, and changes in blood chemistry. The development of the initial injury is, therefore, presumed to involve activation of trypsinogen. Since rhPSTI prevents the serious consequences of experimental pancreatic injury by blocking the action of trypsin, and since the pathobiochemistry of human acute pancreatitis also implies an important role for trypsin, it is possible that rhPSTI could protect humans from the pancreatitis that complicates endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.

Acute Disease↗
PubMed1989

Self-reported symptoms in the neck and upper limbs of female assembly workers. Impact of length of employment, work pace, and selection.

In a questionnaire study 148 women in assembly work reported statistically significantly higher rates of pain, in the last 7 d, in their shoulders (odds ratio 3.4) and hands (odds ratio 2.8) as compared to 60 referents age-adjusted. There was a strong association between duration of employment and complaints in the hands. For the younger women, but not the older ones, there was an increase in pain in the shoulders, neck, and upper back with duration of employment. The odds ratio for pain in the shoulders and neck increased with an increasing work pace, except for very high paces, for which there was a decrease. Among 76 former assembly workers 26% reported pain as the cause of having left this work. There was no overall increase in the frequency of complaints among those who had left.

Adolescent↗
PubMed1989

Proteases and protease inhibitor balance in peritonitis with different causes.

Protease activation and protease-antiprotease interactions were sequentially studied in two different groups of patients with peritonitis. The biochemical changes were related to the cause of the disease and to the clinical course. Protease activation and protease inhibitor consumption were most pronounced in the peritoneal fluid, especially in bacterial peritonitis. Plasma changes also indicated activation of the complement, kinin, and fibrinolytic systems and protease inhibitor consumption, especially of alpha 2-macroglobulin and antithrombin III. There was no significant difference between chemical and bacterial peritonitis regarding these plasma changes. Immunohistologic studies showed evidence of active uptake of protease-antiprotease complexes in macrophage-like cells in the peritoneum in both groups. It is concluded that peritonitis results in protease activation and protease inhibitor consumption, especially in the peritoneal fluid. The peritoneum has an active role in the clearance of protease-antiprotease complexes. The intensity, not the type, of the intra-abdominal challenge determines the biochemical changes in peritonitis.

Adult↗
PubMed1989

Secretory leukocyte protease inhibitor in normal, allergic and virus induced nasal secretions.

Secretory leukocyte protease inhibitor (SLPI) and alpha-1-proteinase inhibitor (alpha-1-PI), both inhibitors of granulocyte elastase, were studied in nasal secretions from healthy persons and from patients with allergic rhinitis and common cold. SLPI and granulocyte elastase were found in all samples, while alpha-1-PI was lacking in several. In all three groups SLPI was found in an active form and in excess of granulocyte elastase, which thus was completely inhibited. The results indicate that SLPI is the main inhibitor in nasal secretions and that alpha-1-PI plays a minor role.

Common Cold↗