Biomedical subjects

K Ohlsson

Publications and source records attributed to K Ohlsson.

At least 55 records · Page 3Linked to original sources

PubMed1998

Cytokines and acute phase reactants during flare-up of contact allergy to gold.

BACKGROUND AND OBJECTIVE: Patients with contact allergy experience cutaneous, as well as general reactions, when exposed systemically to their contact allergen. This study focused on the release in blood of pertinent cytokines and acute phase reactants as a consequence of parenteral allergen exposure. DESIGN: Ten patients with contact allergy to gold were given one intramuscular injection of gold sodium thiomalate; plasma levels of some cytokines and acute phase reactants were followed for 24 hours. RESULTS: There was a flare-up of 1-week-old patch tests in all 10 patients; a maculopapular rash in 5 of 10; and a transient fever in 4 of 10. Biochemical analyses showed some increase of plasma levels of several cytokines in most patients, interleukin 1 receptor antagonist (IL-ra) and tumor necrosis factor (TNF) in particular, and of C-reactive protein (CRP) and leukocyte proteins. A marked increase of IL-1ra, TNF-alpha, soluble tumor necrosis factor receptor 1 (sTNF RI), neutrophil gelatinase associated lipocalin (NGAL), human (leukocyte) elastase antitrypsin (HEAT), and CRP was observed mainly in the four patients with fever and general skin reactions. CONCLUSION: Systemic exposure to the allergen in contact allergy elicits cutaneous and general reactions; at least in the case of gold allergy, it is accompanied by an emergence of cytokines and acute phase reactants.

Acute-Phase Proteins↗

PubMed1998

Cytokine response after acute hyperbaric exposure in the rat.

Intravascular gas has earlier been shown to activate leukocytes and platelets, enhance cell adhesion, and promote secretion of vasoactive substances from platelets. Since decompression is known to release gas bubbles in the bloodstream, the present study was undertaken to investigate the effect of a standardized decompression trauma on inflammatory mediators. Two series of experiments were performed in which male Wistar rats were subjected to a sublethal decompression trauma using a dry pressure chamber. Postdive measurements of cytokine levels were performed to look for signs of an inflammatory reaction. All animals subjected to a decompression trauma showed postdive signs of mild to severe decompression illness (DCI) and measurements of interleukin-6 (IL-6) indicated a postdive increase in the majority of these animals. Our finding of a postdive increase in IL-6 suggests that an inflammatory response, probably created by a blood-gas interface, may be a factor in the process leading to DCI.

Animals↗

PubMed1997

Production and secretion of pancreatic secretory trypsin inhibitor in normal human small intestine.

The aim of this study was to prove the production and secretion of pancreatic secretory trypsin inhibitor (PSTI) in human small intestine. To achieve this we analyzed the content of immunoreactive PSTI (irPSTI) in rinsing fluid from isolated small intestine, using the urea method to estimate the volume of epithelial lining fluid recovered. IrPSTI, measured by an enzyme-linked, immunosorbent assay (ELISA), was present in both free and complexed form. The free PSTI showed intact biologic activity, binding trypsin in stable complexes. The complexed PSTI was dissociated on acidification. With the reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot hybridization, PSTI mRNA was demonstrated in the mucosa of the ileum. These findings indicate that PSTI is produced and secreted in the small intestinal epithelium and may be part of defence system in intestinal mucosa.

Adult↗

PubMed1997

Leukocyte activation in atherosclerosis: correlation with risk factors.

Leukocytes have been implicated in the development of atherosclerotic vascular diseases, and numerous abnormalities of leukocytes in conjunction with atherosclerosis have been reported. The aim of this study of middle-aged asymptomatic subjects with early atherosclerosis was to determine whether a relationship exists between the levels of plasma markers of leukocyte activation, i.e. cytokines and proteases and risk factors for atherosclerosis or the degree of atherosclerotic disease. Using ELISAs we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil protease 4 (NP4) as markers for neutrophil activation, tumor necrosis factor alpha (TNF) and soluble TNF receptor-1 (sTNFR-1) as markers of monocyte/macrophage activation in 156 subjects with asymptomatic carotid artery plaque detected at ultrasound examination. Plasma TNF and sTNFR-1 levels were found to correlate with systolic blood pressure (r = 0.32, P < 0.04 and r = 0.22, P < 0.05, respectively). plasma NGAL level to correlate with diastolic blood pressure (r = 0.22; P < 0.005), the plasma levels of sTNFR-1 and NGAL to correlate with age (r = 0.28, P < 0.001 and r = 0.20, P < 0.05, respectively). As compared with non-smokers (n = 112), smokers (n = 43) had higher plasma levels of TNF (2.9 vs. 1.4 microg/l; P < 0.02) and of NP4 (27.5 vs. 23.4 microg/l; P < 0.05). The plasma NGAL level was higher in hypertensive women (n = 7) than in normotensive women (n = 85) (109 vs. 87 microg/l; P < 0.05). We thus demonstrated that, in subjects with asymptomatic early atherosclerosis, the plasma levels of markers of systemic leukocyte activation were correlated with age and blood pressure, and were higher in smokers and hypertensives. These results support the hypothesized relationship between the level of systemic leukocyte activation and risk factors for atherosclerotic vascular disease.

Acute-Phase Proteins↗

PubMed1997

The elimination of secretory leukocyte protease inhibitor (SLPI) from the gastrointestinal tract in man.

Secretory leukocyte protease inhibitor (SLPI) is the dominant protease inhibitor in the mucus secretions of the genital and respiratory tract and it was recently also detected in intestinal mucosa. Furthermore an earlier study showed high concentrations of SLPI in peritoneal fluid from patients with perforations of the large and small intestines. As SLPI is acid-stable, this raised the question of to what extent swallowed SLPI may contribute. The present study investigated the turnover of swallowed SLPI in the gastrointestinal tract. Native 125I-labelled SLPI was instilled in the duodenum of three healthy volunteers and radioactivity in plasma, faeces and urine was measured. Within 72 h 81.4% of the injected radioactivity was excreted in urine and 3.6% in faeces as radioactive low molecular weight proteins (< 1 kDa). Recombinant human SLPI (rh-SLPI) was incubated with porcine pepsin or human gastric or duodenal juice. This resulted in rapid degradation of SLPI to smaller molecules. In conclusion, SLPI is rapidly degraded in the stomach and duodenum. There were no measurable amounts of SLPI in the faeces. We have shown that during normal conditions, swallowed SLPI was rapidly degraded in the stomach and duodenum, and therefore it probably can not be of any importance for inflammatory diseases in the intestines.

Chromatography, Gel↗

PubMed1997

Distribution of the secretory leucocyte proteinase inhibitor in human articular cartilage.

The secretory leucocyte protease inhibitor, SLPI, is a low molecular weight inhibitor of proteases such as elastase and cathepsin G, which are released from leucocytes during phagocytosis. The purpose of this study was to show whether or not SLPI is produced in articular chondrocytes. In articular disorders, the protease-antiprotease balance is disturbed. For this reason it would be interesting to establish the source of SLPI. The presence of SLPI was demonstrated using immunohistochemistry and in situ hybridization, hence we conclude that SLPI is produced in the chondrocytes of human articular cartilage.

Arthroplasty, Replacement, Hip↗

PubMed1996

Localization of immunoreactive secretory leukocyte protease inhibitor (SLPI) in intestinal mucosa.

Secretory leukocyte protease inhibitor (SLPI) is the dominant protease inhibitor in the mucus secretions of the repiratory and genital tracts, and local production seems likely, as immunoreactive SLPI has been found in the corresponding mucosa. To our knowledge, SLPI has not been previously demonstrated in intestinal epithelia or secretions. In an earlier study, however, we found surprisingly high levels of SLPI in peritonitis exudate from patients with gastrointestinal perforations. This study extends these observations by demonstrating the presence of immunoreactive SLPI in intestinal mucosa. In the small intestine, SLPI was present in Paneth cells and in scattered mucosa cells of goblet-type. In normal mucosa of the large bowel, SLPI was also found in scattered cells of goblet-type in the epithelium. In addition, immunoreactive SLPI was frequently found in colonic adenomas. The findings in this study raise several interesting questions on the possible role of SLPI in the gut epithelial defense against inflammatory assaults.

Adenoma↗

PubMed1996

Effects of high-dose intraperitoneal aprotinin treatment on complement activation and acute phase response in acute severe pancreatitis.

Forty-eight patients with severe acute pancreatitis were treated with intraperitoneal lavage in a double-blind randomized multi-center trial. One group (aprotinin group, n = 22) was also treated intraperitoneally with high doses of the protease inhibitor aprotinin. In the group not treated with aprotinin (control group), 6 patients were operated on because of pancreatic necrosis, compared with none in the treated group. Complement activation and the acute phase response were studied with measurements of anaphylatoxin C3a, C1 inhibitor (C1 Inh), interleukin 6 (IL-6), and C-reactive protein (CRP). The control group had higher plasma levels of C3a and lower levels of C1 Inh compared with the aprotinin group. The differences were statistically significant for C3a but not for C1 Inh. Both groups had high plasma levels of IL-6 and CRP. There were no differences between the groups in CRP levels, but the control group had higher IL-6 levels (not statistically significant) than the aprotinin group. This was caused by very high levels in the 6 patients operated on because of pancreatic necrosis, indicating that IL-6 could be a good plasma marker of pancreatic necrosis. The results also show that massive antiprotease treatment reduces complement activation, as illustrated by the lower C3a levels in the aprotinin group. The lower C1 Inh levels in the control group could have been caused by an increased consumption of the inhibitor.

Acute Disease↗

PubMed1996

Extrapancreatic origin of the pancreatic secretory trypsin inhibitor as an acute-phase reactant.

The aim of the present investigation was to study the origin of the elevated levels of the pancreatic secretory trypsin inhibitor (PSTI) seen in the bloodstream during an acute-phase reaction. PSTI and cationic trypsinogen levels in pancreatic juice and plasma from five patients were measured over 8 days following subtotal pancreatoduodenectomy (Whipple's procedure). Cells from a human hepatocellular carcinoma cell line (Hep G2) and from a human pancreatic cancer cell line (CAPAN-1) were cocultured with endotoxin-stimulated mononuclear white blood cells using a double-chamber technique. Hep G2, CAPAN-1, and mononuclear white blood cells were also cultured as single populations. The median plasma level of PSTI increased from 16.6 micrograms/L at the time of surgery to 155 micrograms/L at the fourth postoperative day. No increase in PSTI levels in pancreatic juice or trypsinogen levels in pancreatic juice and plasma was observed. Culture medium from stimulated hepatocellular carcinoma cells contained significantly elevated levels of PSTI compared with the levels of PSTI from unstimulated cells. Culture medium from pancreatic cancer cells alone contained high levels of PSTI but no difference was observed compared with PSTI levels in medium from stimulated pancreatic cancer cells. The mononuclear white blood cells did not produce PSTI. The results support the view of an extrapancreatic origin of plasma PSTI during the acute-phase reaction and indicate that the liver is the probable source.

Acute-Phase Reaction↗

PubMed1996

Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases.

BACKGROUND AND PURPOSE: Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases. In a prospective study we investigated whether the plasma concentrations of inflammatory mediators, ie, proteases and cytokines, as markers for systemic leukocyte activation, are increased in patients with acute ischemic cerebrovascular diseases. METHODS: Using enzyme-linked immunosorbent assays, we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil proteinase 4 (NP4), tumor necrosis factor-alpha (TNF), and soluble TNF receptor protein-1 p55 (sTNFR-1) in 120 patients with acute ischemic cerebrovascular insult (72 with stroke and 48 with transient ischemic attack [TIA]) and in 35 age- and sex-matched healthy subjects. RESULTS: Compared with the control group, plasma NGAL levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); plasma NP4 levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); and plasma sTNFR-1 levels were higher in the stroke group (P < .04). There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 (r = .32; P = .005) and NGAL (r = .40; P = .0001) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 (r = .35; P = .001) and NGAL (r = .34; P = .002). CONCLUSIONS: Our study demonstrated that markers for systemic leukocyte activation, ie, plasma levels of cytokines and proteases, were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects. Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences.

Aged↗

PubMed1996

Release of cytokines and proteases from human peripheral blood mononuclear and polymorphonuclear cells following phagocytosis and LPS stimulation.

Release and cellular contents of pro- and anti-inflammatory cytokines, neutrophilic elastase and secretory leukocyte proteinase inhibitor (SLPI) were measured with enzyme-linked immunosorbent assay in peripheral blood mono- and polymorphonuclear cells stimulated with preopsonized yeast cells or lipopolysaccharide. Tumour necrosis factor alpha (TNF alpha) was also measured with a bioassay. TNF alpha production and soluble TNF alpha receptor I (sTNF RI) were demonstrated in the environment of both cell populations. The bioassay indicated levels of TNF alpha far below those detected by ELISA. The overall secretion of cytokines and their inhibitors was found to favour an anti-inflammatory balance in the environment of the stimulated cells. The interleukin-1 receptor antagonist (IL1-ra), compared with interleukin-1 beta (IL-1 beta), dominated the secretions from both cell types with a 100- to 1000-fold excess respectively. Most of the translated IL-1 beta was not secreted but found associated with the cellular compartments. In contrast to lipopolysaccharide (LPS) stimulation, preopsonized yeast cells stimulated a massive release of elastase from neutrophil cells.

Cell Line↗

PubMed1995

Repetitive industrial work and neck and upper limb disorders in females.

A cross-sectional study was performed in which physical examinations of the neck and upper limbs were conducted on 82 currently working female industrial workers with exposure to repetitive work tasks and on 64 currently working referent subjects without exposure to repetitive work tasks. Associations between results of symptom questions and physical examination were sought with variables related to the work environment and to the individuals. In a multivariate model, there were statistically significant associations between exposure to repetitive work and diagnoses in both the neck/shoulders (prevalence odds ratio, POR = 4.6) and elbows/hands (POR = 3.5). In addition, age (POR = 1.9, 75th vs. 25th percentiles), tendencies towards subjective muscular tension (POR = 2.3), and stress/worry (POR = 1.9) were also associated with diagnoses in the neck/shoulders; however, there was not an association between these variables and the prevalence of diagnoses in elbows/hands. Standardized evaluation of videotape recordings in 74 of the industrial workers revealed significant associations between neck flexion, and elevation and abduction of the arm and the prevalence of neck/shoulder diagnoses. In the multivariate model, neck flexion was significantly associated with diagnoses in the neck/shoulders (p = 0.005). In addition, low muscle strength, lack of emotional well-being at work, and a variety of psychosomatic symptoms were associated with diagnoses in the neck/shoulders (all p < 0.001). Lack of strength was also associated with disorders of elbows/hands (p = 0.007). This study demonstrated a substantial prevalence of neck and upper limb disorders associated with repetitive work performed with a flexed neck and elevated and abducted arms, as well as a possible potentiation of these ergonomic factors by certain personal traits in some workers.

Adult↗

PubMed1995

Pancreatic secretory trypsin inhibitor in human Brunner's glands.

Brunner's glands (duodenal glands) in humans are located mainly in the two proximal thirds of the duodenum. They are known to produce and secrete mucin. In recent years, human Brunner's glands have also been shown to express immunoreactivity toward epidermal growth factor-urogastrone (EGF-uro) and lysozyme. These proteins are considered to have a protective function within the gastrointestinal canal. Human pancreatic secretory trypsin inhibitor (PSTI) was recently identified in Brunner's glands. This present study was done by an immunohistochemical method, using monospecific polyclonal antibodies against human PSTI and human lysozyme, respectively. McManus/Alcian blue mucin staining was used to clarify the distribution of mucin. We found immunoreactive PSTI (irPSTI) in seven out of ten specimens. Lysozyme and mucin were present in all ten. While virtually all cells were stained for lysozyme and mucin, irPSTI was restricted to separate lobules and to cells in the ducts.

Brunner Glands↗

PubMed1995

Secretory leukocyte protease inhibitor in the cervical mucus and in the fetal membranes.

OBJECTIVE: The purpose was to determine the concentration of leukocyte elastase and SLPI in the cervical mucus plug, cervical tissue, fetal membranes, amniotic fluid and serum from pregnant women. STUDY DESIGN: Samples were analysed using radioimmunoassay, immunodiffusion, immunohistological and enzyme assay techniques. Statistical comparisons were performed by the Mann-Whitney two-sample rank sum test. RESULTS: Concentrations of SLPI and elastase in cervical tissue are significantly increased during pregnancy and after delivery. Very high concentrations of SLPI and elastase were found in the cervical mucus plug. The concentrations of SLPI and elastase in human fetal membranes are highest at the rupture site. The concentration of elastase in amnion from preterm delivery was significantly higher than in amnion from term deliveries. CONCLUSION: The high molar ratio of SLPI/elastase in the cervical mucus plug suggests that inhibition of elastase is important during normal pregnancy. The role of SLPI may be protection of the fetal membranes and cervical tissue.

Amnion↗

PubMed1995

Intrapancreatic turnover of recombinant human pancreatic secretory trypsin inhibitor in experimental porcine pancreatitis.

Experimental porcine pancreatitis was induced by the injection of taurocholate into the pancreatic duct. Recombinant human pancreatic secretory trypsin inhibitor (25 mg) was administered to each animal in one of three different ways: into the pancreatic duct (n = 5), into the abdominal cavity adjacent to the pancreas (n = 2) or intravenously (n = 2). The intrapancreatic turnover was assessed during 6 h using a microdialysis technique. The intraglandular concentration, measured by enzyme-linked immunosorbent assay, was highest after injection of rhPSTI into the pancreatic duct and substantially lower after intravenous and intraperitoneal administration. The intrapancreatic half-life of the inhibitor after intraductal administration was considerably longer (3-6 times) in pigs with pancreatitis than has previously been found in the normal gland. These facts argue in favour of the intraductal administration route in future trials of antiprotease treatment in acute pancreatitis.

Abdomen↗

PubMed1995

Trypsinogen is not activated during cardiac surgery with extracorporeal circulation.

Amylase, immunoreactive cationic trypsin(ogen) and complexes of cationic trypsin and alpha 1-proteinase inhibitor were analysed in plasma samples from 41 patients following cardiac surgery with extracorporeal circulation. Postoperative hyperamylasaemia was seen in seven patients (17%). In 10 patients there were elevated levels (> 100 micrograms 1(-1)) of immunoreactive cationic trypsin(ogen) on the first postoperative day. After gelfiltration, samples from these 10 patients were analysed for trypsin-alpha 1-proteinase inhibitor complexes, with a solid-phase, double-antibody enzyme-linked immunoassay. The median preoperative level of trypsin-alpha 1-proteinase inhibitor complexes was 4.5 micrograms 1(-1) (range 3.3-11.9) and the median value on the first postoperative day was 5.5 micrograms 1(-1) (range 2.6-14). The ratio between complexes and immunoreactive trypsin(ogen) decreased (p < 0.05) showing that activation of trypsinogen did not occur. This fact argues against the development of protease-mediated subclinical pancreatitis during cardiac surgery with extracorporeal circulation.

Adult↗

PubMed1995

Studies of the release and turnover of a human neutrophil lipocalin.

A 24-kDa protein was purified from human neutrophil extracts and shown to be the newly discovered neutrophil gelatinase-associated lipocalin (NGAL), based on structural and immunochemical data. A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of NGAL in human plasma and tissue fluids. Normal human plasma contains 72 micrograms l-1 of NGAL (range 40-109 micrograms l-1) in two main forms, monomer and dimer. 35S-methionine metabolic studies of human neutrophils showed that granulocyte macrophagecolony-stimulating factor (GMCSF) stimulated significant synthesis and secretion of NGAL in a dose- and time-dependent fashion. NGAL was rapidly released as monomer and dimer on incubation of heparinized whole blood with opsonized yeast, reaching a plateau corresponding to about 35% of total cell content after 30 min. Following intravenous injection of 125-iodine labelled NGAL there was a more rapid initial clearance of the monomeric than of the dimeric form; t1/2 10 min vs. 20 min. During the second phase the two forms cleared at similar rates. Severe acute peritonitis was accompanied by a 10-fold increase in NGAL plasma levels and the NGAL level in peritoneal exudates, which reached about 40 mg l-1. There was a good linear correlation between the concentrations of NGAL, leucocyte elastase and NP4 (neutrophil proteinase 4 = P3).

Acute Disease↗

PubMed1994

High-dose intraperitoneal aprotinin treatment of acute severe pancreatitis: a double-blind randomized multi-center trial.

A multi-center double-blind trial was performed on 48 patients with severe acute pancreatitis. All patients were treated with intraperitoneal lavage. One group (n = 22) was also treated with high doses of the protease inhibitor, aprotinin (Trasylol; Bayer AG, Leverkusen, Germany) administered intraperitoneally. Eight patients died, giving a total mortality of 16.6%. No difference was observed between the two groups. Altogether, 12 patients were operated on, corresponding to 25%. In the group not treated with aprotinin, 6 patients were operated on because of pancreatic necrosis, compared with none in the treated group. The difference was statistically significant. There were no significant differences between the two groups with regard to organ failure or other complications. It was concluded that aprotinin counteracts the development of pancreatic necrosis when given intraperitoneally in high doses to patients with severe acute pancreatitis, thus reducing the need for surgical intervention in these patients.

Acute Disease↗