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Biomedical subjects

B Osterud

Publications and source records attributed to B Osterud.

At least 37 records · Page 2Linked to original sources
PubMed1997

The inflammatory properties of contained and noncontained lumbar disc herniation.

STUDY DESIGN: The inflammatory properties of nucleus pulposus were assessed in biopsy samples from patients who underwent surgery for lumbar disc herniation. OBJECTIVES: To investigate the inflammatory properties of the different types of disc herniation. BACKGROUND DATA: High levels of phospholipase A2 previously have been demonstrated in a small number of patients undergoing lumbar disc surgery. Phospholipase A2 is the enzyme responsible for the liberation of arachidonic acid from cell membranes at the site of inflammation and is considered to be the limiting agent in the production of prostaglandins and leukotrienes, which are powerful mediators of inflammation. Cytokines are among the many agonists inducing phospholipase A2 activation. Several reports previously have demonstrated the difference in clinical appearance of different types of lumbar disc herniation. METHODS: Thirty-seven patients undergoing surgery for lumbar disc herniation were investigated. During surgery the disc pathology of each patient was classified into one of three groups: bulging disc, contained herniation, and noncontained disc herniation. Also during surgery, biopsy samples were taken from the nucleus, immediately frozen in liquid nitrogen, and subsequently stored at -70 C until analyzed. RESULTS: No traces of interleukin-6 or tumor necrosis factor alpha were found in the biopsy samples. There was a significant difference in the levels of leukotriene B4 and thromboxane B2 in contained versus noncontained disc herniation, and the highest concentration was found in the noncontained disc herniation group. CONCLUSION: The results support the theory that inflammatory mechanisms are involved in sciatica because of lumbar disc herniation and indicate that the different types of disc herniation have different inflammatory properties.

Adult↗
PubMed1997

The effect of physical conditioning suggests adaptation in procoagulant and fibrinolytic potential.

Acute exercise evokes a transient increase in procoagulant activity. We evaluated the effect of physical conditioning on the activation of the coagulation and fibrinolytic systems. Two groups of subjects of different aerobic endurance levels (athletes and controls with maximal oxygen uptake (VO2max) 68.4 and 52.6 ml kg-1 min-1, respectively), were tested at rest and after standardized exercise at 80% of their individual VO2max. There was a significant increase in prothrombinfragment 1 + 2 (F1 + 2) level among controls in response to standardized exercise (p < 0.05), whereas no significant difference in the level of F1 + 2 between athletes and controls at rest or in response to exercise was demonstrated. Tissue plasminogen activator (tPA) antigen level at rest was significantly lower in athletes compared to controls (p < 0.03). A significant increase was found in the tPA level after standardized exercise in both groups (p < 0.02), which was lower in athletes compared to controls (p < 0.05). There were no significant differences between athletes and controls in plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) levels at rest. Athletes had a significantly lower PAI-1 level than controls after exercise (p < 0.05). In conclusion, the present study suggests an increased activation of the coagulation system in response to exercise in controls only. It also suggests adaptive changes in fibrinolytic potential induced by physical conditioning, as demonstrated by the lower level of tPA at rest and the lower levels of tPA and PAI-1 after exercise in athletes compared to controls.

Adaptation, Physiological↗
PubMed1997

Modulation of blood cell activation by four commonly used anticoagulants.

In the past years, our group has made several observations suggesting that blood cells behave differently and when stimulated, release different levels of cytokines, depending on which anticoagulant the blood has been drawn into. The aim of this study was therefore to compare the effect of the four anticoagulants EDTA, citrate, heparin and hirudin on monocyte, neutrophil (PMN), and platelet function in human whole blood. Human whole blood was employed as an ex vivo model of cytokine production and protein secretion, and lipopolysaccharide (LPS) induced tissue factor (TF) activity in monocytes and LPS induced tumor necrosis factor alpha (TNF alpha) release were chosen as parameters of monocyte activation. Platelet factor 4 (PF4) secretion and LPS induced lactoferrin release were chosen as parameters of platelet and PMN activation, respectively. When human whole blood was stimulated with 5 ng/ml LPS for 2 h, TF activity in monocytes isolated from EDTA blood was found to be 2.9 mU/10(6) cells, whereas TF activity in monocytes isolated from citrated, heparinized and hirudinized blood was 14.7, 24.7 and 28.5 mU/10(6) cells, respectively. TNF alpha concentrations in platelet poor plasma (PPP) isolated from whole blood stimulated with 5 ng/ml LPS for 2 h was increased with 200, 400 and 350% in citrated, heparinized and hirudinized blood respectively, as compared to EDTA blood. Next, the effect of the anticoagulant on PMN secretion was measured. PPP isolated from whole blood incubated with 5 ng/ml LPS for 90 min contained 1170 ng/ml (EDTA blood), 2880 ng/ml (citrated blood), 4220 ng/ml (heparinized blood), and 5520 ng/ml lactoferrin (hirudinized blood). When studying the platelet parameter PF4, whole blood was incubated without any stimuli for 60 min, and we found that heparin PPP contained 1180 ng/ml PF4, while hirudin PPP contained 469 ng/ml, citrate PPP 440 ng/ml, and EDTA PPP 217 ng/ml PF4, respectively. Finally, the low molecular weight heparin compound Fragmin had no enhancing effect on PF4 levels in whole blood. It is concluded that the anticoagulant used in in vitro experiments has a large influence on the parameters measured.

Anticoagulants↗
PubMed1996

Evidence for exclusive role of the p55 tumor necrosis factor (TNF) receptor in mediating the TNF-induced collagenase expression by human dermal fibroblasts.

The aim of this study was to examine the roles of the TNF receptors p55 and p75 in the TNF-enhanced expression of collagenase by human dermal fibroblasts. The agonistic p55 monoclonal antibody Htr9 and TNF induced production of similar amounts of collagenase. Polyclonal or monoclonal agonistic p75 antibodies failed to enhance collagenase production, and the antagonistic p75 antibody 5E12 did not inhibit TNF-enhanced expression of collagenase. This strongly suggests that p55, but not p75, is involved in TNF-induced production of collagenase. Cells continued to produce an elevated level of collagenase after the removal of TNF or Htr9. These data suggest that it may be useful to use specific inhibitors of collagenase rather than to block cytokine action directly in the treatment of diseases with chronic enhanced collagenolytic activity. A peptide of residues 36-62 of TNF previously reported to be chemotactic to leukocytes was also able to enhance the expression of collagenase activity by dermal fibroblasts. Thus, design of peptides with specific TNF effects may offer a novel approach for treatment of fibrotic disorders.

Antibodies, Monoclonal↗
PubMed1996

Monocyte-platelet function and protection against cardiovascular disease.

Observational studies reveal a cardioprotective effect of hormone replacement therapy. The precise mechanisms whereby this treatment influences disease risk are not fully understood. Much attention has been paid to changes in lipid and lipoprotein metabolism, but this explains only part of the protective effect. In this short review, the roles of monocyte and platelet function in atherogenesis and thrombus formation are discussed. It is shown that hormone replacement therapy favourably down-regulates monocyte and platelet reactivity, which may be important in explaining the beneficial effect on the risk of cardiovascular disease.

Adult↗
PubMed1995

A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes.

In a previous study we have shown that granulocytes enhance lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes in a platelet-dependent reaction. The present investigation was undertaken to examine the role of a platelet activation product, platelet factor 4 (PF4), in LPS-induced TF activity in monocytes. Platelet lysate supernatant, purified PF4, and the COOH-terminal tridecapeptide of PF4, termed PF4(58-70), enhanced LPS-induced TF activity in monocytes of whole blood dose dependently. A monoclonal antibody against P-selectin eliminated the enhancing effect of PF4(58-70) on LPS-induced TF activity in monocytes, and PF4(58-70) was shown to act synergistically with tumor necrosis factor alpha (TNF-alpha). However, PF4(58-70) did not enhance TNF-alpha secretion in LPS-stimulated whole blood. The major effect of PF4(58-70) was granulocyte dependent. Our results suggest that PF4 might play an important role in LPS-stimulated monocyte TF activity of whole blood.

Amino Acid Sequence↗
PubMed1995

Effect of marine oils supplementation on coagulation and cellular activation in whole blood.

A study was performed to explore the effects of supplemental intake of various marine oils known to be part of the Eskimo diet. Healthy men and women (134) were randomly selected to consume 15 mL/d of oil from blubber of seal, cod liver, seal/cod liver, blubber of Minke whale, or no oil for ten weeks. Total cholesterol was unchanged in the oil groups, whereas high density lipoprotein cholesterol increased 7% in the seal/cod liver oil (CLO) group (P < 0.05) and 11% in the whale oil group (P < 0.005). Triacylglycerol was significantly reduced in the CLO group only. The concentration of prothrombin fragment 1 + 2 was reduced 25% (P < 0.05) after whale oil supplementation. No change in fibrinogen or factor VIIc was detected. Tumor necrosis factor generation in lipopolysaccharide (LPS)-stimulated blood was 30% reduced after whale oil (P < 0.05), but was unaffected by intake of seal or CLO. The LPS-induced tissue factor activity in monocytes was reduced to a significant degree only in the seal/CLO group (34%) and whale oil group (35%) (P < 0.05). The most dramatic change in thromboxane B2 in LPS-stimulated blood was seen after whale oil intake with 44% reduction (P < 0.01). Supplementation of a regular diet with a combination of seal oil and CLO and especially with whale oil seems to have beneficial effects on several products thought to be associated with cardiovascular and thrombotic diseases.

Adolescent↗
PubMed1995

Hormone replacement therapy reduces the reactivity of monocytes and platelets in whole blood--a beneficial effect on atherogenesis and thrombus formation?

OBJECTIVE: Our purpose was to investigate the effects of hormone replacement therapy on the reactivity of monocytes and platelets in whole blood, measured by tissue factor activity, tumor necrosis factor-alpha, and thromboxane B2. STUDY DESIGN: Thirty-two women were randomized into either transdermal or oral combined hormone replacement therapy and underwent blood sampling before and after 3 and 12 months of treatment. The tissue factor activity in monocytes was measured both in unstimulated whole blood and after a weak lipopolysaccharide stimulation. Tumor necrosis factor-alpha and thromboxane B2 formation in plasma were measured after a weak lipopolysaccharide stimulation of whole blood. RESULTS: After 12 months of hormone replacement therapy there were significant reductions of tissue factor activity in both unstimulated and lipopolysaccharide-stimulated monocytes (p < 0.001) and significant reductions in the formation of tumor necrosis factor-alpha (p < 0.03) and thromboxane B2 (p < 0.02). There were no differences in these parameters between the transdermal and the oral groups. No changes were observed after 3 months of therapy. CONCLUSION: Twelve months of hormone replacement therapy reduces cellular activation of blood monocytes and platelets; these changes may account for some of the beneficial effects in reducing the risk of cardiovascular disease.

Administration, Cutaneous↗
PubMed1995

C3 is activated in hereditary angioedema, and C1/C1-inhibitor complexes rise during physical stress in untreated patients.

Seven patients with hereditary angioedema (HAE) were studied to understand further how physical exercise may induce attacks. The most pronounced differences between patients and controls, however, were independent of the controlled bicycle run (mean values in patients/ controls); C4(g/L): 0.12/0.28 (P = 0.0122); C4bc (AU/ml): 137.0/18.0 (P = 0.0002); C4d (mg/mL): 5.03/2.35 (P = 0.0004); C3bc (AU/ml): 8.4/6.3 (P = 0.0049); C3a (AU/ml): 11.1/5.6 (P = 0.0102). The ratio C4bc to C4 was 1141 versus 64. Consequently, a substantial part of the low amount of C4 left in HAE patients consists of activation products, and the authors show for the first time that a mild but significant activation of C3 occurs in HAE. The two HAE patients treated with danazol had values of C1-INH function and antigen, C4, and C2 in-between those of normal and untreated patients, and lower levels of split products from C4 and high molecular weight kininogen than untreated patients. As a result of the exercise, fibrinolysis increased significantly in both patients and controls, while C1/C1-INH complexes rose significantly only in the five HAE patients without treatment when compared to the seven controls (P = 0.0089). This study thus suggests that complement activation is enhanced in untreated HAE patients following physical stress.

Angioedema↗
PubMed1995

Sites of tissue factor pathway inhibitor (TFPI) and tissue factor expression under physiologic and pathologic conditions. On behalf of the Subcommittee on Tissue factor Pathway Inhibitor (TFPI) of the Scientific and Standardization Committee of the ISTH.

Under normal conditions, TFPI expression is restricted to megakaryocytes and the endothelium of the microvasculature. It is not synthesized by normal hepatocytes or by the endothelium of larger vessels. In contrast, endothelium and peripheral blood cells do not express tissue factor under normal conditions. Expression of tissue factor under normal physiologic conditions is widespread and is localized in areas which are physically separated from the circulating blood. During an inflammatory response, circulating monocytes have been shown to express tissue factor, whereas in general, expression of tissue factor has not been observed in the endothelium. Adherent monocytes/macrophages express both tissue factor and TFPI under pathologic conditions. Whether or not circulating peripheral blood monocytes under inflammatory conditions express TFPI is not known.

Animals↗
PubMed1995

Cellular interactions in tissue factor expression by blood monocytes.

Tissue factor (TF) is the cellular receptor for factor VIIa. In complex with TF, factor VIIa initiates coagulation by activation of factor IX and factor X. TF is normally not in contact with blood, but is expressed on extravascular cells which forms a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. However, under pathological conditions monocytes, but probably not endothelial cells, are stimulated to express TF activity on the surface of the cells and may thereby trigger activation of blood coagulation. For several years we have observed some individuals (high responders) with a very high response to lipopolysaccharide (LPS) as judged by induction of TF activity in their monocytes in whole blood. This phenomenon has been shown to be mediated by a P-selectin dependent interaction between granulocytes, platelets and monocytes where the release of platelet factor 4 (PF4) plays an important role. It is concluded that cellular interactions play a central role in the expression of TF activity in circulating monocytes.

Blood Platelets↗
PubMed1995

Factor VIIa in patients with C1-inhibitor deficiency.

In hereditary angioedema (HAE), normal C1-inhibitor (C1-INH) is low and the contact system activated. Recently, the findings of a tissue factor mutant selectively deficient in promoting the conversion of FVII to FVIIa, but with retained cofactor for FVIIa, made it possible to examine reliably the pre-existing content of FVIIa in HAE patients. This was of interest as FXIIa (mainly inhibited by C1-INH) is able to activate FVII directly. FVIIa in 21 remission HAE patients were within normal limits but nearly doubled as compared to their 23 normal siblings (p = 0.0017). Cold promoted activation of FVII (CPA) (common clot assay) was displayed in plasma of all 5 untreated patients (C1-INH function < 35%), but not in plasma of 2 patients treated prophylactically with danazol (C1-INH function about 40%). These results suggest that there is a minute, yet significant activation of FVII in patients with C1-INH deficiency.

Angioedema↗
PubMed1993

Lipopolysaccharide induced monocyte thromboplastin synthesis and coagulation responses in patients undergoing coronary bypass surgery after preoperative supplementation with n-3 fatty acids.

Twenty patients with coronary heart disease (CHD) and elevated serum lipids were randomized into 2 groups of 10 to receive encapsulated preparations of either a concentrated ethylester form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil in doses of 6 g per day, given double blindly for approximately two months prior to coronary bypass surgery. Lipopolysaccharide (LPS) induced monocyte thromboplastin synthesis was studied during the preoperative period and one week following surgery. The ability of n-3 fatty acids to modify tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator inhibitor (PAI-1) was also evaluated along with fibrinogen and thrombin-antithrombin III (TAT) complexes. No significant changes were noted preoperatively. Monocyte reactivity, PAI-1, fibrinogen and TAT increased significantly after surgery. These changes were not modified by preoperative loading with n-3 fatty acids.

Acute-Phase Reaction↗
PubMed1993

Human leukocyte elastase and cathepsin G inactivate factor VII by limited proteolysis.

The effect of supernatant from phorbol myristate acetate (PMA) stimulated human polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro. The supernatant caused a rapid loss in factor VII coagulant activity by the action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as demonstrated by the use of specific inhibitors of the two serine proteases, respectively. Preincubation of the supernatant with the elastase inhibitor and the cathepsin G inhibitor preserved 80% and 25% of the clotting activity, respectively. Calcium protected factor VII completely from the supernatant mediated inactivation. Cathepsin G and HLE purified from PMN each destroyed the coagulant activity of factor VII when added to a non-plasma system. There were, however, no effect on factor VII activity when cathepsin G was added to plasma. Polyacrylamide gel electrophoresis in the presence of SDS indicated that HLE and cathepsin G cleaved the zymogen in the same manner, producing (a) peptide(s) of low molecular mass and a single large product of 48 kDa. Preincubation of factor VII with calcium ions inhibited the proteolytic action of HLE and cathepsin G. It is suggested that HLE and cathepsin G from activated granulocytes may be partly responsible for the loss in factor VII activity that is observed during sepsis.

Amino Acid Sequence↗
PubMed1993

Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets.

In the present study we have investigated the effect of platelets and granulocytes on bacterial lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes. Experiments were performed on freshly isolated cells resuspended in heparinized plasma and recombined with platelet-poor or platelet-rich plasma. In a platelet-dependent reaction the granulocytes enhanced LPS-induced TF activity by an average of 100%. The effect was dose dependent with regard to the number of both granulocytes and platelets, respectively. Granulocytes and/or platelets did not affect LPS-induced tumor necrosis factor (TNF) secretion from monocytes. Phorbol myristate acetate (PMA) per se was not able to induce TF activity in our system. In contrast, the agonist caused a substantial increase in TF activity induced by LPS. The effect was totally dependent on the presence of platelets and was shown to be due to stimulation of both granulocytes and monocytes (the activity rose from 30 +/- 7 to 83 +/- 12 mU/10(6) cells in the presence of platelets and from 69 +/- 8 to 143 +/- 22 mU/10(6) cells in the presence of platelets and granulocytes). Effects similar to those observed with PMA were obtained with physiological concentrations (10 ng/ml) of TNF. A combination of these two agonists gave no further amplification of LPS-induced TF activity compared with the effect of the agonists separately. Low concentrations of a monoclonal anti-CD15 antibody abolished the stimulatory effects of platelets and granulocytes. Furthermore, the anti-CD15 antibody neutralized the effect of TNF, whereas the PMA effect was reduced by almost 75%. These results were confirmed in a whole-blood system. The inhibitory effect of the antibody may be associated with CD15's role as a complementary ligand for PADGEM. Our study indicates that a close interaction between granulocytes, platelets, and monocytes is essential for optimal TF activity induced by LPS. It is hypothesized that the effect of granulocytes is related to their ability to activate platelets. We propose that upon activation granulocytes secrete a product that enhances the capacity of platelets to stimulate TF activity in monocytes.

Blood Platelets↗