Biomedical subjects

B Nakstad

Publications and source records attributed to B Nakstad.

12 recordsLinked to original sources

PubMed1993

[Pathogenetic mechanisms in acute respiratory failure in adults].

A large variety of mediators and mediator systems are involved in the pathogenesis of acute respiratory failure in adults, and the complexity of the syndrome should be considered in both prophylaxis and therapy. The locally accentuated and organ-related activation of several mediator systems over a long period of time is likely to be responsible for the irreversible damage to cells and tissue. Surfactant dysfunction or degradation, regardless of the cause, contributes to the pathophysiology of severe respiratory failure, and might be a common denominator in the pathogenesis of the syndrome. Cytokines from macrophages are important, since these mediators have the potential to convert a primarily functional and reversible systemic reaction into irreversible damage to specific organs.

Adult↗

PubMed1993

[Integrins, structure and function].

Integrins are molecules of central importance in physiological and pathological processes. Integrins are an important factor in intercellular adhesion processes and cell migration leading to normal architecture of tissue, in inflammatory and tumour cell migration and in reparatory processes of damaged tissue. The integrin designation is derived from the role of these substances in integrating processes within and outside the cell. Therefore these membrane proteins play a role in cell growth, differentiation and gene expression. The role played by integrins in cell signal transduction and inflammation is discussed in this article. During the past few years we have seen an explosion of research in this field, which may lead to therapeutic benefits in a few years time.

Humans↗

PubMed1991

Immunohistochemical localization of coagulation, fibrinolytic and antifibrinolytic markers in adenocarcinoma of the lung.

Extravascular coagulation and fibrinolysis are intimately involved in and modulate cancer cell growth, invasion and metastasis. Samples from resection specimens of patients with primary lung cancer (adenocarcinomas) were tested with monoclonal (MAb) and polyclonal (PAb) antibodies against various factors of the coagulation or fibrinolysis systems, or against antigens of inflammatory or proliferating cells. MAb Ki-67 specific to nuclear antigens of proliferating cells showed a distinct but variable staining of cell nuclei throughout the tumor tissue. Nests of tumor tissue stained with cytokeratin-specific antibodies (PKK1), whereas other parts were negative. Fibrin(ogen) and fibronectin were found throughout the tumor tissue stroma and in the alveolar lining, and the most densely stained areas were at the transition zone between normal and tumor tissue. Fibrinolytic system components like tissue plasminogen activators (t-PA), and urokinase (u-PA), and their inhibitors PAI-1 and PAI-2 were all studied. All specimens were negative for t-PA (except endothelial linings), whereas urokinase-specific antibodies stained loosely packed tumor cells and macrophages within the tumor stromal tissue and alveolar septa. Both PAI-1 and PAI-2 were most prominently expressed within interstitial and alveolar macrophages. A weaker staining of tumor tissue cells was demonstrated. Inflammatory cells like macrophages and T lymphocytes were located in aggregates or diffusely spread within tumor stromal tissue. The inflammatory reaction was most intense at the border between normal lung and tumor tissue.

Adenocarcinoma↗

PubMed1990

Characterization of cytoadhesion molecules on human monocytes and tissue macrophages.

The presence of proteins antigenically related to the GPIIb/IIIa complex expressed on platelets have been investigated on tissue macrophages recovered by bronchoalveolar lavage (lung alveolar macrophages, LAM) or peritoneal lavage (peritoneal macrophages, PM) as well as on monocytes. Polyclonal antibodies (pab) directed against human platelet GPIIb/IIIa and the vitronectin receptor (VnR), and mouse monoclonal antibodies (mab) against human GPIIb, GPIIIa or the GPIIb/IIIa-complex were used. Triton X-100 extracts of bronchoalveolar cells (BAC) (containing 94% LAM) and the ultrasedimentable fraction of cell-free bronchoalveolar lavage (US) reacted with the polyclonal antibodies against the GPIIb/IIIa-complex and the VnR, but only with one (P4) of the mabs. Cell microscopy after immunogold labelling and alkaline phosphatase immunostaining, as well as immunofluorescence using the P4 mab and the polyclonal anti-GPIIb/IIIa clearly demonstrated positive membrane staining of LAM, PM and monocytes. Both BAC and US extracts gave rise to immunoprecipitates in crossed and rocket immunoelectrophoresis using anti-GPIIb/IIIa and anti-VnR. Our data indicate that monocytes and their monocyte-derived tissue counterparts constitutively express GPIIb/IIIa-like antigen(s) on their membrane. The presence of such antigen(s) on tissue macrophages makes it unlikely that platelet contamination is responsible for these findings.

Antigens, Surface↗

PubMed1990

Polymorphism of a platelet polypeptide.

Polymorphism of a platelet protein is described. The gene products are represented by two peptides of MW around 30 kD. The allele frequency was estimated to 0.85 and 0.15, the common variant being of slightly higher MW and about 2 charge units more acidic than the other. The peptides were neither released nor phosphorylated, and subcelluar fractionation indicated localization to the cytosol. Attempts to raise antibodies failed, and further characterization could not be done, but the peptides seem to differ from all reasonably well characterized platelet proteins so far.

Alleles↗

PubMed1990

Local activation of the coagulation and fibrinolysis systems in lung disease.

Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. Patient groups with chronic obstructive disease (COLD) (n = 76), idiopathic pulmonary fibrosis (IPF) (n = 29), sarcoidosis (n = 22), lung cancer (n = 36), pneumonia (n = 39), acquired immunodeficiency syndrome (AIDS) (n = 17) and a control group (n = 60) were studied by bronchoalveolar lavage (BAL). In all patient groups tissue thromboplastin (TPL) and fibrinopeptide A (FPA) were significantly increased compared to controls. Plasminogen activator (PA) activity was significantly lower in patients than in normals, and usually associated with high levels of antifibrinolytic activity. The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Distribution of bronchoalveolar cells and fibronectin levels in bronchoalveolar lavage fluids from patients with lung disorders.

Differential cell counts and fibronectin levels were recorded in bronchoalveolar lavage fluids (BALF) from patients with lung cancer, idiopathic pulmonary fibrosis (IPF), sarcoidosis, pneumonia, acquired immunodeficiency syndrome (AIDS), and chronic obstructive lung disease (COLD). In all groups fibronectin levels were significantly higher than in the control group; patients with sarcoidosis had a six-fold higher fibronectin level (mean values), AIDS 5.4-fold, pneumonia 4.4-fold, lung cancer, IPF and COLD 2.4-3.0-fold. In control smokers the fibronectin level was significantly higher compared to healthy nonsmokers (p less than 0.002). The increased fibronectin levels could not be explained by contamination of BALF with blood or leakage of plasma proteins. Thus, increased fibronectin levels probably reflect local (e.g. macrophage/fibroblast) synthesis.

Adult↗

PubMed1990

Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages.

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.

Bronchoalveolar Lavage Fluid↗

PubMed1989

Antigenic specificity of human alveolar macrophages and blood monocytes studied by an immunofluorescence technique.

Lung alveolar macrophages (AM) and blood monocytes (BM) are part of the mononuclear phagocyte system (MPS) and have been shown to be composed of several functionally and biochemically distinct subsets. AM and BM were each fractionated into four subfractions by centrifugation over Percoll, 95 per cent of the monocytes having a higher buoyant density than the high-density AM fraction. Antigen distribution within the cell subfractions was studied by an immunofluorescence technique using a panel of ten monoclonal antibodies (MoAbs) reacting with separate antigenic determinants previously found on mononuclear phagocytes. Several antigens were present on both types of cells (Ki-M1, Ki-M6, Leu-M3, Leu-M5, 1D5, Dako-Ma, and HLA-DR), while other antigens were expressed exclusively on BM (MAS 072 and MAS 081) or on AM (Ki-M8). Ki-M1, Leu-M3, Leu-M5, and HLA-DR were expressed to a greater degree on the surface of AM (95-96 per cent of cells) than on BM (56-68 per cent), while an inverse relationship was noted for 1D5 antigen (present on 41 per cent of BM and 11 per cent of AM). Ki-M6 and Dako-Ma MoAbs recognized an intracellularly restricted antigen present in both AM and BM. Ki-M1, Ki-M8, MAS 072, MAS 081, Leu-M3, Leu-M5, 1D5, and HLA-DR were expressed both in the cytoplasm and at the cell surface. Some antigens (1D5, Leu-M3, MAS 072, MAS 081, and Dako-Ma) showed an uneven distribution among subsets of both AM and BM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Dissociation of the aggregating effect and the inhibitory effect upon cyclic adenosine monophosphate accumulation by adrenaline and adenosine diphosphate in human platelets.

Recent evidence indicates that adrenaline and adenosine diphosphate each have separate stimulus-response pathways for induction of aggregation and inhibition of cAMP accumulation. We have used a natural model to test the validity of this evidence, i.e. patients from two kindreds with an inherited bleeding disorder due to absent aggregation to adrenaline and no secondary wave response to large concentrations of adenosine diphosphate. Our studies showed that the inhibitory effect of adrenaline and adenosine diphosphate on PGE1-induced increase of cAMP in the patients was not different from that of the controls both for adrenaline and adenosine diphosphate. These results therefore support the present evidence that both adrenaline and adenosine diphosphate apply separate pathways in these two platelet functions.

Adenosine Diphosphate↗

PubMed1987

Procoagulant activities in human alveolar macrophages.

The coexistence of fibrin and tissue macrophages is a common finding in the histopathology of chronic lung inflammatory diseases. Human lung alveolar macrophages (LAM) obtained by lavage of healthy donors can initiate the coagulation sequence by expressing procoagulant factors. The procoagulants of LAM were in this study identified to be either thromboplastin (tissue factor) or a direct factor X activator, probably a thromboplastin/factor VII complex. LAM did not show inducible thromboplastin synthesis as did monocytes when stimulated in vitro. LAM were separated into four subpopulations by density gradient centrifugation. The specific thromboplastin activity of subpopulation cells varied inversely with their density. Low-density subpopulations of LAM released microvesicles from their surface which could be recovered in the culture medium, and which expressed procoagulant activities with the same characteristics as the LAM procoagulants. These findings suggest that alveolar macrophages and the membrane vesicles shed from their surface contribute to local fibrin deposition in the lungs by expressing procoagulant factors.

Adult↗

PubMedDate not supplied

Subpopulations of human lung alveolar macrophages: ultrastructural features.

Lung alveolar macrophages (LAM), obtained by bronchoalveolar lavage of healthy donors, were separated into four subfractions on discontinuous gradients of Percoll and subjected to light microscopic, transmission (TEM) and scanning electron microscopic (SEM) studies. Alveolar macrophage morphometric analysis was performed on cytocentrifuged preparations. TEM of subpopulations revealed considerable morphologic heterogeneity. By SEM, cells of the most dense (D) subfraction were small, round, and, typically, the surface was highly ruffled with small membrane pseudopods. Cells of the least dense subfraction (A) showed a low degree of membrane folding or filopodia and were often totally disorganized. In smokers, macrophages of fraction A had a greater area and perimeter compared with non-smokers, whereas the inverse relationship was observed for C and D cells. Also, the number of electron-dense inclusions and the level of acid phosphatase were higher in smokers than in non-smokers. Coupled with functional heterogeneity the morphologic differences described in this paper suggest that density-separated subpopulations of LAM may represent different stages of differentiation or maturation.

Adult↗