Biomedical subjects

I Clemmensen

Publications and source records attributed to I Clemmensen.

At least 37 records · Page 2Linked to original sources

PubMed1991

A tetranectin-related protein is produced and deposited in extracellular matrix by human embryonal fibroblasts.

Tetranectin is a tetrameric human plasma protein that binds to plasminogen kringle 4. Its amino acid sequence is homologous with the C-terminal parts of asialoglycoprotein receptors and proteoglycan core proteins. In the present study, we have demonstrated that the human embryonal fibroblast cell line WI-38 produce a tetranectin-related molecule, which might, by several criteria, be similar to tetranectin from plasma. These criteria include immunoblotting analysis of conditioned cell medium revealing a protein band with Mr 17,000, indistinguishable from the Mr of plasma tetranectin. A preparation obtained by purification of conditioned medium by affinity chromatography on an anti-(plasma tetranectin) IgG column also contained the Mr 17,000 protein. This protein (partly purified from the conditioned medium) was shown by crossed immunoelectrophoresis to bind to heparin, CaCl2 and plasminogen kringle 4, as previously described for tetranectin in plasma. Importantly, this tetranectin-related protein is not only present in conditioned culture medium, but the Mr 17,000 protein reacting with anti-(plasma tetranectin) IgG was also present in the extracellular material, remaining after removal of WI-38 cells from the culture dishes, as demonstrated by immunoblotting analysis and immunocytochemical staining. We conclude that WI-38 cells produce a tetranectin-related protein and secrete it into the extracellular matrix.

Blood Proteins↗

PubMed1991

Differences in tetranectin immunoreactivity between benign and malignant breast tissue.

Tetranectin (TN) is a human, plasminogen kringle 4 binding plasma protein with ubiquitous cellular distribution and lectin-like characteristics. By means of the peroxidase-antiperoxidase staining technique a polyclonal and a monoclonal antibody were used to demonstrate TN within the intracellular as well as the extracellular compartment of invasive breast carcinoma. Whereas cell associated TN was universal showing only quantitative differences depending of the growth pattern of the tumor, 78 of 133 tumors displayed TN extracellularly as well. The occurrence of this stromal TN immunoreactivity was closely associated with desmoplasia, recognized morphologically by an increase in fibroblastic cells and immunohistochemically by an intense staining for the connective tissue glycoprotein fibronectin (FN). Benign breast tissue displayed a universal, intense cytoplasmic but no extracellular reaction for TN, with the exception of rare foci of granulation tissue and around dilated cysts. Functional studies have shown that human embryonal lung fibroblasts increase their release of TN to the growth medium upon stimulation. The presence of TN extracellularly within fibroblast-rich foci of desmoplasia (and granulation tissue) suggests that a similar increased release of the protein takes place in vivo during active states. Desmoplasia has been found to have a protective effect on tumor cell propagation and metastasis in a murine model. The molecular interactions, which are responsible for this effect, are undoubtedly complex. However, TN may, by its specific binding to kringle 4 of plasminogen and its high affinity for sulphated polysaccharides, add to the understanding of how plasminogen activation is modulated at the local extracellular level.

Blood Proteins↗

PubMed1991

Plasma tetranectin and ovarian neoplasms.

Plasma tetranectin was measured in 67 controls, 121 patients with a benign or malignant ovarian tumor, and 24 patients with another benign gynecologic disease to evaluate the predictive value of plasma tetranectin. A significant reduction of plasma tetranectin was found in every malignant tumor type except for mucinous tumors. Further a significant correlation was found between stage of tumors and plasma tetranectin. Depending on the cutoff level the sensitivity for stage 1 cancer ranged from 52 to 71%. In stage 1 + 2 the sensitivity ranged from 58 to 75% and for advanced cancer (stage 3 + 4) from 80 to 95%. The corresponding specificities ranged from 97 to 84%. Plasma tetranectin may be a useful tool for detecting early stages of ovarian cancer.

Adult↗

PubMed1991

Tetranectin in amniotic fluid, maternal serum and fetal fluids.

The concentration of the newly discovered protein tetranectin has been measured in different fetal and maternal compartments. In amniotic fluid a significant, positive correlation between the tetranectin concentration and gestational age was found (a mean of 0.2 mg l-1 at week 14 to a mean of 0.5 mg l-1 at week 21). In maternal serum a slight negative correlation was found between tetranectin concentration and gestational week (a mean of 6.17 mg l-1 at week 14 to a mean of 5.79 mg l-1 at week 21). In-term cord blood collected at delivery a mean level of 6.0 mg l-1 was found, and no difference was found between arterial- and venous-blood tetranectin concentration. In fetal serum the overall mean level was 2.6 mg l-1 and a significant positive correlation between tetranectin concentration and gestational age was found. The mean level was 1.1 mg l-1 in fetal cerebrospinal fluid and no correlation to gestational age was found. Fetal tetranectin may, therefore, be correlated to fetal maturation.

Amniotic Fluid↗

PubMed1990

Decreased tetranectin in multiple myeloma.

Tetranectin, a recently described human protein widely distributed in the body and with possible importance for cell growth and differentiation, has previously been observed to be decreased in patients with solid malignant tumors. In patients with multiple myeloma, either untreated or previously treated, serum levels were found to be significantly reduced. A negligible interindividual variation was observed. Levels of serum tetranectin were not correlated with serum albumin, hemoglobin, or M-component. Low levels of tetranectin may be related to the growth and spread of malignant cells or reflect a general catabolic state of chronic disease.

Aged↗

PubMed1990

Identification of a highly mobilizable subset of human neutrophil intracellular vesicles that contains tetranectin and latent alkaline phosphatase.

Tetranectin, a protein recently identified in a wide variety of human secretory cells (Christensen, L., and I. Clemmensen. 1989. Histochemistry. 92:29-35) was found to colocalize with latent alkaline phosphatase activity in fractions well separated from azurophil granules, specific granules, gelatinase-containing granules, and plasma membranes when postnuclear supernatants of nitrogen-cavitated neutrophils were fractionated on discontinuous Percoll density gradients. Stimulation of intact neutrophils with nanomolar concentrations of FMLP, leukotriene B4, 10-100 U/ml of tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor resulted in parallel release of tetranectin and translocation of alkaline phosphatase to the plasma membrane. Furthermore, intracellular pools of tetranectin and latent alkaline phosphatase were completely released from neutrophils under conditions that barely induced release of specific granules containing B12-binding protein. These findings indicate that tetranectin and latent alkaline phosphatase define an easily mobilizable population of cytoplasmic storage organelles in human neutrophils which are functionally distinguishable from azurophil, specific, and gelatinase-containing granules. These organelles may play an important role as stores of membrane proteins that are mobilized to the cell surface during stimulation by inflammatory mediators.

Alkaline Phosphatase↗

PubMed1990

Attachment of staphylococci to silicone catheters in vitro.

The adherence of radiolabeled staphylococci to silicone catheters was investigated in vitro. Staphylococcus aureus and Staphylococcus epidermidis strains bound to the same extent to the catheters. Also, S. epidermidis strains isolated from patients with plastic-related infections showed binding similar to that of other S. epidermidis strains. By preincubation of catheters the influence of purified staphylococcal cell surface components on the binding was evaluated. The most potent inhibitors of the binding of S. aureus were the two surface proteins, clumping factor and protein A, and the cytoplasmic membrane. Surface proteins and the cell membrane of S. epidermidis also blocked the binding. Only protein-containing surface proteins inhibited the binding. The production of slime correlated with the degree of S. epidermidis binding. Human plasma and serum, as well as purified albumin and IgG, inhibited the binding of both staphylococcal species. Fibrinogen, and to a certain extent fibronectin, inhibited the binding of S. epidermidis, while both these purified plasma proteins enhanced the binding of S. aureus.

Bacterial Adhesion↗

PubMed1989

Quantitation of plasma levels of tetranectin--effects of oral contraceptives, pregnancy, treatment with L-asparaginase and liver cirrhosis.

Tetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 +/- 16 (SD)%, (100% = 0.15 mumol/l). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years. Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction. It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.

Adolescent↗

PubMed1989

Calcium-dependent binding of tetranectin to fibrin.

The plasma protein, tetranectin, capable of binding to kringle-4 of plasminogen, is reduced in serum after clotting of plasma. Fibrin binding is confirmed by the presence of tetranectin in clot lysates. The amount of tetranectin bound to the fibrin varies with the plasma level, but constitutes a constant percentage of 13-17% of the plasma tetranectin. The fibrin binding of tetranectin requires the presence of CaCl2, but is independent of factor XIII. Further, it is independent of the presence and fibrin binding of plasminogen. Reduction of tetranectin in serum of fresh blood (9%) is less than reduction in serum made from platelet-poor plasma (13-17%). This difference could be attributed to a releasable platelet pool of tetranectin. Extracts of platelets show around 15% tetranectin (relative to the plasma concentration). It is concluded that tetranectin can, upon coagulation, be released from platelets and become partially bound to fibrin.

Blood Coagulation↗

PubMed1989

Tetranectin immunoreactivity in normal human tissues. An immunohistochemical study of exocrine epithelia and mesenchyme.

A recently discovered human plasma protein, tetranectin (TN), which has previously been demonstrated immunohistochemically within various endocrine tissues, was in this study identified in an additional number of epithelial and mesenchymal cells by two polyclonal antibodies and one monoclonal using the conventional immunoperoxidase staining technique and a modification of the CLONO-GLAD procedure. TN was found in endothelial and epithelial tissues, particularly in cells with a high turn-over or storage function such as gastric parietal and zymogenic cells, absorptive surface epithelium of the small intestine, ducts of exocrine glands and pseudostratified respiratory epithelium. Also mesenchymal cells produced a TN positive staining reaction, which was most conspicuous in mast cells, but also present in some lymphocytes, plasma cells, macrophages, granulocytes, striated and smooth muscle cells and fibroblasts. SDS-PAGE and Western blotting analysis of cultured human embryonal fibroblasts (WI-38) showed that the cells besides TN contain another protein with a molecular weight of 82,000. As this protein, however, reacted with our affinity purified antibodies it probably represents a precursor of TN or a protein with a molecular weight of approximately 60,000, which is covalently linked to TN. This and the fact that TN shows amino acid sequence homologies to the carboxyterminal part of the asialo-glycoprotein receptor and a cartilage proteoglycan core protein as well a binding affinity to plasminogen points to TN as being part of a larger molecule, which possibly has been cleaved by proteolysis at the cellular site and then passed into the blood, where it polymerizes into a tetramer.

Antibodies↗

PubMed1989

Interaction of tetranectin with sulphated polysaccharides and trypan blue.

Tetranectin is a recently discovered plasminogen binding protein from human plasma, with a known primary structure. Its interactions with various sulphated polysaccharides and trypan blue has been investigated by crossed immunoelectrophoresis, immunosorbent assay (ELISA) and gel filtration experiments. Interaction of tetranectin with chondroitin sulphate A, B, and C, heparan sulphate and trypan blue could be demonstrated by crossed immunoelectrophoresis against monospecific rabbit anti-tetranectin. Interaction of tetranectin with fucoidan could be demonstrated by all three methods, and this interaction could be prevented by heparin and to a lesser degree by chondroitin sulphate A and C, but not by fucose. These findings, together with the recently published findings, that tetranectin is present in exocrine and endocrine glands as well as in secreting surface epithelia and mesenchyme, suggest that tetranectin, in conjunction with proteoglycans, may have a function in the packaging of granules or as a participant in exocytocic processes.

Animals↗

PubMed1988

Stromal fibronectin staining pattern and metastasizing ability of human breast carcinoma.

The peripheral stromal fibronectin (FN) staining patterns of invasive breast carcinomas (IBC) from 77 women were compared to the aggressivity of the tumors, which in each case had been determined through a complete clinical follow-up and autopsy investigation. Polyclonal, monospecific rabbit antibody to human FN was applied on formalin-fixed, paraffin-embedded tissue sections using the peroxidase-antiperoxidase staining technique. An FN-positive staining reaction was defined as a constant, diffuse, or pericellular demarcation of FN-positive fibers surrounding tumor cells at the invasive border. In lack of such a staining pattern, FN-negative staining was recorded. The FN-positive staining reaction was significantly associated with a low metastatic potential and appeared in a multivarians analysis to be an excellent prognostic factor, which surpassed other known parameters, such as clinical stage, histological type or grade, and lymph node status. 27 out of 31 women, who died without evidence of metastatic spread, had FN-positive IBC (87%) in contrast to women with metastatic disease, where only 15 out of 46 had FN-positive tumors (33%). An extensive histopathological examination of the contralateral breast revealed in this latter group a high rate of second primaries (22/46), which might have been responsible for the metastatic spread. If these women with bilateral IBC were excluded, only three metastasizing tumors with a FN-positive staining pattern remained, suggesting that the prognostic value of the FN-staining pattern along the invasive border of IBC might be even higher than anticipated from this study.

Analysis of Variance↗

PubMed1988

Plasma tetranectin is reduced in cancer and related to metastasia.

Tetranectin, a recently identified and characterized human plasma protein related to the fibrinolytic system, was significantly reduced in patients with various malignancies. Plasma tetranectin, measured by enzyme-linked immunosorbent assay (ELISA), was a significant discriminator regarding metastatic or nonmetastatic cancer. It had a high predictive specificity (0.93) and sensitivity (0.75) and only misclassified 14% of patients. Tetranectin may be related to the pathogenetically important processes leading to cancer spread and metastasis. In this respect, it may prove to be of discriminative importance clinically.

Adult↗

PubMed1988

Non-invasive evaluation of bone formation: measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease.

Three noninvasive indices of bone formation, serum alkaline phosphatase (s-AP), 24-h whole body retention of diphosphonate (WBR), and serum osteocalcin (s-OC), the two lastnamed clearance-corrected, were compared in 121 patients with various bone disorders and in 50 patients with thyroid disease. In conditions with qualitatively normal matrix formation and mineralization, i.e. thyrotoxicosis, primary hyperparathyroidism, myxoedema and osteoporosis, the three indices deviated from average normal by about the same extent: 134%/128%/200%, 120%/113%/133%, 105%/100%/79% and 89%/86%/69%, respectively. A disproportionately marked deviation of s-AP was observed in states of abnormal matrix formation or mineralization, i.e. osteomalacia and Paget's disease: 430%/145%/282% and 348%/145%/202%, respectively. Furthermore, the formation indices correlate differently with s-calcium in hyper- and hypocalcaemic conditions. In primary hyperparathyroidism the respective r-values were 0.32/0.62/0.68, while an inverse pattern was observed in osteomalacia: -0.60/-0.51/-0.47. As very little is known about the secretion of AP and OC and their role in bone formation and mineralization, the cause(s) for the observed differences remain(s) uncertain.

Adult↗

PubMed1987

Primary structure of tetranectin, a plasminogen kringle 4 binding plasma protein: homology with asialoglycoprotein receptors and cartilage proteoglycan core protein.

Tetranectin binds to plasminogen and to isolated kringle 4 [Clemmensen, I., Petersen, L. C., & Kluft, C. (1986) Eur. J. Biochem. 156, 327-333], apparently to its lysine-binding site. Each of the four identical chains consists of 181 amino acid residues. The three intrachain disulfide bonds connect Cys residues 50-60, 77-176, and 152-168. The tetranectin sequence is homologous (17-24% identical positions) with those parts of the asialoglycoprotein receptor family that are considered to be extracellular. Tetranectin has no structures corresponding to those parts of the receptors considered to be intracellular and membrane anchoring. The sequence of tetranectin is also homologous (22-23% identical positions) with the C-terminal globular domain of the core protein of the cartilage proteoglycan. All six Cys residues in tetranectin are located at positions that are also Cys residues in this proteoglycan. Therefore, a plausible disulfide bond pattern can now be proposed for both the asialoglycoprotein receptors and the C-terminal domain of the proteoglycan core protein. No covalently bound carbohydrate has been found.

Aggrecans↗

PubMed1987

Immunohistochemical localization of a novel, human plasma protein, tetranectin, in human endocrine tissues.

A monospecific antibody to a plasminogen kringle 4-binding tetramer protein of human blood, tetranectin, was applied to various human endocrine tissues employing the peroxidase-antiperoxidase staining technique. Endocrine cells with a known protein or glycoprotein hormonal production such as chromophils (pituitary), follicular and parafollicular cells (thyroid), chief cells (parathyroid), hepatocytes (liver), islet cells (pancreas) and ganglion cells of the adrenal medulla displayed a convincing, positive staining reaction for tetranectin, which varied from cell to cell within the different tissues. The liver showed a distinct and universal reaction within almost all hepatocytes, thus raising suspicion of producing the bulk of tetranectin to the blood. Tetranectin has recently been characterized as a lectin-like protein with amino acid sequence homology to the core protein of a rat chondrosarcoma proteoglycan. Proteoglycans have been demonstrated in secretory granules of rat pituitary and pancreatic islet cells, where they probably serve as modulators in hormonal production. The granular, cytoplasmic immunohistochemical localization of tetranectin demonstrated in this study combined with the fact that tetranectin is known to attach to plasminogen and promote plasminogen activation catalysed by tissue plasminogen activator suggests that this protein might have a dual function, serving both as a regulator in the secretion of certain hormones and as a participant in the regulation of the limited proteolysis, which is considered important for the activation of prohormones.

Blood Proteins↗

PubMed1987

Plasma fibronectin in idiopathic myelofibrosis and related chronic myeloproliferative disorders.

Plasma fibronectin concentrations were measured in 49 patients with chronic myeloproliferative disorders and compared to sex- and age-matched controls. A significantly lower plasma fibronectin concentration was observed in patients with idiopathic myelofibrosis as compared with the control group (p less than 0.01). In addition, plasma fibronectin concentrations in myelofibrosis patients differed significantly, when compared with patients with polycythaemia vera (p less than 0.01), whereas no significant difference was found between myelofibrosis patients and those with a transitional myeloproliferative disorder or chronic myelogenous leukaemia (p greater than 0.05). An inverse relationship was demonstrated between plasma fibronectin and spleen size, the lowest plasma fibronectin levels being found in patients with large spleens. It is supposed that low plasma fibronectin concentrations in splenomegalic patients may be due to enhanced consumption of the opsonin in the expanded splenic mononuclear-macrophage system.

Adult↗

PubMed1987

Plasma tetranectin in healthy male and female individuals, measured by enzyme-linked immunosorbent assay.

Tetranectin is a novel protein recently isolated from human plasma. It is a tetramer, composed of four identical, non-covalently bound, 181-amino-acid polypeptide chains (Mr = 20,100). We report here the quantification of plasma tetranectin in 457 healthy individuals, aged from birth to 85 years, using a newly developed sensitive and reproducible enzyme-linked immunosorbent assay (ELISA). Tetranectin was demonstrable in all subjects investigated, and within each sex and defined age group the concentration was well controlled within a relatively narrow range. The mean plasma tetranectin level in newborn infants (cord plasma) was about 8 mg/L. This was significantly less than in later life, during which mean plasma tetranectin level varied between 10 and 12 mg/L. After the age of 9 years, tetranectin level was continuously higher in males than in females, but the variations through the span of life were almost identical. Thus, a transitory increase in plasma tetranectin was observed in early puberty, reaching its climax about the age of 11 to 12 in girls and 14 to 15 in boys. A quantitatively similar, additional peak was observed during the period of 50 to 59 years of age in both sexes, whereupon the tetranectin concentration gradually decreased. The biologic function of tetranectin remains to be elucidated. Recently, we have reported that tetranectin is contained within hepatocytes and various endocrine cells, all known to process peptide hormones or glucoproteins. We propose that tetranectin may be involved in intracellular and extracellular serine protease-mediated proteolysis.

Adolescent↗