Biomedical subjects

I Clemmensen

Publications and source records attributed to I Clemmensen.

At least 19 recordsLinked to original sources

PubMed1995

The role of serum tetranectin, CA 125, and a combined index as tumor markers in women with pelvic tumors.

Serum tetranectin (Se-TN) and CA-125 were measured in 315 patients with a pelvic tumor and 458 healthy females. At a false-positive rate of 0.7% the sensitivity for ovarian cancer stage 1 and 2 was 33% for Se-TN and 76% for both CA 125 and an index based on Se-TN and CA 125 (Index 1). At a false-positive rate of 0.4% the sensitivity was 29% for Se-TN, 62% for CA 125 (35 U/ml), and 76% for Index 1. A negative correlation was found between the Se-TN level and the stage of cancer. The sensitivity for benign tumors was 6% for Se-TN, 17% for CA 125, and 21% for Index 1 at a false-positive rate of 0.4%. In the present study the sensitivity and specificity levels of Se-TN were not sufficiently high to warrant the use of Se-TN as an individual marker for ovarian cancer. The sensitivity rose with the index-based Se-TN and CA 125 without causing a concomitant increase in the rate of false-positive results. None of the markers rose to levels that would allow their use in clinical diagnosis to discriminate between localized cancer and benign tumors.

Adolescent↗

PubMed1995

Plasma tetranectin and colorectal cancer.

The prognostic significance of plasma tetranectin (PL-TN) in colorectal cancer was retrospectively examined in 504 patients (80 Dukes' A, 174 Dukes' B, 98 Dukes' C and 152 Dukes' D). Follow-up time was 7-12 years. No significant prognostic variable was found for Dukes' A patients by Cox multivariate analysis. In stage B, PL-TN was the second strongest prognostic variable [relative hazard (RH) = 3.3 for patients with PL-TN < or = 7.5 mg/l]. The other prognostic variables were perineural invasion (RH = 3.7), tumour distance < or = 10 cm from the anal verge (RH = 3.0), postoperative radiotherapy (RH = 2.9) and a high carcinoembryonic antigen (CEA) score (RH = 1.8). In Dukes' C, only CEA score and gender were of prognostic significance. For Dukes' D, PL-TN was the only prognostic variable (RH = 1.7). Testing all patients in one multivariate analysis, Dukes' staging was the strongest and PL-TN the second strongest prognostic variable. The shortened survival for patients with low PL-TN levels is illustrated with lifetables.

Aged↗

PubMed1994

Serum tetranectin and CA-125 used to monitor the course of treatment in ovarian cancer patients.

Serum tetranectin (Se-TN) and CA-125 were measured in serum samples obtained before primary surgery, before start of chemotherapy and monthly during chemotherapy in 8 patients with ovarian cancer. The median Se-TN level before chemotherapy (7.3 mg/l) increased significantly after the start of chemotherapy (13.7 mg/l), with the highest increase for one survivor (145%). Five patients who died of cancer in the study period, had pronounced decreases (30-50%) in Se-TN with a maximal concentration during chemotherapy to the lowest concentration in the last sample. One patient who died 10 months after closure of the study had continuously normal Se-TN values, but the last CA-125 value elevated. The lead time could be calculated in four patients for Se-TN and six patients for CA-125. Median lead times of 3.6 months and 3.8 months were found for Se-TN and CA-125 respectively. In conclusion, chemotherapy induces significant increases in Se-TN levels. A decrease in Se-TN during chemotherapy is highly suspect for recurrence and a poor outcome. Measurements of TN should therefore be included in other comparative studies.

Aged↗

PubMed1994

Tetranectin expression in human colonic neoplasia.

The expression of tetranectin in colonic neoplasia was evaluated by determining the tissue distribution by immunohistological analysis of tissue sections and the antigen levels in tissue homogenates and plasma. In normal colonic mucosa tetranectin staining was predominantly found in the goblet cells whereas in adenocarcinomas this staining was confined to the tumour stroma. Colonic adenomas, benign precursors of adenocarcinomas, showed fewer tetranectin positive goblet cells and in some cases showed tetranectin expression in the stroma. Within the tissue homogenates no differences were found in the tetranectin levels between normal mucosa, adenomas and carcinomas. Patients with colonic cancer were found to have significantly decreased plasma tetranectin levels compared to healthy controls. Thus, colonic neoplasia is associated with a change in the tissue distribution of tetranectin, without an obvious change in the tissue level, and a low plasma tetranectin level.

Adenocarcinoma↗

PubMed1992

Changes in plasma tetranectin following hip surgery with or without thrombotic complications.

The fibrinolytic system seems to play a role in the development of postoperative thromboembolic complications (DVT). The newly described tetrameric protein tetranectin (TN), which has been found to enhance the activation of plasminogen to plasmin, therefore was studied in 55 patients who had total hip replacement and solely elastic stockings as physical thromboprophylaxis. No significant difference in plasma TN was found between the 5 patients with DVT and those without DVT, neither preoperatively or postoperatively at day 0, 1, 3, 7 or 10. A significant decrease in plasma TN was found from preoperative to postoperative values, indicating that TN may be a possible marker for other postoperative events. Because of the observed postoperative decrease it is important to consider the sampling time in the future research with TN.

Adult↗

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↗