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D Kvale

Publications and source records attributed to D Kvale.

48 records · Page 3Linked to original sources
PubMed1987

Interferon-gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins.

Recombinant interferon-gamma (IFN-gamma) increased in a dose-dependent manner the intracellular pool, the membrane expression, and the shedding of secretory component (SC) in human colonic adenocarcinoma cell line (HT-29). A similar dose-response relationship was observed when we examined the binding of polymeric IgA to HT-29 cells treated with IFN-gamma, thus reflecting expression of functional SC. Because IFN-gamma is produced by T cells during immune responses, activated T cells may be able to promote the external transport of dimeric IgA and pentameric IgM and thereby enhance the efferent limb of the secretory immune system. This is, therefore, the first observation indicating how the secretory transport capacity may be adjusted to increased local immunoglobulin production.

Adenocarcinoma↗
PubMed1987

Elevated levels of secretory immunoglobulins A and M in serum of patients with large bowel carcinoma indicate liver metastasis.

Preoperative serum levels of secretory IgA (SIgA) and secretory IgM (SIgM) were quantified by an enzyme-linked immunosorbent assay in 100 patients with large bowel carcinoma. The values obtained were related to tumor characteristics such as Dukes' stage, differentiation, DNA ploidy pattern, expression of secretory component (SC), volume, and plasma level of carcinoembryonic antigen (CEA). Statistical comparison was made with matched controls. Only patients with Stage D tumors showed significantly increased serum levels of SIgA and SIgM (P less than 0.004). The combined diagnostic sensitivity of SIg and CEA in Stage D was 0.94. In patients with liver involvement, serum SIgA and SIgM were elevated in 67% and 53%, respectively. However, circulating SIg was neither correlated with tumor SC expression nor with any other studied variable. Thus, the raised serum SIg levels were apparently not caused by release of SC from the tumors but, instead, by hampered liver function due to hepatic metastasis.

Adult↗
PubMed1987

Circulating secretory immunoglobulins of the A and M isotypes in chronic liver disease.

Serum levels of secretory IgA (SIgA) and secretory IgM (SIgM) were quantified by an enzyme-linked immunosorbent assay in 97 patients with various chronic liver diseases and 17 patients with uncomplicated ulcerative colitis. The values obtained were compared with 89 matched controls and related to other serum variables. All types of liver disease had elevated median levels of serum SIg. Patients with primary biliary cirrhosis (PBC) had the highest SIg levels, particularly SIgM, but increased total serum IgM was slightly more specific for PBC. Thus, the SIg levels did not add more discriminative information than several other variables. Elevated levels of circulating SIgA correlated mainly with variables that indicate reduced liver function. The difference observed between patients with PBC and primary sclerosing cholangitis (PSC) in the alkaline phosphatase (ALP)-to-SIg ratio is discussed.

Alkaline Phosphatase↗
PubMed1987

Early detection of liver metastasis in patients with colorectal carcinoma by increased levels of circulating IgA- and IgM-associated secretory component.

One hundred patients operated for colorectal carcinoma were followed clinically and with serial blood samples from 5 to 8 years. Levels of secretory component (SC) associated with IgA and IgM in serum were measured and related to Dukes' stage, histological differentiation, tumour expression of SC, and circulating carcinoembryonic antigen (CEA). On the whole, elevated levels of SC in serum were found in 15 of the 20 patients who already had (n = 15), or later developed (n = 5), liver metastasis. Four of the latter 5 patients showed raised SC levels with a 5.5 months median lead time from the first positive serum sample to clinically manifest liver disease. These data are interesting in view of the promising results reported for liver resection in patients with colorectal carcinoma.

Adult↗
PubMed1987

Induction of various HLA class II molecules in a human colonic adenocarcinoma cell line.

The colonic carcinoma cell line HT-29 had no constitutive expression of HLA class II molecules. Gamma interferon (IFN-gamma) induced expression of HLA class II molecules in a dose-dependent manner with 100 U/ml as an optimal dose. The expression of HLA-DR, HLA-DP, and HLA-DQ molecules seemed to follow different kinetics. While DR and DP molecules were maximally induced after 2 days, DQ molecules appeared later with maximum percentage positive cells after 8 days. Treatment with a prostaglandin synthesis inhibitor (indomethacin) neither induced class II expression nor altered the dose-response curve for IFN-gamma; this indicated that possible endogenous production of prostaglandins in this cell line did not interfere with its class II expression. The lectins phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and wheat germ agglutinin (WGA) did not induce class II expression.

Adenocarcinoma↗
PubMed1987

Circulating secretory component in breast neoplasms.

The serum concentrations of IgAp and IgMr associated secretory component (SIgA and SIgM) of 98 patients with neoplasms of the breast were measured. Of the 56 patients with carcinomas, 11 had increased concentrations of circulating SIgM, which was almost twice as sensitive as SIgA as a marker for carcinoma. Concentrations of circulating SIgA and SIgM were independent of expression of secretory component, IgA, and carcinoembryonic antigen (CEA); histological tumour grade; and tumour cell DNA ploidy, whereas a weak correlation between SIgA and SIgM and circulating CEA was seen. The three patients who had liver metastases indicated had particularly high concentrations of circulating SIgA and SIgM, whereas no difference was generally seen between patients with malignancy and those with benign tumours.

Adult↗
PubMed1987

Production and secretion of immunoglobulins in the gastrointestinal tract.

Two decades ago it was shown that the major immunoglobulin (Ig) present in human secretions is a dimeric IgA covalently bound to an epithelial glycoprotein of about 80 kD, now called the secretory component (SC). Pentameric IgM is likewise actively enriched in most exocrine fluids and is associated with SC, although not in a covalently stabilized complex. Three findings explain the selective translocation of polymeric Ig (pIg) into exocrine fluids: (1) preferential local production; (2) J-chain-expressing capacity of pIg-producing immunocytes; and (3) SC-mediated epithelial transport. Human hepatocytes lack SC and the human liver, therefore, cannot act as an efficient "IgA pump". This is in contrast to the rat liver which shows a remarkable capacity for transport of dimeric IgA from blood into the bile. The J chain of pIg and the epithelial SC represent the "lock and key" in the glandular transport of secretory IgA (SIgA) and SIgM. It has recently been shown that SC is synthesized as a transmembrane protein of about 95 kD and constitutes the actual pIg surface receptor. Complexing between ligand and receptor in the plasma membrane is followed by endocytosis. The completed SIgA and SIgM molecules are then translocated in cytoplasmic vesicles through the epithelial cell to the gland lumen along with an excess of free SC. The main function of SIgA is to exert immune exclusion; that is, by intimate cooperation with innate nonspecific defense factors it decreases penetration of soluble antigens and inhibits epithelial colonization of bacteria and viruses. Especially in selective IgA deficiency, SIgM may exert a similar protective function since its synthesis is markedly increased in the intestinal mucosa. Leakage of IgG into exocrine fluids is enhanced by mucosal irritation. Although IgG should not be considered as a SIg, it may contribute to immune exclusion. This is seen especially in the respiratory tract where IgG is less easily subjected to proteolytic degradation than in the intestinal juice. In contrast, by activating complement, IgG antibodies may at the same time be phlogistic and accelerate mucosal penetration of antigens. IgG may thus contribute to persistent immunopathology in mucosal disease. The same is true for IgE antibodies which may be carried into mucous membranes and secretions by mast cells and cause their degranulation with local histamine release. Traces of IgD may likewise be found in the secretions but without obvious biologic significance. Regulation of secretory immunity takes place both in organized lymphoepithelial structures, such as the Peyer's patches, and adjacent to the glands in the lamina propria.(ABSTRACT TRUNCATED AT 400 WORDS)

Celiac Disease↗
PubMed1986

An enzyme-linked immunosorbent assay for differential quantitation of secretory immunoglobulins of the A and M isotypes in human serum.

An enzyme-linked immunosorbent assay was developed for differential quantitation of secretory IgA (SIgA) and secretory IgM (SIgM) in human serum. The assay was based on non-competitive binding of SIgA and SIgM to microplates coated with an excess of antibodies to secretory component (SC). Appropriate standards were included to obtain absolute values. Mutual competition of SIgA and SIgM was avoided by testing the serum samples at sufficiently high dilutions. The assay is fast, simple, sensitive and reproducible. All of the 138 healthy individuals tested (1-91 years old) were found to have both SIgA and SIgM in their serum (medians, 10 mg/l and 14 mg/l, respectively). Lactating women, SIgA-deficient healthy individuals, and particularly patients with hepatitis had significantly increased serum SIgM levels compared with controls. Differential quantitation of SIgA and SIgM may turn out to be of diagnostic value and provide pathogenetic information.

Adolescent↗
PubMedDate not supplied

Expression and release of plasminogen activators, their inhibitors and receptor by human tumor cell lines.

Plasminogen activators (PAs) and their inhibitors (PAIs) can be produced by tumor cells and surrounding inflammatory cells and fibroblasts. The present study evaluate both the expression and release of PAs (uPA and tPA) and PAIs (PAI-1 and PAI-2) from cultured cells, and also the expression of uPA receptor (uPAR). Immunocytochemistry showed that PAs, PAIs and uPAR were present to different extents on the surface of colon carcinoma cells (Caco-2, HT-29), malignant melanoma cells (LOX) and normal fibroblasts. uPA immunoreactivity was intermediate in Caco-2, HT-29 and LOX and weak in the fibroblasts. tPA immunoreactivity was intermediate in Caco-2 and LOX and weak in HT-29 and fibroblasts. PAI-1 and PAI-2 immunoreactivities were absent in HT-29, weak in Caco-2 and strong in fibroblasts. In LOX the immunoreactivity was intermediate for PAI-1 and strong for PAI-2. uPAR immunoreactivity was weak in Caco-2, HT-29 and LOX and negative in fibroblasts. ELISAs on conditioned medium detected that the colon carcinoma cells Caco-2 and HT-29 did not release any PAs or PAIs. LOX released tPA (median 9 ng/million cells at 72 hours), PAI-1 (1050 ng/million cells) and PAI-2 (245 ng/million cells), and fibroblasts released uPA (1 ng/million cells) and PAI-1 (910 ng/million cells). These results show that both tumor cells and fibroblasts express tissue destructive enzymes, PAs and PAIs, whereas only the tumor cells express the uPAR required for focalization and regulation of PA activity at the cell surface. The melanoma cells LOX and fibroblasts also released PAs and PAIs, in contrast to the colon carcinoma cells Caco-2 and HT-29.

Cell Line↗