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D Kvale

Publications and source records attributed to D Kvale.

At least 37 records · Page 2Linked to original sources
PubMed1993

Interferon-gamma stimulation of messenger RNA for human secretory component (poly-Ig receptor) depends on continuous intermediate protein synthesis.

Secretory component (SC or poly-Ig receptor) plays a key role in mucosal external body fluids. The aim of this study was to elucidate the molecular events underlying IFN-gamma-dependent up-regulation of SC. Using a human SC cDNA clone isolated by our laboratory, we found that IFN-gamma up-regulated SC mRNA levels in a time- and concentration-dependent manner. Moreover, in situ hybridization showed a striking increase of SC mRNA-positive HT-29 cells after IFN-gamma treatment. Inhibition with 5,6-dichloro-1-beta-ribofuranosyl-benzimidazole (DRB) indicated a half-life for IFN-gamma-induced SC mRNA of approximately 1 h. Cycloheximide (CHX) abolished the IFN-gamma-induced accumulation of SC mRNA in a reversible manner; the time-course suggested that de novo synthesis of protein factor(s) with a turnover time shorter than 6 h was required for accumulation of SC message. IFN-gamma-stimulated up-regulation of SC expression therefore appears to depend on molecular events similar to those taking place for the activation of several other genes in the Ig supergene family.

Colonic Neoplasms↗
PubMed1992

Molecular cloning and exon-intron mapping of the gene encoding human transmembrane secretory component (the poly-Ig receptor)

Secretory component (SC or the poly-Ig receptor) plays a crucial role in mucosal immunity by translocating polymeric IgA and IgM through secretory epithelial cells into external body fluids. Labeled restriction fragments from human SC cDNA were used to screen a human genomic leukocyte library. Three overlapping clones, spanning a total of 19 kb of the human SC gene, including 3 kb of the 5' flanking region, were characterized. The putative TATA box candidate, preceded by a CAAT-like box, was found 329 nucleotides upstream of the first exon. Altogether 11 exons covering the entire coding region were identified. The exon size ranged from 59 to 657 nucleotides and exon-intron junctions followed known consensus sequences. Three of the five extracellular Ig-related domains (D1, D4 and D5) were confined to one exon each (E3, E5 and E6), whereas D2 and D3 were encoded by the same exon (E4). The latter exon corresponds to that involved in alternate splicing of rabbit SC. The membrane-spanning segment was confined to part of one exon (E8). The cytoplasmic tail was encoded by four exons (E8-E11), whose boundaries encompassed fairly well the structural determinants proposed to be responsible for intracellular sorting of SC in the rabbit. The polymorphic restriction site reported earlier for Pvu II was localized to the third intron.

Amino Acid Sequence↗
PubMed1992

Expression and regulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human intestinal epithelial cell lines.

T cells and other leucocytes regularly occur within and subjacent to the gut epithelium. Recent data suggest that intestinal epithelial cells may exert accessory immunological functions. Although interactions between leucocytes and accessory cells usually require expression of adhesion molecules, intestinal epithelium has generally been considered negative for intercellular adhesion molecule-1 (ICAM-1) by immunohistochemical techniques. We therefore studied the expression of ICAM-1 and lymphocyte function-associated antigen-3 (LFA-3) by two colonic epithelial cell lines and found that both adhesion molecules were constitutively present at low levels. ICAM-1 protein expression could be enhanced within 4 h by cytokines, particularly after co-incubation with interferon-gamma (IFN) and tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), or IL-6. IFN also resulted in accumulation of ICAM-1 mRNA. Conversely, the LFA-3 expression was virtually unaffected by cytokine stimulation. These data imply that intestinal epithelial cells under certain conditions may bear adhesion molecules required for cooperation with juxtaposed leucocytes in situ, and that the expression of some of these molecules is modulated by cytokines from activated mucosal leucocytes.

Antigens, CD↗
PubMed1992

Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract.

Epithelial HLA class II is differentially expressed (DR >> DP) only after birth in salivary glands and small intestinal mucosa, in contrast to class I determinants and secretory component (SC) which appear early in gestation. However, there is a brisk postnatal increase in SC expression along with the class II induction, suggesting stimulation by cytokines from activated immune cells. T lymphocytes remain quite scanty in postnatal salivary glands, and the striking SC and class II expression might reflect a synergistic effect of IFN-gamma and TFN-alpha on immature epithelial cells. Enhanced epithelial expression of both SC and class II in salivary glands from sudden infant death victims could be the effect of immunostimulation caused by an infectious agent. Strikingly upregulated SC and epithelial class II expression (DR > DP > DQ) is seen in various inflammatory lesions such as obstructive sialadenitis, Sjögren's syndrome, chronic gastritis, and celiac disease. IFN-gamma and TNF-alpha are most likely involved as the expression patterns can be reproduced with these cytokines in vitro on colonic epithelial cell lines. However, these molecules of the Ig supergene family do not show a selective response in epithelia of inflammatory lesions because increased expression is also seen for lysozyme, lactoferrin and some other proteins. ICAM-1 can be upregulated on epithelial cells by various cytokines in vitro although the situation remains uncertain in mucosal inflammation. The expression pattern in IBD is complicated by dysplastic epithelial changes leading to reduced SC levels which may thus, in turn, jeopardize the poly-Ig transport mechanism. Epithelial class II molecules appear to have antigen-presenting properties, but the immunopathologic role of their increased expression in inflammatory disease in terms of induction of autoimmunity and/or abrogation of oral tolerance is a matter of continuing dispute.

Animals↗
PubMed1992

Circulating secretory component in relation to early diagnosis and treatment of liver metastasis from colorectal carcinomas.

AIMS: To evaluate serum secretory component in relation to early detection and clinical management of liver metastasis in patients with colorectal cancer. METHODS: Secretory component and carcinoembryonic antigen (CEA) were analysed in serial serum samples from 23 patients who had liver metastases as the only apparent recurrence, and in sera from 54 matched controls. Results of surgical treatment of recurrences were classified peroperatively as radical when no residual tumour was apparent and resection margins were free of disease. RESULTS: In total, 18 (78%) patients had increased secretory component during the whole follow up period (median 16 months); 12 (52%) had raised secretory component concentrations before clinical recurrence (median lead time 5.2 months). There was no difference before recurrence between circulating secretory component and CEA in sensitivity and lead times. Seventeen patients underwent surgery for hepatic metastasis; seven had radical hepatic resection of which only two (29%) showed increased secretory component concentrations before clinical recurrence; both had concurrent raised CEA values. By contrast, secretory component was raised in 83% of those cases considered inoperable. CONCLUSIONS: Although serum secretory component clearly increases in most patients with liver metastases, its clinical value seems questionable because secretory component apparently indicates mainly inoperable hepatic metastases.

Adult↗
PubMed1991

[Symptomatic cytomegalovirus infection in patients with acquired immunodeficiency syndrome].

During a seven-year period, symptomatic cytomegalovirus (CMV)-infection was diagnosed in 21.5% (n = 10) of all AIDS patients at the National Hospital of Norway (retinitis n = 8, colitis n = 3, pneumonitis n = 2, gastritis n = 1). Symptomatic cytomegalovirus-infection was associated with a poor long-term prognosis (median survival 174 days, range 10-415). Median CD4+ lymphocyte counts at onset of symptomatic cytomegalovirus-infection was 24 x 10(6)/l (range 6-68). Regular ophthalmological examination of HIV-infected patients with severe immunodeficiency, and endoscopy with multiple mucosal biopsies in patients with suspected cytomegalovirus-infection of the gastrointestinal tract, were of major importance in diagnosing symptomatic cytomegalovirus-infection. Six patients received an induction course of ganciclovir, and foscarnet was administered in two patients due to leukopenia. Problems of toxicity to the available anti-CMV agents make the development of additional therapeutic approaches desirable.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Protein kinase C activation selectively increases mRNA levels for one of the regulatory subunits (RI alpha) of cAMP-dependent protein kinases in HT-29 cells.

We have examined the effect of the protein kinase C activator, TPA, on mRNA levels for subunits of cAMP-dependent protein kinases in the human colonic cancer cell line HT-29, subline m2. Messenger RNA for the regulatory subunit, RI alpha, of cAMP-dependent protein kinases was shown to be present and regulated by TPA. Other mRNAs for subunits of cAMP-dependent protein kinases (RI beta, RII alpha, RII beta, C alpha, C beta) were also present in these cells, but revealed no or only minor changes upon TPA stimulation. When HT-29 cells were cultured in the presence of 10 nM TPA for various time periods, a biphasic response was observed in RI alpha mRNA levels with a maximal increase (approximately 4 fold) after 24 hours. TPA stimulated RI alpha mRNA increased in a concentration-dependent manner and maximal response (4-8 fold) was seen at 3-10 nM. The TPA-induced increase in RI alpha mRNA was not obtained when cells were incubated with TPA together with the protein kinase C inhibitors, staurosporine or H7. The cAMP-analog 8-CPTcAMP alone induced RI alpha mRNA levels 50% more than TPA. Combined treatment with TPA (10 nM) and 8-CPTcAMP (0.1 mM) gave an increase in RI alpha mRNA similar to TPA. These results demonstrate an interaction between the protein kinase C pathway and mRNA levels for the RI alpha subunit of cAMP-dependent protein kinases in HT-29 cells.

Blotting, Northern↗
PubMed1990

The significance of anti-hepatitis C virus antibodies measured in chronic liver disease.

The frequency of hepatitic C virus (HCV) antibodies was determined in two different laboratories in stored sera from 128 consecutive patients with chronic liver disease and from 41 healthy blood donors. Repeated measurements were performed in most patients. At the first determination the frequency of HCV antibodies was 7% in primary sclerosing cholangitis, 42% in primary biliary cirrhosis, 40% in autoimmune chronic active hepatitis, and 27% in alcoholic liver disease. The reproducibility of the determinations was rather poor, with a within-assay variation of 9.9%, whereas the between-assay variation was 34% and 47% in the two laboratories. There was a significant difference in the results obtained in the controls, depending on the handling of the sera. Freezing and thawing and, possibly, protracted storing of sera had a major impact on the assay and may have invalidated the results obtained in many studies. A significant association between IgG levels and titers of HCV antibodies was found in the total group of patients (p less than 0.005), in autoimmune chronic active hepatitis (p less than 0.005), and in primary biliary cirrhosis (p less than 0.01). It may be questioned whether the assay really is specific for anti-HCV antibodies in these patients. Whether HCV has anything to do with the etiology and pathogenesis of chronic liver disease apart from NANB-hepatitis is still undetermined.

Adolescent↗
PubMed1989

[New biotechnologic products in treatment and prevention].

Biotechnology will create new generations of DNA and peptide products in pharmacology. Such products may change clinical practice in the treatment of a variety of diseases, for example cancer and infectious, cardiovascular, and genetic diseases. Development of new vaccines using biotechnology may be effective in preventing or treating serious infectious diseases or cancer. We discuss approved and putative applications of biotechnological products in clinical medicine.

Genetic Engineering↗
PubMed1988

Rapid selection of cultured cells with increased expression of a membrane marker (secretory component).

This study showed how immunomagnetic monodisperse microspheres (Dynabeads) can be used for rapid selection of stable and homogeneous sublines of cancer cells. The beads were activated with antibody to a specific surface membrane marker. We used a monoclonal antibody (MAb) to human secretory component (SC), the epithelial receptor for polymeric immunoglobulins (pIg). A relatively low number of particles favored rosetting of strongly positive cells. SC-expressing cells were isolated within 30 min from a colonic carcinoma cell line (HT-29.E10). After 13 months of continuous culture the selected cells had a 15 times higher cellular content and a 10 times higher secretory rate of SC than parallel cultures of the original cell line. Immunomagnetic microspheres can be recommended in experimental cancer research, e.g., in order to minimize cellular heterogeneity and to isolate cells with particular surface membrane phenotypes in differentiation studies. The selection method is rapid and simple, and eliminates laborious test systems for conventional subclone screening.

Animals↗
PubMed1988

Tumor necrosis factor-alpha up-regulates expression of secretory component, the epithelial receptor for polymeric Ig.

Secretory component (SC) is the receptor that facilitates transcytosis of polymeric IgA and polymeric IgM through secretory epithelial cells and into exocrine fluids. The present study showed that rTNF-alpha enhanced the cellular pool, membrane expression, and secretion of functionally SC in a human colonic carcinoma cell line (HT-29m2) which is known to express and process SC like normal glandular cells. TNF-alpha also up-regulated membrane expression of the constitutive HLA class I molecules, whereas the cells remained HLA class II-negative.

Cell Membrane↗
PubMed1988

Up-regulation of the expression of secretory component and HLA molecules in a human colonic cell line by tumour necrosis factor-alpha and gamma interferon.

Secretory component (SC) acts as a receptor for polymeric IgA (pIgA) and pIgM on the basolateral face of secretory epithelia. This study showed that both the production and surface membrane expression of SC were additively up-regulated by tumour necrosis factor-alpha (TNF) and gamma interferon (IFN-gamma) in a human colonic cell line (HT-29m2). TNF likewise enhanced membrane expression of HLA class I determinants. Moreover, TNF augmented synergistically the IFN-induced de novo synthesis of HLA class II (DR) molecules. These data suggest that there are different regulatory mechanisms for the action of TNF and IFN and for the expression of HLA-DR and SC/HLA class I. Addition of actinomycin D abolished the cytokine-mediated increase of SC synthesis and expression. This observation suggested that transcriptional events are required for the cytokine-mediated up-regulation of SC.

Antigens, Surface↗