Ulcerative colitis-linked antineutrophil cytoplasmic antibody in the cotton-top tamarin model of colitis.

The presence of antineutrophil cytoplasmic antibodies (ANCA) in serum has recently been shown to be a good disease marker for ulcerative colitis. An animal model of colitis expressing serum ANCA would allow prospective studies of the relationship between ANCA expression and development of colitis. The cotton-top tamarin model of spontaneous colitis was investigated for presence of ANCA to evaluate its potential as a model for the study of the immune response in human ulcerative colitis.

The molecular basis of colon cancer.

There are approximately 160,000 new cases of colon cancer every year in the United States. Colon carcinoma results from the aggregate effects of multiple genetic alterations. Some genetic alterations may be inherited, while others reflect somatic mutations.

Identification and characterization of rat intestinal trefoil factor: tissue- and cell-specific member of the trefoil protein family.

The trefoil peptide family encompasses a group of small proteins that appear to assume a distinctive secondary structure that leads to intrinsic resistance to protease digestion. Induction of these peptides has been associated with response to injury in the gastrointestinal tract and related organs. Using an oligonucleotide derived from N-terminal amino acid sequencing of a transformed growth-inhibiting protein, a cDNA was cloned from rat intestinal villus epithelial cells that encodes a protein 81 amino acids in length with the characteristic trefoil peptide cysteine residue motif.

Regulation of transforming growth factor expression in rat intestinal epithelial cell lines.

Autocrine and paracrine modulation of transforming growth factor expression was assessed in rat intestinal epithelial cell lines designated IEC-6 and IEC-7. Addition of the transforming growth factor alpha (TGF alpha) homologue epidermal growth factor (EGF) to media of subconfluent IEC-6 cells led to autocrine stimulation of TGF alpha expression as well as increased expression of the transforming growth factor beta 1 (TGF beta 1). Increased expression of TGF alpha was maximal between 3 and 6 h after addition of EGF and subsequently declined coincident with increasing level of expression of TGF beta 1, which achieved maximal levels 6 h after addition of EGF and was sustained for more than 12 h.

Colonic glycoproteins in monozygotic twins with inflammatory bowel disease.

Colonic glycoprotein composition was evaluated in monozygotic twins with inflammatory bowel disease using ion-exchange chromatography. Fifty-three individuals, 12 pairs and 1 single twin with ulcerative colitis and 14 pairs with Crohn's disease, were evaluated. Seven twin pairs were concordant for the presence of ulcerative colitis or Crohn's disease, whereas twin siblings of 10 ulcerative colitis probands and 9 Crohn's disease probands were not known to have inflammatory bowel disease.

Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein.

The cell surface antigen, epithelial glycoprotein, defined by the monoclonal antibody HEA 125, is expressed on virtually all epithelial cell membranes but not on mesodermal or neural cell membranes. The cDNA encoding epithelial glycoprotein was isolated by HEA 125 antibody enrichment of colon tumor cDNA expressed transiently in COS cells. The sequence of the epithelial glycoprotein antigen is identical to the cell membrane protein recognized by the monoclonal antibody KS 1/4 and is homologous to the tumor-associated antigen GA733.

Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer.

Study Objective: To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder.

Design: Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years.

Setting: A general university teaching hospital serving both primary and referral patient populations.

Differential expression of transforming growth factors alpha and beta in rat intestinal epithelial cells.

Expression of transforming growth factor alpha (TGF alpha), and transforming growth factor beta (TGF beta) was assessed in isolated primary rat intestinal epithelial cells as well as a rat intestinal crypt cell-derived cell line (IEC-6). A gradient in TGF beta was present, with high concentrations of a 2.5-kb transcript found in undifferentiated crypt cells and progressively lower amounts of the TGF beta transcript in increasingly differentiated villus cell populations.

The colonic goblet cell and glycoprotein heterogeneity.

Mucin glycoproteins are an important 'nonspecific' host defense at the interface of mucosal surface and lumen. However insights into structural and functional features of these enormously complex and heterogeneous glycoproteins have been markedly limited. In recent studies, the presence of several distinct colonic mucin glycoproteins has been demonstrated and their oligosaccharide side chains extensively characterized through conventional structural analysis and utilization of monoclonal antibodies.

Alterations in mucosal content of colonic glycoconjugates in inflammatory bowel disease defined by monoclonal antibodies.

The presence of several glycoconjugates in colonic mucosa of patients with inflammatory bowel disease was assessed through indirect immunofluorescent staining using a collection of 23 monoclonal antibodies directed against human colonic mucin glycoproteins (anti-HCM MAbs). Intensity and distribution of staining by three anti-HCM MAbs were significantly altered in mucosa from patients with ulcerative colitis (UC) (n = 14) when compared with normal tissue (n = 15) and with tissue from patients with Crohn's disease as well as other inflammatory disorders (n = 15). Staining by anti-HCM MAb 17, which binds to colonic mucin glycoprotein species IV and V, was absent or diminished in 86% of samples from patients with active UC in contrast to 14% of normal and disease control specimens.

Emergence of antigenic glycoprotein structures in ulcerative colitis detected through monoclonal antibodies.

The emergence of new glycoprotein structures in colonic mucosa from patients with ulcerative colitis (UC) was assessed through the development of monoclonal antibodies (MAbs). Hybridomas were prepared from mice immunized with mucin glycoproteins purified from UC colonic tissue. Supernatants of 11 fusion products among 1200 fusion products that were screened in a solid-phase binding assay differentially bound UC-derived colonic mucin glycoproteins relative to comparable preparations from normal or Crohn's colitis tissue.

Human intestinal goblet cells in monolayer culture: characterization of a mucus-secreting subclone derived from the HT29 colon adenocarcinoma cell line.

HT29-18N2 (N2) cells, a subclone of the HT29 human colon carcinoma cell line, are shown in this report to be a model system for the study of human goblet cell differentiation and mucin secretion. Grown in the absence of glucose, these cells formed homogeneous epithelial monolayers of columnar cells with typical goblet cell morphology. Differentiation occurred on uncoated glass; laminin, fibronectin, or collagen type I or IV did not enhance differentiation.

Multiplicity of transforming growth factors in human malignant effusions.

Human malignant effusions were found to contain transforming growth factor (TGF) activity capable of stimulating anchorage independent growth of nontransformed rodent fibroblasts. Bio-Gel P-60 chromatography of acid-ethanol extracts demonstrated the presence of three populations of TGF activities in 57% of malignant effusions. Two activities were similar to those of TGF alpha and TGF beta as judged by their size (Mr approximately equal to 6,000 and approximately equal to 25,000, respectively), biological activity (ability to stimulate anchorage independent growth of NRK fibroblasts in the absence or presence of epidermal growth factor, respectively), and capacity to competitively inhibit binding of 125I-labeled epidermal growth factor to A-431 membranes and 125I-TGF beta to baby hamster kidney fibroblasts, respectively.

Latent transformed growth-inhibiting factor in human malignant effusions.

An inhibitor of soft agar colony formation by a human breast carcinoma-derived cell line was found to be present in latent form in the majority of cytology-positive human malignant effusions. Prior to dialysis, addition of human malignant effusions resulted in less than 10% alteration in efficiency of colony formation by the BT-20 human breast carcinoma cell line (mean efficiency 1 colony/4.3 cells plated at 14 days; mean colony diameter greater than 0.

Biosynthesis and secretion of human colonic mucin glycoproteins.

Synthesis and secretion of colonic mucin glycoprotein species were assessed during in vitro culture of colonic mucosal explants. DEAE-cellulose chromatography of endogenously labeled mucin glycoproteins from explant tissue demonstrated the presence of six mucin species (I-VI) similar to those identified earlier in surgical specimens of human colonic tissue. The relative proportions of mucin species I-VI in tissue explants remained constant throughout a 30-h culture period.

Effects of growth factors on an intestinal epithelial cell line: transforming growth factor beta inhibits proliferation and stimulates differentiation.

The effects of epidermal growth factor transforming growth factor beta (TGF beta) and other growth factors on the proliferation and differentiation of a cell line derived from rat intestinal crypt epithelium (IEC-6) were defined. Incorporation of [3H]-thymidine was stimulated 1.4-2.