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P Möller

Publications and source records attributed to P Möller.

At least 73 records · Page 4Linked to original sources
PubMed1999

Detailed marker chromosome analysis in cell line U-BLC1, established from transitional-cell carcinoma of the bladder.

A permanent cell line, U-BLC1, was established from a primary transitional-cell carcinoma, TCC, of the urinary bladder. Karyotype analysis showed the line to be highly aberrant, with a near-triploid chromosome number of 68 to 73. Comparative genomic hybridization revealed some distinct differences between the primary tumor and the established cell line. Karyotype analysis showed 3 marker chromosomes with homogeneously staining regions, HSRs, in the cell line. The HSRs were isolated by microdissection and the microdissection probes were hybridized to normal metaphase chromosomes. The HSRs contain sequences known to be frequently involved in amplification in transitional-cell carcinoma of the bladder, 6p22, 7p11-p12, 9p23-pter, and one region not yet reported to be amplified in primary TCC of the bladder, 1p31-p32. A candidate-gene approach showed that in the region 7p11-p12 the EGFR locus is amplified and highly expressed.

Aged↗
PubMed1999

Colitis-inducing potency of CD4+ T cells in immunodeficient, adoptive hosts depends on their state of activation, IL-12 responsiveness, and CD45RB surface phenotype.

We studied the induction, severity and rate of progression of inflammatory bowel disease (IBD) induced in SCID mice by the adoptive transfer of low numbers of the following purified BALB/c CD4+ T cell subsets: 1) unfractionated, peripheral, small (resting), or large (activated) CD4+ T cells; 2) fractionated, peripheral, small, or large, CD45RBhigh or CD45RBlow CD4+ T cells; and 3) peripheral IL-12-unresponsive CD4+ T cells from STAT-4-deficient mice. The adoptive transfer into SCID host of comparable numbers of CD4+ T cells was used to assess the colitis-inducing potency of these subsets. Small CD45RBhigh CD4+ T lymphocytes and activated CD4+ T blasts induced early (6-12 wk posttransfer) and severe disease, while small resting and unfractionated CD4+ T cells or CD45RBlow T lymphocytes induced a late-onset disease 12-16 wk posttransfer. SCID mice transplanted with STAT-4-/- CD4+ T cells showed a late-onset IBD manifest > 20 wk posttransfer. In SCID mice with IBD transplanted with IL-12-responsive CD4+ T cells, the colonic lamina propria CD4+ T cells showed a mucosa-seeking memory/effector CD45RBlow Th1 phenotype abundantly producing IFN-gamma and TNF-alpha. In SCID mice transplanted with IL-12-unresponsive STAT-4-/- CD4+ T cells, the colonic lamina propria, mesenteric lymph node, and splenic CD4+ T cells produced very little IFN-gamma but abundant levels of TNF-alpha. The histopathologic appearance of colitis in all transplanted SCID mice was similar. These data indicate that CD45RBhigh and CD45RBlow, IL-12-responsive and IL-12-unresponsive CD4+ T lymphocytes and lymphoblasts have IBD-inducing potential though of varying potency.

Adoptive Transfer↗
PubMed1999

CD95 ligand (CD95L) in normal human lymphoid tissues: a subset of plasma cells are prominent producers of CD95L.

CD95(Fas/APO-1)-ligand (CD95L) mediates apoptosis by trimerization of the CD95 receptor on the surface of sensitive cells. In vitro studies have shown CD95L expression mainly by activated T cells and suggested a role for CD95L in the regulation of immune responses. Little is known, however, about the cellular distribution of CD95L in situ in the normal human immune system. We investigated CD95L expression in tissue sections of the thymus, lymph node, spleen, tonsil, and gastrointestinal tract using in situ hybridization and two monoclonal antibodies. In all these organs, cells expressing CD95L message and protein were scarce and comprised scattered lymphocytes, rare nonlymphoid cells, and a subset of epithelioid endothelial cells. Surprisingly, a subset of plasma cells turned out to be the most prominent producers of CD95L, matching the reports on CD95L in myeloma cells. CD95L+ plasma cells were most numerous in the mucosa-associated lymphoid tissue. This also applied to acquired mucosa-associated lymphoid tissue in chronic gastritis in which CD95L+ plasma cells were found scattered in the lamina propria. Our data suggest that plasma cells as yet may be neglected modulators of immune responses.

Antibodies, Monoclonal↗
PubMed1999

Mediastinal B-cell lymphoma: a study of its histomorphologic spectrum based on 109 cases.

Mediastinal B-cell lymphoma (MBL) is a distinct variant of aggressive non-Hodgkin's lymphoma with characteristic clinical and biological features but less well-defined histomorphology. We reevaluated 124 biopsy specimens from 109 MBL patients of an Italian/French/German retrospective clinical study. MBL was primarily diagnosed on clinical and histological grounds in conjunction with the detection of CD20 expression by immunohistology. Cytologically, MBL features limited intralesional but considerable interindividual cytological diversity, ranging from medium-sized to very large, atypical cells. Sclerosis and necrosis are restricted to extrathymic and extranodal sites of involvement, predominantly the lung, as is angioinvasion, which predominantly affects larger vessels. The medium-sized and the large cell variants resemble marginal zone lymphoma variants, whereas the very large cell variant of MBL has not so far been found to have any extramediastinal counterpart. We conclude that MBL displays a broad morphological spectrum covering more than is implied by the term "diffuse large cell lymphoma." Because statistical analysis of cytological and histological criteria failed to correlate with prognosis in this comprehensive group of patients, we think it inadvisable further to subclassify MBL.

Humans↗
PubMed1999

Surface-expressed invariant chain (CD74) is required for internalization of human leucocyte antigen-DR molecules to early endosomal compartments.

Transport of major histocompatibility complex (MHC) class II molecules to the endocytic route is directed by the associated invariant chain (Ii). In the endocytic pathway, Ii is proteolytically cleaved and, upon removal of residual Ii fragments, class II alpha beta dimers are charged with antigenic peptide and recognized by CD4+ T cells. Although distinct peptide-loading compartments such as MIIC (MHC class II loading compartment) and CIIV (MHC class II vesicles) have been characterized in different cells, there is growing evidence of a multitude of subcellular compartments in which antigenic peptide loading takes place. We employed a physiological cellular system in which surface Ii (CD74) and surface human leucocyte antigen (HLA)-DR were induced either alone or in combination. This was achieved by transient exposure of HT-29 cells to recombinant interferon-gamma (rIFN-gamma). Using distinct cellular variants, we showed that: (i) the majority of Ii molecules physically associate on the cell membrane with class II dimers to form DR alpha beta:Ii complexes; (ii) the presence of surface Ii is a prerequisite for the rapid uptake of HLA-DR-specific monoclonal antibodies into early endosomes because only the surface DR+/Ii+ phenotype, and not the DR+/Ii- variant, efficiently internalizes; and (iii) the HLA-DR:Ii complexes are targeted to early endosomes, as indicated by co-localization with the GTPase, Rab5, and endocytosed bovine serum albumin. Internalization of HLA-DR:Ii complexes, accommodation of peptides by DR alphabeta heterodimers in early endosomes and recycling to the cell surface may be a mechanism used to increase the peptide repertoire that antigen-presenting cells display to MHC class II-restricted T cells.

Antigens, CD↗
PubMed1999

In vivo selective expansion of a tumour-specific cytotoxic T-cell clone derived from peripheral blood of a melanoma patient after vaccination with gene-modified autologous tumour cells.

Melanoma-specific cytotoxic T lymphocytes (CTL) can be generated from peripheral blood lymphocytes (PBL) by mixed lymphocyte-tumour cell cultures. Analysis of CTL precursor frequencies in peripheral blood of melanoma patients is generally used for immunomonitoring purposes to evaluate vaccination efficacy. At present, it is unclear whether PBL-derived CTL generated in vitro are indicative of an anti-tumour immune response in vivo. Three tumour-specific human leucocyte antigen (HLA)-B/C-restricted CTL clones were derived from peripheral blood of a melanoma patient immunized with interleukin-7 (IL-7) gene-modified tumour cells. CTL clones differing in their T-cell receptor-gamma (TCRgamma) rearrangement produced interferon-gamma, IL-4 and/or IL-10. On the basis of their unique TCRgamma gene rearrangements clone-specific primers were generated for detection of clone-specific DNA by polymerase chain reaction. One CTL clone (E5) of the three was found to be selectively expanded in one of seven metastases obtained at autopsy, as determined by Southern blot hybridization. However, the presence of E5 in only one of seven metastases at death indicates that the in vivo accumulation of the specific CTL clone was not sufficient to contain tumour progression. Nevertheless, our data support the proposition that analysis of anti-tumour activity of PBL-derived CTLs may reflect an anti-tumour immune response in vivo.

Blotting, Southern↗
PubMed1999

Prospective evaluation of brush cytology of biliary strictures during endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: Cytological methods may be used to differentiate benign from malignant biliary strictures. We evaluated the diagnostic accuracy of an endobiliary cytotechnique which can easily be performed during endoscopic retrograde cholangiopancreatography. PATIENTS AND METHODS: Cytological samples were obtained by brushing biliary strictures via a guide wire in 86 patients with strictures of unknown status. Samples were classified by an expert cytologist as normal (including reactive cells), severely dysplastic (atypical cells suspicious of malignancy) and clearly malignant. A final diagnosis was achieved in 78 patients based on intraoperative findings and histological investigation, autopsy or prolonged follow-up. Strictures were malignant in 57 cases (31 pancreatic carcinoma, 20 cholangiocarcinoma, 6 others) and benign in 21 cases (11 chronic pancreatitis, 5 chronic nonspecific inflammation, 5 others). RESULTS: The overall results for brush cytological investigation were sensitivity 56.1%, specificity 90.5%, positive predictive value 94.1%, negative predictive value 43.2 %, and accuracy 65.4 %. Sensitivity was significantly higher (P<0.005) in cholangiocarcinoma (80%) compared with pancreatic carcinoma (35.5%). The overall specificity of less than 100 % resulted from dysplasia in two patients with chronic pancreatitis and inflammatory mass. No procedure-related complications occurred. CONCLUSIONS: Brush cytology is helpful for differentiating between benign and malignant biliary strictures, especially in suspected cholangiocarcinoma. Dysplastic cells may occur in the absence of malignancy and their presence should therefore be interpreted cautiously.

Adult↗
PubMed1999

[Ocular bacteriosis in a patient with aplastic anemia].

BACKGROUND: For more than a century it has been recognized that bacteria may infect the eye by way of the blood stream. Until fifty years ago, eyes so afflicted nearly always were blinded and a majority of the victims died from overwhelming sepsis. Although effective antibiotics are available today the prognosis is still guarded. CASE REPORT: A 39-year-old physician died 6 years after he was diagnosed for idiopathic aplastic anemia. He had developed pseudomonas aeruginosa bacteremia and later a therapy refractive pneumonia caused by aspergillus which had led to respiratory failure. The patient had experienced a marked loss of visual acuity in his left eye ten days before he died. Ophthalmic examination at that point displayed signs of endophthalmitis, hyphaema, and heterochromic irises. The eyes were obtained postmortem and histologic examination of the left eye displayed numerous bacilli forming cuffs around blood vessels and a sheet between the necrotic retinal pigment epithelium and Bruch's membrane. No inflammatory response to the bacilli was present. The bacilli could be demonstrated with a Giemsa stain and could also be identified with electron microscopic examination. DISCUSSION: The histologic results in our patient displayed numerous bacilli without inflammatory reaction which was a result of the aplastic state. Therefore, this disease was classified as "ocular bacteriosis". The blood-ocular barrier undergoes direct assault with intraocular inflammation and the impermeability to blood-borne antibiotics is lost. However, with the lack of an inflammatory reaction the permeability to antibiotics may be too low and the achieved concentration insufficient.

Adult↗
PubMed1999

Gastrostomy by various techniques: evaluation of indications, outcome, and complications.

BACKGROUND: Gastrostomy can be performed with a percutaneous fluoroscopic technique, a percutaneous endoscopic technique, or open surgery. Since all three methods are in use at our hospital, we made this retrospective study to compare indications, complications, and outcomes for the different techniques. METHODS AND RESULTS: During the period January 1990 to December 1994, 147 patients admitted to Lund University Hospital required gastrostomy. The records of these patients were retrospectively studied. Six patient records could not be found, and these patients were therefore excluded. Of the remaining 141 patients, 94 had undergone fluoroscopic percutaneous gastrostomy, 12 percutaneous endoscopic gastrostomy (PEG), and 35 gastrostomy at open surgery. The 30-day overall mortality was 15% in the fluoroscopy group, 17% in the endoscopy group, and 29% in the open surgery group. The 30-day mortality as related to the procedure was 3.2% in the fluoroscopy group, 0% in the PEG group, and 2.9% among the patients with open surgery. The morbidity related to the procedure was 16%, 8%, and 20%, respectively. For the 30-day overall mortality and for the procedure-related mortality there was no statistically significant difference between the groups (P = 0.2019, P = 0.8215). For the percutaneous procedures the indication was nutrition in most patients. For the patients receiving gastrostomy at open surgery drainage was the main indication. Even though the complication rate was higher in this group, most complications were minor, and there was only one procedure-related death. Gastrostomy at open surgery is often performed in severely ill patients. Despite this, it does not seem to cause more complications than the percutaneous techniques in our study. CONCLUSION: The study shows that gastrostomies are safe procedures, with few complications and a low procedure-related mortality independent of the technique being used.

Adult↗
PubMed1999

Chromosomal aberrations in lymphomas of the gastrointestinal tract.

B-cell lymphomas of the gastrointestinal (GI) tract have represented a field of extensive research ever since a close association was shown with chronic inflammatory processes such as Helicobacter pylori infection. Much evidence has accumulated to suggest that the mucosa-associated lymphoid tissue (MALT) induced by inflammation and autoimmune processes is the environment which gives rise to the small cell lymphomas of the GI tract (e.g. extranodal marginal B-cell lymphoma according to REAL). The small B-cell lymphoma may then progress to the large cell variants. Hence, B-cell lymphomas of the GI tract may present a model for lymphomagenesis and progression. In this review, recent cytogenetic data are discussed which yield new insights into the biology of gastrointestinal lymphomas.

Chromosome Aberrations↗
PubMed1999

Analysis of chromosomal imbalances in sporadic and NF1-associated peripheral nerve sheath tumors by comparative genomic hybridization.

Peripheral nerve sheath tumors arise either sporadically or in association with neurofibromatosis type 1 (von Recklinghausen's neurofibromatosis, NF1) or type 2. In this study, comprehensive screening for relative chromosome copy number changes was performed on 10 benign and 19 malignant peripheral nerve sheath tumors (MPNSTs) by applying comparative genomic hybridization (CGH). In benign tumors, no chromosomal imbalances were found by CGH, whereas in MPNSTs chromosomal gains and losses were frequently detected. No differences regarding the frequency and distribution of chromosomal imbalances were observed between the 13 sporadic and 6 NF1-associated MPNSTs analyzed. In both, the number of gains was significantly higher than the number of losses, suggesting a predominant role of proto-oncogene activation during MPNST progression. Candidate regions with potentially relevant proto-oncogenes included chromosomal bands 17q24-q25, 7p11-p13, 5p15, 8q22-q24, and 12q21-q24; those with putative tumor suppressor genes were 9p21-p24, 13q14-q22, and 1p. High-level amplifications were restricted to sporadic tumors and affected eight different chromosomal subregions. In three of these MPNSTs, identical subregions on chromosomal arms 5p and 12q were coamplified. This study revealed a number of new characteristic chromosomal imbalances and provides a basis for molecular identification of oncogenes and tumor suppressor genes of pathogenetic relevance in both sporadic and NF1-associated MPNSTs. Genes Chromosomes Cancer 25:362-369, 1999.

Adolescent↗
PubMed1998

Stable nontumorigenic phenotype of somatic cell hybrids between malignant Burkitt's lymphoma cells and autologous EBV-immortalized B cells despite induction of chromosomal breakage and loss.

Fusion of the highly tumorigenic Burkitt's lymphoma (BL) cell line BL60-P7 with the nontumorigenic autologous EBV-immortalized lymphoblastoid cell line (LCL) IARC 277 results in suppression of the tumorigenic phenotype of the parental cell line BL60-P7 after s.c. inoculation into T cell-deficient nude mice. We analyzed whether, after long-term cultivation of these lymphoma hybrid cells, expression of tumorigenicity could be observed and correlated to the loss of particular chromosomes or chromosomal fragments, akin to numerous nonlymphoid hybrid cell models described previously. Two years after fusion, in vitro proliferation of some BL x LCL hybrid cells accelerated, and they partially lost LCL-typical aggregation. However, no major changes in the expression pattern of B cell-associated surface antigens and the EBV latent membrane protein LMP 1 were observed. Cytogenetic evaluation of these cells revealed spontaneous loss of chromosomes. Karyotyping of long-term cultivated hybrid cells demonstrated the occurrence of disomy for each chromosome in at least one metaphase analyzed. Therefore, if suppression of tumorigenicity in these hybrid cells would have been the result of the presence of a single LCL-derived chromosome, there should have been a high probability of its loss, leading to tumorigenic segregants. Surprisingly, the tumorigenic phenotype remained suppressed in nude mice. To induce chromosomal breakage and maldistribution, in addition to spontaneous chromosomal loss, the hybrid cell lines were irradiated at various doses. Again, none of the hybrid cell clones treated in this manner became tumorigenic in nude mice. Immunohistological analysis of the regressing hybrid cell tumors revealed that the hybrid cells had retained their LCL-like differentiation phenotype in vivo. In addition, infiltration with mononuclear cells of murine origin was observed in these regressing hybrid grafts. We conclude that suppression of the tumorigenic Burkitt's lymphoma phenotype in these hybrid cells cannot be attributed to a function encoded by a distinct chromosome or chromosomal fragment. Rather, the unexpected stable nontumorigenic phenotype reflects a LCL-specific activated B-cell phenotype of these hybrids, most probably induced by the expression of numerous copies of episomal latent EBV proteins.

Animals↗
PubMed1998

T cell-mediated, IFN-gamma-facilitated rejection of murine B16 melanomas.

The murine melanoma cell line B16.F10 (H-2b) was used to study specific T cell responses that reject tumors. Stable B16 transfectants were established that express viral Ags, either the hepatitis B surface Ag (HBsAg) or the large tumor Ag (T-Ag) of SV40. B16 cells and their transfected sublines were CD40+ CD44+ but expressed no (or low levels of the) costimulator molecules CD154 (CD40L), CD48, CD54, CD80, and CD86. Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-gamma. CD95 (Fas) and CD95 ligand (CD95L (FasL)) were "spontaneously" expressed by B16 cells growing in vitro in serum-free medium; these markers were strikingly up-regulated by IFN-gamma. B16 cells coexpressing CD95 and CD95L were irreversibly programmed for apoptosis. In vitro, noninduced B16 transfectants stimulated a specific IFN-gamma release response, but no cytolytic response (in a 4-h assay) in MHC class I-restricted CTL; in contrast, IFN-gamma-induced B16 targets were efficiently and specifically lysed by CTL. In vivo, B16 transfectants were specifically rejected by DNA-vaccinated syngeneic hosts through a T-dependent immune effector mechanism. The tumors showed evidence of massive apoptosis in vivo during the rejection process. The data suggest that CTL-derived IFN-gamma enhances an intrinsic suicide mechanism of these tumor cells in addition to facilitating lytic interactions of effectors with tumor targets.

Animals↗
PubMed1998

Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract.

In contrast to low-grade B-cell lymphomas originating in the gastrointestinal (GI) tract, only few cytogenetic data are available for the large cell, highly malignant variants. We studied 31 large B-cell lymphomas of the GI tract by comparative genomic hybridization (CGH) and fluorescence in situ hybridization using specific DNA probes (FISH). The most frequent aberrations were gains of all or of parts of chromosomes 11 (11 cases), 12 (9 cases), 1q (4 cases), and 3q (4 cases). Losses of parts of chromosome 6q and of parts of the short arm of chromosome 17 (6 cases each) were found most frequently. In four cases a total of seven high-level DNA amplifications was detected. In two of these cases, involvement of specific protooncogenes (REL and MYC) was shown. Some genetic aberrations seemed to be associated with an inferior clinical course: patients with >/=2 aberrations had a significantly shorter median survival. Furthermore, all patients with gains of all or parts of chromosome arm 1q and with high-level DNA amplifications as well as seven of nine patients with gains of all or parts of chromosome 12 died of lymphoma. In conclusion, the pattern of chromosomal gains and losses in large B-cell lymphomas was different from data reported for low-grade (MALT) lymphomas of the stomach and bowel, especially with respect to the high incidence of partial gains of chromosome arm 11q and of all or parts of chromosome 12 and the low frequency of polysomy 3. In addition, our data suggest that chromosomal gains and losses detected by CGH and FISH may predict for the outcome of patients with this tumor entity.

Adult↗
PubMed1998

Colon carcinoma cells use different mechanisms to escape CD95-mediated apoptosis.

CD95(APO-1/Fas) is a cell surface receptor that, when oligomerized by natural ligand, CD95L, or antibody, confers an apoptotic signal to apoptosis-sensitive cells. Whereas CD95 is expressed in every colonocyte of normal colon mucosa, CD95 is down-regulated or lost in the majority of colon carcinomas. To investigate the sensitivity to CD95-mediated apoptosis of normal and neoplastic colonocytes, we applied cross-linking CD95(anti-APO-1) monoclonal antibody to freshly isolated colon crypts and colon carcinoma cell lines and monitored apoptosis by DNA fragmentation and morphology. Normal colonocytes were constitutively sensitive to CD95-mediated apoptosis. All carcinoma lines were constitutively resistant but were sensitized upon pretreatment with IFN-gamma. Transcription blocking, protein synthesis, and export in carcinoma cells indicated that even low surface levels of CD95 were sufficient to efficiently transmit the signal. Despite low CD95 surface levels of non-IFNgamma-treated cells, actinomycin D, cycloheximide, and brefeldin A each sensitized all cell lines, but at different rates and kinetics. In this context, it was observed that a greatly delayed apoptotic response of SW620 cells was associated with the absence of antibody-induced CD95 capping. Phorbol 12-myristate 13-acetate inhibited CD95-mediated apoptosis by counteracting the IFNgamma-, actinomycin D-, and cycloheximide-mediated but not the brefeldin A-mediated sensitization. This phorbol 12-myristate 13-acetate-induced protection against apoptosis was completely abolished by staurosporine and by a selective protein kinase C inhibitor, Goe 6983. We conclude that, during malignant transformation, colonocytes acquire different mechanisms to escape CD95-mediated apoptosis. These include abrogation of CD95, inhibition of CD95 capping, and activation of antiapoptotic programs, both governed by and independent of protein kinase C.

Antigens, Neoplasm↗
PubMed1998

Chromosomal changes during progression of transitional cell carcinoma of the bladder and delineation of the amplified interval on chromosome arm 8q.

The cascade of genetic alterations leading to malignant transformation has been described for adenocarcinoma of the colon but is not established for other common tumor entities. In the present study, different stages of transitional cell carcinoma (TCC) of the bladder are analyzed by comparative genomic hybridization. A dynamic pattern of the chromosomal changes during tumor progression is described. Deletion of chromosome arm 9q is the earliest genetic alteration in pTa tumors. In stage pT1 carcinomas, losses of 9q, 9p, and 11p and gain of 1q and 8q are the most common. In addition to the changes specific for earlier stages, gain of 5p and 20q becomes prominent in carcinomas stage > or =pT2. Association analysis reveals a remarkable cooccurrence of 9p deletion with gain of 5p and 20q in > or =pT2 tumors. In order to determine more precisely the size of the amplified segment and the degree of amplification on chromosome arm 8q in stage pT1 tumors, this region was analyzed by semiquantitative PCR using polymorphic microsatellite markers. These studies revealed an up to 13-fold amplification. The common region of amplification could be narrowed down to 8q22.3 and between GAAT1A4 and D8S1834 (about 7 cM).

Carcinoma, Transitional Cell↗
PubMed1998

Mucosal tenascin C content in inflammatory and neoplastic diseases of the large bowel.

PURPOSE: Tenascin C is a glycoprotein of the extracellular matrix. It is upregulated during embryologic development, wound healing, and under conditions of normal and neoplastic growth. Most available data on tenascin C expression in tissues is based on immunohistologic studies. The present study was designed to quantify tissue concentrations in patients with inflammatory and neoplastic diseases of the large bowel. METHODS: Fifty patients with ulcerative colitis, 19 patients suffering from familiar adenomatous polyposis without malignant transformation, and 69 patients with colorectal carcinoma were investigated. Tenascin C concentrations in tissue extracts were determined by semiquantitative Western blotting. RESULTS: The tenascin C tissue concentration of normal mucosa was 2.6 +/- 3.4 microg/mg (n = 55), 2.9 +/- 2.1 microg/mg in colorectal adenomas (n = 19), 7.5 +/- 4.7 microg/mg in ulcerative colitis (n = 50), and 18 +/- 15 microg/mg in colorectal carcinomas (n = 69; mean +/- standard deviation). In ulcerative colitis, the mucosal tenascin C content correlated with histopathologic disease activity. No differences were found between subgroups of adenomas or carcinomas. CONCLUSIONS: Tenascin C tissue concentrations were not altered in adenomas, slightly elevated in ulcerative colitis, and substantially increased in colorectal carcinomas. Although less useful as a diagnostic parameter, tenascin C tissue levels serve as an instrument for assessing the activity of stromal remodeling in large-bowel diseases generally. Specifically, they may reflect disease activity in ulcerative colitis.

Adenomatous Polyposis Coli↗