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Biomedical subjects

F A Offner

Publications and source records attributed to F A Offner.

At least 19 recordsLinked to original sources
PubMed2004

[Pathology of small intestine transplantation].

Small bowel transplantation is being increasingly performed to treat patients with irreversible intestinal failure or short bowel syndrome. Worldwide approximately 100 transplantations are currently performed per year. Technical advances and new immunosuppressive strategies adopted during the last 10 years have significantly improved the quality of live and survival rate of the patients. The 5-year survival rate is currently around 60%. However, the procedure still bears significant live threatening risks. Mayor problems include surgical complications like anastomotic leakage or peritonitis, acute allograft rejection, systemic infection and in later stages loss of graft function due to chronic rejection. Acute rejection is common after intestinal transplantation. It may occur any time after transplantation and is seen in 50%-80% of the patients. The characteristic changes are enterocyte apoptosis in the crypts, cryptitis and mononuclear cell infiltration with activated lymphocytes. Severe cases may reveal ulcerations or even sloughing and widespread exfoliation of the epithelium and are almost invariably associated with graft loss. The histopathological abnormalities may be patchy and occur in grossly normal mucosa. Therefore, multiple biopsies should be generally sampled for histology. Acute rejection must be distinguished from infections in particular opportunistic viral infections caused by Cytomegalovirus (CMV) or Adenovirus as well as from Epstein-Barr virus-related B-lymphocyte proliferations. Differential diagnosis also includes preservation injury and ischemia resulting in damage of the mucosal surface epithelium. Long-term graft function and survival are now increasingly determined by chronic rejection. The hallmarks of chronic rejection are obliterative arteriopathy of mesenterial vessels and progressive fibrosis of the transplant including its mesentery.

Graft Rejection↗
PubMed2003

Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.

Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.

Adult↗
PubMed2001

Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis.

Baseline platelet production is dependent on thrombopoietin (TPO). TPO is constitutively produced and primarily regulated by receptor-mediated uptake by platelets. Inflammatory thrombocytosis is thought to be related to increased interleukin-6 (IL-6) levels. To address whether IL-6 might act through TPO to increase platelet counts, TPO was neutralized in vivo in C57BL/10 mice treated with IL-6, and hepatic TPO mRNA expression and TPO plasma levels were studied. Transcriptional regulation of TPO mRNA was studied in the hepatoblastoma cell line HepG2. Furthermore, TPO plasma levels were determined in IL-6-treated cancer patients. It is shown that IL-6-induced thrombocytosis in C57BL/10 mice is accompanied by enhanced hepatic TPO mRNA expression and elevated TPO plasma levels. Administration of IL-6 to cancer patients results in a corresponding increase in TPO plasma levels. IL-6 enhances TPO mRNA transcription in HepG2 cells. IL-6-induced thrombocytosis can be abrogated by neutralization of TPO, suggesting that IL-6 induces thrombocytosis through TPO. A novel pathway of TPO regulation by the inflammatory mediator IL-6 is proposed, indicating that the number of platelets by themselves might not be the sole determinant of circulating TPO levels and thus of thrombopoiesis. This regulatory pathway might be of relevance for the understanding of reactive thrombocytosis.

Animals↗
PubMed2000

B lymphocyte-derived IL-16 attracts dendritic cells and Th cells.

Interaction of B lymphocytes with Th cells is a fundamental step in the establishment of humoral immunity, and recent evidence suggests that direct interaction between B lymphocytes and dendritic cells (DCs) is also an important prerequisite. Factors involved in the selective recruitment of Th cells and DCs by B lymphocytes are insufficiently defined. We set out to delineate the role of IL-16, the soluble ligand of CD4, which is expressed on Th cells and DCs. B lymphocytes express IL-16 mRNA and synthesize bioactive IL-16 protein, and IL-16 is expressed in lymph node follicles in situ. B lymphocyte supernatant efficiently induces migration of CD4+ Th cells, monocyte-derived DCs, and circulating blood DCs in nitrocellulose filter-based assays. Neutralization of IL-16 bioactivity strongly inhibits this migratory response, suggesting that IL-16 might be a major chemotactic factor derived from B cells. The present data further support the idea that IL-16 might have a role in the initiation of cellular as well as humoral immunity by mediating the cellular cross-talk among T lymphocytes, B cells, and DCs, leading to recruitment of these cell types at common anatomical sites.

B-Lymphocytes↗
PubMed2000

Regulation of transforming growth factor-beta secretion by human peritoneal mesothelial and ovarian carcinoma cells.

This study was conducted to compare the secretion of TGF-beta isoforms by human ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells (HPMC;n=6) and to examine the regulation of their production by inflammatory cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42 pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8 pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta1 (median 187 pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells; range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and 11/12 of the cell lines, respectively. The levels detected varied widely for TGF-beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14 pg/10(5)cells; range 0-419) and there was no correlation between the two isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model for the analysis of the molecular mechanisms of aberrant TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta.

Ascites↗
PubMed2000

Epstein-Barr virus-associated Hodgkin's lymphoma and legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A.

We describe the case of a 53-month-old girl with juvenile rheumatoid arthritis (JRA), complicated by the occurrence of Hodgkin's lymphoma and Legionella pneumophila infection during immunosuppressive treatment with methotrexate (MTX) and cyclosporine A (CSA). The girl had received variable anti-inflammatory combination therapy, including MTX for 28 months and CSA for 3 months. Thirty-six months after the onset of arthritis, the girl presented with an enlargement of the lymph nodes of the mediastinum, the hilum of the lungs, and the abdomen. Concomitantly, a diagnosis of Legionella pneumonia was rendered. Autopsy showed Epstein-Barr virus (EBV)-associated nodular sclerosing Hodgkin's lymphoma. The neoplastic cells were positive for CD15, CD 30, and latent membrane protein 1 (LMP 1). The present case is the second reported to occur in a child, and it lends support to the hypothesis that immunosuppressive treatment may contribute to an increased risk of the development of EBV-associated lymphoproliferative disorders (LPD) in pediatric patients suffering from JRA.

Arthritis, Rheumatoid↗
PubMed1999

A role for IL-16 in the cross-talk between dendritic cells and T cells.

Dendritic cells (DCs) in the periphery capture and process Ags, migrate to lymphoid organs, and initiate immune responses in T cells. IL-16, the soluble ligand for CD4, is a potent chemoattractant for CD4+ T cells, eosinophils, and monocytes and is mainly derived from activated T cells. Because migration is a fundamental property of DCs, we asked whether IL-16 induces chemotaxis in DCs and whether DCs are a source of IL-16. DCs were generated by culture of monocytes in IL-4 and GM-CSF for 6 days and subsequently highly purified employing magnetic beads. Migration was assayed by nitrocellulose and polycarbonate filter-based assays, and distinction of chemotaxis and chemokinesis was performed by a checkerboard analysis. Messenger RNA and protein data revealed constitutive expression and release of IL-16 by day-6 DCs. Gradients of rIL-16 induced a chemotactic response of DCs. Furthermore, the chemotactic activity of DC supernatant toward DCs themselves and T cells was mainly due to IL-16, because the addition of neutralizing Abs completely abrogated the migratory response. However, after induction of maturation by the addition of TNF-alpha and PGE2 DCs, neither expressed IL-16 mRNA nor produced IL-16 protein. We conclude that IL-16 may play a role in the trafficking of DCs and may be a major chemotactic signal from DCs toward themselves and toward T cells.

Cell Communication↗
PubMed1999

Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells: induction by interleukin-1.

Peritoneal mesothelial cells are uniquely located to regulate cellular events in the peritoneal cavity and are an important source for various cytokines and growth factors. This study was conducted to analyze the capacity of human peritoneal mesothelial cells (HPMCs) to synthesize and release basic fibroblast growth factor (bFGF) and to characterize its regulation by inflammatory cytokines. HPMCs constitutively synthesized and released considerable amounts of bFGF as detected by a specific immunoassay. Almost 80% of bFGF (1547 +/- 173 pg/10(5) cells) was localized intracellularly. Approximately 20% of the bFGF (357 +/- 27 pg/10(5) cells) was associated with extracellular matrix components on the HPMC surface. Small amounts of bFGF (<1%) were detectable in tissue culture supernatants (8.4 +/- 1.4 pg/10(5) cells). Treatment of HPMCs with interleukin-1beta (IL-1beta; 1 ng/ml) resulted in a significant increase in bFGF production. The intracellular bFGF content showed a rapid but only transient increase, which was significant above background levels after 24 hours (41% increase; P < 0.05). This increase in intracellular bFGF concentration was associated with an induction of the release of bFGF. Within 96 hours, the release of bFGF to the cell surface and into the supernatant increased by 58% (564 +/- 52.4 pg/10(5) cells; P < 0.01) and by 214% (26.4 +/- 3.2 pg/10(5) cells; P < 0.001), respectively. Neither tumor necrosis factor-alpha nor interferon-gamma affected bFGF synthesis by HPMCs. Stimulation of HPMCs with IL-1beta increased steady-state levels of bFGF-specific mRNA. Immunohistochemical analyses of peritoneal tissue revealed constitutive expression of bFGF by HPMCs. This in situ expression proved to be most pronounced in areas of serosal inflammation in activated HPMCs. Our study demonstrates that HPMCs synthesize and release significant amounts of bFGF and that the expression of this growth factor is significantly up-regulated by the proinflammatory cytokine IL-1beta. The data support the view that HPMCs are key regulators of abdominal disease processes such as peritonitis, peritoneal fibrosis, or peritoneal tumor metastasis.

Cells, Cultured↗
PubMed1999

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis. We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium. The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm. Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis.

Adult↗
PubMed1998

Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium.

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.

Apoptosis↗
PubMed1998

Peritoneum and tissues of the female reproductive tract as physiological sources of CA-125.

The origin of physiological CA-125 serum levels, which in normally menstruating women were shown to depend on their actual menstrual cycle phase, has not yet been completely elucidated. It is furthermore conceivable that physiological CA-125 sources may contribute to serum elevations in the various pathologies associated with increased circulating CA-125. The present review deals with menstrual cycle-dependent expression of CA-125 in normal tissues of the female reproductive tract in relation to the actual circulating CA-125 levels together with in vivo data concerning the inductive effect of medroxyprogesterone acetate on circulating CA-125 studied in 24 postmenopausal women. Furthermore, in vitro results on constitutive, steroid hormone- and cytokine-modulated CA-125 shedding from human peritoneal mesothelial and ovarian surface epithelial cells are summarized.

Adult↗
PubMed1998

Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.

PURPOSE: The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity. PATIENTS AND METHODS: Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors. RESULTS: Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P < .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P < .005) and overall (P < .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P < .03 for disease-free and P < .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age. CONCLUSION: In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression.

Adult↗
PubMed1997

Induction of heat shock protein 70 by zinc-bis-(DL-hydrogenaspartate) reduces cytokine liberation, apoptosis, and mortality rate in a rat model of LD100 endotoxemia.

A prospective, randomized model of LD100/24 h endotoxemia was performed in male Wistar rats (n = 26; 250-300 g). The animals were divided into four groups: Group I (n = 5; saline treatment only), Group II (n = 5; Zn2+ treatment only), Group III (n = 8; saline pretreatment, lipopolysaccharide (LPS) treatment), and Group IV (n = 8; Zn2+ pretreatment, LPS treatment). Zn2+ pretreatment was carried out by intraperitoneal injection of 50 mg/kg zinc-bis-(DL-hydrogenaspartate) (10 mg/kg Zn2+). LD100/24 h endotoxemia was induced by intraperitoneal administration of 20 mg/kg LPS of the Escherichia coli strain WO111:B4. Tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were detected by enzyme-linked immunosorbent assay (ELISA). HSP70 expression in the lungs, the liver, and the kidneys was determined by immunohistochemistry, Western blotting, and an HSP70 ELISA. Apoptosis was also detected by an in situ apoptosis detection kit (TUNEL) and a cell death detection ELISA, respectively. This rat model of endotoxemia proves the close relationship between HSP70 expression, cytokine liberation, and development of apoptosis. The data demonstrate that: 1) Zn2+ is a potent inducer of HSP70 expression; 2) the application of Zn2+ leads to slightly increased cytokine plasma levels; and 3) the manipulation of the heat shock response by Zn2+ significantly increases the survival rate after LD100 endotoxemia. Enhanced survival rate in animals pretreated with Zn2+ may be explained by increased tissue levels of HSP70, a subsequent significantly decreased liberation of the proinflammatory cytokines after LPS challenge, and a significantly decreased rate of apoptosis.

Animals↗
PubMed1996

Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia.

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Human peritoneal mesothelial cells are more potent than ovarian cancer cells in producing tumor marker CA-125.

The aim of the present study was to investigate the extent to which human peritoneal mesothelial cells (HPMCs) are able to participate in the release of tumor marker CA-125 in ovarian cancer and other conditions associated with an involvement of the peritoneum. For this purpose CA-125 shedding was measured in the supernatant culture medium of HPMCs obtained from various donors and seven well-established ovarian cancer cell lines (OVCAR-3, 2780, 2774, SKOV-6, SKOV-8, HOC-7, HTB-77). Furthermore, the influence of inflammatory cytokines [interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma)] on CA-125 release in normal and malignant cells was also studied. Constitutive CA-125 shedding was found to be about five times higher in HPMCs as compared with the investigated ovarian cancer cell lines. IL-1 beta and TNF-alpha treatment of HPMCs resulted in a significant reduction in CA-125 release; however, no consistent pattern in CA-125 secretion was found during incubation with either IL-1 beta or TNF-alpha in the various malignant cell lines. IFN-gamma, on the other hand, induced a highly significant increase in CA-125 secretion in ovarian cancer cells, but did not influence the shedding of CA-125 in HPMCs.

CA-125 Antigen↗
PubMed1996

Tumour-cell-endothelial interactions: free radicals are mediators of melanoma-induced endothelial cell damage.

Damage to vascular endothelium may play an important role during metastasis. We used a three-dimensional model of tumour cell extravasation to test the hypothesis that certain types of tumour cells are able to induce vascular endothelial cell injury. Multicellular tumour spheroids (MCTS) of 14 human cancer cell lines and spheroids from two benign cell lines were transferred onto confluent monolayers of human endothelial cells (EC). MCTS from 4 of 7 melanoma cell lines induced damage of the endothelium which was closely associated with tumour cell attachment. Endothelial cell injury became evident morphologically by loss of cell membrane integrity and sensitivity to shear stress. Similar results were obtained with EC derived from human umbilical veins, umbilical arteries and saphenous veins. Addition of the oxygen radical scavenger catalase showed a dose- and time-dependent inhibition (up to 48 h) of EC damage in the case of the melanoma cell lines ST-ML-11, ST-ML-14 and SK-MEL-28. The scavenging enzyme superoxide dismutase proved to be protective (up to 12 h) in ST-ML-12 MCTS. In contrast, allopurinol, deferoxamine mesylate, ibuprofen, nor-dihydroguaretic acid, soybean trypsin inhibitor or aprotinin had no protective effect. None of the non-melanoma cancer cell lines or benign cells induced endothelial cell damage. Endothelial injury has been shown to enhance the process of metastasis. Our results suggest that free-radical-mediated endothelial cell damage may be one of the mechanisms contributing to the devastating metastatic potential of melanoma.

Catalase↗
PubMed1996

Metaplastic columnar cells in Barrett's esophagus: a common and neglected cell type.

Goblet cells are considered by most to be a prerequisite for the diagnosis of Barrett's esophagus. Columnar cells that are alcian blue (AB) positive (as are goblet cells) are commonly observed in the surface epithelium of Barrett's esophagus, but their distribution in relation to goblet cells has not previously been defined. The authors analyzed the prevalence and distribution of these cell types in the surface but not pit epithelium (where they may sometimes be present in normal gastric mucosa). The distribution of the AB-positive columnar cells was mapped out in the entire mucosa of nine esophagectomy specimens, resected for Barrett's-associated high-grade dysplasia or carcinoma, and compared with other cell types, especially goblet cells. AB-positive goblet and columnar cells were present in 87.1% +/- 5.6% and 85.7% +/- 5.9%, respectively, of the evaluated sections of Barrett's mucosa, whereas gastric-type, AB-negative cells were observed in 46.3% +/- 8.7% of the sections. In 53% of the sections, the surface epithelium contained more than 25% AB-positive cells, and in more than three quarters of these sections, AB-positive columnar cells were the dominant AB-positive cell type. No difference in the distribution of the AB-positive epithelial cells was noticed between the proximal and distal halves of the Barrett's mucosae. In the cardia region, seven of nine cases showed a few scattered AB-positive columnar cells, and five of nine cases showed a few scattered goblet cells. No AB-positive cells were found in fundic gland mucosa. These findings indicate that the metaplastic AB-positive columnar cells are more prevalent than goblet cells. They may be analogous to incomplete metaplastic cells of the stomach, and, therefore, their role in the development of neoplasia needs further study.

Aged↗