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Tumor cell settling and early invasion of the peritoneum.

A Sewall Wright strain-2 guinea pig model producing malignant ascites after injection of a diethylnitrosamine-induced hepatocellular carcinoma cell suspension (Line-10) was used to demonstrate the multilayered settling of tumor cells on the peritoneal surface, frequently followed by the formation of papillary projections and the early invasion in a proliferating submesothelial tissue. At the border of tumor cells and the desmoplastic tissue the malignant cells changed their shape and generally two categories were recognized. Often multilayering, atypical flat cells covered the stromal tissue, while mostly rounded ones invaded using their branched penetration processes, being devoid of cationized ferritin, which was only present on the luminal sides of all cellular elements. Flattened malignant cells, penetrating processes and invading cells lost their microvillous surface pattern. The infiltrating cells were often only detectable with the monoclonal antibody 10 TL 40 and the anti-cytokeratin OV TL 12-5, demonstrating the need for immunohistochemistry in diagnosing solitary invading malignant cells in light microscopy. It appeared that still numerous mesothelial cells were found scattered deeply within the desmoplastic tissue. These former lining cells were identified by their junctions and the presence of remnants of basal lamina as well as by their microvillous 5'-nucleotidase activity.

5'-Nucleotidase↗

Studies of iodixanol in the rabbit lung and peritoneum.

OBJECTIVE: To evaluate a new water-soluble contrast agent, iodixanol. The study evaluates absorption from the peritoneal cavity and toxicity in the lung. MATERIALS AND METHODS: Thirty New Zealand white rabbits were given the study agent and comparative agents into an endotracheal tube. Serial chest radiographs were evaluated for development of pulmonary edema. All lungs were evaluated histopathologically for toxic inflammatory response. Fifteen different rabbits were given intraperitoneal injection of the study and comparative contrast agents. Serial abdomen radiographs, taken up to 24 h after injection, were evaluated for contrast absorption from the peritoneal cavity. RESULTS: Evaluation of indicators of pulmonary edema demonstrated that iodixanol caused the same or less pulmonary edema than comparative agents. Histopathologic analysis showed that iodixanol caused less macrophage response than saline (P = 0.010), the same lymphocyte infiltration as saline (P = 0.472), the same neutrophil response as saline (P = 0.297), and the same vasculitic reaction as saline (P = 0.128). Compared to iohexol 270, iodixanol caused the same macrophage infiltrate (P = 0.924), the same lymphocyte infiltration (P = 0.523), more neutrophil reaction (P = 0.007), and less vasculitic reaction (P = 0.042). Iodixanol was rapidly absorbed from the peritoneal cavity. CONCLUSION: Iodixanol is a new contrast agent that is isotonic at all clinically useful iodine concentrations. It appears safe in the lung and is absorbed from the peritoneal cavity.

Animals↗

Antigen-presenting function of human peritoneum mesothelial cells isolated from a pancreatic carcinoma patient after mutant Ras peptide vaccination.

Mesothelial cells obtained from ascites fluid of a Ras-peptide vaccinated pancreatic adenocarcinoma patient were cultured in vitro. Fresh isolated cells expressed HLA class II molecules, which were lost upon culture, but could be up-regulated after coculture with human recombinant interferon-gamma. The antigen-presenting capacity of these mesothelial cells was tested with allogeneic peripheral blood mononuclear cells (PBMC) in a mixed lymphocyte mesothelial cell culture and by stimulating autologous PBMC with purified protein derivative of Mycobacterium tuberculosis. Cloned T cells from the same patient allowed us to test the ability of mesothelial cells to present a mutant Ras-derived peptide to specific T cells in a DLA-DR-restricted manner. Mesothelial cells effectively stimulated allogeneic resting T lymphocytes to proliferate and presented soluble protein antigen or a mutant Ras-derived peptide to specific T cells, indicating that they display processing and presenting capabilities. Since mesothelial cells are in close anatomical relationship with intraabdominal malignancies, they may contribute to stimulation of specific T cells by endocytosing tumour-specific antigens and presenting them to T lymphocytes. This could be a possible mechanism in which mesothelial cells participate in maintaining local specific immunity in patients already primed.

Adenocarcinoma↗

Mesothelial lamellar bodies in norm and experimental conditions. Transmission and scanning electron microscopic observations on the peritoneum, pleura and pericardium.

The ultrastructural characteristics of the mesothelial intracellular and extracellular lamellar bodies (LB) in norm, and especially in pathological conditions are still unknown. After routine fixation procedure, material from organs in the three serous cavities of Wistar rats, as control group were compared with animals following experimental hemothorax (EH) and experimental peritonitis (EP), using transmission and scanning electron microscopy (TEM, SEM). Different membrane-bound profiles, short strip-like structures and single LB characterize the control group. Five days after EH small groups of LB were observed. Single balloon-like profiles, numerous particles and larger groups of LB with wide varieties in size, form and membrane structure characterize the 8th day after EH. Thin and concentric membranes build single LB the 5th day of EP. Eight days after the same treatment, groups of LB, complex structures with several multilamellar centers, strip-like structures with rough granulo-filamentous material and uninterrupted covering over wide areas were observed. We conclude that constant components in the untreated rats are different membrane profiles, as initial lamellar formations and single typical LB with predominant intracellular position. The preferable sites for exocytosis of LB are the intercellular spaces. The present data demonstrate simultaneous findings of the two main groups of formations by using routine fixation in the control group and in the treated animals. The first represent LB as well as other round profiles, observed by TEM and particles, observed by SEM, which are widespread and probably have a basic role. The second ones are strip-like structures and its SEM-equivalents, i.e. uninterrupted covering. TEM-profiles and their SEM-images show significant organ differences and in some cases lack of correspondence between both electron microscopic techniques in the same treatment. Significant enlargement of the number of LB and the length of the strip-like structures characterize the mesothelium after pathologic conditions. LB with considerable differences in the structure and larger particles over the microvillous border predominate after EH. Strip-like profiles, continuous covering and smaller groups of LB with similar morphology and preferable submesothelial position characterize the mesothelium after EP.

Animals↗

Influence of endotoxin on arachidonate metabolism in isolated rabbit peritoneum.

The serous membranes of the rabbit peritoneal cavity are tissues in which cyclo-oxygenase and lipoxygenase pathways of arachidonate metabolism can be studied simultaneously. After elaboration of the optimum conditions, the metabolism of two concentrations of arachidonic acid (AA) was studied in the presence and absence of endotoxin lipopolysaccharide (LPS) from E. coli O127:B8 (0.1 and 1.0 mg/ml). LPS suppressed the formation of radiolabelled cyclo-oxygenase products (predominantly prostacyclin) at the lower concentration of exogenous AA (0.8 microM), but not at the higher substrate concentration (34.5 microM). The biosynthesis of lipoxygenase metabolites, i.e. monohydroxyeicosatetra-enoic acids (HETEs), was not influenced by LPS. These findings can be explained by an enhanced release of endogenous AA in the prostacyclin forming mesothelial cells in the presence of LPS. Measurements of the endogenous biosynthesis of prostacyclin supported this assumption.

Animals↗