Aberrant S100 expression in cutaneous malignant fibrous histiocytoma: a potential pitfall in diagnosis.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
D Cottell
Publications and source records attributed to D Cottell.
Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo.
Lipoxins (LXs) are lipoxygenase-derived eicosanoids and putative endogenous braking signals for inflammation in the gastrointestinal tract and other organs. Aspirin triggers the production of 15-epimers during cell-cell interaction in a cytokine-primed milieu, and aspirin-triggered 15-epi-5(S),6(R),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi-LXA(4)) may contribute to the bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in vivo. We determined the effect of LXA(4), 15-(R/S)-methyl-11,12-dehydro-LXA(4) methyl ester (15-(R/S)-methyl-LXA(4)), and stable analogs of LXA(4) on TNF-alpha-stimulated neutrophil-enterocyte interaction in vitro and TNF-alpha-stimulated chemokine release, changes in mucosal architecture, and enterocyte apoptosis in cytokine-activated intact human colonic mucosa ex vivo. LXA(4), 15-(R/S)-epi-LXA(4), and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA(4) methyl ester (16-phenoxy-LXA(4)) inhibited TNF-alpha-stimulated neutrophil adherence to epithelial monolayers at nanomolar concentrations. In parallel experiments involving human colonic mucosa ex vivo, LXA(4)potently attenuated TNF-alpha-stimulated release of the C-X-C chemokine IL-8, and the C-C chemokines monocyte-chemoattractant protein-1 (MCP-1) and RANTES. Exposure of strips of normal human colonic mucosa to TNF-alpha induced disruption of mucosa architecture and enhanced colonocyte apoptosis via a caspase-3-independent mechanism. Prior exposure of the mucosa strips to 15-(R/S)-methyl-LXA(4) attenuated TNF-alpha-stimulated colonocyte apoptosis and protected the mucosa against TNF-alpha-induced mucosal damage. In aggregate, our data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA(4) are potent antagonists of TNF-alpha-mediated neutrophil-enterocyte interactions in vitro, attenuate TNF-alpha-triggered chemokine release and colonocyte apoptosis, and are protective against TNF-alpha-induced morphological disruption in human colonic strips ex vivo. Our observations further expand the anti-inflammatory profile of these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for the treatment of inflammatory bowel disease.
Anti-Inflammatory Agents, Non-Steroidal↗
Effect of low doses of ionizing radiation on cells cultured from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus.
Explant cultures from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus, were exposed to low doses of (60)Co gamma radiation. Cells growing from the explants were examined 7 days after irradiation using light and transmission electron microscopy and were also tested for their ability to produce signals indicative of a bystander effect. The exposed cultures displayed pronounced damage and were orders of magnitude more sensitive than the data in the literature would suggest for arthropod cells. The cultures were also more sensitive than mammalian cells that were exposed to similar doses. Cellular abnormalities included damage to cytoplasmic organelles, particularly the cytoskeleton. Abnormal mitochondria were also prominent. At low doses (0.5 Gy), nuclear damage was not apparent in the cultures, but there was evidence of a dose-dependent increase in apoptosis. The irradiated cultures released a factor into the medium that was capable of inducing apoptosis and cell death in unirradiated fish and human cells. This bystander effect was of a similar magnitude to that reported for mammalian cell systems. It is suggested that these crustaceans may be highly sensitive to radiation, unlike terrestrial arthropods and certain other invertebrates, which are generally considered to be radioresistant.
Animals↗
The effects of cadmium exposure on the cytology and function of primary cultures from rainbow trout.
Cultured epidermal cells from explants of skin of rainbow trout were used to study the cytological and functional changes following sublethal exposure to cadmium stress. The aim was to develop diagnostic markers for ecotoxicology. Cultures were exposed to the pollutant for 48 h. Cell structural and cytological changes were established by light and electron microscopy. Metabolic alterations were detected by immunohistochemistry. The relation between the initiation of cellular alterations and cadmium concentrations was compared in cultures exposed in commercially-available serum-free and serum-containing medium. The expression of stress proteins (metallothionein and heat shock protein) was also studied. Rainbow trout epithelial cells exposed to cadmium showed typical morphological changes indicative of cell death by apoptosis. Sublethal exposure also resulted in cellular metabolic disturbances with increased deposits of glycogen. Increased melanization was also observed. These changes appeared at lower concentrations of cadmium when cells were exposed in serum-free media than in serum-containing media. Cadmium induced the expression of heat shock proteins but not of metallothioneins. The results broadly confirm in vivo findings for cadmium toxicity and suggest that this in vitro technique may have applications in aquatic toxicology.
Animals↗
Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays.
Recent results using very low doses of radiation have suggested that there is a hypersensitive region where cultures show an enhanced level of cell killing leading to a non-monotonic survival curve. This effect has been observed at doses below 2 Gy in mammalian systems and at much higher doses in insect cells. In this paper we report observation of the effect in primary human uroepithelial cell cultures. The effect was measured using a postirradiation proliferation assay where irradiated explants of standard size were allowed to proliferate for 14 days after exposure to 60Co gamma irradiation. By 14 days the majority of cultures derived from explants irradiated with 2-5 Gy showed little evidence of growth inhibition and cell numbers approached or even exceeded those obtained in the controls. There was, however, a significant reduction in cell number and growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c-myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and were significantly increased. Morphological evidence of apoptosis was present in all irradiated cultures at 4 h after exposure, but this persisted for longer periods in cultures exposed to low doses.
Cell Survival↗
The effect of caerulein induced pancreatitis on the hepatic microvasculature.
A three-dimensional morphological study of the hepatic microvasculature in caerulein induced oedematous pancreatitis was performed using scanning electron microscopy (SEM) vascular casts and transmission electron microscopy (TEM) of hepatocytes and hepatic sinusoids. TEM studies provided ultrastructural evidence of hepatocellular damage while SEM views demonstrated gross irregularity of the sinusoidal outline with abruptly terminating sinusoidal buds and extravasation of cast material, findings which were similar to those previously reported in the pancreas itself using the same model and which were supported by TEM cross-sectional views of the hepatic sinusoids. The results suggest that caerulein induced pancreatitis is associated with extrapancreatic microvascular damage which may be an important factor in the pathogenesis of extrapancreatic organ impairment associated with acute pancreatitis.
Amylases↗
Three-dimensional morphological study of the pancreatic microvasculature in caerulein-induced experimental pancreatitis.
A morphological study of the pancreatic microvasculature in experimental pancreatitis was performed in dogs, using three-dimensional scanning electron microscopy vascular casting and transmission electron microscopy. Animals with pancreatitis were characterized by a marked reduction in the number of capillaries outlined by the cast and by distortion of those that were outlined, with irregularity of the capillary lumen, abruptly terminating capillary buds and leakage of the cast material through the capillary membrane. The study provides convincing morphological evidence that one of the earliest changes in acute pancreatitis is distortion of the capillary circulation.
Acute Disease↗
Ethanol teratogenicity in mice: an electron microscopic study.
In this study, the neuroepithelium (NE) cells of the mouse embryo were examined with the electron microscope at various intervals after maternal injection of 0.03 ml/g body weight 25% (v/v) ethanol on day 9 of gestation (plug day = day 1), by the intraperitoneal route. Within 1 hour of treatment, the mitochondria of the NE cells became greatly swollen but could recover. Recovery occurred in two phases: a rapid one during the second hour after treatment, followed by a more gradual one that lasted until 12 hours after treatment. About 5 hours after treatment, dying and fragmenting cells were seen in the NE of all embryos examined. The debris from this necrosis was phagocytosed by neighbouring healthy cells. Also at 5 hours after treatment there was an apparent expansion of the intercellular space of the NE and an enlargement of the apical pseudopodial processes of the NE cells. The latter two changes may have been the result of failure of energy-dependent cell fluid homeostasis consequent to mitochondrial dysfunction. All of these changes were reversed by 15 hours after treatment. Although all embryos examined had abnormalities of the NE, including cell necrosis, at 24 hours after treatment only 28% had failed to complete neural tube formation. Hence, either the degree of ethanol-induced damage varies between embryos in the same litter, or the sensitive period is so restricted that variations in stage of development within a litter can account for the lack of concordance between the presence of cellular damage and the subsequent occurrence of a neural tube defect.
Abnormalities, Drug-Induced↗