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Biomedical subjects

L J Nicholson

Publications and source records attributed to L J Nicholson.

7 recordsLinked to original sources

Expression of E-cadherin, P-cadherin and involucrin by normal and neoplastic keratinocytes in culture.

We have compared expression of involucrin, E-cadherin and P-cadherin in cultures of normal keratinocytes and in five different lines derived from squamous cell carcinomas (SCCs), using Northern analysis and immunofluorescence. In normal keratinocytes there was an inverse correlation between P-cadherin and involucrin expression, whereas E-cadherin was expressed by both basal and terminally differentiating cells. In SCC lines involucrin expression was lower than in normal keratinocytes, and there was variable expression of P- and E-cadherin: E-cadherin mRNA levels tended to be lower in SCC lines than in normal keratinocytes, whereas P-cadherin levels were similar. Our results are consistent with observations of cadherin expression in vivo and suggest that the cultures provide a useful experimental model for investigating the role of cadherins in determining the spatial organization of normal and neoplastic keratinocytes.

Cadherins

Decreased expression of fibronectin and the alpha 5 beta 1 integrin during terminal differentiation of human keratinocytes.

We have examined the expression of fibronectin and the alpha 5 beta 1 fibronectin receptor during terminal differentiation of human epidermal keratinocytes, using involucrin as a terminal differentiation marker. The levels of mRNAs encoding fibronectin and the alpha 5 and beta 1 integrin subunits were measured in keratinocyte populations that had been enriched for involucrin-negative or -positive cells by unit gravity sedimentation or suspension-induced terminal differentiation. All three mRNAs decreased in abundance during terminal differentiation, and the corresponding proteins were localised by immunofluorescence to the basal layer in stratified colonies. We also examined expression in ndk, a strain of epidermal cells with a complete block in terminal differentiation, which, as a result, do not express involucrin. Messenger RNA levels for fibronectin and the alpha 5 and beta 1 subunits were higher in ndk, than in unfractionated keratinocytes and the corresponding proteins were expressed by all ndk, consistent with a basal keratinocyte phenotype. We conclude that expression of fibronectin and the alpha 5 beta 1 fibronectin receptor decreases during terminal differentiation and that such changes are likely to play a role in the selective migration of terminally differentiating cells from the basal epidermal layer.

Antibodies, Monoclonal

Effects of sodium cyclamate and sodium saccharin on focus induction in explant cultures of rat bladder.

The tumour-promoting activities of sodium cyclamate and sodium saccharin were investigated in an assay based on the induction of epithelial foci exhibiting enhanced growth potential in a rat bladder explant culture system. An initiating, non-focus-inducing dose was defined for the carcinogen N-methyl-N-nitrosourea (MNU) to make promotion studies possible. Saccharin induced epithelial foci when added to cultures pretreated with an initiating dose of MNU, and also increased the incidence of foci in cultures treated with transforming doses of MNU. Cyclamate was found to induce a high incidence of foci when added to cultures by itself. When MNU and cyclamate treatments were combined, an additive effect could be detected. These results indicate that both cyclamate and saccharin can contribute to epithelial transformation in this system.

Animals

Cigarette smoke-induced injury of peritoneal mesothelial cells.

Cultured rat peritoneal mesothelial cells have been exposed to plasma obtained from healthy adult male volunteers before and after the smoking of two medium-tar cigarettes. The pre-smoking plasma had little effect on the mesothelial cells as observed by scanning electron microscopy. Post-smoking plasma produced extensive cellular damage evidenced by the production of blebs and microvillus-like structures on the cell surface. Some cells were also found to have a perforated luminal membrane. These results suggest that factors cytotoxic for these cells are present in plasma following exposure of humans to cigarette smoke.

Adult

The mesothelial cell as a non-thrombogenic surface.

A technique for harvesting mesothelial cells is described. This entails collagenase digestion of omentum after which the cells can be cultured. The technique has been developed using the rat, but has also been successfully applied to human tissue. Cultured rat mesothelial cells obtained in this way have been examined by scanning electron microscopy. Rat mesothelial cells grown on plastic film have been exposed to blood in an in vitro system using a Baumgartner chamber and have been demonstrated to support blood flow. No adhering platelets were observed on the mesothelial cell surface. Fibroblasts similarly exposed to blood as a control were washed off the plastic.

Animals

Seeding Dacron arterial prostheses with peritoneal mesothelial cells: a preliminary morphological study.

A preliminary laboratory study has been undertaken using dogs, in which porous Dacron arterial prostheses have been seeded with autologous peritoneal mesothelial cells before implantation into the arterial system. These cells were harvested from omentum by collagenase digestion and were introduced into the graft at the time of preclotting. Examination of the grafts by scanning and transmission electron microscopy one month after insertion showed no organized cellular lining in the control graft. In three seeded grafts there was a lining of mesothelial cells which extended over the whole surface of the grafts up to 1 cm from the suture lines. Selected areas of the grafts have been analysed morphometrically. In the seeded grafts there is a cellular layer which on average covers 94 per cent of the luminal surface. These results suggest that mesothelial cells, which both secrete prostacyclin and possess fibrinolytic activity, present a possible alternative to endothelium as a cellular lining for prosthetic grafts.

Animals

Declogging small-bore feeding tubes.

Nine substances (Pancrease, Viokase, pork pancreatin, bromelain, papain, cranberry juice, Coca-Cola, chymotrypsin, and distilled water) were tested every half-hour for 4 hr using 900 mm of water pressure to determine their effectiveness in declogging small-bore feeding tubes. At the end of 4 hr the tubes were irrigated with air using a 50-cc syringe. None of the substances tested were effective within 4 hr. Three substances allowed for successful syringe irrigation at the end of 4 hr. They were: chymotrypsin, papain, and distilled water.

Enteral Nutrition