Biomedical subjects

A Emmerson

Publications and source records attributed to A Emmerson.

7 recordsLinked to original sources

PubMed1998

Costello syndrome: two cases with embryonal rhabdomyosarcoma.

Costello syndrome is a well delineated mental retardation syndrome of unknown aetiology in which the occurrence of benign tumours, especially papillomata, is recognised. We report two children in whom the diagnosis of Costello syndrome was made in the first months of life, who both developed a retroperitoneal embryonal rhabdomyosarcoma. Although not previously reported, the occurrence of this relatively uncommon childhood tumour in two girls with Costello syndrome suggests that an increased risk of malignancy may be part of this condition. The genetic basis of this susceptibility requires further clarification.

Child, Preschool↗

PubMed1984

Benzoyl peroxide interferes with metabolic co-operation between cultured human epidermal keratinocytes.

The ability of benzoyl peroxide to inhibit metabolic co-operation in rodent cell cultures may be relevant to its recently reported tumour promoting activity in mouse epidermis. We show here that non-toxic doses of this compound reduce metabolic co-operation between human epidermal keratinocytes to approximately 30% of that found in controls. The doses of benzoyl peroxide used did not affect keratinocyte morphology or their rate of attachment to the culture substratum. These results could be important as benzoyl peroxide is widely used in industry.

Animals↗

PubMed1984

Non-promoting hyperplasiogenic agents do not mimic the effects of phorbol, 12-myristate, 13-acetate on terminal differentiation of normal and transformed human keratinocytes.

We have studied the effects of the potent tumour promoter phorbol, 12-myristate, 13-acetate (PMA) and two non-promoting hyperplasiogenic compounds ethyl phenylpropriolate (EPP) and the divalent cation ionophore A23187 on the terminal differentiation of normal and transformed human keratinocytes using the loss of cloning efficiency and the formation of cornified envelopes as markers of the differentiated state. PMA induced terminal differentiation in a far greater proportion of normal keratinocytes than it did in the squamous cell carcinoma line SCC-27 but EPP and the calcium ionophores A23187 and Br-X537A had no such differential effect, possibly explaining the poor promoting ability of the last three compounds.

Alkynes↗

PubMed1984

Differential effects of complete and second-stage tumour promoters in normal but not transformed human and mouse keratinocytes.

The complete tumour promoter phorbol, 12-myristate, 13-acetate (PMA) induces terminal differentiation in the majority of normal cultured human and mouse keratinocytes but a subpopulation exists which is resistant to this effect (PMAR). We have compared with PMA the effects of mezerein (Mez) and phorbol, 12-retinoate, 13-acetate (PRA) on the ability of normal and transformed human and mouse keratinocytes to terminally differentiate in an attempt to elucidate why the latter two compounds are inefficient complete tumour promoters but are effective as second-stage promoters when given after PMA in the two-stage promotion regimen. Both PMA and Mez increased cornified envelope formation in a similar way in normal and transformed keratinocyte cultures inducing a 20- to 25-fold increase over the solvent controls in normal keratinocytes but only a 2-fold increase in line SCC-27 (a cell line derived from a human squamous cell carcinoma). However, while quantitative dose response studies of the effect of phorbol esters on colony forming ability revealed a proportion of normal human and mouse keratinocytes which were resistant to PMA, no normal keratinocytes were resistant to Mez or PRA. In contrast, cell lines derived from papillomas and squamous cell carcinomas showed a resistant fraction of similar size with all three compounds. Furthermore, when Mez or PRA were mixed with PMA the survival of line SCC-27 was the same as when the cultures were treated with the compounds individually indicating that the keratinocytes which were resistant to PRA or Mez were also the PMAR subpopulation. A non-tumorigenic subclone of line SCC-12 (clone F.2), previously shown to possess all known properties of transformed keratinocytes except defective terminal differentiation in suspension culture responded to PMA and Mez in a similar way to normal keratinocytes, suggesting that resistance of the PMAR subpopulation to second-stage promoters requires the expression of a defect in the keratinocyte terminal differentiation programme.

Carcinogens↗

PubMed1983

A subpopulation of cultured human keratinocytes which is resistant to the induction of terminal differentiation-related changes by phorbol, 12-myristate, 13-acetate: evidence for an increase in the resistant population following transformation.

We have studied the action of phorbol, 12-myristate, 13-acetate (PMA) on human keratinocytes grown with lethally-irradiated 3T3 cells using medium supplemented with hydrocortisone, cholera toxin and epidermal growth factor. Normal keratinocyte cultures show a heterogeneous response to PMA; 90-93% of the colony-forming cells lose their colony-forming ability and form cornified envelopes when treated for 24 h with doses of 100 nM or less, but the remainder are resistant to doses of 1000 nM. The resistant cells are the precursors of the sensitive ones and heterogeneity is restored to those cells and their progeny after 8 days culture in the absence of PMA. Cultures of 3 squamous cell carcinoma lines, a SV40-transformed human keratinocyte line, and three clones of these lines were found to contain 3-17 times more PMA-resistant keratinocytes than the normal strains, and the size of the PMA-resistant fraction in each line was inversely related to the competence of that line to lose colony-forming efficiency when placed in suspension culture (which is the first detectable change in an ordered programme of events resembling terminal differentiation of the keratinocyte). The number of cells with cornified envelopes in surface cultures of normal human keratinocytes increased from approximately 3% in control cultures to approximately 70% in those treated for 6 days with 100 nM PMA. The transformed human keratinocyte cultures showed a 3-25-fold smaller increase in cornified envelope formation when treated with 100 nM PMA, and the increase in envelope formation by each line when exposed to this dose of PMA was related to the competence of that line to lose cloning efficiency in suspension culture. No relationship was found between the ability of any human keratinocyte strain or line we studied to metabolically inactivate PMA and their resulting response to the compound. The results are discussed in relation to the mechanism of action of PMA as a promoter of epidermal carcinogenesis.

Animals↗

PubMed1982

The effects of tumour promoters on the multiplication and morphology of cultured human epidermal keratinocytes.

The tumour promoter phorbol, 12-myristate, 13-acetate (PMA) was shown to inhibit the multiplication of five strains if human epidermal keratinocytes, co-cultivated with 3T3 feeders in the presence of hydrocortisone, cholera toxin and epidermal growth factor. The effect was dose dependent between 10(-9) M and 10(-8) M and this dose response was not affected by omission of any of the tissue culture additives. Experiments performed in 3T3-conditioned medium demonstrated that PMA acted directly on the keratinocytes. Exposure to 10(-8) M PMA for greater than 12 h resulted in a loss of keratinocyte colony-forming efficiency, followed 24-48 h later by altered cell morphology, loss of cell to cell and cell to substratum adhesion and accelerated cytoplasmic and nuclear destruction. PMA-treated keratinocytes also became permeable to Trypan Blue, and many eventually formed cornified envelopes. Other phorbol esters tested produced similar effects to PMA in accordance with their reported tumour promoting activity, although mezerein (a weak tumour promoter) was more potent than PMA. The non-diterpene tumour promoters anthralin and phenobarbital did not have the same effects as PMA. The morphological effects were not produced in other cell types tested consistent with the specific low dose effects of PMA.

Animals↗

PubMed1977

The preformed socket and modular assembly for primary amputees.

A method is described by which an artificial limb can be fitted as soon as an above-knee or below-knee amputation wound is healed, by using preformed sockets which enable the prosthetist to fit the limb within the hour. The method has been found safe, and better than other methods previously described to facilitate the early mobilisation and rehabilitation of the amputee.

Amputation, Surgical↗