Biomedical subjects

J E Paddle-Ledinek

Publications and source records attributed to J E Paddle-Ledinek.

4 recordsLinked to original sources

PubMed1998

Proteinase inhibitor 6 (PI-6) expression in human skin: induction of PI-6 and a PI-6/proteinase complex during keratinocyte differentiation.

Proteinase inhibitor 6 (PI-6) is a 42-kDa intracellular protein present in epithelial cells and endothelial cells. It is capable of inhibiting a number of serine proteinases, including trypsin and chymotrypsin. In this study we examined PI-6 expression in human skin and its primary cell type, the keratinocyte. By immunohistochemical analysis, PI-6 staining is absent from the basal cells, weak in the spinous layer, and strongest in the granulosa layer of human epidermis. Immunoblotting of cultured primary keratinocytes revealed that PI-6 production increases 24-fold on differentiation. Analysis of an immortalized keratinocyte cell line, HaCat, showed a 5-fold increase in PI-6 mRNA and a 7-fold increase in PI-6 protein upon differentiation, and indirect immunofluorescence revealed that this is due to an increase in the number of differentiated cells expressing high levels of PI-6. Of particular interest is the appearance of a preformed complex between PI-6 and an endogenous serine proteinase in differentiating HaCat cells, which was detected by a monoclonal antibody demonstrated to preferentially recognize PI-6 in complex with a proteinase. This identification of a PI-6/proteinase complex is the first example of a serpin bound to a proteinase in keratinocytes. We postulate that a physiological role of PI-6 is to regulate a serine proteinase associated with keratinocyte differentiation.

Animals↗

PubMed1997

Skin replacement by cultured keratinocyte grafts: an Australian experience.

We have prepared and supplied cultured epithelial autografts (CEA) to treat 37 burn patients around Australia. The method is a modification of the original methods of Green et al. The confluent 75 cm2 secondary cultures, obtained after less than 3 weeks, are 8-10 cell layers thick after detachment and have a shrinkage of only 7-14 per cent. The patients had full-thickness skin loss to 55-95 per cent of their total body surface area (TBSA) or deep partial-thickness burns to 3-50 per cent TBSA owing to scald injuries. In the case of full-thickness burns the CEA take in the 17 surviving patients for which data was available averaged 53 per cent (range 10-100 per cent). The take for seven patients with partial-thickness burns averaged 73 per cent (range 25-100 per cent). The variability and early graft failure is attributed largely to the presence of infection. The durability and percentage take of CEA grafts is discussed together with future developments in the replacement of both dermis and epidermis in burns injury.

Adolescent↗

PubMed1996

Modification of growth of desmoid tumours in tissue culture by anti-oestrogenic substances: a preliminary report.

BACKGROUND: Tamoxifen and toremifene have been used in patients with advanced desmoid tumours with response rates of 51%. METHODS: We developed an experimental model of desmoid tumour cells in tissue culture to study their effect. Four cell lines were established in tissue culture. All native and corresponding cultured tumours were oestrogen receptor negative. Tumour 1 was from a 22 year old with familial adenomatous polyposis (FAP) and recurrent abdominal wall desmoid tumours. She remains disease free on tamoxifen 4 years following surgery. Both her mother and sister also have shown regression of their FAP-associated desmoid tumours at the menopause and on tamoxifen, respectively. We assessed the effect of tamoxifen on desmoid tumours in tissue culture at 780 ng/mL. The results were assessed by cell density counting. RESULTS: Tumours 1 and 2 have responded with an approximately. 50% reduction in growth to tamoxifen at 780 ng/mL. CONCLUSIONS: This apparent growth inhibitory effect of tamoxifen on two desmoid tumour cell lines appears to be independent of oestrogen and correlates with the in vivo effect of tamoxifen on three desmoid tumours in an FAP family.

Abdominal Neoplasms↗

PubMed1975

Variations in thyroid function and sleep in healthy young men.

1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men. 2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day. 3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary. 4. The subjects' sleep at night was assessed by electro-encephalogram. In days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain.

Adult↗