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I Farmer

Publications and source records attributed to I Farmer.

8 recordsLinked to original sources

Diversity of gammadelta T cells in patients with Behcet's disease is indicative of polyclonal activation.

OBJECTIVE: Behcet's disease (BD) is a multisystemic disease, with vasculitic lesions in the oral and genital mucosa, eyes, joints, skin and brain. We have previously found that gammadelta T cells are increased in peripheral blood of BD patients. The aim of this study was to investigate the extent of gammadelta T cells in oral biopsies from BD patients with special emphasis on the restriction of Vgamma and Vdelta usage. PATIENTS AND METHODS: Expression of Vgamma and Vdelta chains on peripheral blood gammadelta T cells from 31 BD patients and 19 healthy controls was analysed by flow cytometry and the expression of Vgamma and Vdelta chains in nine ulcerated and eight non-ulcerated oral mucosa from BD patients and non-ulcerated oral mucosa from three healthy controls was analysed by immunohistochemistry. RESULTS: Vgamma9 and Vdelta2 were the predominant chains expressed in peripheral blood of BD patients, although other Vgamma and Vdelta chains were also expressed. The presence of gammadelta T cells was only observed in the ulcerated oral mucosa but not in the non-ulcerated mucosa from the BD patients, and not in the non-ulcerated mucosa from the healthy controls. These gammadelta T cells showed no preferential expression of any of the Vgamma or Vdelta chains. CONCLUSION: These data suggest a polyclonal rather than oligoclonal activation of the gammadelta T cells. This may indicate that during repeated inflammation of the oral mucosa, the gammadelta T cells are responding to a wide variety of antigenic stimuli with consequent expansion of gammadelta T cells expressing various Vgamma and Vdelta chains and that different antigenic stimuli or responses may be responsible for the clinical heterogeneity of the disease.

Antigenic Variation↗

The anti-oestrogen ICI 182,780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling.

Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERalpha and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competitive anti-oestrogen tamoxifen (TAM) on oestrogen and IGF signalling in these cells. Wt MCF-7 and LTED cells were treated with a log 7 concentration range of E2, TAM or ICI. Effects on cell growth, ERalpha transactivation, expression of ERalpha, ERbeta and components of the IGF pathway were measured with and without insulin. In the presence of insulin, growth of LTED cells was refractory to TAM but inhibited by ICI and E2. In the absence of insulin, LTED cells showed persistent hypersensitivity to E2, and remained inhibited by ICI but were largely unaffected by TAM. ICI but not TAM inhibited ER-mediated gene transcription and treatment with ICI resulted in a dose-dependent reduction in ERalpha levels whilst having no effect on ERbeta expression. IGF-I receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF-7 cells, and ICI but not TAM reduced their expression in a dose-dependent fashion. Thus IGF signalling as well as ERalpha expression and function are enhanced during LTED. While the resultant cells are resistant to TAM, ICI down-regulates ERalpha, reducing IGF signalling and cell growth. These results support the use of ICI in women with ER-positive breast cancer who have relapsed on an aromatase inhibitor.

Antineoplastic Agents, Hormonal↗

Expression of adhesion and activation molecules in human buccal epithelial cell lines and normal human buccal epithelium in situ.

An in vitro culture system may be used to analyse interactions between T cells and epithelium. We have analysed two human buccal squamous epithelial cell lines: SqCC/Y1, derived from a buccal carcinoma, and SVpgC2a, an SV-transformed healthy buccal squamous epithelium. Under serum-free culture conditions, the cell lines resemble normal buccal squamous epithelium in situ in their expression of MHC class I, CD29 (beta1 integrin), CD40, CD44, CD54 (ICAM-1), CD58 (LFA-3), CD95 (Fas), and E-cadherin. Furthermore, when the SVpgC2a cell line was treated with T-cell derived cytokines, upregulation of CD40 expression was observed when the cells were treated with IL-4, whereas IFN-gamma caused upregulation in expression of CD40, CD54 and MHC class II. These buccal squamous epithelial cell lines, therefore, provide a good tool for analysing interactions between epithelium and T cells in vitro.

CD40 Antigens↗

Experiences in a war zone.

War surgery presents a different set of problems to those encountered in the conventional surgery. I was fortunate enough to travel to Afghanistan, under the auspices of the International Committee of the Red Cross, and participate in such surgery. This article describes my experiences in this ancient land.

Afghanistan↗

Postoperative wound infections: a study of bacteriology and pathogenesis.

Of 200 patients, 6.5% were skin carriers of Staphylococcus aureus and 3.5% became skin carriers after admission. Development of skin carrier state was associated with a long preoperative hospital stay. A second study of 275 cases showed that skin carriers of S. aureus had a significantly higher subsequent staph wound infection rate than non-carriers, but nose and/or throat carriers of S. aureus did not. Peroperative wound contamination was a significant factor in the subsequent development of wound infection. In clean surgery the infection rate was 5.9%. Both wound contamination and infection was due to gram positive organisms, usually S. aureus. When the gastrointestinal or biliary tract had been opened, the infection rate was 28%, the usual contaminating and infecting organisms were enteric and only occasionally S. aureus. There is a need for improved methods of minimizing peroperative wound contamination.

Bacteriological Techniques↗