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Historically, the Association has had as one of its key objectives, the fostering and promotion of strong links with clinicians within developing countries. Each year the association provides awards for educational and research projects globally. More recent funding has been awarded for: (a) an education outreach programme in rural Ethiopia; (b) ophthalmology clinical training in rural Africa; (c) clinical trial educational opportunities in Vietnam; and (d) medical student education in Bangladesh. In the current issue of the Journal, Dr. Howell and colleagues at Imperial College London, describe their substantial clinical and …

Tumor cells maintain an especially high glycolytic rate to supply the anabolic precursors essential for de novo nucleotide synthesis. We recently cloned an inducible isozyme of 6-phosphofructo-2 kinase (iPFK-2) that bears an oncogene-like regulatory element in its mRNA and functions to produce fructose-2,6-bisphosphate, which is a powerful allosteric activator of glycolysis. Rapidly proliferating cancer cells constitutively express iPFK-2 in vitro, and inhibition of iPFK-2 expression decreases tumor growth in experimental animal models. We report herein that the expression of iPFK-2 mRNA and protein, as assessed by in situ hybridization and immunohistochemistry, is increased in many human cancers when compared with corresponding normal tissues. In particular, iPFK-2 expression was found to be markedly elevated in multiple aggressive primary neoplasms, including colon, breast, ovarian, and thyroid carcinomas. iPFK-2 mRNA and protein expression were induced by hypoxia in cultured human colon adenocarcinoma cells, and an examination of normal lung fibroblasts showed that iPFK-2 and fructose-2,6-bisphosphate levels increased specifically during the S phase of the cell cycle. These data indicate that iPFK-2 is abundantly expressed in human tumors in situ and may serve as an essential regulator of glycolysis during cell cycle progression and growth in an hypoxic microenvironment.

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Currently there are limited effective therapeutics for pulmonary fibrosis due to an inadequate understanding of the pathogenic process and underlying mechanisms. We now show that in human idiopathic pulmonary fibrosis (IPF) the cytokine interleukin (IL)-25 positively correlates with periostin a marker human pulmonary fibrosis, and the presence of IL-13-producing type 2 innate lymphoid cells (ILC2) in the lung. Using murine models of pulmonary fibrosis we demonstrate an essential role for IL-25-elicited ILC2 in the generation of pulmonary collagen deposition, independent of an adaptive T cell response. Furthermore, we define a mechanism whereby IL-25 evokes ILC2 to induce pulmonary fibrosis via the alternative activation of macrophages in the lung. Collectively, we present a new innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2 that occurs independently of T cell-mediated antigen-specific immune responses. These results indicate that IL-25 and ILC2 are potential therapeutic targets for the treatment of human fibrotic diseases where antigen-independent damage responses may magnify the disease.

An analysis was made of an outpatient population attending a specialized sarcoidosis clinic in order to identify and quantify the number of patients who had become lost to follow up. In addition we wished to elucidate the reasons why they had not returned and to determine the consequences, if any, of not having continuing medical surveillance. Ninety-four patients were identified as being lost to follow up from our specialized sarcoidosis clinic and were invited to return for review. Forty-six patients (49%) responded and were evaluated. The main reason for clinic non-attendance given by 91% (42/46) of the clinic reattenders was that they were asymptomatic. Comparing this group with a cohort of 50 patients who are regular clinic attenders, we found that the lost to follow up patients had a strikingly more benign disease profile. In spite of this, analysis of this respondent group revealed some evidence of continuing disease activity or progression, with 37% (17/46) of the group fulfilling at least one of our defined criteria for disease progression. While none of these patients warranted the immediate addition of corticosteroid medication at their first recall visit, their continuing disease activity warrants close supervision at a specialized sarcoidosis clinic. We conclude that educational strategies require to be developed in order to minimize clinic non-attendance by patients with sarcoid. Furthermore more positive action needs to be taken by clinicians in attracting those patients, who become lost to follow up, to return for clinic review.