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J Halpin

Publications and source records attributed to J Halpin.

7 recordsLinked to original sources
PubMed1994

Public health medicine training and the NHS changes.

The current round of mergers between Health Authorities and Family Health Service Authorities (FHSAs), when set in the competitive context of markets, has profound implications for training in Public Health Medicine. This paper considers the phases in the management of change and the costs, benefits and principles for trainers, trainees and organisations as mergers take place. Particular emphasis is placed on understanding the motives of and learning from the change that is taking place.

Health Facility Merger↗
PubMed1993

1 alpha,25-dihydroxyvitamin D3 plus gamma-interferon blocks lung tumor production of granulocyte-macrophage colony-stimulating factor and induction of immunosuppressor cells.

Metastatic Lewis lung carcinoma (LLC-LN7) cells have previously been shown to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) which induces the appearance of immunosuppressive granulocytic-macrophage progenitor cells (GM-suppressor cells). The present in vitro studies showed that treatment of LLC-LN7 tumor cells with 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] plus low dose gamma-interferon (IFN-gamma) resulted in a synergistic reduction in tumor GM-CSF secretion and a blockage in the capacity of the tumor cells to induce GM-suppressor cells. The production of GM-CSF by bulk cultures of enzymatically dissociated LLC-LN7 tumors that had been excised as s.c. tumors from mice was also blocked when the dissociated tumor was cultured with 1,25(OH)2D3 plus IFN-gamma. Our previous and present studies showed that GM-suppressor cells persist in bulk cultures of dissociated LLC-LN7 tumors after a 1-week period of culture. Addition of either 1,25(OH)2D3 or IFN-gamma did not diminish the persistence of GM-suppressor cells. However, when tumor production of GM-CSF was inhibited by culture with both 1,25(OH)2D3 and IFN-gamma, the ability of the dissociated tumor culture to sustain the presence of GM-suppressor cells was blocked. This elimination of GM-suppressor cells by treatment of the dissociated tumor with 1,25(OH)2D3 and IFN-gamma coincided with increased expansion of CD8+ tumor-infiltrating leukocytes and increased cytotoxic T-lymphocytes activity of tumor-infiltrating lymphocytes. These results suggest that blocking tumor production of GM-CSF can interrupt the suppressor-inducing cascade of the tumor and enhance expansion and anti-tumor cytolytic reactivity of tumor-infiltrating leukocytes.

Animals↗
PubMed1993

Inhibition of tumor production of granulocyte-macrophage colony-stimulating factor by 1 alpha, 25-dihydroxyvitamin D3 reduces tumor motility and metastasis.

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma tumors (LLC-LN7) has been shown to increase their migration and invasion in vitro, and metastasis in vivo. The present studies showed that treatment of the LLC-LN7 cells by 2 days culture with 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited their production of GM-CSF. The 1,25(OH)2D3-treated cells also became less migratory and invasive. This inhibitory effect on tumor motility could not be readily reversed upon removal of 1,25(OH)2D3. The mechanism by which 1,25(OH)2D3 reduced tumor motility was attributed to the inhibition of tumor GM-CSF production since the capacity to migrate and invade could be restored by supplementing the medium with recombinant GM-CSF. In vivo studies showed that treatment of LLC-LN7-bearing mice with 1,25(OH)2D3 had no effect on growth of s.c. primary tumors, but reduced the formation of tumor metastases. These results show that 1,25(OH)2D3 can interrupt the autocrine motility-stimulation cascade by reducing tumor production of GM-CSF, thus reducing the expression of properties that are characteristic of metastatic tumor cells.

Animals↗