Incidence, causes and outcomes of lameness cases in a working military horse population: a field study.

REASONS FOR PERFORMING STUDY: Lameness is a common problem in the horse. Despite this, information on the incidence of lameness in horses in the UK is restricted to studies of lameness in performance horses, racehorses or referral hospital populations. OBJECTIVES: To determine the overall incidence and common causes of lameness in a working horse population and incidence, duration and outcome of conditions observed. STUDY DESIGN: Prospective questionnaire study. METHODS: Questionnaires were used to record lameness episodes in 294 horses in an equine military establishment. Information recorded included age, years of service, type of work, causal lesion, time taken to return to work and outcome. Lameness problems could be reported by any staff involved in the horses' care and were diagnosed by a veterinary surgeon or qualified farrier. Trends between lame and nonlame populations were compared using Chi-square analysis. Lameness diagnoses were grouped and analysed by disease category. RESULTS: Completed questionnaires for 273 horses were analysed. The mean monthly incidence of lameness was 2.1%, equivalent to an annual rate of 25.4 cases per 100 horses per annum, with a mean of 1.2 lameness episodes per horse in the lame population. Horse age and duration of service were not significantly different between lame and nonlame populations. The most common diagnoses were cellulitis (18.6%), skin wounds (16.3%) and foot/shoeing problems (11.6%) and 88% of cases had returned to previous levels of work by the conclusion of the study. CONCLUSIONS: This initial field study showed that lameness is a common occurrence in this working military horse population and the majority of cases make a full return to work. The most common causes of lameness identified in this study and outcomes of these conditions differ from existing literature. POTENTIAL RELEVANCE: This study highlights the need for further studies of lameness in the wider horse population.

A rapid, novel strategy to induce tumor cell-specific cytotoxic T lymphocyte responses using instant dentritomas.

The generation of fused cells between dendritic cells (DC) and tumor cells is a very effective approach for tumor antigen presentation in cancer immunotherapy. However, the application of this approach in clinical studies is limited by the need for established tumor cell lines and the time-consuming procedures for selecting and expanding the fused cells. In the current study, the authors report a rapid, novel approach to produce fused cells between DCs and primary tumor cells from patients with malignant melanoma. Peripheral blood DCs and a primary tumor cell culture were generated from the same patients, labeled with fluorescent green and red dyes, respectively, and fused. The fused cells were isolated by fluorescence-activated cell sorting. Because the fused cells do not need to be expanded, these cell hybrids have been named instant dendritomas. Fluorescence-activated cell sorting analysis showed that instant dendritomas express the key molecules for antigen presentation (HLA-A, B, C; HLA-DR; CD80; and CD86). In vitro studies have shown that instant dendritomas effectively activated autologous CD8+ T lymphocytes to proliferate and secret interferon-gamma. More importantly, the activated CD8+ T lymphocytes effectively lysed the patients' primary tumor cells. This approach represents a practical clinical strategy for cancer immunotherapy.

Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity.

The use of fusions between dendritic cells (DCs) and tumor cells as vaccines has been proved very effective in stimulating antitumor immune responses, both in animal studies and in early human clinical trials. Because of the difficulty of purifying the hybrid cells from the fusion, fusion mixtures were used in these studies. Recently, we developed a technique using fluorescent-dye staining and fluorescence-activated cell sorting that enabled the hybrid cells to be instantly purified from the fusion mixture. In the present study, the hybrid cells were purified from a fusion between mouse DCs and B16F0 melanoma tumor cells using the new technique. The purified cells, named instant dendritomas (IDs) were then compared with fusion mixtures in stimulating antitumor immune responses. The results from cytotoxicity assays, interferon-gamma production and in vivo lung tumor metastasis demonstrated that IDs are more effective than fusion mixture in stimulating antitumor immunity. Meanwhile, there was no significant difference in the antitumor immunities activated by IDs from allogenic fusion or IDs from syngenic fusion.

Murine tyrosinase expressed by a T7 vector in bone marrow-derived dendritic progenitors effectively prevents and eradicates melanoma tumors in mice.

Dendritic cell (DC)-mediated cancer immunotherapy is a very promising alternative approach to cancer treatment. In a previous study, we successfully transfected bone marrow-derived dendritic progenitors (BMDDPs) with a T7 vector--a nonviral, cytoplasmic-based autogene expression system--encoding a model tumor antigen, firefly luciferase, and subsequently stimulated the transfected cells to differentiate into DCs. When injected into experimental mice, those DCs generated a strong immune response against tumor cells bearing luciferase, which not only prevented occurrence of metastasis but also eradicated existing tumors. In the present study, we constructed a T7 vector encoding mouse tyrosinase, a well--known melanoma associated tumor antigen, and used it to transfect BMDDPs. Reverse transcriptase polymerase chain reaction and Western analysis confirmed the expression of tyrosinase by DCs differentiated from transfected BMDDPs. Two immunizations of these DCs at a dose of 2 x 10(6) of each successfully prevented tumor growth. More importantly, one injection of 2 x 10(6) of these DCs into mice followed by five doses of recombinant human interleukin-2 administration effectively eradicated existing tumors as indicated by pulmonary metastasis assay.