The academic nursing practice dean: an emerging role

This article describes the contributions of academic nursing practice to nursing education; delineates the role characteristics and competencies needed by academic practice deans; and provides examples of the challenges and issues academic practice deans face related to nursing education, research, and practice. While schools' missions vary from a strong focus on education to multiple emphases on education, research, and practice, academic nursing practice has the potential to facilitate achievement in each of these areas. Academic nursing practice deans play important roles in advancing the missions of their schools through the clinical practice activities within the schools. Strong academic nursing practice programs can serve as catalysts for the development and refinement of new models of care delivery and for the development of future nursing leaders who are comfortable with innovation.     

Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients

Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in innate IFNγ and IL-17 responses to <Emphasis Type="Italic">Bordetella pertussis</Emphasis> between BALB/c and C57BL/6 mice: role of γδT cells,NK cells,and dendritic cells

Cell-mediated immune responses characterized by the secretion of IFNγ and IL-17 play an important role in the immune response to Bordetella pertussis (B. pertussis). We investigated innate sources of IFNγ and IL-17 upon stimulation of spleen cells from BALB/c (B/c) and C57BL/6 (B6) mice with heat-killed B. pertussis (hkBp). Spleen cells from B/c mice secreted less IFNγ and more IL-17 than those from B6 mice. Innate IFNγ was produced predominantly by NK cells in B/c mice and by CD8 T cells and NK cells in B6 mice. Innate IL-17 was produced primarily by γδT cells in both mouse strains. The secretion of IFNγ was abrogated by anti-IL-12, and the production of IL-17 was abolished by anti-IL-1β- and anti-IL23-neutralizing antibodies. B/c dendritic cells (DCs) stimulated with hkBp secreted significantly more IL-1β and less IL-12 than B6 DCs. Differences in JNK phosphorylation in DCs suggest that this pathway plays a role in the differences between B/c and B6 strains. Mixed cultures of DCs and γδT cells from B/c and B6 showed that cytokines from DCs as well as γδT cell-intrinsic factors contributed to the robust innate IL-17 response in B/c strain. Stimulation of γδT cells with IL-1β and IL-23 was sufficient for IL-17 secretion whereas IL-12 inhibited the secretion of IL-17. A larger fraction of γδT cells were γδT-17 cells in B/c mice than B6 mice. Our data indicate important roles for genetically determined factors in the innate IFNγ and IL-17 responses to B. pertussis.     

Paracrine regulation of vascular endothelial growth factor--a expression during macrophage-melanoma cell interaction: role of monocyte chemotactic protein-1 and macrophage colony-stimulating factor.

Tumor-associated macrophages are major infiltrates of human solid malignancies and play an important role in tumor angiogenesis by production of angiogenic factors. In the present study, we examined whether macrophage- melanoma cell interaction regulates vascular endothelial cell growth factor-A (VEGF-A) expression in macrophages. We analyzed the expression of mediators of monocyte recruitment and differentiation, such as monocyte chemotactic protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) in malignant melanoma specimens and tumor cells with different metastatic potential. Our data demonstrate that MCP-1 and M-CSF are differentially expressed in human malignant melanomas from different thickness and depth of invasion and cell lines. Next, we examined the effect of MCP-1 and M-CSF on modulation of VEGFA expression in monocytes/macrophages. Treatment of human monocytes with M-CSF and MCP-1 enhanced VEGF-A expression by increased hypoxia-inducible factor-1alpha (HIF-1alpha) expression and enhanced activation of the hypoxia response element (HRE). Further activation of monocytes and monocyte-derived macrophages (MDM) by lipopolysaccharide (LPS) caused an increase in VEGF-A expression. We demonstrate that coculture of melanoma cells with monocytes enhanced VEGF-A secretion, and conditioned medium from MDMs enhanced melanoma cell expression of VEGF-A. Furthermore, conditioned medium from melanoma cells enhanced VEGF-A expression in human monocytes, which was abrogated by anti-M-CSF neutralizing antibody. In summary, we demonstrate that MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage- mediated tumor angiogenesis.     

Immune responses to Aspergillus antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent,selective, melanocortin subtype-4 receptor agonist

Synthetic and natural peptides that act as nonselective melanocortin receptor agonists have been found to be anorexigenic and to stimulate erectile activity. We report the design and development of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the MC4 receptor. Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity.