BACKGROUND: Acinetobacter bacteremia is an emerging nosocomial infection. We tried to find significant risk factors associated with the prognosis of patients with Acinetobacter bacteremia. METHODS: Retrospective case-control study was designed. The odds ratio estimation and multiple logistic regression for the categorical variables and Mann-Whitney test for the continuous variables were done. RESULTS: From September 1, 1999 to December 31, 2000 there were 25 adult patients with Acinetobacter bacteremia in Ajou University Hospital and 24 patients were confirmed as hospital acquired. The median age and hospital length of stay before bacteremia was 52 years old and 9.5 days respectively. There were 16 male patients. The overall mortality was 45.8 % (11 of 24). Thus there were 11 cases (death) and 13 controls (survival) of mortality. Statistical analysis revealed statistically significant differences between cases and controls in the terms of types of wards, central venous catheter, mechanical ventilation, total parenteral nutrition, and multi-resistant organisms. The multiple logistic regression analysis revealed that the more significant independent factors associated with mortality were mechanical ventilation and multi-resistant organisms. CONCLUSION: Acinetobacter bacteremia is a significant nosocomial infection. Especially mechanical ventilation and multi-resistant organisms were independent risk factors associated with high mortality with Acinetobacter bacteremia.
Acinetobacter* ; Adult ; Bacteremia* ; Case-Control Studies ; Central Venous Catheters ; Cross Infection ; Humans ; Length of Stay ; Logistic Models ; Male ; Middle Aged ; Mortality ; Odds Ratio ; Parenteral Nutrition, Total ; Prognosis* ; Respiration, Artificial ; Retrospective Studies ; Risk Factors*

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.
Adenoviridae ; Antigen Presentation/genetics ; Antigens, Neoplasm/immunology ; Carcinoma/*therapy ; Cell Line, Tumor ; Colorectal Neoplasms/*therapy ; Cytotoxicity, Immunologic/genetics ; Dendritic Cells/immunology ; Humans ; *Immunotherapy, Adoptive ; Interferon-gamma/secretion ; Lymphocyte Activation/genetics ; Proteins/genetics/*metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transduction, Genetic ; Transgenes/genetics ; Tumor Markers, Biological/immunology

The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins. In addition, CCL21 did not affect the mRNA levels of SERCA2 or its interacting protein Hax-1. Interestingly, SERCA2 expression was inversely related to DC migration in response to chemokine stimulation. The migratory capacity of CCL21-treated mDCs was decreased by the phospholipase C inhibitor U73122 and by the protein kinase C inhibitor BAPTA-AM. The migratory capacities of mDCs were increased in response to SERCA2 siRNA expression but were decreased by SERCA2 overexpression. In addition, DCs treated with a SERCA2-specific inhibitor (cyclopiazonic acid) had significantly increased migratory capacities as mDCs regardless of SERCA2 expression. Moreover, SERCA2 expression was dependent on DC maturation induced by cytokines or Toll-like receptor agonists. Therefore, the migratory capacities differed in differentially matured DCs. Taken together, these results suggest that SERCA2 contributes to the migration of CCL21-activated DCs as an important feature of the adaptive immune response and provide novel insights regarding the role of SERCA2 in DC functions.
Adaptive Immunity ; Adenosine Triphosphatases* ; Chemokine CCL21 ; Chemokines ; Cytokines ; Dendritic Cells* ; Mitogen-Activated Protein Kinases ; Protein Kinase C ; Receptors, Chemokine ; RNA, Messenger ; RNA, Small Interfering ; Sarcoplasmic Reticulum* ; Toll-Like Receptors ; Type C Phospholipases

Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK cells are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs and NK cells induce the maturation and activation of these cells when engaged with their cognate ligand. We investigated to generate potent DCs by maturation with NK cells in the presence of TLR agonist in vitro and tested the efficacy of these DC vaccinations in mouse colon cancer model. The optimal ratios of DCs versus NK cells were 1:1 to 1:2. Immature DCs were mature with NK cells in the presence of lipopolysaccharide, which is TLR4 agonist, and further addition of IL-2 induced phenotypically and functionally mature bone marrow-derived DCs. These potent DCs exhibited not only high expression of several costimulatory molecules and high production of IL-12p40 and IL-12p70, but also high allogeneic T cells stimulatory capacity, and the induction of the high activities to generate tumor-specific CTLs. Consistently, vaccination with these DCs efficiently inhibited CT-26 tumor growth in mouse colon cancer model when compared to other vaccination strategies. Interestingly, combination therapy of these DC-based vaccines and with low-dose cyclophosphamide showed dramatic inhibition effects of tumor growth. These results suggest that the DCs maturated with NK cells in the presence of TLR agonist are potent inducer of antitumor immune responses in mouse model and may provide a new source of DC-based vaccines for the development of immunotherapy against colon cancer.
Animals ; Cancer Vaccines/immunology/metabolism ; Carcinoma/immunology/pathology/*therapy ; Cell Line, Tumor ; Cells, Cultured ; Colonic Neoplasms/immunology/pathology/*therapy ; Dendritic Cells/*drug effects/*immunology/transplantation ; Female ; Immunotherapy, Adoptive/*methods ; Killer Cells, Natural/*immunology/physiology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Toll-Like Receptor 4/agonists ; Toll-Like Receptors/*agonists

This study examined the prevalence of oral microbes in the saliva of oncological patients and healthy subjects. PCR was used to assess the frequency of oral microbes including 3 cariogenic bacteria, 5 periodontopathic bacteria and 4 Candida species in the saliva of 104 oncological patients and 52 healthy subjects. Among these microorganims, Streptococcus mutans, Fusobacterium nucleatum and Candida albicans were most frequently detected in both groups. There were no significant differences in the prevalence of cariogenic bacteria between the patient and healthy groups, whereas significant differences in the frequency of Porphyromonas gingivalis and Tannerella forsythia were observed between the two groups (p < 0.05). The prevalence of all five periodontopathogens was higher in the healthy group than in the patient group. The prevalence of C. albicans in patients was significantly higher than that of healthy group (p < 0.05). In conclusion, there were significant differences in the prevalence of P. gingivalis, T. forsythia and C. albicans between the oncological patient group and healthy group.
Bacteria ; Candida ; Candida albicans ; Forsythia ; Fusobacterium nucleatum ; Humans ; Polymerase Chain Reaction ; Porphyromonas gingivalis ; Prevalence ; Saliva ; Streptococcus mutans