ABSTRACT: BACKGROUND: Legionella pneumophila is the causative agent of human Legionnaire's disease. During infection, the bacterium invades macrophages and lung epithelial cells, and replicates intracellularly. However, little is known about its interaction with T cells. We investigated the ability of L. pneumophila to infect and stimulate the production of interleukin-8 (IL-8) in T cells. The objective of this study was to assess whether L. pneumophila interferes with the immune system by interacting and infecting T cells. RESULTS: Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T cells. On the other hand, wild-type L. pneumophila and Dot/Icm-deficient Legionella, but not flagellin-deficient Legionella or heat-killed Legionella induced IL-8 expression. L. pneumophila activated an IL-8 promoter through the NF-kappaB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-kappaB, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and transforming growth factor beta-associated kinase 1 (TAK1). Transfection of dominant negative mutants of IkappaBalpha, IkappaB kinase, NF-kappaB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-kappaB, p38 MAPK, and JNK blocked L. pneumophila-induced IL-8 expression. In addition, c-Jun, JunD, cyclic AMP response element binding protein, and activating transcription factor 1, which are substrates of p38 MAPK and JNK, bound to the AP-1 site of the IL-8 promoter. CONCLUSIONS: Taken together, L. pneumophila induced a flagellin-dependent activation of TAK1, p38 MAPK, and JNK, as well as NF-kappaB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease.

Primary liver cancer with lymph node metastasis was recognized as poor prognosis. We herein report a case of post operative lymph node recurrence treated with UFT. A 74-year-old man with a huge mass lesion in the right liver with para Aortic lymph node metastasis admitted our hospital in April 2007. Extended right lobe hepatectomy and lymph node dissection were performed in May. A histological examination of the resected specimen showed a combined hepatocellular-cholangiocarcinoma with three lymph node metastasis. Computed tomography(CT)revealed intra hepatic metastasis(S3)and right adrenal grand metastasis 5-month after surgery. Transarterial embolization(TAE)and right adrenalectomy were performed for each metastasis. CT revealed a lymph node metastasis at the right side of infra vena cava 1 year after surgery. He was treated by oral administration of UFT(200 mg/day). The AFP and PIVKA-II value gradually decreased after administration of UFT. The size of lymph node metastasis became small confirmed by CT. But the AFP and PIVKA-II value increased 1 year and 7 months after surgery. TAE was performed against lymph node metastasis 1 year and 9 months after surgery. This case suggests UFT is useful for suppressing the growth of the lymph node metastasis.

A new family of cytokines, the interleukin (IL)-17 family, has recently been defined, which reveals unique functions and distinct ligand-receptor signaling systems. This family contains six members, IL-17 (also called IL-17A), IL17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F. The IL-17F gene was discovered in 2001, and is located on chromosome 6p12. Notably, among this family, IL-17F has been well characterized both in vitro and in vivo, and has been shown to have a pro-inflammatory role in asthma. IL-17F is clearly expressed in the airway of asthmatics and its expression level is correlated with disease severity. Moreover, a coding region variant (H161R) of the IL-17F gene is inversely associated with asthma and encodes an antagonist for the wild-type IL-17F. IL-17F is able to induce several cytokines, chemokines and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts and eosinophils. IL-17F utilizes IL-17RA and IL-17RC as its receptors, and activates the MAP kinase related pathway. IL-17F is derived from several cell types such as Th17 cells, mast cells and basophils, and shows a wide tissue expression pattern including lung. Overexpression of IL-17F gene in the airway of mice is associated with airway neutrophilia, the induction of many cytokines, an increase in airway hyperreactivity, and mucus hypersecretion. Hence, IL-17F may have a crucial role in allergic airway inflammation, and have important therapeutic implications in asthma.

Objective Tuberculosis (TB) in patients undergoing hemodialysis (HD) for end-stage renal disease (ESRD) is commonly thought to be associated with a very poor prognosis. Moreover, it is difficult to diagnose. This report was designed to describe this condition and to determine the mortality rate and risk factors associated with mortality. In addition, the study evaluated the usefulness of QuantiFERON TB-2G((R))(QFT-2G). Methods Retrospective study Patients Patients with confirmed TB admitted between January 2001 and May 2009 were retrospectively identified and enrolled. The clinical, radiological, and bacteriological data at the time of admission were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. Results A total 19 TB patients (6 females; median age, 73 years) were included. TB occurred in most cases within 1.3 years from the initiation of dialysis. Most patients presented with fever (84.2%) and extrapulmonary TB (57.9%). The mortality rate within 24 weeks of the initiation of TB treatment was 36.8%. The factors associated with mortality were: a short duration of dialysis (HR 8.86, 95% CI 1.03-75.7, p=0.04), and underweight (HR 10.88, 95% CI 1.28-92.6, p=0.02). The sensitivity of QFT-2G, acid-fast smear, and polymerase chain reaction was 50, 80, and 88.2% respectively. Conclusion These data indicate a high incidence of TB in the early stages of HD and a high mortality rate among these patients. The clinical utility of QFT-2G was found to be limited. Hypoalbuminemia might therefore be related to either indeterminate or negative results of QFT-2G.

A 79-year-old woman with colon cancer and multiple liver metastases was admitted to our hospital for systemic chemotherapy. She underwent first cycle of modified FOLFOX6 chemotherapy. She was confused on treatment day 5. Blood test revealed her serum ammonia level to be 121 mug/dl. We diagnosed 5-fluorouracil (5FU)-induced hyperammonemia. Conservative treatment resulted in improvement of metal status. The reason for hyperammonemia after administration of 5FU was the excess production of ammonium from metabolites of 5FU.

This study aimed to identify the major odor contributing components produced during swine feces composting which have an impact on the olfactory senses. A total of 64 gas samples collected at different stages of composting were analyzed by both a gas chromatograph and human panel test using the triangle odor bag method. Multiple regression analysis of representative odor substances present in the outlet gas was carried out employing the odor index (OI) as the dependent variable and the odor unit as the independent variable. The recorded changes in OI indicated that turning was an important event during odor evolution, and that the odor emission during the thermophilic phase should be the main target for odor abatement. The model incorporating ammonia, methyl mercaptan and dimethyl sulfide as independent variables confirmed the value of the OI (R(2)=0.70). These compounds were identified to be the key odor components significantly determining the OI.

Legionella pneumonia typically presents as lobar pneumonia with multiple-lobe involvement, but Legionella lung abscess is rare. To identify the predisposing factors for Legionella abscess, we analyzed 62 of the 79 case reports on Legionella abscess found in literature; 28 (45.2%) were of hospital-acquired infection and 28 (45.2%), community-acquired infection. Seventeen patients (27.4%) died. L. pneumophila serogroup 1 was the most common, but other serogroups of L. pneumophila, L. micdadei, L. bozemanii, L. dumoffii, and L. maceachernii were also isolated from the abscess. Corticosteroids were administered for underlying diseases to 43 (69.4%) patients. Peripheral neutrophil counts were higher in patients with abscess than in those with only pulmonary infiltration. In certain cases, Legionella abscess developed during neutropenia recovery. However, lymphocyte counts were low in most cases. Clinical factors like corticosteroid treatment, which causes impaired cellular immunity and subsequent neutrophil accumulation in the lesion, might function as predisposing factors for Legionella abscess.

To explore the calcium homoeostasis of red blood cells (RBC) in patients with end-stage renal disease (ESRD), which plays an important role in RBC deformability and survival, we measured free calcium-ion concentration of RBC([Ca2+]i).[Ca2+]i was measured by fluorescent spectrophotometry using fura-2. The subjects constituted 5 groups; normal controls(C group), patients with diabetes mellitus(DM) without renal failure (DM group), ESRD patients with DM (HD-DM group), non-diabetic ESRD patients with lower intact parathyroid hormone (i-PTH)(HD-NDM-A group), and with higher i-PTH(HD-NDM-B group).[Ca2] i was significantly higher in the HD-NDM group than in the C group, in the HD-DM group than in the DM group, in the DM group than in the C group, in the HD-DM group than in the HD-NDM group, and in the HD-NDM-B group than in the HD-NDM-A group. There was a significant positive correlation between i PTH and [Ca2+]i, and between C-PTH and [Ca2+]i. In stepwise multivariate regression analysis, ESRD, DM, and secondary hyperparathyroidism (SHPT) appeared as independent determinants of [Ca2+]i.[Ca2+]i was significantly decreased after a hemodialysis session comparing to that of before the session. These data indicate that [Ca2+] i of RBC is elevated in ESRD probably due to uraemia, DM, and SHPT.