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Background: Strongyloidiasis is a chronic parasitic infection caused by Strongyloides stercoralis. Severe cases such as, hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), can involve pulmonary manifestations. These manifestations frequently aid the diagnosis of strongyloidiasis. Here, we present the pulmonary manifestations and radiological findings of severe strongyloidiasis.Methods: From January 2004 to December 2014, all patients diagnosed with severe strongyloidiasis at the University of the Ryukyus Hospital or affiliated hospitals in Okinawa, Japan, were included in this retrospective study. All diagnoses were confirmed by the microscopic or histopathological identification of larvae. Severe strongyloidiasis was defined by the presence of any of the following: 1) the identification of S. stercoralis from extra gastrointestinal specimens, 2) sepsis, 3) meningitis, 4) acute respiratory failure, or 5) respiratory tract hemorrhage. Patients were assigned to either HS or DS. Medical records were further reviewed to extract related clinical features and radiological findings.Results: Sixteen severe strongyloidiasis cases were included. Of those, fifteen cases had pulmonary manifestations, eight had acute respiratory distress syndrome (ARDS) (53%), seven had enteric bacterial pneumonia (46%) and five had pulmonary hemorrhage (33%). Acute respiratory failure was a common indicator for pulmonary manifestation (87%). Chest X-ray findings frequently showed diffuse shadows (71%). Additionally, ileum gas was detected for ten of the sixteen cases in the upper abdomen during assessment with chest X-ray. While, chest CT findings frequently showed ground-glass opacity (GGO) in 89% of patients. Interlobular septal thickening was also frequently shown (67%), always accompanying GGO in upper lobes.Conclusions: In summary, our study described HS/DS cases with pulmonary manifestations including, ARDS, bacterial pneumonia and pulmonary hemorrhage. Chest X-ray findings in HS/DS cases frequently showed diffuse shadows, and the combination of GGO and interlobular septal thickening in chest CT was common in HS/DS, regardless of accompanying pulmonary manifestations. This CT finding suggests alveolar hemorrhage could be used as a potential marker indicating the transition from latent to symptomatic state. Respiratory specimens are especially useful for detecting larvae in cases of HS/DS. [ABSTRACT FROM AUTHOR]

Background: Hepatocyte growth factor (HGF) is known to be involved in the resolution of pulmonary inflammation and repair of acute lung injury. Legionella pneumonia is sometimes complicated by acute lung injury. Our study aimed to determine the role of serum HGF levels in Legionella pneumonia. Methods: Sera from patients with Legionella pneumonia (42 cases), other bacterial pneumonia (33 cases), pulmonary tuberculosis (19 cases), and normal controls (29 cases) were collected. The serum HGF levels for each serum sample were determined by sandwich ELISA. Clinical and laboratory data were collected by reviewing the medical charts. Results: Serum HGF levels were higher in patients with Legionella pneumonia than in those with other bacterial pneumonia, pulmonary tuberculosis, and controls. The HGF levels were compared with white blood cell counts, C-reactive protein, Alanine amino- transferase, and lactate dehydrogenase (LDH). The HGF levels were correlated to serum LDH levels. Moreover, serum HGF levels were significantly higher in non-survivors than in survivors. Conclusions: HGF levels increased in severer pneumonia caused by Legionella, suggesting that HGF might play a significant role in the Legionella pneumonia. [ABSTRACT FROM AUTHOR]

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-κB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-κB, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and transforming growth factor β-associated kinase 1 (TAK1). Transfection of dominant negative mutants of |κBα, |κB kinase, NF-κB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-κB, 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-κB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease. [ABSTRACT FROM AUTHOR]

Background: The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-κB activation. Results: Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominantnegative Akt inhibited H. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression. Conclusion: The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods: Nuclear deoxyribonucleic acid (DNA) fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP)-biotin nick end labeling method (TUNEL method) and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results: The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining) and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1) protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 µM) did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion: Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a major virulence factor of L. pneumophila, is involved in the effects we measured in alveolar epithelial cells. Methyl prednisolone may modulate the interaction of Legionella and these cells. [ABSTRACT FROM AUTHOR]

Background: Human T-cell leukemia virus type I (HTLV-I) is associated with pulmonary diseases, characterized by bronchoalveolar lymphocytosis, which correlates with HTLV-I proviral DNA in carriers. HTLV-I Tax seems to be involved in the development of such pulmonary diseases through the local production of inflammatory cytokines and chemokines in T cells. However, little is known about induction of these genes by HTLV-I infection in lung epithelial cells. Results: We tested infection of lung epithelial cells by HTLV-I by coculture studies in which A549 alveolar and NCI-H292 tracheal epithelial cell lines were cocultured with MT-2, an HTLV-I-infected T-cell line. Changes in the expression of several cellular genes were assessed by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. Coculture with MT-2 cells resulted in infection of lung epithelial cells as confirmed by detection of proviral DNA, HTLV-I Tax expression and HTLV-I p19 in the latter cells. Infection was associated with induction of mRNA expression of various cytokines, chemokines and cell adhesion molecule. NF-κB and AP-1 were also activated in HTLV-I-infected lung epithelial cells. In vivo studies showed Tax protein in lung epithelial cells of mice bearing Tax and patients with HTLV-I-related pulmonary diseases. Conclusion: Our results suggest that HTLV-I infects lung epithelial cells, with subsequent production of cytokines, chemokines and cell adhesion molecules through induction of NF-?B and AP-1. These changes can contribute to the clinical features of HTLV-I-related pulmonary diseases. [ABSTRACT FROM AUTHOR]

Background: Legionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. We investigated the effect of L. pneumophila on the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines. Results: Infection of L. pneumophila strain, but not heat-killed strain, resulted in upregulation of IL-8. IL-8 mRNA expression was induced immediately after the infection and its signal became gradually stronger until 24 h after infection. On the other hand, IL-8 expression in A549 cells infected with L. pneumophila lacking a functional type IV secretion system was transient. The IL-8 expression was slightly induced at 16 h and increased at 24 h after infection with flagellin-deficient Legionella. Activation of the IL-8 promoter by L. pneumophila infection occurred through the action of nuclear factor-κB (NF-κB). Transfection of dominant negative mutants of NF-κB-inducing kinase, IκB kinase and IκB inhibited L. pneumophila-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressed L. pneumophila-induced IL-8 mRNA due to deactivation of NF-κB. Conclusion: Collectively, these results suggest that L. pneumophila induces activation of NF-κB through an intracellular signaling pathway that involves NF-κB-inducing kinase and IκB kinase, leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator in L. pneumophila-induced IL-8 expression, presumably contributing to immune response in L. pneumophila. The presence of flagellin and a type IV secretion system are critical for Legionella to induce IL-8 expression in lung epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Strongyloidiasis is a chronic parasitic infection caused by Strongyloides stercoralis. Severe cases such as, hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), can involve pulmonary manifestations. These manifestations frequently aid the diagnosis of strongyloidiasis. Here, we present the pulmonary manifestations and radiological findings of severe strongyloidiasis., Methods: From January 2004 to December 2014, all patients diagnosed with severe strongyloidiasis at the University of the Ryukyus Hospital or affiliated hospitals in Okinawa, Japan, were included in this retrospective study. All diagnoses were confirmed by the microscopic or histopathological identification of larvae. Severe strongyloidiasis was defined by the presence of any of the following: 1) the identification of S. stercoralis from extra gastrointestinal specimens, 2) sepsis, 3) meningitis, 4) acute respiratory failure, or 5) respiratory tract hemorrhage. Patients were assigned to either HS or DS. Medical records were further reviewed to extract related clinical features and radiological findings., Results: Sixteen severe strongyloidiasis cases were included. Of those, fifteen cases had pulmonary manifestations, eight had acute respiratory distress syndrome (ARDS) (53%), seven had enteric bacterial pneumonia (46%) and five had pulmonary hemorrhage (33%). Acute respiratory failure was a common indicator for pulmonary manifestation (87%). Chest X-ray findings frequently showed diffuse shadows (71%). Additionally, ileum gas was detected for ten of the sixteen cases in the upper abdomen during assessment with chest X-ray. While, chest CT findings frequently showed ground-glass opacity (GGO) in 89% of patients. Interlobular septal thickening was also frequently shown (67%), always accompanying GGO in upper lobes., Conclusions: In summary, our study described HS/DS cases with pulmonary manifestations including, ARDS, bacterial pneumonia and pulmonary hemorrhage. Chest X-ray findings in HS/DS cases frequently showed diffuse shadows, and the combination of GGO and interlobular septal thickening in chest CT was common in HS/DS, regardless of accompanying pulmonary manifestations. This CT finding suggests alveolar hemorrhage could be used as a potential marker indicating the transition from latent to symptomatic state. Respiratory specimens are especially useful for detecting larvae in cases of HS/DS.

Background: In Japan, the clinical characteristics and recent serotype distribution among adult patients of invasive pneumococcal disease (IPD) have not been fully investigated since the introduction of the pneumococcal conjugate vaccine (PCV) in children. From November 2010, PCV7 was encouraged by an official program, funded by government, subsequently included in the routine schedule in April 2013, and replaced with a PCV13 in November 2013., Methods: Between April 2013 and March 2015, patients with IPD older than 15 years were evaluated based on the enhanced national surveillance in ten prefectures of Japan. The serotype distribution of the isolates was analyzed in these patients., Results: The analysis included 291 patients: 107 patients (37%) were female and the median age was 70 years. Of 281 patients with available data, 202 (72%) had underlying diseases, including 107 patients (38%) with immunocompromised status. The case fatality proportion for all case was 20%. In subgroup analysis, the case fatality proportion (29%) in immunocompromised patients was much higher than that (0-16%) in each age group of nonimmunocompromised patients (15-39 years, 40-64 years, and ≥ 65 years). While the proportion of bacteremia without any focus (27%) was higher than that (8-10%) in nonimmunocompromised patients, the proportions of vaccine types (PCV13, 32%; PPSV23, 51%) of the causative isolates were lower than those in each age group of nonimmunocompromised patients. Among 291 isolates, the most frequent serotypes were 3 (17%), 19A (13%), and 22F (10%). Twelve percent of the isolates were PCV7 serotypes, 46% were PCV13 serotypes, and 66% were PPSV23 serotypes., Conclusions: The majority of adult patients of IPD had underlying diseases, including immunocompromised conditions. A low proportion (12%) of PCV7-type IPD was observed in this population where PCV7 for children had been included in the routine immunization schedule.

Background: The epidemic patterns of influenza B infection and their association with climate conditions are not well understood. Influenza surveillance in Okinawa is important for clarifying transmission patterns in both temperate and tropical regions. Using surveillance data, collected over 7 years in the subtropical region of Japan, this study aims to characterize the epidemic patterns of influenza B infection and its association with ambient temperature and relative humidity, in a parallel comparison with influenza A., Methods: From January 2007 until March 2014, two individual influenza surveillance datasets were collected from external sources. The first dataset, included weekly rapid antigen test (RAT) results from four representative general hospitals, located in the capital city of Okinawa. A nation-wide surveillance of influenza, diagnosed by RAT results and/or influenza-like illness symptoms, included the age distribution of affected patients and was used as the second dataset. To analyze the association between infection and local climate conditions, ambient temperature and relative humidity during the study period were retrieved from the Japanese Meteorological Agency website., Results: Although influenza A maintained high number of infections from December through March, epidemics of influenza B infection were observed annually from March through July. The only observed exception was 2010, when the pandemic strain of 2009 dominated. During influenza B outbreaks, influenza patients aged 5 to 9 years old and 10 to 14 years old more frequently visited sentinel sites. Although both ambient temperature and relative humidity are inversely associated with influenza A infection, influenza B infection was found to be directly associated with high relative humidity., Conclusion: Further studies are needed to elucidate the complex epidemiology of influenza B and its relationship with influenza A. In the subtropical setting of Okinawa, epidemics of influenza B infection occur from March to July following the influenza A epidemic, and primarily affect school-age children. These findings help to define unknown aspects of influenza B and can inform healthcare decisions for patients located outside temperate regions.

Background: The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-kappaB (NF-kappaB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-kappaB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-kappaB activation., Results: Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-kappaB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-kappaB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression., Conclusion: The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-kappaB activation associated with mucosal inflammation and carcinogenesis.

Background: Legionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. We investigated the effect of L. pneumophila on the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines., Results: Infection of L. pneumophila strain, but not heat-killed strain, resulted in upregulation of IL-8. IL-8 mRNA expression was induced immediately after the infection and its signal became gradually stronger until 24 h after infection. On the other hand, IL-8 expression in A549 cells infected with L. pneumophila lacking a functional type IV secretion system was transient. The IL-8 expression was slightly induced at 16 h and increased at 24 h after infection with flagellin-deficient Legionella. Activation of the IL-8 promoter by L. pneumophila infection occurred through the action of nuclear factor-kappaB (NF-kappaB). Transfection of dominant negative mutants of NF-kappaB-inducing kinase, IkappaB kinase and IkappaB inhibited L. pneumophila-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressed L. pneumophila-induced IL-8 mRNA due to deactivation of NF-kappaB., Conclusion: Collectively, these results suggest that L. pneumophila induces activation of NF-kappaB through an intracellular signaling pathway that involves NF-kappaB-inducing kinase and IkappaB kinase, leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator in L. pneumophila-induced IL-8 expression, presumably contributing to immune response in L. pneumophila. The presence of flagellin and a type IV secretion system are critical for Legionella to induce IL-8 expression in lung epithelial cells.