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Many eukaryotic membrane-dependent functions are often spatially and temporally regulated by membrane microdomains (FMMs) also known as lipid rafts. These domains are enriched in polyisoprenoid lipids and scaffolding proteins belonging to the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) protein superfamily that was also identified in Gram-positive bacteria. By contrast, little is still known about FMMs in Gram-negative bacteria. InEscherichia coliK12, 4 SPFH proteins, YqiK, QmcA, HflK, and HflC, were shown to localize in discrete polar or lateral inner-membrane locations, raising the possibility thatE. coliSPFH proteins could contribute to the assembly of inner-membrane FMMs and the regulation of cellular processes.Here we studied the determinant of the localization of QmcA and HflC and showed that FMM-associated cardiolipin lipid biosynthesis is required for their native localization pattern. Using Biolog phenotypic arrays, we showed that a mutant lacking all SPFH genes displayed increased sensitivity to aminoglycosides and oxidative stress that is due to the absence of HflKC. Our study therefore provides further insights into the contribution of SPFH proteins to stress tolerance inE. coli.IMPORTANCEEukaryotic cells often segregate physiological processes in cholesterol-rich functional membrane micro-domains. These domains are also called lipid rafts and contain proteins of the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) superfamily, which are also present in prokaryotes but were mostly studied in Gram-positive bacteria. Here, we showed that the cell localization of the SPFH proteins QmcA and HflKC in the Gram-negative bacteriaE. coliis altered in absence of cardiolipin lipid synthesis. This suggests that cardiolipins contribute toE. colimembrane microdomain assembly. Using a broad phenotypic analysis, we also showed that HflKC contribute toE. colitolerance to aminoglycosides and oxidative stress. Our study, therefore, provides new insights into the cellular processes associated with SPFH proteins inE. coli.

In the hyperalgebra [Formula: see text] of the [Formula: see text]th Frobenius kernel [Formula: see text] of the algebraic group [Formula: see text], we construct a basis of the [Formula: see text]-module generated by a certain element which was given by the author before. As its applications, we also prove some results on the [Formula: see text]-modules and the algebra [Formula: see text].

Staphylococcus aureus is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in S. aureus remains largely unknown. The only known LTs in S. aureus are immunodominant staphylococcal antigen A (IsaA) and Staphylococcus epidermidis D protein (SceD). Our study demonstrates that, in a strain of methicillin-resistant S. aureus (MRSA), IsaA and SceD contribute differently to biofilm formation and β-lactam resistance. Deletion of isaA, but not sceD, led to decreased biofilm formation. Additionally, in isaA-deleted strains, β-lactam resistance was significantly decreased compared to that of wild-type strains. Plasmid-based expression of mecA, a major determinant of β-lactam resistance in MRSA, in an isaA-deleted strain did not restore β-lactam resistance, demonstrating that the β-lactam susceptibility phenotype is exhibited by isaA mutant regardless of the production level of PBP2a. Overall, our results suggest that IsaA is a potential therapeutic target for MRSA infections.

Objective The aims of this study were to elucidate the frequency and etiology of community-acquired lobar pneumonia (CALP) and the clinical and radiological differences between CALP and tuberculous lobar pneumonia (TLP). Patients and Methods We retrospectively reviewed medical records of patients with community-acquired pneumonia (CAP) (n = 1032) and tuberculosis (n = 1101) admitted to our hospital. Results Sixty-nine (6.7%) patients with CAP and 23 (2.1%) with pulmonary tuberculosis developed CALP. Legionella species were the most common pathogen (27 patients, 39.1%), followed by Streptococcus pneumoniae (19 patients, 27.5%) and Mycoplasma pneumoniae (18 patients, 26.1%). Symptom duration was longer in the patients with TLP than in those with CALP. On chest radiographs, cavitation in the area of lobar pneumonia and nodular shadows were radiological findings predictive of TLP. High-resolution computed tomography showed cavitation in the area of lobar pneumonia, well-defined centrilobular nodules, and tree-in-bud sign to be the radiological findings predictive of TLP by multivariate logistic regression models. Conclusion Common causes of CALP are Legionella species, S. pneumoniae, and M. pneumoniae. TLP should be considered in patients with lobar pneumonia, particularly in patients with long symptom duration, cavitation, and nodular shadows on chest radiographs, and cavitation, well-defined centrilobular nodules, and tree-in-bud sign on CT.

We describe the structure of projective indecomposable modules for the subalgebra consisting of the elements of degree 0 in the hyperalgebra of the r r -th Frobenius kernel for the algebraic group SL 2 ( k ) \textrm {SL}_2(k) , using the primitive idempotents which were constructed before by the author.

Background Respiratory tract infection is a major cause of acute exacerbation of bronchial asthma (AEBA). Although recent findings suggest that common bacteria are causally associated with AEBA, a comprehensive epidemiologic analysis of infectious pathogens including common/atypical bacteria and viruses in AEBA has not been performed. Accordingly, we attempted to detect pathogens during AEBA by using real-time polymerase chain reaction (PCR) in comparison to conventional methods. Methods We prospectively enroled adult patients with AEBA from August 2012 to March 2014. Infectious pathogens collected in nasopharyngeal swab and sputum samples were examined in each patient by conventional methods and real-time PCR, which can detect 6 bacterial and 11 viral pathogens. The causal association of these pathogens with AEBA severity and their frequency of monthly distribution were also examined. Results Among the 64 enroled patients, infectious pathogens were detected in 49 patients (76.6%) using real-time PCR and in 14 patients (21.9%) using conventional methods (p

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Let G be a connected, semisimple, and simply connected algebraic group defined and split over the finite field of order p, and let G(q) be the corresponding finite Chevalley or twisted group, where q = pr. Recently, Anwar determines the direct sum decomposition of the tensor product of the rth Steinberg module and a simple G-module with a (p,r)-minuscule highest weight λ. In this paper, we determine that of the tensor product regarded as a module for G(q) under some weak assumptions for λ.

Background Dosages of anti-tuberculosis (TB) drugs are recommended to be adjusted according to renal function for patients complicated with chronic kidney disease (CKD). However, the efficacy and safety outcomes of such renal function-based dosage adjustments are not fully elucidated. Methods We retrospectively reviewed cases of pulmonary TB susceptible to first-line drugs that were treated at Jikei University Daisan Hospital between 2005 and 2014 with standard regimens based on dosage adjustments according to renal function recommended by international guidelines. Patients were divided into four groups, those with no, mild, moderate or severe CKD. In-hospital TB-related mortality, the rate of sputum culture conversion at 2 months, the frequency of adverse events (AEs), for which at least the temporal discontinuation of the suspect drug was required for patient improvement, and the rate of regimen change due to AEs were assessed. Results In the 241 enrolled patients (mean age, 64.1 years; 143 men), fourteen patients (5.8%) died due to TB during their hospitalization. The rate of sputum culture conversion at 2 months was 78.0%. The frequency of in-hospital TB-related death and the conversion rate in the groups did not vary significantly according to CKD severity including those in the non-CKD group (P = 0.310 and P = 0.864). Meanwhile, a total of 70 AEs were observed in 60 patients (24.9%) and the difference between the groups in the overall frequency of AEs was almost significant (P = 0.051). Moreover, for the 154 patients with CKD, severe CKD stage was a significant risk factor for regimen change (OR = 5.92, 95% CI = 1.08–32.5, P = 0.041), as were drug-induced hepatitis and cutaneous reaction (OR = 35.6, 95% CI = 8.70–145, P

Community-acquired pneumonia (CAP) has high morbidity and mortality. Unfortunately, the pathogen detection rate using conventional culture methods is relatively low. We compared comprehensive real-time polymerase chain reaction (real-time PCR) analysis of nasopharyngeal swab specimens (NPS) and sputum samples against conventional methods for ability to detect causative pathogens of CAP.We prospectively enrolled adult CAP patients, including those with prior antibiotic use, from December 2012 to May 2014. For each patient, causative pathogens were investigated conventionally and by real-time PCR that can identify 6 bacterial and 11 viral pathogens.Patients numbered 92 (mean age, 63 years; 59 male), including 30 (33%) with prior antibiotic use. Considering all patients, identification of causative pathogens by real-time PCR was significantly more frequent than by conventional methods in all patients (72% vs. 57%, p = 0.018). In patients with prior antibiotic use, identification rates also differed significantly (PCR, 77%; conventional, 50%; p = 0.027). Mixed infections were more frequent according to real-time PCR than conventional methods (26% vs. 4%, p 0.001). By the real-time PCR, Streptococcus pneumoniae was most frequently identified (38%) as a causative pathogen, followed by Haemophilus influenzae (37%) and Mycoplasma pneumoniae (5%). PCR also identified viral pathogens (21%), with sensitivity enhanced by simultaneous examination of both NPS and sputum samples rather than only NPS samples.Real-time PCR of NPS and sputum samples could better identify bacterial and viral pathogens in CAP than conventional methods, both overall and in patients with prior antibiotic treatment.

Formation of bacterial biofilms on medical devices can cause severe or fatal infectious diseases. In particular, biofilm-associated infections caused by methicillin-resistant Staphylococcus aureus are difficult to eradicate because the biofilm is strongly resistant to antibiotics and the host immune response. There is no effective treatment for biofilm-associated infectionss, except for surgical removal of contaminated medical devices followed by antibiotic therapy. Here we show that norgestimate, an acetylated progestin, effectively inhibits biofilm formation by staphylococcal strains, including methicillin-resistant S. aureus, without inhibiting their growth, decreasing the selective pressure for emergence of resistance. 17-Deacetyl norgestimate, a metabolite of norgestimate, shows much weaker inhibitory activity against staphylococcal biofilm formation, indicating that the acetyl group of norgestimate is important for its activity. Norgestimate inhibits staphylococcal biofilm formation by inhibiting production of polysaccharide intercellular adhesin and proteins in the extracellular matrix. Proteome analysis of S. aureus indicated that norgestimate represses the expression of the cell wall-anchored protein SasG, which promotes intercellular adhesion, and of the glycolytic enzyme enolase, which plays a secondary role in biofilm formation. Notably, norgestimate induces remarkable changes in cell wall morphology, characterized by increased thickness and abnormal rippled septa. Furthermore, norgestimate increases the expression level of penicillin binding protein 2 and resensitizes methicillin-resistant S. aureus to β-lactam antibiotics. These results suggest that norgestimate is a promising lead compound for the development of drugs to treat biofilm-associated infections, as well as for its ability to resensitize methicillin-resistant S. aureus to β-lactam antibiotics., Biofilm formation: Benefits of selective inhibition A synthetic molecule related to the hormone progesterone might keep medical devices free of biofilms without promoting antibiotic resistance. Implanted devices that have become contaminated with biofilms generally must be surgically removed prior to treating the underlying infection with antibiotics. Ken-ichi Okuda and colleagues at The Jikei University School of Medicine in Tokyo, with co-workers elsewhere in Japan, found that the synthetic progesterone analog norgestimate inhibits biofilm formation without inhibiting bacterial growth. They regard this selective effect on biofilm formation as a significant advantage, as it reduces the risk of inducing resistance in the targeted bacteria. They demonstrated the effect using staphylococcal bacteria, including the problematic and highly dangerous methicillin-resistant Staphylococcus aureus (MRSA). The research also indicated that norgestimate can resensitize MRSA bacteria to some of the antibiotics they are resistant to.

A correction to this article has been published and is linked from the HTML version of this article.

Background and objective It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. Methods We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. Results A total of 29 patients were diagnosed with ‘definite MAC’ based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). Conclusions The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases.

Let G be a connected, semisimple and simply connected algebraic group and G ( q ) the corresponding finite Chevalley group over the finite field of order q = p r . In a recent paper the author determined a direct sum decomposition of the k G ( q ) -submodule generated by a highest weight vector of a certain Weyl module when q is not too small, which is a generalization of Pillen's result in 1997. In this article, we claim that the result does not need the assumption on q.

A 76-year-old man complaining of exertional dyspnea was admitted to our hospital. Chest computed tomography revealed bilateral diffuse ground-glass opacities and small nodules. A transbronchial lung biopsy revealed tumor cell emboli in the pulmonary arteries. The patient was diagnosed with gastric adenocarcinoma using an endoscopic stomach biopsy; however, the interstitial opacities progressively worsened and he died of acute respiratory failure. An autopsy revealed extensive pulmonary tumor embolisms (PTE) with associated ischemic damages, e.g., infarctions, alveolar wall thickening with cuboidal metaplasia, hemorrhage, and diffuse alveolar damage. The ground-glass opacities in the chest computed tomography findings appear to correlate with the pathological ischemic changes associated with PTE.

Formation of bacterial biofilms on medical devices can cause severe or fatal infectious diseases. In particular, biofilm-associated infections caused by methicillin-resistant Staphylococcus aureus are difficult to eradicate because the biofilm is strongly resistant to antibiotics and the host immune response. There is no effective treatment for biofilm-associated infectionss, except for surgical removal of contaminated medical devices followed by antibiotic therapy. Here we show that norgestimate, an acetylated progestin, effectively inhibits biofilm formation by staphylococcal strains, including methicillin-resistant S. aureus, without inhibiting their growth, decreasing the selective pressure for emergence of resistance. 17-Deacetyl norgestimate, a metabolite of norgestimate, shows much weaker inhibitory activity against staphylococcal biofilm formation, indicating that the acetyl group of norgestimate is important for its activity. Norgestimate inhibits staphylococcal biofilm formation by inhibiting production of polysaccharide intercellular adhesin and proteins in the extracellular matrix. Proteome analysis of S. aureus indicated that norgestimate represses the expression of the cell wall-anchored protein SasG, which promotes intercellular adhesion, and of the glycolytic enzyme enolase, which plays a secondary role in biofilm formation. Notably, norgestimate induces remarkable changes in cell wall morphology, characterized by increased thickness and abnormal rippled septa. Furthermore, norgestimate increases the expression level of penicillin binding protein 2 and resensitizes methicillin-resistant S. aureus to β-lactam antibiotics. These results suggest that norgestimate is a promising lead compound for the development of drugs to treat biofilm-associated infections, as well as for its ability to resensitize methicillin-resistant S. aureus to β-lactam antibiotics.

Background Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation. In this study, the effect of PFD on autophagy/mitophagy activation in lung fibroblasts (LF) was evaluated, specifically the anti-fibrotic property of PFD for modulation of myofibroblast differentiation during insufficient mitophagy. Methods Transforming growth factor-β (TGF-β)-induced or ATG5, ATG7, and PARK2 knockdown-mediated myofibroblast differentiation in LF were used for in vitro models. The anti-fibrotic role of PFD was examined in a bleomycin (BLM)-induced lung fibrosis model using PARK2 knockout (KO) mice. Results We found that PFD induced autophagy/mitophagy activation via enhanced PARK2 expression, which was partly involved in the inhibition of myofibroblast differentiation in the presence of TGF-β. PFD inhibited the myofibroblast differentiation induced by PARK2 knockdown by reducing mitochondrial ROS and PDGFR-PI3K-Akt activation. BLM-treated PARK2 KO mice demonstrated augmentation of lung fibrosis and oxidative modifications compared to those of BLM-treated wild type mice, which were efficiently attenuated by PFD. Conclusions These results suggest that PFD induces PARK2-mediated mitophagy and also inhibits lung fibrosis development in the setting of insufficient mitophagy, which may at least partly explain the anti-fibrotic mechanisms of PFD for IPF treatment.

An 80-year-old man was admitted withright pleural effusion and bilateral axillary lymph node enlargement. Histopathological examination of the axillary lymph node biopsy specimen showed diffuse large B-cell lymphoma (DLBCL). The pleural effusion was exudative and predominantly lymphocytic, and cytology of the effusion was compatible with malignant lymphoma. Although acid-fast bacillus smear and polymerase chain reaction analysis of the pleural effusion were negative, pleural adenosine deaminase (P-ADA) was high (79.2 IU/L). We suspected tuberculous pleurisy and performed thoracoscopy. We diagnosed DLBCL with tuberculous pleurisy and started tuberculosis treatment. When P-ADA is high, thoracoscopy should be performed to explore tuberculous pleurisy.

Cigarette smoke (CS)–induced cellular senescence has been implicated in the pathogenesis of chronic obstructive pulmonary disease, and SIRT6, a histone deacetylase, antagonizes this senescence, presumably through the attenuation of insulin-like growth factor (IGF)-Akt signaling. Autophagy controls cellular senescence by eliminating damaged cellular components and is negatively regulated by IGF-Akt signaling through the mammalian target of rapamycin (mTOR). SIRT1, a representative sirtuin family, has been demonstrated to activate autophagy, but a role for SIRT6 in autophagy activation has not been shown. Therefore, we sought to investigate the regulatory role for SIRT6 in autophagy activation during CS-induced cellular senescence. SIRT6 expression levels were modulated by cDNA and small interfering RNA transfection in human bronchial epithelial cells (HBECs). Senescence-associated β-galactosidase staining and Western blotting of p21 were performed to evaluate senescence. We demonstrated that SIRT6 expression levels were decreased in lung homogenates from chronic obstructive pulmonary disease patients, and SIRT6 expression levels correlated significantly with the percentage of forced expiratory volume in 1 s/forced vital capacity. CS extract (CSE) suppressed SIRT6 expression in HBECs. CSE-induced HBEC senescence was inhibited by SIRT6 overexpression, whereas SIRT6 knockdown and mutant SIRT6 (H133Y) without histone deacetylase activity enhanced HBEC senescence. SIRT6 overexpression induced autophagy via attenuation of IGF-Akt-mTOR signaling. Conversely, SIRT6 knockdown and overexpression of a mutant SIRT6 (H133Y) inhibited autophagy. Autophagy inhibition by knockdown of ATG5 and LC3B attenuated the antisenescent effect of SIRT6 overexpression. These results suggest that SIRT6 is involved in CSE-induced HBEC senescence via autophagy regulation, which can be attributed to attenuation of IGF-Akt-mTOR signaling.

A 32-year-old female with epilepsy presented at our hospital with high-grade fever, seizures, and unconsciousness. She was initially treated for aspiration pneumonia with ampicillin/sulbactam. Despite antibiotic therapy, her chest X-ray findings dramatically worsened, showing extension to the bilateral lung field. Her PaO2/FiO2 ratio decreased to 70.6. Rapid progression of hypoxia, unconsciousness, and hyponatremia led to the suspicion of Legionella pneumonia; however, it was difficult to make a definitive diagnosis because she had denied using a whirlpool spa and the initial urinary Legionella antigen test results were negative. Therefore, we repeated the Legionella urinary antigen test, which was positive. On the basis of these results, sputum polymerase chain reaction findings, and the four-fold elevation of paired antibodies, the patient was diagnosed as having Legionella pneumonia accompanied by acute respiratory distress syndrome. We considered administering fluoroquinolone antibiotics, that are recommended for severe Legionella pneumonia, although quinolones have a potential risk for causing convulsions. In this case, we carefully administered ciprofloxacin. The patient recovered consciousness after treatment without any relapse of epileptic seizures. We also administered a corticosteroid for severe pneumonia with the expectation of clinical improvement and to avoid intubation. We emphasize the importance of aggressive workup and empirical therapy for patients with Legionella pneumonia with rapidly worsening symptoms and clinical features such as unconsciousness, epilepsy, and hyponatremia and in whom fluoroquinolone and corticosteroid therapy are effective despite the presence of epilepsy.

Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

We report a case with an atypical presentation of descending necrotizing mediastinitis (DNM). A 47-year-old woman with a medical history of untreated type 2 diabetes mellitus and influenza type A virus infection 2 weeks prior to admission was referred to our hospital complaining of right cervical pain and right upper limb swelling. A chest enhanced computed tomographic (CT) scan showed a ring-enhanced mass-like shadow extending from the right sternomastoid muscle down to the right upper mediastinum, compressing the right subclavicular vein. We diagnosed the patient as having DNM based on a physical examination and the CT findings. Because the abscess extended from deep in the neck to the upper mediastinum and right upper pleural space, emergent abscess debridement and drainage was required. After hospitalization, antibiotics (Ampicillin/Sulbactam 12 g/day) were also administered based on Gram-stain findings from the drainage fluid, which showed Gram-positive cocci resembling a string of beads. A culture of the drainage fluid identified Streptococcus agalactiae. Aggressive abscess drainage and early antibiotic therapy resulted in a favorable response. She was discharged without complications on the 33rd hospital day. DNM is well known as a rare but lethal disease. In this case, the presence of diabetes mellitus and post-influenza infection might have been risk factors for a serious S. agalactiae infection. Early aggressive therapy and adequate drainage are recommended for patients with DNM.

Objective In the emergency department, it is sometimes difficult to differentiate heart failure (HF) from other diseases (e.g., respiratory diseases) in patients who develop dyspnea. The plasma B-type natriuretic peptide (BNP) levels increase in patients with HF, and various levels are associated with specific New York Heart Association classes. Although the diagnosis of HF should not be made based only on the plasma BNP levels, the identification of a cut-off value for BNP to diagnose HF would be helpful. Methods Patients admitted to the emergency department of our hospital with dyspnea between January 2010 and December 2011 were retrospectively reviewed. The patients whose estimated glomerular filtration rate was less than 30 mL/min/1.73 m(2) were excluded. Patients were divided into two groups: those with HF (n=131) and those without HF (n=138). The cut-off value for BNP was determined by the receiver-operating characteristic curve. Results The area under the curve of this curve was 0.934. The optimal cut-off point for detection of HF was 234 pg/mL. The sensitivity and specificity were 87.0% and 85.5%, respectively. The fifth and 95th percentiles of the HF group were 132.2 and 2,420.8 pg/mL, respectively. Those of the non-HF group were 9.7 and 430.2 pg/mL, respectively. Conclusion Our study suggests that a plasma BNP level cut-off value of 234 pg/mL can be used to detect HF in the emergency department.

This paper describes circuit design and measurement results of a bipolar field-effect transistor monolithic microwave integrated circuit power amplifier (PA) module operating with a 2.5-V low reference voltage (Vref) and a 2.8-V low collector supply voltage (Vcc). While covering 824-925-MHz broadband CDMA operation at 2.8 V of Vcc, the PA allows a 1.1-V low Vcc and 18-dBm output power (Pout) operation. This is realized using an on-chip step quiescent current control scheme depending on Vcc. In addition, an input high electron-mobility transistor single-pole double-throw switch is integrated on the PA die for selecting 800/900-MHz operating bands, thereby providing easy connectivity between a transmit surface acoustic wave filter and the PA. Measurement results under the 2.8/1.1-V Vcc and 2.5-V Vref bias conditions show that the PA meets J-CDMA/W-CDMA power and distortion specifications sufficiently over a wide temperature range from -20 °C to 85 °C while realizing a broadband operation ranging from 824 to 925 MHz. For J-CDMA (IS-95B) modulation, the PA can deliver a 28-dBm Pout, a 36% power-added efficiency (PAE), and a - 50-dBc adjacent channel power ratio, while a 29-dBm Pout, a 38% PAE, and a -40-dBc adjacent channel leakage power ratio (ACLR) are achieved for W-CDMA (3GPP R99) modulation. Under 3:1 load mismatching condition, the PA also suppresses ACLR of less than - 36 dBc while keeping a forward power of 27.5 dBm. Moreover the PA is capable of delivering a 18-dBm Pout and more than 26% PAE under 824-925-MHz and 1.1-V J-CDMA modulation test conditions. To the best of authors' knowledge, this is the first report on a broadband production-level CDMA PA operating with low Vref and low Vcc.

We study integrality of the Frobenius–Perron eigenvalues of the Cartan matrices for the principal blocks of some finite groups of Lie type with noncyclic abelian Sylow p-subgroups.

Let A be the principal 3-block of a finite group G with an abelian Sylow 3-subgroup P. Let C A be the Cartan matrix of A, and we denote by ρ ( C A ) the unique largest eigenvalue of C A . The value ρ ( C A ) is called the Frobenius–Perron eigenvalue of C A . We shall prove that ρ ( C A ) is a rational number if and only if A and the principal 3-block of N G ( P ) are Morita equivalent. This generalizes earlier Wada's theorem in 2007, where he proves it only for the case that the order of P is nine, while we prove it for the case that P is an arbitrary finite abelian 3-group. The result presented here uses the classification of finite simple groups.

M. Broue gives an important conjecture which is called Broue's abelian defect group conjecture. This conjecture says that a p-block, where p is a prime number, of a finite group with an abelian defect group is derived equivalent to its Brauer correspondent in the normalizer of the defect group. In this paper, we prove that this conjecture is true for the nonprincipal block of SL ( 2 , p n ) for a positive integer n.

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test.We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital.A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029).The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases.

Mitochondria are dynamic organelles that continuously change their shape through fission and fusion. Disruption of mitochondrial dynamics is involved in disease pathology through excessive reactive oxygen species (ROS) production. Accelerated cellular senescence resulting from cigarette smoke exposure with excessive ROS production has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Hence, we investigated the involvement of mitochondrial dynamics and ROS production in terms of cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBEC). Mitochondrial morphology was examined by electron microscopy and fluorescence microscopy. Senescence-associated β-galactosidase staining and p21 Western blotting of primary HBEC were performed to evaluate cellular senescence. Mitochondrial-specific superoxide production was measured by MitoSOX staining. Mitochondrial fragmentation was induced by knockdown of mitochondrial fusion proteins (OPA1 or Mitofusins) by small-interfering RNA transfection. N-acetylcysteine and Mito-TEMPO were used as antioxidants. Mitochondria in bronchial epithelial cells were prone to be more fragmented in COPD lung tissues. CSE induced mitochondrial fragmentation and mitochondrial ROS production, which were responsible for acceleration of cellular senescence in HBEC. Mitochondrial fragmentation induced by knockdown of fusion proteins also increased mitochondrial ROS production and percentages of senescent cells. HBEC senescence and mitochondria fragmentation in response to CSE treatment were inhibited in the presence of antioxidants. CSE-induced mitochondrial fragmentation is involved in cellular senescence through the mechanism of mitochondrial ROS production. Hence, disruption of mitochondrial dynamics may be a part of the pathogenic sequence of COPD development.

A 32-year-old female with epilepsy presented at our hospital with high-grade fever, seizures, and unconsciousness. She was initially treated for aspiration pneumonia with ampicillin/sulbactam. Despite antibiotic therapy, her chest X-ray findings dramatically worsened, showing extension to the bilateral lung field. Her PaO2/FiO2 ratio decreased to 70.6. Rapid progression of hypoxia, unconsciousness, and hyponatremia led to the suspicion of Legionella pneumonia; however, it was difficult to make a definitive diagnosis because she had denied using a whirlpool spa and the initial urinary Legionella antigen test results were negative. Therefore, we repeated the Legionella urinary antigen test, which was positive. On the basis of these results, sputum polymerase chain reaction findings, and the four-fold elevation of paired antibodies, the patient was diagnosed as having Legionella pneumonia accompanied by acute respiratory distress syndrome. We considered administering fluoroquinolone antibiotics, that are recommended for severe Legionella pneumonia, although quinolones have a potential risk for causing convulsions. In this case, we carefully administered ciprofloxacin. The patient recovered consciousness after treatment without any relapse of epileptic seizures. We also administered a corticosteroid for severe pneumonia with the expectation of clinical improvement and to avoid intubation. We emphasize the importance of aggressive workup and empirical therapy for patients with Legionella pneumonia with rapidly worsening symptoms and clinical features such as unconsciousness, epilepsy, and hyponatremia and in whom fluoroquinolone and corticosteroid therapy are effective despite the presence of epilepsy.

A patient with a past history of renal cell carcinoma (RCC) presented to us with an exudative pleural effusion. Because pleural effusion cytology was inconclusive, we performed medical thoracoscopy under local anesthesia. Multiple white tumors measuring approximately 2 cm in diameter were observed on the parietal pleura. Metastatic carcinoma from RCC was diagnosed histologically. Although malignant effusions are rare in cases of RCC metastasis, clinicians should be aware of this possibility. When pleural effusion cytology is inconclusive in a patient with a past history of RCC, medical thoracoscopy can be useful for making the diagnosis of pleural metastasis.

We report a case with an atypical presentation of descending necrotizing mediastinitis (DNM). A 47-year-old woman with a medical history of untreated type 2 diabetes mellitus and influenza type A virus infection 2 weeks prior to admission was referred to our hospital complaining of right cervical pain and right upper limb swelling. A chest enhanced computed tomographic (CT) scan showed a ring-enhanced mass-like shadow extending from the right sternomastoid muscle down to the right upper mediastinum, compressing the right subclavicular vein. We diagnosed the patient as having DNM based on a physical examination and the CT findings. Because the abscess extended from deep in the neck to the upper mediastinum and right upper pleural space, emergent abscess debridement and drainage was required. After hospitalization, antibiotics (Ampicillin/Sulbactam 12 g/day) were also administered based on Gram-stain findings from the drainage fluid, which showed Gram-positive cocci resembling a string of beads. A culture of the drainage fluid identified Streptococcus agalactiae. Aggressive abscess drainage and early antibiotic therapy resulted in a favorable response. She was discharged without complications on the 33rd hospital day. DNM is well known as a rare but lethal disease. In this case, the presence of diabetes mellitus and post-influenza infection might have been risk factors for a serious S. agalactiae infection. Early aggressive therapy and adequate drainage are recommended for patients with DNM.

The effects of 2-(2,6-diethylphenylimino)thiazolidine (HSO-783) and 2-(4-chloro-2-methylphenylimino)thiazolidine (HSO-786) were compared with those of 2-(2,6-diethylphenylimino)imidazolidine (NC-5) and 2-(4-chloro-2-methylphenylimino)oxazolidine (AC-6) in stimulating adenylate cyclase of Periplaneta americana ventral nerve cord homogenates. These activities were nonadditive with respect to the activity of a maximally effective concentration of octopamine. Washing of homogenates of ventral nerve cord incubated with NC-5, HSO-783, AC-6, and HSO-786 removed nearly all of the stimulatory activities of these agonists. Maximal stimulation of nerve cord adenylate cyclase activity by NC-5, HSO-783, AC-6, and HSO-786 was inhibited by several antagonists, including mianserin, cyproheptadine, chloromazine, and gramine. The rank-order ability of these antagonists to block the maximal adenylate cyclase activation by NC-5, HSO-783, AC-6, and HSO-786 was identical to the rank-order ability of the same antagonists to block the enzyme activation by an optimally effective concentration of octopamine. The β-adrenergic antagonist propranolol was less potent in this respect. AC-6 was a much better acaricide than HSO-783, HSO-786, and NC-5, which were much less potent octopaminergic agonists than AC-6. HSO-786 was a more potent acaricide and octopaminergic agonist than HSO-783. These observations suggest that the toxicity of NC-5, HSO-783, AC-6, and HSO-786 may be due to their octopaminergic agonist action.

2-(Substituted benzylamino)-2-thiazolines (SBAT) were synthesized by a hydrochloric acid-catalyzed cyclization of the corresponding thioureas, using a reaction of 2-methylthio-2-thiazoline with substituted benzylamines or by alkylating 2-amino-2-thiazoline. 2-(Alkylthio)-2-thiazolines were obtained by alkylating 2-mercaptothiazoline. Most of the SBAT compounds activated adenylate cyclase in homogenates of cockroach ventral nerve cords; the effect of introducing substituents at the phenyl of the SBAT compounds on octopaminergic agonist activity was not significant. 2-[β-(Substituted phenyl)ethylamino]-2-thiazolines and 2-(alkylthio)-2-thiazolines were not significant octopaminergic agonists. Washing removed nearly all of the activity of one of the SBAT compounds, suggesting that the SBAT compounds bound reversibly to the octopaminergic receptor.

The aim of the current study was to investigate the lethal complications of Legionella pneumonia. Severe complications and their outcomes in 65 patients with Legionella pneumonia were studied. All patients who eventually had a fatal outcome or who had severe complications received antimicrobial agents active against Legionella on the admission day. Many patients in the severe complication category had multiple severe complications. Six deaths occurred (mortality rate 9.2%), 4 of which were due to septic shock/multiple organ dysfunction syndrome (MODS) (2 patients) or interstitial pneumonia/pulmonary fibrosis after Legionella pneumonia (2 patients), whereas the other 2 deaths were due to causes unrelated to Legionella pneumonia. Mortality rates for each severe complication were as follows: acute respiratory distress syndrome 27.3% (3 of 11); renal failure 33.3% (2 of 6); disseminated intravascular coagulation 33.3% (2 of 6); severe sepsis 0% (0 of 1); septic shock/MODS 66.7% (2 of 3); interstitial pneumonia/pulmonary fibrosis 50% (2 of 4). Despite prompt diagnosis and appropriate treatment with antimicrobial agents active against Legionella, the lethal complications of Legionella pneumonia are septic shock/MODS and interstitial pneumonia/pulmonary fibrosis.