Structural basis of HEAT-kleisin interactions in the human condensin I subcomplex.

Condensin I is a multi-protein complex that plays an essential role in mitotic chromosome assembly and segregation in eukaryotes. It is composed of five subunits: two SMC (SMC2 and SMC4), a kleisin (CAP-H), and two HEAT-repeat (CAP-D2 and CAP-G) subunits. Although balancing acts of the two HEAT-repeat subunits have been demonstrated to enable this complex to support the dynamic assembly of chromosomal axes in vertebrate cells, its underlying mechanisms remain poorly understood. Here, we report the crystal structure of a human condensin I subcomplex comprising hCAP-G and hCAP-H. hCAP-H binds to the concave surfaces of a harp-shaped HEAT-repeat domain of hCAP-G. Physical interaction between hCAP-G and hCAP-H is indeed essential for mitotic chromosome assembly recapitulated in Xenopus egg cell-free extracts. Furthermore, this study reveals that the human CAP-G-H subcomplex has the ability to interact with not only double-stranded DNA, but also single-stranded DNA, suggesting functional divergence of the vertebrate condensin I complex in proper mitotic chromosome assembly.

Detection of pathogens by real-time PCR in adult patients with acute exacerbation of bronchial asthma.

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 < 0.001). Real-time PCR detected bacteria in 29 patients (45.3%) and respiratory viruses in 28 patients (43.8%). Haemophilus influenzae was the most frequently detected microorganism (26.6%), followed by rhinovirus (15.6%). Influenza virus was the significant pathogen associated with severe AEBA. Moreover, AEBA occurred most frequently during November to January. CONCLUSIONS: Real-time PCR was more useful than conventional methods to detect infectious pathogens in patients with AEBA. Accurate detection of pathogens with real-time PCR may enable the selection of appropriate anti-bacterial/viral agents as a part of the treatment for AEBA.

Increased levels of prostaglandin E-major urinary metabolite (PGE-MUM) in chronic fibrosing interstitial pneumonia.

BACKGROUND: Dysregulation of the prostaglandin E2 (PGE2) signaling pathway has been implicated in interstitial pneumonia (IP) pathogenesis. Due to the unstable nature of PGE2, available detection methods may not precisely reflect PGE2 levels. We explored the clinical usefulness of measuring stable prostaglandin E-major urinary metabolite (PGE-MUM) with respect to pathogenesis and extent of chronic fibrosing IP (CFIP), including idiopathic pulmonary fibrosis (IPF), as PGE-MUM is reflective of systemic PGE2 production. METHODS: PGE-MUM was measured by radioimmunoassay in controls (n = 124) and patients with lung diseases (bronchial asthma (BA): n = 78, chronic obstructive pulmonary disease (COPD): n = 33, CFIP: n = 44). Extent of lung fibrosis was assessed by fibrosing score (FS) of computed tomography (CT) (FS1-4). Immunohistochemical evaluation of COX-2 was performed to find PGE2 producing cells in IPF. Human bronchial epithelial cells (HBEC) and lung fibroblasts (LFB) were used in in vitro experiments. RESULTS: Compared to control, PGE-MUM levels were significantly elevated in CFIP. PGE-MUM levels were positively correlated with FS, and inversely correlated with %DLCO in IP (FS 1-3). COX-2 was highly expressed in metaplastic epithelial cells in IPF, but lower expression of EP2 receptor was demonstrated in LFB derived from IPF. TGF-ß induced COX-2 expression in HBEC. CONCLUSIONS: PGE-MUM, elevated in CFIP, is a promising biomarker reflecting disease activity. Metaplastic epithelial cells can be a source of elevated PGE-MUM in IPF.

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis.

Fibroblastic foci, known to be the leading edge of fibrosis development in idiopathic pulmonary fibrosis (IPF), are composed of fibrogenic myofibroblasts. Autophagy has been implicated in the regulation of myofibroblast differentiation. Insufficient mitophagy, the mitochondria-selective autophagy, results in increased reactive oxygen species, which may modulate cell signaling pathways for myofibroblast differentiation. Therefore, we sought to investigate the regulatory role of mitophagy in myofibroblast differentiation as a part of IPF pathogenesis. Lung fibroblasts were used in in vitro experiments. Immunohistochemical evaluation in IPF lung tissues was performed. PARK2 was examined as a target molecule for mitophagy regulation, and a PARK2 knockout mouse was employed in a bleomycin-induced lung fibrosis model. We demonstrated that PARK2 knockdown-mediated mitophagy inhibition was involved in the mechanism for activation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway accompanied by enhanced myofibroblast differentiation and proliferation, which were clearly inhibited by treatment with both antioxidants and AG1296, a PDGFR inhibitor. Mitophagy inhibition-mediated activation of PDGFR signaling was responsible for further autophagy suppression, suggesting the existence of a self-amplifying loop of mitophagy inhibition and PDGFR activation. IPF lung demonstrated reduced PARK2 with concomitantly increased PDGFR phosphorylation. Furthermore, bleomycin-induced lung fibrosis was enhanced in PARK2 knockout mice and subsequently inhibited by AG1296. These findings suggest that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis.

Identification of pathogens by comprehensive real-time PCR versus conventional methods in community-acquired pneumonia in Japanese adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods.

Respiratory infection is a major cause of exacerbation in chronic obstructive pulmonary disease (COPD). Infectious contributions to exacerbations remain incompletely described. We therefore analyzed respiratory tract samples by comprehensive real-time polymerase chain reaction (PCR) in combination with conventional methods. We evaluated multiple risk factors for prolonged hospitalization to manage COPD exacerbations, including infectious agents. Over 19 months, we prospectively studied 46 patients with 50 COPD exacerbations, collecting nasopharyngeal swab and sputum samples from each. We carried out real-time PCR designed to detect six bacterial species and eleven viruses, together with conventional procedures, including sputum culture. Infectious etiologies of COPD exacerbations were identified in 44 of 50 exacerbations (88%). Infections were viral in 17 of 50 exacerbations (34%). COPD exacerbations caused by Gram-negative bacilli, including enteric and nonfermenting organisms, were significantly associated with prolonged hospitalization for COPD exacerbations. Our results support the use of a combination of real-time PCR and conventional methods for determining both infectious etiologies and risk of extended hospitalization.

Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

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.

PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.

Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation. Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis. Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC). Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation. To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed. PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry. We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence. CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC. Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs. These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC. Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD.

Lung adenocarcinoma complicated by Trousseau's syndrome successfully treated by a combination of anticoagulant therapy and chemotherapy.

A 63-year-old woman was diagnosed with advanced lung adenocarcinoma complicated by Trousseau's syndrome characterized by non-bacterial thrombotic endocarditis, asymptomatic brain infarction, deep venous thrombosis, and low-grade disseminated intravascular coagulation (DIC). The patient's DIC rapidly became widespread, and multiple micropulmonary embolisms led to severe respiratory failure. She received a blood transfusion and anticoagulant treatment with heparin and recombinant human soluble thrombomodulin, which modestly ameliorated her symptoms, and additional chemotherapy led to tumor shrinkage with concomitant resolution of Trousseau's syndrome. Although there are no established medical approaches for managing Trousseau's syndrome, intensive anticoagulant treatment may be effective for improving the patients' general condition in order for them to be able to undergo subsequent combination chemotherapy.

Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence.

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 ß-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.

Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence.

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 ß-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 case of Legionella pneumophila pneumonia accompanied by acute respiratory distress syndrome and epilepsy].

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.

An effective active surveillance method for controlling nosocomial MRSA transmission in a Japanese hospital.

Hospital-wide active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) targeted to adult patients with a history of MRSA carriage within the past 5 years was performed in Juntendo University Hospital (JUH) over a 2-year period. In the first year, MRSA screening culture was ordered by physicians in charge. In the second year, infection-control practitioners (ICPs) took samples for active surveillance culture. The average monthly transmission rate of MRSA in JUH was 0.35 per 1,000 bed-days in the first year and decreased significantly to 0.26 per 1,000 bed-days in the second year (P < 0.05). In the second year, more active commitment of ICPs to MRSA screening was effective in improving the performance rate of screening, shortening turn-around time of screening results, and decreasing transmission rate. Increasing compliance with active MRSA surveillance by involvement of ICPs, targeting patients with a previous history of MRSA carriage in the previous 5 years, was effective to control nosocomial MRSA transmission.

Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD.

BACKGROUND: Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure. METHODS: Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM. RESULTS: The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure. CONCLUSIONS: These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.

A survival case of invasive thymoma accompanied by acute fulminant myocarditis.

Thymomas are associated with a wide spectrum of autoimmune paraneoplastic diseases. Here we report the case of 31-year-old male with invasive thymoma, myasthenia gravis, polymyositis, and acute fulminant myocarditis that presented with cardiogenic shock requiring intra-aortic balloon pumping and percutaneous cardiopulmonary support. Corticosteroid therapy was effective. To our knowledge, this is the first case of thymoma with acute fulminant cardiomyositis that was successfully treated by assisted circulation and corticosteroids, despite a poor prognosis.

Organizing pneumonia complicated by cyst and pneumothorax formation.

We present a case of organizing pneumonia complicated by pneumothorax in association with cyst formation that developed during corticosteroid treatment. Although it has been reported that the check-valve mechanism is a plausible cause of cyst and pneumothorax formation in patients with organizing pneumonia, the details of the corresponding pathological changes that occur in air-trapping have not been elucidated. A pathological examination of lung specimens obtained with video-assisted thoracoscopic surgery suggested that granulation tissues plugging the bronchiole lumens might be a potential cause of the check-valve mechanism in this case. In this report, we also reviewed eight other cases of organizing pneumonia with pneumothorax or cyst formation.

Involvement of creatine kinase B in cigarette smoke-induced bronchial epithelial cell senescence.

Cigarette smoke induces damage to proteins and organelles by oxidative stress, resulting in accelerated epithelial cell senescence in the lung, which is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Although the detailed molecular mechanisms are not fully understood, cellular energy status is one of the most crucial determinants for cell senescence. Creatine kinase (CK) is a constitutive enzyme, playing regulatory roles in energy homeostasis of cells. Among two isozymes, brain-type CK (CKB) is the predominant CK in lung tissue. In this study, we investigated the role of CKB in cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBECs). Primary HBECs and Beas2B cells were used. Protein carbonylation was evaluated as a marker of oxidative protein damage. Cellular senescence was evaluated by senescence-associated ß-galactosidase staining. CKB inhibition was examined by small interfering RNA and cyclocreatine. Secretion of IL-8, a hallmark of senescence-associated secretary phenotype, was measured by ELISA. CKB expression levels were reduced in HBECs from patients with COPD compared with that of HBECs from nonsmokers. CSE induced carbonylation of CKB and subsequently decreased CKB protein levels, which was reversed by a proteasome inhibitor. CKB inhibition alone induced cell senescence, and further enhanced CSE-induced cell senescence and IL-8 secretion. CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD.

[A case of descending necrotizing mediastinitis caused by infection with Streptococcus agalactiae in a patient with diabetes mellitus].

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.

Neurally mediated syncope associated with small cell lung cancer: a case report and review.

We encountered a case of limited-disease small cell lung cancer with episodic syncope. The frequency of the syncopal attacks increased with the increase in the tumor size, thus a relationship was suspected to exist between the SCLC and syncope. Syncope was evaluated by history taking, 24-hour ECG monitoring, and coronary angiography. As orthostatic hypotension and cardiac disease could be excluded, we finally diagnosed this case as neurally mediated syncope. Serum tests for anti-Hu and anti-Yo antibodies were negative. A temporary pacemaker was inserted for sick sinus syndrome. This patient showed good response to the chemotherapy. No further syncopal attacks were observed after the second course of chemotherapy. Here, in addition we review four cases of SCLC with episodic syncope. Interestingly, in all cases, the tumor was located in the left hilum in close vicinity of the afferent vagal nerve (C-fibers) and mechano-receptor. Therefore, we thought that the mechanism underlying the syncope was mechano-receptor hypersensitivity.