Yukimasa Ooi

Myocarditis Associated with Influenza A H1N1pdm2009

Acute myocarditis is a well-known complication of influenza infection. The frequency of myocardial involvement in influenza infection varies widely, with the clinical severity ranging from asymptomatic to fulminant varieties. The worst cases can result in death due to impaired cardiac function, although such fulminant myocarditis associated with influenza infection is rare, as shown by previous papers. Following the 2009 influenza pandemic, we reported on the clinical features of a cohort of 15 patients in Japan with H1N1pdm2009 myocarditis. In our subsequent survey of the literature for case reports or series of patients with myocarditis associated with H1N1pdm2009, we identified 58 detailed cases. We discuss here the high prevalence of fulminant myocarditis (36/58, 62%) among patients reported to have myocarditis associated with H1N1pdm2009. Mechanical circulatory support was required in 17 of the patients with fulminant myocarditis, 13 of whom recovered. We stress the need for increased awareness of influenza-associated myocarditis; such knowledge will facilitate earlier diagnosis and treatment of this fatal complication during future influenza pandemics.

Nanotransportation system for cholera toxin in Vibrio cholerae 01.

Vibrio cholerae (V. cholerae) cholera toxin (CT), which causes a severe watery diarrheal illness, is secreted via the type II secretion machinery; it remains unclear, however, how this toxin is transported toward the machinery. In this study, we determined that the pH-dependent intrabacterial transport system correlates with the priming of CT secretion by V. cholerae. The secretion and production of V. cholerae treated at different pHs were examined by enzyme immunoassay. The localization of the CT was analyzed by immunoelectron microscopy. The CT secretion level rapidly increases in the alkaline-pH-treated V. cholerae but does so more slowly in neutral- and acidic-pH-treated V. cholerae. The CT was found to be densely localized near the membrane in the alkaline-pH-treated bacterial cytoplasm, suggesting that the CT shifts from the center to the peripheral portion of the cytoplasm following an extracellular rise in pH. The shift was observed in V. cholerae treated at alkaline pH for more than 10 min. The pH treatment did not enhance CT production at the same stage at which secretion and intrabacterial transport of the CT were enhanced. We propose that V. cholerae possesses a pH-dependent intrabacterial nanotransportation system that probably accelerates priming for CT secretion.

National Survey of Influenza Myocarditis in Japanese Children in Three Seasons

An Influenza pandemic occurred in 2009. A nationwide, retrospective survey of Influenza myocarditis in Japanese children in 3 consecutive Influenza seasons was performed to compare Influenza myocarditis in the 2009/2010 season (the pandemic season), the 2010/2011 season, and the 2011/2012 season, by mailing questionnaires to 514 hospitals in Japan that have pediatric departments and collecting data from 285 hospitals. A questionnaire-based survey related to Influenza myocarditis was also conducted to evaluate the attitudes of Japanese pediatricians concerning the diagnosis of Influenza myocarditis. Fifteen Influenza myocarditis patients were reported, with 8 (H1N1pdm:6, type A:1, type B:1) from the 2009/10 season, 4 (type A:1, type B:3) from the 2010/11 season, and 3 (type B:3) from the 2011/12 season. Only 8 patients with Influenza A virus myocarditis were reported, with 7 patients from the 2009/2010 season, one from the 2010/2011 season, and none in the 2011/2012 season. Mortality was 33.3% (5/15) among the myocarditis patients. Twelve patients (12/15, 80%) were diagnosed with fulminant myocarditis with fatal arrhythmias and/or cardiogenic shock. In the pediatricians’ attitude survey, only 3.3% of pediatricians routinely examined the electrocardiograms of children hospitalized with Influenza infection in Japan. The number of Japanese children with myocarditis associated with Influenza A virus seemed to increase in the pandemic season. Increased awareness of Influenza myocarditis in children is needed during future Influenza pandemics.

Route of intrabacterial nanotransportation system for CagA in Helicobacter pylori

Helicobacter pylori (H. pylori) possesses an intrabacterial nanotransportation system (ibNoTS) for transporting CagA and urease within the bacterial cytoplasm; this system is controlled by the extrabacterial environment. The transportation routes of the system have not yet been studied in detail. In this study, we demonstrated by immunoelectron microscopy that CagA localizes closely with the MreB filament in the bacterium, and MreB polymerization inhibitor A22 obstructs ibNoTS for CagA. These findings indicate that the route of ibNoTS for CagA is closely associated with the MreB filament. Because these phenomena were not observed in ibNoTS for urease, the route of ibNoTS for CagA is different from that of ibNoTS for urease as previously suggested. We propose that the route of ibNoTS for CagA is associated with the MreB filament in H. pylori.

Morphology and infectivity of virus that persistently caused infection in an AGS cell line

A recent report has indicated that proteins and genes of simian virus 5 (SV5) are detected in a human gastric adenocarcinoma (AGS) cell line, which is widely provided for oncology, immunology, and microbiology research. However, the production of infective virions has not been determined in this cell line. In this study, the morphology and infectivity of the virus particles of the AGS cell line were studied by light and electron microscopy and virus transmission assay. The virus particles were approximately 176.0 ± 41.1 nm in diameter. The particles possessed projections 8–12 nm long on the surface and contained a nucleocapsid determined to be 13–18 nm in width and less than 1,000 nm in length. The virus was transmissible to the Vero cell line, induced multinuclear giant cell formation, and reproduced the same shape of antigenic virions. In this study, the persistently infected virus in the AGS cell line was determined to be infective and form reproducible virions, and a new morphological feature of SV5 was determined.

Enhancement of adherence of Helicobacter pylori to host cells by virus: possible mechanism of development of symptoms of gastric disease

It remains unclear why gastric disease does not develop in all cases of Helicobacter pylori infection. In this study, we analyzed whether simian virus 5 (SV5) enhanced adherence of H. pylori to adenocarcinoma epithelial cells (AGS). H. pylori in AGS (harboring SV5) and SV5-infected Vero cells, and an agglutination of H. pylori mixed with SV5 were observed by light microscopy, scanning and transmission electron microscopies. The adherent rate of H. pylori to SV5-infected Vero cells and treated with an anti-SV5 antibody was determined. H. pylori adhered to the surface of AGS cells near SV5 particles, as shown by scanning and transmission electron microscopies. The adherence of H. pylori to SV5-infected Vero cells was significantly enhanced compared with that to Vero cells. In contrast, the adherence of H. pylori to Vero cells was decreased by treatment with the anti-SV5 antibody. Agglutination of H. pylori mixed with SV5 was observed by scanning and transmission electron microscopies. Agglutination did not occur when SV5 was treated with the anti-SV5 antibody before mixing. These findings demonstrated that SV5 enhanced the adherence of H. pylori to host cells, suggesting that a persistently infected virus may be a factor enhancing the pathogenicity of H. pylori in humans.

Bacillus cereus pneumonia in an immunocompetent patient: a case report

BackgroundBacillus cereus (B. cereus) rarely causes lower respiratory tract infections, although most reported cases of B. cereus pneumonia are fatal despite intensive antibiotic therapy. We present a case of B. cereus pneumonia in an immunocompetent patient.Case presentationAn 81-year-old woman was transferred from a district general hospital to our hospital for treatment of congestive heart failure. The patient presented with a nonproductive cough, dyspnea, edema in both lower extremities, orthopnea, fever, and occult blood in the stool. A chest radiograph indicated bilateral pleural effusion and pulmonary congestion. After diuretic therapy and chest drainage, bilateral pleural effusion and pulmonary congestion improved. On day 2, she experienced severe respiratory distress. B. cereus was isolated from two blood sample cultures. On day 4, her condition had progressed to severe respiratory distress (PaO2/FiO2 ratio = 108). A chest radiograph and computed tomography indicated extensive bilateral infiltrates. She was transferred to the intensive care unit and was intubated. B. cereus was also isolated from five blood sample cultures at that time. After isolating B. cereus, we switched antibiotics to a combination of imipenem and levofloxacin, which were effective. She had no history of immunodeficiency, surgery, ill close contacts, risk factors for HIV or tuberculosis, recent central venous catheter insertion, or anthrax vaccination. She improved and was discharged from the intensive care unit after several days.ConclusionThis is a rare case of B. cereus pneumonia in an immunocompetent patient, who subsequently recovered. Bacillus should be considered as a potential pathogen when immunocompetent patients develop severe pneumonia.

The Neuraminidase Inhibitor Peramivir Ameliorates Myocarditis Induced byInfluenza A (H1n1pdm) Virus in a Murine Model

Severe influenza sometimes causes myocarditis. To analyze the effects of peramivir on influenza A (H1N1pdm) virus myocarditis, we investigated survival rates, cardiac function, histological findings and cytokine induction in murine influenza A (H1N1pdm) virus-induced myocarditis. Eight-week-old BALB/c male mice were infected intranasally with influenza A (H1N1pdm) virus, and then divided into 2 groups: control group, which was injected with saline; and peramivir-treatment group, which was treated with peramivir. Histological studies, echocardiograms and quantitative analysis of viral RNA and mRNA for inflammatory cytokines and adhesion molecules were performed. Treatment with peramivir led to a significant improvement in survival (p<0.01 vs. control group). Fractional shortening (FS) of peramivir-treatment group (44.7%, p<0.01) was significantly higher than that of control group (27.7%) on day 8. Histological examinations revealed localized myocarditis with lymphocyte infiltration, and myocarditis lesions were found in perivascular areas or associated with pericarditis; treatment with peramivir improved these findings. Quantity of influenza virus genome in heart and lung tissues was suppressed in peramivirtreatment group. The expression of cytokine and adhesion molecule mRNA was suppressed in peramivir-treatment group. Peramivir improved influenza A (H1N1pdm) virus-induced myocarditis.