Gamma-irradiated influenza A virus provides adjuvant activity to a co-administered poorly immunogenic SFV vaccine in mice

Many currently available inactivated vaccines require "adjuvants" to maximize the protective immune responses generated against the antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU) have shown its superior efficacy compared to other forms of inactivated FLU vaccines and its ability to induce both potent interferon type-I (IFN-I) responses and the IFN-I-associated partial lymphocyte activation. Commonly, IFN-I responses induced by adjuvants, combined in vaccine preparations, have been shown to effectively enhance the immunogenicity of the antigens of interest. Therefore, we investigated the potential adjuvant activity of γ-FLU and the possible effect on antibody responses against co-administrated antigens, using gamma-irradiated Semliki Forest virus (γ-SFV) as the experimental vaccine in mice. Our data show that co-vaccination with γ-FLU and γ-SFV resulted in enhanced SFV-specific antibody responses in terms of increased titers by sixfold and greater neutralization efficacy, when compared to vaccination with γ-SFV alone. This study provides promising evidence related to the possible use of γ-FLU as an adjuvant to poorly immunogenic vaccines without compromising the vaccine efficacy of γ-FLU

Analysis of Differentially Expressed Genes in Neuroendocrine Carcinomas of the Lung

IntroductionLarge cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) show considerable differences in their histology but share neuroendocrine (NE) characteristics and also genetic and/or expression patterns.MethodsWe used the subtractive expression method to identify differences in gene expression that would allow discrimination between these two types of NE lung carcinoma.ResultsEight cDNA fragments were transcribed at a higher level in LCNEC compared with SCLC, and these corresponded to five mitochondrial genes, two ribosomal genes, and one fetal regulation factor, neuronatin (NNAT). Immunohistochemically, NNAT protein was detected in 43% (6/14) of LCNECs but in only 8% (1/13) of SCLCs (p < 0.05). Positive staining for NNAT was observed in areas that did not show the NE morphology, such as palisading and rosettes.ConclusionsThe present results suggest that NNAT has the potential to be used as a differential maker between LCNEC and SCLC

Intranasal Flu Vaccine Protective against Seasonal and H5N1 Avian Influenza Infections

Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.Mohammed Alsharifi, Yoichi Furuya, Timothy R. Bowden, Mario Lobigs, Aulikki Koskinen, Matthias Regner, Lee Trinidad, David B. Boyle and Arno Müllbache

Gamma-Irradiated Influenza Virus Uniquely Induces IFN-I Mediated Lymphocyte Activation Independent of the TLR7/MyD88 Pathway

Background: We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression of CD69 and CD86, but not CD25. This partial lymphocytes activation is mediated by type-I interferons (IFN-I). Importantly, we have shown that c-irradiated SFV does not induce IFN-I and the associated lymphocyte activation. Principal Findings: Here we report that, in contrast to SFV, c-irradiated influenza A virus elicits partial lymphocyte activation in vivo. Furthermore, we show that when using influenza viruses inactivated by a variety of methods (UV, ionising radiation and formalin treatment), as well as commercially available influenza vaccines, only c-irradiated influenza virus is able to trigger IFN-I-dependent partial lymphocyte activation in the absence of the TLR7/MyD88 signalling pathways. Conclusions: Our data suggest an important mechanism for the recognition of c-irradiated influenza vaccine by cytosolic receptors, which correspond with the ability of c-irradiated influenza virus to induce cross-reactive and cross-protective cytotoxic T cell responses.Yoichi Furuya, Jennifer Chan, En-Chi Wan, Aulikki Koskinen, Kerrilyn R. Diener, John D. Hayball, Matthias Regner, Arno Müllbacher, Mohammed Alsharif

OMAE2011-49594 DEVELOPMENT OF 6% NICKEL STEEL FOR LNG STORAGE TANKS

ABSTRACT 9% Ni steel has been used for LNG storage tanks for more than four decades although 5.5% Ni steel (N-TUF CR196) was developed in the 1970&apos;s using a special heat treatment method named L-treatment. The reason why the actual application of 5.5% Ni steel has not been attained to LNG storage tanks is mainly because the requirement of fracture properties is not confirmed for the tanks. Under the circumstances of expanding demand for natural gas and double-integrity in LNG storage tanks, we restarted developing low Ni steel for LNG storage tanks by using both conventional and advanced techniques. For the application of low Ni steel to the present LNG storage tanks, both fracture initiation and propagation properties of base metal plates and welded joints should be concerned. The fracture initiation and propagation properties of base metal were compensated with the intercritical reheating process (L-treatment), and the propagation property was additionally enhanced by combining TMCP with L-treatment. In addition, the chemical composition adjustment and the homogenization treatment of solute elements were conducted for improving the fracture initiation and propagation properties of welded joints. 6% Ni steel plates were manufactured by the process of continuous casting, reheating, hot rolling, direct quenching (TMCP), L-treatment, and tempering, and their chemical composition was 0.05C-0.06Si-1.0Mn-6.3Ni-Cr-Mo. As the results of fracture property evaluation including large-scale fracture tests such as the duplex ESSO test and the wide plate tensile test, it was demonstrated that 6% Ni steel has good characteristics regarding brittle fracture initiation and propagation in base metal plates and welded joints

Prevalence of Antimicrobial Resistance in Haemophilus influenzae and Streptococcus pneumoniae : Comparison of Clinical Isolates of Japan and The Philippines

For clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae in Japan (356 and 179 strains, respectively) and in the Philippines (98 and 59 strains, respectively), minimum inhibitory concentrations (MICs) of ampicillin, cefazolin, cefotiam, ceftizoxim, ofloxacin, erythromycin, and minocycline were examined. The rates of β-lactamase producing H. influenzae were 17.7% (63/356) in Japan and 2.0% (2/98) in the Philippines, and all of these strains were ampicillin MICs 〓1.56 ugml^. In addition, 5 strains in Japan that lacked β-lactamase activity were also less susceptible to ampicillin. Among the antimicrobials tested, ceftizoxim was the most active against H. influenzae in both countries (MICs 〓0.2 ugml^). Five strains of S. pneumoniae in Japan were relatively resistant to ampicillin (MIC=0.1 ugml^), whereas there were no such strains among isolates in the Philippines. Forty strains (22.3%) and 108 strains (60.3%) among S. pneumoniae in Japan exhibited erythromycin MICs 〓0.2 ugml^ and minocycline MICs 〓1.56 ugml^, respectively. In contrast, all isolates in the Philippines were erythromycin MICs 〓0.05 ugml^ and minocycline MICs 〓0.39 ugml^. Present study indicates that H. influenzae and S. pneumoniae in the Philippines remained still susceptible to the antimicrobials tested except for 2 β-lactamase-positive, ampicillin-resistant H. influenzae, whereas ampicillin-resistant H. influenzae mediated by β-lactamase or non-β-lactamase mechanisms and ampicillin-, erythromycin- or minocycline-resistant S. pneumoniae were included among isolates in Japan

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors