The gene pool of influenza A viruses in aquatic birds provides all of the genetic diversity required for human and lower animals. Host range selection of the receptor binding specificity of the ...influenza virus hemagglutinin occurs during maintenance of the virus in different host cells that express different receptor sialo-sugar chains. In this paper, functional roles of the hemagglutinin and neuraminidase spikes of influenza viruses are described in the relation to 1) host range of influenza viruses, 2) receptor binding specificity of human and other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host range variation of influenza viruses, 5) role of the neuraminidase spike for the host range of influenza viruses, and 6) Development of anti-influenza drugs.
Influenza virus hemagglutinin (HA) contains antigenic sites recognized by the host immune system, cleavage sites cleaved by host proteases, receptor binding sites attaching to sialyl receptors on the ...target cell, and fusion peptides mediating membrane fusion. Change in an amino acid(s) in these sites may affect the potential of virus infection and spread within and between hosts. Influenza viruses with H1 HA infect birds, pigs and humans and have caused two of the four pandemics in the past 100 years: 1918 pandemic that killed 21–50 million people and 2009 pandemic that caused more than 18,000 deaths. Understanding the relationship between antigenic structure and immune specificity, the receptor binding specificity in virus transmission, how the cleavage site controls pathogenicity, and how the fusion peptide causes membrane fusion for the entry of influenza virus into the host cell should provide information to find more effective ways to prevent and control influenza. (Communicated by Hiroshi KIDA, M.J.A.)
Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, ...recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Almost a quarter century has passed since the first nationwide survey on ulcerative colitis (UC) and Crohn’s disease (CD) was conducted in Japan. In this study, we used a nationwide survey ...to estimate the number of patients and prevalence of these diseases in Japan in 2014.
Methods
We conducted a mail-based survey targeting hospitals to estimate the annual numbers of patients with UC and CD in 2014. Respondents were asked to report the numbers of patients who met specific diagnostic criteria for these two conditions. A stratified random sampling method was used, and a total of 3712 departments (internal medicine, surgery, pediatrics, and pediatric surgery) were selected for analysis. The overall and sex-specific annual numbers of UC and CD patients were estimated. The corresponding prevalence rates per 100,000 population were calculated by dividing the number of patients with each disease by the mid-year population of Japan in 2014.
Results
The overall survey response rate was 56.7% (2016 departments). The estimated numbers of patients with UC and CD were 219,685 (95% confidence interval: 183,968–255,403) and 70,700 (56,702–84,699), respectively. The annual prevalence rates of UC and CD per 100,000 population were 172.9 (men: 192.3; women: 154.5) and 55.6 (men: 79.5; women: 33.1), respectively. These numbers are almost tenfold increase in comparing the previous survey (22,300 in UC and 7,400 in CD). The male-to-female ratios were 1.24 for UC and 2.40 for CD, and the UC-to-CD ratio was 3.11.
Conclusions
The prevalence of UC and CD in Japan has risen substantially over the past two decades, and their disease burden requires further examination.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe ...economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry. It is unknown whether the H7N9 viruses can acquire additional mutations during their circulation in nature and become lethal to poultry and more dangerous for humans. Here, we evaluated the evolution of H7N9 viruses isolated from avian species between 2013 and 2017 in China and found 23 different genotypes, 7 of which were detected only in ducks and were genetically distinct from the other 16 genotypes that evolved from the 2013 H7N9 viruses. Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin （HA） cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet. H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
On the cell sur "face", sialoglycoconjugates act as receptionists that have an important role in the first step of various cellular processes that bridge communication between the cell and its ...environment. Loss of Sia production can cause the developmental of defects and lethality in most animals; hence, animal cells are less prone to evolution of resistance to interactions by rapidly evolved Sia-binding viruses. Obligative intracellular viruses mostly have rapid evolution that allows escape from host immunity, leading to an epidemic variant, and that allows emergence of a novel strain, occasionally leading to pandemics that cause health-social-economic problems. Recently, much attention has been given to the mutual recognition systems via sialosugar chains between viruses and their host cells and there has been rapid growth of the research field "sialoglycovirology." In this chapter, the structural diversity of sialoglycoconjugates is overviewed, and enveloped and non-enveloped viruses that bind to Sia are reviewed. Also, interactions of viral lectins-host Sia receptors, which determine viral transmission, host range, and pathogenesis, are presented. The future direction of new therapeutic routes targeting viral lectins, development of easy-to-use detection methods for diagnosis and monitoring changes in virus binding specificity, and challenges in the development of suitable viruses to use in virus-based therapies for genetic disorders and cancer are discussed.
Objectives
We examined the relationship between disease activity and anti-CADM-140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA).
Methods
Sera from 63 patients with dermatomyositis ...(DM) 46 classic DM, 17 clinically amyopathic DM (CADM) were screened for autoantibody using immunoprecipitation assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti-CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and clinical course or outcome were analyzed.
Results
Sera from 14 patients with DM (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti-CADM-140/MDA5 before treatment was significantly lower in patients who responded to therapy and survived (responder group,
n
= 4) than in those who did not respond and died (nonresponder group,
n
= 6) (110.3 vs. 356.9,
P
= 0.019). In the responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased down to below the cutoff level after treatment (
n
= 3, 113.4 vs. 1.6,
P
= 0.033), whereas that of the nonresponder group did not decrease sufficiently and sustained high level (
n
= 4, 372.5 vs. 198.4,
P
= 0.31).
Conclusions
These results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels to predict outcomes of RP-ILD as well as to monitor disease activity in patients with DM and RP-ILD.
Health-promoting effects of green tea SUZUKI, Yasuo; MIYOSHI, Noriyuki; ISEMURA, Mamoru
Proceedings of the Japan Academy, Series B,
03/2012, Volume:
88, Issue:
3
Journal Article
Peer reviewed
Open access
Green tea is manufactured from the leaves of the plant Camellia sinensis Theaceae and has been regarded to possess anti-cancer, anti-obesity, anti-atherosclerotic, anti-diabetic, anti-bacterial, and ...anti-viral effects. Many of the beneficial effects of green tea are related to the activities of (−)-epigallocatechin gallate (EGCG), a major component of green tea catechins. For about 20 years, we have engaged in studies to reveal the biological activities and action mechanisms of green tea and EGCG. This review summarizes several lines of evidence to indicate the health-promoting properties of green tea mainly based on our own experimental findings. (Communicated by Takao SEKIYA, M.J.A.)
Background
Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to ...be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response.
Methods
Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes.
Results
Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (
p
= 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95 % confidence interval 2.84–27.07,
p
< 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing.
Conclusions
IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range ...determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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