bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Morbillivirus Receptor SLAM (CD150)
Authors: Tatsuo Hironobu , Yanagi Yusuke 
Published: November 2013

AbstractMorbilliviruses are highly contagious pathogens that cause some of the most devastating viral diseases of humans and animals, including measles virus (MV), canine distemper virus (CDV), and rinderpest virus (RPV). They replicate mainly in lymphoid organs throughout the body and cause severe immunosuppression accompanied with lymphopenia. We have recently shown that human, canine, and bovine signaling lymphocyte activation molecules (SLAMs; also known as CD150) act as cellular receptors for MV, CDV, and RPV, respectively. In these three morbilliviruses, all strains examined were shown to use SLAMs of their respective host species, and laboratory strains passaged on SLAM‐negative cells were found to use, besides SLAM, alternative receptors, such as human CD46 for the Edmonston strain of MV. The use of SLAM as a receptor may be a property common to most, if not all, of the members of morbilliviruses. Human SLAM is a membrane glycoprotein selectively expressed on the cells of the immune system (immature thymocytes, activated lymphocytes, activated monocytes, and mature dendritic cells) and seems to mediate lymphocyte activation and to control interferon‐γ production. The destruction and/or impairment of infected SLAM‐positive cells may be a mechanism for the immunosuppression induced by morbilliviruses, but other mechanisms may be also involved.
Fine Mapping of the Subunit Binding Sites of Influenza Virus RNA Polymerase
Authors: Ohtsu Yasushi , Honda Yoshikazu , Sakata Yasutaka , Kato Hirohisa , Toyoda Tetsuya 
Published: November 2013

AbstractInfluenza virus RNA polymerase consists of three subunits, PB1, PB2 and PA, and catalyzes both transcription and replication of the RNA genome. PB1 is a catalytic subunit of RNA polymerization and a core of the subunit assembly. The subunit binding sites were mapped at about several hundred amino‐acid size. Fine mapping of the subunit binding sites was determined. The PB1‐PA binding regions were mapped within in the N‐terminal 25 amino acids of PB1 and 668–692 of PA. PB1 and PB2 interacted within wider regions, 600–757 of PB1 and 51–259 of PB2. In these amino‐acid spans, 206–259 of PB2 may be the most important region of PB1 binding and 718–732 of PB1 may be the most important region of PB2 binding because the binding activity was lost when the regions were lost in the subunits. The additional regions contributed to strong binding of these subunits.
Detection of Herpesvirus DNA in the Serum of Immunocompetent Children
Authors: Hara Shinya , Kimura Hiroshi , Hoshino Yo , Tanaka Naoko , Nishikawa Kazuo , Ihira Masaru , Yoshikawa Tetsushi , Morishima Tsuneo 
Published: November 2013

AbstractThe DNA of herpesviruses such as Epstein‐Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus‐6 (HHV6), and human herpesvirus‐7 (HHV7) has been detected in the serum of patients with primary infection or with immunosuppression. However, it is unknown how frequently herpesvirus DNA can be detected in the serum of immunocompetent children, or whether the detection of herpesvirus DNA indicates an active infection or virus‐related diseases. Using a real‐time polymerase chain reaction assay, attempts were made to detect herpesvirus DNA in the serum of 176 ambulatory children who visited a hospital for various reasons. EBV was detected in 4 (2.2%), HHV6 in 4 (2.2%), and HHV7 in 2 (1.1%) of 176 children, but CMV was not detected. Of the 10 positive patients, only 4 were considered, by virtue of clinical and serological characteristics, to have primary infections. The other 4 positive patients had other infections, such as mycoplasma and salmonella. Although herpesvirus DNA could be detected in the serum of immunocompetent children, there was not always a relationship between clinical manifestations and the detection of virus DNA. When herpesvirus DNA is detected in the serum, a careful interpretation is necessary to diagnose a primary infection or a virus‐associated disease.
IL‐10 Producing CD14low Monocytes Inhibit Lymphocyte‐Dependent Activation of Intestinal Epithelial Cells by Commensal Bacteria
Authors: Haller Dirk , Serrant Patrik , Peruisseau Genneviève , Bode Christiane , Hammes Walter P. , Schiffrin Eduardo , Blum Stephanie 
Published: November 2013

AbstractIntestinal epithelial cell (IEC) activation by non‐pathogenic, commensal bacteria was demonstrated to require the presence of immunocompetent cells. In this study, HT‐29 and CaCO‐2 transwell cultures, reconstituted with CD4+ and CD8+ T cells, CD19+ B cells and CD14high monocytes, were challenged with nonpathogenic Gram negative Escherichia coli and Gram positive lactobacilli. Cytokine expression was analysed by reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme linked immunosorbent assays (ELISA). Expression of tumour necrosis factor alpha (TNF‐α) and interleukin (IL)‐8 mRNA in E. coli or L. sakei challenged IEC was promoted by lymphocyte populations predominantly CD4+ T cells, while monocytes failed to mediate an inflammatory cytokine response. The monocyte phenotype and function were further characterised by flow cytometry and mixed lymphocyte reaction (MLR). During the co‐culture with IEC and bacterial stimulated IEC, CD14high peripheral blood monocytes acquired a CD14low CD16low phenotype with reduced expression co‐stimulatory (CD80, CD86, CD58) cell surface molecules. Immunosuppressive functions of IEC conditioned CD14low monocytes were demonstrated by the predominant secretion of IL‐10 and IL‐1Ra and their reduced potential to trigger an allogeneic lymphocyte response. In conclusion, IEC contribute to the development of CD14low CD16low monocytes with immunosuppressive function and antagonised a lymphocyte‐mediated activation of the intestinal epithelium in response to intestinal and food derived bacteria. These results strengthen the hypothesis that the gut epithelium constitutes an important functional element in the regulation of mucosal immune homeostasis towards commensal bacteria.
Phylogenetic Analysis of Spotted Fever Group Rickettsiae Isolated from Ticks in Japan
Authors: Ishikura Mitsuhiro , Fujita Hiromi , Ando Shuji , Matsuura Kumiko , Watanabe Mamoru 
Published: November 2013

AbstractEight spotted fever group (SFG) rickettsiae isolated from ticks in Japan were classified by phylogenetic analysis based on the nucleotide sequences of both the citrate synthase‐encoding gene (gltA) and 190‐kDa antigen‐encoding gene (rOmpA). In the phylogenetic tree of gltA, strains DT‐1 and FLA‐1 isolated from the Dermacentor taiwanensis and Haemaphysalis frava ticks, respectively, were placed as Rickettsia japonica, and strains IO‐1, IO‐2, IO‐25, IM‐1 and IP‐2 from genus Ixodes ticks were placed as Rickettsia helvetica. Strain AT‐1 isolated from the Amblyomma testudinarium belonged to the cluster including Rickettsia akari, Rickettsia australis and Rickettsia felis. In the phylogenetic tree of the rOmpA, strains DT‐1 and FLA‐1 were placed as R. japonica, and strain AT‐1 belonged to the cluster including Rickettsia cooleyi and the symbiont of Ixodes scapularis. The rOmpA fragments of 5 Ixodes isolates could not be amplified by PCR. The present study showed that strains DT‐1 and FLA‐1 were genotypically identical to R. japonica, and 5 Ixodes isolates were associated with the R. helvetica. Based on previous genotypic and antigenic data, and the phylogenetic analysis presented here, strain AT‐1 should be considered as a new species among SFG rickettsiae.
Mycoplasmal Lipoproteins Induce Toll‐Like Receptor 2‐ and Caspases‐Mediated Cell Death in Lymphocytes and Monocytes
Authors: Into Takeshi , Nodasaka Yosinobu , Hasebe Akira , Okuzawa Tsugumi , Nakamura Jun‐ichiro , Ohata Noboru , Shibata Ken‐ichiro 
Published: November 2013

AbstractLipoproteins of Mycoplasma salivarium and Mycoplasma fermentans preferentially induced necrotic cell death in lymphocytic cell lines, MOLT‐4 and Raji, and in one monocytic cell line, THP‐1, whereas they preferentially induced apoptotic cell death in another monocytic cell line, HL‐60. These findings were also supported by ultrastructural observations by the use of scanning and transmission electron microscopes and by agarose gel electrophoresis of the genomic DNA. The lipoproteins activated caspase‐3 in both MOLT‐4 and HL‐60 cells, which was assessed by the cleavage of the synthetic substrate DEVD‐pNA and the endogenous substrate poly(ADP‐ribose) polymerase. The cytotoxicity to MOLT‐4 and HL‐60 cells was inhibited by various caspase inhibitors, Ac‐DMQD‐CHO, Ac‐IETD‐CHO, and Z‐VAD‐FMK. The cytotoxicity was also partially suppressed by the monoclonal antibody to Toll‐like receptor 2. Thus this study demonstrated that mycoplasmal lipoproteins induce caspases‐dependent necrotic and apoptotic cell death in lymphocytes and monocytes/macrophages, which is partially induced by TLR2‐mediated signaling.
Persistent Parapoxvirus Infection in Cattle
Authors: Iketani Yuko , Inoshima Yasuo , Asano Akihiro , Murakami Kenji , Shimizu Shinya , Sentsui Hiroshi 
Published: November 2013

AbstractThe possibility of persistent parapoxvirus (PPV) infection was investigated by serologically and genetically using cattle infected with the virus experimentally and naturally. Three cattle were inoculated with the virus subcutaneously at several spots in the lips and abdominal regions. Small papules developed in the inoculated regions, and antibodies to the virus developed and continued persistently. One animal, from which one PPV had been previously isolated, was also subjected to serological and viral detection tests as a naturally infected case. Two of these four cattle were injected with dexamethasone (DM), and one was injected with interferon‐γ (IFN‐γ). The viral genome was rarely detected from the peripheral blood leukocytes in the ordinary condition, but frequently when the animals were injected with IFN‐γ. The viral genome was also detected from the lymph nodes as these PPV infected animals were euthanized. These results indicated that cattle were infected with PPV subclinically and persistently, and the virus was activated in stressed or immunosuppressed animals. The virus would be harbored in the lymphotic tissues of the animals when they show no clinical symptoms.
Protection of Mice from Lethal Endogenous Candida albicans Infection by Immunization with Candida Membrane Antigen
Authors: Tansho Shigeru , Abe Shigeru , Mizutani Shigetoshi , Ono Yasuo , Takesako Kazutoh , Yamaguchi Hideyo 
Published: November 2013

AbstractThe protective effects of immunization with Candida membrane antigen (CMA) on a systemic infection originating from intestinally colonized Candida albicans were examined. The colonization of orally inoculated C. albicans in the intestinal tract was established in BALB/c mice that had been concomitantly treated with oral doses of antibacterial drugs. In these animals, a systemic dissemination of C. albicans with fatal outcome was induced by a repeated dosing of prednisolone. In this endogenous infection model, the effects of immunization by CMA on the infection were examined. CMA‐immunized mice showed a longer lifespan than unimmunized mice. The protective effect of CMA immunization in immunosuppressed mice was also measured by a decrease in body weight loss after treatment with prednisolone and in the number of viable Candida cells in the target organs, the kidneys and livers. However, the CFU of C. albicans in the intestinal tract was not significantly lowered. These results suggest that CMA immunization inhibited the dissemination of systemic Candida infection from the intestinal tract induced by treatment with prednisolone.
A Novel Mechanism of Fluconazole Resistance Associated with Fluconazole Sequestration in Candida albicans Isolates from a Myelofibrosis Patient
Authors: Maebashi Kazunori , Kudoh Michinari , Nishiyama Yayoi , Makimura Koichi , Uchida Katsuhisa , Mori Takeshi , Yamaguchi Hideyo 
Published: November 2013

AbstractA series of 10 strains of Candida albicans, from TIMM 3309 to TIMM 3318, were repeatedly isolated in one myelofibrosis‐complicated patient with recurrent candidemia. The latter five isolates, from TIMM 3314 to TIMM 3318, became suddenly resistant to fluconazole during the 10 to 16 weeks after antimycotic therapy. We investigated the resistant mechanism of fluconazole using one susceptible isolate and two of the five resistant isolates in the series. The ergosterol synthesis by cell‐free extracts from the two resistant isolates was less susceptible to fluconazole partly as a result of a decreased affinity of cytochrome P‐450. Unexpectedly, these two resistant isolates showed higher levels of an intracellular accumulation of [3H]fluconazole than the susceptible isolate and the control strain of C. albicans ATCC 10231. In the resistant isolate, TIMM 3318, most intracellular incorporated fluconazole was distributed in the 12,000 × g pellet (P‐120) fraction by centrifugation unlike the two susceptible strains. An observation of the ultrastructure of TIMM 3318 showed the most notable alteration to be the characteristic appearance of numerous vesicular vacuoles (diameter, 150 to 400 nm); these vacuoles were not observed, however, in either of the susceptible strains. A direct observation of the subcellular fraction prepared from TIMM 3318 by the electron microscopy negative‐staining method suggests that most of the vesicular vacuoles were recovered in the P‐120 fraction. These results suggest that fluconazole sequestration caused by vesicular vacuoles of the resistant isolate might act as a novel mechanism of fluconazole resistance besides the decreased affinity of cytochrome P‐450.
Physicochemical and Biological Properties of an Extracellular Serine Protease of Aeromonas sobria
Authors: Yokoyama Ritsuko , Fujii Yoshio , Noguchi Yoko , Nomura Tomohiko , Akita Masahiko , Setsu Kojun , Yamamoto Shigeo , Okamoto Keinosuke 
Published: November 2013

AbstractPreviously, we cloned a protease gene of Aeromonas sobria, determined its nucleotide sequence and established a method of purifying its product. In this study, we examined the properties of the purified protease. The protease was temperature‐labile and had an optimal pH of 7.5. Metallo‐protease inhibitors and a cysteine protease inhibitor did not block the proteolytic activity of the enzyme. The treatment with reagents to modify sulfhydryl group did not reduce the activity. But, serine protease inhibitors did, showing that it was a serine protease. Subsequently, we examined the ability of the protease to enhance vascular permeability in dorsal skin. The protease showed activity and the reaction was inhibited by a simultaneously injected antihistaminic agent. Histopathological examination showed that mast cells appeared around the site where the protease was injected. These findings show that the vascular permeability‐enhancing effect of the protease is due to histamine released at the site. Furthermore, we found that a soybean trypsin inhibitor (Kunitz) did not block the proteolytic action of the protease in vitro, but inhibited its vascular permeability‐enhancing activity in skin. This suggests that a trypsin‐like protease from skin mediates the activity of the protease to enhance its vascular permeability.
Computer Simulations of Slow Progression of Human Immunodeficiency Virus Infection and Relapse during Anti‐HIV Treatment with Reverse Transcriptase Inhibitors and Protease Inhibitors
Authors: Takayanagi Toshiaki , Ohuchi Azuma 
Published: November 2013

AbstractHuman immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been very serious problems since the 1980s. The progression of HIV infection into AIDS can be suppressed to some extent with reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs); however, there are some serious problems with treatments using the anti‐HIV drugs (e.g. very high expense, complicated administration, and drug resistance). Hence, more studies on HIV and the development of more effective anti‐HIV treatments are required. We consider it important to understand the complex dynamics involved in HIV infection, and we therefore propose new mathematical models of HIV infection. In the modeling, we have paid attention to the nonlinear relations between stimuli and responses (i.e., when responses are plotted against the logarithm of stimuli, a sigmoid curve is obtained), and to lymphoid organs which seem more important than the blood compartment (i.e., lymphoid organs are major reservoirs of HIV virions and contain most of the lymphocytes). Using the models, we have found that viral antigenic mutation plays an important role in the slow progression in the chronic phase of HIV infection. We have also found that viral antigenic mutation can cause relapse of HIV infection when the inhibition rate of anti‐HIV drugs is low and that viral antigenic mutation cannot cause relapse when the inhibition rate is high.
In Vivo Fungicidal Effect of KP‐103 in a Guinea Pig Model of Interdigital Tinea Pedis Determined by Using a New Method for Removing the Antimycotic Carryover Effect
Authors: Tatsumi Yoshiyuki , Yokoo Mamoru , Arika Tadashi , Yamaguchi Hideyo 
Published: November 2013

AbstractWe developed a new technique for culture study that successfully recovers fungi from drug‐treated skin tissues, in which tissue specimens were homogenized, dialyzed against water, digested with trypsin, and then washed with PBS, to eliminate the drug that remaining in the skin tissue specimens. With this modified culture method, we reevaluated the efficacy of KP‐103, neticonazole, and lanoconazole in a guinea pig interdigital tinea pedis model. Guinea pigs with tinea pedis were topically treated with a 1% solution of KP‐103 or a reference drug once a day for 10 consecutive days. Five days after the last treatment, left and right feet were subjected to culture study by the conventional and modified recovery culture methods, respectively. One hundred percent (20/20) of lanoconazole‐treated feet were judged as culture‐negative by the conventional culture method, but 85% (17/20) of the feet were shown to be culture‐positive when the modified recovery culture method was used. On the other hand, KP‐103 achieved high rates of culture‐negative rates, 95% (19/20) and 85% (17/20), in both conventional and modified culture methods, respectively. Furthermore, on day‐30 posttreatment, KP‐103 sterilized 14 of the 20 infected feet, whereas neticonazole and lanoconazole were not effective even in reducing fungal burden. KP‐103 proved to be highly effective in achieving mycological cure and preventing relapse against tinea pedis presumably because of its good bioavailability in the skin based on its low keratin‐affinity, along with its potent antifungal activity.
Intraperitoneal Immunization Led to T Cell Hyporesponsiveness to Helicobacter pylori Infection in Mice
Authors: Watanabe Koichiro , Murakami Kazunari , Maeda Kosaku , Fujioka Toshio , Nasu Masaru , Nishizono Akira 
Published: November 2013

AbstractDuring Helicobacter pylori infection, T cell response is critical in the development of active gastritis and in protective immunity against infection. We studied gastric inflammation and T cell response in H. pylori‐challenged mice following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in the absence of adjuvants. H. pylori‐challenged mice without immunization developed moderate to severe gastric inflammation, and splenocytes from these mice produced Th1 polarizing cytokines in response to HpAg and Con A during the acute infection. On the other hand, immunized‐challenged mice (those inoculated with H. pylori following immunization) had little or no gastric inflammation despite persistent H. pylori colonization. Our immunization primed splenocytes to produce IL‐2, IFN‐γ, and IL‐4 in response to HpAg and Con A before infection. However, these cells became hyporesponsive to both stimulants immediately after live bacterial challenge in terms of the production of these cytokines, especially IL‐2 and IFN‐γ. CTLA‐4 has been documented to be a negative regulator of IL‐2 production and lymphoproliferation that induces peripheral tolerance and functions 24–72 hr after the initiation of T cell activation. Compared with challenged mice, T cells from immunized‐challenged mice showed higher levels of CTLA‐4 expression at 72 hr after oral challenge. These data suggested that our immunization inhibited the development of H. pylori‐associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA‐4 following challenge.
Studies on the Rabies Virus RNA Polymerase: 3. Two‐Dimensional Electrophoretic Analysis of the Multiplicity of Non‐Catalytic Subunit (P Protein)
Authors: Eriguchi Yoshiro , Toriumi Harufusa , Kawai Akihiko 
Published: November 2013

AbstractWe described previously (Takamatsu et al., 1998. Microbiol. Immunol. 42: 761–771) the rabies virus P protein as being composed of several components of different sizes, among which the full‐sized major components were termed as p40 and p37 according to their electrophoretic mobilities, and radiolabeling studies with [32P]phosphate implied that p40 was a hyperphosphorylated form. We further examined here these proteins by two‐dimensional (2‐D) gel electrophoresis and immunoblotting, showing that a major component, p37, was composed of multiply modified subcomponents of different pIs (termed p37–1, p37–2, p37–3, etc., based on their acidity) in the virion and infected cells, but the unmodified precursor (termed p37–0) was little in amount. The viral nucleocapsid (NC)‐bound P proteins were composed of multiple forms of p37 (the major one was p37–1) and also a minor component, p40–1. P proteins which were bound to newly synthesized free N proteins were mostly composed of p37–1, indicating that hyperphosphorylation of P proteins occurred after their being used for the encapsidation. Treatment of the infected cells with okadaic acid induced accumulation of the more acidic forms of P proteins, suggesting that heterogeneity in the full‐sized P proteins is a reflection of their dynamic aspects of multiple cycles of phosphorylations and dephosphorylations in the cell. Two‐D gel analyses demonstrated also that p40 was not so acidic as we expected, and implied that our previous data of apparent hyperphosphorylation of p40 was due to very frequently recycled utilization of the protein, and preformed non‐labeled P proteins were also 32P‐phosphorylated in a radiolabeling period and were converted to the p40.
An Application of Microplate Hybridization Assay for the Confirmation and Probe Typing of “Norwalk‐Like Viruses”
Authors: Fukuda Shinji , Takao Shinichi , Shimazu Yukie , Miyazaki Kazuo 
Published: November 2013

Abstract“Norwalk‐like virus” (NLV) genomes are generally detected by using reverse transcription‐PCR and confirmed by blot hybridization and nucleotide sequencing because of their fastidious nature. In the present study, the confirmation and typing of NLV genomes were carried out using a streptavidin‐biotin binding technique and microplate hybridization assay with digoxigenin labeled probes. Eight probe typing sets (G1A, G1B, G2A, G2B, G2C, G2D, G2E, and G2F) formatted from 6 newly designed probes and 8 probes reported elsewhere were used for hybridization. The correlation between probe typing and nucleotide sequencing was found and our 8 probe sets were useful for the typing of NLVs.