キラヤサポニン経口投与による自然免疫の活性化効果

Quillaja saponin (QS) is a food ingredient that contains triterpenoid saponins extracted from the cortex of the South American tree (Quillaja saponaria Molina), a member of the family Rosaceae. Aqueous extracts from the bark of the tree have world widely been used as an emulsifier and a foaming agent, par-ticularly in soft drinks. The present study examined an immunological function of QS as an activating agent for macrophage that is a principal phagocyte in natural immunity to prevent host from infectious pathogens. After 24 hours of oral administration of QS to mice (dose:0.5 mg/kg), both chemotactic and phagocytic activities of the macrophage prepared from either spleen cells or peritoneal exudate cells of mice tested were increased by 2-7 times in comparison to those of control mice. In addition to these results, the mice orally administered the QS shown much higher survival rate for 5 days (80%) than that of control mice (30%), when these mice were infected withE.coli (C11 strain) by intraperitoneal injection after 24hours of the oral administration of the QS. Since QS is a food additive used in the food industry, these results in the present study might lead to develop new physiological functional foods that activate natural immunity. Thus, taking foods containing QS might prevent human, especially elder people whose natural immunity is weaken by aging, from many infectious diseases

Frustration-induced eta inversion in the S=1/2 bond-alternating spin chain

We study the frustration-induced enhancement of the incommensurate correlation for a bond-alternating quantum spin chain in a magnetic field, which is associated with a quasi-one-dimensional organic compound F5PNN. We investigate the temperature dependence of the staggered susceptibilities by using the density matrix renormalization group, and then find that the incommensurate correlation becomes dominant in a certain range of the magnetic field. We also discuss the mechanism of this enhancement on the basis of the mapping to the effective S=1/2 XXZ chain and a possibility of the field-induced incommensurate long range order.Comment: 4 pages, 5 figures, replaced with revised version accepted to PR

Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin

Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset diabetes after transplantation (NODAT) in kidney transplant candidates, who had several predispositions for fluctuated HbA1c levels. Methods. We performed a retrospective study of 119 patients without diabetes who received kidney transplantation between March 2000 and January 2012. Univariate and multivariate logistic regression analyses were used to investigate the association of several parameters with NODAT. Predictive discrimination of HbA1c was assessed using a receiver-operating characteristic curve. Results. Seventeen patients (14.3%) developed NODAT within 1 year of transplantation. Univariate logistic regression analysis revealed that recipient age, gender, and HbA1c were predictors of NODAT. In the multivariate analysis, the association between pretransplant HbA1c and NODAT development did not reach statistical significance ( = 0.07). To avoid the strong influence of high-dose erythropoietin on HbA1c levels, we performed subgroup analyses on 85 patients receiving no or low-dose (≤6000 IU/week) erythropoietin. HbA1c was again an independent predictor for NODAT. Receiver-operating characteristic analysis revealed a cut-off value of 5.2% with an optimal sensitivity of 64% and specificity of 78% for predicting NODAT. Conclusions. Our results reveal that the pretransplant HbA1c level is a useful predictor for NODAT in patients receiving no or low-dose erythropoietin

Mucosal gene therapy using a pseudotyped lentivirus vector encoding murine interleukin-10 (mIL-10) suppresses the development and relapse of experimental murine colitis

BACKGROUND: Therapeutic gene transfer is currently being evaluated as a potential therapy for inflammatory bowel disease. This study investigates the safety and therapeutic benefit of a locally administered lentiviral vector encoding murine interleukin-10 in altering the onset and relapse of dextran sodium sulfate induced murine colitis. METHODS: Lentiviral vectors encoding the reporter genes firefly-luciferase and murine interleukin-10 were administered by intrarectal instillation, either once or twice following an ethanol enema to facilitate mucosal uptake, on Days 3 and 20 in Balb/c mice with acute and relapsing colitis induced with dextran sulfate sodium (DSS). DSS colitis was characterized using clinical disease activity, macroscopic, and microscopic scores. Bioluminescence optical imaging analysis was employed to examine mucosal lentiviral vector uptake and transgene expression. Levels of tumor necrosis factor-α and interleukin-6 in homogenates of rectal tissue were measured by ELISA. Biodistribution of the lentiviral vector to other organs was evaluated by real time quantitative PCR. RESULTS: Mucosal delivery of lentiviral vector resulted in significant transduction of colorectal mucosa, as shown by bioluminescence imaging analysis. Lentiviral vector-mediated local expression of interleukin-10 resulted in significantly increased levels of this cytokine, as well as reduced levels of tumor necrosis factor-α and interleukin-6, and significantly reduced the clinical disease activity, macroscopic, and microscopic scores of DSS colitis. Systemic biodistribution of locally instilled lentiviral vector to other organs was not detected. CONCLUSIONS: Topically-delivered lentiviral vectors encoding interleukin-10 safely penetrated local mucosal tissue and had therapeutic benefit in this DSS model of murine colitis

Universal temperature dependence of electron number in one-dimensional Hubbard model

We investigate the temperature region in which a Tomonaga-Luttinger liquid (TLL) description of the charge sector of the one-dimensional Hubbard model is valid. By using the thermodynamic Bethe ansatz method, electron number is calculated at finite temperatures and fixed chemical potential. We observe maximum electron number as a function of temperature close to the chemical potential of the upper critical value that corresponds to half filling. As the chemical potential approaches the upper critical value from below, the temperature $(T_{\rm M})$ at which the electron number shows its maximum asymptotically approaches a universal relation. We show that, below the energy corresponding to $T_{\rm M}$, the charge excitation spectrum nearly obeys a linear dispersion relation. The results demonstrate that $T_{\rm M}$ marks the important temperature below which TLL is realized.Comment: 4 pages, 4 figure

Tomonaga-Luttinger liquid in quasi-one-dimensional antiferromagnet BaCo2V2O8 in magnetic fields

Motivated by recent studies on the quasi-one-dimensional (1D) antiferromagnet BaCo2V2O8, we investigate the Tomonaga-Luttinger-liquid properties of the 1D S=1/2 XXZ Heisenberg-Ising model in magnetic fields. By using the Bethe ansatz solution, thermodynamic quantities and the divergence exponent of the NMR relaxation rate are calculated. We observe a magnetization minimum as a function of temperature (T) close to the critical field. As the magnetic field approaches the critical field, the minimum temperature asymptotically approaches the universal relation in agreement with the recent results by Maeda et al. in Phys. Rev. Lett. 99 (2007) 057205. We observe T-linear specific heat below the temperature of the magnetization minimum. The field dependence of its coefficient agrees with the results based on conformal field theory. The field dependence of the divergence exponent of the NMR relaxation rate with decreasing temperature is obtained, indicating a change in the critical properties. The results are discussed in connection with experiments on BaCo2V2O8.Comment: 5 pages, 6 figures, J. Phy. Soc. Jpn 77, 074717 (2008

Change of Positive Selection Pressure on HIV-1 Envelope Gene Inferred by Early and Recent Samples

HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo- and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways