The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.

In 1907 Kikunae Ikeda, a professor at the Tokyo Imperial University, began his research to identify the umami component in kelp. Within a year, he had succeeded in isolating, purifying, and identifying the principal component of umami and quickly obtained a production patent. In 1909 Saburosuke Suzuki, an entrepreneur, and Ikeda began the industrial production of monosodium l-glutamate (MSG). The first industrial production process was an extraction method in which vegetable proteins were treated with hydrochloric acid to disrupt peptide bonds. l-Glutamic acid hydrochloride was then isolated from this material and purified as MSG. Initial production of MSG was limited because of the technical drawbacks of this method. Better methods did not emerge until the 1950s. One of these was direct chemical synthesis, which was used from 1962 to 1973. In this procedure, acrylonitrile was the starting material, and optical resolution of dl-glutamic acid was achieved by preferential crystallization. In 1956 a direct fermentation method to produce glutamate was introduced. The advantages of the fermentation method (eg, reduction of production costs and environmental load) were large enough to cause all glutamate manufacturers to shift to fermentation. Today, total world production of MSG by fermentation is estimated to be 2 million tons/y (2 billion kg/y). However, future production growth will likely require further innovation.

Roles of type II pneumocytes in macrophage (Mphi)-mediated host resistance to pulmonary Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) infections were studied. Electron microscopy of the lung sections of mice given intratracheal infection indicated that the organisms invaded both Mphis and type II pneumocytes. When Mono-Mac-6 Mphis(MM6-Mphis) and A-549 type II pneumocytes (A-549 cells) were cocultivated, bacterial growth in MM6-Mphis was reduced by A-549 cell-derived soluble factors, indicating the roles of type II pneumocytes in Mphi-mediated host resistance to mycobacteria. MTB- or MAC-infected A-549 cells showed increased mitochondrial RNA expression of cytokines and surfactant proteins (SPs), in the order tumor necrosis factor-alpha (TNF-alpha) > or = granulocyte-Mphi colony-stimulating factor (GM-CSF) > Mphi chemoattractant protein > or = interleukin-8 > SP-D. Anti-TNF-alpha and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of intramacrophage mycobacteria, indicating their crucial roles in A-549 cell-mediated potentiation of Mphi antimycobacterial activity.

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.

Community organizing with government support, termed local self-governance (LSG), is a form of policy decentralization for community wellbeing through solutions tailored to local issues. One form of LSG is multifunctional autonomy, in which citizens can comprehensively manage their communities with government support. This study clarified the effect of multifunctional autonomy on healthy life expectancy by assessing related advantages and challenges in rural Japanese communities, using a mixed-methods approach. Disability-free life expectancy from 65 years (DFLE-65) was assessed to compare healthy life expectancies between two rural Japanese cities (with/without multifunctional autonomy). Comparisons revealed better DFLE-65 only among older men in a city with multifunctional autonomy. A cost-effectiveness analysis investigated the relationship between the budget and DFLE-65 change using questionnaire data. Cost-effectiveness analysis of multifunctional autonomy indicated 61,147 yen/DFLE-65. Thematic analysis revealed that multifunctional autonomy created new roles for older men, improving community relationships. However, sustainable multifunctional autonomy in LSG communities may be hindered by a generally aging society, generation gap, and lack of mutual understanding between rural communities and local governments. To ensure the sustainability of multifunctional autonomy, collaborations between local communities and governments and among various generations are critical.

We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) against Mycobacterium avium complex (MAC) and the mode of macrophage (mphi) production of these effectors. (1) Intracellular growth of MAC in murine peritoneal mphis was accelerated by scavengers for ROI or RNI and inhibitors of nitric oxide synthase or phospholipase A2, indicating roles of ROI, RNI, and FFA in mphi anti-MAC functions. (2) Acidified NaNO2-derived RNI, FFA (linolenic and arachidonic acids), and the H2O2-mediated halogenation system exhibited a significant anti-MAC bactericidal activity. The combination of RNI with FFA showed a synergistic effect. However, the H2O2-halogenation system in combination with either RNI or FFA showed an antagonism. When Listeria monocytogenes (Lm) was used as a target organism, the combinations of RNI + FFA and RNI + H2O2-halogenation gave a synergistic effect, whereas FFA + H2O2-halogenation showed an antagonism in exerting bactericidal activity. In addition, when ROI generated by the xanthine oxidase-acetaldehyde system was combined with RNI, anti-Lm but not anti-MAC activity was potentiated. (3) ROI production by murine peritoneal mphis was observed immediately after contact with MAC organisms (MAC stimulation) and ceased within 2 h. FFA release was seen 1-24 h after MAC stimulation. RNI production was initiated from 3 h and increased during the first 36 h and continued at least for 4 days. These findings suggest that RNI and FFA rather than ROI are important effectors of anti-MAC functions of mphis, and the collaborating action of RNI with FFA temporarily participates in mphi-mediated killing of MAC in the relatively early phase after MAC stimulation.

In this mixed-methods study, we hypothesized that social cognitive theory (SCT)-based educational interventions for healthcare participation can improve the self-efficacy of older rural citizens in participating in their health management without any difficulties. Quasi-experimental study before and after SCT-based educational interventions and semi-structured interviews were conducted. Participants were Japanese elderly (>65 years) from rural communities. Propensity score matching was performed to estimate the effectiveness of educational interventions on participants’ perception (intervention: n = 156; control: n = 121). Interview contents were transcribed verbatim and analyzed based on thematic analysis. The intervention group scored significantly higher than the control group for participation in planning and managing self-care. Interviews revealed three themes: ability to manage health conditions, relationship with medical professionals, and relationship among citizens. Participants reported difficulties in judging symptoms and communicating with medical professionals. Hierarchy and low motivation to participate in healthcare hindered collaboration. The findings suggest that SCT-based educational interventions can positively impact rural citizens’ self-efficacy in healthcare participation.

SUMMARYWe studied the effects of secretory leucocyte protease inhibitor (SLPI) on the production of the antiinflammatory cytokines, IL-10 and TGF-b , by lipopolysaccharide (LPS)-stimulated macrophages, using half-sized SLPI (1/2 SLPI) containing the C-terminal domain (Arg 58 -Ala 107 ). ELISA testing of macrophage culture fluids showed a temporary production of IL-10 by the macrophages in the early phase (24 h) after LPS stimulation at low (1 ng/ml) or high (10 mg/ml) concentrations. On the other hand, TGF-b production was initiated after day 3 and progressively increased. 1/2 SLPI significantly increased IL-10 and TGF-b production by macrophages in response to a low dose as well as a high dose of LPS. Reverse transcription-polymerase chain reaction analysis showed that 1/2 SLPI caused a significant increase in the expression of both IL-10 and TGF-b mRNAs by LPS-stimulated macrophages. Thus, although the profile of macrophage TGF-b production by LPS-stimulated macrophages is markedly different from that of their IL-10 production, SLPI causes an up-regulation of the production of these anti-inflammatory cytokines by LPS-stimulated macrophages.