Perspective Chapter: Improving Children’s Foot Health and Shoe Education from the Foot Health Education Project

With the aim of improving the foot health of infants and school-age children, Kinjo University in Japan has established the Foot Health Education Project in 2014, under which university faculty members, students, and industrial organizations have conducted joint activities. The results of surveys on approximately 3000 children to date have shown high prevalence rates of bunionette, undeveloped foot arch, floating toes, and a paucity of wearers of right-size shoes. Under such circumstances, a follow-up survey has been conducted to examine whether changes in foot morphology can be reversed by wearing right-size shoes. The results have suggested that wearing right-size shoes facilitated the development of foot arch and improved floating toes. We plan to continue surveys and share the trends obtained from survey results and possible measures with community residents. In addition, we plan to establish scientific evidence that is useful for education and that contributes to the healthy development of children’s feet

Lateralization, maturation, and anteroposterior topography in the lateral habenula revealed by ZIF268/EGR1 immunoreactivity and labeling history of neuronal activity

We report habenular lateralization in a simple transgenic mouse model used for labeling a facet of neuronal activity history. A transgenic construct comprised of a zif268/egr1 immediate-early gene promoter and a gene for normal Venus fluorescent protein with a membrane tag converted promoter activity into long-life fluorescent proteins, which was thought to describe a facet of neuronal activity history by summing neuronal activity. In addition to mapping the immediate-early gene-immunopositive cells, this method helped demonstrate the functionality of the lateral habenular nucleus (LHb). During postnatal development, the LHb was activated between postnatal days 10 and 16. The water-immersion restraint stress also activated the LHb over a similar period. LHb activation was functionally lateralized, but had no directional bias at the population level. Moreover, the posterior LHb was activated in the early stage after the stress, while the anterior LHb was activated in the later stage. Our results indicate lateralization, maturation, and anteroposterior topography of the LHb during postnatal development and the stress response

Promotion of Cognitive Function Maintenance Exercises in the Community: “Brain Wakawaka Club” Activities to Keep the Brain Young

According to estimates by the Japanese Cabinet Office, there will be approximately 6.02 million elderly people with dementia in 2020, and the prevalence of dementia among those age 65 years and above will be very high at 16.7%. Therefore, it is important to prevent dementia in local communities. However, even though exercises for physical strength maintenance are conducted in many local communities, there are very few exercises to prevent declines in cognitive function. Thus, the “Brain Wakawaka Club” makes tours to local communities with the students of the Department of Occupational Therapy, and conducts cognitive function evaluation and maintenance exercises for elderly people. This activity is expected to contribute to the prevention of dementia among the elderly in the community

Long-Term Follow-Up after Surgical Management for Atypical Endometriosis: A Series of Nine Cases

Background and Objective: Atypical endometriosis is reported to possess a precancerous potential attributed to premalignant changes characterized by cytological atypia and architecture proliferation. Although the coexistence of atypical endometriosis and neoplasms has been reported, cases of atypical endometriosis transformation to carcinoma are rarely reported. The purpose of this case series was to evaluate the prognosis of atypical endometriosis. Subjects and Methods: Data from nine women who underwent surgical treatment including cystectomy and salpingo-oophorectomy with or without hysterectomy and diagnosed with atypical endometriosis was analyzed. Between January 2006 and January 2018, the clinical characteristics and prognosis of atypical endometriosis were evaluated. Results: During the follow-up period, eight of nine patients with atypical endometriosis did not develop malignant epithelial tumors, although one patient developed endometrioid carcinoma, grade 1, 48 months after her right laparoscopic cystectomy. The median overall survival period for all patients was 68 (range 13–131) months. Conclusion: When we encounter the cases of atypical endometriosis, it is necessary to consider the possibility of ovarian cancer and carefully follow those cases for long periods

Isolation and Phenotypic Characterization of Lotus japonicus Mutants Specifically Defective in Arbuscular Mycorrhizal Formation

Several symbiotic mutants of legume plants defective in nodulation have also been shown to be mutants related to arbuscular mycorrhizal (AM) symbiosis. The origin of the AM symbiosis can be traced back to the early land plants. It has therefore been postulated that the older system of AM symbiosis was partially incorporated into the newer system of legume-rhizobium symbiosis. To unravel the genetic basis of the establishment of AM symbiosis, we screened about 34,000 plants derived from ethyl methanesulfonate (EMS)-mutagenized Lotus japonicus seeds by microscopic observation. As a result, three lines (ME778, ME966 and ME2329) were isolated as AM-specific mutants that exhibit clear AM-defective phenotypes but form normal effective root nodules with rhizobial infection. In the ME2329 mutant, AM fungi spread their hyphae into the intercellular space of the cortex and formed trunk hyphae in the cortical cells, but the development of fine branches in the arbuscules was arrested. The ME2329 mutant carried a nonsense mutation in the STR-homolog gene, implying that the line may be an str mutant in L. japonicus. On the ME778 and ME966 mutant roots, the entry of AM fungal hyphae was blocked between two adjacent epidermal cells. Occasionally, hyphal colonization accompanied by arbuscules was observed in the two mutants. The genes responsible for the ME778 and ME966 mutants were independently located on chromosome 2. These results suggest that the ME778 and ME966 lines are symbiotic mutants involved in the early stage of AM formation in L. japonicus.ArticlePLANT AND CELL PHYSIOLOGY. 55(5):928-941 (2014)journal articl

A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population

NOS2 polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. One of several complications of SSc, pulmonary arterial hypertension (PAH) can be refractory to treatment, both novel and established. In the present study we investigated the ratio of circulating nitric oxide to endothelin-1 in patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the nitric oxide synthase 2 gene) are associated with susceptibility to PAH. Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. We confirmed the presence of two single nucleotide polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT) at -2.5 kilobases. There were significant differences in single nucleotide polymorphisms between patients with SSc who had PAH and those who did not, and between patients with both SSc and PAH and healthy control individuals. The CCTTT repeat was significantly shorter in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. Transcriptional activity were analyzed using the luciferase reporter assay. The transcriptional activity of NOS2 was much greater in fibroblasts transfected by a vector with a long allele of the CCTTT repeat than in those transfected by a vector with a short allele. Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH

Association of the diplotype configuration at the N-acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus

Although co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective drug for prophylaxis against and treatment of Pneumocystis pneumonia, patients often experience adverse events with this combination, even at prophylactic doses. With the aim being to achieve individual optimization of co-trimoxazole therapy in patients with systemic lupus erythematosus (SLE), we investigated genetic polymorphisms in the NAT2 gene (which encodes the metabolizing enzyme of sulphamethoxazole). Of 166 patients with SLE, 54 patients who were hospitalized and who received prophylactic doses of co-trimoxazole were included in the cohort study. Adverse events occurred in 18 patients; only two experienced severe adverse events that lead to discontinuation of the drug. These two patients and three additional ones with severe adverse events (from other institutions) were added to form a cohort sample and were analyzed in a case-control study. Genotype was determined using TaqMan methods, and haplotype was inferred using the maximum-likelihood method. In the cohort study, adverse events occurred more frequently in those without the NAT2*4 haplotype (5/7 [71.4%]) than in those with at least one NAT2*4 haplotype (13/47 [27.7%]; P = 0.034; relative risk = 2.58, 95% confidence interval = 1.34–4.99). In the case-control study the proportion of patients without NAT2*4 was significantly higher among those with severe adverse events (3/5 [60%]) than those without severe adverse events (6/52 [11.5%]; P = 0.024; odds ratio = 11.5, 95% confidence interval = 1.59–73.39). We conclude that lack of NAT2*4 haplotype is associated with adverse events with co-trimoxazole in Japanese patients with SLE

Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-γ and anti-double-stranded DNA antibody production

Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T-lymphocyte associated antigen-4 family and is involved in the proliferation and activation of T cells. A detailed functional analysis of ICOS on peripheral blood T cells from patients with systemic lupus erythematosus (SLE) has not yet been reported. In the present study we developed a fully human anti-human ICOS mAb (JTA009) with high avidity and investigated the immunopathological roles of ICOS in SLE. JTA009 exhibited higher avidity for ICOS than a previously reported mAb, namely SA12. Using JTA009, ICOS was detected in a substantial proportion of unstimulated peripheral blood T cells from both normal control individuals and patients with SLE. In CD4(+)CD45RO(+ )T cells from peripheral blood, the percentage of ICOS(+ )cells and mean fluorescence intensity with JTA009 were significantly higher in active SLE than in inactive SLE or in normal control individuals. JTA009 co-stimulated peripheral blood T cells in the presence of suboptimal concentrations of anti-CD3 mAb. Median values of [(3)H]thymidine incorporation were higher in SLE T cells with ICOS co-stimulation than in normal T cells, and the difference between inactive SLE patients and normal control individuals achieved statistical significance. ICOS co-stimulation significantly increased the production of IFN-γ, IL-4 and IL-10 in both SLE and normal T cells. IFN-γ in the culture supernatants of both active and inactive SLE T cells with ICOS co-stimulation was significantly higher than in normal control T cells. Finally, SLE T cells with ICOS co-stimulation selectively and significantly enhanced the production of IgG anti-double-stranded DNA antibodies by autologous B cells. These findings suggest that ICOS is involved in abnormal T cell activation in SLE, and that blockade of the interaction between ICOS and its receptor may have therapeutic value in the treatment of this intractable disease