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目的：保健師教育課程修了時の公衆衛生看護学実習において、学生の自己評価を用いて保健師教育評価の指標の到達度を明らかにし、A大学の保健師教育課程の評価を行う。方法：保健師教育課程を履修し、2022年度に公衆衛生看護学実習を行ったA大学4年次学生20人を対象とした。公衆衛生看護学実習経験記録表、保健師教育評価の指標（62項目）を用いて、学生の自己評価の状況を分析し、目標到達者の人数をカウントし、その割合を算出した。結果：保健師教育評価の指標の目標到達者割合の平均は72.4％であり、目標到達割合が100％の項目は5項目であり、80％以上の項目は26項目、50％未満の項目は8項目であった。考察：保健師教育評価の指標の目標到達割合を勘案すると、到達状況は良好であった。目標到達者の割合が低い項目に関する授業・実習内容については、今後、再考する必要性が示唆された。

BackgroundAs a consequence of the COVID-19 pandemic, telecommuting has become a new way of working that has not only changed individuals work, but also their health, lifestyle, family and community relationships. However, the impact of telecommuting on diet is not well understood. The aim of this study was to determine the relationship between telecommuting frequency and unhealthy dietary habits among Japanese workers during the COVID-19 pandemic. MethodsA total of 33,302 Japanese workers completed an Internet survey about telecommuting and dietary habits. Data from 13,468 office workers who telecommuted were analyzed. Telecommuting frequency during the COVID-19 pandemic was extracted from a questionnaire. The odds ratios (ORs) of four types of dietary habits, namely, skipping breakfast, solitary eating, lower meal frequency, and meal substitution associated with telecommuting frequency were estimated using multilevel logistic regression. ResultsThe multivariate OR of skipping breakfast was 1.15 (95% CI: 1.03-1.29, p=0.013) for participants who telecommuted in excess of four days per week compared to those who rarely telecommuted. Similarly, the multivariate OR of solitary eating, lower meal frequency and meal substitution were 1.44 (95%CI: 1.28-1.63, p

OBJECTIVES: This observational study aimed to determine how 1-year changes in work time control (WTC) have an impact upon objectively measured fatigue and sleep among employees. METHODS: Thirty-nine employees were divided into two groups according to whether or not their WTC increased from baseline to 1 year later. Psychomotor vigilance task (PVT) and wrist actigraphy were used to objectively measure fatigue and sleep, respectively. Self-reported outcomes were also measured. RESULTS: The increased WTC group showed gradual improvements in PVT performance and sleep quality over the course of the follow-up period compared with the not-increased WTC group. Between-group differences were statistically significant for PVT lapses and tended to be significant for PVT speed after 1 year. CONCLUSIONS: A progressive increase in WTC could play a crucial role in reducing fatigue and promoting sleep among employees. Language: en

Objectives This study aimed to develop the Career Anchors Scale among Occupational Health Nurses (CASOHN) and evaluate its reliability and validity. Methods Scale items were developed through a qualitative inductive analysis of interview data, and items were revised following an examination of content validity by experts and occupational health nurses (OHNs), resulting in a provisional scale of 41 items. A total of 745 OHNs (response rate 45.2%) affiliated with the Japan Society for Occupational Health participated in the self-administered questionnaire survey. Results Two items were deleted based on item-total correlations. Factor analysis was then conducted on the remaining 39 items to examine construct validity. An exploratory factor analysis with a main factor method and promax rotation resulted in the extraction of six factors. The variance contribution ratios of the six factors were 37.45, 7.01, 5.86, 4.95, 4.16, and 3.19%. The cumulative contribution ratio was 62.62%. The factors were named as follows: Demonstrating expertise and considering position in work (Factor 1); Management skills for effective work (Factor 2); Supporting health improvement in groups and organizations (Factor 3); Providing employee-focused support (Factor 4); Collaborating with occupational health team members and personnel (Factor 5); and Compatibility of work and private life (Factor 6). The confidence coefficient determined by the split-half method was 0.85. Cronbach's alpha coefficient for the overall scale was 0.95, whereas those of the six subscales were 0.88, 0.90, 0.91, 0.80, 0.85, and 0.79, respectively. Conclusions CASOHN was found to be valid and reliable for measuring career anchors among OHNs in Japan.

Aim This study examined the career anchor characteristics that are possessed by Japanese occupational health nurses. Method Sixteen occupational health nurses participated in the semistructured interview. Data analyses were conducted using descriptive qualitative methods. Results The data showed the following five categories: practices concerning relationships and positions; development of occupational health practices; management skills for effective work; practices that are approved inside and outside the organization; and work and private life considerations. Conclusions This study described the career anchors among occupational health nurses in Japan. The participants emphasized the following: the importance of maintaining good cooperative relationships with workers and supervisors; balancing professional and organized labor; and practicing effective occupational health services. Moreover, the occupational health nurses emphasized receiving approval from inside and outside of the organization. These results were consistent with the actual practices of occupational health nursing.

The role of Notch signaling in human innate lymphoid cell (ILC) differentiation is unclear, although IL-7 and IL-15 promote differentiation of natural cytotoxicity receptor (NCR) NKp44+ group 3 ILCs (NCR+ILC3s) and conventional NK (cNK) cells from CD34+ hematopoietic progenitor cells (HPCs) ex vivo. In this study, we analyzed the functions of Notch in the differentiation of NCR+ILC3s and cNK cells from human HPC subpopulations circulating in peripheral blood by limiting dilution and clonal assays using high-throughput flow cytometry. We demonstrated that Notch signaling in combination with IL-7 induced NCR+ILC3 differentiation, but conversely suppressed IL-15–dependent cNK cell generation in CD45RA+Flt-3−c-Kitlow, a novel innate lymphocyte-committed HPC subpopulation. In contrast, Notch signaling induced CD45RA−Flt-3+c-Kithigh multipotent HPCs to generate CD34+CD7+CD62Lhigh, the earliest thymic progenitor–like cells, which preserved high cNK/T cell potential, but lost NCR+ILC3 potential. These findings implicate the countervailing functions of Notch signaling in the fate decision between NCR+ILC3 and cNK cell lineages at different maturational stages of human HPCs. Inhibition of Notch functions by Abs specific for either the Notch1 or Notch2 negative regulatory region suggested that both Notch1 and Notch2 signals were involved in the fate decision of innate lymphocyte-committed HPCs and in the generation of earliest thymic progenitor–like cells from multipotent HPCs. Furthermore, the synergistic interaction between Notch and IL-7 in NCR+ILC3 commitment was primarily explicable by the induction of IL-7 receptor expression in the innate lymphocyte–committed HPCs by Notch stimulation, suggesting the pivotal role of Notch in the transcriptional control required for human NCR+ILC3 commitment.

The relationships between commitments of dendritic cells (DCs) and T cells in human hematopoietic stem cells are not well understood. In this study, we enumerate and characterize conventional DC and plasmacytoid DC precursors in association with T cell and thymus-derived types of NK cell precursors among CD34+ hematopoietic progenitor cells (HPCs) circulating in human peripheral blood. By limiting-dilution analyses using coculture with stroma cells expressing Notch1 ligand, the precursor frequencies (PFs) of DCs in HPCs were found to significantly correlate with T cell PFs, but not with NK cell PFs, among healthy donors. Clonal analyses showed that the majority of T/NK dual- and T single-lineage precursors—but only a minority of NK single-lineage precursors—were associated with the generation of DC progenies. All clones producing both DC and T cell progenies were found with monocyte and/or granulocyte progenies, suggesting DC differentiation via myeloid DC pathways. Analyses of peripheral blood HPC subpopulations revealed that the lineage split between DC and T/NK cell progenitor occurs at the stage prior to bifurcation into T and NK cell lineages. The findings suggest a strong linkage between DC and T cell commitments, which may be imprinted in circulating lymphoid-primed multipotent progenitors or in more upstream HPCs.

Age-associated changes of T and NK cell (T/NK) potential of human hematopoietic stem cells are unknown. In this study, we enumerate and characterize T/NK precursors among CD34+Lin− cell populations circulating in normal human adult peripheral blood (PB) by a limiting-dilution assay using coculture with OP9-DL1 stroma cells expressing Notch 1 ligand, Delta–like 1. The frequency of T cell precursors in CD34+Lin− cells was found to decrease with donor age, whereas the ratio of NK to T cell precursor frequency (NK/T ratio) increased with age, suggesting that lymphoid differentiation potential of PB progenitors shifts from T to NK cell lineage with aging. Clonal analyses of CD34+Lin− cells showed that differences in the NK/T ratio were attributable to different distributions of single- and dual-lineage T/NK precursor clones. Because nearly all of the clones retained monocyte and/or granulocyte differentiation potentials in coculture with OP9-DL1 cells, T/NK precursors in PB are considered to be contained in the pool of T/NK/myeloid multipotent progenitors. The age-associated increase in NK over T cell commitment might occur in precursor cells with T/NK/myeloid potential.

Objectives The period of leisure is an appropriate time to recover from work-induced fatigue, though some recovery takes place during rest breaks at work. Recently, much attention has been paid to the critical role of leisure activity in recovery. However, the findings relevant to shiftwork nurses who cannot take a day-off regularly are limited. This study explored how leisure activity during days off and shift work schedule are associated with recovery from fatigue in nurses working rotating shifts. Methods A total of 426 nurses working rotating shifts at a university hospital returned a questionnaire regarding leisure activity and fatigue (response rate: 81.5%). Nurses were eligible for this study if they were female, worked 2 or 3 shifts, and had no missing data. A total of 390 respondents satisfied the inclusion criteria. A factor analysis classified their responses on how to spend an assumed period of two consecutive days off into three activity types: outdoor-, sleep-, and indoor-oriented. Fatigue (recovery from fatigue, accumulated fatigue, burnout), work conditions (working time, overtime, nightshift napping), sleep (sleep duration before day shift or day off, sleepiness) were measured. These data were analyzed using a two-way mixed model analysis of covariance (type [outdoor, sleep, indoor], shift schedule [two or three-shift system]). Covariates included age, length of career, partner, children, and hospital ward. Multiple regression analyses were performed to examine the factors determining the level of fatigue. Results Outdoor-oriented nurses showed significantly faster fatigue recovery, lower accumulated fatigue and less burnout symptoms than others, regardless of the shiftwork schedule. In contrast, sleep-oriented nurses showed significantly slower recovery from fatigue. Besides, their level of fatigue deteriorated more when they worked under a 3-shift system (counter-clockwise) compared with under 2-shift system (with mainly 16-hour nightshift). Multiple regression analysis indicated that sleep-oriented type of leisure activity, workload perception of working time, work-induced insomnia and length of nightshift naps were significantly related to fatigue-related outcomes. Conclusions The primary finding of this study suggests that the level of fatigue is associated with the type of leisure activity, especially sleep-oriented activity, during shiftwork nurses' days off. Also, ensuring sufficient nightshift nap time may be one of the most important nightshift-related factors for recovery from fatigue. The present findings may have implications for appropriate activities during days off as factors facilitating recovery from work, though further investigations are needed to examine the causal links.

In a series of studies of atomic bomb survivors, radiation-dose-dependent alterations in peripheral T-cell populations have been reported. For example, reduced size in naïve T-cell pools and impaired proliferation ability of T cells were observed. Because these alterations are also generally observed with human aging, we hypothesized that radiation exposure may accelerate the aging process of the T-cell immune system. To further test this hypothesis, we conducted cross-sectional analyses of telomere length, a hallmark of cellular aging, of naïve and memory CD4 T cells and total CD8 T cells in the peripheral blood of 620 atomic bomb survivors as it relates to age and radiation dose, using fluorescence in situ hybridization with flow cytometry. Since telomere shortening has been recently demonstrated in obesity-related metabolic abnormalities and diseases, the modifying effects of metabolic status were also examined. Our results indicated nonlinear relationships between T-cell telomere length and prior radiation exposure, i.e., longer telomeres with lower dose exposure and a decreasing trend of telomere length with individuals exposed to doses higher than 0.5 Gy. There were associations between shorter T-cell telomeres and higher hemoglobin Alc levels or fatty liver development. In naïve and memory CD4 T cells, radiation dose and high-density lipoprotein (HDL) cholesterol were found to positively interact with telomere length, suggesting that the decreasing trend of telomere length from a higher radiation dose was less conspicuous in individuals with a higher HDL cholesterol. It is therefore likely that radiation exposure perturbs T-cell homeostasis involving telomere length maintenance by multiple biological mechanisms, depending on dose, and that long-term-radiation-induced effects on the maintenance of T-cell telomeres may be modified by the subsequent metabolic conditions of individuals.

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure.

It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.

Our previous study showed that radiation exposure reduced the diversity of repertoires of memory thymus-derived cells (T cells) with cluster of differentiation (CD)- 4 among atomic-bomb (A-bomb) survivors. To evaluate the maintenance of T-cell memory within A-bomb survivors 60 years after radiation exposure, we examined functionally distinct memory CD4 T-cell subsets in the peripheral blood lymphocytes of the survivors.Three functionally different subsets of memory CD4 T cells were identified by differential CD43 expression levels and measured using flow cytometry. These subsets consist of functionally mature memory cells, cells weakly responsive to antigenic stimulation, and those cells functionally anergic and prone to spontaneous apoptosis.The percentages of these subsets within the peripheral blood CD4 T-cell pool all significantly increased with age. Percentages of functionally weak and anergic subsets were also found to increase with radiation dose, fitting to a log linear model. Within the memory CD4 T-cell pool, however, there was an inverse association between radiation dose and the percentage of functionally mature memory cells.These results suggest that the steady state of T cell memory, which is regulated by cell activation and/or cell survival processes in subsets, may have been perturbed by prior radiation exposure among A-bomb survivors.

To improve our understanding of ionizing radiation effects on immune cells, we investigated steps leading to radiation-induced cell death in MOLT-4, a thymus-derived human leukemia cell. After exposure of MOLT-4 cells to 4 Gy of X-rays, irradiated cells sequentially showed increase in intracellular reactive oxygen species (ROS), decrease in mitochondrial membrane potential, and eventually apoptotic cell death. In the presence of the caspase inhibitor z-VAD-fmk, irradiated cells exhibited necrotic characteristics such as mitochondrial swelling instead of apoptosis. ROS generation was not detected during this necrotic cell death process. These results indicate that radiation-induced apoptosis in MOLT-4 cells requires elevation of intracellular ROS as well as activation of a series of caspases, whereas the cryptic necrosis program—which is independent of intracellular ROS generation and caspase activation—is activated when the apoptosis pathway is blocked.

Lectin microarray is an emerging technique, which will accelerate glycan profiling and discovery of glycan-related biomarkers. One of the most important stages in realizing the potential of the technique is to achieve sufficiently high sensitivity to detect even the low concentrations of some target glycoproteins which occur in sera or tissues. Previously, we developed a lectin microarray based on an evanescent-field fluorescence-assisted detection principle that allows rapid profiling of glycoproteins. Here, we report optimization of procedures for lectin spotting and immobilization to improve the sensitivity and reproducibility of the lectin microarray. The improved microarray allows high-sensitivity detection of even monovalent oligosaccharides that generally have a low affinity with lectins (K(d)>10(-6) M). The LOD observed for RCA120, a representative plant lectin, with asialofetuin, and an asialo-biantennary N-glycan probe were determined to be 100 pg/mL and 100 pM, respectively. With the improved lectin microarray system, closely related structural isomers, i.e., Le(a) and Le(x), were clearly differentiated by the difference in signal patterns on relevant multiple lectins, even though specific lectins to detect these glycan structures were not available. The result proved a previously proposed concept of lectin-based glycan profiling.

Raman spectra of undeuterated and deuterated rachis from a fowl feather was observed with 488 nm excitation in the 400–1800 cm−1 region. Fowl feather rachis and barbs were subjected to a polarized ...

This study examined the career anchor characteristics that are possessed by Japanese occupational health nurses.Sixteen occupational health nurses participated in the semistructured interview. Data analyses were conducted using descriptive qualitative methods.The data showed the following five categories: practices concerning relationships and positions; development of occupational health practices; management skills for effective work; practices that are approved inside and outside the organization; and work and private life considerations.This study described the career anchors among occupational health nurses in Japan. The participants emphasized the following: the importance of maintaining good cooperative relationships with workers and supervisors; balancing professional and organized labor; and practicing effective occupational health services. Moreover, the occupational health nurses emphasized receiving approval from inside and outside of the organization. These results were consistent with the actual practices of occupational health nursing.

The amide I Raman tensor corresponding to the antiparallel β-sheet structure in proteins has been determined by polarized Raman microspectroscopy of fowl feather rachis using polarized Raman spectra excited in the near-infrared (785 nm). For a Raman tensor principal axis system (XYZ), in which X is perpendicular to the plane of the pleated β-sheet, Y is in the plane of the sheet and perpendicular to the direction of the polypeptide chain, and Z is parallel to the direction of the polypeptide chain, the principal tensor components (αXX, αYY, αZZ) are found to satisfy the following relationships: R1 ≡ αXX/αZZ = 0.32 and R2 ≡ αYY/αZZ = 3.48. With this Raman tensor determination, we show that semiquantitative estimates of the total antiparallel β-sheet content in β-rich proteins can be extracted from polarized Raman intensity measurements on the amide I marker of the β-sheet occurring near 1664 cm−1. We demonstrate this approach for the β-rich silk proteins of the silkworm and spider. Copyright © 2006 John Wiley & Sons, Ltd.

The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors.Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8.CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations.Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

We propose a classification of human CD4+CD45RO+ memory T cells into three new subsets based on cell surface expression levels of CD43. The first subset consists of cells whose CD43 expression is relatively high; this subset also contains the highest proportion of recall Ag-reactive precursors, and its constituent cells respond far more strongly than cells in either of the other subsets to immobilized CD3 Ab in addition to secreting substantially more IFN-γ and IL-4. Cells of the second subset express similar levels of CD43 to naive cells, and they also respond weakly to TCR-mediated stimuli as judged by either their ability to proliferate or capacity for cytokine production. The third subsets consists of cells whose CD43 expression levels are clearly down-regulated; its cells appear to be anergic to TCR-mediated stimuli, and when examined ex vivo many of them appear to be undergoing either spontaneous apoptosis via a caspase-independent pathway or Fas-mediated apoptosis via a caspase-dependent pathway, even in the resting state. An analysis of telomere lengths revealed that the typical telomere of a cell in the second subset was significantly longer than the typical telomere in the first or third subset. Taken together, these results appear to indicate that CD4+CD45RO+ T cells fall into three functionally differing subsets, one being a subset of cells with fully matured memory phenotype, a second being a less mature subset of cells that retain longer telomeres and whose memory functionality is marginal, and a third consisting of anergic cells that give every appearance of being death-prone and/or in the process of dying.

Ataxia-telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradiated and X-irradiated EBV (Epstein-Barr virus)-transformed lymphoblastoid cell lines (LCLs) derived from donors who were normal (ATM + / + ), AT heterozygotes (ATM + / - ), or AT homozygotes (ATM - / - ), respectively. In ATM + / + LCLs, the levels of ATM mRNA were found to have increased by approximately 1.5-fold within 1 h of exposure to 10 Gy of X-rays, while the ATM protein levels had increased by 1.5- to 2.0-fold within 2 to 3 h of irradiation. The wild-type mRNA and protein levels both returned to their basal values fairly quickly after this time. The results obtained with the ATM + / - LCLs were quite different, however: neither the mRNA nor protein levels were found to have increased as a consequence of X-irradiation in any ATM + / - LCL. Twelve of the mutations in the ATM - / - LCLs we used were truncating mutations, and we suspected that the corresponding truncated ATM proteins would be too labile to be detected by western blot analysis. However, five of the ATM - / - LCLs produced mutant ATM proteins that were identical in molecular weight to the wild-type ATM protein. When cells from three of these five clones were exposed to X-rays, transcription of the mutant ATM genes appeared to reduce somewhat, as were the levels of protein being produced. These results suggest that the normal ATM gene responds to ionizing radiation by up-regulating its activity, whereas none of the mutant ATM genes we studied were able to respond in this way.

Reduction of the naive T-cell population represents a deteriorating state in the immune system that occurs with advancing age. In animal model studies, obesity compromises the T-cell immune system as a result of enhanced adipogenesis in primary lymphoid organs and systemic inflammation. In this study, to test the hypothesis that obesity may contribute to the aging of human T-cell immunity, a thousand atomic-bomb survivors were examined for obesity status and ability to produce naive T cells, i.e., T-cell receptor excision circle (TREC) numbers in CD4 and CD8 T cells. The number of TRECs showed a strong positive correlation with naive T cell numbers, and lower TREC numbers were associated with higher age. We found that the TREC number was inversely associated with levels of obesity indicators (BMI, hemoglobin A1c) and serum CRP levels. Development of type-2 diabetes and fatty liver was also associated with lower TREC numbers. This population study suggests that obesity with enhanced inflammation is involved in aging of the human T-cell immune system. Given the fact that obesity increases the risk of numerous age-related diseases, attenuated immune competence is a possible mechanistic link between obesity and disease development among the elderly.

Raman spectra of single cells of Euglena and Chlamydomonas have been examined with 514.5 nm excitation at various points within the cells. At every point, two strong bands, which are assignable to carotenoid, appeared at 1530 and 1159 cm−1. By the use of a Raman mapping system, the Raman intensity at 1530 cm−1 has been plotted against the (x,y) coordinate representing a location within the cell. It has been shown that, for both algae examined, the eyespot has a prominently high carotenoid content, and a small amount of carotenoid is uniformly distributed among the chloroplast. The spatial resolution of the mapping system has been shown to be higher than 1 μm, and the Chlamydomonas eyespot has an elongated shape of 1 μm × 2 μm. By use of a polarizer, the carotenoid chains in the Chlamydomonas eyespot have been found to be aligned along its long axis, which is parallel to the body axis.

Metastasis from breast carcinoma is an uncommon occurrence in skeletal muscle, compared to local invasion into muscle from direct tumor spread. A 49-year-old woman was referred to our hospital with an 8.5-cm mass in the right breast. Core needle biopsy revealed metaplastic carcinoma with squamous metaplasia. The mass was rapidly growing and metaplastic, so mastectomy with dissection of axillary lymph nodes was performed. Pathological examination showed metaplastic carcinoma, histological grade 3, triple negative, and a MIB-1 labeling index of 80%. Six months postoperatively, during adjuvant chemotherapy treatment, she reported numbness and pain in the right lateral thigh and a mass in the right lower abdomen. Computed tomography revealed multiple lined masses in the abdominal wall and iliac muscle. Core needle biopsy showed metastatic breast carcinoma. Radio- and chemotherapy were administered, but the mass in the muscle became enlarged. To control her pain, a combined treatment with morphine, fentanyl, ketamine, antiepilepsy drug, and NSAIDs was administered. Liver metastasis appeared 9 months (15 months postoperatively) after recognition of muscle metastasis, and the patient died 16 months postoperatively. Skeletal muscle metastasis is uncommon, and therapeutic intervention is mainly palliative. The most common symptom of skeletal muscle metastasis is pain; thus, pain control is a pivotal goal of treatment.

In this paper we summarize the long-term effects of A-bomb radiation on the T-cell system and discuss the possible involvement of attenuated T-cell immunity in the disease development observed in A-bomb survivors. Our previous observations on such effects include impaired mitogen-dependent proliferation and IL-2 production, decreases in naive T-cell populations, and increased proportions of anergic and functionally weak memory CD4 T-cell subsets. In addition, we recently found a radiation dose-dependent increase in the percentages of CD25(+)/CD127(-) regulatory T cells in the CD4 T-cell population of the survivors. All these effects of radiation on T-cell immunity resemble effects of aging on the immune system, suggesting that ionizing radiation might direct the T-cell system toward a compromised phenotype and thereby might contribute to an enhanced immunosenescence. Furthermore, there are inverse, significant associations between plasma levels of inflammatory cytokines and the relative number of naïve CD4 T cells, also suggesting that the elevated levels of inflammatory markers found in A-bomb survivors can be ascribed in part to T-cell immunosenescence. We suggest that radiation-induced T-cell immunosenescence may result in activation of inflammatory responses and may be partly involved in the development of aging-associated and inflammation-related diseases frequently observed in A-bomb survivors.

Raman spectroscopic imaging has increasingly gathered momentum as a method of interest for a wide range of users1, including those involved in materials analysis and bio-analysis applications. The relative simplicity and the reliability of modern Raman instrumentation, the higher spatial resolution capabilities and a gradual decline in purchase pricing have continued to attract new and varied users to Raman spectroscopy. Raman spectroscopy can provide the same component identification capability as infrared spectroscopy but without the extensive sample preparation often required for infrared analysis. Raman spectroscopy also offers a ‘confocal’ capability enabling data collection of subsurface sample spectra for laser transparent samples. The use of Raman for spectral imaging has encountered some restrictions, however, due to the length of time required when obtaining Raman image data for larger sample areas.

i b 2 P 1 f c h w i o i d h b w a Atomic bomb survivors have a persistently increased risk f cancer, hepatitis, and cardiovascular and autoimmune iseases. There is no clear explanation for these late ffects of radiation exposure. One hypothesis is that radiaion causes chronic low-grade inflammation, with elevated irculating levels of cytokines. Proinflammatory cytokines, uch as interleukin 6, tumor necrosis factor (TNF) , and nterferon , and anti-inflammatory cytokines, such as inerleukin 10, are synthesized predominantly by macrohages and lymphocytes, and regulate the inflammatory esponse. Interleukin 6 in turn induces the synthesis of cute-phase plasma proteins, such as C-reactive protein. ncreased levels of inflammatory cytokines, even within the ormal range, have been associated with an increased risk of ardiovascular disease. Chronic low-grade inflammation ay also influence the production of immunoglobulins by B ells.

Dietary red pepper suppresses energy intake and modifies macronutrient intake. We have investigated whether a stimulus in the mouth and the sensation of spiciness are necessary for red pepper-induced changes in energy and macronutrient intake in human volunteers. In a preliminary test, sixteen Japanese male volunteers tasted samples of a soup with graded doses of red pepper in order to define a moderate and a maximum tolerable (strong) dose of red pepper. On the day of the experiment, a standardised breakfast was given to the volunteers. At lunchtime, the subjects ingested one of four experimental soups containing either a placebo, a moderate or a strong dose of red pepper plus placebo capsules, or a placebo soup plus capsules delivering a strong dose of red pepper. The rest of the meal was givenad libitumto all subjects. The amount of food, protein and carbohydrate ingested was similar for all conditions. Energy and fat intake were similar after the ingestion of the moderate soup compared with placebo. However, the strong soup significantly lowered fat intake compared with placebo (P=0·043), and ingestion of strong capsules also tended to suppress it (P=0·080). Moreover, energy intake after strong soup and capsules tended to be lower than placebo (P=0·089 and 0·076, respectively). The present results indicate that the maximum tolerable dose is necessary to have a suppressive effect of red pepper on fat intake. The main site of the action of red pepper is not in the mouth.

In a space environment such as Space Shuttle or Space Station, animal experiments with aquatic species in a closed system pose a crucial problem in maintaining their water quality for a long term. In nature, ammonia as an animal wastes is converted by nitrifying bacteria to nitrite or nitrate compounds, which usually become nitrogen sources for plants. Thus an application of the biological reactor with such bacteria attached on some filters has been suggested and experimentally studied for efficient waste managements of ammonia. Although some successful results were reported (Kozu et al. 1995, Nagaoka et al. 1998, Nakamura et al. 1997, 1998) in the space applications, purely empirical approaches have so far been taken to develop a biological filter having a stable nitrifying activity. In this study, we constructed a mathematical model to deal with the dynamics of the ammonia nitrifying processes in a biological reactor. The model describes population dynamics of the ammonia-oxidizing bacteria and the nitrite-oxidizing bacteria cultivated on the same filter. We estimated parameters involved in the model using the experimental data. The result shows that these estimated parameters could be applied to general cases and that the two bacteria are in a symbiotic relationship; they can better perform when both coexist, as has been empirically recognized. Based on the model analysis, we discuss how to prepare a high performance biological filter.

Increased frequencies of cells carrying mutations at several loci have been found in the blood cells of atomic-bomb (A-bomb) survivors upon testing four or five decades after the bombing. Interestingly, though, we have been unable to demonstrate any radiation-associated increases in the frequencies of mutant blood cells in which human leukocyte antigen (HLA)-A expression has been disrupted; this is true both of preliminary tests on the T cells of a small subset of A-bomb survivors and of the much more extensive study reported here in which we screened a much larger group of survivors for HLA-A2 loss mutations in B cells and granulocytes as well as in T cells. In attempting to explain our inability to detect any increases in HLA-A2-negative cell numbers in HLA-A2 heterozygous individuals exposed to A-bomb irradiation, we decided to test the hypothesis that HLA-A mutant lymphocytes might well have been induced by radiation exposure in much the same way as every other type of mutant we encountered, but may subsequently have been eliminated by the strong negative selection associated with their almost inevitable exposure to autologous natural killer (NK) cells in the bloodstream of each of the individuals concerned. We now report that mutant B lymphocyte cell lines that have lost the ability to express the HLA-A2 antigen do indeed appear to be much more readily eliminated than their parental heterozygous counterparts during co-culture in vitro with autologous NK cells. We make this claim first because we have observed that adding autologous NK cells to in vitro cultures of HLA-A2 heterozygous B or T cell lines appeared to cause a dose-dependent decrease in the numbers of HLA-A2-negative mutants that could be detected over a period of 3 days, and second because when we used peripheral blood HLA-A2 heterozygous lymphocyte cultures from which most of the autologous NK cells had been removed we found that we were able to detect newly-arising HLA-A2 mutant T cells in substantial numbers. Taken together, these results strongly support the hypothesis that autologous NK cells are responsible for eliminating mutant lymphocytes that have lost the ability to express self-HLA class I molecules in vivo, and may well therefore explain why we have been unable to detect increased frequencies of HLA-A2 mutants in samples from any of the 164 A-bomb survivors whose HLA-A2 heterozygote status made their lymphocytes suitable for our tests.

Mutant cells generated in vivo can be eliminated when mutated gene products are presented as altered MHC/peptide complexes and recognized by T cells. Diminished expression of MHC/peptide complexes enables mutant cells to escape recognition by T cells. In the present study, we tested the hypothesis that mutant lymphocytes lacking expression of MHC class I molecules are eliminated by autologous NK cells. In H-2b/k F1 mice, the frequency of H-2Kb-negative T cells was higher than that of H-2Kk-negative T cells. The frequency of H-2K-deficient T cells increased transiently after total body irradiation. During recovery from irradiation, H-2Kk-negative T cells disappeared more rapidly than H-2Kb-negative T cells. The disappearance of H-2K-deficient T cells was inhibited by administration of Ab against asialo-GM1. H-2Kk-negative T cells showed higher sensitivity to autologous NK cells in vitro than H-2Kb/k heterozygous or H-2Kb-negative T cells. Adding syngeneic NK cells to in vitro cultures prevented emergence of mutant cells lacking H-2Kk expression but had little effect on the emergence of mutant cells lacking H-2Kb expression. Results in the H-2b/k F1 strain correspond with the sensitivity of parental H-2-homozygous cells in models of marrow graft rejection. In H-2b/d F1 mice, there was no significant difference between the frequencies of H-2Kb-negative and H-2Kd-negative T cells, although the frequencies of mutant cells were different after radiation exposure among the strains examined. H-2b/d F1 mice also showed rapid disappearance of the mutant T cells after irradiation, and administration of Ab against asialo-GM1 inhibited the disappearance of H-2K-deficient T cells in H-2b/d F1 mice. Our results provide direct evidence that autologous NK cells eliminate mutant cell populations that have lost expression of self-MHC class I molecules.

Even after more than 60 years have passed, exposure to atomic-bomb (A-bomb) radiation continues to have long-term health effects in survivors, whose risks of inflammation-related diseases increase with increasing radiation dose. It is known that persistent inflammation underlies several cancers through increased production of reactive oxygen species (ROS) and endogenous tumor promoters (e.g., TNF-α). In our previous study, plasma levels of inflammatory cytokines and biomarkers, IL-6, TNF-α, CRP, IFN-γ, Igs, and erythrocyte sedimentation rate (ESR), increased significantly with radiation dose. We have recently developed an automated plasma ROS assay system based on use of a clinical chemistry analyzer. In this study we investigated association between radiation dose, plasma ROS levels, and sub-clinical inflammatory status in A-bomb survivors in Hiroshima. Excluding patients with history of cancer, rheumatoid arthritis, chronic bronchitis, or myocardial infarction, we randomly selected 442 study subjects from the Adult Health Study population, consisting of A-bomb survivors and unexposed people. We observed statistically significant radiation-associated increase in plasma ROS levels. ROS levels were positively associated with the inflammatory biomarkers IL-6, TNF-α, CRP, and ESR ( P It is evident that total ROS production increased with enhanced inflammatory status, suggesting a plausible mechanistic pathway between radiation-induced persistent inflammation and cancer.

The Pseudomonas bacteriophage Pf1 is a long ( approximately 2000 nm) and thin ( approximately 6.5 nm) filament consisting of a covalently closed, single-stranded DNA genome of 7349 nucleotides coated by 7350 copies of a 46-residue alpha-helical subunit. The coat subunits are arranged as a superhelix of C(1)()S(5.4)() symmetry (class II). Polarized Raman and polarized FTIR spectroscopy of oriented Pf1 fibers show that the packaged single-stranded DNA genome is ordered specifically with respect to the capsid superhelix. Bases are nonrandomly arranged along the capsid interior, deoxynucleosides are uniformly in the C2'-endo/anti conformation, and the average DNA phosphodioxy group (PO(2)(-)) is oriented so that the line connecting the oxygen atoms (O.O) forms an angle of 71 degrees +/- 5 degrees with the virion axis. Raman and infrared amide band polarizations show that the subunit alpha-helix axis is inclined at an average angle of 16 degrees +/- 4 degrees with respect to the virion axis. The alpha-helical symmetry of the capsid subunit is remarkably rigorous, resulting in splitting of Raman-active helix vibrational modes at 351, 445 and 1026 cm(-)(1) into apparent A-type and E(2)()-type symmetry pairs. The subunit tyrosines (Tyr 25 and Tyr 40) are oriented with phenoxyl rings packed relatively close to parallel to the virion axis. The Tyr 25 and Tyr 40 orientations of Pf1 are surprisingly close to those observed for Tyr 21 and Tyr 24 of the Ff virion (C(5)()S(2)() symmetry, class I), suggesting a preferred tyrosyl side chain conformation in packed alpha-helical subunits, irrespective of capsid symmetry. The polarized Raman spectra also provide information on the orientations of subunit alanine, valine, leucine and isoleucine side chains of the Pf1 virion.