Work-related stress and psychosomatic medicine

This article introduces key concepts of work-related stress relevant to the clinical and research fields of psychosomatic medicine. Stress is a term used to describe the body's physiological and/or psychological reaction to circumstances that require behavioral adjustment. According to the Japanese National Survey of Health, the most frequent stressors are work-related problems, followed by health-related and then financial problems. Conceptually, work-related stress includes a variety of conditions, such as overwork, unemployment or job insecurity, and lack of work-family balance. Job stress has been linked to a range of adverse physical and mental health outcomes, such as cardiovascular disease, insomnia, depression, and anxiety. Stressful working conditions can also impact employee well-being indirectly by directly contributing to negative health behaviors or by limiting an individual's ability to make positive changes to lifestyle behaviors, such as smoking and sedentary behavior. Over the past two decades, two major job stress models have dominated the occupational health literature: the job demand-control-support model and the effort-reward imbalance model. In both models, standardized questionnaires have been developed and frequently used to assess job stress. Unemployment has also been reported to be associated with increased mortality and morbidity, such as by cardiovascular disease, stroke, and suicide. During the past two decades, a trend toward more flexible labor markets has emerged in the private and public sectors of developed countries, and temporary employment arrangements have increased. Temporary workers often complain that they are more productive but receive less compensation than permanent workers. A significant body of research reveals that temporary workers have reported chronic work-related stress for years. The Japanese government has urged all employers to implement four approaches to comprehensive mind/body health care for stress management in the workplace: focusing on individuals, utilizing supervisory lines, enlisting company health care staff, and referring to medical resources outside the company. Good communications between occupational health practitioners and physicians in charge in hospitals/clinics help employees with psychosomatic distress to return to work, and it is critical for psychosomatic practitioners and researchers to understand the basic ideas of work-related stress from the viewpoint of occupational health.     

Neuroepithelial cells supply an initial transient wave of MSC differentiation

Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and are able to give rise to multiple mesenchymal lineages. Although MSCs are already used in regenerative medicine little is known about their in vivo behavior and developmental derivation. Here, we show that the earliest wave of MSC in the embryonic trunk is generated from Sox1+ neuroepithelium but not from mesoderm. Using lineage marking by direct gfp knock-in and Cre-recombinase mediated lineage tracing, we provide evidence that Sox1+ neuroepithelium gives rise to MSCs in part through a neural crest intermediate stage. This pathway can be distinguished from the pathway through which Sox1+ cells give rise to oligodendrocytes by expression of PDGFRbeta and A2B5. MSC recruitment from this pathway, however, is transient and is replaced by MSCs from unknown sources. We conclude that MSC can be defined as a definite in vivo entity recruited from multiple developmental origins.     

RANKL-stimulated TNFalpha production in osteoclast precursor cells promotes osteoclastogenesis by modulating RANK signaling pathways

Although TNFalpha is known to be an important factor for bone resorption, particularly in inflammatory bone diseases, the relevance between RANKL and TNFalpha in osteoclastogenesis remains unclear. In this study we examined the mechanism of TNFalpha induced osteoclastogenesis and its downstream signaling. We show that osteoclastogenesis is suppressed by anti-TNFalpha- and anti-TNF receptor type I (TNFRI)-antibodies and in TNFalpha- and TNFRI-deficient mice using in vitro culture systems: (1) co-culture of mouse spleen derived osteoclast precursor cells (pOCs) with osteoblasts, (2) pure pOC culture and (3) RAW264.7 cells in presence of RANKL. Furthermore, TNFalpha production in pOCs was stimulated by RANKL. Endogenous TNFalpha in pOCs induced c-Fos and NFATc1. Expression rates of NFATc1 and c-Fos were significantly decreased in TNFalpha- and TNFRI-deficient pOCs during osteoclastogenesis. These results indicate that TNFalpha is induced by RANKL in pOCs and serves as an autocrine factor promoting osteoclastogenesis through c-Fos and NFATc1 activation.     

Relationships of anti-PAc (361-386) peptide salivary IgA antibody, eosinophils and basophils with periodontal status in the elderly

The amino acid residues 361-386 of Streptococcus mutans PAc includes an important region associated with the interaction between S. mutans and salivary components. We investigated the relationships between levels of the anti-PAc (361-386) peptide antibody (PPA) in saliva and periodontal status in 281 elderly subjects (mean age 77 years; 118 females, 163 males) by assessing dental calculus (CA), attachment loss (AL), pocket depth (PD), bleeding on probing (BOP) and various blood parameters. Enzyme-linked immunosorbent assay results revealed that subjects with a PPA level of greater than 0.1 (PPA detected group) showed a lower average value for number of sites with more than 6 mm of AL/6 points x 100/tooth (rAL6) than those with a PPA level of less than 0.1 (PPA not detected group). Furthermore, average values for rAL6 were significantly lower in the PPA detected group, and BOP, AL and rAL6 correlated positively and significantly with the percentage of eosinophils present in leukocytes in female subjects in both groups. PPA level had a negative correlation with percentages of basophils and eosinophils. The results indicate that systemic increases in numbers of eosinophils and basophils are associated with the development of periodontal diseases, while PPA level may be a useful indicator of periodontal status.     

Enhancement of lipid peroxidation and its amelioration by vitamin E in a subject with mutations in the SBP2 gene

Selenocysteine (Sec) insertion sequence-binding protein 2 (SBP2) is essential for the biosynthesis of Sec-containing proteins, termed selenoproteins. Subjects with mutations in the SBP2 gene have decreased levels of several selenoproteins, resulting in a complex phenotype. Selenoproteins play a significant role in antioxidative defense, and deficiencies in these proteins can lead to increased oxidative stress. However, lipid peroxidation and the effects of antioxidants in subjects with SBP2 gene mutations have not been studied. In the present study, we evaluated the lipid peroxidation products in the blood of a subject (the proband) with mutations in the SBP2 gene. We found that the proband had higher levels of free radical-mediated lipid peroxidation products, such as 7β-hydroxycholesterol, than the control subjects. Treatment of the proband with vitamin E (α-tocopherol acetate, 100 mg/day), a lipid-soluble antioxidant, for 2 years reduced lipid peroxidation product levels to those of control subjects. Withdrawal of vitamin E treatment for 7 months resulted in an increase in lipid peroxidation products. Collectively, these results clearly indicate that free radical-mediated oxidative stress is increased in the subject with SBP2 gene mutations and that vitamin E treatment effectively inhibits the generation of lipid peroxidation products.     

Phylogenetic relationships within Echinococcus and Taenia tapeworms (Cestoda: Taeniidae): an inference from nuclear protein-coding genes

The family Taeniidae of tapeworms is composed of two genera, Echinococcus and Taenia, which obligately parasitize mammals including humans. Inferring phylogeny via molecular markers is the only way to trace back their evolutionary histories. However, molecular dating approaches are lacking so far. Here we established new markers from nuclear protein-coding genes for RNA polymerase II second largest subunit (rpb2), phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold). Bayesian inference and maximum likelihood analyses of the concatenated gene sequences allowed us to reconstruct phylogenetic trees for taeniid parasites. The tree topologies clearly demonstrated that Taenia is paraphyletic and that the clade of Echinococcus oligarthrus and Echinococcusvogeli is sister to all other members of Echinococcus. Both species are endemic in Central and South America, and their definitive hosts originated from carnivores that immigrated from North America after the formation of the Panamanian land bridge about 3 million years ago (Ma). A time-calibrated phylogeny was estimated by a Bayesian relaxed-clock method based on the assumption that the most recent common ancestor of E. oligarthrus and E. vogeli existed during the late Pliocene (3.0 Ma). The results suggest that a clade of Taenia including human-pathogenic species diversified primarily in the late Miocene (11.2 Ma), whereas Echinococcus started to diversify later, in the end of the Miocene (5.8 Ma). Close genetic relationships among the members of Echinococcus imply that the genus is a young group in which speciation and global radiation occurred rapidly.     

Molecular characterization of MHC class I and beta-2 microglobulin in a clonal strain of ginbuna crucian carp, Carassius auratus langsdorfii

Clonal ginbuna crucian carp is, a naturally gynogenetic fish, and is a useful model animal for studying T-cell-mediated immunity. To gain molecular information on MHC class I molecules from this species, we have identified four types of MHC class I (caauUA-S3n, caauUF-S3n, caauZE-S3n, and caauZB-S3n) and five beta 2-microglobulin (β(2)m) (caauβ2m-1a, caauβ2m-1b, caauβ2m-2, caauβ2m-3a and caauβ2m-3b) by an expressed sequence tag (EST) analysis and using homology cloning with degenerated primers. Like UA class I genes in other cyprinid fish, the caauUA-S3n shows features of classical MHC class I, such as conservation of all key amino acids interacting with antigenic peptides, and ubiquitous tissue expression. A phylogenetic analysis shows that the β(2)m-1 and β(2)m-2 isoforms are clustered with those of other cyprinid fishes, while β(2)m-3 isoforms make a cluster that is separated from a common ancestor of salmonid and cyprinid fishes. This finding suggests that the β(2)m isoforms of ginbuna cruician carp comprise two lineages and may possess different functions. The MHC class I and β(2)m sequences from one clonal strain will facilitate our understanding of the interaction of MHC class I with β(2)m in teleosts.