Hardy夫妻の愛と悲しみの歴史 : “Poems of 1912-13”誕生の背景

The purposes of this paper are twofold: (1) to trace the unhappy relationship between Thomas Hardy and his wife, Emma, and (2) to make clear the reasons why Hardy composed 21 poems immediately after the death of Emma, whom he had treated coldly while she was alive.In spite of their love marriage of four years’ courtship, Hardy and Emma fell out with each other in less than a year, and their love began to fade by degrees. Their life was dyed with gloomy color. However, Hardy made no effort to improve the matter and restore their former love and harmony. The only thing he did was to escape into his own world as a writer. He continued to ignore his wife’s sad, painful feelings.Emma died suddenly in solitude in 1912. After her death, Hardy read “Some Recollections” written by her. This is a private history that describes their loving courtship in detail. Emma’s writing affected Hardy: he recalled their old, happy love and he also regretted his negligence as husband, though too late.Hardy composed 116 poems referring to Emma after her death. Especially he selected 21 poems from the group which he composed from December 1912 to March 1913, named “Poems of 1912-13” and released them in “Satires of Circumstance” in 1914. “Poems of 1912-13” is, therefore, Thomas and Emma Hardy’s autography of love and sorrow, and at the same time, Hardy’s confession of his guilt.論

TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes

BACKGROUND: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases' pathogenesis, the regulation mechanism of serine proteases and the inhibitors' expression in epidermal keratinocytes must be clarified. OBJECTIVES: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. METHODS: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. RESULTS: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3-5 days later but attenuated 6-7 days later period by these cytokines. CONCLUSIONS: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation

The treatment effect of endovascular therapy for chronic limb‐threatening ischemia with systemic sclerosis

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients

Up-regulation of activation-induced cytidine deaminase and its strong expression in extra- germinal centres in IgG4-related disease

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic disorder involving benign mass formation due to fibrosis and intense lymphoplasmacytosis; the chronic inflammation associated with the disease might also contribute to oncogenesis. Activation-induced cytidine deaminase (AID), normally expressed in germinal centre activated B-cells, is an enzyme that edits DNA/RNA and induces somatic hypermutation and Ig class switching. AID expression is strictly controlled under physiological conditions; however, chronic inflammation and some infectious agents induce its up-regulation. AID is overexpressed in various cancers and may be important in chronic inflammation-associated oncogenesis. We examined AID expression in IgG4-related sialadenitis (n = 14), sialolithiasis (nonspecific inflammation, n = 13), and normal submandibular glands (n = 13) using immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Immunohistochemistry revealed significantly more AID-expressing cells in IgG4-related sialadenitis than in sialolithiasis or normal submandibular gland samples (P = 0.02 and P < 0.01, respectively); qPCR yielded similar results. Thus, AID was significantly more up-regulated and had higher expression in extra-germinal centres in IgG4-RD than in non-specific inflammation or normal conditions. This report suggests that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation. Furthermore, chronic inflammation-associated AID-mediated oncogenesis is possible in IgG4-RD

A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease

We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis

A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation

Malaria parasites proliferate by repeated invasion of and multiplication within erythrocytes in the vertebrate host. Sexually committed intraerythrocytic parasites undergo sexual stage differentiation to become gametocytes. After ingestion by the mosquito, male and female gametocytes egress from erythrocytes and fertilize within the mosquito midgut. A complex signaling pathway likely responds to environmental events to trigger gametogenesis and regulate fertilization; however, such knowledge remains limited for malaria parasites. Several pseudokinases are highly transcribed at the gametocyte stage and are possible multi-functional regulators controlling critical steps of the life cycle. Here we characterized one pseudokinase, termed PypPK1, in Plasmodium yoelii that is highly expressed in schizonts and male gametocytes. Immunofluorescence assays for parasites expressing Myc-tagged PypPK1 confirmed that PypPK1 protein is expressed in schizonts and sexual stage parasites. Transgenic ΔpPK1 parasites, in which the PypPK1 gene locus was deleted by the CRISPR/Cas9 method, showed significant growth defect and reduced virulence in mice. In the blood stage, ΔpPK1 parasites were able to egress from erythrocytes similar to wild type parasites; however, erythrocyte invasion efficacy was significantly reduced. During sexual stage development, no clear changes were seen in male and female gametocytemias as well as gametocyte egress from erythrocytes; but, the number of exflagellation centers and oocysts were significantly reduced in ΔpPK1 parasites. Taken together, PypPK1 has an important role for both erythrocyte invasion and exflagellation center formation

Retention rate of physicians in public health administration agencies and their career paths in Japan

<p>Abstract</p> <p>Background</p> <p>Physicians who serve as public health specialists at public health centers and health departments in local or central government have significant roles because of their public health expertise. The aim of this study is to analyze the retention and career paths of such specialists in Japan.</p> <p>Method</p> <p>We analyzed the data of seven consecutive surveys, spanning 1994 to 2006. We first analyzed the 2006 survey data by sex, age group, and facility type. We then examined the changes over time in the proportion of physicians working in public health administration agencies. We also examined the distribution of the facility types and specialties in which physicians worked both before beginning and after leaving their jobs. These analyses were performed by using physician registration numbers to cross-link data from two consecutive surveys.</p> <p>Results</p> <p>The proportion of physicians working in public health administration agencies was 0.7% in 2006. The actual numbers for each survey ranged between 1,800 and 1,900. The overall rate remaining in public health administration agencies during the two-year survey interval was 72.8% for 1994-1996. The ratio declined to 67.2% for 2004-2006. Among younger physicians with 1-10 years of experience, the retention rate showed a sharp decline, dropping from 72.6% to 50.0%. Many of these physicians came from or left for a hospital position, with the proportion entering academic hospital institutions increasing in recent years. In many cases, physicians left or entered internal medicine clinical practices.</p> <p>Conclusion</p> <p>At present in Japan, the number of physicians who leave and the number who begin a position are almost the same; thus, some of the problems associated with physicians leaving are yet to become apparent. However, the fact that the retention period is shortening for younger physicians may represent a future problem for ensuring the quality of physicians in public health administration agencies. Possible strategies include: increasing the number of physicians entering positions; reducing the number leaving positions; and creating a system where physicians can easily reenter positions after leaving while also establishing a revolving door type of career development system, involving both public health departments and hospital clinical departments.</p