トクシマ コウエン トクシマ チュウオウ コウエン ノ ゾウエン セッケイ ニツイテ : ヒビヤ コウエン オヨビ ザイファースドルフジョウ トノ ヒカク

Tokushima Park (originally named Tokushima Central Park) is the Japan’s second western-style park that was opened in 1906. We investigated landscape architecture of Tokushima Park based on a blueprint made in 1905 to understand its purpose and function of the park, and compared with Hibiya Park that is the Japan’s first western-style park. Tokushima Park consisted of five areas. The central area included Mt. Shiroyama (Castle Mountain), and primeval forest was protected without allowing to make a big building within the area. A commercial museum, an athletic field, and a botanical garden and a library were placed in the southern, western and eastern areas respectively, so that each area was designed to exhibit each function. Tokushima Park and Hibiya Park were designed by the same two persons Seiroku Honda and Takanori Hongo. The two parks were equipped with a wide road, an athletic field, a botanical garden and so on, and these facilities were adopted to the park made since them. Because Seiroku Honda adopted three design drawings of German parks from the book Gärtnerisches Planzeichnen into a blueprint of Hibiya Park, we investigated the book to ascertain whether any design drawing was also used in Tokushima Park. We found that Seifersdorf Castle, the castle of count Brühl that was built at Seifersdorf in Germany in 13th century, is similar to the southern area of Tokushima Park

Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tamoxifen may occasionally precipitate serious and potentially life-threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors.</p> <p>Case presentation</p> <p>A 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer.</p

Dimethyl fumarate dampens IL-17-ACT1-TBK1 axis-mediated phosphorylation of Regnase-1 and suppresses IL-17–induced IκB-ζ expression

The signaling elicited by the cytokine interleukin-17A (IL-17) is important for antimicrobial defense responses, whereas excessive IL-17 production leads to autoimmune diseases such as psoriasis and multiple sclerosis. IL-17–induced stabilization of mRNAs has been recognized as a unique and important feature of IL-17 signaling. Previously, we demonstrated that IL-17 signaling protein ACT1 is required to counteract constitutive inhibitor of nuclear factor kappa B zeta (IκB-ζ) mRNA degradation by the ribonuclease Regnase-1. However, information about the mechanism of mRNA stabilization in IL-17–stimulated cells remains insufficient. In the present study, we aimed to clarify the mechanism in more detail and identify an agent that can inhibit IL-17–induced mRNA stabilization. Experiments using small interfering RNA and an inhibitor of TANK-binding kinase 1 (TBK1) revealed that TBK1 was required for IκB-ζ mRNA stabilization through Regnase-1 phosphorylation. Intriguingly, this TBK1-mediated phosphorylation of Regnase-1 was suppressed by the addition of dimethyl fumarate (DMF), an electrophilic small molecule that has been used to treat IL-17–related autoimmune diseases. Confocal microscopic observation of the cellular localization of ACT1 revealed that DMF treatment resulted in the disappearance of ACT1 nuclear dots and perinuclear accumulation of ACT1. These results suggested that DMF is a small molecule that compromises IL-17–induced activation of the ACT1-TBK1 pathway, thereby inhibiting IL-17–induced mRNA stabilization

IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17–Regulated mRNA Stabilization

Cytokine IL-17A (IL-17) acts on various cell types, including epidermal keratinocytes, and induces antimicrobial peptide and chemokine production to elicit antibacterial and antifungal defense responses. Excess IL-17 leads to inflammatory skin diseases such as psoriasis. The IκB family protein IκB-ζ mediates IL-17–induced responses. However, the mechanism controlling IκB-ζ expression in IL-17–stimulated cells remains elusive. In this study, we showed that JAK kinase TYK2 positively regulates IL-17–induced IκB-ζ expression. TYK2-deficient mice showed reduced inflammation and concomitant reduction of IκB-ζ mRNA compared with wild-type mice in imiquimod-induced skin inflammation. The analysis of the IκB-ζ promoter activity using human cell lines (HaCaT and HeLa) revealed that catalytic activity of TYK2 and its substrate transcription factor STAT3, but not IL-17, is required for IκB-ζ promoter activity. In contrast, IL-17–induced signaling, which did not activate STAT3, posttranscriptionally stabilized IκB-ζ mRNA via its 3′-untranslated region. IL-17 signaling protein ACT1 was required to counteract constitutive IκB-ζ mRNA degradation by RNase Regnase-1. These results suggested that transcriptional activation by TYK2–STAT3 pathway and mRNA stabilization by IL-17–mediated signals act separately from each other but complementarily to achieve IκB-ζ induction. Therefore, JAK/TYK2 inhibition might be of significance in regulation of IL-17–induced inflammatory reactions