This paper presents new approach for unobtrusive indoor fall detection by an IR thermal array sensor. Unlike existing methods that run fall detection at server and require high communication and processing rates, we perform fall detection within the sensor node by a computationally inexpensive algorithm that signals the server only when a fall occurs. Experiments with prototype design show that such formulation provides robust and real-time fall detection even in a noisy environment.

This article presents new approach for unobtrusive indoor fall detection by an IR thermal array sensor. Unlike existing methods that run fall detection at a server and require high communication rates, we perform fall detection within the sensor node by using a computationally inexpensive algorithm that only signals the server when a fall occurs. Experiments with prototype design show that such formulation provides robust and real-time fall detection even in a noisy environment.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life-threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5days consecutively, in an open-label, multicenter, single-arm study in patients with SJS or TEN. IVIG (400mg/kg per day) administrated for 5days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side-effects from the use of IVIG were not observed. IVIG (400mg/kg per day) administrated for 5days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.

Purpose: LOX-1, a vascular endothelial cell receptor for oxidized low-density lipoprotein (ox-LDL), is reportedly involved in the progression of knee osteoarthritis (OA); however, the underlying mechanism has not been elucidated. In the present study, we established a mouse model of OA through destabilization of the medial meniscus (DMM) to investigate the role of LOX-1 in the pathogenesis of OA progression. Methods: In this study, we used 9-week-old LOX-1+/+ and LOX-1-/- mice. The mice underwent DMM at the right knee (DMM side) as well as a skin incision along with placement of a joint capsule on the contralateral knee (sham-operation side). Samples were obtained from both the knee joints at 4 and 8 weeks after surgery. Safranin staining was performed for each section to assess the osteoarthritic change. Cartilage degeneration, osteophyte formation were assessed by using a scoring system . Moreover, the expression levels of LOX-1 and ox-LDL were assessed in each sample by immunostaining. Results: On the DMM side, osteophyte formation and cartilage degeneration were significantly suppressed in LOX-1-/- mice at 8 weeks after surgery. However, no significant difference in osteophyte formation or cartilage degeneration was noted on the sham-operation side at both 4 and 8 weeks; OA progression was only slightly observed among these mice . Expression was observed cartilage cells, the formation of osteophytes section . Moreover, the expression levels of LOX-1 and ox-LDL in LOX-1+/+ mice were found to be increased from 4 weeks to 8 weeks after surgery. Conclusions: Thus, we believe that LOX-1 may play an important role in the pathogenesis of OA progression. Moreover, we suggest that LOX-1 could be used as a potential target for the prevention and treatment of OA progression.

Drug-induced hypersensitivity syndrome (DIHS), which is also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi-organ systemic reaction characterized by rashes, fever, leukocytosis with eosinophilia and atypical lymphocytes, liver dysfunction, and reactivation of human herpesvirus-6 (HHV-6) [ 1 Tohyama M. Hashimto K. New aspects of drug-induced hypersensitivity syndrome. J Dermatol. 2011; 38: 222-228 Crossref PubMed Scopus (56) Google Scholar , 2 Bocquet H. Bagot M. Roujeau J.C. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg. 1996; 15: 250-257 Crossref PubMed Scopus (772) Google Scholar , 3 Kardaun S.H. Sekula P. Valeyrie-Allanore L. Liss Y. Chu C.Y. Creamer D. et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013; 169: 1071-1080 Crossref PubMed Scopus (494) Google Scholar , 4 Wei C.H. Chung-Yee Hui R. Chang C.J. Ho H.C. Yang C.H. Lin Y.J. et al. Identifying prognostic factors for drug rash with eosinophilia and systemic symptoms (DRESS). Eur J Dermatol. 2011; 21: 930-937 PubMed Google Scholar ]. The mortality rate of DIHS/DRESS has recently been demonstrated to be 2–14% [ 3 Kardaun S.H. Sekula P. Valeyrie-Allanore L. Liss Y. Chu C.Y. Creamer D. et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013; 169: 1071-1080 Crossref PubMed Scopus (494) Google Scholar , 4 Wei C.H. Chung-Yee Hui R. Chang C.J. Ho H.C. Yang C.H. Lin Y.J. et al. Identifying prognostic factors for drug rash with eosinophilia and systemic symptoms (DRESS). Eur J Dermatol. 2011; 21: 930-937 PubMed Google Scholar ]. However, the pathogenesis of this serious syndrome has not been fully elucidated.

症例は47歳の男性で，前日からの腹痛の増悪，嘔吐の出現，意識レベル低下にて救急搬送となった．来院時，意識レベルIII-200（JCS），血圧測定不能，血液ガス検査で代謝性アシドーシス認め，ショック状態であった．腹部造影CTにて腹腔内に多量の遊離ガスと腹水を認め，肝臓と腎臓実質の造影効果は不良であった．消化管穿孔に起因するショック状態と診断し，緊急開腹手術を施行した．多量の汚染腹水，遊離ガス，食物残渣を認め，肝臓は虚血性変化を呈していた．胃底部から体部前壁に壊死を伴う破裂部を認めたため，胃全摘術を施行した．成人の特発性胃破裂はまれであり，過食などによる胃拡張状態に，嘔吐などに伴う胃内圧の急激な上昇や，あるいは胃壁の血流障害に伴う壊死が原因とされている．破裂孔が大きいため，胃内容物の腹腔内流出量が多く，腹部コンパートメント症候群を呈し重症化することがあり，一般的に予後不良とされている．

In atopic dermatitis, IL-17 producing cells infiltrate in acute lesion but decrease in chronic lesion. CCL20/MIP-3α recruits IL-17-producing cells and its expression is significantly suppressed in chronic lesion of atopic dermatitis. Since IL-17 is an inducer of CCL20 in epidermal keratinocytes, we hypothesized that Th2 cytokine suppresses IL-17-induced CCL20 production. To examine the mechanism, we focused on cytokine inducible SH2-containing protein (CISH), a member of SOCS/CIS family. Previously we have shown that IL-4 enhances CISH expression in keratinocytes. However, the role of CISH remains unclear. First, we studied whether Th2 cytokines suppress CCL-20 production in human keratinocytes. In both of monolayer keratinocytes and human keratinocytes using living skin equivalent models (LSEs), Th2 cytokines IL-4/IL-13 suppressed IL-17-induced CCL20 production by 50%. Furthermore, IL-4/IL-13 enhanced the CISH expression by tenfold. Next, to clarify the role of CISH, CISH was expressed in keratinocytes using adenoviral vectors. CISH expression significantly suppressed IL-17-induced CCL20 mRNA expression, while IL-17-induced HBD2 mRNA expression was not altered. In addition, CISH expression did not affect IL-1 or TNF-α-induced CCL20 production. From these data, we suggest the following mechanisms. In an acute phase, pro-inflammatory cytokines IL-1 and TNF-α induces CCL20 production from keratinocytes, recruiting IL-17 producing cells into the lesion. The IL-17 contributes to antimicrobial defense and production of additional CCL20 which may recruit more IL-17-producing cells. However, in a chronic stage, enhanced CISH expression suppresses IL-17-induced CCL20 production, which may decrease IL-17 producing cells resulting in a disturbance of antimicrobial defense. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF

症例は気管支喘息治療中の58歳の男性で，2か月前より腹痛を認めていたが，白血球数40,200/μl（好酸球68%），CRP 18.6 mg/dlと上昇，右上下肢神経障害認め，アレルギー性肉芽腫性血管炎が疑われた．プレドニゾロン45 mg/day，アスピリン100 mg/day，ベラプロストナトリウム120 μg/dayの内服を開始するも下腹部に激痛認め当院総合診療科紹介受診，腹部造影CTにてfree air認め小腸穿孔の疑いで外科紹介となった．身体所見は血圧109/77 mmHg，脈拍数136 bpm，体温37.5度，るい痩著明で腹部全体に筋性防御を認めた．血液検査所見は白血球数29,600/μl，CRP 24.6 mg/dlと高度の炎症所見上昇を認めた．以上より小腸穿孔による汎発性腹膜炎と診断し緊急手術を施行した．手術所見はTreitz靭帯から回腸終末約30 cmに至るまでの小腸腸間膜対側壁がとび石状に壊死および穿孔所見を呈する多発小腸穿孔・壊死および汎発性腹膜炎の状態であったため，小腸亜全摘術，腹腔ドレナージ術，胃瘻および腸瘻造設術を施行した．現在術後20か月が経過するがプレドニゾロン10 mg/day内服にて全身状態は良好である．小腸穿孔を伴うアレルギー性肉芽腫性血管炎の報告は少なく，なかでも広範囲な多発小腸穿孔による大量小腸切除例の報告は極めてまれである．今回，我々は貴重な症例を経験できたので若干の文献的考察を含め報告する．

Delayed gastric emptying without mechanical obstruction after Roux-en-Y reconstruction has been defined as Roux stasis syndrome. It occurs in 10-30% of patients after such reconstruction. So far, the cause of this stasis has not been completely identified. This study aimed to reduce Roux stasis using surgical techniques.From November 2007 to October 2010, we performed 101 distal gastrectomies with Roux-en-Y reconstruction. All the gastrojejunostomies were performed with end-to-end anastomoses. Roux stasis was analyzed with respect to tumor location, extent of the dissection, tumor progression, operation time, antecolic/retrocolic reconstruction, and the shape of the gastrojejunostomy. The shape of the gastrojejunostomy was evaluated by contrast gastroradiography 4 days after the operation.Roux stasis syndrome was observed in 17 of the 101 patients. There was no relationship between the extent of the dissection, tumor progression, or operation time and the occurrence of Roux stasis. There was no difference in the incidence of Roux stasis between antecolic and retrocolic reconstructions. However, the group that displayed a straight anastomotic shape on contrast radiography demonstrated an apparently lower incidence of Roux stasis (p = 0.0003). In addition, Roux-en-Y reconstruction following gastric cancer was more frequently followed by Roux stasis in the antrum than in the midstomach (p = 0.0036). Cases of Roux stasis occurred 11.8 days after surgery on average and resolved within 2 weeks on average.Our findings demonstrate the substantial benefits of a straight anastomosis of the gastrojejunostomy for the prevention of Roux stasis syndrome.

BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS. METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.

Purpose: Recently, the local renin-angiotensin system (RAS) has attracted many researchers in many pathophysiological issues. In Orthopedics, expression of local RAS was found in bone tissues, fracture callus and arthritic synovium. The purpose of this study is to reveal immunohistological localization of the RAS components in the epiphyseal plates of mice and to analyze function of the local RAS in the processes of hypertrophic differentiation using ATDC5 chondroprogenitor cells. Methods: The epiphyseal plates of 8-week-old mice was immunostained with antibodies to angiotensinogen, angiotensinogen converting enzyme 1 (ACE1), angiotensinII type 1 receptor (AT1R) and angiotensinII type 2 receptor (AT2R). We cultured ATDC5 in long term and evaluated the expression of angiotensinogen, ACE1, AT1R, AT2R and type 2 collagen (COL2) by real- time PCR and Western blot analysis. Results: In the epiphyseal plates of mice, angiotensinogen and AT1R expressed in the resting chondrocytes, the proliferative chondrocytes and hypertrophic chondrocytes; however, ACE1 and AT2R expressed only in the hypertrophic chondrocytes. In ATDC5 chondroprogenitor cells, the local RAS components expressed both in proliferative and hypertrophic differentiating stages. Conclusions: The local RAS expresses in the epiphyseal plates of mice and might play an important role in the process of hypertrophic differentiation.

Angiogenesis is required for physiological tissue repair processes, such as cutaneous wound healing. However, recent studies indicate that endogenous angiogenic factors may enhance photo-induced skin alterations in response to experimental ultraviolet (UV)-B exposure. Angiopoietin-related growth factor (AGF), also known as angiopoietin-like protein 6 (Angptl6), is known to promote new blood vessel formation and vascular hyperpermeability. Importantly, epidermal overexpression of Angptl6/AGF in mice promotes wound healing in the skin. However, it remains unclear whether overexpression of Angptl6/AGF facilitates tissue repair processes in response to UV-B irradiation. To test this hypothesis, we subjected Angptl6/AGF transgenic mice to acute or chronic UV-B exposure. Surprisingly, transgenic mice showed enhanced photosensitivity to subthreshold doses of UV-B that did not induce skin alterations in wild-type littermates. Marked enlargement of blood vessels was observed after a single exposure to UV-B in Angptl6/AGF transgenic mice, although no epidermal changes were observed. Chronic UV-B exposure over 14 weeks promoted cutaneous skin damage in Angptl6/AGF transgenic mice, whereas wild-type mice showed little or no macroscopic skin alteration. In addition to pronounced angiogenesis and epidermal hyperplasia, marked enlargement of dermal lymphatic vessels was observed in UV-B-exposed Angptl6/AGF transgenic mice. Electron microscopy analysis further revealed that the number and size of collagen bundles in the dermis was markedly reduced after chronic UV-B exposure in Angptl6/AGF transgenic mice. Taken together, these results indicate that ectopic expression of Angptl6/AGF in mice likely promotes UV-B-induced skin alterations, and that angiogenesis could be a therapeutic target in prevention of skin photo-aging.

Drug-induced hypersensitivity syndrome (DIHS) is caused by a limited number of specific drugs and is characterized by late onset, infectious mononucleosis-like symptoms, and herpesvirus 6 (HHV-6) reactivation. Recently, the involvement of herpes viruses other than HHV-6, such as Epstein-Barr virus and cytomegalovirus, has been reported. Many approaches have been used to analyze the pathological mechanism, and have revealed new aspects of DIHS. Here, we focused on three key recent findings regarding DIHS: (i) overlap between DIHS and Stevens-Johnson syndrome/toxic epidermal necrolysis; (ii) the relevance of Epstein-Barr virus in the development of infectious mononucleosis-like symptoms of DIHS; and (iii) roles of monomyeloid precursors increased in the blood and plasmacytoid dendritic cells increased in the lesion skin in HHV-6 reactivation.

82歳，男性。2009年5月より水疱が口腔内に出現し，軟口蓋を中心に出現消退を繰り返し，徐々に疼痛を伴うようになったため，2010年3月当科紹介受診した。病理組織検査では，粘膜上皮下に水疱を認め，正常ヒト皮膚を基質とした蛍光抗体間接法では，抗基底膜IgG抗体が40倍まで陽性であった。1M食塩水で剥離した正常ヒト皮膚を基質とした蛍光抗体間接法では，抗基底膜部抗体は水疱底に反応した。ELISA法による抗デスモグレイン1，3抗体，抗BP180抗体，抗BP230抗体は陰性で，真皮抽出液を用いた免疫ブロットにて患者血清は290kDの蛋白に反応したが，抗VII型コラーゲンELISAは陰性であった。以上の結果より，VII型コラーゲンが抗原と思われる粘膜類天疱瘡と診断した。ミノマイシン，ニコチン酸アミド，コルヒチンは副作用出現のため内服継続できずプレドニゾロン内服にて加療した。

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube length by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions.

The Journal of DermatologyVolume 38, Issue 3 p. 292-294 Possible association of vascular endothelial growth factor with the development of edema in drug-induced hypersensitivity syndrome Satoshi HIRAKAWA, Satoshi HIRAKAWA Department of Dermatology,Ehime University Graduate School of Medicine Department of Cell Growth and Tumor Regulation, Ehime Proteo-Medicine Research Center, Ehime University, Ehime, JapanSearch for more papers by this authorHidenori OKAZAKI, Hidenori OKAZAKI Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorKoji SAYAMA, Koji SAYAMA Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorMikiko TOHYAMA, Mikiko TOHYAMA Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorKoji HASHIMOTO, Koji HASHIMOTO Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this author Satoshi HIRAKAWA, Satoshi HIRAKAWA Department of Dermatology,Ehime University Graduate School of Medicine Department of Cell Growth and Tumor Regulation, Ehime Proteo-Medicine Research Center, Ehime University, Ehime, JapanSearch for more papers by this authorHidenori OKAZAKI, Hidenori OKAZAKI Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorKoji SAYAMA, Koji SAYAMA Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorMikiko TOHYAMA, Mikiko TOHYAMA Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this authorKoji HASHIMOTO, Koji HASHIMOTO Department of Dermatology,Ehime University Graduate School of MedicineSearch for more papers by this author First published: 11 November 2010 https://doi.org/10.1111/j.1346-8138.2010.01086.xCitations: 3 Satoshi Hirakawa, M.D., Ph.D., Department of Dermatology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon-shi, Ehime 791-0295, Japan. Email: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume38, Issue3Special Issue: SPECIAL ISSUE: Severe Adverse Cutaneous Drug Reaction (pages 215‐260)March 2011Pages 292-294 RelatedInformation

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by multiple factors. Among them, house dust mite (HDM) allergens are important in the development of AD. In airway allergy, HDM allergens activate innate immunity. However, information regarding the activation of innate immunity by HDM allergens in the skin is limited.Objectives: The inflammasome is a key regulator of pathogen recognition and inflammation. We investigated whether HDM allergens activate the inflammasome in epidermal keratinocytes.Methods: Keratinocytes were stimulated with Dermatophagoides pteronyssinus, and the activation of caspase-1 and secretion of IL-1 beta and IL-18 were examined. Formation of the inflammasome was studied by analyzing the subcellular distributions of inflammasome proteins. The importance of specific inflammasome proteins was studied by knocking down their expression through transfection of keratinocytes with lentiviral particles carrying short hairpin RNAs (shRNAs).Results: D pteronyssinus activated caspase-1 and induced caspase-1-dependent release of IL-1b and IL-18 from keratinocytes. Moreover, D pteronyssinus stimulated assembly of the inflammasome by recruiting apoptosis-associated specklike protein containing a caspase-recruitment domain (ASC), caspase-1, and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin-domain containing 3 (NLRP3) to the perinuclear region. Finally, infection with lentiviral particles carrying ASC, caspase-1, or NLRP3 shRNAs suppressed the release of IL-1 beta and IL-18 from the keratinocytes. Activation of the NLRP3 inflammasome by D pteronyssinus was dependent on cysteine protease activity.Conclusion: House dust mite allergens are danger signals for the skin. In addition, HDM-induced activation of the NLRP3 inflammasome may play a pivotal role in the pathogenesis of AD. (J Allergy Clin Immunol 2011;127:806-14.)