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Background Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). Methods This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The ‘malaria indicator questionnaire’ (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. Results There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p

Background Malaria is one of the most prevalent and deadliest illnesses in sub-Saharan Africa. Despite recent gains made towards its control, many African countries still have endemic malaria transmission. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme. Methods Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (a WASH action site) and Kasangulu (a WASH control site) in DRC between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys were conducted with the use of World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action programme aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both study sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among the respondents. Furthermore, a six-month hospital-based epidemiological study was conducted at selected referral hospitals at each site from 1 January through June 2017 to determine malaria trend. Results Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%); 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) reported at least one episode occurring in the previous six months; of them only 66.5% received malaria care at a health setting. In the Action Research, mean incident household malaria cases decreased significantly at WASH action site (2.3 ± 2.2 cases vs. 1.2 ± 0.7 cases, respectively; p Conclusion This research showed high prevalence of positive malaria RDT among the responders and high household malaria incidence, which were reduced by a 6-month WASH intervention. DRC government should scale up malaria control strategy by integrating efficient indoor and outdoor preventive measures and improve malaria care accessibility.

Summary: Malaria is one of the most prevalent and deadliest illnesses in the Sub-Saharan Africa. Despite recent gains made towards its control or elimination in past decades, many African countries still have endemic malaria transmission. Therefore, the search for novel disease control strategies and approaches are in progress. This study aimed to evaluate household malaria burden in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory water, sanitation and hygiene (WASH) action. Methods: Mixed method study was conducted in two semi-rural towns, Mbanza-Ngungu (WASH action site) and Kasangulu (control site), involving 625 households (3,712 individuals). Baseline and post-intervention surveys were conducted; an action research consisting of six-month prospective study was carried out which comprised two interventions: (1) community participatory WASH action and (2) anti-malaria education campaign. The latter was implemented in both study sites. In addition, rapid diagnostic test (RDT) for malaria was performed in respondents. Findings: Prevalence of positive malaria RDT among respondents decreased (38% vs. 20%) at WASH-action site, whereas it increased at the control site but not significantly. Of 96% of respondents who reported at least one malaria event occurring in the previous six-month period, only 66.5% of them received malaria care at a health setting. At household level, long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%), followed by mosquito repellent (15%), indoor residual spraying (IRS) (2%), LLIN-IRS combination (2%); however, 24% of households did not use any measures. Mean household malaria incidence decreased in WASH action site; 2.3±2.2 cases vs. 1.2±0.7 cases, whereas no significant change was noted in control site. Moreover, malaria incidence rate was highest (60.9%) among households living in proximity to grassy and stagnant water spots. Proximity to high risk area (grassy/stagnant water spots) for malaria (ORa=5.13; 95%CI: 2-29-8.07; p

Atopic dermatitis (AD) is a skin disorder characterized by filaggrin (FLG) defect. We evaluated sacran’s effects on dust-mite extracts (DME)-induced AD-like disease and also its effect on profilaggrin (proFLG) in a murine model of 2,4-dinitroflurobenze (DNFB)-induced contact hypersensitivity. In the murine AD-like disease model, allergic NC/Nga mice (N = 60) were randomly divided into five treatment groups of 12 animals each: 0.2% and 1%sacran; 0.1% Tacrolimus; Vaseline and buffer-treated controls. Blood samples were drawn and serum levels of representative Th-1, Th-2 and also Th-17 (IL-17A) cytokines were assayed by Cytometric Bead Array (CBA). In the contact hypersensitivity model, diseased NC/Nga mice (N = 20) were divided into four groups of five mice each [0.05%sacran, 0.05% chondroitin sulfate (CS), 0.5% prednisolone (PD), non-treated control group] and were treated for 14 days. Skin biopsies were performed for the measurement of proFLG-mRNA by real-time PCR. Sacran solutions and 0.1%Tacrolimus reduced disease severity, suppressed histological changes and decreased the serum Th-1 (IFN-γ, TNF-α, IL-2) and Th-2 (IL-4, IL-6, IL-10) cytokines in allergic mice (vs. controls). Additionally, a marked increase of proFLG-mRNA expression was observed in 0.05%sacran group (vs. control 0.05% CS and 0.5% PD groups). Thus, Sacran might be useful as a natural skin barrier enhancer and anti-allergic agent.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control massive postpartum hemorrhage. Case presentation A 41-year-old woman transferred to hospital following cesarean section presented in refractory hemorrhagic shock. REBOA was blindly performed in the emergency department. She immediately underwent hysterectomy and damage control surgery in the operating room. The aortic balloon, whose position was confirmed at zone II by postoperative X-ray, provided intermittent occlusion for 40 min during surgery. Hemodynamics were stabilized with these interventions, with massive transfusion required for severe coagulopathy perioperatively. She gradually recovered with intensive care but suffered ascending colon ischemia with perforation on day 16. She received a colostomy and was discharged without sequelae after 130 days. Amniotic fluid embolism was diagnosed according to clinical criteria and supplemental serum markers. Conclusions This patient suffered colonic ischemia possibly due to REBOA used to manage amniotic fluid embolism. REBOA requires careful consideration to avoid complications.

Objective Gastrointestinal dysmotility in critically ill patients is important as enteral nutrition is crucial. However, normal gut motility is impaired under conditions of critical illness subsequent to severe insult. Interstitial cells of Cajal (ICC) form an extensive network associated with the myenteric plexus in the enteric nervous system. There are few reports about ICC distribution in critically ill patients. The aim of this study was to evaluate ICC in critically ill patients. Methods Postmortem colon harvest was obtained from critically ill patients. Control specimens were obtained from patients without bowel movement problems who underwent hemicolectomy. The tissues were stained with c-Kit for ICC. The number of ICC was identified by counting from 10 high-power fields (HPFs). Results Specimens from six patients were analyzed and compared with those from six control patients. All patients had abnormalities of crypt architecture and inflammatory cell infiltrations. Mucosal thickness tended to be lower in the critically ill patients than in the controls (147 ± 47 versus 231 ± 127 μm; P = 0.15). Muscle layer thickness tended to be higher in the critically ill patients than in the controls (494 ± 163 versus 394 ± 258 μm; P = 0.44). ICC in the critically ill patients were almost depleted in the colon compared with those in the controls. Significantly fewer ICC were present in the critically ill patients than in the controls (0.45 versus 7.25 cells/HPF; P Conclusions Critical illness is associated with diminished numbers of ICC in the colon. This finding could have implications for dysmotility in critically ill patients.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Bacterial translocation is a major cause of multiple organ dysfunction syndrome in critical illness, and its management is an important therapeutic strategy. In this study, we focused on the key factors responsible for bacterial translocation including the intestinal microbiome and investigated the impact of molecular hydrogen therapy as a countermeasure against bacterial translocation in a murine model of sepsis. The experimental protocols were divided into the sham, saline treatment (control), and hydrogen treatment (H2) groups. In the H2 group, 15 mL/kg of hydrogen-rich saline (7 ppm) was gavaged daily for 7 days following cecal ligation and puncture (CLP). In the control group, normal saline was gavaged in the same way. In the results, the 7-day survival rate was significantly improved in the H2 group versus the control group (69% vs. 31%, P 0.05). The incidence of bacterial translocation at 24 h after CLP as assessed by cultivation of mesenteric lymph nodes and blood was significantly decreased in the H2 group versus the control group. Administration of hydrogen-rich saline also prevented the expansion of facultative anaerobic Enterobacteriaceae and ameliorated intestinal hyperpermeability at 24 h after CLP. Intestinal tissue levels of inflammatory mediators such as inducible nitric oxide synthases, tumor necrosis factor α, interleukin (IL)-1β, IL-6, and oxidative stress marker malondialdehyde at 6 h after CLP were down-regulated in the H2 group. These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.

Numerous environmental factors are incriminated in the occurrence of skin disorders. Here, we provide an overview on dermatitis caused by bacteria, Kawasaki disease (KD), and the association between silica-dust exposure and cutaneous autoimmune diseases. Common bacterial skin infections are caused by Staphylococcus (S. aureus, S. beta-hemolytic) and Streptococcus (S. pyogenes) species, and they include cellulitis, erysipelas, ecthyma, impetigo, and others. On the other hand, folliculitis is caused by a gram-negative bacteria known as Pseudomonas aeruginosa. Recently, reports have suggested the infectious origin of KD, and there have been several KD cases reported in Asia and western countries, and KD is considered as a leading cause of acquired heart disease in children population. Recent researchers have discovered KD-specific molecules that share the same structures with microbe-associated molecular patterns (MAMPs), suggesting that KD might have an infectious origin. In the acute phase, KD patients often present with fever, erythema, edema in the extremities and accompanied by pain, exanthema, cervical lymphadenopathy (mostly unilateral, nonsuppurative), conjunctival injection, and changes in the lips and tongue (strawberry tongue, a common sign in KD patients) and oropharyngeal mucosa. Occupational silica-dust exposure has been associated with the development of a number of autoimmune diseases, including scleroderma. Additionally, since the work by Erasmus, several case-control studies have demonstrated this association and provided clues on biomarkers (anti-centromeric proteins (anti-CNEP-B in particular), anti-Scl70) that can serve in the early diagnosis of systemic sclerosis or scleroderma as well as a screening tool among silica-dust-exposed workers.

Atopic dermatitis (AD) is a chronic relapsing, and severely pruritic skin disorder. AD is considered one of the major public health problems in the world, and its prevalence is increasing, especially in industrialized countries. This report contains updated knowledge on AD, its epidemiology, and current diagnostic and management approaches. There are approximately 10–20% of children and 1–3% of adult population affected worldwide. According to the International Study of Asthma and Allergies in Childhood (ISAAC), AD is most prevalent in developed and westernized countries. In most western countries, AD diagnosis is made by considering a number of clinical features (Fig. 3.1) and patient’s history, classified into two categories, major and minor criteria, a system developed by Hanifin and Rajka in the 1980s. Sometimes, AD diagnosis is challenging, given the similarities in clinical features with other conditions. The disease severity is estimated using a number of scoring systems, of whom SCORAD is the most commonly used. It takes into account the intensity of each of the five AD skin lesions (redness, swelling, oozing/crusting, scratch marks, lichenification), in addition to pruritus (itch) and sleeplessness, and also the area of affected body parts. With the rising AD incidence and its familial association, new prophylactic strategies are being investigated. Currently, emollient and probiotic preparations provide a new hope in AD prevention in individuals at risk. Bacterial (Staphylococcus aureus) and viral (herpes simplex) infections are the most prevalent in complications. These complications may justify the use of anti-allergic agent combined with an antibiotic or antiviral drug in some AD patients, in addition to conventional anti-allergic drugs. Finally, most commonly used conventional AD treatment agents are presented in this work.

The preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients.Critically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12 h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics.We included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; p 0.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; p 0.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; p 0.001). The incidences of bacteremia did not have significant differences.Prophylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Background Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. Methods Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. Results Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p

Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

Purpose One of the pathophysiological processes in sepsis is endothelial dysfunction, which leads to disseminated intravascular coagulation (DIC). Syndecan-1 is a major structural component of the endothelium and plays a key role in endothelial function. The purpose of this study was to assess the value of syndecan-1 as a predictive marker for DIC in sepsis. Methods We performed a prospective observational study of patients with sepsis from February 2014 to July 2015. Serial change of hemostatic markers, anticoagulant and fibrinolytic markers (antithrombin, PAI-1), endothelial markers (syndecan-1, VCAM-1, E-selectin), and inflammatory markers (IL-1β, IL-6, IL-8, HMGB-1, histone-H3) were analyzed. Clinical data including APACHE II, SOFA, and DIC scores and 28-day mortality were also evaluated. Results During the study, 39 septic patients and 15 healthy controls were included. Syndecan-1 levels were significantly increased in the septic patients compared with the healthy controls. Of the septic patients, non-survivors had higher syndecan-1 levels than did the survivors on days 1, 2, and 4. Significant correlations on day 1 were found between syndecan-1 levels and APACHE II, SOFA, and DIC scores, hemostatic markers, IL-1β, IL-8, and PAI-1. Syndecan-1 levels on day 1 were also significantly higher in patients with than without DIC and had strong discriminative power for the prediction of both DIC development and subsequent mortality, with AUCs of 0.79 and 0.85, respectively. Conclusion Syndecan-1 levels were associated with not only the severity of illness and mortality but also DIC development in sepsis, suggesting that syndecan-1 could be a predictive marker of DIC.

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

A 71-year-old female presented to our hospital with recent increase in diarrhea and body weight loss. Radiologic and endoscopic examinations revealed rectal adenocarcinoma with synchronous multiple liver metastases accompanied by widespread intrabiliary tumor thrombi. After primary tumor resection, systemic treatment using 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI), and panitumumab was given. The disease responded well to treatment and about two years after rectal surgery she underwent left hemihepatectomy with removal of tumor thrombi. Histological examination showed that intrahepatic bile dusts were filled with tumor thrombi indicative of a tubular adenocarcinoma resembling rectal adenocarcinoma. No tumor invasion was observed on the surgical margins. She received 5-fluorouracil and leucovorin as adjuvant treatment for six months, and she has not shown any evidence of recurrence for one year after hepatectomy.

45歳，女性。初診の3ヵ月前より両下腿に紅斑，紫斑，潰瘍が出現した。初診時，両下腿および内足縁に網状の紅斑，紫斑が散在し，一部に痂皮を付着する潰瘍を認めた。病理組織では真皮全層に小血管が増生し，内腔は拡張して好酸性無構造物質による閉塞像を認めた。臨床検査から単クローン性のI型クリオグロブリン血症による末梢循環障害および皮膚潰瘍と診断した。更に，骨髄およびリンパ節に濾胞構造と，IgM（＋），λ（＋）の大型のリンパ球を認め，濾胞性リンパ腫と診断した。化学療法によるリンパ腫の寛解に伴って，血中のクリオグロブリンは消失し，皮疹は軽快した。

Drug reaction can be one of the triggering factors either for exacerbation of pre-existing psoriasis or precipitation of psoriasis de novo. Herein, we report a case with psoriasiform drug eruption due to pravastatin, but it relapsed after discontinuance of the drug. Serial investigation of the histopathology and immunohistochemistry with anti-signal transducer and activator of transcription 3 (STAT3) revealed drug reaction-associated lesions intermingled with psoriasiform changes, which later predominated, suggesting a conversion into psoriasis de novo.

49歳, 男性。体幹・四肢に自覚症状のない紅斑, 丘疹が生じ増加してきた。病理組織にてCD4陽性を示す異型細胞の浸潤, TCR遺伝子再構成を認め, 皮膚T細胞リンパ腫 (CTCL) と診断した。ステロイドパルス療法後, ステロイドと低用量MTX内服投与で治療していたが, 皮疹が再燃した。病理組織にて大型の異型リンパ球の密な浸潤を認め, CD4陽性を示す異型T細胞とCD20, CD79a陽性を示す異型B細胞が混在していた。免疫グロブリンH鎖に遺伝子再構成を認めた。EBERs陽性細胞を少数認め, 組織学的にEBV感染が証明できた。以上よりCTCL患者にメトトレキセート関連リンパ増殖性疾患 (MTX-LPD) が発症したと考えた。MTX中止のみでは軽快せず, フルダラビンによる化学療法を施行した。MTX-LPDについて原疾患, Epstein-Barr Virusとの関連など過去の報告例と比較検討した。MTX-LPDは重篤な医原性疾患の一つであると考え報告する。

ステロイドと低用量メソトレキセート (以下MTXと略す) の併用療法が奏功した未分化型大細胞リンパ腫 (Anaplastic large cell lymphoma; 以下ALCLと略す) の1例を経験したので報告する。症例は60歳, 女性。初診の4年前に下肢に出現した皮疹をALCLの診断のもと, 近医および当科でステロイド外用・内服, PUVA療法, IFN-γ注射, エトレチナート内服, 電子線照射などで治療されていたが軽快再発を繰り返していた。平成16年の再発時にCHOP療法施行後に本治療を開始したところ, CHOP療法後に残存していた病変はすべて速やかに消退した。以後38ヵ月間再発はみられない。本治療はCHOPなどの多剤併用化学療法施行前の, あるいは施行後の補助・維持療法として推奨される治療法であると考えられる。

6歳, 女児。4歳頃より右側腹部に腫瘤が出現し徐々に増大した。やがて中央が潰瘍化したため当科を受診した。中央が潰瘍化した直径18mmのドーム状に隆起する淡紅色腫瘤が右側腹部に単発性に認められ, 診断目的に単純摘出術を施行した。病理組織では胞体内に好酸性の顆粒を持つ細胞が真皮内に密に浸潤し, 被膜に取り囲まれた腫瘤を形成していた。腫瘍細胞はS-100蛋白, vimentin陽性で, 顆粒がPAS陽性であったことより, 顆粒細胞腫と診断した。臨床的に潰瘍がみられ, 紡錘形腫瘍細胞を混じていたこと, 一部に被膜外浸潤を認めたことから追加拡大切除を行った。再切除標本では腫瘍細胞の残存はなく, 1年後の現在まで再発を認めていない。本疾患は小児には稀な疾患であり, また臨床的および病理組織学的に悪性顆粒細胞腫との鑑別を要したので報告する。

76歳, 女性。外陰部から大腿に境界明瞭な紅斑と黒褐色斑と脱色素斑の混在を認め, 紅斑上に紅色結節を認めた。結節部の病理組織所見はPaget細胞が真皮全層に浸潤していた。右鼠径リンパ節を触知し, CTでは右鼠径と右外腸骨動脈領域のリンパ節腫大を認めた。CEAは正常範囲内であった。病変境界部から2cm離して拡大切除し, 両側浅深鼠径リンパ節と右外腸骨動脈領域リンパ節郭清術を施行した。右鼠径, および右外腸骨動脈領域リンパ節にPaget細胞の浸潤を認め, Stage III(T3N1M0)と診断した。手術5ヵ月後に腹部大動脈分岐部にリンパ節転移を認めた。ドセタキセル(タキソテール®)療法を開始したところ, 3ヵ月半後(9回投与後)には画像診断上complete responseを得た。治療開始13ヵ月後の現在, 再発および転移を認めていない。

Background: The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen’s original article was published in 1912. Methods: We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease. Results: Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35βH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas. Conclusions: Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.

Background Activated mast cells enhance the uptake of mast cell–derived proteoglycan–low-density lipoprotein complexes by macrophages. Objective We sought to investigate mast cell contribution to the pathogenesis of xanthoma. Methods Twenty cases of xanthelasma palpebrarum and 6 cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results Xanthelasma lesions contained up to 5-fold more tryptase-stained mast cells than tuberous xanthoma lesions. Tuberous xanthoma lesions especially showed extensive staining of tryptase around mast cells and within some macrophages and foam cells. More than 99% of mast cells in xanthelasma lesions contained both tryptase and chymase. Approximately 60% of mast cells represented only tryptase in tuberous xanthoma lesions where the ratio of macrophages to tryptase-stained mast cells was extremely high (15:1) as compared with xanthelasma lesions (2:1). Limitations A change in mast cell phenotype has not been necessarily proven. Conclusion Mast cells are activated under the microenvironment in which macrophages predominate rather than mast cells, which thus reflects the clinical phenotypes of xanthoma lesions.

7例の落葉状天疱瘡，1例の尋常性天疱瘡に対して血漿交換療法とステロイドパルス療法の併用療法を施行した。有用であった7例では臨床症状の改善，抗体価の減少，ステロイド投与量の減量が可能であった。併用療法を早期より積極的に施行することで臨床症状を速やかに改善させ，ステロイド剤投与量の減量が容易となり寛解維持にも好影響が得られた。併用療法は，血漿交換療法による直接的な病因抗体の除去に加え，ステロイドパルス療法によりさらに臨床症状を効果的に改善したと考えた。この併用療法は天疱瘡に対する優れた導入初期治療であり長期的予後にも好結果を与えると結論した。

Summary Background The source of accumulated lipids in the foam cells of xanthoma is primarily the lipoproteins existing in the lesional dermis. Objective This study was designated to clarify the contribution of low density lipoprotein (LDL) density substances existing in xanthoma tissue to foam cell formation. Methods An LDL density fraction was obtained from homogenized rabbit experimental xanthoma tissue. Biochemical and functional characteristics of xanthoma-extracted LDL density substance were examined. The in vivo foam cell-inducing ability of xanthoma-extracted LDL density substance was examined microscopically at the intradermal injection site. Results Xanthoma-extracted LDL density substance showed more negatively charged mobility on agarose gel electrophoresis than plasma native LDL. A small amount of aggregated material remained at the origin on agarose gel electrophoresis. Xanthoma-extracted LDL density substance contained much higher level of lipid peroxides than native LDL. Mouse peritoneal macrophages internalized xanthoma-extracted LDL density substance extensively and transformed into foam cells by incubation with xanthoma-extracted LDL density substance. Intradermal injection of the xanthoma-extracted LDL density substance induced foam cell infiltration in the skin of a normolipemic rabbit. Conclusion LDL density substances prepared ex vivo from experimental xanthoma tissue contained lipid–protein complexes that have physiochemical properties of oxidized LDL. The lipid–protein complexes were incorporated into foam cells. The substances were considered to contribute to foam cell recruitment during the persistence of xanthoma lesions.

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

53歳，女性。下顎では色素沈着を残し，下腿では色素沈着を残さない固定薬疹が繰り返し出現した。パッチテスト(皮疹部および無疹部)およびスクラッチパッチテスト(無疹部)は陰性。ミノサイクリン5mg投与による内服誘発テストでは，下顎と下腿に皮疹が再燃し，前額にも紅斑が新生した。病理組織像では下腿に比べ下顎の真皮にメラノファージが著明に多く認められた。免疫組織化学では，トリプターゼ陽性肥満細胞が下腿と比較して下顎の特に真皮乳頭層において有意に多く認められた。肥満細胞由来のケミカルメディエーターやサイトカインが，メラノサイトのメラニン合成やメラニンのケラチノサイトへの輸送を促進することも色素沈着を増強させる因子であると考えた。

53歳, 女性。D-ペニシラミンの内服開始1年4カ月後, 肉眼的には落葉状天疱瘡, 病理組織学的には尋常性天疱瘡の所見を示す皮疹を生じた。免疫ブロット法で, デスモグレイン (Dsg)-1抗体が証明されたが, Dsg-3抗体は認められなかった。ELISA法では, Dsg-1およびDsg-3抗体ともに陽性だった。内服中止後も水疱の新生は続いた。プレドニゾロンの内服減量中に水疱が再燃した際には, Dsg-3抗体は陰性化していたがDsg-1抗体は陽性であったことから, Dsg-3抗体は薬剤によって修飾されたDsg-3に対する抗体であり, Dsg-1抗体は持続的に産生されていると考えた。抗核抗体と抗細胞質抗体が陽性であったことから, 自己抗体を産生しやすい素因があると考えた。水疱蓋および水疱内の多くの棘融解細胞が変性していたことも特徴であった。

Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

Repeated ultraviolet (UV) irradiations have been shown to induce keratinocyte proliferation with acanthosis, stimulate the cutaneous nerve proliferation, and increase the synthesis of calcitonin gene-related peptide (CGRP). In the current study, we examined the role of CGRP in the UVB-induced proliferation of murine keratinocytes. UVB irradiation increased the number of bromodeoxyuridine (BrdU)-labeled basal keratinocytes and caused acanthosis. In addition, CGRP expression was up-regulated in the peripheral nerves of the upper dermis and lower epidermis. Repeated intradermal injections of CGRP increased the number of BrdU-labeled basal cells and caused acanthosis. Intradermal injections of capsaicin prior to UVB-irradiation inhibited the UVB-induced CGRP expression, BrdU labeling in basal keratinocytes and epidermal thickening. Intradermal injections of anti-CGRP antibody inhibited the UVB-induced BrdU labeling in basal keratinocytes, but epidermal thickening was not significantly inhibited. These results indicate that CGRP is one of the stimulators to UVB-induced keratinocyte proliferation. On the other hand, expression of substance P, another neuropeptide in the peripheral nerve, was not up-regulated by UVB irradiation.

Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported to be associated with healthy longevity and prevents a number of cardiovascular and metabolic disorders. This report highlights the anti-allergic and skin health enhancing effects of Sujiaonori-derived ulvan (Tosalvan) and supplement, respectively. RBL-2H3 cell line was used to investigate the anti-allergic effect of algal SP through the evaluation of β-hexosaminidase activity. Algal sulfated polysaccharides or SP (Tosalvan, Yoshino SP) were extracted from powders of dried alga samples provided by local food manufacturers. Report on the effect of daily dietary intake of Sujiaonori-based supplement on skin health is part of a four-week clinical investigation that, in comparison with a supplement made of 70% corn starch powder and 30% spinach powder mixture (twice 3 g daily), explore the beneficial effects of Sujiaonori algal biomaterial (SBM; 3 g taken twice daily) on cardiovascular, gastrointestinal and skin health in a sample of Japanese women. Transepidermal water loss (TEWL) was the skin health marker used in this study and was measured with the use of a corneometer. Significant reduction of β-hexosaminidase activity was observed in Tosalvan and Yoshino SP-treated cells (vs. control; p < 0.05), whereas dietary intake of SBM markedly reduced TEWL level after four weeks of supplementation, as compared to baseline TEWL (p < 0.001). Additionally, SBM improved TEWL better than the control product (p < 0.001). Findings contained in this report suggest that Sujiaonori-derived Tosalvan and Yoshino SP have anti-allergic potential and that the dietary intake of SBM has a beneficial effect on skin health.

Constipation is a gastrointestinal motility disorder that represents a major health problem in Japan. Approximately 26% of young Japanese adult women are reported to have this complaint. We report on the health effects of daily intake of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women. Data are from a four-week dietary intervention study on the health effects of daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal health in which 32 adult Japanese volunteers (age range: 20–54 years) participated. They underwent clinical and laboratory investigations, and completed two study questionnaires (the brief diet history questionnaire (BDHQ) and the current health questionnaire) before and after dietary intervention. Of the 12 women volunteers with functional constipation, there were six SBM-supplemented subjects who received 3 g of Sujiaonori powder twice daily during meal, whereas the six others (controls) were from the group of those who took 3 g of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis of data on daily nutrient intake showed no significant dietary changes for nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol intake that was reduced) in both groups. In SBM group, a significant reduction of the proportion of women with constipation was observed (p < 0.001), whereas no significant change was noted within the control group (p > 0.05). When both groups were compared, SBM was more effective than the control product; 66.7% (4/6) of SBM-supplemented women had their constipation relieved, whereas only one control (16.7%) controls benefited from dietary intervention (p < 0.001). In addition, no adverse effect was reported in the SBM group, whereas two controls reported nausea at post-survey. These results suggest that Sujiaonori contains compounds that can improve gastrointestinal function and relieve constipation.

A 53-year-old female developed erythema elevatum diutinum (EED) twelve years after the onset of rheumatoid arthritis. The arthritis had been well controlled for the last several years. Annular purpuric macules were characteristically complicated by common nodular and plaque lesions. Both leukocytoclastic vasculitis and fibrosis were observed in the macular lesions, indicating that the lesions were a manifestation of an early phase of EED. Both types of skin lesions disappeared with treatment with dapsone. They have not relapsed for two years after stopping the dapsone. The leukocytoclastic vasculitis was thought to have developed independently of the rheumatoid arthritis. She had noticed sicca symptoms two years before the appearance of EED, but she did not satisfy the diagnostic criteria for Sjögren's syndrome.

38歳, 男性。深部静脈血栓症による下腿潰瘍を呈した。抗カルジオリピンβ2グリコプロテインI抗体, ループスアンチコアグラントおよび抗核抗体陽性で, 原発性抗リン脂質抗体症候群と考えた。通常の治療では難治であった潰瘍は, ワーファリン®とブコローム内服により短期間で治癒した。ワーファリン®単独投与では効果が不十分な場合には, トロンボテストを指標にブコロームを併用することが重要である。潰瘍再発の4ヵ月前に小腸イレウスを発症し, Degos病類似の皮疹が出現したが, 腸穿孔はなく, 皮疹の病理組織像には特徴的な所見は認められなかったことから, 抗リン脂質抗体症候群に伴うDegos病様症候と考えた。

A 71-year-old Japanese man presented with asymptomatic, firm, brown-red papules on the dorsum of his left hand and back. A biopsy specimen revealed granulomatous infiltration consisting of multinucleated giant cells and histiocytes in the upper dermis. Elastic fibers were absent in the upper dermis, having been phagocytosed by giant cells. These papular elastolytic giant cell granuloma lesions regressed very well with narrow-band ul traviolet B irradiation, with only residual brown pigmentation left after treatment.

A rare case of papular mucinosis on the back of a 78-year old man is described. The patient developed approximately 20 discrete papules on the upper back. His serum glucose concentration was borderline elevated, but no other systemic symptoms or signs were apparent. A biopsy revealed mucin deposits only in the upper reticular dermis. The papules were distinctly different from lichen myxedematosus in clinical and histochemical appearance. The present case may represent very early-stage lichen myxedematosus complicated by borderline diabetes mellitus.

Two patients with disseminated superficial porokeratosis (DSP) with amyloid deposition are reported. The skin lesions were distributed over both sun-exposed areas and sun-protected areas. No exacerbation by sun exposure was noted. Abundant amyloid substances were deposited at the papillary dermis, not only beneath the cornoid lamellae but also within the annular margin. The skin lesions and amyloid deposition regressed with topical application of dimethyl sulfoxide in one patient, suggesting that DSP is one of the clinical phenotypes of primary localized cutaneous amyloidosis. Another possibility is that amyloid substances are produced by poorly differentiated keratinocytes in DSP.

40歳の男性。全身諸処に有痛性の丘疹および周辺堤防状に隆起する暗紅色結節が散在, 一部では虫喰い状の潰瘍となり排膿を認めた。生検組織像では, 表皮はpseudoepitheliomatous hyperplasiaを示し, 真皮では膿瘍形成を伴う多数の好中球浸潤を主体とする肉芽腫形成を認めた。細菌培養では無菌性のことが多かったが, 時に二次感染としてS. epidermidis, S. aureus, E. faecalisが検出された。抗酸菌培養および真菌培養は陰性, 白血球減少, 単球増加, 好中球機能低下を認め, 骨髄像より慢性骨髄単球性白血病(CMMoL)と判明。CMMoLによる好中球機能低下を基盤とした壊疽性膿皮症と診断した。ミノサイクリンは皮疹に対してある程度有効であったが, 他の抗菌剤は無効。プレドニゾロンは用量依存性に奏効し, 皮疹は瘢痕治癒するものもあり, 自潰して潰瘍となることは抑制できた。しかし糖尿病の合併により, 充分量投与できなかったため, 新しい結節の出現を完全には抑制できなかった。G-CSFを投与するも, 汎血球減少症および皮疹は改善されず, 肺炎を併発して死亡した。

Epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3, and increased levels of cytokines and growth factors that promote Stat3 activation have been found within psoriatic lesions. K5.Stat3C transgenic mice, in which keratinocytes express a constitutively active Stat3, develop psoriasis-like skin lesions. In this study, we examined whether STA-21, a small Stat3 inhibitor, could be useful in ameliorating the skin lesions not only in the model mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent manner through downregulation of c-Myc and cyclin D1, whereas involucrin, transglutaminase 1, and keratin 10 levels were upregulated. Topical application of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we treated psoriasis patients with STA-21-containing ointment in a nonrandomized study. Psoriatic lesions in six of the eight patients showed improvement after topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3 may lead to a therapy for psoriasis.

A case of non-clostridial gas gangrene (NCGG) developing in a plantar recalcitrant ulcer associated with diabetes mellitus (DM) is reported. A 63-year-old female was admitted to the hospital, because of a recalcitrant ulcer in the right first toe associated with DM. Following admission her right foot swelled, and plantar gangrene, excretion of pus with a foul smell, crepitation on pressing, and a gas picture on XP were noted. Therefore, a diagnosis of NCGG was made. Conservative treatment including administration of antibiotics and random skin cutting was carried out. However, her right leg was amputated after CT indicated expansion of the gas picture. NCGG often occurs in association with such underlying diseases as DM. Since this patient did not have her DM under adequate control, it is thought that the ulcer in the right first tow was the source of infection for the NCGG. The pathological progression of NCGG is relatively gradual, and the suitable period when it can be cured may be easily missed. Prognosis may become unfavorable. It is important to determine the causative bacteria in an early stage by gram-staining of the pus in order to make the differential diagnosis between NCGG and clostridial gas gangrene (CGG). If a curative tendency by conservative treatment is not observed, one should not hesitate to amputate the affected limb.

We developed a new radiosensitization treatment using a hydrogen peroxide solution (Oxydol)-soaked gauze named KORTUC I (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) for superficially exposed and unresectable neoplasms, such as malignant melanoma and malignant fibrous histiocytoma (MFH), based on our experimental results which demonstrated hydrogen peroxide as a strong radiosensitizer for the highly radioresistant osteosarcoma cell line, HS-Os-1. Five patients entered our clinical trial, one of whom had unresectable malignant melanoma; one, unresectable MFH; one, unresectable extramammary Paget's disease; one, locally advanced breast cancer and one with locally recurrent skin cancer. These patients were treated with radiation therapy using a high-energy electron beam from a linear accelerator. The total dose was 48 Gy, and each fraction size was 4 Gy. Radiation therapy for these patients was performed three times per week. Each time the radiation therapy was carried out, the superficially exposed tumors of these patients were covered with hydrogen peroxide solution (Oxydol)-soaked gauze, and the lesion was gently massaged for several minutes so as to allow the hydrogen peroxide solution to soak deeply into the tumor. In the treatment results, two of these five patients showed a clinically complete response (cCR) two to three months following the end of the KORTUC I radiosensitization treatment. The other three patients showed a clinically partial response (cCR) showing a decrement of more than half of the pretreatment volume. KORTUC I was completed without any severe complications, excluding mild radiation-induced dermatitis/mucositis (Grade I). In conclusion, this newly developed radiosensitization treatment using hydrogen peroxide solution (Oxydol)-soaked gauze for superficially exposed unresectable/radioresistant neoplasms appears to be an effective and valuable method of radiosensitization in terms of the blockade of anti-oxidative enzymes such as peroxidases, resulting in local oxygen production. Moreover, the KORTUC I radiosensitization treatment is relatively inexpensive and the method can therefore be utilized worldwide for many patients suffering from superficially exposed and locally advanced radioresistant neoplasms such as malignant melanoma, malignant fibrous histiocytoma (MFH) and various types of sarcomas.

Herpetiform vesicles and erythema with erosion developed on the trunk of a 48-year-old Japanese man. Acantholysis was observed in the spinous layer of the lesional epidermis and direct immunofluorescence revealed cell surface deposition of immunoglobulin IgG and C3. Indirect immunofluorescence could not detect circulating anti-cell surface antibodies. Immunoblot analysis detected neither anti-desmoglein (Dsg)1 antibody nor anti-Dsg3 antibody. Enzyme-linked immunosorbent assay could detect IgG and IgA anti-Dsg 1 antibodies and IgA anti-Dsg3 antibody, in addition to a gray zone titer of IgG anti-Dsg3 antibody. Intraepidermal neutrophilic infiltration with neutrophilic microabscesses and intense dyskeratotic cells were histopathologically characteristic in this case. Skin lesions improved within 1 month and remission has continued for 9 years under oral administration of dapsone.

A 5-month-old boy was noted to have brown macules with palpable infiltration on the head, trunk, and extremities a few weeks after birth, with recurrent episodes of generalized flushing and blistering in some of the macules. These lesions developed into yellowish plaques after 1 year of topical treatment with clobetasol propionate. Serum lipid levels were within normal limits. The appearance of the yellowish lesions was similar to that of the xanthelasmoid type of cutaneous mastocytosis. The brown macules showed infiltration of a large number of mast cells and a small number of scattered foam cells, whereas in the yellowish plaques, the number of foam cells was greatly increased. The yellowish plaques regressed spontaneously within a year after cessation of topical corticosteroid treatment. Immunohistochemical analysis found that the foam cells were stained with monocyte/macrophage markers including HAM56, and with SRA-C6, a monoclonal antibody to macrophage scavenger receptor class A (CD204). Therefore, the yellowish plaques were considered to be plane xanthoma associated with cutaneous mastocytoma.

Background: The migration of circulating monocytes into the dermis is considered to be essential for both the initiation and the progression of xanthoma. The contribution of vascular endothelial cells to the migration process is unclear. Methods: Twenty cases of xanthelasma and six cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results: Xanthoma lesions contained up to 25-fold more von Willebrand factor-stained endothelial cells than normal skin. The prevalence of E-selectin-positive endothelial cells increased by up to threefold more in xanthoma lesions than in normal skin. In contrast, the prevalence of intercellular cell adhesion molecule-1 (ICAM-1) decreased up to 3.5-fold more in xanthoma lesions than in normal skin. In xanthoma lesions, almost all ICAM-1-positive endothelial cells co-expressed with E-selectin but many endothelial cells, which only expressed E-selectin, were also found in the lesions and the ratio of macrophages to endothelial cells was higher (10:1) than that in normal skin (5:1). Conclusions: Endothelial cells proliferate and express E-selectin rather than ICAM-1 under a microenvironment in which macrophages predominate rather than endothelial cells, thereby promoting macrophage migration into xanthoma lesions.

Pseudoxanthoma elasticum is an inherited systemic disorder of connective tissue characterized by fragmentation of elastic fibers and calcification in cutaneous, ocular, and cardiovascular systems. Mutation in the ATP-binding cassette subfamily C member 6 gene has recently been found in people with pseudoxanthoma elasticum (1). However, the precise mechanisms of elastic fiber fragmentation and calcification remain obscure. Recently, it has been reported that mild chronic oxidative stress affects pseudoxanthoma elasticum fibroblasts (2). This suggests that reactive oxygen scavengers might improve this disorder.

生後5日目に右足に水疱が初発し, 中心治癒傾向を示す配列をし, 瘢痕を残さず治癒する水疱が出没しているDowling-Meara型単純型先天性表皮水疱症の男児例を報告した。光顕的には表皮下水疱であったが, 電顕的には表皮内水疱および表皮基底細胞にトノフィラメントが異常凝集していることから, Dowling-Meara型単純型先天性表皮水疱症と診断した。ビタミンEの内服は無効で, 2歳の現在, 新しい皮疹の出現が続いているが, 自覚症状は乏しいらしく機嫌は良い。父親にも同症が認められたが, 小学校低学年時には寛解しており, 患児も自然軽快することが期待される。

Intense pruritus and cutaneous reactivity represent cardinal features of eczema. The resulting scratching behaviors alter neuronal conditions of the spinal dorsal horn where the primary sensory afferent fibers transmit cutaneous stimulation and deteriorate eczematous skin lesions. We investigated the effects of olopatadine hydrochloride (olopatadine) on alteration of neuronal conditions of the spinal dorsal horn and eczematous skin lesions induced by contact dermatitis. Eczematous lesions were induced by repeated application of diphenylcyclopropenone (DCP) in BALB/c mice. Olopatadine suppressed scratching behavior caused by repeated application of DCP in mice. Increased expressions of c-Fos and substance P in the spinal dorsal horn following DCP application were improved by olopatadine. Furthermore, olopatadine diminished the number of infiltrating cells and levels of cytokines in eczematous skin lesions resulting from DCP application. Olopatadine improves neurological conditions in the spinal cord and eczematous skin lesions in a murine contact dermatitis model.