Record 400-Gb/s/lane net-rate (155-GBd PAM-8) IM-DD signals are transmitted in the O-band over installed 10-km 4-core fibre using in-house broadband InP-DHBT amplifier and our nonlinear-MLSE, achieving a 1.6-Tb/s total capacity for future data-centre Ethernet networks.

Both docetaxel and paclitaxel are a class of microtubule-stabilizing anticancer agents. Partial cross-resistance between docetaxel and paclitaxel was indicated in breast and ovary cancers. In advanced gastric cancer, retrospective study showed comparable efficacy of subsequent weekly paclitaxel with or without prior docetaxel-based chemotherapy. Therefore, we evaluated the efficacy and safety of weekly paclitaxel in patients with advanced or recurrent esophageal cancer who had previously received docetaxel-containing chemotherapy.

Oz virus is a novel thogotovirus isolated from ticks that causes lethal infection in mice. We conducted serosurveillance of Oz virus infection among humans and wild mammals in Japan using virus-neutralization tests and ELISAs. Results showed that Oz virus may be naturally infecting humans and other mammalian hosts.

Kabuto Mountain virus (KAMV), the new member of the genus Uukuvirus, was isolated from the tick Haemaphysalis flava in 2018 in Japan. To date, there is no information on KAMV infection in human and animals. Therefore, serological surveillance of the infection among humans and wild mammals was conducted by virus-neutralization (VN) test and indirect immunofluorescence assay (IFA). Sera of 24 humans, 59 monkeys, 171 wild boars, 233 Sika deer, 7 bears, and 27 nutria in Yamaguchi Prefecture were analyzed by VN test. The positive ratio of humans, monkeys, wild boars, and Sika deer were 20.8%, 3.4%, 33.9% and 4.7%, respectively. No positive samples were detected in bears and nutria. The correlation coefficients between VN test and IFA in human, monkey, wild boar, and Sika deer sera were 0.5745, 0.7198, 0.9967 and 0.9525, respectively. In addition, KAMV was detected in one pool of Haemaphysalis formosensis ticks in Wakayama Prefecture. These results indicated that KAMV or KAMV-like virus is circulating among many wildlife and ticks, and that this virus incidentally infects humans.

A 41-year-old Japanese male patient with a half-year history of pruritic severe erythema on his face, neck, trunk, and upper extremities, specifically on his sun-exposed areas, was diagnosed with chronic actinic dermatitis (CAD) at the Department of Dermatology at Yamaguchi University Hospital and was referred to the Saisei Mirai Clinic in Kobe, Japan, in September 2015. He was hypersensitive to UVA at a dose of 1.7 J/cm2 (tested with a TOREX/FL20S-BL/DMR, Toshiba emitting light ranging from 315 to 410 nm, peaking at 360 nm; normal minimal erythema dose = >10-15 J/cm2), but had a normal response to UVB (minimal erythema dose: 114 mJ/cm2, tested with a Philips TL20W/12RS emitting light from 270 to 360 nm, peaking at 310 nm; normal minimal erythema dose = 60-100 mJ/cm2). The patient did not respond to a low dose (5 mg/d) of systemic corticosteroid hormone or to various topical treatments with steroid hormones and a calcineurin inhibitor, tacrolimus, prescribed at other hospitals, for more than half a year. The patient had not taken any medication capable of inducing photosensitivity before the onset of CAD. Physical examination at his first visit to the Saisei Mirai Clinic in September 2015 revealed severe erythema with partly exudative, crusted lesions, and scratch marks, similar to the characteristics of atopic dermatitis, on his face. Further, he had Hertoghe's sign, often observed in severe atopic dermatitis, and diffuse pigmentation on his face and erythema and pigmentation on his neck but was free from eruptions on his lower extremities. He was found to suffer from cataracts in both eyes. In September 2015, the patient started to take two capsules daily of colostrum-macrophage-activating factor (colostrum-MAF), which is a health food containing degalactosylated/desialylated bovine colostrum frequently used successfully by patients with other indications such as atopic dermatitis and autism. He was also treated topically with weak and strong steroid hormone ointments on his face and neck, and on his trunk and extremities, respectively. Each capsule contained 1 mg colostrum-MAF and other non-identified components. After 2 weeks of treatment, he stopped the topical treatment since the itchy erythema seen on most of his body except his lower extremities had improved dramatically, although diffuse pigmentation remained (Figure 1A). The patient continued to take oral colostrum-MAF every day for nearly 10 months. After the cessation of the oral treatment with colostrum-MAF, the patient was free from erythema for 4 months and used only sunscreen for his daily care, and finally, he began to work outdoors in the daytime. Blood cell counts, and liver and kidney functions were all within normal limits. Serum IgE and TARC (thymus and activation-regulated chemokine) were 1425 IU/mL and 222 pg/mL at his first visit (September 2015) and were 590 IU/mL and 206 pg/mL at his visit on July 2016 to the Clinic, respectively. Eosinophils were in the normal range. His SCORAD index improved from 36.0 at his first observation to 0.4 at his last visit (Figure 1B). Colostrum is rich in immunoglobulins IgA, IgG, and IgM and is expected to modulate immunity, since IgA has an O-linked sugar chain similar to that in group-specific component (Gc) protein, a precursor of Gc protein-derived macrophage-activating factor (Gc-MAF), which is produced from colostrum Gc protein by cleaving sialic acid and β-galactoside.1, 2 Further, we have found that colostrum-MAF has a suppressive effect on the LPS/IFN-γ-induced expression of TNF-α (Figure 2A) and increased the intensity of CD206 (a marker of M2 macrophages) similar to that induced by IL-4/IL-13 stimulation (Figure 2B). Those results suggest that colostrum-MAF may play a role in immune modulation by activating type 2 macrophages with regulatory functions.3 Chronic actinic dermatitis is a rather rare photosensitive disease commonly affecting elderly men4 and often is difficult to differentially diagnose from photoaggravated dermatitis, although CAD can arise in young people with pre-existing dermatoses, such as allergic contact dermatitis, atopic dermatitis, and HIV infection.5 An alternative diagnosis in this patient was severe photoaggravated dermatitis, especially as the patient's sensitivity was to UVA rather than UVB. The exact pathological mechanism of CAD still remains to be clarified. It had been regarded as a contact dermatitis-like reaction,6 but Ko et al7 recently proposed that CAD may be caused by a Th1/Th2 dysbalance, based on the positive relationship between clinical severity and total IgE level and eosinophilia in the peripheral blood of patients with CAD. For the correct diagnosis of CAD, photosensitivity tests using an artificial light source from UVB to visible light are essential, and patch tests using European Standards Allergen Series plus sunscreens, corticosteroids cosmetic series, and photo-patch tests are also recommended.6, 7 In this case, a patch test was not performed, since the patient did not agree to that test. For clinical management, the avoidance of active wavebands is basically the most important. To manage acute eczematous dermatitis, topical use of corticosteroid- or calmodulin inhibitor-containing ointments is commonly recommended, but these topical treatments are not so effective in most patients with CAD. The present 41-year-old male patient was photosensitive to UVA and was refractory to topical treatment with the strongest class corticosteroids for more than 3 months and to oral intake of small amounts of predonisolone (5 mg/d) for approximately 2 months. Severe exudative erythema with scratch marks on his face responded quite well to oral uptake of two capsules of bovine colostrum-MAF. The exact amount of colostrum-MAF contained in each capsule is calculated to be around 1 μg based on the conversion rate of human Gc-MAF (group-specific-macrophage-activating factor) from Gc protein by enzymatic cleavage. Severe erythema significantly subsided on his second visit after initiation of colostrum-MAF treatment with supportive short-term (5-7 days) application of steroid hormone or tacrolimus ointment and oral intake of anti-allergic agent for 2 weeks. After 9 months of treatment, the UVA hypersensitivity disappeared. Clinical and laboratory characteristics strongly suggest that the main cause of CAD may be immunological, although the detailed mechanism still remains to be clarified. Patients with CAD show a Th-2 polarization with the co-existence of tissue eosinophilia and disease severity,8 and further, Ko et al7 recently suggested that a Th1/Th2 dysbalance caused by suppressor T cells may play a role in CAD occurrence. In the present study, we found that colostrum-MAF increased the number of and activated M2 macrophages, but not M1 macrophages, and significantly suppressed LPS-induced inflammatory cytokines activation in an in vitro study of mouse intra-peritoneal macrophages. These findings suggested that colostrum-MAF may modulate immune dysfunction in allergic skin diseases, such as atopic dermatitis, and in photosensitive diseases including CAD and polymorphous light eruptions. Surprisingly, the present patient with CAD responded quite well to the oral intake of bovine colostrum-MAF even after only 2 weeks, and severe and erythema refractory to conventional therapies almost disappeared after 2 months of treatment. Based on our in vitro study and recent reports by others, we speculate that colostrum-MAF may modulate M1/M2 macrophage polarization, leading to the subsidence of inflammatory reactions in the skin. To recommend the general use of colostrum-MAF on inflammatory skin diseases will require further clinical studies on a number of cases to confirm the efficacy and safety with optimal dose for each disease in the future. The authors, except Dr. Inui T and Prof. Uto Y, have no conflict of interest to declare. Dr. Inui T is President of Saisei Mirai Clinic where colostrum-MAF is produced. Prof. Uto Y is supported by Dr. Inui for his study.

Importance Epidemiological evidence regarding the long-term effects of higher dietary protein intake on mortality outcomes in the general population is not clear. Objective To evaluate the associations between animal and plant protein intake and all-cause and cause-specific mortality. Design, Setting, and Participants This prospective cohort study included 70 696 participants in the Japan Public Health Center-based Prospective Cohort who were aged 45 to 74 years and had no history of cancer, cerebrovascular disease, or ischemic heart disease at study baseline. Data were collected from January 1, 1995, through December 31, 1999, with follow-up completed December 31, 2016, during which 12 381 total deaths were documented. Dietary intake information was collected through a validated food frequency questionnaire and used to estimate protein intake in all participants. Participants were grouped into quintile categories based on their protein intake, expressed as a percentage of total energy. Data were analyzed from July 18, 2017, through April 10, 2019. Main Outcomes and Measures Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were estimated using Cox proportional hazards regression models with adjustment for potential confounding factors. Results Among the 70 696 participants, 32 201 (45.5%) were men (mean [SD] age, 55.6 [7.6] years) and 38 495 (54.5%) were women (mean [SD] age, 55.8 [7.7] years). Intake of animal protein showed no clear association with total or cause-specific mortality. In contrast, intake of plant protein was associated with lower total mortality, with multivariable-adjusted HRs of 0.89 (95% CI, 0.83-0.95) for quintile 2; 0.88 (95% CI, 0.82-0.95) for quintile 3; 0.84 (95% CI, 0.77-0.92) for quintile 4; and 0.87 (95% CI, 0.78-0.96) for quintile 5, with quintile 1 as the reference category (P = .01 for trend). For cause-specific mortality, this association with plant protein intake was evident for cardiovascular disease (CVD)-related mortality (HRs, 0.84 [95% CI, 0.73-0.96] to 0.70 [95% CI, 0.59-0.83]; P = .002 for trend). Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total (HR, 0.66; 95% CI, 0.55-0.80), cancer-related (HR, 0.61; 95% CI, 0.45-0.82), and CVD-related (HR, 0.58; 95% CI, 0.39-0.86) mortality; substitution for processed meat protein was associated with lower total (HR, 0.54; 95% CI, 0.38-0.75) and cancer-related (HR, 0.50; 95% CI, 0.30-0.85) mortality. Conclusions and Relevance In this large prospective study, higher plant protein intake was associated with lower total and CVD-related mortality. Although animal protein intake was not associated with mortality outcomes, replacement of red meat protein or processed meat protein with plant protein was associated with lower total, cancer-related, and CVD-related mortality.

Speckled lentiginous nevus (SLN) is characterized by a brownish macule studded with blackish, multiple melanocytic nevi, although the cutaneous manifestations may vary by cases, and change by age. Therefore, there has been disagreement as to whether SLN is a congenital or acquired disease 1, 2). In rare cases of SLN, halo phenomenon may occur around the pre-existing lesion, associated with the coexistence of distant vitiligo 3). Here, we report a patient whose café-au-lait spot at birth changed to SLN, followed by the occurrence of vitiligo and poliosis through the process of spontaneous regression phenomenon against the SLN. We examined T-cell clones infiltrating around the melanocytic nevi and in the patient's peripheral blood. This article is protected by copyright. All rights reserved.

To investigate the trends of antimicrobial resistance in pathogens isolated from skin and soft-tissue infections (SSTI) at dermatology departments in Japan, a Japanese surveillance committee conducted the first nationwide survey in 2013. Three main organisms were collected from SSTI at 30 dermatology departments in medical centers and 10 dermatology clinics. A total of 860 strains - 579 of Staphylococcus aureus, 240 of coagulase-negative Staphylococci, and 41 of Streptococcus pyogenes - were collected and shipped to a central laboratory for antimicrobial susceptibility testing. The patient profiles were also studied. Among all 579 strains of S. aureus, 141 (24.4%) were methicillin-resistant (MRSA). Among 97 Staphylococcus epidermidis strains, 54 (55.7%) were methicillin-resistant (MRSE). MRSA and MRSE were more frequently isolated from inpatients than from outpatients. Furthermore, these methicillin-resistant strains were also isolated more frequently from patients with histories of taking antibiotics within 4 weeks and hospitalization within 1 year compared to those without. However, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains between patients with a history of hospitalization within 1 year and those without. Therefore, most of the isolated MRSA cases at dermatology departments are not healthcare-acquired, but community-acquired MRSA. S. pyogenes strains were susceptible to most antibiotics except macrolides. The information in this study is not only important in terms of local public health but will also contribute to an understanding of epidemic clones of pathogens from SSTI. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The aryl hydrocarbon receptor (AHR) is a dioxin receptor that activates the differentiation of T helper 17 (Th17) cells and regulatory T (Treg) cells to produce interleukin-22 (IL-22). In whole exome sequence analysis, we found two single nucleotide polymorphisms (SNPs) in AHR, rs2074113 and rs2066853. In addition, we investigated the correlation between these AHR SNPs and susceptibility to psoriasis in 185 patients with psoriasis vulgaris (PV) and 145 healthy controls by using TaqMan SNP Genotyping assays. For rs2074113, in both groups the frequency of the G allele was 0.59 and that of the T allele was 0.41. For rs2066853, in both groups the frequency of the A allele was 0.42 and that of the G allele was 0.58. Thus both allele frequencies in both groups were not significantly different and therefore the frequency of AHR SNPs and susceptibility to PV were not correlated. However, in a comparison of HLA-C*06:02-positive and -negative patients, rs2066853 AA homozygotes were significantly decreased in HLA-C*06:02-positive PV patients compared to HLA-C*06:02negative PV patients after Bonferroni correction. These observations suggested that AHR rs2066853 may be a protective gene for psoriasis in the Japanese population.

Heat shock factor 1 (HSF1) is a major transactivator of the heat shock response. Recent studies have demonstrated that HSF1 is involved in tumor initiation, maintenance, and progression by regulating the expression of heat shock proteins (HSPs) and other molecular targets. Furthermore, HSF1 was identified as a potent proinvasion oncogene in human melanomas. Our previous studies demonstrated that silencing HSF1 suppressed proliferation, migration and invasiveness of human melanoma cells in vitro and HSF1 is required for melanoma invasion and metastasis, as well as tumorigenic potential in vivo. Triptolide is a pharmacologically active compound that has previously been shown to abrogate transactivation of HSF1. In the current study, we found that triptolide led to a marked reduction in proliferation, migration and invasive ability in human melanoma cells via inhibiting transactivastion of HSF1. Our findings suggest that HSF1 could be a promising therapeutic target for melanoma.

Patients with classic type of Ehlers–Danlos syndrome (cEDS) suffer from the connective tissues caused by genetic abnormalities in the extracellular matrices molecules. In this study we identified pathogenetic mutations in three patients. Case 1, a 10-year-old boy presented skin hyperextensibility, easy bruising, joint hypermobility. A 19-year-old sister had same symptoms. We examined COL5A1. We extracted genomic DNA from blood of the patient, sister and mother, which were used for direct sequence of genome after exon amplification by PCR. The patient and sister had one heterozygous ins T in exon 65 of COL5A1 gene. This mutation lead premature terminal codon. Mother had not this mutation. Fibroblasts obtained from the patient and sister revealed significant decrease of pericellular fibers consists of COL1 as well as those of COL5. Decrease of both types of collagen was also confirmed by Western blot using cell layers proteins. The result suggests that COL5 involved in COL 1 fiber formation and a haploinsufficiency of COL5 resulted in severe effect to COL1 fiber formation in vitro. Case 2, an 18-year-old woman, had same symptoms, suspected cEDS. We examined COL5A1 of the patient as well as her mother as described above. The genetic analysis revealed heterozygous substitution mutation, G>T, in recipient site of intron 61, which was supposed to induce exon skipping including exon 62. Mother had not this mutation. None of these two mutations have been reported so far. Conclusion, We are required genetic analysis not only clinical symptoms for definite diagnosis. This decreases diagnostic accuracy. Thus, we have studied COL5A1 in order to increase diagnostic accuracy of cEDS. In this study, we could detect COL1 gene mutations with similar sensitivity to previous reports.

BACKGROUND:Patients with steroid-resistant bullous pemphigoid (BP) require an appropriate treatment option.OBJECTIVE:A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in BP patients who showed no symptomatic improvement with prednisolone (≥0.4mg/kg/day) administered.METHODS:We evaluated the efficacy using the disease activity score on day15 (DAS15) as a primary endpoint, and changes in the DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days as secondary endpoints.RESULTS:We enrolled 56 patients in this study. The DAS15 was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The mean DAS of the IVIG group was constantly lower than that of the placebo group throughout the course of observation, and a post hoc analysis of covariance revealed a significant difference (p=0.041). Furthermore, when analyzed only in severe cases (DAS≥40), the DAS15 differed significantly (p=0.046). The anti-BP180 antibody titers showed no difference between the two groups.CONCLUSION:IVIG provides a beneficial therapeutic outcome for patients with BP who are resistant to steroid therapy.

Objectives: Recently, we reported that the majority of GPP that is not accompanied by PV (GPP alone) is caused by homozygous or compound heterozygous mutations of IL36RN, which encodes interleukin-36 receptor antagonist (Sugiura K et. al. J Invest Dermatol 2013). In the present study, we analyzed IL36RN mutations and CARD14 variants as predisposing factors for impetigo herpetiformis (IH) and GPP accompanied by psoriasis vulgaris (PV; GPP with PV).

Nevus depigmentosus is leukoderma present at birth or onset early in life. We examined melaninogenesis with scalp hair from a 1-year-old Japanese boy with nevus depigmentosus involving skin, hair and an eye. The patient showed a hypopigmented lesion with yellow-brown hair on the left face and the left scalp following the lines of Blaschko. It surrounded the left eye. The patient had the dark brown iris of the right side and the bright brown iris of the left side. The amounts of eumelanin and pheomelanin were evaluated with black hair and yellow- brown hair samples. Black hair was composed of eumelanin (16.24 ug/mg) and pheomelanin (0.06 ug/mg) and yellow-brown hair was composed of eumelanin (4.82 ug/mg) and pheomelanin (0.07 ug/mg). The assay showed that the yellow- brown hair apparatus had about 30% ability to produce eumelanin and almost same ability to produce pheomelanin. The impaired step of melanogenesis was signified by the only decreased production of eumelanin in the affected hair. Most of natural melanin pigments including hair melanin are believed to be present as copolymers of eumelanin and pheomelanin (‘mixed’ melanogenesis). We have suggested the model of mixed melanogenesis in which pheomelanin production constantly proceeds initially and eumelanin is deposited subsequently on the preformed pheomelanin, giving melanin granules consisting of pheomelanin in the core and eumelanin on the surface. We previously showed that hypopigmented hair color in nevus pigmentosus and hypomelanosis of Ito was caused by inhibition of eumelanin synthesis but not pheomelanin synthesis. Our case showed similar insufficient eumelaninogenesis and unchanged pheomelanogenesis in nevus depigmentosus with simultaneous involvement of skin, hair and an eye.

症例は 75 歳，男性。約 3 カ月前から両足部に疼痛を伴った網状皮斑があった。造影 CT 検査にて腹部大動脈内壁の不整な血栓像を認め，血栓は内腔に向かって突出していた。壊疽に陥った右第 5 趾の切除標本の病理組織像では，真皮中層から脂肪織の血管内腔に紡錘形の裂隙形成を伴う好酸性無構造物質による閉塞および器質化を認めた。以上からコレステロール結晶塞栓症である shaggy aorta 症候群と診断した。 コレステロール結晶塞栓症の原因としては，カテーテル検査などの血管内操作に基づく場合がよく知られているが，誘因が不明の症例では shaggy aorta 症候群を考慮することが重要と考える。

Hepatitis E virus (HEV) is the causative agent of hepatitis E, a food- and water-borne disease. In developed countries, consumption of meats from pigs, wild boars and deer is a major source of infection. Although HEV and HEV-related viruses have been detected in many animal species, their zoonotic potential and prevalence has not been completely understood. To detect anti-HEV antibody in mammalian species, a simple enzyme-linked immunosorbent assay (ELISA) was established using extract from cells expressing HEV capsid protein and protein A/G as an antigen and a reagent for detection of antibody. Absorbance in the ELISA was compared with those in our previous ELISA using VLPs and anti-swine antibody, suggesting that newly established ELISA was similarly specific and sensitive as the previous ELISA. Seroprevalence of HEV infection among wild boars was examined in Yamaguchi Prefecture, confirming that 111 of 364 wild boars (30.5%) were positive for anti-HEV antibody. Next, this ELISA was applied to humans, dogs, cats, ferrets, raccoons and masked palm civets in Japan, and anti-HEV antibodies were detected in humans, ferrets, dogs and cats. This ELISA is thus useful for serological surveys and comparison of HEV infection among various mammals, including humans.

Dermal mucinosis is often associated with collagen diseases such as rheumatoid arthritis, lupus erythematosus, and dermatomyositis, in addition to autoimmune thyroiditis. We report eight cases of dermal mucin deposition secondary to typical dermatomyositis with cutaneous lesions known as heliotrope rash and Gottron’s papules. Striking mucin deposition was observed in both the papillary dermis and reticular dermis of all biopsy specimens. Immunohistochemical analysis showed that CD34+ dermal dendritic cells（DDCs） in the perilesional area in combination with vimentin+ cells within the mucinous lesion might be important in giving rise to abnormal deposition of dermal mucin. On the other hand, numbers of factor ⅩⅢa+ DDCs and tryptase+ mast cells were reduced within and surrounding the mucin deposition, as compared with those in the dermis of normal controls. A pathogenic mechanism of dermal mucin deposition is proposed.

67歳，男性．頭頂部から左上眼瞼および右鼻翼にかけて広範囲に存在する紅斑と結節，潰瘍を主訴に当科紹介受診となった．病理組織学的所見において異型性のある腫瘍細胞が血管を模倣した管腔構造を呈しており，免疫染色においてCD31が陽性であったため，血管肉腫と診断した．明らかな遠隔転移は存在しなかったが，腫瘍が多発しており手術による完全切除が不可能と判断し，MAID（Mesna，Adriamycin，Ifosfamide，Dacarbazine）療法を行った．grade3の好中球減少とそれに伴う発熱を認めたが５コース終了時には腫瘍は著明に縮小しPR（partial response）が得られた．頭部血管肉腫は高齢者に好発するのが，自験例のように60歳代でpeformance status（以下PS）が０でありMAID療法を行うことができた稀な症例を経験したので，若干の文献的考察を加えここに報告した．