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Cores recovered during the International Continental Scientific Drilling Program project "Drilling into Seismogenic zones of M2.0 to M5.5 earthquakes in deep South African Gold Mines" include fault breccia from within the aftershock cloud of the 2014 Orkney earthquake (M5.5). The breccia and surrounding intrusive rocks, probably lamprophyres rich in talc, biotite, calcite, and amphibole, had high magnetic susceptibilities owing to the presence of magnetite. All of these characteristics can be attributed to fluid-related alteration. Both the breccia and the lamprophyres had low friction coefficients and showed evidence of velocity strengthening, which is inconsistent with the occurrence of earthquakes. Variable amounts of talc, biotite, calcite, and amphibole within the lamprophyres might have produced complex frictional properties and spatial heterogeneity of fault stability. The altered lamprophyres may be the host rocks of the 2014 Orkney earthquake, but frictional complexity may have governed the magnitudes of the main- and aftershocks and their distributions., Geophysical Research Letters, 49 (14), ISSN:0094-8276, ISSN:1944-8007

Terahertz (THz) spectroscopy of solids in high magnetic fields can often provide new insight into the microscopic physics behind complex many-body behaviors [1].

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.\ud The Harmonising Outcome Measures for Eczema (HOME) initiative is an international group working together to develop a core outcome set (COS) for clinical trials in eczema (synonymous with atopic eczema and atopic dermatitis). HOME is coordinated from the Centre of Evidence Based Dermatology, University of Nottingham, U.K. Participation in HOME is open to anyone with an interest in outcomes for eczema. A COS is the agreed upon minimum set of instruments that should be included in all clinical trials for a particular condition. Use of a COS does not preclude using other instruments; other domains and instruments can also be included to meet the specific requirements of individual trials. COS initiatives are active across many fields of medicine and should enable better synthesis of trial data and reduce selective outcome reporting bias.\ud The HOME initiative follows the best current guidance on developing a COS. Four core domains have been identified: clinician-reported signs; patient-reported symptoms; quality of life; and long-term control. The core outcome measurement instruments for clinician-reported signs and patient-reported symptoms have been established: the Eczema Area and Severity Index (EASI) for measuring clinician reported signs was agreed on at the HOME III meeting, and the Patient-Oriented Eczema Measure (POEM) was chosen to measure patient-reported symptoms at the HOME IV meeting.\ud This is a report from the fifth consensus meeting of the HOME initiative (HOME V), which was held on 12–14 June 2017 in Nantes, France. The local organizers were Sebastien Barbarot and Jean-Francois Stalder of Nantes University Hospital, France.

We describe the present status of future high-precision measurements of nuclear g-factors utilizing laser-microwave double and laser-microwave-rf triple resonance methods for online-trapped, laser-cooled radioactive beryllium isotope ions. These methods have applicability to other suitably chosen isotopes and for beryllium show promise in deducing the hyperfine anomaly of 11Be with a sufficiently high precision to study the nuclear magnetization distribution of this one-neutron halo nucleus in a nuclear-model-independent manner.

Terahertz-field-induced carrier generation processes were investigated in Dirac electron systems, single-crystalline bismuth antimony alloy thin films ($\mathrm{B}{\mathrm{i}}_{1\ensuremath{-}x}\mathrm{S}{\mathrm{b}}_{x}$; $0\ensuremath{\le}x\ensuremath{\le}0.16$). This investigation was performed by precisely tuning, via the substituent ratio $x$, the band structure of the films from that associated with a semimetal to that characteristic of a narrow-gap semiconductor. Terahertz-field-induced absorption was clearly observed within a few picoseconds after the terahertz pump-pulse illumination of $\mathrm{B}{\mathrm{i}}_{1\ensuremath{-}x}\mathrm{S}{\mathrm{b}}_{x}$ semimetal and semiconductor samples. The field-strength dependence of the induced absorption was compared with the calculated Zener tunneling probability in the Dirac-like band dispersion. Through this comparison, the mechanism of the induced absorption was attributed to the carrier generation via the terahertz-field-induced Zener tunneling. The tunneling occurred in subpicosecond timescales even at room temperature, demonstrating that $\mathrm{B}{\mathrm{i}}_{1\ensuremath{-}x}\mathrm{S}{\mathrm{b}}_{x}$ thin films are promising for future high-speed electronics and the investigation of universal ultrafast tunneling dynamics.

Summary Background. Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive skin disease caused by mutations in the type VII collagen gene (COL7A1), resulting in detachment of the entire epidermis due to loss or hypoplasticity of the anchoring fibrils that normally secure the basement membrane to the underlying dermis. Trauma-induced blistering is often complicated by chronic erosions and scarring. From that perspective, pregnancy in RDEB might be considered an indication for elective caesarean section in a bid to minimize perineal blistering. To date, only four cases of pregnancy and delivery in patients with RDEB have been reported. Cases. We report three more women, each with RDEB-generalized other (RDEB-GO), all of whom had successful vaginal deliveries without major cutaneous or mucosal complications. One woman also had a second child, by vaginal delivery, indicating a lack of vaginal stenosis after the first birth. Conclusions. These cases show that RDEB-GO is not an absolute primary indication for elective caesarean section and that, perhaps surprisingly, genital/perineal blistering and scarring are not inevitable consequences of childbirth. Moreover, breastfeeding is also feasible in women with RDEB-GO.

BACKGROUND AND PURPOSE: Ameloblastomas and keratocystic odontogenic tumors are major aggressive odontogenic tumors in the maxillomandibular regions, but the differentiation between these 2 tumors is frequently ineffective based on only conventional CT and MR imaging findings. Here, we evaluated diffusion-weighted MR imaging for the differentiation of these 2 odontogenic tumors. MATERIALS AND METHODS: We prospectively studied 9 patients with ameloblastoma and 7 patients with keratocystic odontogenic tumor using diffusion-weighted MR imaging. Apparent diffusion coefficients (ADCs) of the nonenhancing and solid lesions in these tumors were determined with use of 2 b factors (500 and 1000). RESULTS: Two types of nonenhancing lesions were identified; one with high signal intensity on fat-suppressed T2-weighted images (type A) and the other with low or intermediate intensity (type B). The type A nonenhancing lesions were observed in all the ameloblastomas, but they were evident in only 2 keratocystic odontogenic tumors. It is interesting to note that the ADCs of the nonenhancing lesions in the ameloblastomas were significantly higher than those of the nonenhancing lesions in the keratocystic odontogenic tumors (2.48 ± 0.20 × 10(−3) mm(2)/s vs 1.13 ± 0.56 × 10(−3) mm(2)/s; P < .001). The ADCs of the solid lesions in the ameloblastomas (1.39 ± 0.15 × 10(−3) mm(2)/s) were significantly lower than those of the nonenhancing lesions in the ameloblastomas and were similar to those of the nonenhancing lesions in the keratocystic odontogenic tumors. CONCLUSION: ADC determination may be used as an adjunct tool for differentiation between ameloblastomas and keratocystic odontogenic tumors.

The Japan Arteriosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC) is a pooled study based on individual participant data from existing prospective cohort studies in Japan. Its purpose was to consider associations between risk factors and cardiovascular disease (CVD) outcomes, as well as differences between subgroups, defined by age, gender or geographical region, which could not be detected in the smaller samples.Individual records for 66,691 participants in 21 cohort studies were pooled, accounting for a total of 575,628 person-years. From this data, there were 409 deaths attributed to stroke and 169 deaths attributed to coronary heart disease (CHD). Total stroke and CHD events were 1,478 and 178, respectively. Of the 1,424 total stroke events with a reported stroke subtype, 975 were classified as ischemic, 267 as hemorrhagic, and 178 as subarachnoid hemorrhage.The JALS-ECC collected data from existing cohort studies covering a diverse Japanese population, which has provided information about the effects of modifiable factors on the risks of the CVD. Such information should provide a reliable basis for establishing prevention strategies.

An ISOL-based radioactive nuclear beam (RNB) facility, Tokai Radioactive Ion Accelerator Complex (TRIAC), has been jointly developed by High Energy Accelerator Research Organization (KEK) and Japan Atomic Energy Agency (JAEA). The facility started to supply RNBs for experiments in 2005 and RNBs including fission fragments with energies up to 1.1MeV/A are available in the present. Several experimental studies were performed successfully using 8Li beams with various energies.

Summary Background and objective: Yusho occurred in western Japan in 1968 and was caused by ingestion of rice bran oil that was contaminated with polychlorinated biphenyls (PCBs) and dioxins such as polychlorinated dibenzofurans (PCDFs). At that time, the skin symptoms presented by patients with Yusho were at their most prominent and worst severity. Analysis of blood to determine the concentration of dioxins started in 2001 in Fukuoka prefecture, and in 2002 the examination was performed throughout Japan. There have been no reports on the relationship between blood concentration of dioxins and skin symptoms in Yusho. This is the first report to examine the relationship between blood concentration of dioxins and skin symptoms in Yusho, using statistical analyses. Methods: Using the global skin severity grade, we analyzed the change in skin symptoms, which were examined at the annual medical check-up of patients with Yusho. We also investigated the relationship between the items of the annual dermatological examination and blood concentrations of total PCDFs and total PCBs. Results: The severity of skin symptoms improved significantly in the first 20 years; nowadays, however, further improvement can hardly be observed. Using three-way analysis of variance (ANOVA), we found that of the 21 items of the dermatological examination, nine were significantly related to total PCDFs, and five were related to total PCBs. Only one item was significantly related both to total PCDFs and total PCBs. Conclusion: More than 36 years have passed since the Yusho incident, and about 60% of the patients currently present with no skin symptoms. In contrast, in about 40% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could still be observed. Our analysis of the relationship between skin symptoms and blood concentrations of total PCDFs and total PCBs proves that not only PCBs but also PCDFs have an important role in the skin symptoms of Yusho.

To establish a cell culture system that reflects the dentin formation in dental pulp tissue, we used dental pulp cells enzymatically isolated from rat incisor teeth. During the 20-day culture period, the cells exhibited various phenotypes of the odontoblast differentiation process, from the immature stage to the terminal mineralization stage. The cells began to form the mineralized nodules from day 10, and the nodules became larger by day 20. Alkaline phosphatase (ALP)-positive cells surrounded the mineralized nodules. The ALP activity in the cell layers was maximal on day 5, and gradually decreased to day 20. The calcium content in the cell layers was very low by day 10, and significantly increased from day 15. Sulfated glycosamino-glycans (GAGs) contained in the cell layers increased by day 15, but the content then decreased by day 20. The dental pulp cells produced a small amount of osteocalcin that was released into the culture medium by day 10, and the amount secreted increased markedly from day 15. The expression of osteocalcin and parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor mRNA was evident as early as day 5, and the expression of each gradually increased with the number of days in culture. Dentin matrix protein (Dmp1) mRNA gene transcripts were identified by use of the reverse transcription polymerase chain reaction (RT-PCR) in the cells throughout the culture period. The present results demonstrate that this culture system is useful for studying the differentiation process of the odontoblast-like cells.

Background: Solar urticaria is a rare disorder characterized by pruritus, erythema and wheal upon sunlight exposure. Inhibition spectra (IS), which prevent wheal formation, have been found mainly in Japanese patients and lie mostly in longer wavelengths than the action spectrum (AS). The exact mechanism of AS and IS has not been clarified. Patients and Methods: To elucidate the mechanism of AS and IS, we conducted photobiological studies including in vitro irradiated serum injection tests and measurements of plasma histamine levels in 3 patients with IS. Results: All patients had AS ranging between 400 and 490 nm and IS ranging between 520 and 610 nm. A wheal reaction appeared soon after the termination of IS irradiation. The patients developed no wheal or erythema upon intradermal injection of preirradiated serum. Plasma histamine levels were not elevated during irradiation with slide projector light, but marked elevation of histamine was observed when wheals developed after the termination of inhibitory irradiation. Conclusion: These results suggest that the IS in our cases might inactivate photoallergens produced by AS and, additionally, stabilize mast cell degranulation.

Experimental thermodynamic studies of liquid Al-Mg alloys have been performed by several methods resulting in: (1) Mg activities from galvanic cells with liquid electrolytes at temperatures from 910 to 1070 K, at XMg = 0.1 to 0.7 and for the dilute range when XMg = 0.0126 to 0.1430 at 927 K; (2) Mg activities from the emf method with solid CaF2 electrolyte at temperatures 921 to 1093 K, with concentrations XMg = 0.05 to 0.9; (3) Mg activities from vapor pressure measurements (Knudsen effusion method) at temperatures ranging from 722 to 1188 K, at XMg = 0.0424 to 0.8885. Vapor pressures of pure solid Mg at temperatures 674 to 851 K. In addition, liquidus temperatures for Mg- and Al-rich alloys were obtained; and (4) Partial and integral enthalpies from reaction calorimetry at 1023 K, starting from pure Mg bath at concentrations, XAl = 0.066 to 0.499, and starting from pure Al bath at XMg = 0.522 to 0.906. The mutual consistency of these four sets of data was analyzed. New results together with the selected thermodynamic information reported in literature were optimized to describe the liquid phase with the Redlich-Kister equation, as a preliminary step for phase diagram calculations of the Al-Mg system.

Stem cell factor (SCF) distribution in basal cell carcinomas (BCCs) was examined by immunohistochemistry. Eighteen BCCs (11 nodular, three superficial, two cystic, one adenoid and one morphoeic type) showed positive expression of SCF in the tumour islands. The centre of the tumour island was strongly positive in nodular, superficial and morphoeic types. In cystic BCCs, SCF-positive tumour cells were also located in the peripheral lesion around the cystic space. SCF was also detected on fibroblast-like cells and mast cells in the stroma. SCF was positively stained within the upper keratinocytes in the overlying epidermis, more strongly as compared with normal skin. The mast cell number (mean +/- SD) was significantly increased in the peritumoral stroma (85.7 +/- 28.3/mm2) compared with normal skin (32.1 +/- 4.2/mm2) (P < 0.005). SCF was also positive in the tumour nests of four cases of tricho-epithelioma, in which fibrosis of the surrounding stroma was found histologically. This study demonstrates that abundant SCF produced by the tumour cells may account for the increased number of stromal mast cells, which induce fibroplasia of the surrounding stroma.

Cutaneous plasmacytosis is a rare disorder without systemic plasma cell proliferation in organs other than the skin, with a possible malignant transformation. However, there are few effective therapies available. It has been reported that interleukin-6 (IL-6), which is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells, plays a part in systemic plasmacytosis. In this study, we performed intralesional steroid therapy in the lesions of cutaneous plasmacytosis in three patients, which resulted in sufficient clinical effects. We demonstrated that before treatment, plasma IL-6 levels were significantly elevated in all the patients, and that levels were reduced in parallel with the clinical improvement after therapy. Immunohistochemistry revealed IL-6 protein expression on tumour cells in the lesional skin. Reverse transcription-polymerase chain reaction (RT-PCR) detected IL-6 mRNA in the lesional skin in all cases, levels of which were decreased after the effective intralesional steroid therapy, but which were unchanged after ineffective topical photochemotherapy (PUVA). Peripheral blood mononuclear cells from the patients produced significantly large quantities of IL-6 which were reduced by addition of steroid in vitro. These results suggest that the generation of IL-6 plays the key role in cutaneous plasmacytosis and that intralesional steroid therapy is effective in reducing the production of IL-6 in this disorder.

CD80 (B7-1) and CD86 (B7-2/B70) have recently been identified in cultured human Langerhans cells (LCs), although their role and regulatory properties remain unclear. We present our comparison of the expression of the molecules, mRNAs and the function between CD80 and CD86 in human LCs treated by interferon gamma (IFN-gamma). We examined the regulatory properties of CD80 and CD86 expression in human LCs pretreated with IFN-gamma. Flow cytometric analysis indicated that the mean fluorescence intensity of CD86 but not CD80 was enhanced. However, the percentage modulation of both CD80 and CD86 positive cells were significantly up-regulated in a dose-dependent manner, after 48-h culturing with IFN-gamma. The regulatory properties of CD80 and CD86 mRNA expressions in human LC were studied using polymerase chain reaction methods. We found that both CD80 and CD86 mRNA of enriched LCs following IFN-gamma pretreatment for 12 h were higher than those without pretreatment. We have demonstrated that the primary allogeneic mixed epidermal cell-lymphocyte reaction induced by human LCs treated by IFN-gamma increased in a dose-dependent manner. There was a 61.5% inhibition by anti-CD86 monoclonal antibody and a 32.5% inhibition by anti-CD80 monoclonal antibody. These data indicate that the CD80 and CD86 expression of human LCs may be differently regulated by IFN-gamma.

51歳の男性。初診6日前に咽頭痛出現, 3日前に四肢, 躯幹に紫斑が生じ, 顔面にも拡大したため, 東京医科歯科大学皮膚科受診となった。既往歴では47歳時に修正大血管転位症, 肺動脈狭窄症, 僧帽弁三尖弁閉鎖不全症に対する弁置換術およびHCV感染症あり。初診時に下腿, 前腕に血疱, 潰瘍を形成する鳩卵大までの紫斑が播種状に認められ, 顔面, 躯幹にも粟粒大の紫斑が多数認められた。紫斑部の組織像では真皮上層から下層まで広汎な細小血管にleukocytoclastic vasculitisが認められた。扁桃マッサージ試験により紫斑の新生が認められたため, 扁桃腺炎に由来する皮膚アレルギー性血管炎と診断し, 種々の抗生物質を使用したが, 4年後の現在も紫斑は持続し, 腎機能障害は進行中である。顔面に紫斑が生じた要因は皮膚アレルギー性血管炎の病勢と心疾患による顔面の静脈圧の上昇と考えたが, HCV感染症による紫斑の分布域の拡大も否定できなかった。文献的考察では下肢以外に紫斑が認められた例で統計学的に有意に腎障害発生が多かった。

La f.e.m. de la pile (-)W|Zn,ZnO|ZrO 2 (+Y 2 O 3 )|Zn-Bi,ZnO|W(+) est measuree afin de determiner l'activite du zinc sur tout le domaine de concentrations des alliages liquides Zn-Bi, entre 750 et 950 K. Celle-ci presente d'importants ecarts positifs par rapport a la loi de Raoult. A partir des activites, on calcule, a la limite des grandes longueurs d'onde, les fluctuations de concentration Scc(0) et on les compare aux previsions d'un modele de demixtion des alliages binaires liquides. La lacune de miscibilite est obtenue grâce aux series de points E vs T.

A gas circulation and purification system was developed at the RIKEN Radioactive Isotope Beam Factory that can be used for gas-cell-based low-energy RI-beam production. A high-flow-rate gas cell filled with one atmosphere of buffer gas (argon or helium) is used for the deceleration and thermalization of high-energy RI-beams. The exhausted buffer gas is efficiently collected using a compact dry pump and returned to the gas cell with a recovery efficiency of >97%. The buffer gas is efficiently purified using two gas purifiers as well as collision cleaning, which eliminates impurities in the gas. An impurity level of one part per billion is achieved with this method.

Background: Multiple dermatofibromas (DFs) are often associated with systemic lupus erythematosus (SLE). An increased number of mast cells is observed in the upper portion or over the lesion of DF Objective: To investigate the role of the serum of a patient with multiple DFs, we examined its growth effects on fibroblasts. Method: 3H-Thymidine incorporation was used to examine the effects of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF and normal skin. Results: The serum of the SLE patient with multiple DFs exhibited a stronger growth-stimulatory activity on normal and DF-derived fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or normal sera. The growth effects were inhibited in 40% by anti-platelet-derived-growth-factor antibody and almost completely inhibited by antibody against basic fibroblast growth factor. Cultured fibroblasts derived from the upper portion of the DF lesion, which included most of the numerous mast cells, demonstrated a higher level of 3H-thymidine uptake after stimulation of autologous serum compared to that from the mid and lower portions of DF. Conclusion: These results suggested the existence of various fibroblast growth factors derived from the mast cells in SLE patients with multiple DFs.

The hyperfine splittings of ground state Be+11 have been measured precisely by laser-microwave double resonance spectroscopy for trapped and laser cooled beryllium ions. The ions were produced at relativistic energies and subsequently slowed down and trapped at mK temperatures. The magnetic hyperfine structure constant of Be+11 was determined to be A11=-2677.302 988(72) MHz from the measurements of the mF-mF'=0-0 field independent transition. This measurement provides essential data for the study of the distribution of the halo neutron in the single neutron halo nucleus Be11 through the Bohr-Weisskopf effect.

A Monte Carlo simulation method for calculating the probability of soil liquefaction of a finite area in which the ground motion is propagated upward from the bedrock through the soil layers is presented. The vertical propagation of the ground motion through the soil layers is analyzed using random vibration analysis. To account for the variability of soil properties with depth, the soil deposit is divided into layers. Within each layer the horizontal statistical correlation of the undrained cyclic shearing strength against liquefaction is taken into consideration by describing it as a two-dimensional homogeneous random field. The method computes the probability of liquefaction spreading over a specified area under a given earthquake loading considering the effects of spatial correlation of soil properties.

Paraneoplastic cutaneous disorders (PCDs) or dermadromes are skin conditions that have an association with internal malignancies but are not themselves malignant. We report the first two cases of systemic anaplastic large cell lymphoma (s-ALCL) accompanied by erythroderma and multiple leg ulcers as PCDs. CASE 1: A 52-year-old Japanese man presented with disseminated itchy papular erythemas which he had over his entire body for the preceding 5 years that later exacerbated to erythroderma. Multiple punched-out ulcers also developed on his lower legs. Superficial lymph nodes (LNs) were swollen, and a left axillary LN biopsy demonstrated dense CD30(+) atypical large cell (ALC) infiltration. By contrast, lymphocytes infiltrating into the erythroderma and leg ulcers were CD30(-) , and T-cell receptor β (TCRβ) chain gene rearrangement was negative in skin biopsy specimens. Thus, he was diagnosed with s-ALCL. Not only his s-ALCL but also his erythroderma and leg ulcers responded well to chemotherapy. CASE 2: A 71-year-old Japanese woman presented with erythroderma that persisted for approximately 20 years after mastectomy. At her initial hospital visit, she was diagnosed with s-ALCL by biopsy of swollen left inguinal LNs. Similar to Case 1, CD30(+) ALCs were negative in skin samples with normal TCRβ chain gene rearrangement. As the erythrodermic skin lesion responded well to chemotherapy for s-ALCL, it was considered a PCD. s-ALCL development may be predicted by the precedence and concurrence of intractable paraneoplastic erythrodermic and ulcerative skin lesions, as reported in our two cases.

The ferroelectric soft mode in a SrTiO(3) thin film was impulsively driven to a large amplitude using intense picosecond terahertz pulses. As the terahertz electric field increased, the soft-mode absorption peak exhibited blueshifting and spectral narrowing. A classical anharmonic oscillator model suggests that the induced displacement is comparable to that of the ferroelectric phase transition. The spectral narrowing indicates that the displacement exceeds that induced by any inhomogeneities in the film, demonstrating that the method can be used to explore intrinsic quartic anharmonicity.

A 61-year-old man presented with a skin tumour in the right axilla of 2 months' duration. An excision biopsy revealed a malignant lymphoma, of diffuse mixed small and large cell type, morphologically suggestive of T-cell lymphoma, but shown to be a T-cell-rich B-cell lymphoma by subsequent immunohistochemical staining. A review of the literature revealed 47 cases of T-cell-rich B-cell lymphoma with descriptions of primary sites, 35 nodal and 12 extranodal, of which only one was a cutaneous primary.

Extramammary Paget disease (EMPD) often develops in external genitalia. Paget cells can, however, adopt an invasive phenotype and metastasize to regional lymph nodes and beyond, leading to poor patient outcomes. Based on this clinical observation, multiple lymphadenopathy may represent an initial sign of EMPD. To address the potential significance of multiple lymph node swelling in EMPD, we report two patients with cutaneous primary EMPD who showed multiple lymphadenopathy as an initial sign during the clinical course of the disease as well as tumour metastasis. Significantly, marked lymphatic vessel growth was observed in regional lymph nodes that underwent massive tumour cell invasion. Therefore, nodal lymphangiogenesis may promote tumour cell invasion and metastasis to distant organs, including the lymph nodes, emphasizing the clinical relevance of multiple lymphadenopathy.

Keratinocytes can obtain cholesterol either by de novo synthesis or by extraction, primarily from low-density lipoprotein (LDL). LDL is internalized following binding to the LDL receptor (LDLR). Because LDLR is expressed at a higher level in the cells of the basal layer of the epidermis, it might be assumed that LDLR upregulation is associated with keratinocyte proliferation. However, the effect of LDLR stimulation on keratinocyte function remains unclear.To investigate the effects and mechanism of action of pitavastatin and effects of LDL on proliferation and migration of keratinocytes.Pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was used to induce upregulation of LDLR. LDLR expression was evaluated by immunofluorescence staining, fluorescence-activated cell sorting, immunohistochemical staining and real-time polymerase chain reaction (PCR). HaCaT cells and normal human keratinocytes (NHKs) were used for evaluation of migration. 5-Bromo-2'-deoxyuridine incorporation was used to evaluate keratinocyte proliferation and differentiation. C57BL6 mice were used for in vivo evaluation of the effect of topical pitavastatin or lovastatin.Pitavastatin was most effective in LDLR induction at a concentration of 1 micromol L(-1) in NHKs. Real-time PCR showed that pitavastatin significantly increased LDLR and liver X receptor (LXR) beta mRNA expression in these cells. Similar results were obtained in vivo. However, pitavastatin had no effect on the migration of NHKs. After the addition of LDL and/or mevalonate concomitantly with pitavastatin to NHK cultures, or topical application of pitavastatin on mouse skin, keratinocyte proliferation was significantly increased.Pitavastatin significantly upregulates LDLR in both NHKs and C57BL6 mouse skin, resulting in increased keratinocyte proliferation. LXRbeta may be involved in the pitavastatin-induced keratinocyte proliferation.