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Four-colored fluorescence in situ hybridization (FISH) is an ancillary diagnostic tool for melanoma. However, most studies that have investigated the usefulness of FISH primarily focused on advanced melanomas. The aim of the current study was to evaluate the effectiveness of FISH in distinguishing acral melanoma (AM) in situ from benign acral junctional nevus (AJN), two types of lesions that are difficult to differentiate via traditional clinical means. The authors investigated the usefulness of FISH in 91 acral melanocytic lesions, including 50 lesions with diagnostic discrepancies between dermoscopic and pathologic approaches or difficulty diagnosing between AM in situ and AJN, on the volar skin of Japanese patients. The authors classified the lesions based on the diagnosis of dermatologists and pathologists into four groups: (I) lesions with a unanimous diagnosis by dermatologists and pathologists as AM in situ or AJN (n = 41); (II) lesions with a unanimous diagnosis by dermatologists only as AM in situ or AJN (n = 21); (III) lesions with a unanimous diagnosis by pathologists only as AM in situ or AJN (n = 15); and (IV) all other lesions (n = 14). The dermatologists diagnosed the lesions by clinical and dermoscopic photographs alone, while the pathologists diagnosed the lesions by microscopy of hematoxylin and eosin-stained slides alone. In group I (AM in situ [n = 20] and AJN [n = 21]), four-colored FISH demonstrated 90% sensitivity and 81% specificity in distinguishing AM in situ from AJN. There was a significant correlation between the FISH results and the unanimous diagnoses by pathologists alone (p = 0.03) in group III. However, FISH results were not significantly correlated with the unanimous diagnoses by dermatologists alone (p = 0.33) in group II. In conclusion, the four-colored FISH probe kit was useful in distinguishing between AM in situ and AJN and may be an ancillary method when pathologists who are not experts of dermatopathology diagnose melanocytic lesions.

Background With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long‐term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once‐daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. Methods APeX‐J is a phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group, 3‐part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run‐in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert‐confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs., APeX‐J is a phase 3, placebo‐controlled trial conducted in Japan to assess the efficacy and safety of oral berotralstat in patients with HAE. Patients were randomized 1:1:1 to receive once‐daily berotralstat 110 mg, berotralstat 150 mg, or placebo. Berotralstat 150 mg significantly reduced the frequency of HAE attacks compared with placebo, supporting its use as a prophylactic therapy. Abbreviation: HAE, hereditary angioedema.

The "Guidelines for the management of dermatomycosis" of the Japanese Dermatological Association were first published in Japanese in 2009 and the Guidelines Committee of the Japanese Dermatological Association revised it in 2019. The first guidelines was prepared according to the opinions of the Guidelines Committee members and it was of educational value. The revised version is composed of introductory descriptions of the disease concepts, diagnosis, medical mycology and recent advances in treatment, along with clinical questions (CQ), which is intended to help in general practice for dermatologists. The CQ are limited to those involved in therapy but include some of the recently launched antifungal agents. The level of evidence and the degree of recommendation for each item were reviewed by the committee based on clinical studies published by 2018. For rare dermatomycoses, recommendations by the committee are described in the guidelines. In this field, there are still few good quality studies on treatment. Periodic revision in line with new evidence is necessary.

Interface-resolved large eddy simulations were performed to reproduce hyperconcentrated water-particle mixture flows in a laboratory experiment conducted by Egashira et al. (2001). The flows were simulated at sediment concentrations of 0.196 and 0.444 using spheres and gravel particles. Simulations using gravel with a suitable shape properly reproduced the discharge rates of water and particles as well as the wall-normal distributions of the particle velocities in the experiments. The study involved an examination of the effects of particle shapes and the coefficients of contact forces (coefficients of restitution and friction angles of particle surfaces) used in the discrete element method on mixture flows. Significantly different flows were obtained for spherical and gravel particles under dense conditions, whereby the particle shear stress became much greater than that for water. The simulations of spheres at different coefficients of contact forces could not adequately represent the mixture flows of nonspherical particles.

Background Muir-Torre syndrome (MTS) is currently considered as a clinical variant of Lynch syndrome (LS). The clinical significance of the screening of patients with MTS-associated cutaneous tumors for the identification of LS has not yet been established. In addition, the prevalence and molecular characteristics of mismatch repair (MMR) protein deficiency in such tumors has scarcely been investigated in the Japanese population. Methods Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from 16 sebaceous neoplasms (SNs) resected from 13 patients and 32 keratoacanthomas (KAs) resected from 31 patients at our institution between January 2005 and March 2014. Tumors showing MMR protein loss were further subjected to genetic analysis for detecting the presence of germline and/or somatic alterations of the MMR genes to identify the precise molecular mechanisms underlying the protein loss. Results Among the 16 SNs resected from 13 patients, eight SNs resected from five patients (38.5%) showed loss of expression of MMR proteins (MLH1/PMS2 loss, one patient; MSH2/MSH6 loss, four patients). Genetic analyses showed a pathogenic germline MSH2 mutation in one patient, somatic hypermethylation of the MLH1 promoter region in one patient, and somatic alterations of MSH2 without detectable germline mutations of MSH2 in three patients. None of the KAs examined in the study showed any loss of MMR protein expression. Conclusions The efficacy of routine screening of cutaneous neoplasms known to be associated with MTS by IHC for MMR proteins to identify LS may be fairly limited. MMR protein loss as determined by IHC in SNs is not always diagnostic of LS, and appears, in most cases, to be a result of somatic inactivation of the MMR genes.

Background: Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS. Objective and Methods: Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS. Results: The proportions of circulating IL-4- and IL-13-producing CD4+ T cells, but not CD8+ T cells, were significantly higher in patients with DRESS during the active stage of the disease than in healthy subjects, and these proportions declined during the recovery stage. No differences in the proportions of circulating IFN-γ-, IL-17-, and IL-22-producing CD4+ and CD8+ T cells were observed between patients with DRESS and healthy subjects. A strong correlation between the proportion of IL-13-producing CD4+ T cells and serum levels of thymus and activation-regulated chemokine was observed. The proportion of CLA-expressing CD4+ T cells was significantly higher during the active stage of the disease. Moreover, the proportion of IL-13-producing CD4+ T cells was higher in the CLA+ subset than in the CLA- subset. Conclusions: Skin-homing IL-13-producing CD4+ T cells may be involved in the pathogenesis of DRESS.

Chromomycosis is an infection caused by dematiaceous fungi. These fungi belong to several genera with varied clinical presentations and parasitic forms. The disease is roughly classified into three types: chromoblastomycosis, black-grain mycetoma, and phaeohyphomycosis. While there are many kinds of dematiaceous fungi, the major etiologic agent is Fonsecaea pedrosoi, which to date has accounted for 90% of chromoblastomycosis cases. The genus Fonsecaea has recently been assessed via rRNA ITS sequence analysis, and species have been classified into F. pedrosoi, F. monophora, and others. We encountered two cases of chromomycosis that had developed on facial and upper arm areas. Neither of the etiologic agents could be identified through morphological examination under a microscope; however, F. monophora was confirmed using molecular phylogenetic analysis. Indeed, molecular phylogenetic analysis has revealed that the etiologic agents in many reported cases of F. pedrosoi infections were actually F. monophora. This suggests that it is now necessary to reconsider the classification of genus Fonsecaea.

The paper presents a numerical movable-bed channel capable of simulating three-dimensional motions of flows and gravel particles in different shapes. At first, the numerical channel was tested against results of fixed-bed channel experiments in which gravel particles were transported. Simulated particle motions were validated in comparison with those in the laboratory experiment. Next, numerical movable-bed experiments with sphere particles and gravel particles were conducted. The results of these experiments clearly elucidated the difference in motion between the large and the small particles, effects of shapes of gravel particles on sediment-transport rates, and hydrodynamic forces and contact forces at incipient motion and at settling.

Tinea capitis is a fungal infection of the scalp. This disease is primarily caused by dermatophytes that invade the hair shaft. The clinical appearance is typically single or multiple lesions of hair loss that may be accompanied by inflammation, scaling, and pustules. The incidence in girls and females overall has recently increased, although many boys were previously affected. Trichophyton or Microsporum species of dermatophytes transmitted by humans or animals are commonly associated with this disease. The treatment requires an oral antifungal agent such as itraconazole or terbinafine.

We report a patient with primary lymphocutaneous Nocardia brasiliensis infection affecting the face and left arm. The mode of infection was via skin abrasions which occurred 2 weeks prior to the development of the skin lesions. Treatment with intravenous minocycline for 4 weeks resulted in a cure. We also review 12 previously reported Japanese cases of lymphocutaneous nocardiosis.

Bixbyite (Mn,Fe)2O3has a C-type rare-earth oxide structure with space group ofIa-3 and different from corundum structureR-3c. Single-crystal structure analyses and powder diffraction experiments were carried out using synchrotron radiation under high pressures up to 41.21 GPa. Lattice constants and bond distances were elucidated as a function of pressure. Single crystal structure analyses under high pressures up to 9.64 GPa have been executed using DAC. There are two octahedral Mn3+sites: M1 (-3) and M2 (-2.). M1O6and M2O6octahedral volumes and void space of vacant sites show different compression curves. M1O6octahedron is less compressive than M2O6octahedron. The former is a little deformed from an ideal octahedron withm-3mof MnO6but the latter is a largely distorted octahedron. The quadratic elongation is applied in order to comprehend the polyhedral distortion and finite homogeneous strain. Both octahedra do not show a noticeable Jahn-Teller distortion induced from Mn3+. Six bond lengths of M1O6are equivalent but the octahedron more elongates along the direction of -3 axis with increasing pressure and is more deformed from the regular octahedron. The M2O6octahedron has two long bond distances among six bonds, which are most compressive. The octahedral deformations seem to reduce the Jahn-Teller effect due to the compression. The bulk modulus:Ko= 169.1(4.9) GPa andKo′ = 7.35(0.99), was observed from the volume change with pressure.Pressure-induced phase transition was confirmed at about 21 GPa with a large hysteresis. The transition is reversible and non-quenchable. Powder indexing of the high-pressure phase was carried out using diffraction pattern taken at 35.06 GPa. It has a monoclinic symmetry and is not a corundum, Rh2O3(II) or perovskite structure.

At the present it has been clarified that soil masses covered with reeds that had fallen from the banks are not easily transported and still protect banks by reducing the flow velocity surrounding them. Therefore, this study aims to develop riparian protection measures against bank erosion using soil masses covered with reeds by placing them along river bank at an streamwise intervals. Two experiments on erosion have been done by using undisturbed soil masses covered with reeds that were obtained from the field. One is made by observing the erosion of soil masses one by one in a laboratory experiment. The other is made in at a channel for agricultural use of Hii river to observe an erosion of soil masses for longer period by placing some soil blocks longitudinally along the river bank. The reeds' density resisting the erosion of soil mass is found from the experiments. Moreover, it is proved that soil masses covered with reeds can be available for riparian protection for a long period.

We assayed the fungicidal effects of antifungal agents using neutral red staining. Fungal elements of Trichophyton mentagrophytes and T. rubrum were treated with various concentrations of antifungal agents in 96-well filtration plates and then stained with neutral red. The amount of neutral red incorporated by the surviving viable cells was determined from the automated spectrophotometric readings at 550 nm. The minimum fungicidal concentrations (MFCs) of antifungal agents determined by this assay correlated well with those determined by conventional assay. This newly developed procedure should provide a rapid, reproducible, quantitative, qualitative and semi-automated susceptibility test for determination of the MFCs of the fungicidal agents.

薬剤希釈系列溶液(0.12μg～2mg/mlの2倍希釈系列)を加え,培養した真菌浮遊液にneutral red(NR)を添加,生菌に取り込まれたNR量を測定することによりその薬剤の効果を評価する新しい薬剤感受性試験法を開発した.Trichophyton mentagrophytesの発芽小分生子浮遊液に各種抗真菌剤希釈系列溶液を1/100量加え,28℃で培養,24時間毎にNRを添加し,28℃に1時間静置後,遠心し,上清を除去.残った沈殿物を4%ホルマリン-1%塩化カルシウム水溶液で固定,洗浄した後,0.1M酢酸-50%エタノールを加え菌構造を破壊.遠心して回収した上清より,生菌に取り込まれたNR量を吸光度(A540)で測定し,各種薬剤の殺菌効果を評価した.その結果,全ての薬剤において,すでに従来報告されている最小発育阻止濃度と比較し,妥当な最小殺菌濃度が得られた.本法は従来法と比較して最小殺菌濃度を容易に迅速に測定でき,且つ薬剤の抗真菌力の定量的評価が可能であるという点で有用な方法であると考えられた.

In vitroにおいて抗真菌剤 (NND-318) に暴露されたTrichophyton mentagrophytesのviabilityの経時的変化をneutral red染色と培養を用いて比較検討した結果, neutral red染色陽性の菌要素の割合と培養によって算定された生菌数の割合がほぼ一致して変動し, 減少するのが認められた. このことからin vitroにおいても, T. mentagrophytesの菌要素のviabilityの評価にneutral red染色が有用であることが示されたとともに, 白癬菌が抗真菌剤に暴露された場合には, 菌は死滅しても菌要素は死菌のまま残っている可能性が強いことが判明した, 従って, 臨床的に直接鏡検で鱗屑中に菌要素が認められても, 抗真菌剤により治療中であれば, その菌要素はすでに死菌となっていることも十分考えられ, 抗真菌剤の効果判定においては, 鱗屑中の菌要素の有無より, むしろこの菌要素のviabilityを評価することが重要と思われた.

The ultrastructure of Trichophyton mentagrophytes cells stained with neutral red was investigated using electron microscopy and X-ray microanalysis. Fixatives containing molybdenum and chromium were used to prevent the outflow of neutral red. Electron-dense particles composed of metals and dye were observed exclusively in the vacuoles, which were increased in number and size, but not near the cell wall. Results indicate that neutral red passes directly through the fungal cell wall and is incorporated into the vacuoles.

Antifungal agents and therapeutic approaches for tinea unguium have been increasing in number. Itraconazole, terbinafine and fluconazole were developed in the 1990s, and many useful methods with them for tinea unguium have been reported, including pulse therapy and short duration therapy. There have been many reports of not only oral treatments but also contrived topical treatments, in most of which improvement rates were high. However, each treatment has had some drawbacks and did not seem to gain the complete compliance of patients. Many patients dropped out, still having affected nails. It seems important to us to understand thoroughly the merits and demerits of each diversified treatment for tinea unguium and to provide the preferential treatment for each patient.

The possibility of one-week application of terbinafine cream for tinea pedis was studied in a double-blind test at four institutes, comparing four-week application as a control. Of a total of forty-three patients studied, nineteen were randomized into a four-week application group, Group I, and twenty into a one-week application group, Group II. Group I was evaluated as moderate to extremely useful in twelve (63.2%) of the nineteen patients and Group II in twelve (60.0%) of the twenty patients. No statistical differences were observed between two groups. These findings appeared to indicate that the short term, one-week application of terbinafine cream had results equivalent to the four-week application. This short-term treatment which aids in improving patient compliance and reducing the total amount of drug applied, thus lowering drug cost, is viewed as a useful way of treating tinea pedis.

In the Asahi River, riffles and pools had been scaled down in the downstream reach of Asahi Dam due to sediment deposition in Asahi Dam reservoir. To improve this environmental problem, a flushing sediment tunnel was constructed so as to bypass Asahi Dam reservoir. In this study, first, the authors demonstrated the recovery of riffles and pools and the grain size distribution in the downstream reach by using the data of cross-sectional surveying, air photographs and field investigation. Next, authors’ two-dimensional model was applied to a series of flood events in the Asahi River. As a result, the flushing mechanism of Asahi Dam reservoir sedimentation, the recovery process of riffles and pools and the change in grain size distribution in the downstream reach were clarified by the model.

Pseudoxanthoma elasticum (PXE) is a rare, inherited disorder of the connective tissue. Possible association of autoimmune thyroiditis and PXE has been suggested, but reports of other autoimmune diseases complicating PXE are rare. We report a case of rheumatoid arthritis (RA) in a patient with PXE. Since the frequency of PXE is likely to be underdiagnosed, further studies to elucidate the true incidence and significance of the association of RA and PXE will be needed.(Internal Medicine 32: 508-509, 1993)