Maki Hata

Induction of Therapeutically Relevant Cytotoxic T Lymphocytes in Humans by Percutaneous Peptide Immunization

Percutaneous peptide immunization (PPI) is a simple and noninvasive immunization approach to induce potent CTL responses by peptide delivery via skin with the stratum corneum removed. After such a barrier disruption in human skin, epidermal Langerhans cells, although functionally matured through the up-regulation of HLA expression and costimulatory molecules, were found to emigrate with a reduced number of dendrites. CD8(+) populations binding to MHC-peptide tetramers/pentamers and producing IFN-gamma appeared in the blood after PPI with HLA class I-restricted antigenic peptides. PPI with melanoma-associated peptides reduced the lesion size and suppressed further development of tumors in four of seven patients with advanced melanoma. These beneficial effects were accompanied by the generation of circulating CTLs with in vitro cytolytic activity and extensive infiltration of tetramer/pentamer-binding cells into regressing lesions. PPI elicited neither local nor systemic toxicity or autoimmunity, except for vitiligo, in patients with melanoma. Therefore, PPI represents a novel therapeutic intervention for cancer in the clinical setting.

Three-dimensional electromagnetic imaging of upwelling fluids in the Kyushu subduction zone, Japan

A three-dimensional (3-D) lithospheric-scale electrical resistivity model, developed using network-magnetotelluric (network-MT) data, contains structures associated with arc magmatism beneath Kyushu Island in the Southwest Japan arc. Kyushu Island, where the Philippine Sea Plate (PSP) subducts beneath the Eurasian plate, can be divided into northern and southern volcanic regions separated by a nonvolcanic region. Many active Quaternary volcanoes occur along the volcanic front (VF) associated with the PSP in the two volcanic regions. Our 3-D electrical resistivity model shows three different shapes of upwelling fluid-like conductive anomalies, indicative of either slab-derived aqueous fluid and/or partial melt beneath the volcanic and nonvolcanic regions. A conductive anomaly in the northern volcanic region, located at some distance from the subducting PSP, extends from the surface to depths of 70 km depth, extends from the surface to depths of >100 km. In the nonvolcanic region, the upper region of a relatively conductive anomaly extends upward to a depth of ~50 km along the subducting plate. The degrees of magmatism and the relative contribution of slab-derived fluids to the magmatism vary spatially in the one nonvolcanic and two volcanic regions.

Efficacy and safety of preprandial versus postprandial administration of low-dose cyclosporin microemulsion (Neoral) in patients with psoriasis vulgaris

A study of therapeutic drug monitoring indicated that cyclosporin administered before meals produces higher blood concentrations than an equivalent dose administered after meals. Our objective was to compare the efficacy of cyclosporin administered before and after meals, respectively, in psoriasis vulgaris patients. We performed an open trial study. Patients were randomly assigned to receive cyclosporin before (group B, n = 20) or after meals (group A, n = 17), and were followed up in 10 dermatology clinics. The difference between groups was evaluated in severity. The percent reduction in psoriasis area and severity index score from baseline was 29.8% in group A and 75.4% in group B (A vs B, P = 0.00005). Two patients in each group withdrew due to abnormality of laboratory data. Short‐term, low‐dose treatment with cyclosporin before rather than after meals is suggested as a new effective treatment regimen for psoriasis, with the added advantage of lowering costs.

Crustal magma pathway beneath Aso caldera inferred from three‐dimensional electrical resistivity structure

At Naka-dake cone, Aso caldera, Japan, volcanic activity is raised cyclically, an example of which was a phreatomagmatic eruption in September 2015. Using a three-dimensional model of electrical resistivity, we identify a magma pathway from a series of northward dipping conductive anomalies in the upper crust beneath the caldera. Our resistivity model was created from magnetotelluric measurements conducted in November–December 2015; thus, it provides the latest information about magma reservoir geometry beneath the caldera. The center of the conductive anomalies shifts from the north of Naka-dake at depths >10 km toward Naka-dake, along with a decrease in anomaly depths. The melt fraction is estimated at 13–15% at ~2 km depth. Moreover, these anomalies are spatially correlated with the locations of earthquake clusters, which are distributed within resistive blocks on the conductive anomalies in the northwest of Naka-dake but distributed at the resistive sides of resistivity boundaries in the northeast.

3‐D electrical resistivity structure based on geomagnetic transfer functions exploring the features of arc magmatism beneath Kyushu, Southwest Japan Arc

Our 3-D electrical resistivity model clearly detects particular subsurface features for magmatism associated with subduction of the Philippine Sea Plate (PSP) in three regions: a southern and a northern volcanic region, and a non-volcanic region on the island of Kyushu. We apply 3-D inversion analyses for geomagnetic transfer function data of a short-period band, in combination with results of a previous 3-D model that was determined using Network-Magnetotelluric response function data of a longer-period band as an initial model in the present inversion to improve resolution at shallow depths; specifically, a two-stage inversion is used instead of a joint inversion. In contrast to the previous model, the presented model clearly reveals a conductive block on the back-arc side of Kirishima volcano at shallow depths of ~50 km; the block is associated with hydrothermal fluids and hydrothermal alteration zones related to the formation of epithermal gold deposits. A second feature revealed by the model is another conductive block regarded as upwelling fluids, extending from the upper surface of the PSP in the mantle under Kirishima volcano in the southern volcanic region. Third, a resistive crustal layer, which confines the conductive block in the mantle, is distributed beneath the non-volcanic region. Fourth, our model reveals a significant resistive block, which extends below the continental Moho at the fore-arc side of the volcanic front and extends into the non-volcanic region in central Kyushu.

Temperature and melt fraction distributions in a mantle wedge determined from the electrical conductivity structure: Application to one nonvolcanic and two volcanic regions in the Kyushu subduction zone, Japan

We propose a new method for estimating the temperatures and melt fractions of the upper mantle. Our method is based on connecting the electrical conductivity structure from geophysical observations with laboratory-determined relationships between the electrical conductivity and temperature of four nominally anhydrous minerals (olivine, orthopyroxene, clinopyroxene, and garnet) and basaltic melt. The temperatures are expressed as the upper limit temperatures using the Hashin-Shtrikman lower bound in solid phases and using the Hashin-Shtrikman upper bound in solid-liquid mixed phases. We apply the method to a nonvolcanic and two volcanic regions in the Kyushu subduction zone, southwest Japan. Our results suggest that the temperatures of the upper mantle are 1100–1450°C for dry mantle and 900–1350°C for wet mantle and that the melt fractions of the upper mantle are <20% beneath the two volcanic regions and <5% beneath the nonvolcanic region for both dry and wet mantle.

Psychological aspects of patients with intrinsic atopic dermatitis.

Atopic dermatitis (AD) is classified into the IgE-high extrinsic and IgE-normal intrinsic types. While extrinsic AD is the classical type with high prevalence, intrinsic AD occupies approximately 20% of total AD with female predominance [1]. The skin barrier is perturbed in the extrinsic, but not intrinsic type [1], and thus filaggrin gene mutations are not a feature of intrinsic AD [2]. While the two types have comparable frequencies of circulating Th2 cells, intrinsic AD shows a significantly increased [...]

Acquired hemophilia eclipsed by psoriatic arthralgia

1 Keshtgarpour M, Dudek AZ. SU-011248, a vascular endothelial growth factor-tyrosine kinase inhibitor, controls chronic psoriasis. Transl Res 2007; 149: 103–106. 2 Narayanan S, Callis-Duffin K, Batten J, Agarwal N. Improvement of psoriasis during sunitinib therapy for renal cell carcinoma. Am J Med Sci 2010; 339: 580–581. 3 Fournier C, Tisman G. Sorafenib-associated remission of psoriasis in hypernephroma: case report. Dermatol Online J 2010; 16: 17. 4 Canavese M, Altruda F, Ruzicka T, Schauber J. Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis-a possible target for novel therapies? J Dermatol Sci 2010; 58: 171–176. 5 Finke JH, Rini B, Ireland J et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 2008; 14: 6674–6682.