A novel keratin 5 mutation in an African family with epidermolysis bullosa simplex Iidicates the Importance of the amino acid located at the boundary site between the H1 and coil 1A domains

No abstractThis work was supported in part by Grant-in-Aid for Research Activity Start-up (to S. S.; 23890006) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by “Research on Measures for Intractable Diseases” Project: matching fund subsidy (H23-028) from the Ministry of Health, Labour and Welfare.http://www.medicaljournals.sehb201

Biostratigraphy, paleomagnetism and sedimentology of Late Cenozoic sediments in northwestern Hokkaido, Japan

Four Neogene sedimentary basins in northwestern Hokkaido (latitudes 44°-45° N.), the northernmost island of Japan, were studied to establish a combined microfossil-paleomagnetic sedimentologic stratigraphy. The measured section near Atsuta encompasses a shoaling depositional sequence from upper bathyal depths in the lower part to stagnant, nearshore conditions near the top of the sequence. Magnetostratigraphic evidence and age-diagnostic diatoms indicate the section to be Late Miocene age covering the interval from early Epoch 5 through Epoch 6, and possibly to late Epoch 7. The second measured section located north of Shosanbetsu exposes sediments derived from a volcano-clastic source and deposited on a continental slope with oversteepened slopes. Rich diatom floras from the sequence are assignable to the Denticula seminae var. fossilis-D. kamtschatica and D. kamtschatica Zones. A magnetic signature containing one reversal was observed in the upper part of the section, although the data seem to indicate the lower section to be dominantly normally magnetized. In the northwest Pacific deep-sea sequences, the zonal boundary of these two diatom zones lies between the Nunivak ( = "b") and "c" Events of the Gilbert Epoch, thus the distinct magnetic reversal observed in the upper part of the sequence is correlated with the top of the Nunivak Event. Neogene strata developed near Wakkanai City, the northwestern tip of Hokkaido, appear to have been deposited during a time interval of predominantly reversed geomagnetic polarity. Diatom floras suggest a correlation of these strata with the Denticula kamtschatica Zone which in turn corresponds, in the northwest Pacific deep-sea sequences, to the lower Gilbert Series below a horizon midway between the Nunivak and "c" Events. Diatom rich sediments of the Shimo-Ebekorobetsu area belong to the Yuchi Formation and comprise two assemblages assignable to the D. kamtschatica Zone and the superjacent Denticula seminae var.fossilis-D. kamtschatica Zone. From northern Honshu through Hokkaido to Sakhalin, in the western Pacific coastal region, beds containing the large pecten Fortipecten takahashii (YOKOYAMA) constitute a marker horizon useful for inter-regional correlation. In its southern range of distribution, F. takahashii is a diagnostic species in the lower part of the Tatsunokuchi Formation from which diatom floras assignable to the D. seminae var. fossilis-D. kamtschatica Zone are described. The F. takahashii bed occurs in the Shosanbetsu section, lying within the same diatom zone as the Tastunokuchi Formation and is in a reversely magnetized interval above the Nunivak Event (3.9 m.y. B.P.). The Neogene marine sediments of northwestern Hokkaido were deposited in the back-arc basin and reveal evidence of active arc magmatism at the time of deposition. In this tectonically active back-arc region, sediment-collecting basins shifted from area to area, accumulating sediments only for a relatively short period of time when spurts of active subsidence occurred in a given sedimentary basin

Investigation on the Floor Heating System with Thick Hot Water Panels

departmental bulletin pape

Meeting Report of the Pathogenesis of Pemphigus and Pemphigoid Meeting in Munich, September 2016

Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lubeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases. Considerable advances have been made in describing incidences and prevalences of these diseases and linking comorbidities with autoantibody reactivities and clinical variants, for example, dipeptidyl peptidase-IV inhibitor-associated noninflammatory bullous pemphigoid. Although new entities are still being described, diagnosis of most autoimmune blistering diseases can now be achieved using standardized and widely available serological test systems. Various experimental mouse models of pemphigus and pemphigoid disease are increasingly being used to understand mechanisms of central and peripheral tolerance and to evaluate more specific treatment approaches for these disorders, such as molecules that target autoreactive T and B cells and anti-inflammatory mediators, that is, dimethyl fumarate, phosphodiesterase 4, and leukotriene B4 inhibitors in pemphigoid disorders, and chimeric antigen receptor T cells in pemphigus. Very recent experimental data about the immunopathology and the determinants of autoantibody formation and keratinocyte susceptibility in pemphigus were discussed. With regard to cellular mechanisms leading to the loss of cell-cell adhesion, new ideas were shared in the field of signal transduction. Major steps were taken to put the various partly contradictory and controversial findings about the effects of pemphigus autoantibodies and other inflammatory mediators into perspective and broaden our view of the complex pathophysiology of this disease. Finally, two investigator-initiated multicenter trials highlighted doxycycline and dapsone as valuable medications in the treatment of bullous pemphigoid.Non peer reviewe

Direct Immunofluorescence Using Non-Lesional Buccal Mucosa in Mucous Membrane Pemphigoid

Mucous membrane pemphigoid (MMP) is a rare organ-specific autoimmune subepithelial blistering disease with predominantly mucosal erosions, most frequently affecting the gingiva. Erosions in the oral cavity usually result in markedly decreased quality of life. The major autoantigens are BP180 and laminin332, which are components of basement membrane proteins in the skin and mucosa. Diagnosis is usually difficult due to histological destruction of the tissue and low autoantibody titers. In this study, we evaluated the diagnostic value of direct immunofluorescence (DIF) using non-lesional buccal mucosa in seven cases of MMP. In all seven patients, gingival lesions were clinically observed, and in one of the seven patients, buccal lesions were also clinically observed. First, we performed DIF to detect tissue-bound autoantibodies and complement. DIF from non-lesional buccal mucosa revealed linear deposits of IgG and C3 at the basement membrane zone in all cases. To detect autoantibodies, indirect immunofluorescence (IIF), BP180-NC16A ELISA and immunoblotting were performed. Surprisingly, circulating autoantibodies were unable to be detected in any of the cases by ELISA, IIF, or immunoblotting. Furthermore, histological separation was observed in one patient. In conclusion, DIF using non-lesional buccal mucosa was found to be superior to histological and serological tests for diagnosing mucous membrane pemphigoid. The procedure is technically easy and has high diagnostic value

Solitonic Windkessel Model for Intracranial Aneurysm

The Windkessel model, which is known as a successful model for explaining the hemodynamic circulation, is a mathematical model with a direct correspondence with the electric circuit. We propose a theoretical model for the intracranial aneurysm based on the Windkessel-type steady blood flow. Intracranial aneurysms are well known vascular lesions, which cause subarachnoid hemorrhages. Since an aneurysm is an end-sack formed on the blood vessel, it functions as an unusual blood path that has characteristic features such as a reservoir and bottle neck orifice. We simulate an aneurysm by an electric circuit consisting of three different impedances, resistance, capacitance and inductance. A dumbbell-shaped aneurysm is the most dangerous aneurysm to easily rupture. Our aneurysmal model is created as a two-story aneurysm model for this point, thus namely the five-element Windkessel. Then, the mathematical formula was solved in numerical simulations by changing the size of the aneurysm and the elasticity of the aneurysm wall. An analysis of this model provided that the presence of the daughter aneurysm and the thinning of the aneurysm wall are positively correlated with a sharp increase in blood pressure in the aneurysm dome. Our mathematic aneurysm model proposes a good analogue to the real aneurysm and proved that this model includes soliton that is a non-decreasing wave propagation