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Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous diseases. Autoantibodies against hemidesmosomal adhesion proteins might be involved in the developing process. BP usually affects the elderly with high mortality whereas the drug-induced BP is often improved and rarely relapses after the withdrawal of the suspected drug. An accumulated evidence suggests that dipeptidyl peptidase-4 inhibitor (DPP-4I), which has been widely used as the antidiabetic drug improves glycemic control with little risk for hypoglycemia, could be an inducer of DPP-4I-associated BP (DPP-4I-BP). While the precise mechanism remains unclear, a unique immunological profile with human leukocyte antigen (HLA)-DQB1*03:01 could be a biomarker of genetic susceptibility to DPP-4I-BP. Here, we encountered an interesting case of DPP-4I-BP with HLA-DQB1*03:01, which was likely triggered by scabies. A 56-year-old Japanese male with type 2 diabetes on hemodialysis was referred to our hospital due to worsened blisters. Prior to his admission, he had been on linagliptin, a DPP-4I, for 5 months. He then suffered from scabies 2 weeks before his admission while the treatment with ivermectin failed to improve his symptom. Based on his clinical symptom, positive for anti-BP180 autoantibody in serum, and the pathological alterations of skin biopsy specimens, he was diagnosed with DPP-4I-BP. Importantly, he also carried an HLA-DQB1*03:01 allele. Oral prednisolone was subsequently administered after the discontinuation of linagliptin, and his symptom gradually disappeared. Given the fact that the DPP-4I-BP could be a life-threating disease, we should be cautious of prescribing DPP-4I in hemodialysis patients, whose immune system could be impaired.

Quandles can be regarded as generalizations of symmetric spaces. In the study of symmetric spaces, the notion of flatness plays an important role. In this paper, we define the notion of flat quandles, by referring to the theory of Riemannian symmetric spaces, and classify flat connected finite quandles., Comment: 15 pages

We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography–computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG-PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG-PET/CT, and we measured their serum hTERT mRNA levels using real-time RT-PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG-PET/CT were demonstrated to be correlated with the clinical parameters of metastasis and recurrence (P

Background We have previously shown that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a dedifferentiation by a demethylation mechanism. Methods We tested the effect of miR-520d-5p on human fibroblasts to determine whether it could be safely used in normal cells for future clinical therapeutic applications. After we transfected the microRNA into fibroblasts, we analyzed the phenotypic changes, gene expression levels, and stemness induction in vitro, and we evaluated tumor formation in an in vivo xenograft model. Results The transfected fibroblasts turned into CD105+ cell populations, survived approximately 24 weeks, and exhibited increases in both the collagen-producing ability and in differentiation. Combinatorial transfection of small interfering RNAs for miR-520d-5p target genes (ELAVL2, GATAD2B, and TEAD1) produced similar results to miR-520d-5p transfection. These molecules converted normal cells into MSCs and not iPSCs. Conclusions In vitro data indicate the potent usefulness of this small molecule as a therapeutic biomaterial in normal cells and cancer cells because CD105+ cells never converted to iPSCs despite repeated transfections and all types of transfectants lost their tumorigenicity. This maintenance of a benign state following miR-520d-5p transfection appears to be caused by p53 upregulation. We conclude that miR-520d-5p may be a useful biomaterial at an in vitro level. Electronic supplementary material The online version of this article (doi:10.1007/s40268-014-0064-6) contains supplementary material, which is available to authorized users.

In order to elucidate the effects of nanomechanical stimulation on the regulation of cellular functions, we have been developing a cell culture microdevice integrated with piezoelectric thin film actuators. In this paper, we propose a new geometric configuration of the device to allow cell culture on a relatively flat surface and in an open space. An improved fabrication process for PZT actuators overcame a serious problem that sometimes occurred in the previous process; photoresist patterned on PZT film cannot be completely removed due to its degradation in a dry etching process. Then we demonstrate the driving performance of a fabricated prototype microdevice. Moreover, individual cells can be arranged precisely at the desired positions of the PZT actuators by a positive dielectrophoretic force at frequencies above 100 kHz with an application of an AC voltage of 20 Vpp. The trapping rate was dramatically improved up to 90% by using microchannel to efficiently supply cells onto the surface of the PZT act...

We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epithelial–mesenchymal transition and stemness-mediated processes in normal cells and cancer cells, respectively. On the basis of the synergistic effect of p53 upregulation and demethylation induced by 520d-5p, the current study investigated the effect of this miRNA on apoptotic induction by ultraviolet B (UVB) light in normal human dermal fibroblast (NHDF) cells. 520d-5p was lentivirally transfected into NHDF cells either before or after a lethal dose of UVB irradiation (302 nm) to assess its preventive or therapeutic effects, respectively. The methylation level, gene expression, production of type I collagen and cell cycle distribution were estimated in UV-irradiated cells. NHDF cells transfected with 520d-5p prior to UVB irradiation had apoptotic characteristics, and the transfection exerted no preventive effects. However, transfection with 520d-5p into NHDF cells after UVB exposure resulted in the induction of reprogramming in damaged fibroblasts, the survival of CD105-positive cells, an extended cell lifespan and prevention of cellular damage or malfunction; these outcomes were similar to the effects observed in 520d-5p-transfected NHDF cells (520d/NHDF). The gene expression of c-Abl (Abelson murine leukemia viral oncogene homolog 1), ATR (ataxia telangiectasia and Rad3-related protein), and BRCA1 (breast cancer susceptibility gene I) in transfectants was transcriptionally upregulated in order. These mechanistic findings indicate that ATR-dependent DNA damage repair was activated under this stressor. In conclusion, 520d-5p exerted a therapeutic effect on cells damaged by UVB and restored them to a normal senescent state following functional restoration via survival of CD105-positive cells through c-Abl-ATR-BRCA1 pathway activation, p53 upregulation, and demethylation. As hsa-miR-520d-5p has an innovating effect of reversion of undifferentiated cancer cells to benign or normal status via a stemness-mediated process, we attempted to examine its reprogramming effect on differentiated normal cells (dermal fibroblasts). We found that miR-520d-5p has a restoration effect on fibroblasts exposed to lethal ultraviolet B irradiation and that it induced these cells to the mesenchymal status with CD105 expression. The therapeutic effect indicates that miR-520d-5p is deeply involved in DNA repair (non-canonical pathway against nuclear stress), and it may function as the main regulator in the response mechanism to fragmented DNA and severely damaged nucleic acids. Therefore, this study may pave the way to elucidating a new mechanism because miRNA may play a role in the biogenesis of cells that are getting lethal due to cell damage or aging.

The effects produced in vitro by minocycline (MINO), aminobenzyl penicillin (ABPC) and cefotiam (CTM) on polymorphonuclear leukocytes (PMN) chemotaxis were investigated in this study using the Boyden chamber technique and polarization assay. The following results were obtained: CTM brought about a significant increase of PMN chemotaxis at the therapeutic dose (10, 100 micrograms/ml), MINO reduced PMN chemotaxis significantly at a concentration as low as 1 microgram/ml and ABPC did not influence PMN chemotaxis at concentrations up to 100 micrograms/ml in both methods. Furthermore, using a checkerboard assay, it was shown that CTM worked as a chemokinetic factor.

Herpes Zoster is the viral disease of skin and mucosa characterized by grouped vesicular eruptions along a peripheral nerve, and it is thought that cell-mediated immunoactivity is involved. A case of Herpes Zoster in the right region along the second trigeminal nerve branch of a 58-year-old male was reported. The relation between clinical behavior and serum immunological examination was studied. The results were as follows:1. A possible decrease of cell-mediated immunoactivity in the serum examination at the initial stage of the disease.2. The comlement fixation test (CF test) is dependable as a differential diagnostic procedure for Herpes Zoster.3. Close relations between complement system, antibody titer and clinical behaviors.

Typical Sturge-Weber syndrome of a 27 year-old female was reported. She had vascular nevus on the right side of her face, right maxillary hemangioma, epilepsy, intercranial calcification, paralysis on the left side of her extremitie 1 and glaucoma.Hemangioma on the right maxilla associated with this syndrome was treated successfully with carbon dioxide laser. The tumor was cut by focused beam and small blee ding vessels were sealed off by defocused beam. Bleeding was minimal. Postoperative healing was excellent, but left maxillary central incisor was damaged by carbon dioxide beam.We considered that vascular-rich lesions were effectively extirpated with carbon dioxidelaser. But the manipulation of the apparatus was a little difficult in molar region cases, therefore, without careful operation, surrounding tissue might be damaged.