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A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non-metropolitan regional area.

Summary The Matsumoto Eosinophilic Shinshu (MES) rat is an inbred mutant strain that spontaneously develops systemic hypereosinophilia with eosinophilic inflammatory lesions similar to those associated with hypereosinophilic syndrome in humans and other mammals. To elucidate the pathogenic mechanisms that underlie these features of MES rats, we examined the pattern of cytokine gene expression in mesenteric lymph nodes (MLNs), the thymus, and peripheral blood mononuclear cells as well as the blood clinicopathology and MLN lymphocytic subsets of these animals. MES rats exhibited both leucocytosis, attributable in large part to hypereosinophilia and neutrophilia, and immunoglobulin M (IgM) and IgA gammaglobulinaemia, with increased titres of IgM autoantibodies to nuclear antigens. Reverse transcription and polymerase chain reaction analysis revealed that the amounts of interleukin (IL)-5, IL-4, eotaxin, and interferon-γ mRNAs were increased in the MLN lymphocytes of MES rats compared with the corresponding values for Sprague-Dawley rats. Intraperitoneal administration of a monoclonal antibody specific for IL-5 resulted in an immediate suppression of hypereosinophilia and a delayed suppression of neutrophilia in MES rats. Flow cytometry revealed an increased percentage of CD3+ CD4– CD8– T lymphocytes in MLNs of MES rats. Our results suggest that the hypereosinophilia of MES rats results from an increased production of IL-5, and that the eosinophilic inflammatory lesions of these animals, which are largely restricted to the gut, may be related both to cytokine overexpression in MLNs and to T helper 1 and 2 immunological responses.

WOS: 000401429400033, DEKOSIM; Turkish Ministry of Development

Fibrinogen Matsumoto II is a hereditary dysfibrinogenaemia identified in a woman with Basedow's disease and a bleeding tendency. Coagulation tests of the patient's plasma revealed a prolonged thrombin time and a decreased fibrinogen level determined by functional method. Release of fibrinopeptide A and B was normal, whereas fibrin monomer polymerization was delayed. Fibrinogen gamma-chain gene of the propositus was heterozygous for a missense mutation that resulted in Asn-->Lys substitution at codon 308. Though the same amino acid substitution was also attributed to fibrinogen Kyoto I and Bicetre II, fibrinogen Matsumoto II showed different clinical manifestations from them.

Background and Purpose: The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. Methods: A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing. Results: Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%–3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40–48 years and their disease course had been unremarkable apart from the early onset. Conclusions: Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population. publishedVersion

Melanoma has been a prototype for cancer immunology research, and the mechanisms of anti-tumor T cell responses have been extensively investigated in patients treated with various immunotherapies. Individual differences in cancer-immune status are defined mainly by cancer cell characteristics such as DNA mutations generating immunogenic neo-antigens, and oncogene activation causing immunosuppression, but also by patients' genetic backgrounds such as HLA types and genetic polymorphisms of immune related molecules, and environmental and lifestyle factors such as UV rays, smoking, gut microbiota, and concomitant medications; these factors have an influence on the efficacy of immunotherapy. Recent comparative studies on responders and non-responders in immune-checkpoint inhibitor therapy using various new technologies including multi-omics analyses on genomic DNA, mRNA, metabolites and microbiota, and single cell analyses of various immune cells have led to the advance of human tumor immunology and the development of new immunotherapy. Based on the new findings from these investigations, personalized cancer immunotherapies along with appropriate biomarkers and therapeutic targets are being developed for patients with melanoma. Here, we will discuss one of the essential subjects in tumor immunology: identification of immunogenic tumor antigens and their effective use in various immunotherapies including cancer vaccines and adoptive T cell therapy.

To meet cellular bioenergetic and biosynthetic demands, cancer cells remodel their metabolism to increase glycolytic flux, a phenomenon known as the Warburg effect and believed to contribute to cancer malignancy. Among glycolytic enzymes, phosphofructokinase-1 (PFK1) has been shown to act as a rate-limiting enzyme and to facilitate the Warburg effect in cancer cells. In this study, however, we found that decreased PFK1 activity did not affect cell survival or proliferation in cancer cells. This raised a question regarding the importance of PFK1 in malignancy. To gain insights into the role of PFK1 in cancer metabolism and the possibility of adopting it as a novel anti-cancer therapeutic target, we screened for genes that caused lethality when they were knocked down in the presence of tryptolinamide (TLAM), a PFK1 inhibitor. The screen revealed a synthetic chemical-genetic interaction between genes encoding subunits of ATP synthase (complex V) and TLAM. Indeed, after TLAM treatment, the sensitivity of HeLa cells to oligomycin A (OMA), an ATP synthase inhibitor, was 13,000 times higher than that of untreated cells. Furthermore, this sensitivity potentiation by TLAM treatment was recapitulated by genetic mutations of PFK1. By contrast, TLAM did not potentiate the sensitivity of normal fibroblast cell lines to OMA, possibly due to their reduced energy demands compared to cancer cells. We also showed that the PFK1-mediated glycolytic pathway can act as an energy reservoir. Selective potentiation of the efficacy of ATP synthase inhibitors by PFK1 inhibition may serve as a foundation for novel anti-cancer therapeutic strategies.