A possible case of maculopapular eruption associated with glecaprevir/pibrentasvir treatment for chronic hepatitis C virus infection

Tomiyasu et al. report a possible case of maculopapular eruption associated with G/P treatment. Based upon the clinical course and histological analysis, the present case may be mediated by allergic mechanism. Since G/P treatment is widely used because of its efficacy and safety, clinical dermatologists should be aware that G/P may cause cutaneous drug eruption mediated by allergic responses

An Examination of the Processes of Clearing a Space in Difficult Sessions

ジェンドリン（1982）が示すフォーカシング簡便法のステップのうち、最初に位置付けられているClearing A Space（以下CAS）はそれ自体で用いても臨床的に有効であることは既に指摘されている。本研究は上村・山見・冨宅ら（2012）の研究の一部として筆者らが行ったCASセッションにおいて難行したと考えた事例を検討・考察し、どのようなプロセスが生じていたかを特定したものである。その結果、難行したと考えられたセッションには4つのパターンがみられ、それらは次のようなものである。①クライエント自身がフェルトセンス（以下FS）に対して否定的なパターン②クライエントとセラピストの共同作業的な関係が成立しないパターン③FS がはっきり感じられないパターン④展開のプロセスが語られないパターン。これらの4つの難行パターンについて、主としてGendlinの心理療法論文より対応を検討した結果、セラピストが自分自身の反応や気持ちに注意を向け、それがどのように相互作用に関連しているかを捉えることが重要であると考察された。Clearing a space (CAS) is often introduced as the first step of the Focusing Short Form developed by Gendlin (1982). However, many therapists have found that CAS itself is effective as a method of therapy. This study was carried out in conjunction with the study by Uemura et al. (2012), and examines the CAS sessions that were considered to be difficult by the listeners to examine the manner of process in these sessions. As a result, the authors extracted 4 patterns from the difficult sessions: (1) clients were unfavorable towards their own felt senses; (2) positive therapeutic relationships could not be established; (3) clients were unable to feel their felt senses clearly; and (4) the client\u27s experiential processes during sessions were not shared to the therapist. Based on Gendlin\u27s psychotherapy theories, the authors discussed how to deal with these difficult processes, and concluded that these difficult processes could have been facilitated by the therapists\u27 attention to their own responses and felt senses towards their clients and to understand how these are affecting the therapeutic relationship

A Phenotypic Analysis of Involucrin-Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8⁺ T Cells

To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 and keratin 14, were employed in combination with adoptive transfer of CD8⁺ T cells from OT-I mice (OT-I T cells) that recognize an ovalbumin-derived peptide. However, these strains showed bodyweight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. In this study, we generated a mouse strain expressing mOVA under the control of human involucrin promoter (involucrin-mOVA mice). In contrast to previous strains, involucrin-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant bodyweight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite the remaining OT-I T cells in the skin. Our involucrin-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity

The Reduction of State Anxiety by Clearing a Space : An Empirical Study with Graduate School Students

Clearing A Space（以下CAS）はフォーカシング簡便法の最初のステップとして位置づけられており、フォーカシングをするための準備段階として考えられてきた。しかし、フォーカシング研究が展開するにつれてCASを単独で取り扱った研究や事例報告が数多くなされ、CASの有効性が示されてきた。しかしそれらの研究はほとんどが事例研究であり、実証研究は、集団法によるCASを除くとほとんどみられないのが現状である。そこで本研究では、フォーカサーとリスナーのペアによるCASの効果を質問紙によって検討することを目的とした。CAS前後の新版STAI得点の比較では、状態不安得点の有意な低下が認められ（ W+=–2.936, p<.01, N=11）（（t 10）=7.142, P<.01, N=11）、CASの抗状態不安効果が確認された。また、CASの効果にはどのような要素が関連しているのかを検討するために、STAI以外にFMSとYG性格検査や、セッションの逐語記録などの録音データを用いて探索的な研究を行った。これらの結果、CASセッション全体にかかる時間が多い群が、少ない群よりも有意に状態不安が低減していることが分かり、問題や気がかりと距離を取り終えた後のからだの感覚をじっくり味わう時間をとることが状態不安の低減に役立つと考えられた。Clearing A Space (CAS), the first step of Focusing Short Form, was originally developed as a preparation for Focusing. A number of research studies and case studies have demonstrated the effectiveness of CAS, but empirical studies on CAS are limited. This study was aimed at measuring the effects of CAS by statistical comparison of responses to psychological questionnaires. It was found that state anxiety as measured by STAI decreased significantly (W+=-2.936, p<.01,N=11), (t(10)=7.142, P<.01, N=11) following CAS sessions, demonstrating that CAS reduces state anxiety. In addition to STAI, FMS, Yatabe-Guilford Personality Inventory, and verbatim records of sessions were used to explore what factors may be related to the effects of CAS. It was found that state anxiety in a group of subjects who took more time for CAS showed more reduction in state anxiety when compared to a group of subjects who took less time. It was thought that savoring and staying with the cleared space after CAS may enhance the reduction of state anxiety

Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus

Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus.BackgroundThe detailed mechanisms of glucocorticoid action in idiopathic nephrotic syndrome and progressive glomerulonephritides have not been clearly elucidated. The pharmacological actions of glucocorticoids are mediated by their binding to an intracellular protein, the glucocorticoid receptor (GR). The determination of GR localization in normal glomerular cells is essential to elucidate the mechanisms of glucocorticoid action in various glomerular diseases.MethodsWe carried out an immunoblot examination using antihuman GR-specific antibody and homogenates of isolated normal human glomeruli and mesangial cells in culture. Immunohistochemical examinations were also performed on normal human kidney specimens at light and electron microscopic levels. The nuclear translocation of GRs elicited by ligand binding was further investigated by confocal laser-scanning microscopic inspection of freshly isolated glomeruli and mesangial cells cultured with dexamethasone.ResultsAn immunoblot examination demonstrated the presence of a 94 kDa protein, a molecular weight consistent with that of GRs, in the homogenates of glomeruli and cultured mesangial cells. By light microscopic examination, GRs were strongly detected in the nucleus and moderately in the cytoplasm of all glomerular cells, parietal and visceral epithelial cells, endothelial cells, and mesangial cells. By electron microscopic examination, the nuclear GRs of all glomerular cells were found to be diffusely distributed in the euchromatin. Additionally, the immunofluorescence intensities of nuclear GRs in isolated glomeruli and mesangial cells in culture became more intense by the addition of dexamethasone.ConclusionsOur findings suggest that all subsets of human glomerular cells definitely express the GR protein, which potentially undergoes translocation by glucocorticoids

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

肉芽腫形成に特異的な代謝経路の発見 --ペントースリン酸回路の制御による新規治療--. 京都大学プレスリリース. 2023-12-01.More than skin-deep: Kyoto researchers discover metabolic pathway specific to granuloma formation in patients. 京都大学プレスリリース. 2023-12-07.Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2–positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1, 6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity

The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit W/Wv mouse model, since Kit W/Wv mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas-TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca2+ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF-α dependent manners Furthermore, stimulated BMDCs increased intracellular Ca2+ of MC upon direct interaction and up-regulated membrane-bound TNF-α on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS

Plasma Cathepsin S and Cathepsin S/Cystatin C Ratios Are Potential Biomarkers for COPD

Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD. Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses. Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001). Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD