近赤外線スペクトロスコピィを用いた成人期注意欠如・多動症の前頭前野における血液動態反応の低下

AIM: Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. In pediatric attention-deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi-channel NIRS. Therefore, in this study, we used multi-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color-Word Task (SCWT) in adult ADHD patients and in age- and sex-matched control subjects.　METHODS: Twelve treatment-naïve adults with ADHD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. We used 24-channel NIRS to measure the oxygenated hemoglobin (oxy-Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy-Hb changes between adults with ADHD and control subjects by t-tests with Bonferroni correction.　RESULTS: During the SCWT, the oxy-Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy-Hb changes.　CONCLUSION: The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.博士（医学）・乙第1422号・平成30年11月30日© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and NeurologyThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12643], which has been published in final form at [https://doi.org/10.1111/pcn.12643]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Quantitative Evaluation of Pain during Electrocutaneous Stimulation using a Log-Linearized Peripheral Arterial Viscoelastic Model

In clinical practice, subjective pain evaluations, e.g., the visual analogue scale and the numeric rating scale, are generally employed, but these are limited in terms of their ability to detect inaccurate reports, and are unsuitable for use in anesthetized patients or those with dementia. We focused on the peripheral sympathetic nerve activity that responds to pain, and propose a method for evaluating pain sensation, including intensity, sharpness, and dullness, using the arterial stiffness index. In the experiment, electrocardiogram, blood pressure, and photoplethysmograms were obtained, and an arterial viscoelastic model was applied to estimate arterial stiffness. The relationships among the stiffness index, self-reported pain sensation, and electrocutaneous stimuli were examined and modelled. The relationship between the stiffness index and pain sensation could be modelled using a sigmoid function with high determination coefficients, where R2 ≥ 0.88, p < 0.01 for intensity, R2 ≥ 0.89, p < 0.01 for sharpness, and R2 ≥ 0.84, p < 0.01 for dullness when the stimuli could appropriately evoke dull pain.This work was supported by the Center of Innovation Program from Japan Science and Technology Agency.Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-21223-1

Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease

Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations

SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation.

Inflammatory bowel disease (IBD) is initiated and perpetuated by a dysregulated immune response to unknown environmental antigens such as luminal bacteria in genetically susceptible hosts. SR-PSOX/CXCL16, a scavenger receptor that binds phosphatidylserine and oxidised lipoprotein, has both phagocytic activity and chemotactic properties. The aim of this study was to investigate the role of SR-PSOX/CXCL16 in patients with IBD and experimental murine colitis

Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature

Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL

Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation

Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group). A further group of C57BL/6 mice received isografts (Iso group). The occlusion rate was significantly higher in the Allo group than in the Iso group (p = 0.0075), and also higher in the aPD-L1 group (p = 0.0066) and lower in the PD-L1 Fc group (p = 0.030) than in the Allo group. PD-L1 Fc recombinant protein treatment significantly decreased interleukin-6 and interferon-γ levels and reduced the CD4+/CD8+ T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4+ T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4+ T cells without exhaustion. The PD-L1-mediated immune checkpoint mechanism was associated with rejection in the murine tracheal transplant model, suggesting a potential novel target for immunotherapy in lung transplantation

近赤外線スペクトロスコピィを用いた覚醒剤精神病と統合失調症の鑑別

Despite some slight differences in symptomatology, differential diagnosis of methamphetamine-induced psychosis (MAP) versus schizophrenia can be challenging because both disorders present a large overlap in their clinical symptoms. However, a recent study has shown that near-infrared spectroscopy (NIRS) performed during a cognitive task can be a powerful tool to differentiate between these two disorders. Here, we evaluated verbal fluency task performance during NIRS in 15 patients diagnosed with MAP and 19 with schizophrenia matched for age and sex. We used prefrontal probes and a 24-channel NIRS machine to measure the relative concentrations of oxyhaemoglobin every 0.1 s during the task. For each patient, the neurocognitive function and clinical psychopathology were evaluated using the Positive and Negative Symptom Scale (PANSS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Oxyhaemoglobin changes in the prefrontal cortex were significantly higher in the MAP group compared to those in the schizophrenia group, particularly in the right dorsolateral prefrontal cortex. In contrast, we found no significant difference in PANSS and BACS scores. Our findings suggest that NIRS measurement could be applied to differentiate patients with MAP from those with schizophrenia, even in cases where clinical symptoms are similar.博士（医学）・甲第645号・平成28年3月15日This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

Factors in glucocorticoid regimens associated with treatment response and relapses of IgG4-related disease: a multicentre study

Glucocorticoids (GC) are effective for treating IgG4-related disease (IgG4-RD); however, relapse is often observed. We conducted a retrospective multicentre study to investigate risk factors in GC regimens associated with relapses of IgG4-RD. Data on 166 patients with definitive IgG4-RD diagnosis were collected from 12 institutions. Comprehensive surveillance of clinical backgrounds and GC regimens as well as multivariate analysis of factors associated with treatment responses and relapses was performed. To determine the initial maximal GC dose, the patients were stratified into three groups depending on the initial prednisolone (PSL) dosage: 0.7 mg/kg/day. The multivariate analysis extracted the disease duration and reduction speed of initial GC dose. Patients treated with initial GC 0.7 mg/kg/day of PSL showed higher relapse rates than those treated with 0.4–0.69 mg/kg/day. The relapse rates were significantly higher in patients with fast reduction of the initial dose (>0.4 mg/day) than in patients with slow reduction (<0.4 mg/day). To avoid relapse, 0.4–0.69 mg/kg/day of initial PSL with slow reduction speed (<0.4 mg/day) is needed in the early treatment of IgG4-RD