Development of a Training-Assist Robotic System Adapting to Individual Motor Abilities in Virtual Tennis Task

The present paper develops a training-assist robotic system that can adapt a reference hand motion for a virtual tennis task to individual motor abilities. The system first measures maximum hand force and velocity in reaching arm movements prior to the training, and designs a suitable reference trajectory for teaching motion smoothness and timing in the virtual tennis task based on the measured results. A quantitative index for evaluating task performance and motor functions are then defined with consideration of task dynamics. Finally, the effectiveness of the developed training system is validated through a set of preliminary training experiments with health subjects

Upshaw-Schulman症候群の糸球体障害には補体活性とADAMTS13欠損が関連している可能性がある

Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.博士（医学）・甲第792号・令和3年3月15日Copyright © 2018 Elsevier Ltd. All rights reserved

Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure

This is the peer-reviewed but unedited manuscript version of the following article: Nephron 2020;144(suppl 1):43–48 (DOI: 10.1159/000512330)]. The final, published version is available at http://www.karger.com/?doi=10.1159/000512330

Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report

Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies targeting at least red blood cells and platelets. HS and Evans' syndrome have different mechanisms of pathophysiology one another. We reported the quite rare case of an infant who had these diseases concurrently. Possible explanations of the unexpected complication are discussed

Influenza A (H3N2) infection followed by anti-signal recognition particle antibody-positive necrotizing myopathy: A case report

A 60-year-old Japanese woman presented with subacute progressive muscle pain and weakness in her proximal extremities. She was diagnosed with influenza A (H3N2) infection a week before the onset of muscle pain. At the time of admission, she exhibited weakness in the proximal muscles of the upper and lower limbs, elevated serum liver enzymes and creatinine kinase, and myoglobinuria. She did not manifest renal failure and cardiac abnormalities, indicating myocarditis.Electromyography revealed myogenic changes, and magnetic resonance imaging of the upper limb showed abnormal signal intensities in the muscles, suggestive of myopathy. Muscle biopsy of the biceps revealed numerous necrotic regeneration fibers and mild inflammatory cell infiltration, suggesting immune-mediated necrotizing myopathy (IMNM). Necrotized muscle cells were positive for human influenza A (H3N2). Autoantibody analysis showed the presence of antibodies against the signal recognition particle (SRP), and the patient was diagnosed with anti-SRP-associated IMNM. She was resistant to intravenous methylprednisolone pulse therapy but recovered after administration of oral systemic corticosteroids and immunoglobulins. We speculate that the influenza A (H3N2)infection might have triggered her IMNM. Thus, IMNM should be considered as a differential diagnosis in patients with proximal muscle weakness that persists after viral infections

MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons

Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here, we show that SPAST, which encodes a microtubule-severing protein called SPASTIN, was a novel target gene of miR-33 in human. Actually, the miR-33 binding site in the SPAST 3′-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of miR-33 on SPAST in mice. We demonstrated that inhibition of miR-33a, a major form of miR-33 in human neurons, via locked nucleic acid (LNA)-anti-miR ameliorated the pathological phenotype in hereditary spastic paraplegia (HSP)-SPG4 patient induced pluripotent stem cell (iPSC)-derived cortical neurons. Thus, miR-33a can be a potential therapeutic target for the treatment of HSP-SPG4

Assessment of Outcome of Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma by the Combination of RECIST and Tumor Markers

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC

Hepatitis C Virus Infection Suppresses the Interferon Response in the Liver of the Human Hepatocyte Chimeric Mouse

BACKGROUND AND AIMS: Recent studies indicate that hepatitis C virus (HCV) can modulate the expression of various genes including those involved in interferon signaling, and up-regulation of interferon-stimulated genes by HCV was reported to be strongly associated with treatment outcome. To expand our understanding of the molecular mechanism underlying treatment resistance, we analyzed the direct effects of interferon and/or HCV infection under immunodeficient conditions using cDNA microarray analysis of human hepatocyte chimeric mice. METHODS: Human serum containing HCV genotype 1b was injected into human hepatocyte chimeric mice. IFN-α was administered 8 weeks after inoculation, and 6 hours later human hepatocytes in the mouse livers were collected for microarray analysis. RESULTS: HCV infection induced a more than 3-fold change in the expression of 181 genes, especially genes related to Organismal Injury and Abnormalities, such as fibrosis or injury of the liver (P = 5.90E-16∼3.66E-03). IFN administration induced more than 3-fold up-regulation in the expression of 152 genes. Marked induction was observed in the anti-fibrotic chemokines such as CXCL9, suggesting that IFN treatment might lead not only to HCV eradication but also prevention and repair of liver fibrosis. HCV infection appeared to suppress interferon signaling via significant reduction in interferon-induced gene expression in several genes of the IFN signaling pathway, including Mx1, STAT1, and several members of the CXCL and IFI families (P = 6.0E-12). Genes associated with Antimicrobial Response and Inflammatory Response were also significantly repressed (P = 5.22×10(-10)∼1.95×10(-2)). CONCLUSIONS: These results provide molecular insights into possible mechanisms used by HCV to evade innate immune responses, as well as novel therapeutic targets and a potential new indication for interferon therapy