Autonomic nervous system network and liver regeneration

To date, various signal transducers, cytokines, growth factors, and hormones have been reported to play an important role in homeostasis of various organs. Various cells and organs are involved in the hepatic regeneration process, which proceeds as a result of the coordination of many factors. While these factors are well known to be involved in the liver regeneration after the liver injury, however, as the details of such mechanisms have not been sufficiently elucidated, the practical applicability of hepatic regeneration based on the action of these and cytokines growth factors is still unclear. In terms of the involvement of the autonomic nervous system in hepatic regeneration, cell proliferation resulting from direct signal transduction to the liver has also been reported and recent studies focusing on the inter-organ communication via neural network opened a novel aspect of this field for therapeutic applicability. Therefore, the appropriate understanding of the relationship between autonomic neural network and liver regeneration through various organs including brain, afferent nerve, efferent nerve, etc. is essential. This mini-review explains the principle of neural system involved in the inter-organ communication and its contribution on the liver regeneration upon the liver injury reviewing recent progress in this field.     

The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.     

Balloon-hooking technique for stabilizing a guiding catheter in tortuous supra-aortic vessel: A case report

Objective: When performing endovascular interventions for supra-aortic vessels, the tortuous vascular anatomy observed in patients with atherosclerotic lesions often limits the ability to maintain a stable guiding catheter position. Here, we report a case of right vertebral artery (VA) stenosis treated with transfemoral stenting and discuss the utility of balloon-hooking technique using partially inflated balloon for stabilizing the balloon guiding catheter (BCG) in the supra-aortic vessel. Case presentation: A 74-year-old man who underwent right carotid artery stenting, coronary artery bypass grafting, and bilateral iliac artery stenting was admitted to our emergency department because of dizziness related to head movement. Computed tomography angiography revealed right VA origin stenosis and left subclavian artery (SA) occlusion. The patient underwent stenting of the right VA. After several unsuccessful cannulation attempts into the right VA through transradial access, transfemoral access was obtained through the left iliac stent. A 9-Fr BGC was navigated into the right SA. The balloon was partially inflated just distal to the first curve of the right SA and used as hook by pulling back until the proximal edge of the balloon was pushed distally by the lesser curvature of the SA, resulting in stabilization of the BGC and successful angioplasty and stent deployment at the VA stenosis. The patient''s symptoms resolved completely, without any neurological deficits. Conclusions: Balloon-hooking technique using a partially inflated BGC is feasible for stabilizing the guiding catheter in tortuous supra-aortic vessel.     

Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever

Chest symptoms and pleural effusion due to serositis in familial Mediterranean fever (FMF) are occasionally misdiagnosed as acute pneumonia. However, the actual pulmonary involvement of FMF is extremely rare. A 67-year-old man was referred to our hospital due to repeated and transient anterior chest pain. Chest images revealed a moderate amount of pericardial fluid, slight bilateral pleural effusion, and infiltrations in both lower lung lobes. Colchicine treatment without antibiotics rapidly improved these symptoms and findings. Pericarditis, pleurisy and the response to colchicine indicated FMF. FMF should be considered as a causative disease of pulmonary infiltrations, especially if it occurs repeatedly.     

Non-High-Density Lipoprotein Cholesterol and Risk of Cardiovascular Disease: The Japan Epidemiology Collaboration on Occupational Health Study

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes. Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group. Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19–5.72), 2.02 (0.95–4.29), 2.10 (1.01–4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction. Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers.     

Idiopathic Pulmonary Hemosiderosis Associated with Emphysematous Change in an Adult Who Underwent Lung Transplantation

Idiopathic pulmonary hemosiderosis is characterized by repeated alveolar hemorrhaging. We herein report a 52-year-old Japanese woman who had shortness of breath, diffuse small nodules, thin-walled cysts, and bronchiolectasis. A surgical lung biopsy revealed peribronchial hemosiderosis, centrilobular emphysema, and fragile elastic fibers of the alveolar septa and small vessels. She ultimately underwent living-donor lung transplantation five years after the first visit.     

Relationship between frailty and methotrexate discontinuation due to adverse events in rheumatoid arthritis patients

Clinical Rheumatology - Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). Frailty is the intermediate condition between being healthy and disabled, and can lead to...