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Glucocorticoid remains the mainstay for treatment of large vessel vasculitis (LVV) including giant cell arteritis (GCA); however, the disease affects the elderly for whom the adverse effects of glucocorticoid are problematic. Recently, some reports have suggested that intravenous tocilizumab (TCZ) monotherapy is effective for this disease. To date, it remains unknown whether subcutaneous TCZ monotherapy is also effective. Here, we present a first case of GCA successfully treated with subcutaneous TCZ monotherapy. A 75-year-old woman presented with shoulder and hip pain. She was diagnosed with polymyalgia rheumatica (PMR) and treated with low-dose prednisolone (15 mg daily); however, she discontinued glucocorticoid therapy at her discretion due to the psychiatric adverse effect (cognitive dysfunction). Seven months later, her shoulder and hip pain relapsed. Furthermore

Myositis-specific autoantibody is associated with the clinical phenotype and prognosis of dermatomyositis. Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are generally mutually exclusive. We herein present an extremely rare case of dermatomyositis which showed double positivity for anti-MDA5 and anti-ARS antibodies. There have been very few reported cases of double positive anti-MDA5, anti-ARS antibodies. In such cases, the clinical characteristics of each autoantibody can coexist. Thus, we should pay attention to the rapidly progressing features of anti-MDA5 as well as the chronic relapsing features of anti-ARS for the better management of this rare condition.

The passive optical network (PON) is widely deployed in access networks, and various specifications have become standards designed to meet demands of each market. To accelerate new PON-based service creation, software-defined network enabled broadband access (SEBA) is being studied; it uses a common API to abstract various optical line terminal (OLT)/optical network units (ONUs) and manages the devices via a controller. However, the current abstraction unit in SEBA supports only ITU-T PON. In order to support IEEE PON, multiple package types and switching management functions must be considered. This paper proposes a technology profile including package types for IEEE specification and an adapter that abstracts IEEE PON and switches functions according to the specified package type. The logical link configuration settings for ITU-T PON and IEEE PON are implemented in common, and the adapter abstracts IEEE PON OLT/ONU by switching between extended operation, administration, maintenance (eOAM) functions for package B and other eOAMs. We demonstrate the proposed software on a system implemented using commercially available OLT/ONU and OSS in SEBA. The results show that OLT/ONUs can be managed via a common API, differences in package types can be abstracted by technology profiles and our adapter, and that a common SEBA platform can manage, in a unified manner, both ITU-T PON and IEEE PON.

Aseptic meningitis is a rare life-threatening complication of primary Sjögren’s syndrome (pSS), and its characteristics and prognosis remain unknown. We present our case of aseptic meningitis associated with pSS and reviewed the published literature to elucidate their characteristics and prognosis. An 84-year-old man was admitted to our hospital for fever and disturbance of consciousness. Acute aseptic meningitis was diagnosed based on the results for cerebrospinal fluid and head imaging tests. As an aetiological investigation for his aseptic meningitis, serum anti-Sjögren’s-syndrome–related antigen A and anti-Sjögren’s-syndrome–related antigen B antibodies were found to be positive, and the biopsy specimen of his labial salivary gland revealed lymphocytic sialadenitis, confirming a diagnosis of pSS. Treatment with moderate-dose glucocorticoid completely improved his aseptic meningitis. Relapse of the disease was not observed during his clinical course over 12 months. Our present case and literature review suggest that aseptic meningitis can be an initial manifestation of pSS and be treatable by immunosuppressive therapy. Thus, early recognition and treatment initiation are critical to prevent the irreversible damage of central nervous system in pSS-associated aseptic meningitis. In aseptic meningitis of unknown origin, pSS should be included in differential diagnoses, and testing for serum anti-Sjögren’s-syndrome–related antigen A and anti-Sjögren’s-syndrome–related antigen A antibodies may be useful as an initial screening.

Liver kinase B1 (LKB1) is a serine/threonine protein kinase that acts as a key tumor suppressor protein by activating its downstream kinases, such as AMP-activated protein kinase (AMPK). However, the regulatory actions of LKB1 and AMPK on DNA damage response (DDR) remain to be explored. In this study, we investigated the function of LKB1 in DDR induced by cisplatin, a representative DNA-damaging agent, and found that LKB1 stabilizes and activates p53 through the c-Jun N-terminal kinase (JNK) pathway, which promotes cisplatin-induced apoptosis in human fibrosarcoma cell line HT1080. On the other hand, we found that AMPKα1 and α2 double knockout (DKO) cells showed enhanced stabilization of p53 and increased susceptibility to apoptosis induced by cisplatin, suggesting that AMPK negatively regulates cisplatin-induced apoptosis. Moreover, the additional stabilization of p53 and subsequent apoptosis in AMPK DKO cells were clearly canceled by the treatment with the antioxidants, raising the possibility that AMPK suppresses the p53 activation mediated by oxidative stress. Thus, our findings unexpectedly demonstrate the reciprocal regulation of p53 by LKB1 and AMPK in DDR, which provides insights into the molecular mechanisms of DDR.

A high prevalence of allergic diseases was found in patients with adult-onset Still's disease (AOSD). However, the relative prevalence is unknown compared with other diseases.We sought to compare the prevalence of allergic diseases in the control group of patients with rheumatoid arthritis (RA).We retrospectively examined consecutive patients diagnosed with AOSD or RA in our hospital from 2010 to 2020. The patients with AOSD met the preliminary criteria for classification of AOSD. The patients with RA met the EULAR/ACR 2010 criteria. We included patients with RA without other rheumatic diseases. The analysis was performed on six types of allergic reactions: food allergy, drug allergy, allergic contact dermatitis, allergic rhinitis and/or allergic conjunctivitis, and asthma.Twenty-four patients with AOSD and 409 patients with RA were enrolled. The median ages (AOSD, RA) were 46.6, 68.2 years old. Females were 83.3%, 78.0%. Fifty% of AOSD patients and 34.5% of RA patients presented at least one type of allergic diseases (p = 0.12). These included food allergy (4.2%, 6.4%: p = 1.0), drug allergy (37.5%, 16.6%: p = 0.02), allergic rhinitis/allergic conjunctivitis (25.0%, 8.6%: p = 0.02), contact dermatitis (4.2%, 4.4%: p = 1.0), and asthma (4.2%, 5.9%: p = 1.0).Patients with AOSD had a higher prevalence of drug allergy, and allergic rhinitis/allergic conjunctivitis than patients with RA.

Acute encephalitis is an extremely rare condition in primary Sjogren's syndrome (pSS), and its characteristics and prognosis remain unclear. Here we report the case of pSS presented with acute encephalitis. She was admitted to our hospital for acute disturbance of consciousness. Acute encephalitis was diagnosed based on the results for cerebrospinal fluid test (the increase of leukocyte counts, protein, and interleukin-6 level), magnetic resonance imaging (a high signal intensity of the white matter around lateral ventricle on T2 FLAIR images), and single photon emission computed tomography with 99mTc (hypoperfusion in the bilateral cerebrum with frontal lobe predominance). The infectious etiologies and underlying malignancies were excluded. Serum anti-SSA/Ro antibody was positive with extremely high titer, whereas anti-dsDNA, anti-Sm, anti-ribosomal P, anti-RNP, and anti-phospholipid antibodies were all negative. Anti-NAE, anti-NMDAR, and anti-ribosomal P antibodies in cerebrospinal fluid were absent. The biopsy specimen of her labial salivary gland revealed a focal lymphocytic sialadenitis with a score of grade 4 in Greenspan grade. She also developed diffuse alveolar hemorrhage during the clinical course. She was diagnosed with pSS complicated with acute encephalitis followed by diffuse alveolar hemorrhage and successfully treated with pulse steroids, high dose of prednisolone and intravenous cyclophosphamide. Our present case and literature review suggest that acute encephalitis associated with pSS can be treatable with the immunosuppressive therapy, and thus, early recognition and treatment initiation are important for this life-threatening condition. Thus, pSS should be included in the differential diagnosis of unexplained encephalitis. Notably, our case characteristically showed diffuse alveolar hemorrhage, adding the new insight in the pathogenesis of acute encephalitis associated with pSS that capillaritis might be the underlying cause of this condition. (272 words).

Dropped head syndrome is a rare disease entity characterized by severe weakness of the cervical para-spinal muscles, resulting in a chin-on-chest deformity. Systemic sclerosis is one of the causes of dropped head syndrome, but its characteristics and prognosis remain unclear due to the extreme rarity of this condition. We present a case of dropped head which occurred in systemic sclerosis. He presented with severe dropped head and relatively mild weakness of the proximal limb muscles. Serum level of creatine kinase was elevated, myopathic change was observed in electromyography, and gadolinium enhancement was found in magnetic resonance imaging of his posterior neck muscles. Anti-topoisomerase I antibody was positive, while other autoantibodies such as anti-PM/Scl and anti-Ku antibodies were negative. Since his dropped head acutely progressed, high dose of glucocorticoid therapy was initiated, which successfully improved dropped head, serum level of creatine kinase, and gadolinium enhancement in magnetic resonance imaging. Our present case and literature review suggest that dropped head occurring in systemic sclerosis can be treatable with immunosuppressive therapy. It is important to recognize this rare but treatable involvement of systemic sclerosis because early diagnosis and treatment initiation are crucial to prevent the irreversible organ damage and the significant decrease of daily activities.

Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. The reciprocal functions of RIPK1 in TNF signaling are determined by the state of the posttranslational modifications (PTMs) of RIPK1. However, the underlying mechanisms associated with the PTMs of RIPK1 are unclear. In this study, we found that RING finger protein 4 (RNF4), a RING finger E3 ubiquitin ligase, is required for the RIPK1 autophosphorylation and subsequent cell death. It has been reported that RNF4 negatively regulates TNF-α-induced activation of the nuclear factor-κB (NF-κB) through downregulation of transforming growth factor β-activated kinase 1 (TAK1) activity, indicating the possibility that RNF4-mediated TAK1 suppression results in enhanced sensitivity to cell death. However, interestingly, RNF4 was needed to induce RIPK1-mediated cell death even in the absence of TAK1, suggesting that RNF4 can promote RIPK1-mediated cell death without suppressing the TAK1 activity. Thus, these observations reveal the existence of a novel mechanism whereby RNF4 promotes the autophosphorylation of RIPK1, which provides a novel insight into the molecular basis for the PTMs of RIPK1.