Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is characterized by the recruitment of lymphocytes into sites of allergic inflammation. Because of the unavailability of suitable animal models for metal allergy, the role of T cells in the pathogenesis of metal allergy has not been explored. Thus, we developed a novel mouse model for metal allergy associated with infiltration of T cells by multiple injections of palladium (Pd) plus lipopolysaccharide into the footpad. Using this model, we characterized footpad-infiltrating T cells in terms of phenotypic markers, T cell receptor (TCR) repertoires and cytokine expression. CD3+ CD4+ T cells accumulated in the allergic footpads 7 days after Pd challenge. The expression levels of CD25, interleukin-2, interferon-γ and tumor necrosis factor, but not interleukin-4 and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T helper 1 (Th1) cells locally expanded in response to Pd. Infiltrated T cells in the footpads frequently expressed AV18-1 and BV8-2 T cell receptor (TCR) chains compared with T cells in the lymph nodes and exhibited oligoclonality. T-cell clones identified from Pd-allergic mouse footpads shared identical CDR3 sequences containing AV18-1 and BV8-2. These results suggest that TCR AV18-1 and BV8-2 play dominant and critical parts in the antigen specificity of Pd-specific Th1 cells.

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BackgroundNon-surgical treatment has generally been recommended for stage II medication-related osteonecrosis of the jaw (MRONJ) in preference to surgery. However, non-surgical treatment is not empirically effective. The aim of this study was to evaluate whether surgical or non-surgical treatment leads to better outcomes for stage II MRONJ.Material and MethodsIn this retrospective study, surgery was performed in a total of 28 patients while 24 patients underwent non-surgical treatment. The outcomes of both treatment approaches after 6 months were evaluated and statistically compared. In addition, risk factors for surgical and non-surgical treatments were assessed for each.ResultsSurgical treatment in 25 patients (89.3%) resulted in success, with failure in 3 patients (10.7%). Non-surgical treatment was successful for 8 patients (33.3%) and failed in 16 patients (66.7%). There was therefore a significant difference between surgical and non-surgical treatment outcomes (P<0.01). Regarding risk factors, in non-surgical treatment primary diseases, medications, and drug holiday had a significant effect on outcomes (P<0.01). Risk factors for surgical treatment could not be clarified.ConclusionsSurgical treatment is more effective than non-surgical treatment for stage II MRONJ, and drug holiday, primary disease, and medication constitute risk factors in non-surgical treatment. Key words:Bisphosphonate, bisphosphonate-related osteonecrosis of the jaw, denosumab, management, medication-related osteonecrosis of the jaw.

Chromium (Cr) causes delayed-type hypersensitivity reactions possibly mediated by accumulating T cells into allergic inflamed skin, which are called irritants or allergic contact dermatitis. However, accumulating T cells during development of metal allergy are poorly characterized because a suitable animal model is not available. This study aimed to elucidate the skewing of T-cell receptor (TCR) repertoire and cytokine profiles in accumulated T cells in inflamed skin during elucidation of Cr allergy. A novel model of Cr allergy was induced by two sensitizations of Cr plus lipopolysaccharide solution into mouse groin followed by single Cr challenge into the footpad. TCR repertoires and nucleotide sequences of complementary determining region 3 were assessed in accumulated T cells from inflamed skin. Cytokine expression profiles and T-cell phenotypes were determined by qPCR. CD3+CD4+ T cells accumulated in allergic footpads and produced increased T helper 1 (Th1) type cytokines, Fas, and Fas ligand in the footpads after challenge, suggesting CD4+ Th1 cells locally expanded in response to Cr. Accumulated T cells included natural killer (NK) T cells and Cr-specific T cells with VA11-1/VB14-1 usage, suggesting metal-specific T cells driven by invariant NKT cells might contribute to the pathogenesis of Cr allergy.

Megawatt power gyrotrons are being developed for collaborative electron cyclotron heating (ECH) studies of advanced fusion devices and demonstration power plant (DEMO). (1) In the first experiment of a 300 GHz gyrotron, an output power above 0.5 MW in the TE32,18 single mode was achieved with a pulse width of 2 ms. This was the first observation of MW-scale oscillations in a DEMO-relevant gyrotron mode. It was also found that the reflection at the output window affected the determination of the oscillation mode. Furthermore, several single mode oscillations in the 226–254 GHz range were confirmed, which is important for the step-frequency tunable gyrotron in the sub-THz frequency range. (2) Based on the successful results of the 77 and 154 GHz large helical device (LHD) tubes, a new 154/116 GHz dual-frequency gyrotron with an output of over 1.5 MW is being designed. (3) A new record output of 1.38 MW was obtained using an existing 28 GHz gyrotron. A newly designed tube aimed at achieving a dual-frequency output power of 2 MW at 28 GHz (0.4 MW continuous wave) and 1 MW at 35 GHz was built. In the first experimental test, main mode oscillations were observed at the frequencies of 28.036 and 34.831 GHz with Gaussian-like output beams and output power of 1.27 and 0.48 MW, respectively. A total efficiency of 50% was achieved at 28 GHz operation.

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

It is not widely known that incorrect use of oral bisphosphonates (BPs), such as chewing the medication, can cause oral ulcers. An 83‐year‐old woman with dementia was referred to our clinic with multiple oral ulcers. Blood and histopathological examinations were inconclusive. Further questioning revealed that the patient chewed the oral BP, resulting in oral ulceration. Patients with loss of cognitive function, such as dementia, are at risk of oral ulcers caused by incorrect use of BPs.

Megawatt-class gyrotrons covering a wide frequency range (14 GHz-300 GHz) are in increasing demand for nuclear fusion. Recent electron cyclotron heating and electron cyclotron current drive experiments highlight a requirement of megawatt-scale gyrotrons at a relatively lower frequency (14-35 GHz) range of some plasma devices, like GAMMA 10/PDX of the