Takanori Eguchi

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

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.

Characterization of T Cell Receptors of Th1 Cells Infiltrating Inflamed Skin of a Novel Murine Model of Palladium-Induced Metal Allergy

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.

Accumulation of Metal-Specific T Cells in Inflamed Skin in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis

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.

Accumulation of invariant NKT cells into inflamed skin in a novel murine model of nickel allergy.

Nickel (Ni) can cause delayed-type hypersensitivity reactions, which are thought to be mediated by the accumulation of T cells into inflamed skin. Accumulated T cells at the developmental stages in metal allergy are poorly characterized because a suitable animal model has not been established. To investigate the accumulated T cells in allergic inflamed skin, we generated a novel murine model of Ni-induced allergy. The murine model of Ni allergy was induced by two sensitizations of Ni plus lipopolysaccharide solution into the groin followed by three challenges with Ni solution into the footpad. Here we show that a specific TCR repertoire bearing Vα14Jα18, called natural killer (NK) T cells, was expanded monoclonally in BALB/c or C57BL/6 mice. Accumulation of NKT cells was characterized as CD4(+) or CD4(-)CD8(-) T cells. These results suggested that NKT cells are major pathogenic T cells at the elicitation phase of Ni allergy.

Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis.

The assessment of surgical and non-surgical treatment of stage II medication-related osteonecrosis of the jaw

Background Non-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 Methods In 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. Results Surgical 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. Conclusions Surgical 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.

Intraoperative real-time assessment of blood flow using indocyanine green angiography after anastomoses in free-flap reconstructions

w t c I e e d s i i v i A ndocyanine green (ICG) is a cyanine dye generally used n liver function tests. It emits near-infrared fluorescence, nd can be detected in the body by specific charged-coupled evice cameras.1 This technique, called ICG angiography, llows real-time imaging of the bloodstream. In reconstrucive surgery ICG angiography can confirm the presence of enetrating vessel branches, particularly in flaps for breast econstruction, and evaluation of the bloodstream during kidey transplantation.2,3 However, we know of only one report f its use in free flaps in head and neck surgery.4 We have sed ICG angiography to evaluate the quality of the bloodtream at the anastomotic site in three cases of reconstruction ith free flaps after resections for oral cancer. Between July 2015 and December 2016 we operated on hree patients with advanced oral cancer (Table 1). Cases and 2 had hemiglossectomy and neck dissection on the ffected side. Case 3 had resection of a tumour of the buccal ucosa and neck dissection on the affected side. All patients ad reconstructions with radial forearm free flaps. Each arteial anastomosis was made end-to-end with 9/0 nylon, and wo veins in each case had end-to-side or end-to-end anas-

A diffuse traumatic neuroma in the palate: a case report.

BackgroundA traumatic neuroma is not a true neoplasm but a reactive proliferation of neural tissue that commonly occurs after the transection or damage of a nerve bundle. Traumatic neuromas are rare in the oral region and usually occur as a solitary nodule of the mental foramen, lower lip, or tongue. This is the first report of a diffuse traumatic neuroma of the palate.Case presentationA 30-year-old Japanese man was referred to our clinic complaining of painful swelling of the left side of his palate. The swelling was diffuse and his pain increased with palpation of his palate. He had no noteworthy medical or family history, and was not aware of any history of trauma or inflammation in his head or neck area. We administered antibiotics and non-steroidal anti-inflammatory drugs because we suspected that his symptoms were the result of inflammation caused by an infection. However, his symptoms did not change. An incisional biopsy was performed, and histopathologic examination indicated that the lesion was a traumatic neuroma. Under general anesthesia the lesion was resected with a 5-mm margin using an electric scalpel because of the diffuse expansion and indistinct borders of the mass. Some tumor cells were observed within the surgical margins of the resected specimen, but there has been no recurrence of either the pain or mass in the 3 years since the surgery.ConclusionsThe location and diffuse nature of this traumatic neuroma are both very rare. While we were initially unsure about the diagnosis and treatment of this mass, the treatment outcome has been good. However, a postoperative recurrence can occur at any time following the excision of a traumatic neuroma, and close long-term follow-up will continue.