Synergistic Pathogenic Effects of Combined Mouse Monoclonal Anti-Desmoglein 3 IgG Antibodies on Pemphigus Vulgaris Blister Formation

Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies. Previously, we generated an active mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3−/− mice. In this study, we isolated 10 anti-Dsg3 IgG mAbs (NAK-series) from PV model mice generated by transfer of naive Dsg3−/− splenocytes. We characterized their epitopes using domain-swapped and point-mutated Dsg1/Dsg3 molecules and examined their pathogenic activities in blister formation in three different assays. In a passive transfer model using neonatal mice, eight of 10 NAK mAbs showed pathogenic activity when injected together with half the minimum pathogenic dose of anti-Dsg1 IgG autoantibodies from pemphigus foliaceus (PF) patients. None of the mAbs could induce the PV phenotype when individual hybridoma clones were inoculated by peritoneal injection into adult Rag2−/− mice. NAK mAbs displayed a range of potency in an in vitro dissociation assay using primary cultured mouse keratinocytes. Interestingly, when multiple hybridoma clones recognizing different epitopes were inoculated in combination, recipient mice developed the PV phenotype. In vitro dissociation assays confirmed that combined NAK mAbs had synergistic pathogenic effects. These findings indicate that although an individual anti-Dsg3 IgG is not sufficient to cause blistering in adult mice, several together can induce the PV phenotype. These mAbs will provide a valuable tool to investigate the molecular mechanisms of blister formation, mimicking the effects of the polyclonal IgG antibodies found in patients

Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia

<p>Abstract</p> <p>Background</p> <p>Oral leukoplakia is a precancerous change developed in the oral mucosa, and the mechanism that oral leukoplakia becomes malignant through atypical epithelium is not known. Here we compared the β-catenin expression detected by immunohistochemical staining in the normal oral epithelium and in the oral leukoplakia with or without dysplasia.</p> <p>Results</p> <p>The normal oral epithelium showed β-catenin expression only in the cell membrane, but not in the nuclei. In the oral leukoplakia without dysplasia, 7 out of 17 samples (41%) showed β-catenin expression in the cell membrane, and 5 samples (29%) showed expression in the nuclei. In the oral leukoplakia with dysplasia, nuclear expression of β-catenin was shown in 11 out of 12 samples (92%). Incidence of nuclear β-catenin expression was significantly different between dysplasia and normal oral epithelium (P < 0.01), and also between oral leukoplakia with dysplasia and those without dysplasia (P < 0.01). Wnt3 expression was detected in the epithelial cell membrane or cytoplasm in oral leukoplakia where nuclear expression of β-catenin was evident, but not in epithelial cells without nuclear expression of β-catenin.</p> <p>Conclusion</p> <p>The components of canonical Wnt pathway, such as Wnt3, β-catenin, and cyclin D1, were detected, implying that this pathway is potentially involved in the progression of dysplasia in oral leukoplakia.</p

C1-INHの低下がみられた放射線性潰瘍に伴う舌浮腫の1例

66歳の男性が嚥下困難を伴う突然の舌の腫脹を自覚した.組織内照射による舌癌治療の既往があるために,再発疑いで3週間前に右側舌潰瘍から細胞診を受けていた.細胞診はクラスIで,悪性所見は認めなかった.放射線性粘膜潰瘍を伴う血管神経性浮腫(クインケ浮腫)の診断のもとにトラネキサム酸,d-マレイン酸クロルフェニラミン,エピネフリンを投与した.6日後には舌浮腫はほとんど消退した.舌腫脹時の検査成績では,CH50, C1, C3, C4は基準値内であったが,補体第1成分阻止因子活性は低値を示した.家族歴はなく遺伝性血管神経性浮腫が疑われたが,舌浮腫の消退後は同因子活性は基準値内に回復していた.A 66-year-old man became aware of sudden swelling of the tongue with swallowing disturbance. He had a medical history of tongue cancer treated by interstitial radiotherapy and had undergone a cytological examination of an ulcer on the right side of the tongue three weeks earlier because of suspected recurrence. The cytological examination result was classI with no malignant findings. Angioneurotic edema, so-called "Quinke\u27s edema", associated with radiation-induced ulcer of the tongue, was diagnosed. Tranexamic acid, d-chlorpheniramine maleate, and epinephrine were administered. After six days, the tongue edema had almost disappeared. Laboratory examination revealed a low level of C1 inhibitor activity with normal levels of CH50. C1, C3, and C4 at the time of swelling. Hereditary angioneurotic edema with absence of hereditary trait was suspected based on the sudden edema attack and low level of C1 inhibitor activity. The C1 inhibitor activity returned to norma after disappearance of the tongue edema

Structural basis of lignocellulose deconstruction by the wood-feeding anobiid beetle Nicobium hirtum

The details of the lignocellulose deconstruction processes in the digestive systems of wood-feeding insects remain elusive. This study aimed to examine the biochemical conversion of lignocellulose in the digestive system of a wood-feeding anobiid beetle, Nicobium hirtum, one of the most important pests of wooden products in Japan. To this end, N. hirtum larvae were fed with Japanese red pine (softwood) and Japanese beech (hardwood) sapwood diets, as well as an artificial diet containing Shorea wood (hardwood) sapwood sawdust. The structural differences between the original and digested (feces) lignocellulose samples were examined using wet-chemical and two-dimensional (2D) nuclear magnetic resonance (NMR) methods. Cellulose and hemicelluloses, especially mannan in the softwood diet, were preferentially degraded over lignin in the larval digestive system. As a result, lignin was enriched in the digested lignocellulose residues. Lignin compositional analyses based on thioacidolysis and 2D NMR determined that the proportions of oxidized lignin aromatic units were notably increased after digestion. Further, the 2D NMR analyses revealed the accumulation of aldehyde and hydroxypropiovanillone/syringone end-unit structures in lignin, indicating that oxidative and/or reductive modifications of lignin polymers occur in the larval digestive system. Such structural alterations of lignin may facilitate the dissociation of the lignin barrier, thereby liberating polysaccharides for subsequent enzymatic conversion for assimilation and energy