Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin

Enamel matrix derivative (EMD) is widely considered useful to promote tissue regeneration during periodontal treatment. It has been reported that the main constituent of EMD is amelogenin and that the BMP-like and TGF-β-like activity of EMD promotes osteogenesis. However, it remains unclear whether those activities are dependent on amelogenin or another growth factor contained in EMD. We performed two-dimensional SDS-PAGE analysis of EMD, as well as Western blot analyses using anti-amelogenin, anti-BMP2/4, and anti-TGF-β1 antibodies, and amino acid sequencing. Our results revealed that a large number of splicing forms of amelogenin, BMP2/4, and other unknown molecules were involved in EMD, though TGF-β1 was not. In addition, we have evaluated intracellular signaling of ERK1/2 and Smad1/5/8, binding potential and alkaline phosphatase activity and have explored the potential regulatory relationship between amelogenin and BMP. Amelogenin bound to BMP2 as well as heparin/heparan sulfate. Thus, it was suggested that BMP2/4 carried over in EMD during processing promote binding activity and phosphorylate Smad1/5/8 in osteoblasts. On the other hand, amelogenin did not phosphorylate Smad1/5/8, but rather ERK1/2. Further, high-density amelogenin reduced the inhibition of alkaline phosphatase activity by noggin, though amelogenin did not have antagonistic properties against BMP. Together with the above findings, our findings suggest that the BMP2/4 contaminated during the purification process of EMD because of the avidity of amelogenin plays an important role in signaling pathway of calcification

慢性期移植腎機能低下例におけるIV型コラーゲンの分布の変化に関する検討

IV型コラーゲンは基底膜の主要構成成分であり,生体内に広く分布している.移植後急性期腎機能低下例においては,腎臓のIV型コラーゲン分布に変化が認められる.今回我々は移植腎機能廃絶の主原因である慢性期移植腎機能低下症(chronic allograft nephropathy: CAN)におけるIV型コラーゲンの変化について検討した.当院において施行された腎移植患者を,移植腎機能に基づいて以下の群に分類し,組織所見について検討した.なおCAN症例は,光学顕微鏡所見で診断された症例を用いた.Group A(n=5):腎機能正常群,Group B(n=10):急性期移植腎機能低下群,Group C(n=35): CAN症例で血清クレアチニン値2～4mg/dl,Group D(n=15): CANで血清クレアチニン値>4mg/dl.各症例におけるIV型コラーゲン分布について,IV型コラーゲンのα1鎖に対するモノクローナル抗体であるJK199,JK132を用いて,蛍光顕微鏡により検討した.Group AではJK199,JK132ともにメサンギウム基質(MM),ボーマン嚢基底膜(BBM),尿細管基底膜(TBM)に対する反応のみを認めた.Group Bでは,JK199はMM,BBM,TBMに加え,糸球体基底膜(GBM)および腎間質(INS)に対する反応を認めた.JK132の反応性はGroup Aと同様であった.一方,Group CおよびGroup Dでは,JK199においてはMM,GBM,BBM,TBM,INSに対する反応性が増強していた.JK132についてはMM,BBM,TBMに加え,GBMおよびINSにおいても反応が認められた.また,JK199およびJK132の反応性はGroup CよりもGroup Dにおいて強い傾向が認められた.GBMおよびINSにおけるJK132の反応陽性化はCANに特異的な所見であることが示唆された.Previously, we demonstrated the altered formation of collagen IV, which is the main constituent of the basement membrane, in renal allografts by staining with two monoclonal antibodies against the α1 chain of collagen IV. In the present study, we investigated the alteration of collagen IV in chronic allograft nephropathy (CAN), which is an irreversible change that can occur in renal allografts. Biopsy specimens of normal kidneys (Group A: n=5) and acute rejection (Group B: n=10) were studied as controls. Fifty biopsy specimens from 41 patients who had been diagnosed as having CAN were divided into two groups, according to renal function: Group C (n=35), sCr 2～4 mg/dl, and Group D (n=15), sCr>4 mg/dl. Two monoclonal antibodies, JK199 and JK132, those recognize the α1 chain of collagen IV were used. In Group A, JK199 reacted with the glomerular basement membrane (GBM), the mesangial matrix (MM), the basement membrane of Bowman's capsule (BBM) and the tubular basement membrane (TBM). JK132 only reacted with the MM, BBM and TBM. In Group B, JK199 reacted with GBM, MM, BBM, TBM and the interstitium (INS). JK132 only reacted with MM, BBM and TBM. In Group C and Group D, JK199 and JK132 reacted universally with GBM and INS in addition to MM, BBM and TBM. The intensity of the reaction was higher in Group D than in Group C. Thus, the reactivity of JK132 with GBM and INS was a unique finding for the CAN specimens. These results suggest that collagen IV is upregulated in CAN and the reactivity of JK132 in GBM and INS may represent the point of irreversible dysfunction of renal allografts

慢性期移植腎機能低下例におけるIV型コラーゲンの分布の変化に関する検討

IV型コラーゲンは基底膜の主要構成成分であり,生体内に広く分布している.移植後急性期腎機能低下例においては,腎臓のIV型コラーゲン分布に変化が認められる.今回我々は移植腎機能廃絶の主原因である慢性期移植腎機能低下症(chronic allograft nephropathy: CAN)におけるIV型コラーゲンの変化について検討した.当院において施行された腎移植患者を,移植腎機能に基づいて以下の群に分類し,組織所見について検討した.なおCAN症例は,光学顕微鏡所見で診断された症例を用いた.Group A(n=5):腎機能正常群,Group B(n=10):急性期移植腎機能低下群,Group C(n=35): CAN症例で血清クレアチニン値2～4mg/dl,Group D(n=15): CANで血清クレアチニン値>4mg/dl.各症例におけるIV型コラーゲン分布について,IV型コラーゲンのα1鎖に対するモノクローナル抗体であるJK199,JK132を用いて,蛍光顕微鏡により検討した.Group AではJK199,JK132ともにメサンギウム基質(MM),ボーマン嚢基底膜(BBM),尿細管基底膜(TBM)に対する反応のみを認めた.Group Bでは,JK199はMM,BBM,TBMに加え,糸球体基底膜(GBM)および腎間質(INS)に対する反応を認めた.JK132の反応性はGroup Aと同様であった.一方,Group CおよびGroup Dでは,JK199においてはMM,GBM,BBM,TBM,INSに対する反応性が増強していた.JK132についてはMM,BBM,TBMに加え,GBMおよびINSにおいても反応が認められた.また,JK199およびJK132の反応性はGroup CよりもGroup Dにおいて強い傾向が認められた.GBMおよびINSにおけるJK132の反応陽性化はCANに特異的な所見であることが示唆された.Previously, we demonstrated the altered formation of collagen IV, which is the main constituent of the basement membrane, in renal allografts by staining with two monoclonal antibodies against the α1 chain of collagen IV. In the present study, we investigated the alteration of collagen IV in chronic allograft nephropathy (CAN), which is an irreversible change that can occur in renal allografts. Biopsy specimens of normal kidneys (Group A: n=5) and acute rejection (Group B: n=10) were studied as controls. Fifty biopsy specimens from 41 patients who had been diagnosed as having CAN were divided into two groups, according to renal function: Group C (n=35), sCr 2～4 mg/dl, and Group D (n=15), sCr>4 mg/dl. Two monoclonal antibodies, JK199 and JK132, those recognize the α1 chain of collagen IV were used. In Group A, JK199 reacted with the glomerular basement membrane (GBM), the mesangial matrix (MM), the basement membrane of Bowman\u27s capsule (BBM) and the tubular basement membrane (TBM). JK132 only reacted with the MM, BBM and TBM. In Group B, JK199 reacted with GBM, MM, BBM, TBM and the interstitium (INS). JK132 only reacted with MM, BBM and TBM. In Group C and Group D, JK199 and JK132 reacted universally with GBM and INS in addition to MM, BBM and TBM. The intensity of the reaction was higher in Group D than in Group C. Thus, the reactivity of JK132 with GBM and INS was a unique finding for the CAN specimens. These results suggest that collagen IV is upregulated in CAN and the reactivity of JK132 in GBM and INS may represent the point of irreversible dysfunction of renal allografts

Efficacy of Over-The-Scope Clip Method as a Novel Hemostatic Therapy for Colonic Diverticular Bleeding

Colonic diverticular could bleed recurrently, and, sometimes, fatal massive bleeding could occur. However, the choice of endoscopic hemostasis remains controversial. Although the over-the-scope clip (OTSC) method has been reported to be effective, it has not been fully evaluated due to the small number of cases. This study aimed to evaluate the efficacy of the OTSC method for colonic diverticular bleeding. Between August 2017 and December 2020, 36 consecutive patients, including those who could not be treated using endoscopic band ligation (EBL) and those in whom re-bleeding had occurred after EBL, underwent the OTSC method for hemostasis of colonic diverticular bleeding at Hyogo Prefectural Awaji Medical Center. The procedure success rate, adverse events rate, early phase re-bleeding rate (within 30 days following primary hemostasis), and the requirement rate for additional transcatheter arterial embolization (TAE) or surgery were the outcomes assessed. The outcomes were procedure success rate 100%, adverse events rate 0%, early phase re-bleeding rate 8.3%, and additional TAE or surgery rate 0%. These results suggest that the OTSC method is a safe and effective treatment for managing colonic diverticular bleeding

Usefulness of high suction pressure for sufficient tissue collection during endobronchial ultrasound guided transbronchial needle aspiration.

INTRODUCTION: The optimal suction pressure during endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) remains to be determined. The aim of this study was to compare suction pressures for performance in collecting sufficient tissue specimens from mediastinal and hilar lymph nodes during EBUS-TBNA. METHODS: Retrospective analysis of consecutive patients with mediastinal and hilar lymphadenopathy who underwent EBUS-TBNA over a 3-year period. Results from patients who underwent EBUS-TBNA using a dedicated 20-mL VacLoc (Merit Medical Systems, Inc, South Jordan, UT) syringe (conventional method, group C) were compared with results from patients in whom a disposable 30-mL syringe (high pressure group, group H) was used. The yield for sufficient histologic specimen retrieval and amount of tissue obtained were compared between the 2 groups. RESULTS: Of 178 patients who underwent EBUS-TBNA, 131 had lung cancer confirmed by EBUS-TBNA: 35 in group C and 96 in group H. There were 7 patients in group C and 6 in group H who received final diagnoses by cytology alone. There were 28 in group C and 90 in group H who were diagnosed by both cytology and histology. There was a statistically significant difference between the groups in terms of the rate of sufficient sampling for histological specimens (p = 0.04). The H group revealed a tissue area approximately twice that of the C group (p = 0.003). There were no major procedure-related complications in either group. CONCLUSION: Higher suction pressures with larger syringe volumes during EBUS-TBNA may be useful for safely collecting sufficient tissue specimens

A numerical experiment on the influence of the interannual variation of sea surface temperature on terrestrial precipitation in northern Japan during the cold season

The role of sea surface temperature (SST) anomaly in modulating the terrestrial precipitation in winter around Japan was investigated using a regional atmospheric model. Large amount of snowfall occurs as the westerly winter monsoon carries abundant moisture from the Japan Sea. An experiment with realistic SST gives improved representation of terrestrial precipitation distribution compared to the reanalysis. The standard deviation of interannual variation of precipitation in the experiment was approximately 20% larger over the Kuroshio extension than that in the experiment with climatology SST, suggesting that the SST variability enhances the oceanic precipitation variability. For the role of Japan Sea, the terrestrial precipitation over the Japan Sea side (JSS) region in northern Japan was sensitive to the offshore SST anomaly through affecting moisture flux toward Japan. Since the offshore SST was clearly warmer in the 2000s relative to the 1980s, the effect of the long-term SST variation on the terrestrial precipitation trend was examined. The experiment with realistic SST simulated the observed trend in terrestrial precipitation in the JSS region. In contrast, the precipitation trend was significantly reduced in the experiment with climatology SST. Therefore, the long-term SST trend is an important factor for the precipitation trend in the region of Japan and the adjacent oceans where SST has significant trends. Precipitation in southern Japan facing the Pacific Ocean indicated increasing trend even without the SST trend. This suggests that the long-term variations in extratropical cyclones are also an important factor for precipitation trends around the Kuroshio extension