Summary Objective A new strategy is required in order to regenerate a meniscus for extensive defects. Synovial mesenchymal stem cells (MSCs) are an attractive cell source for meniscus regeneration ...due to their high proliferation and chondrogenic potential. We examined the effect of repetitive intraarticular injections of synovial MSCs on meniscus regeneration in a massive meniscal defect of pigs. We followed up the efficacy using MRI evaluation in addition to macroscopic and histological observations. Design Two weeks before the injection of synovial MSCs, the anterior half of the medial menisci was resected in both knees of pigs. Fifty million allogeneic synovial MSCs were injected into the right knee at 0, 2, and 4 weeks and followed up by sequential MRI. The regenerated meniscus, adjacent articular cartilage, and subchondral bone were evaluated by MRI at 2, 4, 8, 12 and 16 weeks. They were also evaluated macroscopically and histologically at 16 weeks ( n = 7). Results The resected meniscus regenerated significantly better in the MSC group than in the control group based on histological and MRI analyses. Macroscopically, the meniscal defect already appeared to be filled with synovial tissue at 2 weeks. Articular cartilage and subchondral bone at the medial femoral condyle were also significantly more preserved in the MSC group based on MRI, macroscopic, and histological analyses. Conclusions Intraarticular injections of allogeneic synovial MSCs appeared to promote meniscus regeneration and provide protection at the medial femoral articular cartilage in a porcine massive meniscal defect model.
Summary
Background
Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported.
...Objectives
To analyse the clinical and immunological findings in a large cohort of patients with PNP.
Methods
This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme‐linked immunosorbent assays (ELISAs) were analysed.
Results
The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty‐two (60%) of 53 patients had antibodies to alpha‐2‐macroglobulin‐like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans.
Conclusions
We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.
What's already known about this topic?
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease with polymorphous mucocutaneous lesions associated with either benign or malignant neoplasms.
Bronchiolitis obliterans with progressive respiratory failure is a cause of death in PNP.
What does this study add?
Several patients with PNP with typical clinical and immunological features did not show detectable neoplasms.
Antidesmocollin autoantibodies and antialpha‐2‐macroglobulin‐like protein 1 antibodies are useful for the diagnosis of PNP.
Linked Comment: Sprecher, Br J Dermatol 2015; 173: 1363–64.
Summary
Background
Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports.
Objectives
To reappraise the characteristic ...features of LABD with only IgA deposition at the basement membrane zone (BMZ) with direct immunofluorescence (DIF).
Methods
We retrospectively collected data from 101 patients from our archival records from 1 January 1996 to 31 December 2014 who had: (i) blisters on the skin and/or mucous membranes; (ii) subepidermal blisters in a biopsy specimen; and (iii) linear IgA deposition along the BMZ with/without linear C3 deposition at the BMZ with DIF. Most patients were referred for serological evaluation. Patients who showed concurrent linear IgG and/or IgM deposition at the BMZ under DIF were excluded. Clinical manifestations and serological findings were analysed.
Results
Heterogeneity of autoantigens in LABD was confirmed. Fifty‐four of 101 patients (53%) had IgG antibodies detected either by indirect immunofluorescence, immunoblotting or enzyme‐linked immunosorbent assays (ELISA). No statistical difference in clinical manifestations was found between patients in the IgG antibody‐possessing group and patients in the other group.
Conclusions
An association of IgG anti‐BMZ antibodies with LABD may increase if new IgG immunoblotting or ELISA techniques become available. Consensus for diagnostic criteria for LABD is desired for prospective data storage, although it may be arbitrary.
What's already known about this topic?
Linear IgA bullous dermatosis (LABD) lacks common diagnostic criteria.
Some reported cases of LABD show not only linear IgA deposition, but also IgG deposition at the basement membrane zone (BMZ) with direct immunofluorescence (DIF).
In addition to linear IgG deposition, linear IgA deposition at the BMZ with DIF has been reported in several autoimmune bullous diseases other than LABD.
What does this study add?
IgG antibodies were detected by enzyme‐linked immunosorbent assays (ELISAs) or immunoblotting (IB) in approximately 50% of patients with LABD who showed no linear IgG deposition along the BMZ with DIF.
The ratio may increase if IB/ELISAs to detect IgG anti‐BMZ antibodies targeting currently unavailable antigens become available in the future.
What is the translational message?
LABD and bullous pemphigoid may be two poles of the same spectrum, and linear IgA/IgG bullous dermatosis may be in the middle of both poles.
Consensus for diagnostic criteria for LABD is necessary, even if arbitrary.
Respond to this article
We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of ...anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation.
Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP.
Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif −8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, −2.62–1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test).
Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.
Summary Objective We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the ...behaviors and underlying mechanisms of the stem cells after the injection. Design One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. Results Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. Conclusion Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.
Summary Objective In a rat monoiodoacetic acid (MIA)-induced arthritis model, the amount of MIA commonly used was too high, resulting in rapid bone destruction. We examined the effect of MIA ...concentrations on articular cartilage and infrapatellar fat pad (IFP). We also established an original system for “macroscopic cartilage and bone score” and “IFP inflammation score” specific to the rat MIA-induced arthritis model. Design Male Wistar rats received a single intra-articular injection of MIA in the knee. The amount of MIA was 0.1, 0.2, 0.5, and 1 mg respectively. Articular cartilage was evaluated at 2-12 weeks. IFP was also observed at 3-14 days. Results Macroscopically, low MIA doses induced punctate depressions on the cartilage surface, and cartilage erosion proceeded slowly over 12 weeks, while higher MIA doses already induced cartilage erosion at 2 weeks, followed by bone destruction. MIA macroscopic cartilage and bone score, OARSI histological score, and Mankin score increased in a dose- and time-dependent manner. The IFP inflammation score peaked at 5 days in low dose groups, then decreased, while in high dose groups, the IFP score continued to increase over 14 days due to IFP fibrosis. Conclusions Punctate depressions, cartilage erosion, and bone destruction were observed in the MIA-induced arthritis model. The macroscopic cartilage and bone scoring enabled the quantification of cartilage degeneration and demonstrated that MIA-induced arthritis progressed in a dose- and time-dependent manner. IFP inflammation scores revealed that 0.2 mg MIA induced reversible synovitis, while 1 mg MIA induced fibrosis of the IFP body.
In Japan, recycled concrete aggregate (RCA) and recycled-aggregate concrete (RAC) are standardized in the Japanese Industrial Standards (JIS) A 5021–5023. The differences between the specifications ...in JIS and those in foreign countries are explained. In Japan, the durability of RAC under severe conditions, particularly freezing and thawing with/without deicing salt is recently being studied to facilitate its use. In this paper, the test method for freezing and thawing durability of recycled concrete aggregate and the specification of precast concrete made with recycled aggregate, which can be used in freezing and thawing circumstance with deicing salt are described.
Liquids are ubiquitous, but the atomic origin of viscosity remains unknown because of structural disorder and dynamic complexities. By using molecular dynamics simulation for liquid iron, we find a ...strong local correlation between the atomic-level pressure and the relaxation of atomic-level shear stress that is directly connected to viscosity. The results show that atomic sites under compression are more unstable against shear than those under tension, which causes fast relaxation in atomic-level shear stress. This result indicates spatial heterogeneities in the local viscosity in a liquid. We also find a temperature-independent relation between the local shear relaxation time and atomic-level volume strain, which suggests a universal structure-dynamics relationship in liquids. To explain our new findings, we discuss the relationships between the atomic-level pressure and various other parameters, such as the atomic-level shear stress, von Mises stress, local coordination number, and mean-squared displacements of atoms.
Summary Objective The induction of synovial tissue to the meniscal lesion is crucial for meniscal healing. Synovial Mesenchymal stem cells (MSCs) are an attractive cell source because of their high ...proliferative and chondrogenic potentials. We examined whether transplantation of synovial MSCs promoted healing after meniscal repair of extended longitudinal tear of avascular area in a microminipig model. Design Longitudinal tear lesion was made in medial menisci and sutured in both knees, and then a synovial MSC suspension was administered for 10 min only in unilateral knee. The sutured meniscus was evaluated morphologically and biomechanically at 2, 4, and 12 weeks. The behavior of transplanted MSCs was also examined. Results The meniscal healing at 12 weeks was significantly better in the MSC group than in the control group; macroscopically, histologically and by T1rho mapping analysis. Transmission electron microscopic analysis demonstrated that the meniscus lesion was occupied by dense collagen fibrils only in the MSC group. Biomechanical analysis revealed that the tensile strength to failure of the meniscus higher in the MSC group than in the control group in each microminipig. Synovial tissue covered better along the superficial layer from the outer zone into the lesion of the meniscus in the MSC group at 2 and 4 weeks in each microminipig. Synovial MSCs labeled with ferucarbotran were detected in the meniscus lesion and adjacent synovium by MRI at 2 weeks. Conclusion Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.
Summary
Background
The parallel ridge pattern (PRP) is considered the dermoscopic hallmark of acral melanoma (AM). However, it was recently shown that approximately one‐third of AMs do not display a ...PRP dermoscopically, rendering their detection more troublesome.
Objectives
To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of AM.
Methods
Dermoscopic images of consecutive cases of histopathologically diagnosed AMs and acral naevi with histopathological diagnosis or with at least 1 year of follow‐up were evaluated by three independent investigators for the presence of predefined criteria. Crude and adjusted odds ratios and their corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression, respectively. Receiver operating characteristic curves were used to choose among competing classification schemes.
Results
In total 603 lesions (472 naevi and 131 AMs) were included in the study. A scoring system (named BRAAFF) composed of six variables was associated with optimal area under the curve and sensitivity for the diagnosis of AM. This method includes four positive (irregular blotches, ridge pattern, asymmetry of structures and asymmetry of colours) and two negative predictors (furrow pattern and fibrillar pattern).
Conclusions
The BRAAFF checklist significantly improves the diagnostic accuracy of dermoscopy for the diagnosis of AM.
What's already known about this topic?
Approximately one‐third of acral melanomas (AMs) lack a dermoscopic parallel ridge pattern, rendering their detection more troublesome.
What does this study add?
A scoring system composed of six variables achieves the highest diagnostic accuracy for AM.
Application of this diagnostic scheme minimizes the possibility of missing AMs that are not dermoscopically characterized by a parallel ridge pattern.
Linked Comment: Rao and Giambrone, Br J Dermatol 2015; 173: 893–894.
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