Category:
Bunion; Basic Sciences/Biologics
Introduction/Purpose:
It is generally accepted that failure of the medial supporting soft tissue structure of the metatarsophalangeal joint plays an ...important role in the development of hallux valgus. The metatarsosesamoid ligament (MSL), a component of the medial soft tissue, is an important structure that connects the metatarsal head and the sesamoid complex. The sesamoid complex works as a dynamic stabilizer of the metatarsal head. We hypothesized that the failure of the medial MSL causes instability of the first metatarsal bone, which leads to hallux valgus deformities. Therefore, the present study aimed to describe the detailed structure and degenerative findings of MSL and to clarify the mechanical stress of the MSL enthesis, considering the mechanism of failure of the medial supporting soft tissue structure.
Methods:
The first metatarsal heads and sesamoid bones with soft tissue were collected from twelve cadavers. Serial 4-μm thick section4-μm intervals and stained with toluidine blue (Fig. 1a). We described the detailed histological structures and degenerative findings of MSL. In addition, morphometric comparisons were made between the medial and lateral MSL entheses at the metatarsal head to evaluate the mechanical stress they. First, we measured the thickness of the uncalcified fibrocartilage (UF thickness) following a protocol adopted previously (Fig. 1b). Second, the degree of irregularity of the interface between the zones of calcified fibrocartilage and bone (CFB) at each enthesis was assessed as the ratio between the lengths of the CFB and the enthesis (CFB/ E ratio) (Fig. 1c). The differences in these parameters were evaluated using the paired T test and Wilcoxon signed-rank test (P < 0.05).
Results:
We identified that the MSL entheses were fibrocartilaginous entheses, which consisted of four tissue zones. The region in which the MSL wraps around the articular surface of the metatarsal head contains a metachromatic area accompanied by fibrocartilage cells at the deep surface of the MSL, called the sesamoid fibrocartilage. At the MSL enthesis, pathological findings indicating enthesopathy were observed. One specimen showed the tear of the MSL at the wrap around region. The MSL enthesis tear was observed in two specimens with hallux valgus. Both UF thickness (P = 0.12, effect size r = 0.89) and CFB/E ratio (P = 0.17, effect size d = 0.35) were significantly greater in the medial MSL enthesis than those in the lateral MSL enthesis.
Conclusion:
In the present study, the MSL showed enthesis protecting structures such as enthesis fibrocartilage which contributes to dissipating bending forces during insertional angle change, complexed CFB interface which guards an enthesis against shearing forces and wrap around region which contributes to dissipating the shearing force to the enthesis. However, the medial MSL subject to the greater forces and the degenerative findings of enthesopathy were observed. On top of that, all four hallux valgus specimens with sesamoid complex dislocation showed MSL enthesis tear. Enthesopathy, particularly at the medial MSL, may be the cause of hallux valgus.
Immune Thrombocytopenia Abadi Uri; Yarchovsky-Dolberg Osnat; Ellis, Martin H
Clinical and applied thrombosis/hemostasis,
07/2015, Volume:
21, Issue:
5
Journal Article
Peer reviewed
Open access
Immune thrombocytopenia (ITP) is a rare autoimmune disorder with an incidence of 3 to 5 per 100 000 individuals. In children, the disease is self-limited and is most commonly virus related (acute ...ITP) whereas in adults, the disease is typically chronic. The age distribution of adult ITP displays 2 peaks; the first in younger adults aged 18 to 40 with a female predominance and the second in people aged older than 60 with men and women affected equally. Our approach to ITP has evolved over the past several years: there has been a change in nomenclature and ITP now denotes “immune thrombocytopenia” (the “I” no longer denoting “idiopathic”) and “purpura” no longer features in the name of the disease; new insights into the pathogenesis of ITP have revealed the importance of impaired megakaryocytopoiesis in the condition; underlying mechanisms of secondary ITP have been elucidated and finally novel thrombopoietic agents have been shown to be effective in the treatment of ITP in randomized clinical trials. In this article, we review important recent advances in the pathogenesis and treatment of ITP.
SUMMARY
The nonexpressor of pathogenesis‐related (NPR) gene family is well known to play a crucial role in transactivation of TGA transcription factors for salicylic acid (SA)‐responsive genes, ...including pathogenesis‐related protein 1 (PR1), during plants' immune response after pathogen attack in the model dicot Arabidopsis thaliana. However, little is known about NPR gene functions in monocots. We therefore explored the functions of NPRs in SA signaling in the model monocot Brachypodium distachyon. BdNPR1 and BdNPR2/3 share structural similarities with A. thaliana AtNPR1/2 and AtNPR3/4 subfamilies, respectively. The transcript level of BdNPR2 but not BdNPR1/3 appeared to be positively regulated in leaves in response to methyl salicylate. Reporter assays in protoplasts showed that BdNPR2 positively regulated BdTGA1‐mediated activation of PR1. This transactivation occurred in an SA‐dependent manner through SA binding at Arg468 of BdNPR2. In contrast, BdNPR1 functioned as a suppressor of BdNPR2/BdTGA1‐mediated transcription of PR1. Collectively, our findings reveal that the TGA‐promoted transcription of SA‐inducible PR1 is orchestrated by the activator BdNPR2 and the repressor BdNPR1, which function competitively in B. distachyon.
Significance Statement
We present a novel function of Brachypodium distachyon NPR (BdNPR) in the transcriptional machinery for the defensin gene pathogenesis‐related 1 (PR1). We address here the TGA‐activated transcriptional machinery for SA‐inducible PR1 expression, in which BdNPR2 and BdNPR1 work competitively in B. distachyon.
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