Acrolein (CH 2 ACHOCHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine adduct, N -(3-formyl-3,4-dehydropiperidino)lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neointima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu 2؉ generated the acrolein-low-density lipoprotein adducts and (ii) the ironcatalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes.
Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.
It is important to know the precise anatomy of anterior cruciate ligament bundles when performing reconstruction and to evaluate anterior cruciate ligament reconstruction surgery on an anatomical basis.
Peritoneal membrane permeability deteriorates in peritoneal dialysis (PD) patients. We test whether glucose degradation products (GDPs) in PD fluids, glyoxal, methylglyoxal and 3-
Objective. To describe the basis for enthesealassociated bone disease in the spondylarthritides, by analyzing microanatomic and histopathologic relationships between soft tissue, bone cortex, and adjacent trabeculae.Methods. Serial sections from 52 entheses were examined; these entheses encompassed small and large insertions in the upper limb (n ؍ 21), lower limb (n ؍ 27), and spine (n ؍ 4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and reparative changes were evaluated. Contact radiographs were used to ascertain the relationship between entheses and the trabecular network.Results. At virtually all fibrocartilaginous entheses, the deep cortical boundary was extremely thin (typically 50-600 m) or indistinguishable, and 96% of entheses had small holes in the cortical shell (typically 100-400 m wide). Such regions were frequent sites of bone formation and renewal (96%) and microdamage (31%); these changes were more common in the lower limb. The presence of blood vessels near holes in the cortical shell was common; in 85% of attachments, blood vessels were present on the soft tissue side of the enthesis. Highly orientated trabeculae were more obvious in the lower limb than the upper limb (59% versus 29%).Conclusion. The trabecular network supporting the cortical shell is an integral part of the enthesis, transferring load to an extensive skeletal region. In many cases, tendons/ligaments are anchored directly to such networks. This functional integration is associated with microdamage and repair at the hard tissue-soft tissue interface. These findings have implications for understanding bone involvement in SpA and for the SpA concept in general, especially the hypothesis that enthesis-bone architecture may be important in disease initiation.
For posterior cruciate ligament (PCL) reconstruction, two root, anterolateral and posteromedial bundles restruction are performed. However, little has been mentioned of anatomical measurements of the insertions to the bone of these bundles in previous publications. The aim of this study is to determine the precise anatomical measurements of the femoral and tibial insertions for anterolateral and posteromedial bundles of PCL. A total of 32 femur and 33 tibiae were selected from 50 cadavers after exclusion of knees that displayed macroscopically degenerative changes or evidence of trauma. PCL were divided into anterolateral bundles and posteromedial bundles to the insertion footprint, and those locations were measured and described. The distance from the center of the femoral insertions of the anterolateral and posteromedial bundles, and the Wrisberg ligament to the anterior margin of the medial femoral condyle averaged 9.6, 10.6, and 17.1 mm, respectively. The distance from the center of the femoral insertions of the anterolateral, posteromedial bundles, and Wrisberg ligament to the intercondylar roof averaged 4.8, 11.4, and 10.4 mm, respectively. The distance from the medial margin of the articular cartilage of the tibial plateau to the center of the tibial insertions of the anterolateral and posteromedial bundles averaged 51.0 and 50.0% of the total widest width of the tibial plateau, respectively. The vertical distance from the tibial insertion of the center of the posteromedial bundle to the plane of the tibial articular surface averaged 4.6 mm. This study leads to a better definition of the anatomy of the anterolateral and posteromedial bundles of PCL. It is very important to know the precise anatomy of PCL bundles when performing PCL reconstruction, and to evaluate PCL reconstruction surgery on an anatomical basis.
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