Anterior Cruciate Ligament Reconstruction: State of the Art

Abstract The rupture of the Anterior cruciate ligament (ACL) belongs to the most common ligament injuries of the human knee joint. ACL rupture results in an increased anterior translation and internal rotation of the tibia. Untreated knee instability causes a disintegration of the roll and sliding movement and a high incidence of secondary meniscus and chondral damages with consecutive or advanced arthritic changes. For deciding on a conservative or operative therapy, it is necessary to develop a high-risk profile. Elderly, inactive patients without instability symptoms can be treated conservatively; younger, active people and complex ligament injuries should receive an ACL replacement. The goal is to eliminate instability by maintaining the physiological kinematics of the knee. Anterior cruciate ligament may be reconstructed arthroscopically assisted by autologous tendons. Predominantly, hamstring- and bone-patellar-tendon grafts are used. No significant differences in knee laxity, clinically and functionally, were observed between both grafts. Various reconstruction techniques, single- or double-bundle techniques, were described. Successful replacement depends on a correct tunnel placement and reconstruction of the physiological band tension, a sufficient mechanical stability of fixation, an impingement-free range of motion and an adequate rehabilitation. A high degree of patient satisfaction in clinical and functional outcome could be evaluated.     

Effects of two extracellular matrices on morphologic and biochemical properties of human type II cells in vitro

Previous observations have suggested that differentiated functions of adult rat type II alveolar cells are affected in part by cell-matrix interactions. We examined several aspects of differentiated adult human type II cells cultured on either bovine corneal endothelial cell extracellular matrix (BCECM) or matrix derived from the Englebreth-Holm-Swarm tumor (EHS). Compared to cells cultured on BCECM, adult human type II cells grown on EHS assumed a more cuboidal shape, had a more defined apical-basal polarity, and appeared to contain a greater number of lamellar bodies and neutral lipid inclusions. These cells also incorporated a greater percentage of [14C]acetate into saturated phosphatidylcholine (SPC) than did their counterparts grown on BCECM. In contrast, the relative incorporation of [14C]acetate into phosphatidylglycerol (PG) was lower in cells grown on EHS than cells cultured on BCECM. The histochemical stain for alkaline phosphatase was useful in identification of human type II cells. Alkaline phosphatase expression was elevated in cells cultured on EHS compared to those cultured on BCECM. These results suggest that maintenance of a differentiated morphology, lipid synthesis, and expression of alkaline phosphatase activity by primary cultures of adult human type II cells are also influenced by cell-matrix interactions. All markers of differentiated function of type II cells except synthesis of PG are better maintained on EHS than on BCECM. Under the conditions of these experiments, synthesis of SPC and PG appears to be independently regulated.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.