Knee kinematics and kinetics in former soccer players with a 16-year-old ACL injury – the effects of twelve weeks of knee-specific training

BACKGROUND: Training of neuromuscular control has become increasingly important and plays a major role in rehabilitation of subjects with an injury to the anterior cruciate ligament (ACL). Little is known, however, of the influence of this training on knee stiffness during loading. Increased knee stiffness occurs as a loading strategy of ACL-injured subjects and is associated with increased joint contact forces. Increased or altered joint loads contribute to the development of osteoarthritis. The aim of the study was to determine if knee stiffness, defined by changes in knee kinetics and kinematics of gait, step activity and cross-over hop could be reduced through a knee-specific 12-week training programme. METHODS: A 3-dimensional motion analysis system (VICON) and a force plate (AMTI) were used to calculate knee kinetics and kinematics before and after 12 weeks of knee-specific training in 12 males recruited from a cohort with ACL injury 16 years earlier. Twelve uninjured males matched for age, sex, BMI and activity level served as a reference group. Self-reported patient-relevant data were obtained by the KOOS questionnaire. RESULTS: There were no significant changes in knee stiffness during gait and step activity after training. For the cross-over hop, increased peak knee flexion during landing (from 44 to 48 degrees, p = 0.031) and increased internal knee extensor moment (1.28 to 1.55 Nm/kg, p = 0.017) were seen after training, indicating reduced knee stiffness. The KOOS sport and recreation score improved from 70 to 77 (p = 0.005) and was significantly correlated with the changes in knee flexion during landing for the cross-over hop (r = 0.6, p = 0.039). CONCLUSION: Knee-specific training improved lower extremity kinetics and kinematics, indicating reduced knee stiffness during demanding hop activity. Self-reported sport and recreational function correlated positively with the biomechanical changes supporting a clinical importance of the findings. Further studies are needed to confirm these results in women and in other ACL injured populations

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

Human Cytomegalovirus Fcγ Binding Proteins gp34 and gp68 Antagonize Fcγ Receptors I, II and III

Human cytomegalovirus (HCMV) establishes lifelong infection with recurrent episodes of virus production and shedding despite the presence of adaptive immunological memory responses including HCMV immune immunoglobulin G (IgG). Very little is known how HCMV evades from humoral and cellular IgG-dependent immune responses, the latter being executed by cells expressing surface receptors for the Fc domain of IgG (FcγRs). Remarkably, HCMV expresses the RL11-encoded gp34 and UL119-118-encoded gp68 type I transmembrane glycoproteins which bind Fcγ with nanomolar affinity. Using a newly developed FcγR activation assay, we tested if the HCMV-encoded Fcγ binding proteins (HCMV FcγRs) interfere with individual host FcγRs. In absence of gp34 or/and gp68, HCMV elicited a much stronger activation of FcγRIIIA/CD16, FcγRIIA/CD32A and FcγRI/CD64 by polyclonal HCMV-immune IgG as compared to wildtype HCMV. gp34 and gp68 co-expression culminates in the late phase of HCMV replication coinciding with the emergence of surface HCMV antigens triggering FcγRIII/CD16 responses by polyclonal HCMV-immune IgG. The gp34- and gp68-dependent inhibition of HCMV immune IgG was fully reproduced when testing the activation of primary human NK cells. Their broad antagonistic function towards FcγRIIIA, FcγRIIA and FcγRI activation was also recapitulated in a gain-of-function approach based on humanized monoclonal antibodies (trastuzumab, rituximab) and isotypes of different IgG subclasses. Surface immune-precipitation showed that both HCMV-encoded Fcγ binding proteins have the capacity to bind trastuzumab antibody-HER2 antigen complexes demonstrating simultaneous linkage of immune IgG with antigen and the HCMV inhibitors on the plasma membrane. Our studies reveal a novel strategy by which viral FcγRs can compete for immune complexes against various Fc receptors on immune cells, dampening their activation and antiviral immunity.DFG grant He 2526/6-2.European Commission grants QLRT-2001-01112 and MRTN-CT-2005-019248.Helmholtz Association through VISTRIE VH-VI-242.UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí