Bone marrow-derived cells are responsible for the development of autoimmune arthritis in human T cell leukemia virus type I-transgenic mice and those of normal mice can suppress the disease.
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Previously, we reported that human T cell leukemia virus type I env-pX region-introduced transgenic (pX-Tg) mice developed an inflammatory polyarthropathy associated with a development of autoimmunity. To elucidate roles of autoimmunity in the development of arthritis, the immune cells were reciprocally replaced between pX-Tg mice and non-transgenic (Tg) mice. When bone marrow (BM) cells and spleen cells from pX-Tg mice were transferred into irradiated non-Tg mice, arthritis developed in these mice. In contrast, arthritis in pX-Tg mice was completely suppressed by non-Tg BM and spleen cells. Similar results were obtained with BM cells only. After the transplantation, T cells, B cells, and macrophages were replaced completely, whereas cells in the joints were replaced partially. In those mice, serum Ig and rheumatoid factor levels correlated with the disease development, and inflammatory cytokine expression was elevated in the arthritic joints. Furthermore, involvement of T cells in the joint lesion was suggested, because the incidence was greatly reduced in athymic nu/nu mice although small proportion of the mice still developed arthritis. These observations suggest that BM stem cells are abnormal, causing autoimmunity in pX-Tg mice, and this autoimmunity plays an important, but not absolute, role in the development of arthritis in this Tg mouse. (+info)
Joint immobilization reduces synovial fluid hyaluronan concentration and is accompanied by changes in the synovial intimal cell populations.
(58/2057)
OBJECTIVES: Synovial fluid (SF) of normal joints contains high hyaluronan (HA) concentrations. However, the mechanism by which these are controlled and how they are influenced by articulation and loading are not established. In this study, we have examined whether immobilization influences SF HA concentration and whether this is associated with alterations in the synovial lining. METHODS: Hock joints of five adult sheep were immobilized by external fixation. Twelve weeks later, SF and synovium samples were collected. The HA concentration in SF was assayed using an ELISA-based method. Non-specific esterase (NSE) and uridine diphosphoglucose dehydrogenase (UDPGD) activities were assessed in cryostat sections of snap-chilled synovial samples using cytochemical techniques, and UDPGD activity per cell was measured in synovial lining cells by scanning and integrating microdensitometry. RESULTS: We found that the SF HA concentration was decreased from 1.65+/-0.25 mg/ml in control joints to 0.68+/-0.16 mg/ml in immobilized joints. Synovial intimal cell UDPGD activity decreased from 18.0+/-2.7 U/cell in control joints to 12.2+/-1.5 after immobilization. There was also a decrease in UDPGD-positive intimal cell numbers. Intimal surfaces in controls contained numerous NSE-positive cells, which were rarely observed in intima from immobilized joints. CONCLUSIONS: These results suggest that immobilization decreases SF HA levels and that this is associated with reduced intimal cell UDPGD activity (essential for HA formation). Immobilization also decreased the prevalence of (NSE-positive) intimal macrophages. These findings suggest that mechanosensitive homeostatic mechanisms exist within the synovial intima. (+info)
Developmental changes in leg coordination of the chick at embryonic days 9, 11, and 13: uncoupling of ankle movements.
(59/2057)
To understand changes in motor behavior during development, kinematic measurements were made of the right leg during embryonic motility in chicks on embryonic (E) days 9, 11, and 13. This is an interesting developmental period during which the embryo first becomes large enough to be physically constrained by the shell. Additionally, sensory systems are incorporated at that time into the spinal motor circuitry. Previous electromyographic (EMG) recordings have shown that the basic pattern of muscle activity seen at E9, composed of half-center-type alternation of extensor and flexor activation, breaks down by E13. This breakdown in organization could be because of disruption of motor patterns by the immature sensory system and/or new spatial constraints on the embryo. The current article describes several changes in leg movement patterns during this period. Episodes of motility increase in duration and the intervals of time between episodes of motility decrease in length. The range of motion of the leg increases, but the overall posture of the leg becomes more flexed. It was found that in-phase coordination of movement among the hip, knee, and ankle decreased between E9 and E13 in agreement with the previous EMG recordings. However, it was also found that the decrease of in-phase coordination among the three joints was accompanied by an increase in the time any two joints were moving in the same manner. Furthermore, examination of in-phase coordination within pairs of joints showed that all three pairs were well coordinated at E9, but that at E13 the in-phase coordination of the ankle with the other two joints decreased, whereas the knee and hip coordination was maintained. This suggests that the hip-knee synergy was closely coupled and that coupling of the ankle with other joints was more labile. The authors conclude that embryos respond to the reduction of free space in the egg during this period not by decreasing the amplitude or coordination of leg movements in general, but instead by differentially controlling the movements of the ankle from those of the hip and knee. Additionally, the changes in movement patterns do not represent a decrease in organization, but rather an alteration of motor coordination possibly as the result of information from the newly acquired sensory systems. These data also support theories that limb central pattern generators (CPGs) are composed of unit CPGs for each joint that can be modulated individually and that this organization is already established early in embryogenesis. (+info)
Motor cortical activity during drawing movements: population representation during spiral tracing.
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Monkeys traced spirals on a planar surface as unitary activity was recorded from either premotor or primary motor cortex. Using the population vector algorithm, the hand's trajectory could be accurately visualized with the cortical activity throughout the task. The time interval between this prediction and the corresponding movement varied linearly with the instantaneous radius of curvature; the prediction interval was longer when the path of the finger was more curved (smaller radius). The intervals in the premotor cortex fell into two groups, whereas those in the primary motor cortex formed a single group. This suggests that the change in prediction interval is a property of a single population in primary motor cortex, with the possibility that this outcome is due to the different properties generated by the simultaneous action of separate subpopulations in premotor cortex. Electromyographic (EMG) activity and joint kinematics were also measured in this task. These parameters varied harmonically throughout the task with many of the same characteristics as those of single cortical cells. Neither the lags between joint-angular velocities and hand velocity nor the lags between EMG and hand velocity could explain the changes in prediction interval between cortical activity and hand velocity. The simple spatial and temporal relationship between cortical activity and finger trajectory suggests that the figural aspects of this task are major components of cortical activity. (+info)
Templates and anchors: neuromechanical hypotheses of legged locomotion on land.
(61/2057)
Locomotion results from complex, high-dimensional, non-linear, dynamically coupled interactions between an organism and its environment. Fortunately, simple models we call templates have been and can be made to resolve the redundancy of multiple legs, joints and muscles by seeking synergies and symmetries. A template is the simplest model (least number of variables and parameters) that exhibits a targeted behavior. For example, diverse species that differ in skeletal type, leg number and posture run in a stable manner like sagittal- and horizontal-plane spring-mass systems. Templates suggest control strategies that can be tested against empirical data. Templates must be grounded in more detailed morphological and physiological models to ask specific questions about multiple legs, the joint torques that actuate them, the recruitment of muscles that produce those torques and the neural networks that activate the ensemble. We term these more elaborate models anchors. They introduce representations of specific biological details whose mechanism of coordination is of interest. Since mechanisms require controls, anchors incorporate specific hypotheses concerning the manner in which unnecessary motion or energy from legs, joints and muscles is removed, leaving behind the behavior of the body in the low-degree-of-freedom template. Locating the origin of control is a challenge because neural and mechanical systems are dynamically coupled and both play a role. The control of slow, variable-frequency locomotion appears to be dominated by the nervous system, whereas during rapid, rhythmic locomotion, the control may reside more within the mechanical system. Anchored templates of many-legged, sprawled-postured animals suggest that passive, dynamic self-stabilization from a feedforward, tuned mechanical system can reject rapid perturbations and simplify control. Future progress would benefit from the creation of a field embracing comparative neuromechanics. (+info)
Stickler syndrome: further mutations in COL11A1 and evidence for additional locus heterogeneity.
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Stickler syndrome (hereditary arthro-ophthalmopathy) is a dominantly inherited connective tissue disorder with ocular, oro-facial, auditory and skeletal manifestations. It is genetically and phenotypically heterogeneous with the majority of families having mutations in the gene encoding type II collagen (COL2A1) and exhibiting a characteristic 'membranous' or type 1 vitreous phenotype. More recently a novel mutation in the gene encoding the alpha1 chain of type XI collagen (COL11A1) was reported in a Stickler syndrome pedigree with a different 'beaded' or type 2 vitreous phenotype. In the present study five more families with the type 2 vitreous phenotype were examined for linkage to four candidate genes: COL2A1, COL5A2, COL11A1 and COL11A2. Two families were linked to COL11A1 and sequencing identified mutations resulting in shortened alphal(XI) collagen chains, one via exon skipping and the other via a multiexon deletion. One of the families showed weak linkage to COL5A2 but sequencing the open reading frame failed to identify a mutation. In the remaining two families all four loci were excluded by linkage analysis. These data confirm that mutations in COL11A1 cause Stickler syndrome with the type2 vitreous phenotype and also reveal further locus heterogeneity. (+info)
Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
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The hallmark of rheumatoid arthritis (RA) is specific destruction of the synovial joints. In a mouse line that spontaneously develops a disorder with many of the features of human RA, disease is initiated by T cell recognition of a ubiquitously expressed self-antigen; once initiated, pathology is driven almost entirely by immunoglobulins. In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme. Thus, some forms of RA or related arthritides may develop by a mechanism fundamentally different from the currently popular paradigm of a joint-specific T cell response. (+info)
Septic arthritis due to Streptococcus pneumoniae in Nottingham, United Kingdom, 1985-1998.
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Pneumonia and meningitis are the 2 most frequent manifestations of Streptococcus neumoniae infection. Pneumococcal septic arthritis is considered to be relatively uncommon. Between 1985 and 1998, 32 (8. 2%) of 389 cases of septic arthritis seen in the 2 hospitals in Nottingham, United Kingdom, were due to S. pneumoniae. Six of 7 children with pneumococcal septic arthritis were aged <2 years. Of the 25 adults, 20 (80%) were aged >60 years, 11 (44%) had concomitant pneumococcal infection elsewhere, and 23 (92%) had articular or nonarticular diseases and/or other risk factors. In the elderly, a lack of febrile response was striking. S. pneumoniae was isolated from blood and joint cultures in >70% of cases, and gram-positive diplococci were seen in the joint fluids of 90% of patients. The mean duration of antimicrobial therapy for adults was twice as long as that for children. Eight (32%) of the adults died. (+info)