Specific T-cell factor production and lymphocytes in the direct surroundings of a subcutaneous allogeneic tumor.

Antigen-specific T-cell factors (TCF) play a role in the initiation of cellular immune responses. In allogeneic mouse-tumor models lymphocytes from the direct tumor surroundings of both euthymic and nude mice produce TCF. These lymphocytes produce TCF when collected already 1 day after subcutaneous (sc) injection of tumor cells. In contrast to euthymic mice, draining lymph nodes and spleen of nude mice did not contain TCF-producing lymphocytes at any stage after sc tumor cell injection. In sensitized euthymic mice TCF production by lymphocytes is significantly higher in the direct tumor surroundings than in draining lymph nodes or spleen. At 2 and 5 days after tumor cell injection, the mononuclear cell infiltrate of the tissue surrounding the tumor in euthymic mice showed low expression of Thy 1, CD3, TCR alpha beta, TCR gamma delta, CD4, CD8, and asialo GM1, whereas several lymphocytes and mast cells were positive for monoclonal antibody (mAb) 14-30 (directed against TCF). In both euthymic and nude mice, sc injected tumor cells showed apoptosis. In conclusion, the direct tumor surroundings are the first (and, for nude mice, the only) site of TCF production, sc injection of tumor cells attracts mAb 14-30-positive lymphocytes and renders mast cells positive for mAb 14-30.     

Multi-segment foot kinematics and ground reaction forces during gait of individuals with plantar fasciitis

Background

Clinically, plantar fasciitis (PF) is believed to be a result and/or prolonged by overpronation and excessive loading, but there is little biomechanical data to support this assertion. The purpose of this study was to determine the differences between healthy individuals and those with PF in (1) rearfoot motion, (2) medial forefoot motion, (3) first metatarsal phalangeal joint (FMPJ) motion, and (4) ground reaction forces (GRF).

Methods

We recruited healthy (n=22) and chronic PF individuals (n=22, symptomatic over three months) of similar age, height, weight, and foot shape (p>0.05). Retro-reflective skin markers were fixed according to a multi-segment foot and shank model. Ground reaction forces and three dimensional kinematics of the shank, rearfoot, medial forefoot, and hallux segment were captured as individuals walked at 1.35 ms⁻¹.

Results

Despite similarities in foot anthropometrics, when compared to healthy individuals, individuals with PF exhibited significantly (p<0.05) (1) greater total rearfoot eversion, (2) greater forefoot plantar flexion at initial contact, (3) greater total sagittal plane forefoot motion, (4) greater maximum FMPJ dorsiflexion, and (5) decreased vertical GRF during propulsion.

Conclusion

These data suggest that compared to healthy individuals, individuals with PF exhibit significant differences in foot kinematics and kinetics. Consistent with the theoretical injury mechanisms of PF, we found these individuals to have greater total rearfoot eversion and peak FMPJ dorsiflexion, which may put undue loads on the plantar fascia. Meanwhile, increased medial forefoot plantar flexion at initial contact and decreased propulsive GRF are suggestive of compensatory responses, perhaps to manage pain.     

Limitations in the use and interpretation of continuous relative phase

Continuous relative phase (CRP), a variable used to quantify intersegmental coordination, is difficult to interpret if care is not taken regarding the assumptions and limitations of the measure. Specifically, CRP is often interpreted as a higher resolution form of discrete relative phase (DRP). DRP, however, yields information regarding the relative dispersion of events in oscillatory signals while CRP describes their relationship in a higher order phase-plane domain. In this paper we address issues surrounding the calculation of CRP and suggest a new interpretation based on the aforementioned methodological issues. Through the use of test signals, with known properties, it was found that the CRP information will be arbitrary if no normalization procedures are used to account for frequency differences in the component oscillators. In addition, signals with non-sinusoidal trajectories will produce patterns in CRP that are not equivalent to discrete relative phase (DRP) measures. The implications of these issues are discussed.     

Influence of custom foot orthotic intervention on lower extremity intralimb coupling during a 30-minute run

The purpose of this study was to analyze the influence of a custom foot orthotic (CFO) intervention on lower extremity intralimb coupling during a 30-min run in a group of injured runners and to compare the results to a control group of healthy runners. Three-dimensional kinematic data were collected during a 30-min run on healthy female runners (Shoe-only) and a group of female runners who had a recent history of overuse injury (Shoe-only and Shoe with custom foot orthoses). Results from the study revealed that the coordination variability and pattern for the some couplings were influenced by history of injury, foot orthotic intervention and the duration of the run. These data suggest that custom foot orthoses worn by injured runners may play a role in the maintenance of coordination variability of the tibia (transverse plane) and calcaneus (frontal plane) coupling during the Early Stance phase. In addition, it appears that the coupling angle between the knee (transverse plane) and rearfoot (frontal plane) joints becomes more symmetrical in the late stance phase as a run progresses.     

Evaluation of time-to-contact measures for assessing postural stability

Postural stability has traditionally been examined through spatial measures of the center of mass (CoM) or center of pressure (CoP), where larger amounts of CoM or CoP movements are considered signs of postural instability. However, for stabilization, the postural control system may utilize additional information about the CoM or CoP such as velocity, acceleration, and the temporal margin to a stability boundary. Postural time-to-contact (TtC) is a variable that can take into account this additional information about the CoM or CoP. Postural TtC is the time it would take the CoM or CoP, given its instantaneous trajectory, to contact a stability boundary. This is essentially the time the system has to reverse any perturbation before stance is threatened. Although this measure shows promise in assessing postural stability, the TtC values derived between studies are highly ambiguous due to major differences in how they are calculated. In this study, various methodologies used to assess postural TtC were compared during quiet stance and induced-sway conditions. The effects of the different methodologies on TtC values will be assessed, and issues regarding the interpretation of TtC data will also be discussed.     

Predicting dynamic postural instability using center of mass time-to-contact information

Our purpose was to determine whether spatiotemporal measures of center of mass motion relative to the base of support boundary could predict stepping strategies after upper-body postural perturbations in humans. We expected that inclusion of center of mass acceleration in such time-to-contact (TtC) calculations would give better predictions and more advanced warning of perturbation severity. TtC measures were compared with traditional postural variables, which do not consider support boundaries, and with an inverted pendulum model of dynamic stability developed by Hof et al. [2005. The condition for dynamic stability. Journal of Biomechanics 38, 1-8]. A pendulum was used to deliver sequentially increasing perturbations to 10 young adults, who were strapped to a wooden backboard that constrained motion to sagittal-plane rotation about the ankle joint. Subjects were instructed to resist the perturbations, stepping only if necessary to prevent a fall. Peak center of mass and center of pressure velocity and acceleration demonstrated linear increases with postural challenge. In contrast, boundary-relevant minimum TtC values decreased nonlinearly with postural challenge, enabling prediction of stepping responses using quadratic equations. When TtC calculations incorporated center of mass acceleration, the quadratic fits were better and gave more accurate predictions of the TtC values that would trigger stepping responses. In addition, TtC minima occurred earlier with acceleration inclusion, giving more advanced warning of perturbation severity. Our results were in agreement with TtC predictions based on Hof's model, and suggest that TtC may function as a control parameter, influencing the postural control system's decision to transition from a stationary base of support to a stepping strategy.     

Resonant frequencies of arms and legs identify different walking patterns

The present study is aimed at investigating changes in the coordination of arm and leg movements in young healthy subjects. It was hypothesized that with changes in walking velocity there is a change in frequency and phase coupling between the arms and the legs. In addition, it was hypothesized that the preferred frequencies of the different coordination patterns can be predicted on the basis of the resonant frequencies of arms and legs with a simple pendulum model. The kinematics of arms and legs during treadmill walking in seven healthy subjects were recorded with accelerometers in the sagittal plane at a wide range of different velocities (i.e., 0.3-1. 3m/s). Power spectral analyses revealed a statistically significant change in the frequency relation between arms and legs, i.e., within the velocity range 0.3-0.7m/s arm movement frequencies were dominantly synchronized with the step frequency, whereas from 0.8m/s onwards arm frequencies were locked onto stride frequency. Significant effects of walking speed on mean relative phase between leg and arm movements were found. All limb pairs showed a significantly more stable coordination pattern from 0.8 to 1.0m/s onwards. Results from the pendulum modelling demonstrated that for most subjects at low-velocity preferred movement frequencies of the arms are predicted by the resonant frequencies of individual arms (about 0.98Hz), whereas at higher velocities these are predicted on the basis of the resonant frequencies of the individual legs (about 0.85Hz). The results support the above-mentioned hypotheses, and suggest that different patterns of coordination, as shown by changes in frequency coupling and phase relations, can exist within the human walking mode.     

Quantifying rearfoot-forefoot coordination in human walking

A method is proposed to facilitate the quantification and interpretation of inter-joint/-segment coordination. This technique is illustrated using rearfoot-forefoot kinematic data. We expand existing vector coding techniques and introduce a set of operational terms through which the coordinative patterns between the rearfoot segment and the forefoot segment are summarized: in-phase, anti-phase, rearfoot phase and forefoot phase. The literature on foot mechanics has characterized the stable foot at pushoff by a decreasing medial longitudinal arch angle in the sagittal plane, which is accompanied by forefoot pronation and concurrent rearfoot supination-in other words, anti-phase motion. Nine skin markers were placed on the rearfoot and forefoot segments according to a multi-segment foot model. Three healthy subjects performed standing calibration and walking trials (1.35ms(-1)), while a three-dimensional motion capture system acquired their kinematics. Rearfoot-forefoot joint angles were derived and the arch angle was inferred from the sagittal plane. Coupling angles of rearfoot and forefoot segments were derived and categorized into one of the four coordination patterns. Arch kinematics were consistent with the literature; in stance, the arch angle reached peak dorsiflexion, and then decreased rapidly. However, anti-phase coordination was not the predominant pattern during mid- or late stance. These preliminary data suggest that the coordinative interactions between the rearfoot and the forefoot are more complicated than previously described. The technique offers a new perspective on coordination and may provide insight into deformations of underlying tissues, such as the plantar fascia.     

Variability in kinematic coupling assessed by vector coding and continuous relative phase

Variability in the spatio-temporal coordination of human movement kinematics is often assessed by vector coding and continuous relative phase (CRP). To facilitate appropriate comparisons between the findings of studies that have used different techniques to assess variability, the purposes of this study were: (1) to determine if both vector coding and CRP behave according to dynamical systems theories on variability and state space transitions; and (2) to determine if trends in coordination variability during movement are consistent when using either vector coding or CRP. We present both a theoretical case (the Lorenz Attractor) and two experimental cases (rearfoot–forefoot coupling during overground walking for 22 subjects; the effect of treadmill speed on thigh-leg coupling for five subjects). In the theoretical case, variability quantified by CRP agreed with dynamical systems theory on state space transitions more so than variability quantified by vector coding. In experimental cases, this distinction was less clear, although CRP appeared to be a more conservative metric for variability. The magnitudes (all p<0.001) and timings (all p<0.04) of peaks in variability during the stance phase of overground walking depended on whether vector coding or CRP was used for two couplings. Similar distinctions were observed for peaks during the stride cycle of treadmill locomotion (all effect sizes >2.8). However, changes in the average variability during the stride cycle as speed increased were consistent for both methods (all effect sizes <0.2). The results suggest that comparisons between the findings of studies that have quantified variability using CRP and those that have used vector coding should be made with caution.