Effects of passive limb movement on pulmonary ventilation

This study was undertaken to determine if the observed increase in ventilation during passive limb movement was a reflex hyperventilation or a response to an increased metabolic need for oxygen. Experiments on human volunteers were designed to test the hypothesis that the rapid increase of ventilation at the onset of exercise was due to stimulation of the joints. Results of these studies showed significant increases in ventilation, oxygen consumption, carbon dioxide production, ventilation/oxygen consumption ratio, and heart rate compared to rest and recovery values. The data lead to the conclusion that the rapid increase of ventilation at the onset of exercise is a true hyperventilation and that stimulation of the joints can be a significant contributor to increased pulmonary ventilation.     

Polydactyly in the Strong's luxoid mouse is suppressed by limb deformity alleles

The study of limb development has provided insight into pattern formation during vertebrate embryogenesis. Genetic approaches offer powerful ways to identify the critical molecules and their pathways of action required to execute a complex morphogenetic program. We have applied genetic analysis to the process of limb development by studying two mouse mutants, limb deformity (Id) and Strong's luxoid (Ist). These mutations confer contrasting phenotypic alterations to the anteroposterior limb pattern. The six mutant Id alleles are fully recessive and result in oligosyndactyly of all four limbs. By contrast, the two mutant Ist alleles result in a mirror-image polydactylous limb phenotype inherited in a semidominant fashion. Morphological and molecular analysis of embryonic limbs has shown that the Id and Ist alleles affect the extent and distribution of two key signaling centers differentially: the apical ectodermal ridge and the zone of polarizing activity. Molecular characterization of the Id gene has defined a new family of evolutionarily conserved proteins termed the formins. The underlying molecular defect in the Ist mutation has not been identified; however, both loci are tightly linked on mouse chromosome 2, suggesting the possibility that they may be allelic. In this study, we have used genetic analysis to examine the epistatic and allelic relationships of Id and Ist. We observed that in + Id/Ist + double heterozygotes, a single mutant Id allele is able to suppress the semi-dominant polydactylous Ist limb phenotype. By segregating the Ist and Id loci in a backcross, we observed that these loci recombine and are separated by a genetic distance of approximately 6 cM. Therefore, while our observations demonstrate a genetic interaction between Id and Ist, it is probable that Id and Ist are not allelic. Instead, Ist and Id may be operating either in a linear or in a parallel (bypass) genetic pathway to affect the limb signaling centers. © 1996 Wiley-Liss, Inc.     

Motor variability during a repetitive lifting task is impaired by wearing a passive back-support exoskeleton

PurposeEvaluate whether wearing a passive back-support exoskeleton during repetitive lifting impairs motor variability of erector spinae muscle and spine movement and whether this association is influenced by lifting style.Scope: Thirty-six healthy males performed ten lifts in four randomized conditions with exoskeleton (without, with) and lifting style (squat, stoop) as dependent variables. One lifting cycle contained four phases: bending/straighten without/with load. Erector spinae muscular activity, thoracic kyphosis and lumbar lordosis were measured with surface electromyography and gravimetric position sensors, respectively. Absolute and relative cycle-to-cycle variability were calculated. The effects of exoskeleton and exoskeleton × lifting style were assessed on outcomes during the complete lifting cycle and its four phases.ResultsFor the complete lifting cycle, muscular variability and thoracic kyphosis variability decreased whereas lumbar lordosis variability increased with exoskeleton. For lifting phases, effects of exoskeleton were mixed. Absolute and relative muscular variability showed a significant interaction effect for the phase straighten with load; variability decreased with exoskeleton during squat lifting.ConclusionUsing the exoskeleton impaired several motor variability parameters during lifting, supporting previous findings that exoskeletons may limit freedom of movement. The impact of this result on longer-term development of muscular fatigue or musculoskeletal disorders cannot yet be estimated.     

Central and peripheral hemodynamic responses to passive limb movement: the role of arousal

The exact role of arousal in central and peripheral hemodynamic responses to passive limb movement in humans is unclear but has been proposed as a potential contributor. Thus, we used a human model with no lower limb afferent feedback to determine the role of arousal on the hemodynamic response to passive leg movement. In nine people with a spinal cord injury, we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback (M+VF and M-VF, respectively) as well as in a third trial with no movement or visual feedback but the perception of movement (F). Ventilation (Ve), heart rate, stroke volume, cardiac output, mean arterial pressure, and leg blood flow (LBF) were evaluated during the three protocols. Ve increased rapidly from baseline in M+VF (55 ± 11%), M-VF (63 ± 13%), and F (48 ± 12%) trials. Central hemodynamics (heart rate, stroke volume, cardiac output, and mean arterial pressure) were unchanged in all trials. LBF increased from baseline by 126 ± 18 ml/min in the M+VF protocol and 109 ± 23 ml/min in the M-VF protocol but was unchanged in the F protocol. Therefore, with the use of model that is devoid of afferent feedback from the legs, the results of this study reveal that, although arousal is invoked by passive movement or the thought of passive movement, as evidenced by the increase in Ve, there is no central or peripheral hemodynamic impact of this increased neural activity. Additionally, this study revealed that a central hemodynamic response is not an obligatory component of movement-induced LBF.     

Ventilatory response to phasic contraction and passive movement in graded anesthesia

The ventilatory response to electrically induced contraction (EIC) and passive movement (PM) of hindlimb muscles at different levels of anesthesia was studied in 11 chloralose-urethan anesthetized dogs with and without rhizotomy. The level of anesthesia was assessed by corneal reflexes and measurements of the ventilatory response to hypercapnia. Muscle contraction was induced by electrically stimulating the peripheral cut ends of the sciatic and femoral nerves for 4-5 min, and PM was induced manually at the same frequency and amplitude as during EIC. In spinal intact dogs (n = 7), initial rapid increases in minute ventilation (VE) during EIC and PM were found in both light and deep anesthesia. Further increases in VE above the initial rise were seen during EIC but not PM. The initial rapid increases in VE did not differ between the two anesthetic levels. The steady-state ventilatory response during EIC decreased as anesthesia deepened but did not do so during PM. Rhizotomy (n = 4) abolished the initial rapid increase in VE during EIC and PM and the steady-state VE response to PM at both anesthetic levels. These results suggest that the transitional ventilatory response is neurally mediated from the muscles and not affected by the level of general anesthesia. Additionally, the anesthesia-induced reduction of ventilatory response may be due to depression of responsiveness to CO2 rather than to the inspiratory motoneuron pathway.     

Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion

Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6 h that was sustained throughout the 21 day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7 days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7 day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies.     

The proliferative response of human lymphocytes to antigen is suppressed preferentially by lymphocytes precultured with the same antigen.

Human blood lymphocytes activated in vitro with antigen to which the donor is reactive are capable of suppressing the secondary proliferative response of autochthonous fresh cells to antigen. Both antigen-specific and antigen-nonspecific suppression can be detected in each experiment. These suppressor cells act by decreasing the number of lymphocytes entering the proliferative response rather than by slowing or otherwise inhibiting ongoing proliferation. The suppressor cells must be added soon after fresh cells are stimulated with antigen to be effective, but the suppressor cells themselves need not proliferate to exert their effect. Suppressor cells are optimally effective when added in numbers equal to those of the responding population, but still exert a significant effect at one-eighth that number.     

Termination of upper limb movement by cutaneous afferents.

We tested whether cutaneous afferents from the skin field close to an upper limb muscular region would carry information to spinal neurons at the onset or at the offset of a voluntary elbow extension movement lasting 1 s. We detected a depression of EMG activity both at onset and at the offset of the reaching movement but in the latter case depression was significantly larger and immediate. The marked depression of EMG activity suggests an inhibition, via spinal neurons, of the descending excitation to the motoneurones supplying the triceps brachii. This spinal control might be a very efficient mechanism for the termination of voluntary movement.     

Relaxation as a cognitive task

In the present experiment the instruction to relax was given to awake highly (Highs) and non hypnotizable subjects (Lows), while their heart rate, respirogram and skin resistance were recorded together with electroencephalogram, electroculogram and corrugator electromiogram. At the beginning of the experiment, Highs exhibited no significant difference in heart rate (HR), respiratory frequency (RF) and heart rate variability (HRV) with respect to Lows, but showed a higher EEG alpha and theta1 power. During the session, both groups decreased their heart rate, but changes were significant only in Lows, which increased significantly also the parasympathetic component of their HRV (high frequency, HF). In both groups, EEG showed alpha, beta2 and theta2 power decrements; theta1 activity decreased only in Lows, while gamma power increased in Highs and decreased in Lows. Results suggest that Highs and Lows used different cognitive strategies in the elaboration of the relaxation request and that Highs performed the task through a higher integrative activity.     

Splanchnic hemodynamic response to passive hyperventilation.

Two groups of anesthetized, splenectomized, and paralyzed dogs were hyperventilated (Vt 40 ml/kg). Normocapnia was maintained in one group (mean Paco2 37.6 mm"h'g, mean p"h '7.41) and respiratory alkalosis (mean Paco2 8 mmHg, mean pH 7.75) in the other. Splanchnic hemodynamic responses were similar in both groups. Average hepatic venous pressure increased from 3.2 to 6.4 mmHg in the normocapnic group and from 3.8 to 7.7 mmHg in the hypocapnic group. Average portal venous pressure increased from 10.7 to 12.0 mmHg and 10.8 to 12.7 mmHg in the normocapnic and hypocapnic groups, respectively. Mesenteric vascular resistance increased in 93 per cent of dogs. A decrease in functional intestinal capillary surface area during hyperventilation was indicated by a significant reduction in mesenteric Vo2 (from 15 to 11 ml/min, average 30 per cent), and a concomitant reduction in mesenteric O2 extraction ratio. Changes in mesenteric Vo2 were reflected in calculated splanchinic Vo2. Hepatic O2 uptake was essentially unchanged by tidal hyperventilation with or without hypocapnia.     

Export defect adjacent to the processing site of staphylococcal nuclease is suppressed by a prlA mutation.

Plasmids have been constructed in which the Escherichia coli alkaline phosphatase promoter and signal sequence have been fused to the staphylococcal nuclease gene to promote the high-level expression and secretion of this gene product in E. coli. We determined that the first amino acid residue after the signal sequence can determine whether this protein was processed and exported to the periplasmic space. Fractionation and protease accessibility studies were used to show that the export-defective, nuclease precursor is internal to the cytoplasmic membrane barrier of the cell. Furthermore, this export defect was suppressed in a strain containing a prlA mutation. These findings are novel in that this region of the polypeptide chain has been implicated in processing but not export and that prlA mutations have not been previously known to suppress such defects.     

Mast cell-mediated allergic response is suppressed by Sophorae flos: inhibition of SRC-family kinase

Complementary and alternative medicines are considered as a promising direction for the development of anti-allergic therapies in oriental countries. We screened approximately 100 oriental herbal medicines for anti-allergic activity. Sophorae flos exhibited the most potent effect on degranulation in antigen-stimulated mast cells. We further investigated the effect of Sophorae flos on the IgE-mediated allergic response in vivo and its mechanism of action in mast cells. Sophorae flos exhibited a significant inhibitory effect on degranulation in antigen-stimulated mast cells with IC(50) values of approximately 31.6 microg/mL (RBL-2H3 mast cells) and approximately 47.8 microg/mL (bone marrow-derived mast cells). Sophorae flos also suppressed the expression and secretion of TNF-alpha and IL-4 in the cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Sophorae flos inhibited the activating phosphorylation of Syk and LAT in mast cells. Further downstream, activating phosphorylation of Akt and the prototypic MAP kinases, namely, p38, ERK1/2, and JNK, were also inhibited. These results suggest that Sophorae flos inhibits the Src family kinase-dependent signaling cascades in mast cells and may thus exert anti-allergic activity.     

The contact-mediated response of peripheral-blood monocytes to preactivated T cells is suppressed by serum factors in rheumatoid arthritis

Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the excessive TNF-α production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-α production by peripheral-blood monocytes in vitro was investigated and found to be significantly lower in treated and untreated patients with RA than in healthy controls. This suppression was not due to a general deficiency of monocytes to respond, because responses to lipopolysaccharide were comparable in patients and controls. In agreement with the pivotal role of TNF-α in RA, T cell-dependent induction of TNF-α in synovial macrophages was fivefold to tenfold higher than in peripheral-blood monocytes from either patients or controls. The decreased response of peripheral-blood monocytes from patients with RA was found to be mediated by inhibitory serum factors, because the addition of patient sera to monocytes from healthy controls suppressed TNF-α response in the co-culture assay. Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-α response in T cell co-cultures, indicating that inhibitory factors do indeed bind to monocyte surfaces, which might represent a regulatory counter-action of the immune system to the long-standing and consuming autoimmune process in RA. There are some indications that apolipoprotein A-1 might be part of this regulatory system.     

Lateral facilitation of Hoffmann-reflexes prior to voluntary movement in a choice reaction time task.

Hoffmann reflexes (H reflexes) were elicited from both legs simultaneously in human subjects at varying intervals after a reaction signal (RS) in a binary choice reaction time task. A left light RS required a rapid plantar flexion of the left foot and a right light RS required a similar rapid response of the right foot. A large faciliataion of reflex amplitude occurred only in the muscle involved in the movement (right of left soleus). The timing of the facilitation indicated that a decision about the status of the RS occurred within 200 msec and probably was completed somewhat earlier. Furthermore, the facilitation of the H reflexes was shown to be closely linked with the organization required for the contractions of the responding muscle. The results are considered in the light of hypothesized mechanisms regulating voluntary movement.     

The validity and reliability of surface EMG to assess the neuromuscular response of the abdominal muscles to rapid limb movement.

The transversus abdominus muscle (TrA) has been demonstrated to be active prior to rapid movements of the upper and lower limbs. This activity is termed feed forward motivation. The lack of feed-forward activation for TrA has been demonstrated in subjects with low back pain. The measures used for investigation of TrA function have been fine-wire needle EMG. This limits the practical application of TrA study due to the cost and level of specialisation required for this technique. The objective of the current study was to investigate the validity and reliability of using a surface EMG site to replicate the findings for the feed-forward activation of TrA prior to rapid limb movement. A population of healthy, young males (n = 20) were studied and it was found that four of the subjects did not meet feed-forward criteria. These results were shown to be highly reliable after a 2-week period for the TrA/IO site only. The validity of the signal was further investigated using several functional tasks to specifically target muscles of the abdominal region. Using a cross-correlation analysis to evaluate crosstalk from adjacent muscles, it was concluded that the signal representing TrA/IO accurately demonstrates the functional activity of the muscle. This study has demonstrated a viable surface EMG method to evaluate the feed-forward activation of TrA/IO prior to rapid limb movement. This may lead to opportunities for the clinical application of this method. It was also a finding of this study that four asymptomatic subjects did not pre-activate, therefore providing a rationale for future prospective investigations on whether the lack of TrA/IO feed-forward activation is a cause or an effect of low back pain.