Dual inhibition of phosphodiesterase 4 and matrix metalloproteinases by an (arylsulfonyl)hydroxamic acid template.
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3',5'-Cyclic-AMP Phosphodiesterases↗
Biomedical subjects
S M Condon
Publications and source records attributed to S M Condon.
Soleus muscle electromyographic activity and ankle dorsiflexion range of motion during four stretching procedures.
Volitional muscle contractions are used frequently in some combination with muscle stretching to promote muscle relaxation and to increase range of motion. In this study, muscle lengthening procedures were evaluated in the ankle plantar flexors. Four soleus muscle stretching procedures--static stretch (SS), hold relax (HR) (isometric plantar flexor contraction before stretch), agonist contract (AC) (dorsiflexor contraction assisting stretch), and hold relax-agonist contraction (HR-AC)--were performed in the sagittal plane by 12 physically active adults. The dorsiflexion angle, soleus muscle electromyogram, and soleus muscle motoneuron excitability as determined by the Hoffmann-reflex (H-reflex) amplitude were measured throughout the duration of each stretch. The range of dorsiflexion achieved at the end of the stretch did not differ significantly between stretching procedures, although in 8 of the 12 subjects and in the subject group as a whole, the AC and HR-AC procedures were associated with higher levels of soleus muscle EMG than the levels in the SS and HR procedures (p less than .01). The H-reflex amplitudes during the AC and HR-AC procedures were smaller than the amplitudes during the SS and HR procedures (p less than .001), suggesting the possibility of reciprocal inhibition during the agonist contraction. Increased tonic EMG levels produced by input from other neural pathways affecting alpha motoneurons in the AC and HR-AC procedures may have masked this inhibitory reflex. In healthy adults, a complicated procedure, involving muscle contractions for decreasing active resistance to stretch, may be unnecessary because active resistance to stretch is minimal and muscle relaxation during stretch appears to have little or no direct effect on the ROM achieved.
Adult↗
The role of the biomechanics laboratory in the analysis of the gait of individuals with arthritis.
The function of a biomechanics laboratory is to measure those aspects of an individual patient's performance that cannot be quantitatively assessed in the clinical setting. Essential equipment provides the ability to measure gait events, ground reactive forces, kinematics (movement of the body and its segments in 3 dimensions), electromyographic activity, and oxygen consumption. A minicomputer with video screen is required to process the data and allow visual checks of the functioning of the system. Such things as moments around joints and deforming forces may be calculated from the measured variables. Illustrations are given of a schematic laboratory system, computer generated stick diagrams, real-time changes in forces, moment-arms, moments, and excursions, in addition to the alteration of these variables in tibial nerve paralysis and degenerative arthritis of the knee.
Arthritis↗
Gait abnormalities in hemiplegia: their correction by ankle-foot orthoses.
Hemiparetic gait is characterized by slow speed and poorly coordinated movements. Because the values of gait parameters vary with changes in speed, the slow speed that is typical of hemiparetic gait necessitates applying controls for the influence of speed when comparing hemiparetic and able-bodied persons. Gait kinetics and kinematics were measured in seven hemiparetic and seven able-bodied adults to compare their gait patterns at similar speeds and to assess the effectiveness of ankle-foot orthoses which were double-stopped in 5 degrees of dorsiflexion or 5 degrees of plantarflexion. Hemiparetic persons ambulating without the orthoses had a shorter step length, longer duration stance, and shorter duration swing than normal. They displayed greater than normal flexion of the affected hip during midstance, which, by putting the center of mass farther in front of the knee, may explain the increased knee extension moment due to vertical force. Affected hip adduction during single support was less in hemiparetic persons than in able-bodied persons, indicating a decreased lateral shift to the paretic side. During the swing phase, the affected limbs of hemiparetic persons were in less knee flexion and less dorsiflexion than normal, necessitating circumduction to achieve toe clearance. Ankle-foot orthoses increased walking speed to normalize heelstrike duration through use of an optimally adjusted plantarflexion stop. An improperly adjusted orthosis may produce an exaggerated knee flexion moment resulting in knee instability.
Aged↗
Gait abnormalities in peroneal nerve paralysis and their corrections by orthoses: a biomechanical study.
Stroke, brain injury, incomplete spinal cord injuries, and peripheral neuropathies frequently result in dysfunction of the foot dorsiflexors and evertors. A controlled examination of aspects of these disabilities was conducted with normal volunteers who underwent a temporary peroneal nerve block. The effects of peroneal nerve paralysis were analyzed to quantitatively describe the resulting gait abnormalities and to assess the effectiveness of orthoses in restoring a normal gait pattern. Kinematic and kinetic measurements were made during normal ambulation, ambulation with a right peroneal nerve paralysis, and ambulation with a paralysis and an ankle-foot orthosis (AFO) with three different adjustments: a posterior stop set in 5 degrees plantarflexion, a posterior stop set in 5 degrees dorsiflexion, and spring-assisted dorsiflexion. The peroneal paralysis produced abnormalities during both the stance and swing phases of gait. During early stance there was a decrease in the length of the heelstrike phase and a reduction in the peak plantarflexion moment (p less than 0.01). During midstance there was an increase in the range of inversion-eversion achieved suggesting medial-lateral instability (p less than 0.01). The second vertical force peak and the aft-shear force peak were reduced (p less than 0.05) as were the peak dorsiflexion moment and the opposite steplength (p less than 0.01). These reductions are believed to be due to medial-lateral instability during pushoff. Subjects demonstrated a steppage gait during swing phase and increased inversion just prior to heelstrike (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Ankle-foot orthoses: effect on gait abnormalities in tibial nerve paralysis.
To study the biomechanical effects of gastrocnemius-soleus dysfunction and its potential remediation, the gait patterns of six able-bodied young adults were analyzed before and after induced temporary tibial nerve paralysis. Ambulation with the tibial nerve block was performed with and without the assistance of an ankle-foot orthosis (AFO) with a rigid anterior stop adjusted to either 5 degrees plantarflexion or 5 degrees dorsiflexion. The gait abnormalities resulting from tibial nerve paralysis include delayed advancement of the center of pressure, delayed ipsilateral heeloff and early contralateral heelstrike, decreased steplength, decreased ankle dorsiflexion moment, and increased knee flexion moment. This study provides quantitative information on the degree to which these abnormalities were corrected by appropriately adjusted AFOs. When using an AFO with an anterior stop, subjects with tibial nerve paralysis had improved advancement of the center of pressure (p less than 0.01). The body's ground reactive force line moved forward more normally, pivoting over the metatarsal head area and raising the heel earlier than observed with uncorrected tibial nerve paralysis, thus approximating the normal ankle dorsiflexion moment, normal timing of gait events, normal advancement of the hip, and normal steplength. The AFO with the anterior stop set at 5 degrees plantarflexion was more effective in restoring the values to normal than the AFO with the anterior stop set at 5 degrees dorsiflexion, but still did not consistently achieve the normal values. Only by using the AFO with the anterior stop set at 5 degrees plantarflexion was the increased knee flexion moment observed during the block reduced to normal levels (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cognitive spatial processing and the regulation of posture.
Subjects performed the Brooks (1967) spatial and nonspatial memory tasks either while sitting or while maintaining a difficult standing balance position. The balance task disrupted spatial but not nonspatial memory performance. Balance steadiness during spatial and nonspatial memory conditions did not differ. These results suggest that cognitive spatial processing may rely on neural mechanisms that are also required for the regulation of posture.
Adult↗
Gait abnormalities in tibial nerve paralysis: a biomechanical study.
Gastrocnemius-soleus dysfunction is a frequent result of cauda equina lesions and peripheral neurophathies and of stroke and brain injury. Temporary tibial nerve paralysis constitutes a comparable laboratory condition which allows the controlled examination of aspects of these disabilities. The biomechanical effects of temporary tibial nerve paralysis in six normal young adult volunteers were examined to quantitatively define the gait abnormalities resulting from gastrocnemius-soleus paralysis and to provide a basis for the assessment of the effectiveness of different orthotic designs in restoring a normal gait pattern. The motion of the right lower extremity, ground reactive forces acting on the right lower extremity, timing of gait events and step length were recorded, first during normal ambulation and then during ambulation after a right tibial nerve block. Step length was reduced bilaterally after the nerve block (p less than 0.005); the reduction was greater for the left (unblocked) step than for the right (blocked) step (p less than 0.005). Right heeloff was delayed until the time of left heelstrike in all subjects after the right tibial block. Right heeloff occurred later (p less than 0.005) while left heelstrike occurred earlier than normal (p less than 0.005). The shorter left step length and earlier left heelstrike resulted from a reduction in the forward progression of the right hip (p less than 0.001). When subjects were deprived of the plantarflexion activity necessary to counteract dorsiflexion moments at the ankle, they delayed the forward progression of the center of pressure (p less than 0.001) to avoid the unstable collapse of the foot into dorsiflexion.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Can Ib axons be selectively activated by electrical stimuli in human subjects?
A tendon-vibration technique, used to raise the electrical threshold of muscle spindle Ia afferent fibers above that of Golgi tendon organ Ib afferent fibers in animals, was tested on human subjects. After prolonged tendon vibration, electrical stimulation of the posterior tibial nerve was ineffective or markedly less effective in eliciting Hoffmann (H-) reflexes in the soleus muscle at previbration threshold intensities. With stimulus intensity held constant at values between 1.0 to 1.4 X threshold, postvibration H-reflex myoelectric amplitudes returned to previbration values usually within 60 min. However, at higher electrical stimulus intensities (1.8 X threshold), postvibration H-reflex amplitudes were produced at or near previbration values irrespective of postvibration recovery time; in contrast, initial postvibration tendon tap reflexes were potentiated. Findings suggest that it is indeed possible to selectively activate Ib afferent fibers in humans by electrical stimuli.
Achilles Tendon↗
Purification and properties of retinol- and retinoic acid-binding proteins from a transplantable mouse colon tumor.
Cellular retinol-binding protein and retinoic acid-binding protein, the possible mediators of the action of retinoids in epithelial differentiation and control of tumorigenesis, have been reproducibly purified from mouse colon tumor 26, and some of their properties were studied. The main steps of purification involved acid-precipitation, DEAE-Sephadex, CM-cellulose and Sephadex G-100 chromatography. About 2 mg of the binding proteins were isolated from 60 g tumor. The purified preparations showed only two protein bands on polyacrylamide gel electrophoresis. The two binding proteins were partially resolved by sedimentation equilibrium technique; but was completely separable by preparative electrophoresis in the presence of sodium dodecyl sulfate. The retinol- and retinoic acid-binding proteins are presumably monomers with molecular weights of 15,500 and 14,600, respectively, as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. On gel filtration however, both the binding proteins retarded to the same molecular size of 17,800. On preparative columns, both the proteins expressed the same isoelectric pH, 4.5. Both proteins of the tumor possessed functional thiol groups. The mercurial inhibition of the binding capacity of the proteins for their ligands was reversible upon treatment with thiol compounds.
Animals↗
Retinoic acid-binding protein in experimental and human colon tumors.
Retinoic acid-binding protein is present in metastatic murine colon tumors as well as in Lewis lung tumors and in lungs and brains of mice bearing these tumors; however, this protein is below the limits of detection in weakly-metastatic carcinomas and in normal lung, colon, or brains. These observations are interesting since they concern the possibility of measuring the binding protein levels of colon tumors in clinical specimens as biochemical markers in human malignancy. A total of thirty-three human colon tumors and related materials were analyzed for the presence of the binding protein. The interfering serum albumin, which nonspecifically binds retinoic acid, was eliminated by affinity chromatography. Of the twenty colon, cecum, and rectum tumors analyzed, 80% contained the binding protein in detectable amounts, and 20% showed nondetectable or marginally detectable amounts. Twenty-two percent of the human colon segments isolated from patients suspected for colon tumors contained the binding protein in readily detectable amounts, whereas 78% revealed nondetectable to marginally detectable amounts. The retinoic acid-binding protein of human colon tumor shared the same ligand specificity, thiol functions in ligand-binding, and sedimentation coefficient as the binding protein isolated from chick embryo skin. However, the human protein exhibited altered isoelectric pH.
Adenocarcinoma↗