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Biomedical subjects

M J Cohen

Publications and source records attributed to M J Cohen.

At least 91 records · Page 5Linked to original sources

Extensive dendritic sprouting induced by close axotomy of central neurons in the lamprey.

Massive dendritic sprouting was induced in identified giant reticulospinal neurons of the lamprey by axotomy close to the soma. An axonal lesion slightly farther from the cell body induced new growth from both dendrites and axon. The amount of new growth per cell was the same whether it originated from the dendrites alone or from axonal and dendritic compartments. The location of the axonal lesion therefore determines where, in the neuron, membrane is inserted to produce the new neurites. The dendritic tree of a differentiated vertebrate central neuron was shown to have sufficient plasticity to extend new growth for several millimeters beyond the normal dendritic domain.

Animals↗

Group outpatient physical and behavioral therapy for chronic low back pain.

Conducted a treatment-outcome study to investigate the effectiveness of behavioral (BT) or physical therapy (PT) for treating chronic low back pain (CLBP). Thirteen patients received BT; 12 patients received PT. All patients had at least a 6-month history of seeking treatment of CLBP. Prior to treatment patients were assessed in four principal areas of functioning: (1) physical abilities; (2) current physical functioning; (3) psychological and psychosocial functioning; and (4) pain intensity and pain perception. Treatments were conducted in a group (5-8 patients) outpatient setting. Both BT and PT met for 10 weekly 2-hour sessions. BT was designed to address the environmental, social, and emotional influences of the pain experience, depression, and decreased activity from CLBP. PT was based upon traditional rehabilitation theory and was designed to improve low back function. The posttreatment results showed general improvement for patients in both groups, but few treatment-specific differences in outcome measures.

Adaptation, Psychological↗

Frequency of MMPI profile types in three chronic illness populations.

Clinical interpretation of the MMPI most often utilizes configural or profile analysis. However, most MMPI research has focused only on single scale comparisons. In this study sorting rules to identify four common MMPI configurations were developed and applied to four S populations (N = 157): Chronic low back pain patients, migraine headache patients, hypertensives, and diabetics. No differences in frequencies of these profile types were found among the groups, although the chronic low back pain patients did have more elevated profiles. Variables of age, chronicity of illness and gender did not seem to influence profile type, while some differences were found between patients who rated themselves high and low in activity limitation due to the illness.

Adult↗

Regeneration of an identified central neuron in the cricket. II. Electrical and morphological responses of the soma.

The cell body of the medial giant interneuron (MGI) in the cricket normally does not spike in response to injected depolarizing currents. When axotomized 1 mm or more from the cell body (distant axotomy), the membrane properties of the soma remain unchanged. However, after axotomy close to the cell body (200 to 500 micron), the soma membrane becomes capable of generating action potentials by 6 hr after lesion. These regenerative spikes are 1 to 1.5 msec in duration and may reach 100 mV in peak amplitude. Ion substitutions indicate that these action potentials are primarily sodium dependent. A calcium-dependent component of soma membrane excitability that is normally present appears to be unaffected by axotomy. By 48 hr, the close axotomized MGI somata have lost the ability to generate action potentials and the membrane electrical properties return to normal. By 2 days after axotomy close to the soma, large, membrane-bound, electron-lucent vacuoles appear in the cytoplasm of the MGI cell body. Such vacuoles then disappear from axotomized MGI somata by 10 days. In addition, numerous arrays of densely packed, darkly staining microtubules are observed in the cell body, especially concentrated near the initial neurite. Neither of these specialized structures is observed in control, intact MGI somata. We propose that close axotomy disrupts the mechanisms which regulate the stability of the fully mature, differentiated neuron. The characteristic morphological and physiological stability of the MGI is lost: the dendritic arborization has been shown previously to be altered by extensive new outgrowth (Roederer, E., and M. J. Cohen (1983) J. Neurosci. 3: 1835-1847); there is a transient increase in soma membrane excitability, and new cytoplasmic organelles are induced.

Axons↗

Modification of retrograde degeneration in transected spinal axons of the lamprey by applied DC current.

In the spinal cord of the lamprey, regeneration of giant reticulospinal axons occurs following transection. We show that partial degeneration of the proximal axonal segment, or "die-back," also occurs following spinal transection and it precedes regenerative outgrowth. The die-back during the first 5 days post-transection is reduced significantly by application of a 10-microA DC current across the site of transection, with the cathode distal to the lesion. Reversing the polarity of the applied current (cathode proximal to the lesion) increases the extent of axonal die-back relative to the sham-treated controls. Following spinal transection, saline-filled wick electrodes were implanted in the body musculature on either side of the lesion. Electrically treated animals received current across the lesion for 5 days, while the sham-treated controls received no current. After 5 days, several giant axons in each preparation were injected intracellularly in the spinal cord with the dye Lucifer Yellow. The extent of axonal die-back in the proximal cord stump was determined in the filled fibers by measuring the distance of the axon end from the site of lesion. The mean distances of axonal die-back were as follows: controls, 1750 microns +/- 45 SEM; cathode-distal, 740 microns +/- 33 SEM; cathode-proximal, 2820 microns +/- 60 SEM. These differences between the treatment groups proved to be significant using the Wilcoxon rank sum test. We propose that die-back is caused by the entry of cations driven into the cut surface of the cord by the endogenous injury current. The applied DC current interacts with the endogenous current of injury to either decrease or increase the flow of cations into the cord, depending on the direction of applied current flow across the lesion. This in turn causes a corresponding reduction or enhancement of the axonal die-back.

Animals↗

Regeneration of an identified central neuron in the cricket. I. Control of sprouting from soma, dendrites, and axon.

When the axon of the medial giant interneuron (MGI) of the cricket is axotomized close to the cell body, the normally stable, characteristic dendritic arborization is induced to sprout supernumerary neurites. The origin of the induced dendritic sprouts is not random; they emerge preferentially from the dentritic tips and branches close to the exit of the axon from the terminal ganglion. If any growth also occurred from the axon, there was a reciprocal relationship between the extent of dendritic and axonal sprouting. On the other hand, axotomy distant to the cell body induces sprouting only from the axon and does not alter the dendritic structure of the MGI. After crushing the ventral nerve cord distant to the cell body, the MGI sprouted neurites from the proximal axonal stump which crossed the site of lesion and continued growing within the distal cord. After a distant cut of the cord, however, the axonal neurites formed a neuroma in the proximal cord stump at the site of lesion and stopped elongating after 1 month. At this time, supernumerary sprouts first began to emerge from the normally smooth, rounded contours of the cell body. Based on these observations, we propose that axotomized neurons produce membrane at a constant rate. This newly synthesized membrane is preferentially inserted into neurites emerging from the proximal axonal stump. When axonal neurites stop growing in a neuroma following a distant cut, then this new membrane appears as supernumerary neurites from the soma. After a close cut, the axon often dies back into the ganglion and appears unable to receive the full complement of sprouting membrane. In such cases, the balance of the newly synthesized membrane is inserted into the dendrites and the characteristic structure of the arborization is significantly altered.

Animals↗

Coexistence of rheumatoid arthritis and systemic sclerosis in four patients.

The classic skin and internal organ system manifestations of systemic sclerosis developed in 4 individuals, each with an erosive, destructive chronic polyarthritis characteristic of rheumatoid arthritis. All had serum rheumatoid factors, anti-nuclear antibodies, hypergammaglobulinemia and circulating immune complexes. Each of the 4 has been resistant to treatment. The features of these patients, together with an analysis of this unusual coexistence of two connective tissue disorders, are presented.

Adult↗

Comparative analysis of paraspinal and frontalis EMG, heart rate and skin conductance in chronic low back pain patients and normals to various postures and stress.

Eleven chronic low back pain (CLBP) patients were compared with eleven age-matched controls to different postures and stress while measuring paraspinal and frontalis EMG activity, heart rate and galvanic skin response. Contrary to current theory, results indicate that the CLBP group exhibited similar or significantly less paraspinal muscle activity than the control group. Frontalis EMG and skin conductance were significantly higher in the CLBP group. It was concluded that the theories are not supported. An alternative explanation of an increased arousal response and altered ability to respond to demanding tasks leading to pain and eventually to decreased paraspinal muscle activity is suggested.

Adult↗

Enhanced spinal cord regeneration in lamprey by applied electric fields.

After a weak, steady electric current of approximately 10 microamperes was imposed across the completely severed spinal cord of the larval lamprey Petromyzon marinus, enhanced regeneration was observed in the severed giant reticulospinal neurons. The current was applied with implanted wick electrodes for 5 to 6 days after transection (cathode distal to lesion). The spinal cords were examined 44 to 63 days after the operation by means of intracellular fluorescent dye injections and electrophysiology. Extracellular stimulation of whole cords showed that action potentials in most of the electrically treated preparations were conducted in both directions across the lesion, but they were not conducted in either direction in most of the sham-treated controls. In most of the electrically treated animals, processes from giant axons with swollen irregular tips, indicating active growth, were seen in or across the lesion. Only a few of the sham-treated controls showed these features. It is possible that these facilitated regenerative responses were mediated by the effects of the artificially applied electric fields on the natural steady current of injury entering the spinal lesion.

Action Potentials↗

Synaptic regeneration and glial reactions in the transected spinal cord of the lamprey.

We have examined axonal growth and synaptic regeneration in identified giant neurons of the transected lamprey spinal cord using intracellular injection of horseradish peroxidase. Wholemounts together with serial section light and electron microscopy, show that axons from identified Müller and Mauthner reticulospinal neurons grow across the lesion and regenerate new synaptic contacts. Relatively normal swimming returns in these animals by 3-4 weeks after spinal transection. This occurs despite the formation of regenerated synapses in regions of the cord that are not usually occupied by these neurons. The regenerating axons branch profusely in contrast to their unbranched state in the normal animal. In addition to showing the two synaptic configuration found normally, synapses may be formed by slender sprouts from the growing giant axon. These 'sprout' type synaptic contacts appear unique to the regenerating neuron. Only regenerated chemical synapses were seen; the morphologically mixed chemical and electrical (gap junction) synaptic complex common in the normal animal was not observed at regenerated synapses. The site of spinal transection in the functionally recovered animal shows an increase in the number of ependymal and glial cells. Ependymal-like cells appear in regions away from the central canal. The expanded ependymal and glial processes covering the peripheral surface of the injured cord become convoluted, in contrast to their normal smooth configuration. There is no collagen within the cord at the site of transection but a considerable deposition is seen external to the cord surface. Axonal growth across a spinal lesion and subsequent synaptic regeneration can be examined in single identifiable giant interneurons in the spinal cord of the larval lamprey. This preparation may be used as an assay to investigate factors that could contribute to functional recovery following central nervous system injury in the higher vertebrates.

Animals↗

Large and persistent electrical currents enter the transected lamprey spinal cord.

The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial value within an hour; within the next 2 days they gradually decline from about 100 microA/cm2 to about 4 microA/cm2; they then remain constant up to 6 days posttransection, when the measurements were ended. The pattern of current entry included substantial peaks opposite (and presumably into) the cut ends of giant axons. Response to changes in the ionic composition of the medium indicates that about half of the injury current consists of Na+, and that much of the rest may consist of Ca2+. The measured influx of ions, which adds up to several coulombs per cm2 in a few days, should radically alter the ionic composition of the terminal few millimeters of neural tissue. Thus it may be important in the degenerative and regenerative responses of neurons to axotomy.

Action Potentials↗