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A M Corse

Publications and source records attributed to A M Corse.

10 recordsLinked to original sources
PubMed2001

Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons.

BACKGROUND: Both growth and survival of motor neurons may depend on multiple neurotrophic factors. Individually, insulin-like growth factor I (IGF-I) and glial cell line-derived neurotrophic factor (GDNF) are potent neurotrophic/survival factors for postnatal motor neurons. METHODS: We used an organotypic spinal cord model of glutamatergic degeneration in ALS to investigate whether IGF-I and GDNF interact to enhance motor neuron survival, their trophic effect on choline acetyltransferase (ChAT) activity, and their effect on neurite outgrowth. RESULTS: We show that the combination of IGF-I and GDNF at active doses (1) is additively neuroprotective, (2) completely rescues rat motor neurons from chronic glutamate-mediated toxicity, and (3) additively upregulates motor neuron ChAT activity. Further, IGF-I, which by itself does not promote neurite outgrowth in this model, potentiates the neurite promoting action of GDNF. CONCLUSION: The results predict that IGF-I combined with GDNF may provide a better therapy for the treatment of motor neuron disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Autonomic and peripheral (sensorimotor) neuropathy in chronic liver disease: a clinical and electrophysiologic study.

Peripheral neuropathy has been reported in association with chronic liver disease. However, the precise incidence, severity and characteristics of neuropathy, and the relationship of neuropathy to different etiologies of liver disease have not been defined. In this study, 58 patients with advanced liver disease were evaluated in detail for the presence of neuropathy. Peripheral (sensorimotor) neuropathy was found in 71% and autonomic neuropathy was found in 48% of the patients. Although the majority of patients were asymptomatic, neurological examination showed distal sensory loss to pain, or vibration or distal loss of reflexes in 17 patients (29%). Sensory neuropathy was seen more commonly than motor axonal polyneuropathy on nerve conduction studies. Quantitative sensory testing was frequently abnormal (62%) and cooling thresholds were more affected than vibration thresholds. Overall, the pattern of neuropathy in patients with liver disease conformed to the pattern expected in "dying back" or length-dependent neuropathy. The neuropathy was most severe in patients with advanced hepatic decompensation. Comparison of causes of liver disease showed no significant differences in the severity of neuropathy among the different etiologies. In conclusion, axonal sensory-motor polyneuropathy and autonomic neuropathy are commonly seen in patients with end-stage liver disease of different causes.

Adult↗
PubMed1999

Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: comparison with GDNF and persephin.

Neurturin and persephin are recently discovered homologs of glial cell line-derived neurotrophic factor (GDNF). Here, we report that neurturin, like GDNF, increases the choline acetyltransferase activity of normal postnatal motor neurons, induces neurite outgrowth in spinal cord, and potently protects motor neurons from chronic glutamate-mediated degeneration. Persephin, in contrast, does not appear to have neurotrophic or neurite-promoting effects on mature motor neurons and may instead worsen the glutamate injury of motor neurons. This pattern in the TGF-beta family suggests certain receptor specificities, requiring at least the Ret/GFRalpha-1 receptor complex. The results predict potential benefit of neurturin, but not persephin, in the treatment of motor neuron disorders and spinal cord diseases.

Animals↗
PubMed1999

Preclinical testing of neuroprotective neurotrophic factors in a model of chronic motor neuron degeneration.

Many neurotrophic factors have been shown to enhance survival of embryonic motor neurons or affect their response to injury. Few studies have investigated the potential effects of neurotrophic factors on more mature motor neurons that might be relevant for neurodegenerative diseases. Using organotypic spinal cord cultures from postnatal rats, we have demonstrated that insulin-like growth factor-I (IGF-I) and glial-derived neurotrophic factor (GDNF) significantly increase choline acetyltransferase (ChAT) activity, but brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) do not. Surprisingly, ciliary neurotrophic factor (CNTF) actually reduces ChAT activity compared to age-matched control cultures. Neurotrophic factors have also been shown to alter the sensitivity of some neurons to glutamate neurotoxicity, a postulated mechanism of injury in the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). Incubation of organotypic spinal cord cultures in the presence of the glutamate transport inhibitor threo-hydroxyaspartate (THA) reproducibly causes death of motor neurons which is glutamate-mediated. In this model of motor neuron degeneration, IGF-I, GDNF, and NT-4/5 are potently neuroprotective, but BDNF, CNTF, and NT-3 are not. The organotypic glutamate toxicity model appears to be the best preclinical predictor to date of success in human clinical trials in ALS.

Animals↗
PubMed1999

Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration.

Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that may aid the development, differentiation, and survival of adjacent neural retinae, the wider distribution of PEDF mRNA in the central nervous system suggested to us that this factor could have pleiotropic neurotrophic and neuroprotective effects on nonretinal neurons. We examined the distribution of PEDF mRNA and its transcript in the spinal cord. By immunohistochemistry and western blot analysis using an antihuman PEDF antiserum of known specificity, we found that PEDF protein is present in spinal cord, cerebrospinal fluid, and skeletal muscle and that its mRNA appears concentrated in motor neurons of the human spinal cord. These observations indicate that PEDF could have potential autocrine and paracrine effects on motor neurons, as well as being target-derived. We analyzed the pharmacologic utility of PEDF in a postnatal organotypic culture model of motor neuron degeneration and proved it is highly neuroprotective. The effect was biologically important, significantly sparing the spinal cord's gross organotypic morphological appearance and preserving motor neuron choline acetyltransferase (ChAT). PEDF alone did not increase ChAT, indicating that the observed effect is neuroprotective, not merely an upregulation of motor neuron ChAT. Further, PEDF preserved motor neuron number, proving a survival effect. We hypothesize that PEDF may play important roles in the survival and maintenance of spinal motor neurons in their neuroprotection against acquired insults in postnatal life. It should be developed further as a therapeutic strategy for motor neuron diseases such as amyotrophic lateral sclerosis (ALS).

Animals↗
PubMed1996

Sensory nerve pathology in multifocal motor neuropathy.

The nosological status of multifocal motor neuropathy remains controversial. The clinical and electrodiagnostic hallmarks suggest selective motor fiber involvement. In this study, we asked to what extent sensory nerves might be involved pathologically in multifocal motor neuropathy. Examination of sensory nerve biopsy specimens from 11 patients did reveal pathological findings in all, but they were very mild. An increased number of thinly myelinated, large-caliber fibers was the unifying feature common to each specimen. By electron microscopy, each biopsy specimen had thinly myelinated fibers surrounded by minor onion bulbs. Active demyelination, though scant, was seen in 3 nerves. Myelinated fiber density was normal. Subperineurial edema and inflammation were not present. We conclude that multifocal motor neuropathy is not an exclusively motor abnormality, although it appears to be so clinically and electrophysiologically. The frequent, albeit mild, pathological abnormalities in sensory fibers suggest that the demyelinating pathophysiology also affects sensory fibers, but to a lesser degree than motor fibers. Some investigators maintain that multifocal motor neuropathy is within the spectrum of chronic inflammatory demyelinating polyneuropathy. The very mild degree of sensory fiber involvement, the absence of inflammation or edema, and the distinctive clinical features support the concept of multifocal motor neuropathy as distinct from chronic inflammatory demyelinating polyneuropathy.

Adult↗
PubMed1994

Multifocal motor neuropathy: electrodiagnostic features.

Diagnosis of multifocal motor neuropathy (MMN), a syndrome characterized by progressive asymmetric weakness with intact sensation, is important because the disorder often responds to treatment. Multifocal partial motor conduction block (PMCB) has been emphasized as a cardinal feature in the diagnosis of this syndrome, but detailed nerve conduction studies are not available. Nine patients, ages 28-58, had chronic, progressive, asymmetric, predominantly distal limb weakness for 5-18 years. Sensation was normal and reflexes were reduced asymmetrically. Although all 9 demonstrated PMCB localized to short nerve segments, additional features of multifocal motor demyelination were present, including temporal dispersion (5 patients), segmentally reduced motor nerve conduction velocity (7 patients), prolonged distal motor latency (4 patients), and prolonged F-wave latency (9 patients). The strength of all patients improved after treatment with human immune globulin. A reduction in the degree of PMCB or an increase in the distal motor amplitude or both accompanied the clinical improvement. These studies suggest that patients with MMN demonstrate widespread evidence of motor demyelination in addition to the well-described PMCB, and that reduction of PMCB accounts for the increase in strength following therapy.

Adult↗
PubMed1994

Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.

We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Analysis of Variance↗
PubMed1993

Multifocal motor neuropathy: response to human immune globulin.

Multifocal motor neuropathy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis. Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immune globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distal, limb weakness for 5 to 18 years. Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serum titers of anti-GM1 IgM antibody. All patients were treated with HIG, 1.6 to 2.4 gm/kg, given intravenously over 3 to 5 days. Strength improved in all patients 3 to 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement varied from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 of 8 patients. The serum anti-GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conclude that HIG may be an effective therapy for patients with MMN.

Adult↗