PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “PROGRESSIVE MUSCULAR ATROPHY”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1996

CAG-repeat expansion in androgen receptor in Kennedy's disease is not a loss of function mutation.

Expansion of CAG trinucleotide repeats in androgen receptor gene is present in patients with a rare X-linked inherited form of motor neuron disorder termed Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). This is a late onset progressive disease often associated with mild signs of androgen insensitivity. Defects in androgen receptor (AR) action have been linked to the expansion of the CAG trinucleotide repeats and postulated to be the cause of the disease. We have identified a trinucleotide repeat of 45 in the N-terminus of the AR in two brothers with SBMA and several members in their family (range in the general population is 11-35). Treatment of the patients with androgens failed to improve their clinical symptoms and provided no hint of an anomalous function of the AR. Consistently, functional analysis of the mutant receptor showed hormone binding, transactivation and transrepression potentials identical to that of the wild-type receptor. These results together argue against SBMA being a loss of function mutation of the AR.

Androgens↗
PubMed1997

Expression of nerve-regulated genes in muscles of mouse mutants affected by spinal muscular atrophies and muscular dystrophies.

The expression of the genes for the alpha-subunit of AChR (AChR alpha), for the myogenic factors myogenin and MyoD, for the calcium-binding protein parvalbumin (PV), and for the muscular chloride channel CIC-1 was studied in the three mouse spinal muscular atrophies (SMAs). These were the mutants "wobbler" (WR), "muscle deficient" (MDF) and "progressive motor neuronopathy" (PMN). Murine myopathies "muscular dystrophy with myositis" (MDM) and "X-linked muscular dystrophy" (MDX) were used as controls. AChR alpha and myogenin mRNA levels were strongly elevated in muscles affected by SMAs (reflecting denervation), whereas only myogenin mRNA was moderately elevated in MDX and MDM muscles, probably due to fiber regeneration. As in denervated muscle, CIC-1 and PV mRNA levels were lowered in SMAs. No changes were seen in muscles of up to 222-day-old symptomless ciliary neurotrophic factor (CNTF) knockout mice. The patterns of gene expression were characteristic for the type of muscle disease, indicating their possible usefulness for clinical diagnosis.

Animals↗
PubMed2004

Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy.

Transgenic models of neurodegenerative disease have proved uniquely powerful for delineating pathways of neuronal dysfunction and cell death. We have developed a transgenic model of the polyglutamine disease spinal and bulbar muscular atrophy (SBMA), an adult-onset, slowly progressive motor neuron disease caused by polyglutamine expansion in the androgen receptor (AR). Mice bearing a human AR with 112 glutamines reproduce many aspects of SBMA, including slowly progressive, gender-specific motor deficits, and neuronal intranuclear inclusions. Despite substantial motor deficits in male AR112Q mice, no motor neuron loss was observed, indicating that neuronal dysfunction, rather than neuronal death, is central to disease. Moreover, reduced levels of unphosphorylated neurofilament heavy chain (NF-H) were observed in motor neurons, suggesting a role for NF-H in SBMA neuronal dysfunction. The elimination of androgens by surgical castration of severely affected, aged 112Q male mice partially restored motor function as well as NF-H levels. These data suggest that hormone-based therapies designed to treat SBMA patients, even with advanced disease, are likely to be effective.

Animals↗
PubMed1981

Peripheral neurofibromatosis and peroneal muscular atrophy.

We studied four patients with peripheral neurofibromatosis and a neuropathy that had the clinical characteristics of peroneal muscular atrophy. Nerve conduction velocities were slowed by less than 40% of normal, and electromyography demonstrated denervation. Sural nerve biopsies from two patients, which were macroscopically free of nerve sheath tumors, were studied by recording the compound action potentials in vitro and by morphometry. These studies demonstrated a chronic axonal neuropathy with reactive Schwann cell changes. Peroneal muscular atrophy in association with neurofibromatosis may be due to progressive neuronal degeneration and may represent another, uncommon manifestation of peripheral neurofibromatosis.

Action Potentials↗
PubMed1990

Family with dominantly inherited ataxia, amyotrophy, and peripheral sensory loss. Spinopontine atrophy or Machado-Joseph Azorean disease in another non-Portuguese family?

A family of German extraction with progressive ataxia, eye movement abnormalities, peripheral sensory loss, and spinal muscular atrophy of adult onset is described. Three members came to autopsy, and neuropathologically, the major changes included varying degrees of atrophy of the basis pontis and degeneration of the spinocerebellar tracts, Clarke's columns, anterior horn neurons, and fasciculus gracilis. The dentate nucleus was spared, and there was slight neuron loss from the substantia nigra in one patient. Clinically and neuropathologically, our family resembles that reported by Boller and Segarra as having spinopontine atrophy. However, several kindreds with similar findings have recently been described as having Azorean or Machado-Joseph disease in non-Portuguese families. Comparison of clinical and neuropathological features in spinopontine atrophy and Machado-Joseph disease, both in Portuguese and non-Portuguese families, reveals clinical and pathological similarities and differences between the two. The major differences in our patients include only minor extraocular movement abnormality and absence of protuberant eyes, and muscular rigidity clinically, and the sparing of the substantia nigra and the dentate nucleus neuropathologically. These differences suggest that spinopontine atrophy, as manifested in our family, is distinct from Machado-Joseph disease. Our family showed no linkage to the HLA locus on chromosome 6.

Adult↗
PubMed2004

Characterization of neuromuscular transmission in mice with progressive motoneuronopathy.

Progressive motoneuronopathy (PMN) is an autosomal recessive mouse disease, which is characterized by the development of hind limbs paralysis rapidly progressing to the anterior parts of the body, muscular atrophy, respiratory depression, and death at 6-7 postnatal weeks. Here, we recorded the resting membrane potential (RMP), spontaneous miniature endplate potentials (MEPPs), and quantum content of endplate potentials (EPP) at the diaphragm muscle fibers in controls and PMN mice aged 18 to 43 days. In control animals, there was a progressive increase in RMP, MEPP frequency and EPP quantum content, as well as a decrease in mean MEPP amplitude. In PMN mice, the developmental increase in frequency and decrease in the amplitude of MEPPs was practically stopped at the postnatal day 18, whereas RMP increased but only until the age of 31 days and then progressively decreased. The distribution histogram of RMP in PMN mice older than 35 days revealed the existence of two subpopulations of muscle fibers: one showing a denervation-like decrease in RMP and the second, which was matching controls. In addition, EPP quantum content was significantly attenuated in older PMN animals. These results indicate that neurotransmission is severely affected in advanced, but not in early stage of disease, which is apparently due to a partial denervation of the muscles.

Aging↗
PubMed1999

Amyotrophic lateral sclerosis in an adult following acute paralytic poliomyelitis in early childhood.

About 30% of polio survivors develop a post-polio syndrome. Some of these patients develop slowly progressive muscle weakness known as post-poliomyelitis muscular atrophy (PPMA). We describe an unusual form of amyotrophic lateral sclerosis (ALS) in a patient with acute poliomyelitis in childhood. An 80-year-old woman had acute poliomyelitis at 2 years of age and developed weakness limited to the lower extremities. Residual weakness was stable until the age of 75 when she developed rapidly progressive weakness that first affected her left arm and subsequently the right arm. Neurological examination revealed both upper and lower motor neuron signs. These clinical features were more consistent with ALS than PPMA. At autopsy, there was marked atrophy of the precentral gyrus. Microscopic examination revealed a severe loss of all nerve cells and pronounced fibrillary astrocytosis of the lumbar ventral horns in the spinal cord, presumably a result of poliomyelitis. Superimposed on these spinal cord alterations were the pathological features of ALS, consisting of loss of Betz cells, corticospinal tract degeneration and loss of motor neurons of other levels of the spinal cord. The findings included some atypical features for ALS, namely, sparing of the hypoglossal nucleus, absence of Bunina bodies and absence of ubiquitin-immunoreactive inclusions. Although poliomyelitis and ALS may be coincidental, the unusual pathological expression of ALS raise the possibility that it is related to the antecedent poliomyelitis.

Aged↗
PubMed2005

Polyglutamine diseases and transport problems: deadly traffic jams on neuronal highways.

The expansion of CAG repeats encoding glutamine (polyQ) causes, to date, 9 late-onset progressive neurodegenerative disorders, including Huntington disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxias 1, 2, 3, 6, 7, and 17. Although many studies using both knockout and transgenic mouse models suggest that a toxic gain of function is central to neuronal dysfunction, the exact mechanisms of neurotoxic effects remain elusive. Protein aggregations within neurons seem to be a common manifestation in almost all polyQ diseases, and such accumulations are perhaps major triggers of cellular stress and neuronal death. Recent data lead to the tantalizing proposal that disruption of axonal transport pathways within long, narrow-caliber axons could lead to protein accumulations that can elicit neuronal death, ultimately causing a neuronal dysfunction pathway observed in polyQ expanded diseases. Perhaps perturbations in transport pathways are an early event involved in instigating polyQ disease pathology.

Animals↗
PubMed1994

Histopathologic changes in the aging human cricoarytenoid joint.

Detrimental effects of the natural aging process on the human cricoarytenoid joint have been hypothesized as a possible etiology for the voice changes seen in the aging population. Cellular events occurring at the histologic level, such as cricoarytenoid joint erosion or arthritis may lead to alterations in laryngeal structure which ultimately affect its function and performance. Seven normal human larynges of varying ages ranging from 29 to 69 years of age were examined histopathologically for changes in the cricoarytenoid joint. The synovium, joint space, periarticular muscle, and respiratory epithelium were evaluated for the presence of inflammatory changes or edema and degree of vascularity. The location and amount of ossification, elastin, and collagen formation were also noted. There were no appreciable changes noted in the synovium or joint space itself with increasing age. No differences were observed in the degree of elastin or collagen formation. However, there was progressive cricoid and arytenoid ossification and periarticular muscular atrophy and fibrosis. These findings suggest that other laryngeal changes may play a greater role in determining senescent vocal quality rather than changes within the cricoarytenoid joint itself.

Adult↗
PubMed1996

Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.

OBJECTIVE: To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. METHODS: A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. RESULTS: Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. CONCLUSIONS: A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.

Adult↗
PubMed2004

Non-primate EIAV-based lentiviral vectors as gene delivery system for motor neuron diseases.

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are neurodegenerative diseases, which cause progressive paralysis and premature death in affected adults and children. The treatment rational for these diseases is to halt or delay the degeneration of motor neurons but to date there are no effective drugs. This may however change with recent advances in gene therapy using lentiviral vectors. These vectors can transfer genes to motor neurons with high efficiency and give long term expression. One of these vector systems, based on the equine infectious anaemia virus (EIAV), can insert genes into the cells of the central nervous system after remote delivery including delivery into the muscle by exploiting retrograde transport pathways. This opens up the exciting possibility of rescuing the denervation of key muscle groups in patients by simple injections of these neurotropic lentiviral vectors into the muscle. This review will describe the general features of lentiviral vectors derived from the EIAV. It will then describe some key examples of gene transfer and genetic correction in animal models of motor neuron disease. The prospects for the clinical evaluation of lentiviral vectors for the treatment of human motor neuron disease will be outlined.

Genetic Therapy↗