PubMed Health⌕ Search

Biomedical subjects

M J Strong

Publications and source records attributed to M J Strong.

At least 55 records · Page 3Linked to original sources
PubMed1991

Familial amyotrophic lateral sclerosis, 1850-1989: a statistical analysis of the world literature.

We present clinical and pathologic data on four previously unreported familial ALS pedigrees and review and analyze by descriptive and exploratory statistical techniques all published cases of familial ALS (1850-1989). In contrast to the age-dependent incidence of sporadic ALS, the age of onset of familial ALS is normally distributed about a mean of 45.7 years (std. dev. 11.3 years). Survival curves for the familial ALS data also demonstrate a skewed distribution with a median survival time of 24 months with 74% surviving at 12 months, 48% at 24 months and 23% surviving at 60 months. The patient characteristics of age at onset of disease, sex and focus of disease onset are unrelated variables and age at onset of disease is the only predictor of survival (Cox's proportional hazard model, chi-square 14.74, p = 0.0001). By applying accelerated failure time models with a log-normal baseline distribution, estimated probabilities for survival adjusted by age at onset were calculated. It was found that the older the age at disease onset, the shorter the survival.

Adult↗
PubMed1991

Chronic aluminum-induced motor neuron degeneration: clinical, neuropathological and molecular biological aspects.

The monthly intracisternal inoculation of young adult New Zealand white rabbits with low-dose (100 micrograms) aluminum chloride induces aggregates of phosphorylated neurofilament that mimics the intraneuronal inclusions of amyotrophic lateral sclerosis. The chronic progressive myelopathy and topographically-specific motor neuron degeneration that occurs in the absence of suppressions of neurofilament messenger RNA levels in this model contrasts with the acute fulminant encephalomyelopathy and nonspecific gene suppressions that occur subsequent to high-dose (1000 micrograms) aluminum chloride inoculations. Further analysis of this unique model of chronic motor system degeneration can be expected to provide additional insights into the pathogenesis of amyotrophic lateral sclerosis.

Aluminum↗
PubMed1991

Potentiation in the neurotoxic induction of experimental chronic neurodegenerative disorders: N-butyl benzenesulfonamide and aluminum chloride.

Repeated monthly intracisternal inoculations of N-butyl benzenesulfonamide induced a chronic, slowly progressive myelopathy in young adult New Zealand white rabbits that was manifested by hyperreflexia, spasticity, hypertonia, gait impairment and altered tonic immobility responses. The neuropathological features consisted of scattered neuroaxonal spheroids, fusiform distention of the intramedullary portions of the spinal cord ventral roots and, as defined by microtubule-associated protein-2 (MAP 2) immunoreactivity, an initial distention and subsequent loss of dendritic processes in neurons of the nucleus motoris lateralis with the perikaryon of these cells remaining intact. A similar chronic progressive myelopathy was induced by repeated low dose intracisternal inoculations of aluminum chloride in New Zealand white rabbits. However, the neuropathological changes were more extensive and consisted of dendritic, axonal and perikaryal inclusions of phosphorylated and nonphosphorylated neurofilament localized to spinal motor neurons in the nucleus motoris medialis, substantia grisea intermedia and select brainstem nuclei with only minimal involvement of the nucleus motoris lateralis. The co-administration of these two neurotoxins over the course of 8 months induced striking behavioral changes as well as a fulminant myelopathy. This was accompanied by a loss of neuronal perikarya in the nucleus motoris accompanied by a loss of neuronal perikarya in the nucleus motoris lateralis and topographically extensive neocortical neurofilamentous degeneration. These features suggest that potentiation occurs when the two toxins are co-administered, a view supported by an estimation of the co-neurotoxicity coefficient (CNC greater than 1). Our results have implications for understanding human neurodegenerative disorders in which potentiation of insults may occur, producing a clinical and neuropathological disease state not expected from either agent alone.

Aluminum↗
PubMed1991

Neuron-specific thresholds of aluminum toxicity in vitro. A comparative analysis of dissociated fetal rabbit hippocampal and motor neuron-enriched cultures.

Mature dissociated motor neuron-enriched and hippocampal neuron cultures derived from fetal New Zealand white rabbits were continuously exposed to 1, 10, 25, 50, or 100 microM AlCl3 in a chemically defined medium for 14 days. Motor neuron-enriched cultures exposed to low concentrations (1 or 10 microM) of AlCl3 remained viable for the entire experiment but developed perikaryal and neuritic inclusions composed of phosphorylated neurofilament. Similar inclusions developed in cultures exposed to 25 and 50 microM AlCl3, but motor neurons did not survive beyond 10 days exposure. The 100 microM AlCl3-supplemented medium induced cell death within 72 hours without development of inclusions. In contrast, hippocampal neurons exposed to 1, 10, or 25 microM AlCl3 developed no morphological changes or inclusions. Although hippocampal cultures exposed to 50 or 100 microM AlCl3 developed perinuclear and proximal neuritic inclusions of phosphorylated neurofilament after 10 days, they remained viable. These in vitro morphological observations demonstrate a 10-fold greater sensitivity of spinal motor neurons to aluminum toxicity when compared with hippocampal neurons and suggest that the earlier observations of neuron-specific thresholds of aluminum toxicity in vivo are related to unique regulatory mechanisms of neurofilament biosynthesis and catabolism within distinct neuronal cell populations.

Aluminum↗
PubMed1991

Aluminum-induced chronic myelopathy in rabbits.

Young adult New Zealand white rabbits, inoculated intracisternally once monthly with 100 micrograms AlCl3, developed progressive hyperreflexia, hypertonia, gait impairment, weight loss, muscle wasting and abnormal righting reflexes over the course of 8 months. No overt encephalopathic features were present. In spinal motor neuron perikarya, dendrites and axonal processes, argentophilic globular inclusions were extensive. Additionally, neurofibrillary tangle-like argentophilic inclusions were consistently present in the gigantocellularis, reticularis, raphe and trapezoid nuclei, but rarely present in the dorsal and ventral subiculum, parasubiculum and anterior thalamus, and never found in the cerebral cortex, substantia nigra, locus ceruleus, or cerebellum. All neuronal inclusions were immunoreactive with monoclonal antibodies recognizing phosphorylated and nonphosphorylated high and intermediate weight neurofilament proteins (SMI 31, SMI 32). Also, some spinal motor neuron inclusions were immunoreactive with a monoclonal antibody recognizing an 'age-related' phosphorylation state of neurofilament (SMI 34). Ultrastructurally, the inclusions consisted of straight or interwoven skeins of 10 nm filaments. This study demonstrates unique variability in the phosphorylation state of aluminum-induced neurofilamentous inclusions in a predominantly motor system degeneration induced by chronic low dose AlCl3.

Aluminum↗
PubMed1990

The temporal expression of amyloid precursor protein mRNA in vitro in dissociated hippocampal neuron cultures.

The subunit protein of the neurofibrillary tangle, the core protein of the neuritic plaque, and the amyloid of the cerebrovasculature in Alzheimer disease and normal aging is a unique 42-amino acid protein (amyloid beta-protein), suggesting a common origin for these pathological entities. However, the expression of the amyloid precursor protein mRNA (APP mRNA) from which the amyloid beta-protein is derived varies between specific neuronal populations. To determine the conditions under which neuronal synthesis of amyloid beta-protein might contribute to the formation of these structures, we have studied the temporal pattern of APP mRNA expression in developing fetal rabbit hippocampal neurons in vitro. Using in situ hybridization with a biotinylated riboprobe transcribed from a cDNA which includes the region encoding the amyloid beta-protein, we have observed a developmentally specific pattern of APP mRNA hybridization during neuronal maturation in vitro.

Alzheimer Disease↗
PubMed1989

Isolation of fetal mouse motor neurons on discontinuous Percoll density gradients.

The spinal cords of fetal NIH:CR mice, gestational age Day 12 to 14, were dissected free of meninges and dorsal root ganglia, chemically dissociated, and layered onto discontinuous Percoll gradients at densities 1.040, 1.050, and 1.060 g/ml. After centrifugation (800 Xg for 15 min at 4 degrees C), three morphologically, biochemically, and immunohistologically distinct cell populations were collected from the gradient interfaces. The first interface, located at a density of 1.040 g/ml, was choline acetyltransferase enriched (0.86 +/- 0.08) compared to the second and third fractions (0.42 +/- 0.01 and 0 pmol acetylcholine synthesized/microgram protein, respectively). When simultaneously cultured with fetal mouse cardiac muscle on a gelatin-polylysine-laminin substrate in serum-free medium, these cells developed the characteristics of motor neurons.

Animals↗
PubMed1988

Metabolic changes in human muscle denervation: topical 31P NMR spectroscopy studies.

Metabolic changes in human forearm flexor muscle following partial or complete denervation were studied using 31P nuclear magnetic resonance spectroscopy. In resting muscle, patients with electromyographically verified forearm flexor denervation had a lower ratio of PCr/Pi than healthy controls [4.76 +/- 2.50 (SD) versus 6.50 +/- 1.55 (SD); P less than 0.01] and a higher intracellular pH [7.09 +/- 0.06 versus 7.05 +/- 0.04 (SD); P less than 0.01]. These changes were more apparent when the diseased arm was compared to the contralateral healthy arm in patients with strictly unilateral denervation. Five patients with severe denervation had the lowest PCr/Pi ratio (1.94 +/- 0.70) and the highest pH (7.15 +/- 0.04). Four patients with intact innervation and disuse atrophy as a result of a forearm fracture did not exhibit these changes immediately following removal of the forearm cast. The findings show that denervation leads to a reduction in PCr/Pi within muscle and a rise in intracellular pH, and that these changes correlate with the degree of denervation and improve with recovery. 31P MRS may be useful to follow the course of denervation atrophy.

Adult↗
PubMed1988

Motor unit estimates in the biceps-brachialis in amyotrophic lateral sclerosis.

A newly developed technique for estimating the number of motor units in the biceps-brachialis muscles and for studying the innervation patterns of motor units in the same muscles has been applied to the study of 17 patients with amyotrophic lateral sclerosis (ALS). Although severe motor unit losses were seen in many ALS cases, in most there were clear indications of increases in innervation densities, linked potentials, and blocking. This technique provides a powerful new tool for quantitatively assessing the extent of motor unit losses and the accompanying changes in innervation patterns in ALS.

Adult↗
PubMed1988

Methods for estimating numbers of motor units in biceps-brachialis muscles and losses of motor units with aging.

This paper presents a new method, here applied to the biceps-brachialis muscles, for estimating motor unit numbers in healthy subjects. This method combines isometric contraction, intramuscular needle electrode recordings, and spike-triggered averaging techniques to measure the sizes of motor unit potentials as recorded in the innervation zone with surface electrodes. The number of motor units is then estimated by division of the maximum biceps-brachialis "M" potential recorded with the same surface electrodes and evoked by supramaximal stimulation of the musculocutaneous nerve, by the mean of at least 10 surface-recorded motor unit potentials. The requisite intramuscular recordings provide additional information as to innervation density, incidence of linked potentials, and impulse blocking, phenomena that are particularly common in neurogenic and myogenic disorders. There was clear evidence of losses of motor units in older subjects: subjects over 60 years of age having approximately half the numbers of motor units of subjects under 60 years of age.

Adult↗
PubMed1986

Hemiageusia, hemianaesthesia and hemiatrophy of the tongue.

A patient with a submandibular gland carcinoma was found clinically to have a unilateral chorda tympani, lingual and hypoglossal nerve deficit. This unique neurological entity of loss of taste sensation of one-half of the tongue (hemiageusia), hemianaesthesia and hemiatrophy of the tongue, has not previously been reported.

Aged↗