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Biomedical subjects

D L Price

Publications and source records attributed to D L Price.

At least 307 records · Page 17Linked to original sources
PubMed1983

Effect of intermittent high dose parenteral corticosteroids on the alveolitis of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder in which chronic accumulation of neutrophils within the alveolar structures occurs. These cells with their large stores of preformed mediators likely play a major role in subsequent lung derangement. To evaluate the adjunctive use of intermittent high dose "pulse" corticosteroid therapy as a means of inhibiting neutrophil accumulation in the IPF lung, 5 patients were treated in a single blind random fashion with "high dose" corticosteroids (2 g methylprednisolone given intravenously once a week plus 0.25 mg/kg prednisone given orally daily) and 8 patients were treated with "low dose" corticosteroids only (0.25 mg/kg prednisone given orally daily). All patients had biopsy-proved disease in midcourse, and the 2 groups were matched for clinical and physiologic criteria. To evaluate the effect of these therapies on the quantity of neutrophils in the lungs of these patients, both groups underwent bronchoalveolar lavage and 67Ga scanning at the beginning and end of the 6-month study period; both methods gave an estimate of the intensity of the neutrophil alveolitis in these patients. Low dose corticosteroids had little effect on neutrophil accumulation (% neutrophils in lavage, - 5 +/- 8% change from baseline; 67Ga uptake, + 27 +/- 14% change from baseline), whereas high dose corticosteroids significantly reduced neutrophil accumulation (% neutrophils in lavage, - 46 +/- 8% change from baseline, p less than 0.02 compared with that in the low dose group; 67 Ga uptake, - 23 +/- 11% change from baseline, p less than 0.05 compared with that in the low dose group). In addition, 2 patients in the high dose group were reevaluated 6 months after cessation of the intermittent high dose pulse corticosteroids. Both had marked increases in lavage neutrophils compared with when they were receiving the high dose therapy (10 to 22% and 18 to 52%, respectively). These findings suggest that massive doses of intermittent intravenously administered corticosteroids may help to suppress the neutrophil component of the alveolitis of IPF.

Administration, Oral↗
PubMed1983

The nucleus basalis in Huntington's disease.

The nucleus basalis of Meynert (nbM) provides most of the cholinergic input to the cerebral cortex. The loss of cortical choline acetyltransferase (CAT) activity in Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT) appears to be related to a severe depopulation of the nbM in this dementia. In Huntington's disease (HD), by contrast, there is no loss of cortical CAT activity. The present quantitative study indicates that (1) there is no significant loss of neurons from the nbM in HD, and (2) that the previously described cytologic changes in the neurons of this nucleus in HD patients do not differ significantly from controls. These findings are consistent with the working hypothesis that the types of dementia associated with reductions of neocortical CAT activity are characterized by dysfunction or death of neurons in the nbM, but dementing disorders with normal neocortical CAT activity manifest no major abnormalities in this cholinergic nucleus of the basal forebrain.

Aged↗
PubMed1983

Pick's disease (lobar sclerosis): depletion of neurons in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM) has been implicated in the pathogenesis of the presynaptic cholinergic deficiency in the cerebrum of patients with Alzheimer's disease. To further define the role of this cholinergic basal forebrain nucleus in dementia, we examined the nbM in two patients with lobar sclerosis, or Pick's disease (PD). The brains of both of these patients showed substantial reductions in the number of nerve cells in many neuronal populations, including the nbM. Our observations of the changes in the nbM are correlated with previous investigations of cholinergic markers in PD.

Basal Ganglia↗
PubMed1983

Microtubule-neurofilament segregation produced by beta, beta'-iminodipropionitrile: evidence for the association of fast axonal transport with microtubules.

The subperineurial injection of beta,beta'-iminodipropionitrile (IDPN) into rat sciatic nerves resulted in focal disorganization of the axonal cytoskeleton characterized by segregation of neurofilaments and microtubules. Shortly after injection, microtubules clustered together to form a central channel, while neurofilaments became chaotically arrayed between the microtubule channel and axolemma. Electron microscopic autoradiography disclosed that rapidly transported organelles were preferentially associated with the microtubule-enriched central channels. These studies indicate that IDPN acts at the level of the axon to disrupt interactions between cytoskeletal elements and show that rapidly transported constituents are preferentially conveyed in association with microtubules. The model provides an opportunity to dissect the interactions of the cytoskeletal elements and other organelles.

Animals↗
PubMed1983

Slowing of the axonal transport of neurofilament proteins during development.

We examined age-dependent changes in neurofilament transport in motor axons of the rat sciatic nerve. SDS-PAGE and gel fluorography confirmed that the distribution of labeled neurofilament triplet protein coincides with the major slow component a (SCa) wave in these neurons. The velocity of neurofilament transport was calculated on the basis of the location of the 50th percentile Of radioactivity in this wave 33 days after motor neurons were labeled by the intraspinal administration of [3H]leucine and [3H]lysine. Overall, the velocity fell from 1.95 mm/day at 3 weeks of age to 1.12 mm/day at 20 weeks. Between 3 and 10 weeks, it fell at a 6-fold higher rate (0.096 mm/day/week) than between 10 and 20 weeks (0.016 mm/day/week). We also found a marked change in the shape of the slow component wave during development. It appeared to consist of several overlapping peaks moving at slightly different velocities in animals 10 weeks of age or less as compared to a single slower moving peak at 20 weeks. We propose that the velocity of slow axonal transport reflects the level of maturation of the neuron, and that the presence of several overlapping peaks Of transported radioactivity in the sciatic nerve of younger animals reflects the presence of several populations of motor axons at different stages of development. We also discuss the relationship between changes in the velocity of neurofilament transport and alterations in the composition of the cytoskeleton that occur as the axon grows in caliber during postnatal development.

Animals↗
PubMed1982

Cholinergic innervation in neuritic plaques.

Although several studies of Alzheimer's disease suggest that the frequency of neuritic plaques in the cerebral cortex is correlated with the severity of dementia and with reduction in presynaptic cholinergic markers in the cortex, the relationship between cholinergic cortical innervation and the pathogenesis of plaques is unknown. The hypothesis was tested that the neurites in the plaque consist, in part, of presynaptic cholinergic axons, many of which arise from neurons in the basal forebrain. This hypothesis was tested by analyzing the character and distribution of plaques in monkeys, aged 4 to 31 years, with staining for acetylcholin-esterase and also with Congo red and silver stains. Immature and mature plaques were rich in acetylcholinesterase. As the plaques matured, the amount of amyloid increased, and the number of neurites and the activity of acetylcholinesterase decreased. End-stage amyloid-rich plaques lacked acetylcholinesterase. These observations indicate that changes in cortical cholinergic innervation are an important feature in the pathogenesis and evolution of the neuritic plaque.

Acetylcholinesterase↗
PubMed1982

Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain.

Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.

Acetylcholine↗
PubMed1982

Membrane myopathy: morphological similarities to Duchenne muscular dystrophy.

Focal lesions in the plasma membrane overlying wedge-shaped defects in muscle fibers ("delta lesions") are an early pathological change in Duchenne muscular dystrophy (DMD). Abnormalities in the plasma membrane have been suggested as a cause of these lesions and of the degeneration of muscle fibers in DMD. We investigated the role of plasma membrane defects in the production of delta lesions by examining the effects of a series of membrane-active agents--lysolecithin, deoxycholate, Triton X-100, and melittin--on the muscles of rats in vivo. Within minutes after treatment with these agents, the muscle fibers developed typical delta lesions. Identical morphological changes were produced by the calcium ionophore A23187, suggesting that calcium entry may play an important role in this process. We conclude that damage to the plasma membrane or calcium entry can reproduce characteristic features of the muscle pathology seen in DMD. This model should prove useful in elucidating the mechanisms of muscle fiber damage and degeneration in DMD.

Animals↗