MPTP toxicity: implications for research in Parkinson's disease.

In summary, the parkinsonism induced by MPTP in man closely resembles time-telescoped Parkinson's disease. Parkinsonian symptoms can be duplicated in all aspects under controlled conditions in subhuman primates; the biochemical changes are replicated in mice, dogs, and to varying degrees in other species. Mechanisms of bioactivation by MAO-B of MPTP to MPP+, concentration of MPP+ in neurons with a catecholamine uptake system, and vulnerability to cellular toxic effects of MPP+ are the basis for the specificity of MPTP targeting of nigrostriatal dopaminergic neurons.

Factors that control the efficacy of group Ia synapses in alpha-motoneurons.

1.) This review considers factors that produce systematic variations in the amplitude of monosynaptic group Ia EPSPs in triceps surae alpha-motoneurons belonging to different motor unit types. 2.

Pathogenetic studies of motor fluctuations in Parkinson's disease.

Pharmacokinetic and pharmacodynamic mechanisms for levodopa have been studied in relation to the pathogenesis of the motor fluctuations which complicate advanced Parkinson's disease. Since levodopa clearance from the general circulation was found to be similar in patients with wearing-off or on-off phenomena and those with a stable response to levodopa, peripheral pharmacokinetic factors are unlikely to be involved. Efficacy half-time for levodopa, on the other hand, was significantly reduced in patients with mainly wearing-off fluctuations in comparison to those manifesting a stable response to oral levodopa; individuals with predominantly on-off phenomenon had an even more extreme reduction in the duration of the antiparkinsonian action of levodopa.

Dopamine D-1 receptor agonist stimulation of prolactin secretion in man.

SKF 38393, a selective D-1 dopamine receptor agonist, elevated plasma prolactin levels in eight patients with various neurological disorders. Growth hormone concentrations were unaffected by SKF 38393 administration. The results suggest that D-1 receptors may be involved in the regulation of prolactin secretion.

Rat intermediate lobe in culture: dopaminergic regulation of POMC biosynthesis and cell proliferation.

The effects of the selective D-2 selective agonist, quinpirole, on biosynthesis of proopiomelanocortin (POMC) and cell proliferation rate of cultures of rat intermediate lobe (IL) have been examined. Primary cultures of rat IL were prepared by mechanically dispersing IL lobules in medium. Following a six day incubation, approximately 25% of the cells settled onto the culture plate and began to extend into a monolayer.

Immunological findings in neurological diseases associated with antibodies to HTLV-I: activated lymphocytes in tropical spastic paraparesis.

A retrovirus involvement in the etiology of certain neurological diseases is currently an area of intense interest. Tropical spastic paraparesis and other chronic progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I; however, little is known about the cellular immune response. In the present study, activated T-lymphocytes were found in the peripheral blood of patients with this disorder.

Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis.

Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica).

Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis.

High titers of antibody to human T-lymphotropic virus type I (HTLV-I) have been reported in the sera and cerebrospinal fluids of patients with tropical spastic paraparesis. By means of agarose isoelectric focusing and selective immunoblotting, we demonstrated oligoclonal bands of immunoglobulin G antibodies to HTLV-I in the serum and cerebrospinal fluid of patients with tropical spastic paraparesis. Such cerebrospinal fluid-specific immunoglobulin bands indicate intrathecal synthesis of specific antibodies to HTLV-I.

Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica.

The neuropathological examination of the spinal cord of 2 Jamaican patients with classical tropical spastic paraparesis disclosed an intense chronic meningomyelitis with demyelination. In the 1 case in which serum and cerebrospinal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found.

Tropical spastic paraparesis: clinical, immunological, and virological studies in two patients from Martinique.

Two patients from Martinique with tropical spastic paraparesis had antibodies to human T-lymphotropic virus type I (HTLV-I) in serum and spinal fluid but no antibodies to other retroviruses tested. They presented with spastic weakness of both lower extremities, hyperreflexia with upgoing toes, sphincteric dysfunction, and normal sensation. By means of agarose isoelectric focusing and selective immunoblotting we demonstrated an increased intrathecal synthesis of IgG antibodies to HTLV-I in the spinal fluid.

The role of HTLV-I in tropical spastic paraparesis in Jamaica.

We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1).

Rat intermediate lobe in culture: a histological and biochemical characterization.

The histology, immunohistochemistry, peptide synthesis and secretion as well as proliferation rate of rat intermediate lobe (IL) were studied in primary cultures. The cultures contained two populations of cells: melanotrophs either organized in free floating lobules or in lobules which attached to the dishes and formed a monolayer. Both populations retained their in vivo morphology: polyhedral cells with smooth, ovoid nuclei and a large number of cytoplasmic secretory coated vesicles, a well developed Golgi apparatus, abundant mitochondria and extensive areas of rough endoplasmic reticulum.

Stimulation of nerve growth factor mRNA content in C6 glioma cells by a beta-adrenergic receptor and by cyclic AMP.

Authentic beta-nerve growth factor mRNA, approximately 1.35 kb in size, has been detected by Northern blot analysis in C6 glioma cells. Exposure of the cells to the beta-adrenergic agonist isoproterenol leads to a three- to fourfold increase in NGF mRNA, which reaches a peak by 2 hr.

Characterization of glial subpopulations in cultures of the ovine central nervous system.

The cellular composition and in vitro development of glial cultures derived from the rat CNS has been well studied. However, less information is available on similar cultures from other species, particularly higher mammals. To study ovine glial development in vitro, cultures from 50-day fetal to adult animals were characterized with various immunocytochemical markers, which are frequently used to define neural cell subsets in rat cultures.

Biochemical and behavioral effects of sigma and PCP ligands.

The purpose of this study was to examine the binding and behavioral effects mediated by PCP and sigma receptors in the rat. From the radioreceptor assays, it was possible to characterize two binding sites that interact with PCP and sigma ligands. The two sites, a PCP and sigma receptor, could be differentiated based on drug selectivity and potency.

Receptor desensitization.

Although desensitization of the beta AR-coupled adenylate cyclase system has been stressed in this chapter, it appears to be a useful model. Carbachol induces sequestration of muscarinic receptors in several cell lines. More recently, agonist-mediated phosphorylation of muscarinic receptors in chick heart has been observed.

AIDS and neurological disorders: an overview.

Neurological disease occurs frequently in patients infected with the human immunodeficiency virus. Disorders may affect either the central or peripheral nervous systems and may be the presenting manifestation of human immunodeficiency virus-related disease. Opportunistic infections and lymphomas are major causes of central nervous system disease.

Neuromuscular diseases associated with human immunodeficiency virus infection.

The types of neuromuscular diseases associated with human immunodeficiency virus (HIV) infection are described. Our classification includes: (1) six subtypes of peripheral neuropathies--namely, acute Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, mononeuritis multiplex, an axonal, predominantly sensory, painful polyneuropathy, a sensory ataxic neuropathy due to ganglioneuronitis, and an inflammatory polyradiculoneuropathy presenting as cauda equina syndrome; (2) inflammatory myopathies (e.g.