A new silver stain for electrophoretically separated polypeptides can be rapidly and easily used and can detect as little as 0.01 nanogram of protein per square millimeter. When employed with two-dimensional electrophoresis, it should permit qualitative and quantitative characterization of protein distributions in body fluids and tissues. It has been used to demonstrate regional variations in cerebrospinal fluid proteins.

A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.The most prominent pathological change in idiopathic parkinsonism is degeneration of the nigrostriatal dopaminergic pathway with nerve cell loss in the substantia nigra (1). A neurochemical consequence of this loss of dopaminergic neurons is a marked decrease in the concentrations of dopamine and its major metabolite homovanillic acid (HVA) in the caudate nucleus and putamen (2). The effectiveness of L-dopa and directacting dopamine agonists in reversing akinesia, rigidity, resting tremor, and postural abnormalities in patients with idiopathic parkinsonism (3, 4) reflects the pathophysiology of these clinical signs.In 1979 a single case of parkinsonism occurring after intravenous self-administration of an illicit narcotic analgesic was described (5). Recently, a series of similar cases has been reported (6). We had the opportunity to examine two patients included in the later study. In both instances there was evidence that the method of Ziering et al. (7) had been used to synthesize the reverse ester of meperidine, 4-propionoxy-4-phenyl-N-methylpiperidine. The injected mixture also contained the side product N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP). After intravenous administration of multiple doses of the drug mixture over several days, the patients gradually developed persistent symptoms of parkinsonism, with a syndrome characterized by severe akinesia, rigidity, a flexed posture, and a resting tremor associated with low concentrations of HVA in the lumbar cerebrospinal fluid (5-6.7 ng/ml). The clinical signs were reversed by the administration of L-dopa or bromocriptine. A marked loss of pigmented cells in the substantia nigra with minimal changes in the locus ceruleus was found in the one patient who died of other causes 18 months after the onset of symptoms (5).In the present study we show that repeated intravenous administration of NMPTP to the rhesus monkey over a period of 5-8 days produces a chronic disorder with neurological, biochemical, pa...

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We studied the pressor responses to vasoactive agents in patients with orthostatic hypotension. Greater-than-normal slopes of the stimulus-response curves in patients with multiple system atrophy (Shy-drager syndrome) and idiopathic orthostatic hypotension (IOH) were consistent with deficient reflex modulation. Patients with IOH also had a shift to the left of the plasma norepinephrine-blood pressure curves, suggesting "denervation supersensitivity." This was consistent with the deficient plasma norepinephrine response to tyramine in these patients. Patients in whom orthostatic hypotension is attended by tachycardia are subsensitive to administered catecholamines, and may suffer from deficient effector organ responsivity.

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