Search PubMed⌕ Search

Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 577 records · Page 32Linked to original sources
PubMed1981

Lisuride in Parkinson disease: efficacy of lisuride compared to levodopa.

Lisuride hydrogen maleate, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was tested in 10 patients with moderate to marked Parkinson disease whose response to levodopa had diminished. In the group of 10 patients, there was a significant reduction (p less than or equal to 0.05) in bradykinesia, gait disorder, and total Parkinson disease disability score when levodopa was replaced with lisuride. The mean dose of lisuride was 3.6 mg per day. Among the 10 patients, 5 were better on lisuride than on levodopa, and 4 continue on lisuride 1 year later. A decline in efficacy was noted in all four after a mean of 45 months. Adverse effects necessitating discontinuing the drug were mental changes in three patients and nausea in one patient. Lisuride, when used alone, has definite antiparkinsonian activity and is a promising new drug.

Aged↗
PubMed1981

Neurotransmitter analysis of dermal neurofibromas: implications for the pathogenesis and treatment of neurofibromatosis.

We examined 15 dermal neurofibromas from five adults with disseminated neurofibromatosis. All tumors contained axons that reacted for catecholamines and tyrosine hydroxylase on histochemical stains. Assay of tissue homogenates identified norepinephrine as the catecholamine. Assays for dopamine and choline acetyltransferase were negative. Some axonal components of dermal neurofibromas may originate in sympathetic adrenergic neurons. Most dermal neurofibromas do not contain neuronal cell bodies, and some of the axons may maintain functional connections with proximal sympathetic neuronal cell bodies. Sympathetic denervation may therefore affect the growth of these dermal neurofibromas.

Adult↗
PubMed1980

Stimulation of adenylate cyclase in rat striatum by pergolide: influence of GTP.

Pergolide stimulates adenylate cyclase activity in homogenates of rat striatum. In contrast, bromocriptine and lisuride are inactive. GTP enhances the stimulation produced by pergolide and has no effect on the other ergots tested. The stimulation produced by pergolide is inhibited by haloperidol but not by molindone. It is concluded that pergolide acts as an agonist at dopaminergic receptors coupled to adenylate cyclase in rat striatum.

Adenylyl Cyclases↗
PubMed1980

Cellular localization of peptides in neural structures.

By means of the immunohistochemical technique of Coons and collaborators, numerous peptide-containing neurons have been observed in the brain, spinal cord and periphery. These neurons may contain peptides such as substance P, vasoactive intestinal polypeptide (VIP), enkephalin or somatostatin. Some systems are very extensive. For example, immunoreactive substance P has been observed in more than 30 cell groups in the central nervous system, in primary sensory neurons, in sensory neurons in the vagus nerve and in taste buds, and in intestinal neurons. Thus, one and the same peptide can be utilized at many different levels in the nervous system. Several examples are now known where a regulatory peptide occurs together with a classical transmitter, such as a catecholamine, in the same neuron, which suggests the possibility that a neuron can release more than one transmitter substance. Of particular interest is the occurrence of VIP in presumed cholinergic neurons innervating exocrine glands in the cat, and the coexistence of a cholecystokinin (CCK)-like peptide in dopamine neurons projecting mainly to limbic areas. In the former system VIP seems to be responsible mainly for vasodilation, whereas acetylcholine mainly causes secretion. Furthermore, combined infusion of both substances in very low doses results in a marked potentiation of the secretory and vasodilatory responses. Thus, we have an example where two putative transmitters, released from the same nerve endings, seem to cooperate to activate a physiological response (secretion). With regard to the central CCK/dopamine neurons the type of interaction between the two coexisting transmitter candidates is at present unclear. It is suggested that elucidation of different types of coexistence phenomena may advance our understanding of chemical transmission at synapses under normal and pathological conditions, and may lead to new approaches to the treatment of some nervous disorders.

Adrenocorticotropic Hormone↗
PubMed1980

The blockade of alpha 2-adrenoceptors by the PNMT inhibitaor SK&F 64139.

Three tetrahydroisoquinolines were tested for activity on central alpha 2-adrenoceptors by determining their ability to inhibit [3H]clonidine binding to rat cerebral cortical membrane homogenates. The compounds included the PNMT inhibitors SK&F 64139 (7,8-dichloro-1,2,3,4-tetrahydroisoquinoline) and SK&F 29661 (1,2,3,4-tetrahydroisoquinoline 7-sulfonamide) as well as SK&F 72223 (5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline) a structural analogue inactive as a PNMT inhibitor. SK&F 64139 and SK&F 72223 but not SK&F 29661 inhibited [3H]clonidine binding. Studies in the isolated guinea pig atrium confirmed that SK&F 64139 and SK&F 72223 are alpha 2-adrenoceptor antagonists.

Adrenergic alpha-Antagonists↗
PubMed1980

Evidence for coexistence of dopamine and CCK in meso-limbic neurones.

Vanderhaeghen et al. reported the occurrence of gastrin-like immunoreactivity in the mammalian brain. Subsequent studies have revealed that this immunoreactivity corresponded mainly to the COOH-terminal octapeptide of cholecystokinin (CCK-8), which has a COOH-terminal pentapeptide identical to gastrin. Also, two peptides resembling the NH- and the COOH-terminal tetrapeptide fragments of CCK-8 are present in the central nervous system (CNS). Using COOH-terminal-specific antisera raised to gastrin and/or CCK, the distribution of CCK neurones has been described with immunohistochemical techniques. Although high numbers of cells and nerve terminals are found in cortical areas, the CCK systems are also present in most other parts of the brain and spinal cord. In the CNS, true gastrin molecules, gastrin-17 and gastrin-34 have been located only in the neurohypophysis, hypothalamus and occasionally in the medulla oblongata (unpublished results). We describe here the occurrence of peptides in meso-limbic dopamine neurones in the rat brain. Evidence has also been obtained that mesencephalic dopamine neurones in the human brain contain similar peptides.

Animals↗
PubMed1980

The effect of decortication on the basal ganglia GABA receptor.

The effect of unilateral decortication on the GABA receptors in the basal ganglia was investigated. Cortical ablation resulted in significant increase in the binding density of the GABA receptors without significant change in the affinity constant for GABA in the globus pallidus and the substantia nigra reticulata-lateralis. However, there was no change in the receptor density or affinity constant in the striatum or in the substantia nigra compacta.

Animals↗
PubMed1980

Catecholamine-stimulated cyclic AMP formation in phenylethanolamine N-methyltransferase containing brain stem nuclei of normal rats and of rats with spontaneous genetic hypertension.

Stimultaion of cyclic AMP formation by epinephrine and norepinephrine has been studied in discrete areas of rat brain that include the epinephrine-containing brain stem nuclei C-1 and C-2. In the C-1 area, epinephrine-stimulated cyclic AMP formation was partially reversed by 100 microM phentolamine and by 10--100 microM propranolol or alprenolol and hence appeared to involve activation of a mixture of both alpha- and beta-adrenergic receptors as has been reported for other rat brain areas such as the cerebral cortex. However, in the C-2-area, the epinephrine and norepinephrine stimulated cyclic AMP formation involved the activation of a single receptor type which was alpha-like in character. Stimulation of cyclic AMP formation by epinephrine in the C-2 area was antagonized by nanomolar concentrations of both phentolamine and yohimbine. The epinephrine-stimulated formation of cyclic AMP in the C-2 but not in the C-1 area was augmented in a strains of rats which exhibit spontaneous genetic hypertension (SHR) vs. Wistar-Kyoto controls. It is suggested that the enhanced epinephrine-stimulated cyclic AMP formation in the C-2 area of SHR rats could be a physiological compensatory response to some other hypertension-causing lesion which, for example, results in chronically reduced epinephrine release or in ruduced availability of epinephrine at its postsynaptic receptor thereby leading to receptor supersensitivity. Supporting this possibility was the finding that treatment of SHRs and control animals and reserpine resulted in enhancement of epinephrine-stimulated cyclic AMP formation in the C-2 area of control rats, essentially obliterating the difference between control and SHR. The findings are also interepreted as supporting the involvement of epinephrine neurons in central vaso-depressor mechanisms.

Adrenergic alpha-Antagonists↗
PubMed1980

Substance P, VIP, enkephalin and somatostatin immunoreactive neurons in intestinal tissue transplanted to the anterior eye chamber.

Tissue pieces of small and large intestine from pre- and postnatal and adult rats, respectively, were transplanted to the anterior eye chamber of the rat. Immunohistochemical studies revealed high numbers of substance P-, vasoactive intestinal polypeptide (VIP)- and enkephalin-containing nerve fibers, especially in the circular smooth muscle layer and in the myenteric plexus of the intestinal tissue transplants. A small number of somatostatin-containing fibers were observed. The distribution patterns of the various peptide-containing neurons in the grafts resembled those which have been described in the intact gastro-intestinal wall. Substance P, VIP, enkephalin and somato-statin immunoreactive fibers were seen also in the host irides. No obvious differences in peptide innervation in grafts and host irides were observed between normal and sympathectomized animals and animals lesioned in the trigeminal ganglion. These findings suggest that most of the peptide-containing fibers in the intestinal transplants and the host irides originate in the transplanted tissue. Thus, it is shown that peptide neurons can survive in this transplantation model, which may be useful for functional studies of intestinal physiology including peptidergic mechanisms.

Animals↗
PubMed1980

Effectiveness of methyrapone in the treatment of acetaminophen toxicity in mice.

Metyrapone tartrate, 400 mg/kg i.p. raised the LD50 for acetaminophen from 340 mg/kg i.p. to 540 mg/kg i.p. in fasting male Swiss white mice. The minimum protective dose of metyrapone was 200 mg/kg. Metyrapone was effective in preventing death when given up to 2 h after acetaminophen administration. The LD50 for metyrapone tartrate was 760 mg/kg i.p. Metyrapone decreased or prevented acetaminophen induced hepatic damage measured either by histology or plasma glutamate pyruvate transaminase activity. Metyrapone tartrate, 400 mg/kg i.p., inhibited the severe liver glutathione depletion seen with acetaminophen alone. It is proposed that metyrapone protects mice from acetaminophen induced liver toxicity and death by inhibiting the oxidation of acetaminophen to a toxic intermediate.

Acetaminophen↗
PubMed1980

Interaction of pergolide with central dopaminergic receptors.

The activity of pergolide, an N-propylergoline derivative, has been tested for stimulation of central dopaminergic receptors. Binding to dopamine receptors shows that pergolide acts as an agonist with respect to these receptors. GTP decreases the potencies of dopamine agonists and of pergolide, but not of bromocriptine, to displace [3H]spiroperidol ([3H]Spi) from striatal membrane sites. The GTP-sensitive site labeled by [3H]Spi seems to be localized on intrastriatal dopamine receptors. The potency of dopamine agonists and of pergolide to displace [3H]Spi from striatal receptor sites is reduced in membranes exposed to higher temperatures. Pergolide, but not hitherto-tested dopaminergic ergots, stimulates dopamine-sensitive adenylate cyclase in striatal homogenates. Thus, pergolide, unlike other dopaminergic ergots, acts as an agonist on GTP-sensitive components of [3H]Spi binding and stimulates dopamine receptors linked to dopamine-sensitive adenylate cyclase. The drug also induces turning behavior in rats with 6-OH-dopamine lesions and relieves tremor in monkeys with ventromedial tegmental lesions for a longer time at a lower dose than other tested dopaminergic ergots. Other studies have shown that it is effective in the treatment of patients with advanced parkinsonism.

Adenylyl Cyclases↗