Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tolerance and prolactin (PRL) release-inhibiting action of the 8 alpha-aminoergoline, mesurlergine, were investigated. In a blind crossover study in six subjects with hyperprolactinemia, 0.5 mg mesulergine induced fewer side effects than did 2.5 mg bromocriptine, while the PRL release-inhibiting effect of the two was of the same order. Six different subjects with suspected PRL-secreting pituitary adenomas who (repeatedly) had to discontinue bromocriptine because of nausea, vomiting, or symptoms of orthostatic hypotension were treated for 20 mo with mesulergine (1 to 2 mg/day). Mesulergine did not induce side effects and its actions resembled those of bromocriptine. Mesulergine induced cessation of galactorrhea and resumption of normal menstrual cycles in five subjects, while in one subject an insufficient luteal phase persisted. No abnormalities in routine blood parameter estimations were observed. In two of three subjects there was shrinkage of a pituitary tumor after 12 to 15 mo on mesulergine. Mesulergine did not directly inhibit PRL release by cultured normal rat pituitary cells and human prolactinoma cells and it antagonized the action of dopamine in a dose-dependent manner. This suggests that the dopaminergic action is carried out by a metabolite of mesulergine, while the parent drug probably prevents the well-known side effects of dopamine-agonistic drugs by its dopamine receptor blocking activity. Because of its acceptability, mesulergine might be important in the treatment of hyperprolactinemia and perhaps also of acromegaly and Parkinson's disease.
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PMID:Mechanism of action and tolerance of mesulergine. 648 83

Previous studies have used recombinant retroviruses encoding the tyrosine hydroxylase (TH) gene to transduce various cell lines, including fibroblasts (NIH-3T3), a pituitary tumor cell line (AtT20), and a pancreatic endocrine line (RIN). These genetically modified cells, synthesizing either 3,4-dihydroxyphenylalanine, dopamine, or both, are potential donors for treatment of Parkinson's disease. However, the levels of TH protein in such transduced cells have been low and heterogeneous. Using several modified versions of retrovirus vectors encoding TH, we demonstrated that protein stability is an important factor governing levels of TH in NIH-3T3 fibroblasts. Whereas low levels of TH protein were observed in infected NIH-3T3 cells, high levels of a TH-beta gal fusion protein were found. This difference was due to a significantly longer half-life of the TH-beta gal fusion protein relative to TH alone. However, the TH-beta gal fusion protein was found to be enzymatically inactive. We also found that the half-life of the endogenous TH protein in PC-12 cells is sevenfold longer than the TH protein in transduced fibroblasts, implying that a cell-type specific regulator or mechanism may stabilize TH in catecholaminergic cells.
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PMID:The stability of endogenous tyrosine hydroxylase protein in PC-12 cells differs from that expressed in mouse fibroblasts by gene transfer. 750 76

Dopamine D2 receptor imaging was performed with 123I labeled 2'-iodospiperone (2'-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of 123I-2'-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson's disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson's disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2'-ISP can be used for SPECT imaging of D2 dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases.
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PMID:Initial clinical experiences with dopamine D2 receptor imaging by means of 2'-iodospiperone and single-photon emission computed tomography. 853 85