Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We document a case of a patient who had been treated for a medullary cell carcinoma of the thyroid three years previously and who presented with a three month history of ataxia, weakness and headache. A CT scan showed contrast enhancing lesions in the posterior fossa. An MIBG uptake scan showed that there was some uptake in the cerebellar lesions; however, it was not sufficient to rely on this alone for treatment. The larger of these lesions was therefore surgically resected. Immunocytochemistry, using CAM 5.2, CEA and chromogranin, demonstrated a positive reaction which strongly favoured a diagnosis of metastases from a medullary cell carcinoma of the thyroid. However, absolute confirmation of the diagnosis was obtained using immunocytochemistry with calcitonin. Medullary cell carcinomas of the thyroid usually spread locally and metastasis to the brain has never before been reported.
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PMID:Medullary cell carcinoma of the thyroid: metastases to the central nervous system. 778 10

The effects of CR 2945, an antranilic acid derivative member of a novel family of non-peptide CCKB receptor antagonists, have been compared with those of CAM-1028, an analogue of the CCKB receptor antagonist CI-988, L-365,260 a benzodiazepine derivative CCKB antagonist, CR 1795, an analogue of the CCKA receptor antagonist lorglumide and diazepam, a benzodiazepine receptor agonist, in several rodent screens sensitive to conventional anxiolytics. CR 2945 displayed nanomolar affinity for rat CCKB receptors and showed a selectivity ratio of about 9000 for the CCKB over the CCKA receptor. In ex-vivo binding studies, CR 2945, after i.v. and s.c. administration, inhibited the binding of [125I] (BH)-CCK8 in rat cortex homogenate with ID50s of 10.9 mg/kg and 13.5 mg/kg, respectively. In four rodent tests of anxiety (mouse black/white box, rat elevated plus-maze, rat elevated zero-maze and punished licking test in the rat) CR 2945 (0.1-10 mg/kg s.c. or orally) showed significant dose-dependent anxiolytic-like effects. The reference CCKB antagonist compounds CAM-1028 and L-365,260 showed an anxiolytic-like activity less robust than that of CR 2945 in the elevated zero-maze after s.c. administration, and these compounds were inactive in the elevated plus-maze after oral administration. The magnitude of the activity of CR 2945 was comparable to that of diazepam, but without signs of sedation and ataxia. Furthermore, a 7-day repeated treatment with CR 2945 at 10 mg/kg/day s.c. did not induce tolerance or withdrawal anxiety in rats. CR 1795 showed anxiolytic-like activity with a bell-shaped dose-response curve in the elevated zero-maze model in rats (0.1-10 mg/kg, orally and s.c.), whereas in the mouse black/white box test and in the rat elevated plus-maze test it was less effective. The results suggest that CR 2945 might be a promising alternative to the existing therapy of anxiety-related disorders.
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PMID:CR 2945: a novel CCKB receptor antagonist with anxiolytic-like activity. 983 33

Molecular determinants of neuropathogenesis have been shown to be present in the hemagglutinin (H) protein of measles virus (MV). An H gene insertion vector has been generated from the Edmonston B vaccine full-length infectious clone of MV. Using this vector, it is possible to insert complete H open reading frames into the parental (Edtag) background. The H gene from a rodent brain-adapted MV strain (CAM/RB) was inserted into this vector, and a recombinant virus (EdtagCAMH) was rescued by using a modified vaccinia virus which expresses T7 RNA polymerase (MVA-T7). The recombinant virus grew at an equivalent rate and to similar titers as the CAM/RB and Edtag parental viruses. Neurovirulence was assayed in a mouse model for MV encephalitis. Viruses were injected intracerebrally into the right cortex of C57/BL/6 suckling mice. After infection mice inoculated with the CAM/RB strain developed hind limb paralysis and ataxia. Clinical symptoms were never observed with an equivalent dose of Edtag virus or in sham infections. Immunohistochemistry (IHC) was used to detect viral antigen in formalin-fixed brain sections. Measles antigen was observed in neurons and neuronal processes of the hippocampus, frontal, temporal, and olfactory cortices and neostriatum on both sides of symmetrical structures. Viral antigen was not detected in mice infected with Edtag virus. Mice infected with the recombinant virus, EdtagCAMH, became clinically ill, and virus was detected by IHC in regions of the brain similar to those in which it was detected in animals infected with CAM/RB. The EdtagCAMH infection had, however, progressed much less than the CAM/RB virus at 4 days postinfection. It therefore appears that additional determinants are encoded in other regions of the MV genome which are required for full neurovirulence equivalent to CAM/RB. Nevertheless, replacement of the H gene alone is sufficient to cause neuropathology.
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PMID:The H gene of rodent brain-adapted measles virus confers neurovirulence to the Edmonston vaccine strain. 1040 Jul 89