Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleoside analog 2',3'-dideoxycytidine (ddC) is a potent inhibitor of the reverse transcriptase of human immunodeficiency virus and a DNA chain terminator. In clinical trials in patients with acquired immunodeficiency syndrome, ddC treatment has been associated with a dose-limiting and dose-dependent, painful, sensorimotor peripheral neuropathy. In search of an animal model for ddC-induced neurotoxicity we studied 36 New Zealand White rabbits (3 males/3 females/group) given 0, 10, 50, 100, 150, or 250 mg/kg/day of ddC, by oral intubation, for 13 or 18 weeks. Rabbits in the 150 and 250 mg/kg/day groups were sacrificed at 13 weeks because of hematopoietic toxicity. After 16 weeks, rabbits in the 50 and 100 mg/kg/day groups showed hindlimb paresis and/or gait abnormalities. Nerve conduction velocities and amplitudes in the 100 mg/kg/day rabbits were reduced by 30 to 50%. The most prominent pathologic changes in peripheral nerve and ventral roots of ddC-treated rabbits were (a) myelin splitting and intramyelinic edema, (b) demyelination and remyelination of axons, and (c) axonal loss. Treatment-related histologic lesions were not observed in spinal cord, brain, or retina. The pathology in these ddC-treated rabbits is consistent with a peripheral myelinopathy and axonopathy. This represents the first clinical, electrophysiologic, and pathologic description of an animal model of a peripheral neuropathy induced by a nucleoside analog.
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PMID:Peripheral neuropathy induced by 2',3'-dideoxycytidine. A rabbit model of 2',3'-dideoxycytidine neurotoxicity. 130 30

The aim of this longitudinal observational study was to investigate and describe the spectrum of messenger ribonucleic acid (mRNA) expression of multiple inflammatory markers in circulating leukocytes after major orthopaedic surgery. We studied ten elective arthroplasty patients perioperatively on the orthopaedic ward, and eight healthy volunteers for a comparison group. Venous blood specimens were collected preoperatively, and 6, and 24 hours postoperatively, together with 6- and 24-hour postoperative wound drain specimens. The mRNA of 21 different inflammatory mediators was measured by real-time reverse transcriptase Polymerase Chain Reaction. Comparisons were made with the venous blood of eight healthy comparison subjects. There were significant differences (P<0.01) between preoperative specimens and normal comparisons (i.e. higher MPO, PDGF, TREM and IRAKM; lower mtHSP) reflecting the effects of chronic inflammation associated with osteoarthritis. There were significant increases (P<0.01) in expression of IL-8, MPO, IL-1beta, TREM, MMP9, and C5aR in circulating blood at 24 hours postoperatively, but not at six hours. There was no significant decrease in expression of any inflammatory mediator. There was no statistical difference in inflammatory mediator expression between drain specimens and venous specimens taken at the same time. We conclude that, in uncomplicated orthopaedic surgical patients, there was up-regulation of some cytokine mRNAs at both the local and systemic levels during the first day after surgery. We observed no evidence of immune compartmentalization, and found no evidence for innate immune paresis within the first day after surgery.
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PMID:Messenger RNA expression of multiple immune mediators in leukocytes from elective orthopaedic surgical patients. 1595 15

Hereditary congenital facial paresis is a rare autosomal dominantly inherited disorder, in which pathological changes in the brainstem affect the paired facial nuclei and nerves. Previously, the neuropilin-1 protein has been shown to control axon guidance and cell body position of facial motor neurons, and mice with a targeted disruption of neuropilin-1 present with developmental defects of the facial nerve nuclei. Plexin-A1 can function as a signal transducing subunit for the neuronal neuropilin receptor, and its gene is located in the linkage interval for hereditary congenital facial paresis at chromosome 3q21-q22 (MIM601471), making it an excellent candidate gene for this disorder. During mouse embryogenesis, the murine ortholog of plexin-A1 gene showed restricted spatial and temporal expression in the hindbrain, consistent with a role in cell body movement, or axonal guidance during facial nerve development. Sequence analysis of the plexin-A1 gene in patients from the 3q21-q22-linked hereditary congenital facial paresis family revealed several nucleotide changes. However, none of the nucleotide changes led to an amino acid substitution, and reverse transcriptase polymerase chain reaction analysis did not detect aberrant RNA processing. We therefore conclude that it is highly unlikely that Plexin-A1 is involved in the pathogenicity of hereditary congenital facial paresis.
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PMID:Nucleotide variation analysis does not support a causal role for plexin-A1 in hereditary congenital facial paresis. 1599 56