Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several dideoxynucleosides, including 3'-azido-2',3'-dideoxythymidine (zidovudine, azidothymidine, AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyinosine (ddI), have been shown to be potent inhibitors of human immunodeficiency virus (HIV) replication in human T cells and macrophages. These compounds undergo anabolic phosphorylation within target cells to a 3'-triphosphate moiety; as triphosphates, they act at the level of HIV DNA polymerase (reverse transcriptase). AZT has been shown to reduce the morbidity and mortality of patients with severe HIV infection and to at least temporarily ameliorate certain cases of HIV-induced dementia. In phase 1 studies, ddC and ddI have been shown to induce immunologic and virologic improvements in patients with AIDS or related disorders; phase 2 studies of ddC and ddI are underway. The use of these drugs can be associated with toxicity. AZT can cause bone marrow toxicity or myositis with prolonged use, ddC can cause peripheral neuropathy at high doses, and ddI can cause sporadic pancreatitis and peripheral neuropathy at high doses. For each compound, however, a therapeutic window exists in which an anti-HIV effect can be attained without short-term toxicity in most patients. Dose-intensity appears to be an important determinant of the toxicity of dideoxynucleosides. Studies are underway to explore how the therapeutic profiles of these compounds may be enhanced by attention to scheduling or through the use of combination therapy.
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PMID:Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. 207 27

Transforming growth factor-beta 1 (TGF-beta 1) induces angiogenesis in vivo and capillary morphogenesis in vitro. Two receptor serine/threonine kinases (types I and II) have been identified as signal transducing TGF-beta receptors. We explored the possibility of inhibiting TGF-beta-mediated events in glomerular capillary endothelial cells using a TGF-beta type II receptor (T beta R-II) transdominant negative mutant. A mutant TGF-beta type II receptor (T beta R-IIM), lacking the cytoplasmic serine/threonine kinase domain, was produced by polymerase chain reaction using rat T beta R-II cDNA as template. Since T beta R-II and TGF-beta type I receptor (T beta R-I) heterodimerize for signal transduction, the mutant receptor competes for binding to wild-type T beta R-I, hence acting in a dominant negative fashion. Glomerular capillary endothelial cells were stably transfected with T beta R-IIM, and four independent clones were expanded. That the T beta R-IIM mRNA was expressed was shown by reverse transcriptase-polymerase chain reaction, RNase protection assay, and Northern analysis. Presence of cell surface T beta R-IIM protein was shown by affinity cross-linking with 125I-TGF-beta 1. In wild-type endothelial cells, TGF-beta 1 (2 ng/ml) significantly inhibited [3H]thymidine incorporation to 63 +/- 10% of control (n = 4). In transfected endothelial cells carrying T beta R-IIM, TGF-beta 1 stimulated [3H]thymidine incorporation to 131 +/- 9% of control (n = 4, p < 0.005). Also, in wild-type endothelial cells, endogenous and exogenous TGF-beta 1 induced apoptosis and associated capillary formation. Both apoptosis and capillary formation were uniformly and entirely absent in transfected endothelial cells carrying T beta R-IIM. This represents the first demonstration that capillary morphogenesis in vitro is associated with apoptosis, and that interference with T beta R-II signaling inhibits this process in glomerular capillary endothelial cells.
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PMID:Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. 767 46

To investigate the pathogenesis of influenza myositis in animals, juvenile BALB/c mice were inoculated with influenza B/Lee virus intramuscularly into the right quadriceps muscle. Chicken normal allantoic fluid (NAF) or phosphate-buffered saline (PBS) was injected into the left quadriceps of control mice and in some virus-infected mice. Serum creatinine phosphokinase (CPK) levels rose significantly on days 1 and 2 post-inoculation (PI) in only virus-inoculated mice. On days 2 and 3 PI, right quadriceps muscles developed scattered foci of a predominantly mononuclear inflammation in the perimysial connective tissue often adjacent to degenerating or necrotic muscle fibers. Immunofluorescent staining with specific anti-influenza B virus antisera showed muscle fibers that contained specific staining in nuclei and adjacent cytoplasm. Skip areas of staining within muscle fibers suggested that not all muscle nuclei within an individual muscle fiber were infected. A continuous fall in infectious virus titer in the right quadriceps muscles suggested the initial virus inoculum became inactivated and progeny virions were not produced. Left quadriceps muscle never had muscle necrosis or endomysial inflammation, specific staining of viral antigen, virus isolation, or viral RNA detected by the reverse transcriptase polymerase chain reaction assay. These findings support the hypothesis that a non-permissive influenza viral infection can develop in murine skeletal muscle that can damage specific nuclear domains of muscle fibers producing muscle degeneration or necrosis. A similar type of muscle infection may develop in humans that occasionally develop focal myositis during influenza.
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PMID:Experimental influenza B viral myositis. 1144 Jul 46

Myositis in HIV may be due to HIV itself, or to opportunistic infection, malignancy or drug treatment. Severe myositis or rhabdomyolysis have never been reported with the commonly used nucleoside reverse transcriptase inhibitor abacavir, although creatine phosphokinase may rise modestly, particularly if abacavir hypersensitivity occurs. We report an unusual case of abacavir use associated with a thousand-fold rise in creatine phosphokinase in the absence of features of hypersensitivity. The case was also notable firstly in that there was an absence of the HLA-B5701 allele, the most common human leucocyte antigen (HLA) allele associated with hypersensitivity, and, secondly, as the case occurred in an African patient, African people not being prone to abacavir hypersensitivity.
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PMID:Severe myositis on commencement of efavirenz, abacavir and lamivudine, in the absence of lactic acidosis or classical abacavir hypersensitivity. 2168 32

A February 2015 outbreak of highly pathogenic avian influenza (HPAI) H5N8 in a flock of commercial Pekin ducks ( Anas platyrhynchos domesticus) in California was investigated in detail. Approximately 17,349 five-wk-old ducks experienced an increased mortality from a normal of eight birds per day to 24, 18, 24, 33, and 61 birds per day, respectively, in the last 5 days prior to flock depopulation. Clinically, there was decreased water and feed consumption, and approximately 1.0% of the affected flock exhibited neurologic signs. Necropsy of five clinically ill ducks revealed pale, patchy areas on the epicardium in two birds, pale foci of necrosis in the liver of one bird, and airsacculitis in three birds. Histopathology revealed multifocal nonsuppurative encephalomyelitis, myocarditis, myositis, pancreatitis, hepatitis, and glossitis. Immunohistochemistry revealed avian influenza virus (AIV) nucleoprotein in the nucleus and cytoplasm of various cells in the aforementioned organs, as well as in the skin and feathers. Eight of the 10 sera samples tested were positive for avian influenza antibodies by agar gel immunodiffusion serology. Oropharyngeal and cloacal swabs taken from 15 birds, as well as from the lungs, livers, pancreas, and spleen, were positive for AIV by real-time reverse transcriptase (rRT) PCR. AIV was isolated and typed as Eurasian lineage HPAI H5N8, clade 2.3.4.4, by the National Veterinary Services Laboratory, Ames, IA. Extensive surveillance of birds for AIV around the 10-km zone did not reveal any additional cases. Ducks on the affected premises were humanely euthanatized by foam and composted in-house, the houses were heated to 57 C for 4 days, and swabs were taken periodically from the compost to ensure negativity for AIV by rRT-PCR. The compost and litter were then removed, and the house was pressure cleaned, disinfected, and repopulated approximately 120 days after euthanatization of the ducks.
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PMID:Study of an Outbreak of Highly Pathogenic Avian Influenza H5N8 in Commercial Pekin Ducks ( Anas platyrhynchos domesticus) in California. 2962 Apr 70