Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the pathogenesis of either human and experimental myocardial ischaemia. Tacrolimus, formerly known as FK506, has been previously shown to display cardioprotective effects on experimental ischaemia/reperfusion-induced myocardial damage. This study investigated whether cardioprotection induced by tacrolimus in myocardial ischaemia-reperfusion (MI/R) injury might be due to inhibition of the nuclear factor kappa B (NF- kappaB) that in turn causes reduced cardiac ICAM-1 expression and blunted polymorphonuclear leukocyte accumulation. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity, serum creatine kinase (CK) activity, cardiac mRNA for ICAM-1 reverse-transcriptase polymerase chain reaction, the inhibitory protein of NF- kappaB I kappaB alpha (Western blot analysis) in the myocardium-at-risk, and left ventricle d P/d t(max)were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CK activity and myeloperoxidase activity (MPO, a marker of leukocyte accumulation) both in the area at risk and in the necrotic area, and reduced the left ventricle dP/d t(max). Furthermore, inhibitory protein I kappaB alpha levels decreased, and cardiac mRNA for ICAM-1 increased, after 0.5 and 5 h of reperfusion, respectively. Administration of tacrolimus (25, 50 and 100microg/kg as an i.v. infusion 5 min after reperfusion) lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in necrotic area, decreased serum CK activity, increased left ventricle dP/d t(max), reduced the loss the of inhibitory protein I kappaB alpha and blunted the message for ICAM-1. The present data suggest that tacrolimus blocks the early activation of the transcription factor NF- kappaB, suppresses ICAM-1 gene activation, reduces leukocyte accumulation and protects against myocardial ischaemia-reperfusion injury.
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PMID:Tacrolimus limits polymorphonuclear leucocyte accumulation and protects against myocardial ischaemia- reperfusion injury. 1073 42

In this paper, we report our experience with the use of rituximab (RTX) in the treatment of refractory idiopathic inflammatory myopathies (IIM) and review the literature on this topic. Six adult patients (5 female, 1 male) with active IIM, as defined by persistent proximal muscle weakness, elevated serum muscle enzymes, muscle magnetic resonance imaging, electromyographic and histological abnormalities, refractory to at least one immunosuppressant, including methotrexate, were treated with RTX (1,000 mg twice, 2 weeks apart). Patients were regularly followed up for serial assessment of muscle strength by manual muscle test 8 and creatine kinase serum levels. Three patients were affected with polymyositis (PM) and three with anti-t-RNA synthetase syndrome (ASS). A complete B-cell depletion was observed in all patients by 3 months after RTX. A significant clinical improvement was observed in 5 out of 6 cases 6 months after RTX. Only one mild infusion reaction and one case of Herpes zoster infection were observed. A review of the literature to find all the available cases of refractory patients affected with IIM from 1980 to 2012, using the PubMed database, was performed. We were able to find 27 papers, 18 on PM and dermatomyositis and 9 on ASS, including 88 and 40 patients, respectively. A significant improvement was observed in 80% of patients overall and the drug was well tolerated in the majority of cases. In conclusion, RTX can be considered a therapeutic option in refractory IIM.
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PMID:Rituximab in refractory idiopathic inflammatory myopathies and antisynthetase syndrome: personal experience and review of the literature. 2357 27

Of 207 adult patients with idiopathic inflammatory myopathies, detection of autoantibodies by RNA immunoprecipitation showed that 99 patients (48%) were antibody-positive. We divided these 99 into five subgroups: anti-signal recognition particle (SRP), anti-aminoacyl transfer RNA synthetase, anti-Ku, anti-U1RNP, and anti-SSA/B. Younger age at onset, severe weakness, muscle atrophy, elevated creatine kinase, and necrosis in muscle fibers without inflammatory cell infiltration were found significantly more frequently among the patients with anti-SRP antibodies (n=41) compared to the antibody-negative patients (n=108). Autoantibody detection by RNA immunoprecipitation can provide useful information associated with clinical and histological findings.
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PMID:Clinical and histological findings associated with autoantibodies detected by RNA immunoprecipitation in inflammatory myopathies. 2506 97

Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians' knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.
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PMID:[Pulmonary manifestations of antisynthetase syndrome]. 2623 12

A 52-year-old woman was admitted to our hospital with muscle pain and an elevated creatine kinase level. She had experienced wrist pain at onset seven years ago. The initial possible diagnoses were rheumatoid arthritis and adult-onset Still disease. The patient received corticosteroid and immunosuppressant therapy but experienced deterioration of symptoms. The symptoms of muscle pain and mild creatine kinase elevation emerged four years prior to her visit. Further elevation of creatine kinase was observed for three months before her visit despite adjusting the immunosuppressant dose. On admission, she presented with muscle moderate weakness of the trunk and extremities and pain of the shoulder and medial thigh muscles. Elevation of muscle enzymes and inflammatory response were also detected, and the anti-PL7 antibody was positive. Muscle biopsy from biceps brachii revealed necrotizing myopathy with necrotic and regenerated muscle fibers. The final diagnosis was anti-PL7 antibody positive myositis. The patient was treated with a higher dose of prednisolone and an adequate dose of tacrolimus. Following this treatment, the symptoms were improved. Anti-ARS (aminoacyl t-RNA synthetase) antibodies such as anti-PL7 antibody are useful in diagnosis and for prognostic prediction. Further investigation of patients with anti-ARS antibodies positive myositis is required.
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PMID:[A case of anti-PL7 antibody positive myositis and a clinical and pathological review of the anti-synthetase syndrome]. 2645 69

The case is about a 48-year-old man with one week history of progressively worsening shortness of breath and reduced exercise tolerance. Laboratory investigations revealed raised ESR, creatine kinase (CK) and positive anti-aminoacyl-transfer RNA synthetase. High resolution computed tomography (HRCT) chest showed prominent mediastinal lymph nodes and scattered lung nodules. These findings along with clinical features and investigations confirmed the diagnosis of antisynthetase syndrome (ASS). The radiological investigations proved to be the key step in diagnosis and management of this case.
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PMID:Antisynthetase syndrome: a case report. 2719 Jul 73