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)

The ribonucleoprotein (RNP) p67 antigen was purified from rabbit thymus and used in an enzyme linked immunosorbent assay (ELISA) with low interassay variability to detect IgG antibodies to p67 in patients with autoimmune connective tissue diseases. These antibodies were found in eight (80%) patients with a clinical diagnosis of mixed connective tissue disease (MCTD) but also in 27 (40%) patients with systemic lupus erythematosus (SLE). Sixty six per cent of the 12 patients with SLE with high levels of antibodies to p67 (> 50 U) had three or more features of MCTD, including myositis, fibrosing alveolitis, Raynaud's phenomenon, and sclerodactyly. Antibodies to the p67 RNP were not associated with the presence or absence of renal disease in the patients with SLE. This study suggests that antibodies against the p67 RNP are markers for clinical features of MCTD even in the context of SLE.
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PMID:Clinical associations of IgG antibodies to the ribonucleoprotein p67 polypeptide in patients with systemic lupus erythematosus. 148 13

We identify 4 patients with progressive systemic sclerosis (PSS) possessing a previously undescribed serum anti-tRNA Ab (anti-Wa antibody). These sera yielded identical precipitin lines under double immunodiffusion using calf thymus extract and supernatant of pig spleen homogenate as antigen sources. Furthermore, all 4 sera were found to react with a 48 kDa protein using immunoblotting. This protein was subsequently found to be associated with tRNA when immunoprecipitation was conducted. In a survey of autoimmune patients' sera, anti-Wa Ab was observed in 3% (4 of 130) of patients with PSS, but not in other systemic rheumatic diseases. None of the 4 patients with PSS with anti-Wa Ab had myositis except that one patient complained of mild myalgia.
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PMID:A novel autoantibody reactive with a 48 kDa tRNA associated protein in patients with scleroderma. 190 37

Antibodies to Mi, an antigen in calf thymus extract, have been demonstrated by complement fixation inhibition in polymyositis (PM) and dermatomyositis (DM) sera but not in the sera of individuals without myositis. The original Mi reference serum defined 2 precipitating antibodies, using immunodiffusion (ID). Anti-Mi-1 was not active in complement fixation. We have now studied in further detail anti-Mi-2, which appears to be the antibody in Mi serum that fixes complement. Mi-2 antigen was purified by immuno-affinity chromatography. An enzyme-linked immunosorbent assay (ELISA) to measure Mi-2 antibody, using this antigen, was used to test the sera of 139 myositis patients: 52 had DM and 87 had PM. Control sera from 35 normal subjects and 93 patients with other connective tissue diseases were also tested. Only 13 sera were considered definitely positive for anti-Mi-2. All were from patients who had myositis, 11 of whom had DM. Only DM sera had anti-Mi-2 by ID, and all sera with anti-Mi-2 by ID were positive by ELISA. A number of other sera, including many from patients with other connective tissue diseases and 2 from normal subjects (all without precipitating antibodies) had lower elevations which were of uncertain significance. Detection of anti-Mi-2 by ID as well as by ELISA was significantly more frequent in DM than in PM. Anti-Mi-2 appears to be closely linked to DM, and is the first specific serologic marker for this form of myositis.
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PMID:The association between Mi-2 antibodies and dermatomyositis. 240 85

Experimental infection with Herpesvirus sylvilagus produces clinical and histopathologic changes in its natural host, the cottontail rabbit (Sylvilagus floridanus), similar to those observed in humans acutely infected with Epstein-Barr virus (EBV). Twenty-seven seronegative cottontail rabbits were infected with Herpesvirus sylvilagus and all developed antibodies within 10 days. Neutralizing antibody was detected as early as 7 days after infection. Virus was isolated from blood mononuclear cells, spleen, bone marrow, thymus, lymph nodes, kidneys, lung, and liver as early as 3 days after infection. Infected animals showed leucocytosis, monocytosis, and lymphocytosis with the appearance of atypical lymphocytes. Peripheral blood abnormalities peaked at 10-14 days after infection, and returned to normal by 28 days after infection, with the exception of atypical lymphocytosis that persisted in some animals for more than 2 years after experimental infection. More severe histopathologic changes were seen in virus-infected juvenile rabbits than adult rabbits; these changes included viral myocarditis, interstitial pneumonia, and lymphocytic myositis. Reactive hyperplasia and subsequent lymphocytic depletion of spleen and lymph nodes were reminiscent of that seen in virus-associated hemophagocytosis syndrome. Prominent lymphoid hyperplasia of many nonlymphoid organs, most notably the kidney and lungs, was observed. The development of these lymphoproliferative lesions and other lymphoid changes during H. sylvilagus infection suggest that this system may be a model to study similar lesions induced by EBV infection in humans.
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PMID:Pathogenesis of Herpesvirus sylvilagus infection in cottontail rabbits. 284 3

The increased detection of anti-Jo-1 antibody afforded by the use of the purified antigen, histidyl-tRNA synthetase, in counterimmunoelectrophoresis is demonstrated. Using purified antigen, anti-Jo-1 antibody was detected in the sera of 16/33 (48.5%) patients with confirmed myositis and in 20/45 (44.5%) patients with confirmed or possible myositis. This rate is approximately double that obtained with commercial thymus extracts both in this study and seven others reported in the literature. The presence of antibody shows marked correlation with the activity of myositis at the time of serum sampling and with the presence of interstitial lung disease. Detection rates are similar in patients with polymyositis and dermatomyositis both with and without additional connective tissue diseases.
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PMID:Improved detection of anti-Jo-1 antibody, a marker for myositis, using purified histidyl-tRNA synthetase. 310 Jun 49

Syngeneic rat radiation chimeras treated transiently with cyclosporine (CsA) often develop a GVHD-like syndrome after discontinuing the drug. CsA also causes medullary involution and loss of medullary epithelium in the thymus. Chronic graft-versus-host disease (GVHD), a late occurring syndrome following bone marrow transplantation with many features of autoimmune diseases, is thought by many to result from a thymic deficiency leading to a failure to develop specific tolerance for the host. A direct connection between a thymic deficiency and chronic GVHD was tested by transferring thymocytes from CsA-treated syngeneic Lewis chimeras into irradiated Lewis secondary recipients. Nine of 10 of these recipients had evidence of chronic GVHD in skin biopsies taken at 3 weeks posttransplant or in the autopsies at 5 weeks. Changes included characteristic lichen planuslike infiltrates and sclerodermalike changes in the skin, characteristic infiltrates and myositis of the tongue, often chronic hepatitis with bile duct injury, and interstitial and ductal infiltrates in the serous salivary glands. Immunoperoxidase stains of the skin and tongue infiltrates showed a marked predominance of W3/25+:OX8- lymphocytes. The hair follicles had increased expression of Ia antigen. The thymus in the secondary recipient had variable thymocyte reconstitution of the cortex and a mild to marked reduction in the relative size of the medulla. Stains for cytokeratin showed a moderate to marked reduction of cortical epithelium and marked to total loss of the medullary epithelium. These studies demonstrate that the features of post-CsA syngeneic GVHD resembling chronic GVHD result from an abnormal thymic microenvironment. They also provide additional evidence linking a thymus deficiency with chronic GVHD.
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PMID:Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes. Resemblance to chronic graft-versus-host disease. 325 8

A comparative pathogenesis study was performed in neonatal mice using a molecularly cloned laboratory variant of Sindbis strain AR339, designated TRSB, and a single-site attenuated mutant of TRSB derived by site-directed mutagenesis of the E2 glycoprotein from Ser to Arg at residue 114 (TRSBr114). TRSB caused 100% mortality with an average survival time of 3.0 +/- 0.7 days, whereas mice inoculated with TRSBr114 exhibited an attenuated disease course with 46% mortality and an extended average survival time of 7.5 +/- 3.4 days for those animals that died. Reduced virulence of TRSBr114 was characterized by delayed appearance of detectable virus, relative to TRSB, and by lower peak virus titers in both sera and brains of infected mice. TRSB infection induced very high peak serum titers of interferon alpha/beta (215,000 units/ml compared to 2100 units/ml for TRSBr114). In situ hybridization analysis demonstrated replication of TRSB in brain, but only minimal histopathological changes and no evidence of encephalitis were observed. However, extensive extraneural lesions and viral replication were found in skin, connective tissue, and muscle. Moreover, dramatic involution of the thymus and loss of hematopoietic tissues were observed in the absence of virus replication at these sites, suggesting the involvement of a systemic physiological stress response in TRSB infection. TRSBr114 infection did not cause thymic lesions. Otherwise, the attenuated mutant demonstrated a similar pattern of tissue and organ involvement, but lesions and positive in situ hybridization signal were much more limited in scope and intensity compared to TRSB. TRSBr114-infected mice developed myositis and encephalomyelitis approximately 6 days postinfection. Therefore, TRSB-infected animals may succumb to an early syndrome associated with the stress response, preventing their survival for a time sufficient for the development of encephalitis. Alternatively, a systemic stress response, as evidenced by thymic involution, may result in immunosuppression, thus contributing to the absence of encephalitis. In any event, the attenuating mutation in the E2 glycoprotein significantly altered the course of Sindbis-induced disease by limiting virus replication and associated damage early in infection. Mutant-infected animals survived beyond Day 4 and progressed to a classical encephalomyelitis from which about half recovered.
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PMID:Fatal Sindbis virus infection of neonatal mice in the absence of encephalitis. 886 1

In the present study, the autoantibody profile of 31 Slovenian patients with idiopathic inflammatory muscle disease was estimated: 11 with polymyositis, 11 with dermatomyositis--both groups diagnosed according to the criteria of Bohan and Peter--and 9 with myositis-overlap syndromes. Autoantibodies against most relevant muscle specific (Jo-1, Mi-2) and non-specific antigens (PM-Scl, U1RNP, native Ro, Ro60, Ro52, and La) were detected with one or more detection techniques: counter-immunoelectrophoresis, enzyme-linked immunoassay, immunoblot and immunoprecipitation, each using different antigen preparations (native, recombinant). With counter-immunoelectrophoresis using a native antigen substrate (rabbit thymus extract), we were able to detect anti-PM-Scl antibodies more readily than with other techniques, probably due to conformational epitopes of native PM-Scl. Patients with this serological profile constituted a distinct group, sharing features of polymyositis and systemic sclerosis. Compared to previously reported data, the greater frequency of anti-Jo-1 found in all groups of patients (64-87% for PM, 18-20% for dermatomyositis and 33-44% for overlap syndromes) was probably due to the various methods used and the different clinical characteristics of patients. The greater prevalence of anti-Mi-2 antibodies in dermatomyositis patients (67%) and in particular in polymyositis patients (33%) and myositis-overlap syndromes (33%) seemed to be mainly due to methodological differences. A strikingly high prevalence of anti-Ro52 positive patients with polymyositis (55%), dermatomyositis (22%), and myositis-overlap syndromes (33%) was demonstrated, but was detected by only one technique. Moreover, concurrence with anti-Jo-1 antibodies was noted (69%).
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PMID:Immunoserological aspects of idiopathic inflammatory muscle disease. 1102 Sep 64

A STUDY HAS BEEN MADE OF THE LESIONS PRODUCED IN SUCKLING MICE BY THE FOLLOWING VIRUSES: Powers, Matulaitis, DeMole, Kine, McCarthy, Conn. 5, Ohio R, High Point, WS No. 4, EMC, and Col. SK. Pathologic alterations have been found in myocardium, lungs, liver, pancreas, thymus, brain and spinal cord, adipose tissue, and skeletal muscles. A comparison of the lesions produced by the individual strains has disclosed certain differential features which are discussed in detail. Within the group of so called Coxsackie viruses, myositis has not proved to be a constant finding, and it may occur in suckling mice infected with other types of virus.
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PMID:Lesions caused in suckling mice by certain viruses isolated from cases of so called non-paralytic poliomyelitis and of pleurodynia. 1542 85

Checkpoint inhibitors represent a new class of therapeutics in the treatment of cancer that has demonstrated remarkable clinical effectiveness. However, some patients have experienced serious immune-mediated adverse effects including pneumonitis, hepatitis, colitis, nephritis, dermatitis, encephalitis, and adrenal or pituitary insufficiency. These adverse events were not predicted by nonclinical studies. To determine if bone marrow-liver-thymus (BLT) immune humanized mice could demonstrate these adverse effects, we studied the effect of nivolumab on 2 strains of BLT-humanized mice, NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) and NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(SV40/HTLV-IL3, CSF2)10-7Jic/JicTac (NOG-EXL). Mice were treated with 2.5, 5.0, or 10.0 mg/kg nivolumab or saline twice weekly for 28 days. BLT-NOG mice had significantly reduced survival compared with BLT-NOG-EXL mice. In spite of the difference in survival, both BLT-humanized strains showed adverse reactions similar to those reported in humans, including pneumonitis and hepatitis, with nephritis, dermatitis and adrenalitis also noted in some individuals. Additional histopathologic findings included pancreatic atrophy, myositis, and osteomyelitis in some animals. T-cell activation increased with concomitant loss of PD-1 detection. These findings show that BLT immune humanized mice can demonstrate immune-mediated adverse effects of antiPD1 therapy, and may represent a model that can be used to better understand toxicity of this class of drugs.
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PMID:BLT-Immune Humanized Mice as a Model for Nivolumab-Induced Immune-Mediated Adverse Events: Comparison of the NOG and NOG-EXL Strains. 3085 Aug 39


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