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

Electron microscopy of skeletal muscle biopsy from a case of human sarcocystosis revealed a new cyst type of S. lindemanni. The sarcocyst appeared large having a thick cyst wall with evident septa extending into the cyst and, characteristically, broad branched cauliflower like protrusions extending into the pericystic zone. This cyst type appeared to be highly pathogenic. In addition to the complete myofibrillar lysis of the infected muscle-fibre, there were delamination of the neighbouring myofibres, disruption of the sarcomeric orientation with dearrangement and bending oft he Z bands and loss of the T and L myofibrillar pattern in the pericystic zone. Features of myositis such as the presence of abundant lysosomal structures, myofibrillar disarray and glycogen formations were detected. These cytopathogenic signs were obviously attributed to the structural criterion of the cyst wall. The findings not only invalidate the concept that pathological conditions associated with human sarcocytosis are accidental, but also stress the value of electron microscopy in inducing relevant typing of sarcocysts on basis of their morphologically expressed pathogenic properties.
 ...
PMID:Ultrastructure of the cyst wall of S. lindemanni with pathological correlations. 211 Feb 29

In two different groups of mice, the infection with Toxoplasma gondii was produced by intraperitoneal route, with 2 x 10(5) parasites (n = 8) and 14 x 10(5) parasites (n = 3). Five days after infection animals were killed to examine skeletal muscles by light and transmission electron microscopy. Severity of muscle alterations depended upon concentration of parasites. Parasite cysts were not identified in muscle sections. Ultrastructural features revealed different degrees of fibre atrophy, alterations in the sarcomeric structure and, in some cases, disorganization of contractile and sarcotubular systems. Changes in muscular capillaries included loss of the endothelial wall, occlusion of lumen and necrosis. Motor end-plates were abnormal and axonolysis was present. A mononuclear cell infiltrate consisted of macrophages, lymphocytes, mastocytes and eosinophils were observed. In this murine model it was demonstrated that the infection of non-immunocompromised hosts with Toxoplasma gondii produces an acute myositis.
 ...
PMID:Skeletal muscle pathology in mice experimentally infected with Toxoplasma gondii. 893 35

Mammalian skeletal muscle cells are composed of repeated sarcomeric units containing thick and thin filaments of myosin and actin, respectively. Excitation of the myosin ATPase enzyme is possible only with presence of Mg-ATP and Ca(2+). Skeletal muscle fibres may be classified into several types according to the isoform of myosin they contain. Nine isoforms of myosin heavy chain are known to exist in mammalian skeletal muscle including type I, IIA, IIB, IIX, IIM, alpha, neonatal, embryonic, and extra-ocular. Healthy adult human limb skeletal muscle contains type I, IIA, IIB, and IIX myosin heavy chains. The jaw-closing muscles of most carnivores and primates have tissue-specific expression of the type IIM or 'type II masticatory' myosin heavy chain. Adult human jaw-closing muscles, however, do not contain IIM myosin. Rather, they express type I, IIA, IIX (as in human limb muscle), and myosins typically expressed in developing or cardiac muscle. The morphology of human jaw-closing muscle fibres is also unusual in that the type II fibres are of smaller diameter that type I fibres, except in cases of increased function and hypertrophy. This paper describes the relationship of fibre types and motor unit function to changes in human occlusion and masticatory activity. Refereed Scientific Paper
 ...
PMID:Skeletal muscle function and fibre types: the relationship between occlusal function and the phenotype of jaw-closing muscles in human. 1079 Apr 41

Muscular dystrophy with myositis (mdm) is a recessive mouse mutation that is caused by a small deletion in the giant elastic muscle protein titin. Homozygous mdm/mdm mice develop a progressive muscular dystrophy, leading to death at approximately 2 months of age. We surveyed the transcriptomes of skeletal muscles from 24 day old homozygous mdm/mdm and +/+ wild-type mice, an age when MDM animals have normal passive and active tensions and sarcomeric structure. Of the 12488 genes surveyed (U74 affymetrix array), 75 genes were twofold to 30-fold differentially expressed, including CARP (cardiac ankyrin repeat protein), ankrd2/Arpp (a CARP-like protein) and MLP (muscle LIM protein), all of which associate with the titin filament system. The four genes most strongly affected (eightfold to 30-fold change) were all members of the CARP-regulated Nkx-2.5-dependent signal pathway, and CARP mRNA level was 30-fold elevated in MDM skeletal muscle tissues. The CARP protein overexpressed in MDM became associated with the I-band region of the sarcomere. The mdm mutation excises the C-terminal portion of titin's N2A region, abolishing its interaction with p94/calpain-3 protease. Thus, the composition of the titin N2A protein complex is altered in MDM by incorporation of CARP and loss of p94/calpain-3. These changes were absent from the following control tissues (1). cardiac muscles from homozygous mdm/mdm animals, (2). skeletal and cardiac muscle from heterozygous mdm/+ animals, and (3). dystrophic muscles from MDX mice. Thus, the altered composition of the titin N2A complex is specific for the titin-based skeletal muscular dystrophy in MDM.
 ...
PMID:Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling. 1474 Dec 10

Human tibial muscular dystrophy and limb-girdle muscular dystrophy 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for the muscle-specific protease calpain 3 (CAPN3). Muscular dystrophy with myositis (mdm) is a recessive mouse mutation with severe and progressive muscular degeneration caused by a deletion in the N2A domain of titin (TTN-N2ADelta83), disrupting a putative binding site for CAPN3. To determine whether the muscular dystrophy in mutant mdm mice is caused by misregulation of CAPN3 activity, genetic crosses with CAPN3 overexpressing transgenic (C3Tg) and CAPN3 knockout (C3KO) mice were generated. Here, we report that overexpression of CAPN3 exacerbates the mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, in a direct genetic test of CAPN3's role as a mediator of mdm pathology, C3KO;mdm double mutant mice showed no change in the progression or severity of disease indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. To determine whether we could detect a functional deficit in titin in a non-disease state, we examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. Interestingly, these altered gait parameters were completely corrected by CAPN3 overexpression in transgenic C3Tg;+/mdm mice, supporting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction.
 ...
PMID:Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain. 1611 18

Since its belated discovery, our understanding of the giant protein titin has grown exponentially from its humble beginning as a sarcomeric scaffold to recent recognition of its critical mechanical and signaling functions in active muscle. One uniquely useful model to unravel titin's functions, muscular dystrophy with myositis (mdm), arose spontaneously in mice as a transposon-like LINE repeat insertion that results in a small deletion in the N2A region of titin. This small deletion profoundly affects hypertrophic signaling and muscle mechanics, thereby providing insights into the function of this specific region and the consequences of its dysfunction. The impact of this mutation is profound, affecting diverse aspects of the phenotype including muscle mechanics, developmental hypertrophy, and thermoregulation. In this review, we explore accumulating evidence that points to the N2A region of titin as a dynamic "switch" that is critical for both mechanical and signaling functions in skeletal muscle. Calcium-dependent binding of N2A titin to actin filaments triggers a cascade of changes in titin that affect mechanical properties such as elastic energy storage and return, as well as hypertrophic signaling. The mdm phenotype also points to the existence of as yet unidentified signaling pathways for muscle hypertrophy and thermoregulation, likely involving titin's PEVK region as well as the N2A signalosome.
 ...
PMID:N2A Titin: Signaling Hub and Mechanical Switch in Skeletal Muscle. 3249 76