Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoantibodies to striated and smooth muscles myosins were detected by indirect immunofluorescence and confirmed by absorption with purified contractile proteins extracted from human, rabbit and chicken muscle. Myosin antibodies were rare: of fifty-five sera examined from patients with various skeletal and cardiac muscle disorders, only one serum, from a case of Coxsackie viral pericarditis, had anti-myosin activity. It reacted with cardiac muscle and type 1 fibres of skeletal muscle, staining the 'A' band of the sarcomere only. The antibody was absorbed by skeletal myosin and by skeletal heavy meromyosin fragments, but not by smooth muscle myosin. Two types of smooth muscle myosin autoantibodies are described. One is restricted to smooth muscle myosin and examples were found in polyclonal and monoclonal SMA sera. The second type of smooth muscle myosin antibody cross-reacted with skeletal and cardiac muscle and with cytoplasmic myosin in liver, kidney and thyroid cells. It was completely absorbed using either smooth or skeletal myosin and by heavy meromyosin fragments. The different types of myosin autoantibodies reflect the variety of myosins found in mammalian tissues. Cross-reacting myosin antibodies indicate epitopes on the heavy meromyosin fragment which are common to several different tissue myosins.
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PMID:Myosin autoantibodies detected by immunofluorescence. 32 77

The objective of this study was to investigate the localization and hormonal regulation of smooth muscle myosin II (SMM II) and alpha smooth muscle actin (alpha SMA) in the baboon uterus, since cytoskeletal proteins are involved in secretory function and morphological transformation. Uterine tissue was obtained from baboons 1) during the menstrual cycle, 2) following steroid treatment of ovariectomized baboons, 3) during pregnancy (Days 14-60 postovulation [PO]), and 4) during simulated pregnancy (Days 18-32 PO). Tissues were processed for immunocytochemical localization of SMM II or alpha SMA with specific polyclonal or monoclonal antibodies, respectively. SMM II stained all smooth muscle cells of blood vessels and myometrium regardless of treatment. Glandular epithelial staining was present only in endometrium obtained during the luteal phase or following estrogen and progesterone treatment. Staining intensity was greater in the basalis than in the functionalis. The number of glands staining positive for SMM II on Days 18-32 of pregnancy and simulated pregnancy was variable. Glandular stain was absent after Day 32 PO. These immunocytochemical data were confirmed by immunoblot analysis of glandular cytosolic extracts. Stromal staining for SMM II was present under the luminal epithelium during simulated pregnancy (Days 18-32), on Day 25 of steroid treatment in the simulated-pregnant controls, and in nonimplantation sites during pregnancy. In contrast, alpha SMA staining was low or absent in all uterine cell types in ovariectomized baboons. Under estrogen-dominated conditions (follicular phase and estrogen treatment), alpha SMA staining was present in smooth muscle cells, and this staining persisted throughout the remaining treatment periods. Glandular epithelial staining for alpha SMA was absent in all treatment groups. However, alpha SMA staining in stromal fibroblasts underneath the luminal epithelium was evident as early as Day 14 of pregnancy and Day 18 of simulated pregnancy. The number of stromal fibroblasts that stained positive increased in the surface region of the functionalis between Days 18 and 32 PO, and the staining extended throughout the upper functionalis region. There was a decrease in the number of positively stained stromal fibroblasts, particularly at the implantation site, between Days 32 and 40 of pregnancy. By Days 50-60 of pregnancy, this staining was almost absent. The induction of alpha SMA in stromal fibroblasts in the functionalis region in pregnant baboons was confirmed by immunoblot analysis of stromal cell cytosol extracts. We conclude that the progesterone-induced glandular expression of SMM II may be involved in uterine secretory function and that alpha SMA expression in stromal fibroblasts during pregnancy and after long-term steroid treatment is associated with the decidualization process.
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PMID:Smooth muscle myosin II and alpha smooth muscle actin expression in the baboon (Papio anubis) uterus is associated with glandular secretory activity and stromal cell transformation. 757 84

Immunocytochemical and biochemical analyses were carried out on patients affected by chronic SMA. Three groups of patients were identified. In group I, the muscle presented a fascicular atrophy; a high percentage of atrophic type II fibers; and fibers expressing fast, slow, embryonic, and fetal myosin isoforms. In group II, the muscle was characterized by atrophic fibers and normal/hypertrophic fibers expressing only slow myosin isoforms. In group III, the muscle was characterized by fiber type grouping and fibers coexpressing fast and slow myosin isoforms but never embryonic or fetal MHC isoforms. The muscles of groups I and III contained both fast and slow myosins whereas group II muscles were predominantly slow by immunocytochemical analysis or only slow by biochemical analysis. In view of these results, immunocytochemical and histochemical analyses could help to classify chronic SMA and help to understand the different pathogenic processes which seem to be related to the maturational stage of the muscle at the age of onset of the disease.
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PMID:Biochemical and immunocytochemical analysis in chronic proximal spinal muscular atrophy. 817 Apr 86

Myoepithelial cells of salivary glands have a complex cytoskeletal immunophenotype. To elaborate the smooth muscle phenotype of salivary gland myoepithelium and to assess its contribution to the histogenesis of pleomorphic adenomas, we evaluated the immunohistochemical expression of three novel monoclonal antibodies (MAbs) to alpha smooth muscle actin (alpha-SMA), smooth muscle myosin heavy chains (SMMH), and calponin in formalin-fixed tissues of 65 pleomorphic adenomas (51 contained surrounding normal salivary gland as well). Different cell types within the pleomorphic adenomas were classified as inner tubular epithelial cells, myoepithelium-like cells (juxtatubular, cuboidal, and spindle), modified myoepithelium (myxoid, chondroid, hyaline), and transformed myoepithelium (solid epithelioid, squamous, basaloid-cribriform). Periacinar and periductal myoepithelial cells of all of the 51 normal salivary glands were diffusely stained by all of the 3 MAbs, whereas all of the acinar/ductal epithelial cells were entirely negative. Of 65 pleomorphic adenomas, 61 (94%) reacted to all of the 3 MAbs. None of the smooth muscle markers stained the inner-tubular epithelial cells. Both alpha-SMA and SMMH were essentially limited to the myoepithelium-like cells, whereas modified and transformed myoepithelia lacked these myofilaments. Calponin was found in 64 (98%) of the tumors, reacting to almost all of the myoepithelium-like cells, to 60% of the modified myoepithelium, and to 30% of the transformed myoepithelium. We found the expression of these smooth muscle-specific proteins in the neoplastic myoepithelium to be associated with morphologic differentiation. Alpha-SMA and SMMH are only expressed in better differentiated neoplastic myoepithelium. Calponin is the most sensitive marker of neoplastic myoepithelium, and its identification in different cell types of pleomorphic adenomas denotes a major histogenetic role of myoepithelial cells.
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PMID:Immunolocalization of three novel smooth muscle-specific proteins in salivary gland pleomorphic adenoma: assessment of the morphogenetic role of myoepithelium. 938 59

Smooth muscle myosin heavy chains (MHCs), the motor proteins that power smooth muscle contraction, are produced by alternative splicing from a single gene. The smooth muscle MHC gene is capable of producing four isoforms by utilizing alternative splice sites located at the regions encoding the carboxy terminus and the junction of the 25- and 50-kDa tryptic peptides. These four isoforms, SM1A, SM1B, SM2A, and SM2B, are a combination of one of two heavy chains containing different carboxy-terminal tails (1 or 2) without (A) or with (B) an additional motif in the myosin head. In the present study, using RNA analysis and isoform-specific antibodies, we demonstrate the expression patterns of MHC isoforms during development in rat smooth muscle tissues. RNase protection analysis indicates that the mRNAs for SMA and SMB isoforms, which differ by a 21-nucleotide insertion in the region encoding the S1 head region of the myosin molecule, are differentially expressed during development in a highly tissue-specific manner. Smooth muscle MHC transcripts are first detectable in developing rat smooth muscle tissues at 17 days of fetal development. The SMB mRNA is shown to be expressed in smooth muscle from fetal bladder, intestine, and stomach and from neonatal aorta; however, it is not expressed in cultured smooth muscle cells from rat aorta. The SMA mRNA is also present at all stages of development in the smooth muscles examined; however, it is much less abundant than SMB mRNA in most fetal smooth muscles. We show here that the SMB isoform, which contains a unique seven-amino acid insertion at the junction of the 25- and 50-kDa tryptic peptides, is present in conjunction with SM1 and SM2 tails on immunoblots of smooth muscle from stomach, intestine, bladder, and uterus and is expressed during development in a pattern distinct from that of the SM1 and SM2 tail isoforms.
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PMID:Myosin heavy chain isoform expression in rat smooth muscle development. 968 13

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and controversial tumor of skeletal muscle phenotype. Diagnostic criteria for PRMS by combined histology and currently available immunohistochemistry have not been clearly defined. We report 38 pleomorphic rhabdomyosarcomas in adults, explore morphologic variants, and discuss our experience with both specific and nonspecific skeletal muscle markers in these tumors. Clinical data, morphology, and immunohistochemistry were reviewed. Electron microscopy was performed. Of 38 cases, there were 28 males and 10 females. Patient ages ranged from 21 to 81 years (median = 54 y; mean = 51 y). Tumors were located in the lower extremity (n = 18), abdomen/retroperitoneum (n = 6), chest/abdominal wall (n = 5), spermatic cord/testes (n = 4), upper extremity (n = 3), and one each in the mouth and orbit. Tumor sizes ranged from 1.5 to 15.0 cm (mean = 7.3 cm; median = 6.8 cm). The cases were divided into three variants, each with large, atypical, pleomorphic polygonal rhabdomyoblasts (PRMB) with abundant eosinophilic cytoplasm in varying numbers and different morphologic backgrounds of round or spindled rhabdomyoblasts (RMB). 1. Classic PRMS: Predominantly atypical PRMB in sheets (n = 8). 2. Round cell PRMS: Clusters of PRMB throughout the tumor with a background of slightly atypical, medium-sized, round, blue RMB (n = 13). 3. Spindle cell PRMS: Scattered PRMB in a predominance of atypical spindled RMB arranged in a storiform growth pattern (n = 17). Immunohistochemistry revealed the following: myoglobin (37/38), MyoD1 (19/36), skeletal muscle myogenin (myf4; 19/34), fast skeletal muscle myosin (4/5), desmin (36/38), muscle-specific actin (MSA; 25/35), smooth muscle actin (SMA; 15/33), and muscle specific myogenin (myf3; 25/35). Immunohistochemistry was supportive of skeletal muscle differentiation with at least one positive skeletal muscle-specific marker (myoglobin, MyoD1, fast skeletal muscle myosin, or myf4). In addition, all cases had some positivity for nonspecific muscle markers (desmin, MSA, SMA, myf3). Electron microscopy (EM), performed on eight selected cases from all three morphologic groups, demonstrated definitive skeletal muscle differentiation in all cases. Follow-up, available on 30 (79%) cases, revealed that 70% of patients died of disease (mean 20 months, range 1 month-108 months), 3% were alive with disease at 12 months (n = 1); and 27% had no evidence of disease (mean, 83 mo; range, 18 to 108 mo). PRMS, a tumor of predominantly middle-aged adult males in the lower extremity, can be diagnosed by the morphologic presence of scattered PRMB with immunohistochemical evidence of at least one skeletal muscle-specific marker. There are three morphologic variants of PRMS. The appropriate diagnosis of PRMS is significant as it is a high-grade sarcoma, with an aggressive clinical course.
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PMID:Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. 1140 62

To evaluate whether alpha-smooth muscle actin (alpha-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of alpha-SMA, with that of lung fibroblasts (LFs), expressing high levels of alpha-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of alpha-SMA-positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for alpha-SMA. In a second approach, we measured the isotonic contraction of SCF- and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGFbeta1 increased alpha-SMA expression and lattice contraction by SCFs to the levels of LFs; TGFbeta-antagonizing agents reduced alpha-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with alpha-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with alpha-cardiac and beta- or gamma-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased alpha-SMA expression is sufficient to enhance fibroblast contractile activity.
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PMID:Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. 1155 12

Myofibroblasts from rat lung were cultivated. These cells in addition to beta- and gamma-cytoplasmic actins, expressed alpha-smooth muscle actin (alpha-SMA) and formed a system of "supermature" focal contacts, which were connected with thick stress-fibers expressing alpha-SMA and myosin II. Reduction of actin-myison contractility by inhibitors BDM and ML-7 lead to stress fiber reorganization, e.g., decrease in their thickness, a selective disappearance of alpha-SMA expression and myosin translocation from bundles to the cytoplasm. Using immunofluorescence, interference-reflection microscopy and morphometry, we have demonstrated that an inhibition of actin-myosin contractility also leads to dispersion of myofibroblastic focal contacts. Phase-contrast and DIC video-enhanced microscopy of live cells showed morphological reorganization at the leading edge after inhibitory treatment. Thus, actin-myosin contractility controls the structure of "supermature" focal contacts of myofibroblasts and alpha-SMA expression in stress fibers.
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PMID:[Effect of actomyosin contractility on focal contacts of myofibroblasts and structure of stress fibers]. 1186 61

In smooth muscle cells (SMCs) isolated from rabbit carotid, femoral, and saphenous arteries, relative myosin isoform mRNA levels were measured in RT-PCR to test for correlations between myosin isoform expression and unloaded shortening velocity. Unloaded shortening velocity and percent smooth muscle myosin heavy chain 2 (SM2) and myosin light chain 17b (MLC(17b)) mRNA levels were not significantly different in single SMCs isolated from the luminal and adluminal regions of the carotid media. Saphenous artery SMCs shortened significantly faster (P < 0.05) than femoral SMCs and had more SM2 mRNA (P < 0.05) than carotid SMCs and less MLC(17b) mRNA (P < 0.001) and higher tissue levels of SMB mRNA (P < 0.05) than carotid and femoral SMCs. No correlations were found between percent SM2 and percent MLC(17b) mRNA levels and unloaded shortening velocity in SMCs from these arteries. We have previously shown that myosin heavy chain (MHC) SM1/SM2 and SMA/SMB and MLC(17a)/MLC(17b) isoform mRNA levels correlate with protein expression for these isoforms in rabbit smooth muscle tissues. Thus we interpret these results to suggest that 1) SMC myosin isoform expression and unloaded shortening velocity do not vary with distance from the lumen of the carotid artery but do vary in arteries located longitudinally within the arterial tree, 2) MHC SM1/SM2 and/or MLC(17a)/MLC(17b) isoform expression does not correlate with unloaded shortening velocity, and 3) intracellular expression of the MHC SM1/SM2 and MLC(17a)/MLC(17b) isoforms is not coregulated.
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PMID:Shortening velocity and myosin heavy- and light-chain isoform mRNA in rabbit arterial smooth muscle cells. 1194 May 25

The seven amino acid insert in the smooth muscle myosin heavy chain is thought to regulate the kinetics of contraction, contributing to the differences between fast and slow smooth muscle. The effects of this insert on force and stiffness were determined in bladder tissue of a transgenic mouse line expressing the insert SMB at one of three levels: an SMB wild type (+/+), an SMA homozygous type (-/-) and a heterozygous type (+/-). For skinned muscle, an increase in MgADP or inorganic phosphate (Pi) should shift the distribution of crossbridges in the actomyosin ATPase (AMATPase) to increase the relative population of the crossbridge state prior to ADP release and Pi release, respectively. Exogenous ADP increased force and stiffness in a manner consistent with increasing the Ca2+ concentration in both the +/+ and +/- mouse types. However, the -/- type showed a significantly greater increase in force than in stiffness suggesting that immediately prior to ADP release, the AMATPase either has an additional force producing isomerization state or a slower ADP dissociation rate for the -/- type compared to the +/+ or +/- types. Exogenous Pi led to a significantly greater decrease in stiffness than in force for all three mouse types suggesting that there is a force producing state prior to Pi release. In addition, the increase in Pi showed similar changes in the +/+ and -/- types whereas in the +/- type the decreases in both force and stiffness were greater than the other two mouse types indicating that the insert can affect the cooperativity between myosin heads. In conclusion, the seven amino acid insert modulates the kinetics and/or states of the AMATPase, which could lead to differences in the kinetics of contraction between fast and slow smooth muscle.
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PMID:The smooth muscle myosin seven amino acid heavy chain insert's kinetic role in the crossbridge cycle for mouse bladder. 1256 24


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