Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diethyistibestrol was administered orally to 11 boys with Duchene muscular dystrophy (DMD). Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, characteristically high in DMD, and presumably of muscle origin, were reduced significantly (P LESS THAN .05). On ther other hand, the activity of alkaline phosphatase, an enzyme not of muscle origin, increased. These enzyme changes were reversible when diethyistibestrol was discontinued. Despite appreciable alterations in totoal serum enzyme activity, no important change was found in the isozyme patterns. Piperazine estrone sulfate was administered to another patient with DMD. The effects of this physiologic hormone were, in part, similar to those of diethyistibestrol. Experimentally, diethylstilbestrol reduced the efflux of CPK and LDH from mouse skeletal muscle. This may be the manner by which diethylstilbesterol reduced the serum enzyme levels in DMD, but this has not been proved directly. These studies are the first step in an effort to identify various agents that in combinations may normalize serum enzyme levels.
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PMID:Diethylstilbestrol effects on serum enzymes and isozymes in muscular dystrophy. 93 73

The occurrence of alkaline phosphatase was observed in regenerating muscle fibres, especially in polymyositis and muscular dystrophy. No differences in the appearance of this enzyme were seen in these diseases. Alkaline phosphatase was not encountered in neurogenic atrophy, with the exception of cases of an accompanying myopathy. These cases show a clear picture without problems in the morphological differential diagnosis. The histochemical demonstration of the enzyme is helpful in the differential diagnosis of neurogenic atrophy and muscular dystrophy of benign type. It is of no use to distinguish between muscular dystrophy of malignant type and parenchymatous polymyositis.
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PMID:The significance of the detection of alkaline phosphatase in the diagnosis of neuromuscular diseases. 396 33

We applied a simple lead salt-based stain for interstitial and vascular 5'-nucleotidase to 150 muscle biopsy specimens. No reaction was obtained with 2'- or 3'-adenosine monophosphate, indicating that the stain was specific, and distinct from phosphatases. Staining was not inhibited by alpha, beta-methylene adenosine 5'-diphosphate, but was prevented by formaldehyde fixation or by brief immersion in octoxynol 9 (Triton X-100). Nucleotidase stains the following specific histologic sites that distinguish it from alkaline phosphatase: the intima and adventitia of medium-sized and large arteries, perineural and muscle spindle sheaths, and tendon insertions. Aside from these structures, normal muscle shows little reaction, as the sarcoplasm and sarcolemma do not stain. Neither of these enzymes shows a compensatory increase, histochemically, in myo-adenylate deaminase deficiency. In Duchenne's muscular dystrophy, however, and particularly in inflammatory myopathy, interstitial staining of 5'-nucleotidase is increased, leading to investment of most muscle fibers in the affected area. The stain rarely identifies regenerating fibers. Although alkaline phosphatase commonly shows a corresponding increase in interstitial staining, we encountered six cases of inflammatory myopathy in which this was absent, despite pronounced endomysial staining in the 5'-nucleotidase reaction. 5'-Nucleotidase thus appears to provide a valuable adjunct in the diagnosis of inflammatory myopathy.
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PMID:Interstitial 5'-nucleotidase stain for frozen biopsy specimens of skeletal muscle. A useful adjunct in the diagnosis of polymyositis. 619 1

In two separate experiments, 72 crossbred ewes were fed hay, haylage (50% dry matter) and corn diets with ad libitum salt-mineral mixtures (SMM; Exp. 1) or salt (Exp. 2). Calcium phosphates (Ca X P) and(or) zinc (Zn) were added in a 2 X 2 factorial arrangement to salt + trace minerals for ewes 7 mo prepartum through lactation in Exp. 1 and to salt only for ewes 3 mo prepartum through lactation in Exp. 2. The diets fed were estimated to contain 23 and 28 mg Zn/kg dry diet (ppm), respectively, and .08 and .05 ppm Se. Large variations (up to fivefold) were found in SMM intake per month between replicates and from month-to-month within treatment; thus, monthly variations of up to sevenfold occurred in Zn and Se intakes of supplemented groups. There were no significant treatment effects on SMM intake. Small but significant Zn treatment effects were detected for plasma and wool Zn of ewes and lambs, but all values were in the normal range. There was no significant treatment effect on plasma alkaline phosphatase activity. In Exp. 2, erythrocyte glutathione peroxidase (GSH-Px) activity was significantly lower in all treatment groups compared with a Se-supplemented control group but only rare occurrences of subclinical muscular dystrophy were found. There was no significant treatment effect on GSH-Px activity, whole blood Se in ewes and lambs or plasma creatine phosphokinase activity in lambs. These results indicate large animal and seasonal variability in SMM intake and no significant treatment effects of Ca X P on SMM intake or on Zn and Se status. Zinc addition to SMM had no effect on Se status.
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PMID:Effect of calcium phosphates and zinc in salt-mineral mixtures on ad libitum salt-mix intake and on zinc and selenium status of sheep. 652 62

Desmin and vimentin are two intermediate filaments, abundant in fetal skeletal muscle, almost undetectable in mature skeletal muscle which increase in regenerating and partially damaged skeletal muscle fibers. To determine their content in neuromuscular disorders immunohistochemical studies of desmin and vimentin were performed on 53 human muscle specimens. The labelled streptavidin biotin technique (DAKO, LSAB Kit, alkaline phosphatase) was used. Strong staining intensity was seen in regenerating and partially damaged fibers of inflammatory myopathies and muscular dystrophy. Necrotic fibers lost their reactivity for both filaments. Type II glycogenosis showed an increased reactivity for desmin and vimentin. A mild increase in desmin and vimentin staining intensity was observed in the atrophic cells of spinal muscular atrophy, but not in the atrophic fibers from other disease entities. Weaker reactivity for desmin was noted in atrophic cells of myotonic dystrophy. The immunohistochemical study of desmin and vimentin in neuromuscular disorders is helpful in detecting degeneration, or regeneration changes, of muscle fibers and may provide clues to the pathogenesis of various muscular disorders.
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PMID:Immunocytochemical studies on desmin and vimentin in neuromuscular disorders. 774 34

Congenital muscular dystrophy syndromes are characterized by congenital weakness, contractures, and dystrophic features on muscle biopsy. However, these syndromes are often difficult to diagnose precisely because their clinical and pathologic characteristics are not specific and resemble changes in other myopathies. We examined muscle biopsies from 20 children with a congenital muscular dystrophy syndrome. Disease controls with dystrophies or other myopathies (n=19) and normal individuals (n=15) were studied for comparison. In each biopsy we determined (1) numbers of muscle fibers with alkaline phosphatase (AlkP) staining, (2) numbers of acid phosphatase-(AcP) positive cells, (3) dystrophin levels by immunocytochemistry, and (4) the distribution of merosin and laminin-A staining. A ratio of AcP:AlkP staining was calculated for each biopsy. In nine patients with congenital muscular dystrophy (younger than 4 years of age) with normal dystrophin, the AcP:AlkP ratio was low (0.09 +/- 0.03). In contrast, in Duchenne muscular dystrophy, the AcP:AlkP ratio was 15 times higher (1.6 +/- 0.04, p=0.001). The three children with congetial muscular dystrophy syndromes and reduced dystrophin and one child with facioscapulohumeral dystrophy had AcP:AlkP ratios in the range of Duchenne muscular dystrophy patients (2.4 +/- 1.4). Low Ac:AlkP ratios were related to relative absence of AcP-positive cells. Merosin staining was absent in 5 of the 17 congenital muscular dystrophy biopsies tested. None of the 5 children with merosin-negative but all 12 with merosin-positive stains walked (p=0.0002). We conclude that a pattern of few AcP-positive cells in the setting of numerous AlkP staining muscle fibers has specificity for congenital muscular dystrophy syndromes and provides histopathologic support for the diagnosis. Reduced merosin in muscle predicts more severe weakness and long-term disability.
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PMID:Congenital muscular dystrophy syndromes distinguished by alkaline and acid phosphatase, merosin, and dystrophin staining. 861 88

The combination of autosomal dominant, early onset Paget disease of bone (PDB) and muscular dystrophy is an unusual disorder. We recently mapped the disorder in a large family from central Illinois with PDB and proximal limb-girdle type of muscular dystrophy (LGMD), and in 3 additional families with hereditary inclusion body myopathy (HIBM), Paget disease of bone and frontotemporal dementia, to a unique locus on chromosome 9p21.1-q12. The present study describes an unrelated 10-member family with autosomal dominant PDB and a scapuloperoneal type of muscular dystrophy. Clinical, biochemical, and radiological evaluations were performed to delineate clinical features in this family. Progression of the muscular dystrophy begins with weakness in the distal muscles of the legs accompanied by foot drop. EMG and muscle biopsy are compatible with a primary dystrophy. Onset of Paget disease is early, at a mean age of 41 years, with initial distribution in the long bones and eventual infiltration of the spine and pelvis. Creatine phosphokinase (CPK) and alkaline phosphatase levels are elevated in affected individuals. Molecular analyses excluded all known loci for Paget disease of bone, scapuloperoneal muscular dystrophy (SPMD), fascioscapulohumeral muscular dystrophy (FSH), amyotrophic lateral sclerosis (ALS), Bethlem myopathy, two forms of autosomal dominant limb-girdle muscular dystrophy (LGMD), and the critical region for LGMD or HIBM/PDB on chromosome 9p21.1-q12, thus providing evidence for genetic heterogeneity among families with the unique combination of muscular dystrophy and Paget disease of bone.
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PMID:Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy. 1189 83

Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient-X-linked, mouse muscular dystrophy (scid-mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.
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PMID:Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. 1733 Jan 16

Inclusion body myopathy with Paget disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD, OMIM 167320), is a progressive autosomal dominant disorder caused by mutations in the Valousin-containing protein (VCP, p97 or CDC48) gene. IBMPFD can be difficult to diagnose. We assembled data on a large set of families to illustrate the number and type of misdiagnoses that occurred. Clinical analysis of 49 affected individuals in nine families indicated that 42 (87%) of individuals had muscle disease. The majority were erroneously diagnosed with limb girdle muscular dystrophy (LGMD), facioscapular muscular dystrophy, peroneal muscular dystrophy, late adult onset distal myopathy, spinal muscular atrophy, scapuloperoneal muscular dystrophy, or amyotrophic lateral sclerosis (ALS) among others. Muscle biopsies showed rimmed vacuoles characteristic of an inclusion body myopathy in 7 of 18 patients (39%), however, inclusion body myopathy was correctly diagnosed among individuals in only families 5 and 15. Frontotemporal dementia (FTD) was diagnosed in 13 individuals (27%) at a mean age of 57 years (range 48.9-60.2 years); however, several individuals had been diagnosed with Alzheimer disease. Histopathological examination of brains of three affected individuals revealed a pattern of ubiquitin positive neuronal intranuclear inclusions and dystrophic neurites. These families expand the clinical phenotype in IBMPFD, a complex disorder caused by mutations in VCP. The presence of PDB in 28 (57%) individuals suggests that measuring serum alkaline phosphatase (ALP) activity may be a useful screen for IBMPFD in patients with myopathy.
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PMID:Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. 1826 Jan 32

The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Paget's disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Paget's disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia.
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PMID:Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus. 2011 73


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