Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0272170 (SDS)
 50,377 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2-month-old boy had progressive generalized weakness, hypotonia, and respiratory insufficiency requiring assisted ventilation. At age 3 1/2 months, he started having seizures and recurrent pulmonary infections; he died at age 7 months. Serum lactate was chronically elevated, but there was no aminoaciduria. Histochemical and ultrastructural studies of muscle biopsies at ages 2 and 3 months showed excessive mitochondria, lipid, and glycogen; a third biopsy at 6 months showed marked increase in perimysial fibrous and fat tissue. Cytochrome c oxidase activity was 7% of normal in the first biopsy and undetectable in the others. Cytochrome spectra of mitochondria isolated from postmortem muscle showed complete lack of cytochrome aa3. Antibodies were obtained against cytochrome c oxidase purified from normal human heart. Immunotitration and enzyme-linked immunosorbent assay (ELISA) showed decreased immunologically reactive enzyme protein in the patient's muscle, but SDS-PAGE electrophoresis of immunoprecipitates of muscle mitochondrial extracts showed the presence of all cytochrome c oxidase subunits. These data suggest that decreased synthesis of one or more subunits may result in markedly decreased concentration of electrophoretically normal complex IV in skeletal muscle.
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PMID:Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle. 298 57

Neurogenic orthostatic hypotension is a severely disabling condition due to deficient peripheral vasoconstrictor tone in response to the upright position and is characterized by a decrease in blood pressure upon standing associated with symptoms of lightheadedness, dizziness, visual "white-out", weakness, lack of energy, near syncope or even syncope. Previous pharmacologic treatment of neurogenic orthostatic hypotension has been problematic. Midodrine, a new specific alpha-1-agonist has been shown to produce arteriolar constriction and decrease in venous pooling via a constriction of venous capacitance vessels. Therefore, a recent multicenter study evaluated the safety and efficacy of midodrine therapy in 97 patients with neurogenic orthostatic hypotension due to various etiologies: Shy Drager syndrome (No. 18); Bradbury Eggleston syndrome (idiopathic orthostatic hypotension) (No. 20); diabetic autonomic neuropathy (No. 27); Parkinson's disease (No. 22); and miscellaneous (No. 10). Following one week of placebo therapy, the patients were randomized into 4 groups for a 4 week period of time; placebo, 2.5 mg, 5 mg, or 10 mg three times daily. The BE/SDS subgroup demonstrated a 27 +/- 8% (22 mmHg) increase in standing systolic blood pressure for the 10 mg dose. Diabetics achieved a significant increase at 5 mg. Similar increases were observed for the entire group on the 10 mg dose (p < 0.001). Symptoms or fainting, blurred vision, improved energy level, standing time, and depressed feelings were also significantly improved even at lower doses (p < 0.05 or less). Side effects were mild. Therefore, midodrine is an effective and safe agent for the treatment of neurogenic orthostatic hypotension.
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PMID:Midodrine in neurogenic orthostatic hypotension. A new treatment. 769 Mar 83

The importance of the role of acid alpha-glucosidase in the lysosomal degradation of glycogen has been emphasized because the deficiency of this enzyme in glycogenosis type II causes glycogen accumulation in lysosomes. Three clinical variants are distinguished. The infantile type has its onset shortly after birth and is known as generalized glycogen storage disease. The adult variant manifests itself mostly after the second decade of life and is characterized by progressive skeletal muscle weakness. The other is childhood type which is usually fatal by the second decade of life. Many biochemical reports of acid alpha-glucosidase have been published. Martiniuk et al reported the cDNA and amino acid sequence of human acid alpha-glucosidase. In prior studies, they reported that the lysosomal acid alpha-glucosidase was polymorphic with three alleles. The rarer allele GAA2 allozyme had a lower affinity for glycogen and starch. We also reported the enzyme heterogeneity in its affinity to Sephacryl S-200 gel. Whereby the enzyme separated into two fractions, S1 and S2. Each fraction contained 76 kDa and 67 kDa components on SDS/PAGE. The spleen enzyme consisted mainly of S1 fraction, containing only a 76 kDa component. In previous extensive studies, different mutations of Pompe's disease have been inferred from alterations in biochemical parameters. More recently Martiniuk et al, Hoefsloot et al and Van der Ploeg et al reported the analysis of cDNA and mRNA. These studies have revealed an absence or abnormal size of mRNA in large numbers of patients and altered restriction endonuclease fragments in a few patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pompe's disease--acid alpha-glucosidase deficiency--a review]. 841 9

In Duchenne muscular dystrophy (DMD), short stature is a feature of unknown cause. This cross-sectional study of 34 male patients (mean age 8.0 y, age range 1.2-13.7 y) was conducted to examine the relationship between auxological parameters, markers of growth and the extent of muscular weakness. Weight and length at birth (SDS +/- SD; 0.0 +/- 1.2; 0.2 +/- 1.5) and target height SDS (-0.2 +/- 0.7) were normal. Height (HT) SDS (-1.0 +/- 1.1) was lower than the normal population (p < 0.001) and did not correlate with age. Body mass index SDS (-0.1 +/- 1.6) was normal. Tests of insulin-like growth factor-I SDS (-0.6 +/- 1.2) and insulin-like growth factor binding protein-3 SDS (0.1 +/- 1.3) ruled out a severe derangement in the GH-IGF-axis. The carboxy-terminal propeptide of type I procollagen (PICP) SDS (0.6 +/- 1.5) was normal, but bone-specific alkaline phosphatase (BAP) SDS (-1.7 +/- 0.8) was low (p <0.001). HT SDS did not correlate with BAP SDS. The Vignos scale, a grading of muscular function (score: 0 = unaffected; 11 = confined to bed) (median (range): 3 (0-9)) correlated strongly with age (r = 0.77, p < 0.0001), but did not correlate with HT SDS, PICP SDS or BAP SDS. In conclusion, DMD patients are significantly shorter than the normal population, though the HT SDS does not change with age. Growth hormone deficiency does not seem to be the cause of short stature in DMD. Significantly low BAP levels are probably the result of the reduced muscle mass, which leads to a lower biomechanical load on the bone and thus a reduction in bone turnover. The short stature observed in our study is unlikely to be the result of muscular weakness.
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PMID:Short stature in Duchenne muscular dystrophy: a study of 34 patients. 1009 May 50

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and pathogenetic autoantibodies directed against the nicotinic acetylcholine receptor (seropositive myasthenia gravis; SPMG). Nearly 15% to 20% of MG patients do not have these antibodies (seronegative myasthenia gravis; SNMG), but several evidence indicate that these patients have circulating pathogenic autoantibodies directed against other muscle antigens. Using the TE671 rhabdomyosarcoma cell line as an antigen source, we analyzed sera from 63 SNMG and 26 SPMG patients and 26 healthy blood donors by FACS analysis. We found that 40 of 63 SNMG patients and only 1 of 26 SPMG patients had IgG binding to the TE671 cell line. None of the sera bound to the unrelated MRC5 cell line. To identify the antigen, we analyzed sera immunoreactivity in more detail by immunoprecipitation of biotinylated membrane proteins from TE671 cells. When the immunoprecipitated proteins were separated by SDS-PAGE electrophoresis and then transferred to nitrocellulose membranes, we found that SNMG IgG identify a band corresponding to a protein with a molecular weight of 110 kDa (P110), which is not recognized by seropositive MG sera. This anti-P110 immunoreactivity is significantly associated with a distinct clinical picture characterized by a prominent involvement of ocular and bulbar muscles, with frequent respiratory problems (p < 0.005), and is recognized by a specific antimuscle specific kinase (MuSK) antiserum. In a recent article, the presence of anti-MuSK antibodies was described in SNMG. Our results confirm the presence of these antibodies in SNMG and suggest that anti-P110/MuSK autoantibodies identify a subtype of SNMG in which the different pathogenesis induces the distinct clinical picture.
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PMID:Anti-p110 autoantibodies identify a subtype of "seronegative" myasthenia gravis with prominent oculobulbar involvement. 1221 74

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue. Triton-skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver-enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by approximately 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
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PMID:Functional and biochemical modifications in skeletal muscles from malarial mice. 1572 39

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20 degrees C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (+/-SE) in the control and patient group, respectively, amounted to 134 +/- 24 and 77 +/- 9 microM/s in type I fibers (n = 11 and 16), 248 +/- 17 and 188 +/- 13 microM/s in type IIA fibers (n = 14 and 32), 291 +/- 29 and 126 +/- 21 microM/s in type IIA/X fibers (n = 3 and 5), and 325 +/- 32 and 205 +/- 21 microM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 +/- 7 and 43 +/- 5 kN/m(2) in type I fibers, 86 +/- 11 and 58 +/- 4 kN/m(2) in type IIA fibers, 85 +/- 6 and 42 +/- 9 kN/m(2) in type IIA/X fibers, and 90 +/- 5 and 59 +/- 5 kN/m(2) in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of approximately 30%, which exacerbates skeletal muscle weakness due to muscle atrophy.
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PMID:Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure. 1605 11

Iurus dufoureius asiaticus, Birula, 1903 scorpions were collected in Mugla province located in the Aegean region, Turkey. There are few number of publications about I.d. asiaticus, and there are no data regarding minimal lethal dose and effects of the scorpion venom till now. This is the first study about toxicity and effects of I.d. asiaticus scorpion venom in mice. Previously, most of the proteins in venom of I.d. asiaticus from Aydin region in Turkey were reported to be between 14 and 205 kDa in size. In this study, we determined the electrophoretic protein pattern of the venom taken from Mugla province to be between 29 and 116 kDa by SDS-PAGE. Intracerebroventricular (i.c.v.) was determined instead of s.c. injection since there were no deaths in any s.c. test groups. The LD(50) of I.d. asiaticus scorpion venom was found to be 47.7 microg/20 g mouse by i.c.v. injection route. After s.c. injection venom, mice were shown any intoxication symptoms. On the other hand, after i.c.v. administration of venom, mice showed symptoms such as excitability, hyper salivation, weakness, paralysis, coma and resulting in death. The possible cause of death could be due to multi-system organ failure depending on the toxic effect of the venom. These both results showed that the venom was not lethal on s.c. injection, but it was lethal on i.c.v. injection. This may imply that the scorpion is of little danger to humans.
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PMID:Proteins, lethality and in vivo effects of Iurus dufoureius asiaticus scorpion venom. 1753 57

Nemaline myopathy (NM) is the most common non-dystrophic congenital myopathy. Clinically the most important feature of NM is muscle weakness; however, the mechanisms underlying this weakness are poorly understood. Here, we studied the muscular phenotype of NM patients with a well-defined nebulin mutation (NM-NEB), using a multidisciplinary approach to study thin filament length regulation and muscle contractile performance. SDS-PAGE and western blotting revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward-shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and non-uniform thin filament lengths in NM-NEB muscle compared with control muscle. Immunofluorescence confocal microscopy and electron microscopy studies indicated that average thin filament length is reduced from approximately 1.3 microm in control muscle to approximately 0.75 microm in NM-NEB muscle. Thus, the present study is the first to show a distinct genotype-functional phenotype correlation in patients with NM due to a nebulin mutation, and provides evidence for the notion that dysregulated thin filament length contributes to muscle weakness in NM patients with nebulin mutations. Furthermore, a striking similarity between the contractile and structural phenotypes of nebulin-deficient mouse muscle and human NM-NEB muscle was observed, indicating that the nebulin knockout model is well suited for elucidating the functional basis of muscle weakness in NM and for the development of treatment strategies.
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PMID:Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. 1934 29

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is clinically characterized by muscle weakness. However, the mechanisms underlying this weakness are poorly understood. Here, we studied the contractile phenotype of skeletal muscle from NM patients with nebulin mutations (NEM2). SDS-PAGE and Western blotting studies revealed markedly reduced nebulin protein levels in muscle from NM patients, whereas levels of other thin filament-based proteins were not significantly altered. Muscle mechanics studies indicated significantly reduced calcium sensitivity of force generation in NM muscle fibers compared to control fibers. In addition, we found slower rate constant of force redevelopment, as well as increased tension cost, in NM compared to control fibers, indicating that in NM muscle the rate of cross-bridge attachment is reduced, whereas the rate of cross-bridge detachment is increased. The resulting reduced fraction of force generating cross-bridges is expected to greatly impair the force generating capacity of muscle from NM patients. Thus, the present study provides important novel insights into the pathogenesis of muscle weakness in nebulin-based NM.
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PMID:Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2). 1994 67


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