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Affected Muscle (affected + muscle)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

A peptide-based immunoassay for antibodies against botulinum neurotoxin A

JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2007
M. Zouhair Atassi
Abstract Cervical dystonia (CD) is due to neck-muscle spasms that cause pain and involuntary contractions resulting in abnormal neck movements and posture. Symptoms can be relieved by injecting the affected muscle with a botulinum neurotoxin (BoNT, usually type A or type B). The therapeutic benefits are impermanent and toxin injections need to be repeated every 3,6 months. In a very small percentage of patients (less with BoNT/A than with BoNT/B) the treatment elicits blocking anti-toxin antibodies (Abs), which reduce or terminate the patient's responsiveness to further treatment. We have recently mapped (Dolimbek et al., 2006) the CD sera Ab-binding profile using a panel of 60, 19-residue peptides that encompassed the entire H chain sequence 449,1296 and overlapped consecutively by 5 residues. Abs in CD sera bound to one or more of the peptides N25, C10, C15, C20, and C31. This suggested the possibility that binding to these peptides could be used for assay of Abs in CD sera. Data analysis reported here found that Ab binding to these regions showed very significant deviations from the control responses. Of these four peptides, C10 showed the most significant level of separation between patient and control groups (p,=,5,×,10,7) and the theoretical resolution (i.e., ability to distinguish CD patients from control, see full definition under ,Statistical analysis' in Methods), 84%, was about 4% higher than the least resolved response, C31 (p,=,6,×,10,6, resolution 80%). Since the amounts of Abs bound to a given peptide varied with the patient and not all the patients necessarily recognized all four peptides, there was the possibility that binding to combinations of two or more peptides might give a better discriminatory capability. Using two peptides, C10 plus C31, the resolution improved to 87% (p,=,4,×,10,8). These two peptides appeared to compliment each other and negate the lower resolution of C31. Combination of three peptides gave resolutions that ranged from 85 (N25,+,C15,+,C31; p,=,2,×,10,7) to 88% (C10,+,C15,+,C31; p,=,1,×,10,8). Finally, using the data of all four peptides, N25,+,C10,+,C15,+,C31, gave a resolution of 86% (p,=,1,×,10,7). Although these levels of resolution are somewhat lower than that obtained with whole BoNT/A (resolution 97%; p,=,6,×,10,12), it may be concluded that the two-peptide combination C10,+,C31, or the three-peptide combination C10,+,C15,+,C31 (affording resolutions of 87 and 88%, respectively) provide a good diagnostic, toxin-free procedure for assay of total specific anti-toxin Abs in BoNT/A-treated CD patients. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Kell and XK immunohistochemistry in McLeod myopathy

MUSCLE AND NERVE, Issue 10 2001
Hans H. Jung MD
Abstract The McLeod syndrome is an X-linked neuroacanthocytosis manifesting with myopathy and progressive chorea. It is caused by mutations of the XK gene encoding the XK protein, a putative membrane transport protein of yet unknown function. In erythroid tissues, XK forms a functional complex with the Kell glycoprotein. Here, we present an immunohistochemical study in skeletal muscle of normal controls and a McLeod patient with a XK gene point mutation (C977T) using affinity-purified antibodies against XK and Kell proteins. Histological examination of the affected muscle revealed the typical pattern of McLeod myopathy including type 2 fiber atrophy. In control muscles, Kell immunohistochemistry stained sarcoplasmic membranes. XK immunohistochemistry resulted in a type 2 fiber-specific intracellular staining that was most probably confined to the sarcoplasmic reticulum. In contrast, there was only a weak background signal without a specific staining pattern for XK and Kell in the McLeod muscle. Our results demonstrate that the lack of physiological XK expression correlates to the type 2 fiber atrophy in McLeod myopathy, and suggest that the XK protein represents a crucial factor for the maintenance of normal muscle structure and function. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1346,1351, 2001 [source]

Cell death and apoptosis-related proteins in muscle biopsies of sporadic amyotrophic lateral sclerosis and polyneuropathy

MUSCLE AND NERVE, Issue 8 2001
Benedikt G.H. Schoser MD
Abstract To investigate disease-related differences of cell death and apoptosis in human denervation atrophy, we studied DNA fragmentation by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method in 38 biopsies of clinically nonaffected and affected muscles from patients with sporadic amyotrophic lateral sclerosis (sALS), in 13 muscle biopsies from patients with chronic peripheral neuropathies, and in 8 biopsies from control subjects. In addition, expression of apoptosis-related proteins, bax, bcl-2, and Fas, was studied in 20 biopsies of sALS and 10 chronic peripheral neuropathies. We identified DNA cleavage in 10% of myofibers of patients and in up to 1.5% of control samples. In clinically affected muscles of ALS, a larger amount of TUNEL-positive myofibers (mean 10.5 ± 5.9%) was detected, similar to chronic peripheral neuropathies (mean 10.0 ± 7.4%). Atrophic myofibers were immunopositive for bax, bcl-2, and, to a weaker extent, for Fas. However, bax-, bcl-2-, or Fas-positive atrophic myofibers did not reveal consecutive DNA cleavage. Differences between sALS subgroups and chronic peripheral neuropathies were not found. In human denervation atrophy the bcl-2/bax and the FasL/Fas systems are apparently active independently of DNA fragmentation and apoptosis. DNA fragmentation thus displays an additional reaction that is not disease-specific at chronic stages of human denervation processes, probably recapitulating events like skeletal muscle fiber remodeling in embryonic skeletal tissue development. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1083,1089, 2001 [source]

Critical overexpression of thrombospondin 1 in chronic leg ischaemia

THE JOURNAL OF PATHOLOGY, Issue 3 2005
Judith Favier
Abstract The aim of this study was to identify gene expression governing the balance of angiogenic and angiostatic factors in human ischaemic leg tissues. In situ hybridization was used to screen for the expression of angiogenesis-related genes in tissues from 13 amputated limbs from patients suffering from critical leg ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors 1, and 2,, vascular endothelial growth factor, and its receptors VEGFR-1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule thrombospondin 1. The expression levels of the genes in proximal, healthy muscles were compared with those in the distal, ischaemic counterparts. Surprisingly, only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all patients studied. Thrombospondin 1 mRNA was assayed by real-time RT-PCR and the gene was overexpressed 20-fold. The presence of its encoded protein was confirmed by western blotting. The overproduction of this anti-angiogenic molecule was associated with a decrease in capillary density in the affected muscles. Thrombospondin 1 is thus a marker of chronic ischaemia and may affect angiogenesis in ischaemic tissues. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]