T. Kyriakides
C. Angelini
J. Schaefer
T. Mongini
G. Siciliano
S. Sacconi
J. Joseph
J. M. Burgunder
L. A. Bindoff
J. Vissing
M. de Visser and D. Hilton-Jones
Myalgia, defined as any pain perceived in muscle, is very common in the general population and a frequent cause for referral to neurologists, rheumatologists and internists in general. It is however only rarely due to primary muscle disease and often referred from ligaments, joints, bones, the peripheral and central nervous system. A muscle biopsy should only be performed if this is likely to be diagnostically useful. At present no ‘guidelines’ exist.
Slow channel syndrome, first recognized by Engel in 1982, has distinct phenotypic features, dominant inheritance, selective weakness of cervical scapular and finger extensor weakness, ophtalmoparesis. Histochemical findings show type 1 fibers preponderance, small group of atrophic fibers of either fiber type, increased fiber size variability, tubular aggregates.We examined 3 biopsies in 3 patients (2 males - 55 years and 66 years, 1 female - 61 years) presenting a dominant distal myopathy with variable age at onset (from second to third decade). The patients had ophtalmoparesis, upper limb extensor, forearm and finger weakness and distal myopathy with a progressive slow course.The woman had also some difficulty in anterior tibial flexor muscle but also atrophy of forearms muscles. Electrophysiology on single stimulus of ulnar nerve showed repetitive CMAP.The genomic wide linkage analysis identified 3 regions co-segregating with the disease in chromosome 1, 13, 17. Next generation sequencing showed in all patients a known mutation in epsilon-subunit of AchR receptor and a mutation in phospholipase. Muscle showed mild changes consisting in atrophic fibers, mostly of type 2, some fiber type grouping, central nuclei and ring fibers. Such fibers are consistent with abnormal regeneration.We suggest that the occurrence of mutations involving both AchR receptor and phospholipase might concur in determining a new distal phenotype with permanent weakness.Our family was previously diagnosed as myotonic dystrophy or distal myopathy. The presence of the histochemical findings of both myopathy and neuropathy were present. We suggest the possibility of calcium overload due to prolonged open time of the AChR channel with a presynaptic component might determine a distal neuro-myopathy with slow evolution and muscle rearrangement due to a muscle fiber degeneration and functional denervation.The slow channel mutation should be searched in families with permanent distal weakness.
C. Angelini
A. Toscano
T. Mongini
G. Comi
R. Gauthier
S. Servidei
S. Ravaglia
C. Bruno
C. Semplicini
We have used the mdx mice strain (C57BL/10ScSn-mdx) as an experimental subject for the study of reiterative skeletal muscle necrosis–regeneration with basement membrane preservation. In young mdx muscle, by means of Hematoxylin–Eosin staining, different types of degenerative–regenerative groups (DRG) can be recognized and assigned to a defined muscle regeneration phase. To evaluate the expression of known key-regulatory genes in muscle regeneration, we have applied Laser Capture Microdissection technique to obtain tissue from different DRGs encompassing the complete skeletal muscle regenerative process. The expression of MyoD, Myf-5 and Myogenin showed a rapid increase in the first two days post-necrosis, which were followed by MRF4 expression, when newly regenerating fibers started to appear (3–5 days post-necrosis). MHCd mRNA levels, undetectable in mature non-injured fibers, increased progressively from the first day post-necrosis and reached its maximum level of expression in DRGs showing basophilic regenerating fibers. TGFβ-1 mRNA expression showed a prompt and strong increase following fiber necrosis that persisted during the inflammatory phase, and progressively decreased when new regenerating fibers began to appear. In contrast, IGF-2 mRNA expression decreased during the first days post-necrosis but was followed by a progressive rise in its expression coinciding with the appearance of the newly formed myofibers, reaching the maximum expression levels in DRGs composed of medium caliber basophilic regenerating myofibers (5–7 days post-necrosis). mdx degenerative–regenerative group typing, in conjunction with laser microdissection-based gene expression analysis, opens up a new approach to the molecular study of skeletal muscle regeneration.
C. Angelini
A. Toscano
T. Mongini
G. Comi
R. Gauthier
S. Servidei
S. Ravaglia
C. Bruno
C. Semplicini
We have used the mdx mice strain (C57BL/10ScSn-mdx) as an experimental subject for the study of reiterative skeletal muscle necrosis–regeneration with basement membrane preservation. In young mdx muscle, by means of Hematoxylin–Eosin staining, different types of degenerative–regenerative groups (DRG) can be recognized and assigned to a defined muscle regeneration phase. To evaluate the expression of known key-regulatory genes in muscle regeneration, we have applied Laser Capture Microdissection technique to obtain tissue from different DRGs encompassing the complete skeletal muscle regenerative process. The expression of MyoD, Myf-5 and Myogenin showed a rapid increase in the first two days post-necrosis, which were followed by MRF4 expression, when newly regenerating fibers started to appear (3–5 days post-necrosis). MHCd mRNA levels, undetectable in mature non-injured fibers, increased progressively from the first day post-necrosis and reached its maximum level of expression in DRGs showing basophilic regenerating fibers. TGFβ-1 mRNA expression showed a prompt and strong increase following fiber necrosis that persisted during the inflammatory phase, and progressively decreased when new regenerating fibers began to appear. In contrast, IGF-2 mRNA expression decreased during the first days post-necrosis but was followed by a progressive rise in its expression coinciding with the appearance of the newly formed myofibers, reaching the maximum expression levels in DRGs composed of medium caliber basophilic regenerating myofibers (5–7 days post-necrosis). mdx degenerative–regenerative group typing, in conjunction with laser microdissection-based gene expression analysis, opens up a new approach to the molecular study of skeletal muscle regeneration.
A. Bruson
F. Sambataro
G. Querin
C. D’Ascenzo
A. Palmieri
J. Agostini
A. Gaiani
C. Angelini
M. Galbiati
A. Poletti
M. Pennuto
E. Pegoraro
M. Clementi and G. Soraru
Background: Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)-expressing tissues. The AR gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA).
C. Angelini
A. Amaroli
C. Falugi
G. Bella
V. Matranga
The presence and function of acetylcholinesterase (AChE) in blood cells and plasma is well known. The enzyme activity is associated to red blood cell membranes, as well as to the perinuclear region of leucocytes, suggesting a role in the function of the latter. Recently coelomocytes, acknowledged progenitors of immune cells in vertebrate systems, have been shown to respond to stress conditions, both in laboratory experiments and field studies. Bearing in mind the similarity between coelomocytes and vertebrate blood cells, we investigated the presence of AChE activity in coelomocytes of the sea urchin Paracentrotus lividus characterized by specific inhibitors, in relation to cold stress induced in the laboratory. Exposure to stress was followed by electrophoretic analysis of AChE activity and Western blot analysis of AChE-like immunoreactivity. Moreover, quantitative analysis of the different molecular forms of AChE was carried out with the aid of a spectrophotometric method. The effects of stress on AChE activity were time dependent. In fact, the enzyme activity was detected by the catalytic activity in cleaving the substrate acetyl thiocholine iodide, which appears to be formed by different isoforms of the enzyme, compared to that of Electrophorus, which was used as a control. Western blot analyses showed the presence of different immunoreactive molecules, with molecular mass ranging from 265 kDa (corresponding to Electrophorus molecules) to about 180 kDa. According to quantitative analysis, the isoforms that were differentiated corresponded to an AChE with the capacity to cleave acetyl-beta-methyl thiocholine iodide (the so-called true AChE, E.C. 3.1.1.7, corresponding to the 265 kDa band) and to a ChE with the capacity to cleave propionyl thiocholine iodide as well. The latter is an ancestral form of AChE, mainly present in invertebrates. Each of these forms was affected differently by varying time exposures.
C. Angelini
E. Pegoraro
E. Turella
M. T. Intino
A. Pini
C. Costa
A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P lt 0.01), in rising from a chair, Gower's maneuver, and walking (P lt 0.0025) after 6 months of treatment. After 1 year, all the above changes remained significantly improved and the MRC index was significantly better (P lt 0.05) in the treated group. After 2 years, a significant change was found in the MRC index: higher scores in walking, chair rising (P lt 0.02), and grade and time of Gower's maneuver (P lt 0.05) were found. The mean time for loss of ambulation for the treated group after we started the trial was 20.5 +- 11 months; for the placebo group it was 33.2 +- 9 months (placebo vs. deflazacort group, P lt 0.05). Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group. Side effects were mild, consisting of moderate weight gain and slight behavioral changes.
C. Angelini
W. Beusch
A. Cardini
D.J. Crennell
M. De vincenzi
G. Di Vita
A. Duane
J.P. Fabre
V. Flaminio
A. Frenkel
T. Gys
K. Harrison
E. Lamanna
H. Leutz
G. Martellotti
J.G. McEwen
D.R.O. Morrison
G. Penso
S. Petrera
C. Roda
A. Sciubba
E. Vicari
D.M. Websdale
G. Wilquet
C. Angelini
A. Amaroli
C. Falugi
G. Bella and V. Matranga
The presence and function of acetylcholinesterase (AChE) in blood cells and plasma is well known. The enzyme activity is associated to red blood cell membranes, as well as to the perinuclear region of leucocytes, suggesting a role in the function of the latter. Recently coelomocytes, acknowledged progenitors of immune cells in vertebrate systems, have been shown to respond to stress conditions, both in laboratory experiments and field studies. Bearing in mind the similarity between coelomocytes and vertebrate blood cells, we investigated the presence of AChE activity in coelomocytes of the sea urchin Paracentrotus lividus characterized by specific inhibitors, in relation to cold stress induced in the laboratory. Exposure to stress was followed by electrophoretic analysis of AChE activity and Western blot analysis of AChE-like immunoreactivity. Moreover, quantitative analysis of the different molecular forms of AChE was carried out with the aid of a spectrophotometric method. The effects of stress on AChE activity were time dependent. In fact, the enzyme activity was detected by the catalytic activity in cleaving the substrate acetyl thiocholine iodide, which appears to be formed by different isoforms of the enzyme, compared to that of Electrophorus, which was used as a control. Western blot analyses showed the presence of different immunoreactive molecules, with molecular mass ranging from 265 kDa (corresponding to Electrophorus molecules) to about 180 kDa. According to quantitative analysis, the isoforms that were differentiated corresponded to an AChE with the capacity to cleave acetyl--methyl thiocholine iodide (the so-called true AChE, E.C. 3.1.1.7, corresponding to the 265 kDa band) and to a ChE with the capacity to cleave propionyl thiocholine iodide as well. The latter is an ancestral form of AChE, mainly present in invertebrates. Each of these forms was affected differently by varying time exposures.
C. Angelini
W. Beusch
A. Cardini
D.J. Crennell
M. De Vincenzi
G. Di Vita
A. Duane
J.-P. Fabre
V. Flaminio
A. Frenkel
T. Gys
K. Harrison
E. Lamanna
H. Leutz
D. Lucchesi
G. Martelloti
J.G. McEwen
D.R.O. Morrison
G. Penso
S. Petrera
C. Roda
A. Sciubba
E. Vicari
D.M. Websdale
C. Angelini
W. Beusch
D.J. Crennell
M De Vincenzi
A. Duane
J.P. Fabre
V. Flaminio
A. Frenkel
T. Gys
K. Harrison
E. Lamanna
H. Leutz
G. Martellotti
J.G. McEwen
D.R.O. Morrison
G. Penso
S. Petrera
M. Primout
C. Roda
A. Sciubba
E. Vicari
D.M. Websdale
C. Angelini
W. Beusch
A. Cardini
D.J. Crennell
M. De Vincenzi
G. Di Vita
A. Duane
J.-P. Fabre
V. Flaminio
A. Frenkel
T. Gys
K. Harrison
E. Lamanna
H. Leutz
D. Lucchesi
G. Martellotti
J.G. McEwen
D.R.O. Morrison
G. Penso
S. Petrera
C. Roda
A. Sciubba
E. Vicari
D.M. Websdale
The WA84 experiment at CERN has been proposed as a study of heavy-flavour physics using a novel, high-resolution vertex detector, consisting of an active target assembled from coherent bundles of scintillating optical microfibres. This paper is a presentation of work carried out in the development of the vertex detector. Results from tests of prototypes of the detector in a charged-particle beam are reported, and the differences in the performance of glass and plastic active targets are discussed
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