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Jean-Fran ois Marini Fran oise Pons Jocelyne Leger Nathalie Loffreda Monique Anoal Martine Chevallay Michel Fardeau Jean J. Leger 《Neuromuscular disorders : NMD》1991,1(6):397-409
The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression. 相似文献
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HJ Aubin S Tilikete C Laureaux HT Nguyen Hac MC Roullet-Volmi S Troupel D Barrucand 《European psychiatry》1995,10(8)
The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits. 相似文献
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G. Lallement Didier Clarençon Catherine Masqueliez Dominique Baubichon Monique Galonnier Marie-France Burckhart Michel Peoc’h Jean Claude Mestries 《Archives of toxicology》1997,72(2):84-92
Organophosphorus nerve agents are still in use today in warfare and as terrorism compounds. Classical emergency treatment
of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic
cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, recent experiments with
primates have demonstrated that such treatment, even when administered immediately after organophosphate exposure, does not
rapidly restore normal electroencephalographic (EEG) activity and fails to totally prevent neuronal brain damage. The objective
of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an
antiglutamatergic compound, as a complement to the available emergency therapy against organophosphate poisoning. GK-11 was
injected at a dose of 0.1 mg/kg (i.v) after a 45-min latency period to heavily intoxicated (8 LD50) primates. Just after intoxication, man-equivalent doses of one autoinjector containing atropine/pralidoxime/diazepam were
administered. The effects of GK-11 were examined on survival, EEG activity, signs of toxicity, recovery after challenge and
central nervous system histology. The present data demonstrate that treatment with GK-11 prevents the mortality observed after
early administration of classical emergency medication alone. EEG recordings and clinical observations also revealed that
GK-11 prevented soman-induced seizures and motor convulsions. EEG analysis within the classical frequency bands (beta, theta,
alpha, delta) demonstrated that central activity was totally restored to normal after GK-11 treatment, but remained profoundly
altered in animals receiving atropine/pralidoxime/diazepam alone. GK-11 also markedly accelerated clinical recovery of soman-challenged
primates. Lastly, this drug totally prevented the neuropathology observed 3 weeks after soman exposure in animals treated
with classical emergency treatment alone. GK-11 represents a promising adjuvant therapy to the currently available emergency
polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in
a human clinical trial for a different neuroprotective indication.
Received: 16 June 1997 / Accepted: 23 September 1997 相似文献
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Evidence that [3H]-alpha,beta-methylene ATP may label an endothelial-derived cell line 5'-nucleotidase with high affinity. 总被引:1,自引:1,他引:0
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A. D. Michel N. M. Chau T. P. Fan E. E. Frost P. P. Humphrey 《British journal of pharmacology》1995,115(5):767-774
1. In membranes prepared from a permanent cell line of endothelial origin (WEC cells), [3H]-alpha, beta-methylene ATP ([3H]-alpha, beta-meATP) labelled high (pKd = 9.5; Bmax = 3.75 pmol mg-1 protein) and low (pKd = 7.2; Bmax = 23.3 pmol mg-1 protein) affinity binding sites. The high affinity [3H]-alpha, beta-meATP binding sites in the WEC cell membranes could be selectively labelled with a low concentration of the radioligand (1 nM). In competition studies performed at a radioligand concentration of 1 nM, 88.6% of the sites possessed high affinity (pIC50 = 8.26) for alpha, beta-meATP. 2. The high affinity [3H]-alpha, beta-meATP binding sites appeared heterogeneous since in competition studies a number of nucleotide analogues (alpha, beta-meADP, ATP, ADP, AMP, GTP, GppNHp, GMP) and adenosine identified two populations of the sites labelled by 1 nM [3H]-alpha, beta-meATP. The proportion of sites with high affinity for these compounds was found to vary between 42 and 69%. 3. Approximately 60-69% of the binding sites labelled with 1 nM [3H]-alpha, beta-meATP possessed high affinity for alpha, beta-meADP (pIC50 = 8.87), AMP (pIC50 = 7.12), GMP (pIC50 = 7.34), UTP (pIC50 = 6.12), GTP (pIC50 = 7.59), GppNHp (pIC50 = 7.35) and adenosine (pIC50 = 5.45).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献