Biomedical subjects
A Vincent
Publications and source records attributed to A Vincent.
[Prognosis of acute psychotropic drug poisoning. The Lausanne experience].
366 charts are reviewed of patients admitted to the ICU of the Lausanne University Department of Medicine during 5 consecutive years for psychotropic drug overdose and treated by supportive management. 25% were severely intoxicated and 46 patients required ventilatory support either for aspiration pneumonia or CNS depression. The mortality rate was 0.5% and mean stay in the ICU 2.8 days. Neither the two deaths nor the complications (already established upon admission or within 6 hours of presentation) could have been prevented by hemoperfusion. The efficiency of conservative management raises questions about the value of extrarenal clearance technics in the absence of concurrent renal failure.
Acetylcholine receptor antibody: clinical and experimental aspects.
Anti-acetylcholine (ACh) receptor antibody is the specific antibody in myasthenia gravis (MG). Groups of patients distinguished by thymic pathology and age of onset have shown differences in sex and HLA antigen incidence and in anti-ACh receptor antibody levels. Group differences in the characteristics of this antibody, including the percentage of kappa and gamma light chains, IgG subclass and reactivity with other ACh receptor preparations, were detected only in patients with ocular MG. This group alone showed a possible association with Gm allotype in Caucasians; the anti-ACh receptor antibody had a greater proportion of kappa light chain and better reactivity with human ocular ACh receptor than did generalized MG. The results indicate heterogeneity of this disease. Thymic cells from myasthenic patients with thymic hyperplasia spontaneously synthesize anti-ACh receptor antibody in culture and, after irradiation to abrogate antibody production and any suppressor effects, can selectively enhance the synthesis of anti-ACh receptor antibody by autologous blood lymphocytes in co-culture. The cell types that underlie these responses have been investigated by deleting cell subsets by complement-mediated lysis using monoclonal antibodies. Neither cortical (NA1/34+) thymocytes nor mature T cells (MBG6+) are essential for antibody production in vitro by thymic cells. The enhancement of antibody production by irradiated thymic cells may depend on antigen-presenting cells not expressing the HLA-DR surface marker, or possibly antigen-specific helper T cells, or both.
Anti-acetylcholine receptor antibody: use of polyethylene glycol as an aid to precipitation of antibody-receptor complexes in determination of light chain and subclass.
Polyethylene glycol 6000 (PEG) was used as an aid to precipitation of antibody-acetylcholine receptor (AChR) complexes. In the absence of anti-human IgG, 8% PEG can be used to precipitate antibody-AChR complexes. In the presence of low titre specific antiserum, 3% PEG selectively precipitates anti-IgG-IgG-AChR complexes and allows analysis of light chain and subclass contribution to the anti-AChR. The specificity of the various antisera is presented and results in 16 patients described.
Purification of anti-acetylcholine receptor antibody from patients with myasthenia gravis.
The purification of specific anti-acetylcholine receptor antibodies from the plasma of 3 patients with myasthenia gravis was achieved by affinity chromatography using an immunoadsorbent of alpha-bungarotoxin-Sepharose 4B covalently linked to acetylcholine receptor extracted from human leg muscle. The specific antibody was eluted with potassium thiocyanate. The antibody characteristics were monitored throughout the purification procedure. The high avidity of the antibodies for the acetylcholine receptor was preserved but there was some loss of lambda light chain specific antibody.
Eaton-Lambert syndrome: acetylcholine and choline acetyltransferase in skeletal muscle.
In biopsied intercostal muscle from six patients with Eaton-Lambert syndrome, we measured acetylcholine content and release and choline acetyltransferase. Both the spontaneous and the KCl-evoked release of acetylcholine were abnormally low. On the other hand, the acetylcholine content and the level of choline acetyltransferase activity were within the range of values earlier found in healthy human intercostal muscle. These results are consistent with the view that the defect in this syndrome lies not in the synthesis or storage of the transmitter but in the mechanism of release itself.
[Synthesis of aryloxypropanolamines with chromone or coumarin structures. Study of beta-blocking activity].
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Lambert-Eaton myasthenic syndrome: electrophysiological evidence for a humoral factor.
Noncarcinomatous Lambert-Eaton myasthenic syndrome (LEMS) often associates with autoimmune disorders. A course of plasma exchange in both carcinomatous and noncarcinomatous LEMS induced clinical and significant electromyographic improvement which reached its peak 10 to 20 days after the last exchange. Prednisolone and azathioprine treatment was associated with striking clinical and electromyographic improvement in the 3 noncarcinomatous patients. The IgG fraction of LEMS plasma, and to a lesser extent plasma itself, injected daily intraperitoneally into mice induced similar electrophysiological changes to human LEMS, the reduction in the quantal content of the end-plate potential (epp) in diaphragm being highly significant. A train of stimuli at 40 Hz produced early facilitation or a less marked decline in epp amplitudes than occurred in mice injected with control IgG. The results indicate that the electrophysiological abnormalities in both forms of LEMS arise from an IgG autoantibody that binds to nerve terminal determinants which are concerned with the quantal release of transmitter.
Acetylcholine receptor antibody characteristics in myasthenia gravis. I. Patients with generalized myasthenia or disease restricted to ocular muscles.
We have investigated anti-acetylcholine receptor (AChR) characteristics in three forms of generalized myasthenia gravis, which are distinguishable by their thymic pathology, age of onset, sex incidence and HLA antigen associations, and in restricted ocular myasthenia. Light chain, IgG subclass, avidity for denervated human AChR and reaction with various human and mammalian AChR preparations were examined in 9-12 patients from each group. Characteristics varied between individuals in each group but no significant differences were found in mean values between the three groups with generalized myasthenia. When antibody characteristics in ocular myasthenia were compared with those in generalized disease, however, differences were found particularly in relative reactivity with denervated, normal and ocular human AChR. The nature of the humoral response in ocular myasthenia thus differs from that in generalized myasthenia. The similarity in the humoral response between the three groups of generalized myasthenia suggests, on the other hand, that the distinguishing clinical features may reflect differing susceptibilities to diverse precipitating mechanisms.
Acetylcholine receptor antibody characteristics in myasthenia gravis. II. Patients with penicillamine-induced myasthenia or idiopathic myasthenia of recent onset.
Anti-acetylcholine receptor (anti-AChR) antibody characteristics including light chain, IgG subclass, avidity for denervated human acetylcholine receptor and reaction with various human and mammalian AChR preparations were examined in 11 patients who developed myasthenia during penicillamine treatment of rheumatoid arthritis. Results were compared with those already reported in 35 patients with generalized idiopathic myasthenia gravis (MG). We found significant differences in the avidity and the light chain of the anti-AChR. However, anti-AChR characteristics in 12 patients with recent onset (less than 4 months' duration) idiopathic MG did not differ significantly from those in patients with penicillamine-induced MG. In the patients with generalized MG a trend was found towards higher percentage of kappa light chain and higher anti-AChR avidity with duration of disease. Anti-acetylcholine receptor antibodies in penicillamine-induced myasthenia gravis therefore appear to be similar to those of idiopathic myasthenia gravis of recent onset.
The polyribosomal poly(A)-binding protein is highly conserved in vertebrate species. Comparison in duck, mouse and rabbit.
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Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome.
The myasthenic (Eaton-Lambert) syndrome, associated with carcinoma of the bronchus in one patient and with immunological disorders in two others, improved after plasma exchange--observations supported by electromyographic evidence in two cases. Prednisolone and azathioprine treatment led to almost complete remission in one of the non-neoplastic cases and to improvement in the other. The IgG fraction of plasma from all three patients, injected daily (10 mg) into mice for 37-77 days, significantly reduced the initial compound muscle action potential and the quantal content of the end-plate potential measured in the diaphragm, when compared with control human IgG. These results indicate that an IgG autoantibody, binding to nerve terminal determinants, may be responsible for the disorder of neuromuscular transmission in the myasthenic syndrome, and that immunosuppressive drugs may be useful in treating the nonneoplastic form of the disease.
Potential role of mRNP proteins in cytoplasmic control of gene expression in duck erythroblasts.
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Idiotype restriction in myasthenia gravis antibodies.
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Comparisons of proteins associated with duck-globin mRNA and its polyadenylated segment in polyribosomal and repressed free messenger ribonucleoprotein complexes.
EDTA dissociation of polyribosomes from duck erythroblasts allowed us to isolate the 15-S globin messenger ribonucleoproteins (mRNP) by sucrose gradient centrifugation or affinity chromatography on poly(U)-Sepharose or oligo(dT)-cellulose columns. Their protein composition was compared by one and two-dimensional electrophoresis in sodium dodecyl sulfate to the free 20-S mRNP containing the repressed fraction of globin mRNA [Vincent, A., Civelli, O., Maundrell, K., and Scherrer, K. (1980) Eur. J. Biochem. 112, 617--633]. The protein composition of the 15-S mRNP isolated by these methods in different ionic strength conditions, was characterized by a major 73 000-Mr polypeptide and seven minor polypeptides with Mr ranging from 45 000 to 68 000, all of which are slightly basic, and about five acidic ones in the 80 000--130 000-Mr range. All these are retained in the 15-S mRNP core particle isolated at 0.5 M KCl. At low ionic strength, in addition, a specific group of acidic polypeptides in the Mr range 35 000--105 000 was also found associated with globin mRNA. Oligo(dT)-cellulose chromatography of mRNP digested with ribonucleases A and T1 indicated that the 73 000-Mr major protein is bound to the poly(A) segment; some other proteins resolved as minor components interact with both the poly(A) and non-poly(A) regions of globin mRNA. Characterization of proteins interacting with the poly(A) segment of non-polyribosomal globin mRNA in 20-S free mRNP demonstrated the absence of the polyribosomal 73 000-Mr poly(A)-binding protein. Furthermore, it confirmed that the protein compositions of translatable polyribosomal and repressed free globin mRNP are very different. Indeed, the respective core (0.5 M KCl) particles contain only two possibly common polypeptides. The specificity of proteins associated with globin mRNA in two different functional states shown here supports the hypothesis of a role of mRNP proteins in translational control of mRNA.
Choline acetyltransferase in skeletal muscle from patients with myasthenia gravis.
Acetylcholine synthesis in homogenates of human intercostal muscle was measured by a radiochemical method. Choline acetyltransferase activity in control muscle was about 20 nmol . g-1 . h-1. The enzyme was found only in the endplate area of the muscle. At high substrate concentrations its activity was overshadowed by the acetylcholine synthesizing activity of a different enzyme not saturated by 10 mM-choline. The nonspecific enzyme was present at and away from the endplate area. Choline acetyltransferase in parasternal samples of intercostal muscle from myasthenia gravis patients was about 2.5 times higher than in samples, taken from a more lateral location, of control patients, but the Km for choline was not altered (0.24 mM). It is suggested that in myasthenia gravis the shortage of acetylcholine receptors is partially compensated for by increased synthesis, storage, and release of the transmitter.
Anti-acetylcholine receptor antibody synthesis by cultured lymphocytes in myasthenia gravis: thymic and peripheral blood cell interactions.
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Plasma exchange and immunosuppressive drug treatment in myasthenia gravis: no evidence for synergy.
We have investigated whether plasma exchange in myasthenia gravis synergises with additional immunosuppressive drug therapy (azathioprine, cyclophosphamide or cytosine arabinoside). Serum anti-acetylcholine receptor (AChR) antibody titres were followed over 28 days after a course of PE in 20 patients, of whom 17 were taking 20-80 mg prednisone on alternate days. No significant difference was observed in mean anti-AChR antibody recovery following plasma exchange with and without additional immunosuppressive therapy. In paired studies where patients served as their own controls, mean anti-AChR recovery with and without azathioprine or cytosine arabinoside showed no significant differences. Anti-AChR recovery rates after large and small plasma exchange courses also did not differ significantly. Prolonged administration of azathioprine reduced antibody titres independently of plasma exchange. These results fail to demonstrate significant synergy between plasma exchange and the additional immunosuppressive drugs used, and suggest that the effects of plasma exchange were transient.