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P Dreyfus

Publications and source records attributed to P Dreyfus.

At least 19 recordsLinked to original sources
PubMed1989

De novo amplification within a "silent" human cholinesterase gene in a family subjected to prolonged exposure to organophosphorous insecticides.

A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing the "silent" CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorous insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the "onion skin" model, based on amplification of genes in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where we previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. Our findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor. Its occurrence in two generations from a family under prolonged exposure to parathion indicates that organophosphorous poisons may be implicated in previously unforeseen long-term ecological effects.

Butyrylcholinesterase↗
PubMed1988

Cross-homologies and structural differences between human cholinesterases revealed by antibodies against cDNA-produced human butyrylcholinesterase peptides.

To study the polymorphism of human cholinesterases (ChEs) at the levels of primary sequence and three-dimensional structure, a fragment of human butyrylcholinesterase (BuChE) cDNA was subcloned into the pEX bacterial expression vector and its polypeptide product analyzed. Immunoblot analysis revealed that the clone-produced BuChE peptides interact specifically with antibodies against human and Torpedo acetylcholinesterase (AChE). Rabbit polyclonal antibodies prepared against the purified clone-produced BuChE polypeptides interacted in immunoblots with denatured serum BuChE as well as with purified and denatured erythrocyte AChE. In contrast, native BuChE tetramers from human serum, but not AChE dimers from erythrocytes, interacted with these antibodies in solution to produce antibody-enzyme complexes that could be precipitated by second antibodies and that sedimented faster than the native enzyme in sucrose gradient centrifugation. Furthermore, both AChE and BuChE dimers from muscle extracts, but not BuChE tetramers from muscle, interacted with these antibodies. To reveal further whether the anti-cloned BuChE antibodies would interact in situ with ChEs in the neuromuscular junction, bundles of muscle fibers were microscopically dissected from the region in fetal human diaphragm that is innervated by the phrenic nerve. Muscle fibers incubated with the antibodies and with 125I-Protein A were subjected to emulsion autoradiography, followed by cytochemical ChE staining. The anti-cloned BuChE antibodies, as well as anti-Torpedo AChE antibodies, created patches of silver grains in the muscle endplate region stained for ChE, under conditions where control sera did not. These findings demonstrate that the various forms of human AChE and BuChE in blood and in neuromuscular junctions share sequence homologies, but also display structural differences between distinct molecular forms within particular tissues, as well as between similarly sedimenting molecular forms from different tissues.

Acetylcholinesterase↗
PubMed1986

The voltage-dependent sodium channel is co-localized with the acetylcholine receptor at the vertebrate neuromuscular junction.

Isolated motor endplates from mouse intercostal muscles can be obtained after subcellular fractionation. On these motor endplates, localization of the nicotinic receptor and of the voltage-dependent Na+ channel coincides as demonstrated by double labeling with rhodamine alpha-bungarotoxin and a specific anti-Na+ channel monoclonal antibody. High density of Na+ channel at the motor endplate is confirmed by the enrichment in TTX binding sites as compared to the crude homogenate. In contrast isolated motor endplates are almost completely devoid of Ca2+ channel antagonist binding sites.

Animals↗
PubMed1985

[Rheumatological manifestations of adrenal insufficiencies].

Muscular, articular and periarticular symptoms were reviewed in 19 patients with adrenal failure and compared with previously published data. Symptoms are variable and non-specific; muscular cramps and periarticular calcification were common. Hypercalcaemia was uncommon but its incidence was probably underestimated. Calcification of the ear cartilage was rare but characteristic.

Adrenal Insufficiency↗
PubMed1984

Distribution and quantification of ACh receptors and innervation in diaphragm muscle of normal and mdg mouse embryos.

Muscular dysgenesis (mdg) in the mouse is an autosomal recessive mutation, expressed in the homozygous state (in vivo and in vitro) as an absence of skeletal muscle contraction. The distribution of acetylcholine receptors (ACh R) in the diaphragms of phenotypically normal and dysgenic (mdg/mdg) embryos was studied from the 14th to 19th day of gestation by binding of 125I-alpha-bungarotoxin to the muscle, followed by autoradiography of longitudinally sectioned hemidiaphragms and/or of isolated muscle fibers. Localization of ACh R at putative motor end-plate regions begins 14 to 15 days in utero in both normal and dysgenic diaphragms. The distribution of high ACh R density patches is aberrantly scattered beyond the normal innervation pattern in dysgenic diaphragms. Isolated mutant fibers possess (1) multiple ACh R clusters, up to five per single fiber, (2) larger clusters of more variable morphology and variable receptor density than normal clusters, and (3) higher levels of extrajunctional receptors than normal fibers. These autoradiographic results correlate well with higher total level of toxin binding sites per diaphragm and per milligram protein in dysgenic vs normal muscle, as quantified from gamma counting of sucrose density gradient isolation of 125I-toxin-ACh R complexes. The dispersed distribution of ACh R patches on dysgenic muscle may be correlated with extensive phrenic nerve branching as demonstrated by silver impregnation technique. We suggest that the aberrant ACh R cluster distribution is a result of multiple innervation of single fibers from the branched nerve terminals. Possible causes of the excessive nerve branching in the mutant are discussed in light of generalized nerve sprouting found in paralyzed muscle.

Animals↗
PubMed1984

[Cross reactions of HLA A and B antigens in 63 patients with rheumatoid arthritis].

Cross reactions are very frequently observed when HLA A and B antigens are determined by a routine lymphocytotoxicity method. Such cross reactions are probably due to biochemical structural similarities shared by several HLA antigens. In this work, we studied the cross reactions which occurred during HLA A and B typing of 63 patients with classical or definite rheumatoid arthritis (RA) according to the ARA criteria. No association was found between RA and any single HLA A or B antigen. In contrast, when cross reactions were taken into account, the B8 B14 cross reactant group frequency was increased in RA patients (34,9 p. cent) as compared to controls (20 p. cent, p less than 0,004) and was even more clearly elevated in the 42 seropositive RA patients (40,5 p. cent, p less than 0,002). No relation was found between HLA phenotype and Sjögren's syndrome even when cross reactions were considered. The B8 DR3 haplotype has been shown to be associated with drug intolerance . The B8 B14 cross reactant group was present in 22 out of our 63 RA patients, 16 of whom were B8+. Among the latter, 6 patients exhibited poor tolerance to gold salts and 6 other patients did not respond to gold therapy, suggesting that the B8 antigen could predict not only a poor tolerance but also a poor response to disease modifying drugs.

Arthritis, Rheumatoid↗
PubMed1984

[Study of HLA antigens A and B and their cross reactions in B27-negative ankylosing spondylarthritis].

In an attempt to find common immunogenetic features in B27+ and B27- ankylosing spondylitis patients, the B7 cross reactant antigens (BW22, B27, B40, B12, B13) were systematically tested by a lymphocytotoxicity method in 43 patients suffering from ankylosing spondylitis according to the Rome criteria. These included 25 caucasian patients (20 B27+, 5 B27-), 15 north african patients (11 B27+, 4 B27-) and 3 west indian mulattos (all B27-). The frequency of the B7 cross reactant antigens, when compared to controls, was not increased in the B27- patients as a whole, nor in any of the 3 populations studied. Our negative results are in agreement with those of similar published studies in homogeneous populations. They do not support the hypothesis of a direct involvement of HLA B antigens as cofactors favouring ankylosing spondylitis.

Cross Reactions↗
PubMed1981

[Sea urchin spines synovitis. A case report with positive pasteurellosis antigen intradermoreaction (author's transl)].

A case is reported of a 53 years old woman who injured proximal interphalangeal joint of the right fourth finger on a sea urchin spine. She developed an extensive arthritis after synovial biopsy with sequellar fourth and fifth paw fashioned fingers and a palmar fibrositis. The originality of this observation with typical clinical symptoms and characteristic synovial histology (giant cells granulomatous synovitis) is the combination of a pasteurellosis infection. The diagnosis of the last one can be based on the inoculation in extra-aquatic condition, the extension of arthritis and particularly the positivity of pasteurellosis antigen intradermoreaction.

Arthritis, Infectious↗