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Biomedical subjects

A Vincent

Publications and source records attributed to A Vincent.

At least 343 records · Page 19Linked to original sources
PubMed1988

Immunological and pharmacological heterogeneity of alpha-bungarotoxin binding sites extracted from TE671 cells.

A proportion of the acetylcholine receptors (AChR) extracted from the human medulloblastoma cell line, TE671, differed pharmacologically and immunologically from AChR extracted from ischaemic human calf muscle (HCM). 29.6% (mean value) of the total 125I-alpha-bungarotoxin (alpha-BuTx) binding sites in the TE671 extracts was not inhibited by d-tubocurarine (dTC). Three of five monoclonal antibodies (m.abs), all of which precipitated greater than 80% of HCM AChRs, precipitated less than 55% of the total TE671 AChR. However, myasthenia gravis sera bound to TE671, and TE671 cell surface AChRs appeared to be similar to that of HCM.

Antibodies, Monoclonal↗
PubMed1988

Lambert-Eaton syndrome antibodies: reaction with membranes from a small cell lung cancer xenograft.

Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic autoimmune disorder caused by an IgG-mediated reduction in number of presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction. In at least 50% of cases, the stimulus for antibody production may be VGCC on small cell lung cancer (SCLC). In this study membranes isolated from a human small cell lung cancer xenograft (Mar), that bound [3H]PN200-110, a VGCC antagonist, were subjected to Western blotting using plasma from 12 LEMS patients and eight controls. Although one band recognised by 3/12 LEMS IgGs might be associated with the VGCC, a number of other proteins were recognised both by LEMS plasma, and by plasma from patients with other disorders. The results illustrate the difficulties found using Western blotting with autoimmune plasma to identify specific polypeptides in a crude antigen preparation.

Adult↗
PubMed1988

Full oestrogenic activity of C19-delta 5 adrenal steroids in rat pituitary lactotrophs and somatotrophs.

Oestrogens are known to exert specific stimulatory effects on basal and dopamine (DA)-inhibited prolactin (PRL) release as well as on PRL cell content in rat adenohypophysial cells in primary culture. Recently, we have demonstrated that classical oestrogens increase growth hormone (GH) release and cellular GH content in rat pituitary somatotrophs. Since there is evidence that 5-androstene-3 beta, 17 beta-diol (delta 5-diol), a metabolite of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) can induce typical oestrogenic responses in target tissues, we have investigated the effect of C19 adrenal steroids and compared them to that of 17 beta-oestradiol (E2) on the above-indicated parameters. Following a 72-h incubation, maximal concentrations of E2, delta 5-diol and DHEA caused a similar increase in PRL cell content at respective EC50 values of 0.020, 14 and 115 nM. The sensitivity of lactotrophs to DA action was decreased by approximately 4-fold after a 48-h exposure to maximal concentrations of delta 5-diol or DHEA. The time course of the antidopaminergic effect of delta 5-diol and DHEA was almost superimposable to that of E2. A 72-h incubation with 5 microM DHEA-S, a concentration within the range of blood levels found in women, doubled (P less than or equal to 0.001) cellular PRL accumulation. On the other hand, androstenedione (delta 4-dione) was without effect on any of the parameters measured. All stimulatory effects induced by maximal effective concentrations of delta 5-diol, DHEA or DHEA-S were competitively inhibited by simultaneous incubation with the antioestrogen LY156758. The amplitude of the stimulatory effects of delta 5-diol and DHEA on GH cell content as well as on spontaneous GH-releasing factor (GRF)-induced GH release was superimposable to that observed with E2. The effect of the steroids on GH cell content was exerted at 0.016 nM (E2), 12 nM (delta 5-diol) and 250 nM (DHEA). Simultaneous incubation with LY156758 completely blocked the effect of maximally effective concentrations of E2, delta 5-diol and DHEA in somatotrophs. Furthermore, a physiological concentration of DHEA-S (5 microM) enhanced spontaneous as well as GRF-induced GH release. On the other hand, delta 4-dione as well as testosterone and dihydrotestosterone did not alter GH release. The present data demonstrate that delta 5-diol, DHEA and DHEA-S can exert full oestrogenic effects in lactotrophs and somatotrophs, thus supporting their potential oestrogenic role under both physiological and pathological conditions.

Androgens↗
PubMed1988

Neuroimmunology of myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease in which the immune system attacks the nicotinic acetylcholine receptors (AChRs) of the neuromuscular junction. Anti-AChR antibodies are present in 85% of patients and bind to distinct epitopes on the surface of the AChR alpha subunits, as defined by competition with monoclonal anti-AChR antibodies. There are at least three types of the disease, defined by thymic histology, age of onset, and HLA associations, and anti-AChR antibodies show some differences in fine specificity between those with thymic hyperplasia and those with thymic tumors. Peripheral blood lymphocytes from MG patients contain T lymphocytes specifically sensitized to AChR. These are stimulated by purified Torpedo AChR and some human alpha subunit synthetic peptides. The T and B cell epitopes on the primary sequence of the alpha subunit are currently being mapped using recombinant human AChR subunit fragments.

Adult↗
PubMed1988

Electrophysiological effects of intravenous nicaïnoprol, a new antiarrhythmic agent, in 11 patients.

Nicaïnoprol, a new class 1 antiarrhythmic drug was given intravenously in a dose of 2 mg kg-1 of body weight (two patients) and 3 mg kg-1 of body weight (nine patients), and the clinical, electrocardiographic and electrophysiological effects were studied. Fifteen minutes after the end of drug administration, the PR interval was prolonged by 24.4% (P less than 0.001), and the QTc by 3.9% (P less than 0.01). The prolongation of QRS duration (+6%) was not significant. There was a slight (-3.9%) but non-significant decrease of the heart rate, with no alteration in sinus node function. Alteration of atrial conduction and atrioventricular (AV) conduction were due to an increase in the PA interval (+57.4%, P less than 0.05), the AH interval (+10.9%, NS) and the HV interval (+43.8%, P less than 0.01). The anterograde Wenckebach cycle length increased by 11% (P less than 0.01). The effective and functional atrial refractory periods increased respectively by 4.5% and 11.4% (P less than 0.05), and the effective refractory period of the AV node increased by 11.2% (P less than 0.05). None of the other electrophysiological variables changed significantly. A non-significant drop in blood pressure was noted between the second minute following injection (-9.4%) and the 15th minute (-3.4%), and two patients complained of dizziness; one of these two patients reported a heat flush with an oral burning. In conclusion, nicaïnoprol seems to possess the electrophysiological properties of some other class I antiarrhythmic drugs, and is clinically well tolerated.

Adult↗
PubMed1988

Action of antibodies directed against the acetylcholine receptor on channel function at mouse and rat motor end-plates.

1. The acute effects of antibodies (both polyclonal and monoclonal) raised against the acetylcholine receptor were studied at mouse and rat end-plates. Isolated muscles were incubated in solutions containing antibody for 2 1/4 to 3 1/2 h. Intracellular microelectrode techniques were then used to record miniature end-plate potentials (MEPPs) and voltage noise. 2. Most antibody preparations investigated did not reduce MEPP amplitudes as compared with controls. One monoclonal (C7) and one polyclonal (J) preparation irreversibly reduced MEPP amplitudes. Both preparations caused reductions in acetylcholine-induced depolarization and associated channel opening frequency (from voltage noise analysis). Single-channel depolarization was not altered by these antibodies. 3. On the basis of these and previous results, four antibody binding regions on the receptor surface were distinguished according to whether channel function and/or alpha-bungarotoxin binding were affected. Although most antibody preparations did not affect channel function, monoclonal antibody C7 appeared to alter function by acting on the channel itself so as to prevent channel opening.

Animals↗
PubMed1988

sry h-1, a new Drosophila melanogaster multifingered protein gene showing maternal and zygotic expression.

Low-stringency hybridization of the Drosophila serendipity (sry) finger-coding sequences revealed copies of homologous DNA sequences in the genomes of members of the family Drosophilidae and higher vertebrates. sry h-1, a new Drosophila finger protein-coding gene isolated on the basis of this homology, encodes a 3.2-kilobase (kb) mRNA accumulating in eggs and abundant in early embryos. The predicted sry h-1 protein product, starting at an internal initiation site of translation, is a 868-amino-acid basic polypeptide containing eight TFIIIA-like fingers encoded by three separate exons. Links separating individual fingers in the sry h-1 protein are variable in length and sequence, in contrast with the invariant H/C link found in most multi-fingered proteins. The similarity of the developmental pattern of transcription of sry h-1 with that of several other Drosophila finger protein genes suggests the existence of a complex set of such genes encoding an information which is, at least partly, maternally provided to the embryo and required for activation of gene transcription in early embryos or maintenance of gene activity during subsequent development.

Amino Acid Sequence↗
PubMed1988

Anti-acetylcholine receptor antibody specificities in serum and in thymic cell culture supernatants from myasthenia gravis patients.

We investigated the role of the thymus in myasthenia gravis by comparing the antigenic specificities of anti-acetylcholine receptor antibodies (anti-AChR), defined by competition with mouse monoclonal antibodies that bind to five different regions on human muscle AChR, in thymic culture supernatants and in serum pre- and post-thymectomy. Anti-AChR specificities present in the serum were broadly unchanged in 16 non-thymoma and six thymoma patients 7-30 months after thymectomy compared with an initial sample, although total anti-AChR frequently fell. The fine specificities of the anti-AChR synthesized in vitro by cultured lymphocytes from the thymus of ten patients (without thymoma) correlated significantly with that of the anti-AChR in the serum at the same time. We conclude that AChR-specific B cells in the thymus are representative of the total AChR-specific repertoire, and that thymectomy does not selectively deplete particular B cell clones.

Adolescent↗
PubMed1988

Comparison and standardization of measurement of anti-acetylcholine receptor antibody between laboratories.

The presence of autoantibodies to the acetylcholine receptor (anti-AChR) is useful in the diagnosis of myasthenia gravis, and their titre correlates with severity of the disease. Standardization of their measurement is therefore clinically important. Six laboratories world-wide were asked to determine anti-AChR under local conditions in coded samples and to repeat the measurement on the same samples recorded. There was a high degree of consensus over rank order of the samples but a wide systematic variation in the titres obtained. Standardization of units is an important next step in improving the comparability of anti-AChR data between laboratories.

Autoantibodies↗
PubMed1988

Epitopes on human acetylcholine receptor defined by monoclonal antibodies and myasthenia gravis sera.

The mouse monoclonal antibody (m.ab) binding sites on human acetylcholine receptor have been mapped by inhibition by F(ab')2 m.ab fragments, by competition with a rat m.ab against the main immunogenic region (anti-m.i.r), and by their ability to protect the a-Bungarotoxin (a-BuTx) binding sites from inhibition by a myasthenia gravis (MG) plasma. Two m.abs (C3 and D6) that bind to two distinct but overlapping regions on the AChR, were inhibited by the anti-m.i.r. m.ab M35. M.abs binding to three other regions protected the a-BuTx sites by up to 50%. In further inhibition assays these m.abs were used to define the binding sites for MG anti-AChR antibodies. There was considerable heterogeneity in the antigenic specificity of the MG sera. The inhibition of MG anti-AChR by anti-m.i.r. M35 correlated highly with inhibition by mouse m.ab D6, but not with inhibition by m.ab C3. There was a correlation between inhibition by m.abs F8 and B3, although these m.abs bind to two non-overlapping regions. Some MG anti-AChR antibodies bound to epitopes that only partially overlapped those defined by m.abs. Inhibition of human antibody binding by m.abs raised against specific antigens is a useful approach that should help define the epitopes to which autoantibodies bind.

Antibodies, Monoclonal↗
PubMed1988

Differences in fine specificity of anti-acetylcholine receptor antibodies between subgroups of spontaneous myasthenia gravis of recent onset, and of penicillamine induced myasthenia.

The antigenic specificity of anti-acetylcholine receptor antibodies (anti-AChR) from 70 recent onset myasthenia gravis (MG) and nine penicillamine MG patients was determined by inhibition experiments using monoclonal antibodies (m.abs) raised against human AChR. Differences were found between individuals and between the three clinical subgroups of idiopathic MG distinguished by age of onset, thymic pathology and HLA associations. Penicillamine-induced MG anti-AChR differed from that in age-matched MG controls but was similar to that in young-onset cases. The variable and heterogeneous antigenic specificity in MG suggests that AChR itself rather than a cross-reacting epitope is the primary antigen. Differences in specificity between MG subgroups may reflect a diversity of triggering factors or of immunoglobulin genes.

Adolescent↗
PubMed1988

Monoclonal anti-acetylcholine receptor antibodies as probes for human acetylcholine-receptor in myasthenia gravis.

Monoclonal antibodies have been shown to bind to five regions on human acetylcholine receptor, each probably consisting of a discrete epitope on the extracellular surface. Two of these regions are equivalent to the 'main immunogenic region', and the other three appear to be close to the a-Bungarotoxin binding sites. These antibodies have been used to probe differences in myasthenia gravis anti-acetylcholine receptor antibodies, to locate acetylcholine receptor in thymic tissue, and to look for naturally-occurring anti-idiotype antibodies. Anti-acetylcholine receptor antibody specificities differ between groups of patients defined by their age of onset, thymic pathology and HLA associations. Anti-AChR synthesised by the thymus in young onset patients has similar specificity to that found in the individual's serum, and may be stimulated by the presence of AChR on thymic myoid cells. However, myoid cells (defined by staining with anti-troponin and anti-myosin antibodies) do not appear to differ between control and myasthenia gravis patients and show no obvious involvement in an immunological reaction. There was no convincing evidence for the presence of anti-idiotype antibodies in myasthenia gravis patients.

Adult↗
PubMed1988

Genetic mapping of the Xq27-q28 region: new RFLP markers useful for diagnostic applications in fragile-X and hemophilia-B families.

We have characterized and genetically mapped new polymorphic DNA markers in the q27-q28 region of the X chromosome. New informative RFLPs have been found for DXS105, DXS115, and DXS152. In particular, heterozygosity at the DXS105 locus has been increased from 25% to 52%. We have shown that DXS105 and DXS152 are contained within a 40-kb region. A multipoint linkage analysis was performed in fragile-X families and in large normal families from the Centre d'Etudes du Polymorphisme Humain (CEPH). This has allowed us to establish the order centromere-DXS144-DXS51-DXS102-F9-DXS105-FRAX A-(F8, DXS15, DXS52, DXS115). DXS102 is close to the hemophilia-B locus (z[theta] = 13.6 at theta = .02) and might thus be used as an alternative probe for diagnosis in Hemophila-B families not informative for intragenic RFLPs. DXS105 is 8% recombination closer to the fragile-X locus than F9 (z[theta] = 14.6 at theta = .08 for the F9-DXS105 linkage) and should thus be a better marker for analysis of fragile-X families. However, the DXS105 locus appears to be still loosely linked to the fragile-X locus in some families. The multipoint estimation for recombination between DXS105 and FRAXA is .16 in our set of data. Our data indicate that the region responsible for the heterogeneity in recombination between F9 and the fragile-X locus is within the DXS105-FRAXA interval.

Chromosome Mapping↗