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Biomedical subjects

A Vincent

Publications and source records attributed to A Vincent.

At least 379 records · Page 21Linked to original sources

Myasthenia gravis without acetylcholine-receptor antibody: a distinct disease entity.

Immunoglobulin preparations from eight patients with clinical features of myasthenia gravis, in whom no serum antibody against acetylcholine receptor (AChR) could be detected, were injected intraperitoneally into mice. Neuromuscular transmission was significantly impaired compared with mice receiving control human immunoglobulin. No antibody bound to the mouse AChR was detected, but there was a small loss (9.4%) of AChR in the mouse diaphragms. Mice injected with myasthenic AChR-antibody-positive immunoglobulin and mice growing hybridoma cells secreting monoclonal AChR antibody showed similar impairment of neuromuscular transmission, but 75% and 94%, respectively, of their muscle AChR had antibody bound and AChR losses were 47% and 60%. The results suggest that a pathogenetic immunoglobulin antibody interferes with neuromuscular transmission in these AChR-antibody-negative patients by binding to non-AChR determinants at the neuromuscular junction. This form of myasthenia is immunologically and physiologically distinct from the AChR-antibody-positive form.

Adolescent↗

Canine cortical bone autograft remodeling in two simultaneous skeletal sites.

The morphological and physical aspects of cortical bone autografts implanted in dogs for 1-9 months in two differently located skeletal defects are reported with a twofold aim: to provide a reference system for further comparison with various allografts and to delineate a general pattern of cortical bone graft healing. A 3-cm osteoperiosteal gap was created in the diaphyseal segment of the ulna and fibula of mature dogs. The grafts, freed from periosteum and bone marrow, were then inverted and replaced for the autografts in the left limb bone without internal fixation or external splints. On the right side, different allografts were tested. A group of three animals also had an unfilled segmental resection on the right as control. Dogs were observed for 1, 2, 3, 6, and 9 months and were able to bear weight within 3 days. Twenty-eight ulnae and 27 fibulae were available for this autograft study. Fluorochromes were injected at mid-term and at the end of the observation. All the grafts were assessed morphologically by cross-section microradiographs and ultraviolet light microscopy, and a morphometric analysis for porosity and fluorescence was done. To evaluate the physical aspects of graft healing, the recovered ulnar autografts, when available, were submitted to photon absorptiometry and to torsional loading. Morphologically, resorption was found to invade the cortical bone graft transversely through radial tunnels, and in addition to the host-bone-graft junction, the entire transplant surface provided another way for revascularization. The highest porosity level was achieved 2 months after surgery for both ulna and fibula, while new bone formation, as assessed by fluorochromes, was most important at 3 months. At 9 months, porosity remained above the normal range as determined in a set of five nongrafted dogs. While the lack of correlation for porosity between the two grafts suggests that local factors are more important in graft resorption, the observed correlation for fluorescence indicates that new bone deposition is more dependent upon skeletal metabolic activity. Within each graft, porosity and new bone formation were not well correlated. In the ulna, the bone mineral content (BMC) reflected the graft volumetric variations during the remodeling, with the lowest mean value at 3 months. For each graft, BMC was well correlated with the torsional stiffness. When torsionally loaded, the maximal tangential shear stress at failure of the graft was negatively related to its cortical porosity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The spatial distribution of a blastoderm stage-specific mRNA from the serendipity locus of Drosophila melanogaster.

The spatial distribution of a blastoderm stage-specific mRNA was examined by hybridization in situ to tissue sections of early embryos of Drosophila melanogaster. The mRNA examined, the C mRNA, is coded for by the molecularly-complex locus, serendipity (sry). The C mRNA was found to be expressed in embryos in all nuclei and cells except pole cells, during the syncytial and cellular blastoderm stages and its transcription correlates well with the formation of the cellular blastoderm.

Blastoderm↗

Blastoderm-specific and read-through transcription of the sry alpha gene transformed into the Drosophila genome.

The serendipity (sry) locus contains three tightly clustered genes: beta, alpha, and delta. The alpha gene lies between beta and delta and is expressed predominantly at the blastoderm stage of embryogenesis. Additional features of this locus include read-through transcription and the fact that the predicted beta and delta polypeptides show remarkable homology to the Xenopus RNA polymerase III transcription factor TFIIIA. To identify cis-acting elements controlling the expression of the alpha and beta transcripts, we created transformed lines containing modified versions of these genes. In lines containing derivatives of both the alpha and beta genes, the expected modified mRNAs are transcribed. An alpha gene variant containing only 798 bp of upstream DNA is also transcribed, and at the proper time; thus blastoderm-specific alpha gene transcription is independent of expression of the adjacent upstream beta gene. Analysis of transformed lines confirmed the beta-alpha read-through transcription, which was eliminated by the insertion of a different polyadenylation site within the coding region of the beta gene. We conclude that the transcription of the beta and alpha genes is independently regulated.

Animals↗

Monoclonal antibodies that distinguish between normal and denervated human acetylcholine receptor.

Ten monoclonal anti-human acetylcholine receptor (AChR) monoclonal antibodies (m.abs) all exhibited high avidity binding to the human AChR. None was able to inhibit alpha-bungarotoxin (alpha-Butx) binding to the receptor. Five distinct but partially overlapping antibody-binding regions were defined by competition experiments. Four antibodies, which competed with each other for one region on denervated human AChR and also bound to human fetal AChR, failed to bind appreciably to normal human AChR in solution, to normal AChR solubilized from 6 other species, or to human endplates in frozen sections.

Animals↗

Myasthenia gravis: monoclonal antihuman acetylcholine receptor antibodies used to analyze antibody specificities and responses to treatment.

We investigated the heterogeneity of serum antibodies to acetylcholine receptor (AChR) by competition with nine antihuman monoclonal antibodies in a cross-sectional study of 36 patients with myasthenia gravis (MG), and in three who showed clinical improvement associated with decrease in total anti-AChR following immunologic treatment. Two specificities were more prevalent in patients without thymoma, an done of these was more prevalent in cases beginning before age 40. Some specificities were stable during serial studies, whereas other fluctuated. We found evidence of three groups of antibody specificities that had different control mechanisms and may define different regions of the receptor.

Adult↗

Anti-acetylcholine receptor antibodies induced in mice by syngeneic receptor without adjuvants.

Acetylcholine receptor (AChR)-bearing membranes from the BC3H-1 cell lines were injected, without adjuvant, either intrathymically (i.t.) followed by intraperitoneal (i.p.) booster doses, or i.p. alone, into (C57BL X BALB/c)F1 mice. Over 75% of the animals developed serum anti-AChRs which reacted with the cell-line AChR and with normal mouse endplate AChR. The titres were within the lower range of those of myasthenia gravis patients, and some mice showed reduced miniature endplate potential (m.e.p.p) amplitudes. these results indicate that loss of tolerance to acetylcholine receptors can result from immunization against syngeneic AChR without adjuvant. This approach may provide a useful model for studying mechanisms of autoimmunity against acetylcholine receptor.

Action Potentials↗

[Subacute osteomyelitis in young children. Study of 17 cases].

Subacute osteomyelitis is characterised by absence of symptoms of generalised infection and a favourable prognosis. In the last 15 years, the authors have observed 17 such cases in children, aged between 3 months and 4 years. Three were situated in the epiphysis and 14 in the metaphyseal region. On three occasions, a tarsal bone was involved and in five cases the lesion was in the spine. The radiological signs were very characteristic and biological changes were minimal. Exploration of the site of the infection was done on ten occasions, but only on two were organisms found. Treatment was based on antibiotics active against staphylococci and drugs inhibiting prostaglandins. Only one case was treated surgically. Healing occurred eventually in all cases.

Anti-Bacterial Agents↗

Sequence and structure of the serendipity locus of Drosophila melanogaster. A densely transcribed region including a blastoderm-specific gene.

The transcriptional organization of the Drosophila melanogaster serendipity (sry) locus (previously designated EH8) has been investigated by DNA sequencing, S1 nuclease mapping, and primer extension analysis. The data indicate that the five different (and partially overlapping) sry messenger RNAs detectable in early embryos are initiated at three separate sites, each directly upstream from one of the three protein-coding regions, designated (in 5' to 3' order) beta, alpha and delta. All of the sry mRNAs are transcribed in the same direction. The two blastoderm stage-specific sry mRNAs both include the alpha-coding region and have the same 5' terminus, only 183 nucleotides downstream from the 3' terminus of a beta region transcript (which is transcribed in ovaries). Similarly, only 331 nucleotides separate the 5' end of a delta region transcript from the major 3' end of the alpha region transcripts. One of the five sry embryonic mRNAs includes both the beta and alpha protein-coding segments and the spacer region in between, while another mRNA includes both the alpha and delta protein-coding regions as well as the spacer in between. The two read-through transcripts probably result from the failure to undergo a 3' cleavage and polyadenylation event rather than from differential splicing. As the three other sry embryo mRNAs are each transcribed from a single protein-coding region, it would appear that the alpha, beta and delta open reading frames correspond to three separate genes. Codon bias analysis reinforces the notion that these three genes code for bona fide proteins with translation starting at the first in-frame AUG codon. The predicted beta and delta polypeptides show partial amino acid sequence homology, suggesting a common evolutionary origin.

Amino Acid Sequence↗

Monoclonal antibodies to Torpedo acetylcholine receptor. Characterisation of antigenic determinants within the cholinergic binding site.

Thirteen monoclonal antibodies (mAb) to the acetylcholine receptor (AChR) from Torpedo marmorata showed high avidity for the receptor but none exhibited binding to muscle AChR solubilised from seven other animal species. Five mAb and Fab monomer fragments prepared from two of them, inhibited alpha-bungarotoxin (alpha BuTx) binding to receptor by a maximum of 50%. In the presence of excess mAb the 125I-alpha BuTx bound could be precipitated by anti-IgG indicating that the mAb bound to only one of the two alpha BuTx binding sites on each AChR monomer. This site appeared to have a lower affinity for d-tubocurarine and decamethonium than the non-mAb site. Binding of five anti-site mAb was mutually competitive and four of them (AS2-AS5) were inhibited by other cholinergic ligands and influenced by four non-toxin binding site antibodies. One (AS1) bound within the toxin binding site yet outside the main neurotransmitter binding region. It is concluded that these five mAb distinguish between the two alpha BuTx binding sites on the Torpedo AChR, and bind only to the site which displays lower affinity for d-tubocurarine and other competitive ligands.

Animals↗

Acetylcholine receptor antibodies in the elderly and in Down's syndrome.

Serum antibodies to the acetylcholine receptor (anti-AChR) have been reported in Japanese individuals who were elderly or had Down's syndrome at frequencies of 18% and 24%, respectively. We have measured serum anti-AChR in 3 Caucasoid groups: 53 elderly patients (aged 65-92 years) with miscellaneous (non-myasthenic) disorders, 30 individuals with Down's syndrome, and 40 elderly patients (aged 71-93 years) known to have strongly positive thyroid autoantibodies. A raised titre (greater than 0.2 nmol/l) was confined to 3 patients in the third group (7.5%). We conclude that an increased frequency of anti-AChR antibodies is not a feature of Caucasians who are elderly or have Down's syndrome, and that, even in an elderly group with a high titre of another autoantibody, the frequency of anti-AChR is lower than in elderly Japanese individuals.

Aged↗

Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays.

Anti-acetylcholine receptor (AChR) antibody was undetectable in 26/153 (17%) sera from myasthenia gravis patients assayed by standard RIA using human acetylcholine receptor. Eight of these were found to be positive with a modified protocol using a mixture of normal and denervated AChR, reducing the proportion of "negative" sera to 12%. Many of these were from patients with a short history; two such patients later developed low positive values. Anti-AChR without clinical evidence of myasthenia was found in one of three monozygotic twins of myasthenia gravis patients, and in one of thirty other first degree relatives of a further 17 patients. Anti-AChR is a valuable and highly specific diagnostic test which, with the assay used here, is positive in about 88% of patients with clinical features of myasthenia gravis.

Antibody Specificity↗

Acetylcholine receptor antibody characteristics in myasthenia gravis. III. Patients with low anti-AChR antibody levels.

Twenty-five myasthenia gravis (MG) patients whose anti-acetylcholine receptor (anti-AChR) titres against denervated human leg AChR fell in the range of less than 0.1-2.0 nM were tested against AChR preparations from normal human leg muscle, and from human extra-ocular muscle, and the results compared with those of sera with titres greater than 2.0 nM. Seven sera failed to react appreciably with any of the AChR. Many of the remaining 18 low titre sera reacted better with normal leg and ocular AChR than with denervated AChR. In contrast, sera from patients with high anti-AChR titres generally reacted better with denervated, AChR, and as a group this was significantly different from the low titre patients. Sera reacting better with ocular AChR are not restricted to patients with purely ocular symptoms. The results indicate a subgroup of myasthenia gravis patients who have low titres, tend to be male and have relatively mild disease. The aetiology of the autoimmune disorder in this subgroup may differ from that in other MG patients.

Adolescent↗

Anti-acetylcholine receptor idiotypes in myasthenia gravis analysed by rabbit anti-sera.

Anti-idiotype sera, raised in rabbits against anti-acetylcholine receptor (AChR) (idiotype) purified from the serum of three myasthenia gravis patients, inhibited binding of homologous idiotype to the AChR by up to 80%. The expression of idiotype in the three individuals changed very little over a period of several years, during which they showed a declining trend in overall anti-AChR antibody. Only one of the four anti-idiotype sera inhibited the binding of anti-AChR from a number of other patients. Our results indicate a consistency of idiotype expression within an individual, and fail to show substantial idiotype sharing between individuals.

Animals↗