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Biomedical subjects

A Vincent

Publications and source records attributed to A Vincent.

At least 271 records · Page 15Linked to original sources
PubMed1993

Congenital myasthenic syndromes.

The Congenital Myasthenic Syndromes (CMS) constitute a group of rare genetic disorders affecting neuromuscular transmission. They differ from myasthenia gravis and the Lambert-Eaton myasthenic syndrome, which are autoimmune antibody-mediated conditions. CMS can present at any time from birth to adulthood, though usually within the first 2 yr of life, and result in a spectrum of diseases ranging from mild weakness to severe disability with life-threatening episodes. Several of these syndromes have been well documented, and in recent years fully investigated using a variety of electrophysiological, histochemical, and morphological techniques. In this review we describe the main results of these investigations, and attempt to classify the disorders into groups that can be recognized by the clinician. They include defects in acetylcholine release, absence of the endplate-specific form of acetylcholinesterase, and alterations in the number or function of postsynaptic acetylcholine receptors. Clinical features are described in detail, and treatment reviewed. These disorders involve a potentially large number of candidate genes. Further elucidation of the underlying abnormalities will not only lead to improved treatment, but should contribute to our understanding of the molecular biology of the neuromuscular junction.

Acetylcholinesterase↗
PubMed1993

Effects of acute and chronic administration of acebutolol on the right ventricular effective refractory period in conscious dogs.

beta-Adrenergic blocking drugs are effective in reducing sudden cardiac death after acute myocardial infarction but the precise mechanism of this effect is unclear. We investigated the acute and chronic effects of acebutolol, a beta-adrenergic blocker, on electrocardiographic parameters, diastolic excitability threshold (DET), and right ventricular effective refractory period (RVERP) in chronically instrumented conscious dogs. These parameters were determined during spontaneous sinus rhythm and at a fixed pacing rate (200 beats/min). Acebutolol (0.5, 1, and 5 mg/kg i.v.) decreased the heart rate (HR) (by 23, 26, and 24%, respectively) without effects on any electrocardiographic parameters or on the DET. The maximal increases in ERP were 4.7, 7, and 7.8%, respectively, during pacing and 8.5, 13.3, and 10.3%, respectively, during sinus rhythm. Acebutolol, 10 mg/kg/day P.O. for 6 weeks, reduced the HR from the third day onward without altering the PR, QRS, QT, or QTc intervals or the DET. The increase in ERP was significant from the third day (14%) during pacing and from the seventh day (15.5%) during sinus rhythm. The degree of prolongation of the ERP subsequently remained stable during the 6 weeks of treatment. The ERP returned to the baseline value 7 days after acebutolol withdrawal. This increase in ERP, which was more marked during chronic oral treatment, could contribute to the documented protective effect of the beta-blocking drugs against sudden cardiac death after myocardial infarction.

Acebutolol↗
PubMed1993

Relationship between expression of serendipity alpha and cellularisation of the Drosophila embryo as revealed by interspecific transformation.

A dramatic reorganization of the cytoskeleton underlies the cellularisation of the syncytial Drosophila embryo. Formation of a regular network of acto-myosin filaments, providing a structural framework, and possibly a contractile force as well, appears essential for the synchronous invagination of the plasma membrane between adjacent nuclei. The serendipity alpha (sry alpha) gene is required for this complete reorganization of the microfilaments at the onset of membrane invagination. We compare here the structure and expression of sry alpha between D. pseudoobscura, D. subobscura and D. melanogaster. Interspersion of evolutionarily highly conserved and divergent regions is observed in the protein. One such highly conserved region shows sequence similarities to a motif found in proteins of the ezrin-radixin-moesin (ERM) family. Four 7-13 bp motifs are conserved in the 5' promoter region; two of these are also found, and at the same position relative to the TATA box, in nullo, another zygotic gene recently shown to be involved in cellularisation. The compared patterns of expression of D. melanogaster sry alpha and nullo, and D. pseudoobscura sry alpha reveal a complex regulation of the spatiotemporal accumulation of their transcripts. The D. pseudoobscura sry alpha gene is able to rescue the cellularisation defects associated with a complete loss of sry alpha function in D. melanogaster embryos, even though species-specific aspects of its expression are maintained. Despite their functional homologies, the D. melanogaster and D. pseudoobscura sry alpha RNAs have different subcellular localisations, suggesting that this specific localization has no conserved role in targeting the sry alpha protein to the apical membranes.

Amino Acid Sequence↗
PubMed1993

Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV1 RNA.

Two DNA strand transfer reactions take place during reverse transcription of the retroviral genome. The first transfer, that of the minus-strand strong stop DNA from the 5' end of the viral RNA to the 3' end, has been studied in vitro with two RNAs mimicking the 5' and 3' regions of the HIV1 genome and with nucleocapsid protein, NCp7, and reverse transcriptase. The results show that NCp7 strongly activates the 5' to 3' DNA strand transfer during reverse transcription while a basic peptide resembling NCp7 is inactive. Activation of the first transfer by several NCp7 derived peptides and the influence of the terminal redundancies (R) present at the 5' and 3' ends of HIV1 RNA were also examined. The first transfer is optimal in the presence of intact NCp7 and necessitates R on both the 5' and 3' RNAs. Sequencing of full length viral DNA products reveals approximately 40% misincorporations at the first nucleotide beyond the transfer point. If such base misincorporations occur during proviral DNA synthesis with possible homologous recombinations it may well contribute to the high level of genetic variability of HIV.

Capsid↗
PubMed1993

Early onset of lithium-associated hypothyroidism.

In general practice, psychiatrists are confronted with the difficulty of structuring a rational design for the early detection of hypothyroidism. To determine the period during which a patient receiving lithium is most at risk of developing hypothyroidism, a retrospective study was conducted on the records of 154 patients at two general hospital lithium clinics from January 1980 to August 1991. Forty-two cases of hypothyroidism (clinical hypothyroidism and/or abnormally elevated levels of TSH) were detected. A significant difference was found between the onset of hypothyroidism and age (older patients developed more thyroid dysfunction), but no significant differences were found between thyroid abnormality and sex or diagnostic category and menopausal status, although trends were observed for the two former variables. This longitudinal study is the first to describe an outline of thyroid functioning in terms of the duration of treatment. Lithium-associated hypothyroidism develops most often during the first two years. Of the 42 cases of hypothyroidism, 16 were diagnosed within six months (38%), 23 within the first year (55%), and 31 two years (74%). Since thyroid functioning is an important parameter in the course of affective disorders, its close and frequent monitoring is mandatory during the first two years of treatment.

Adult↗
PubMed1992

Stimulation of human T cells by sparse antigens captured on immunomagnetic particles.

The acetylcholine receptor (AChR) of muscle is the target of the pathogenic antibodies in the human autoimmune disease myasthenia gravis (MG). For studies on the autoreactive T cells presumed to be responsible, use of intact human autoantigen would be optimal, but it was thought to be prohibitively scarce. However, adsorption to the surface of immunomagnetic particles (Dynabeads) of intact AChR from whole muscle extracts or from affinity-purified preparations, using mouse anti-human AChR Mabs, largely overcomes this problem. Together with antigen presenting cells (APC), this bead-bound AChR has consistently and maximally stimulated an established MG T cell line (previously selected with recombinant human AChR alpha subunit) that recognises the 144-156 region of the human alpha sequence (Ong et al., 1991). For equivalent T cell stimulation, bead-bound AChR was at least 10(3) times more potent than soluble AChR or recombinant alpha subunit, and 10(6) times more potent than peptide 144-156, implying that antigen in this form is targetted very efficiently to APC and thus to T cells. Finally, we have obtained similar results with T cells specific for other antigens suggesting that this method may have wider applications.

Amino Acid Sequence↗
PubMed1992

The Drosophila melanogaster ribosomal protein L17A-encoding gene.

The structure and sequence of the gene encoding the Drosophila melanogaster homolog of the human and yeast large-subunit ribosomal protein L17A (rpL17A) is presented. The deduced amino acid (aa) sequence of 140 residues exhibits 87% and 77% identity to that of the human (140 aa) and yeast (137 aa) rpL17As, respectively. The D. melanogaster rpL17A gene is single copy and maps at 58F6-59A3, a chromosome region encompassing a previously characterized Minute locus, M(2)I. Despite this extensive homology in their protein products, the D. melanogaster and yeast rpL17A genes display different exon-intron structures, with the first D. melanogaster intron mapping within the 5'-untranslated mRNA leader. The rpL17A gene gives rise to a single 600-nucleotide transcript present throughout development, and is located close to another similarly expressed gene. The 5' end of the D. melanogaster rpL17A mRNA contains a polypyrimidine tract displayed by several mammalian rp genes and involved in translational control of their expression.

Amino Acid Sequence↗
PubMed1992

Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers.

The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C-terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents.

Amino Acid Sequence↗
PubMed1992

Role of acetylcholine receptor antibody complexes in muscle in experimental autoimmune myasthenia gravis.

In experimental autoimmune myasthenia gravis anti-rat nicotinic acetylcholine receptor (AChR) antibody titers correlated significantly with the AChR-antibody complexes found in muscle. It was shown that at least a large part of the AChR-antibody complexes are formed in vitro, which can be prevented by washing of the muscle homogenate. Using a modified assay, no differences in AChR-antibody complexes could be detected between rats with and without symptoms of experimental autoimmune myasthenia gravis. Also no difference in AChR loss nor in inhibition of alpha-bungarotoxin binding to AChR was found between these groups of rats. However, a significant difference in the reduction of AChR function was found, using an assay measuring agonist-induced 22Na+ flux into the TE671 cell line.

Animals↗
PubMed1992

Electrodermal differentiation of deception: potentially confounding and influencing factors.

The demonstration of deception as a psychological process requires a comparison of physiological responding to questions answered honestly or deceptively, under conditions which differ only with respect to deception. Such electrodermal (skin conductance response (SCR) differentiation was recently reported in the Differentiation-of-Deception Paradigm. The present study had two empirical goals: (a) to assess the possible confounding role of retrieval-difficulty and novelty in producing the differentiation effect; (b) to ascertain any influencing effects of a memorial ('cumulative' mental load) and two motivational (Monetary-Incentive and Ego-Involvement) factors on the electrodermal differentiation phenomenon and on overall responding. In addition to the basic Deceptive vs. Honest manipulation of the Differentiation-of-Deception Paradigm, the present study varied, within 60 subjects, Question Type (easily retrieved Autobiographical vs. more difficult-to-retrieve Biographical). The two two-level motivational factors were varied between subjects. Finally, to assess the confounding issue, voice latency (VL), known to be sensitive to retrieval-difficulty, was measured in addition to SCR. SCRs to deceptive answers exceeded those to the honestly-answered questions, demonstrating the differentiation phenomenon. Results showed that although VL and SCR was significantly greater to Biographical than to Autobiographical questions, the differentiation effect emerged only in the SCR and not in VL, which suggests that memorial difficulty does not confound the electrodermal differentiation effect.

Adolescent↗
PubMed1992

Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality.

The Drosophila serendipity (sry) delta (delta) zinc finger protein is a sequence-specific DNA binding protein, maternally inherited by the embryo and present in nuclei of transcriptionally active cells throughout fly development. We report here the isolation and characterization of four ethyl methanesulfate-induced zygotic lethal mutations of different strengths in the sry delta gene. For the stronger allele, all of the lethality occurs during late embryogenesis or the first larval instar. In the cases of the three weaker alleles, most of the lethality occurs during pupation; moreover, those adult escapers that emerge are sterile males lacking partially or completely in spermatozoa bundles. Genetic analysis of sry delta thus indicates that it is an essential gene, whose continued expression throughout the life cycle, notably during embryogenesis and pupal stage, is required for viability. Phenotypic analysis of sry delta hemizygote escaper males further suggests that sry delta may be involved in regulation of two different sets of genes: genes required for viability and genes involved in gonadal development. All four sry delta alleles are fully rescued by a wild-type copy of sry delta, but not by an additional copy of the sry beta gene, reinforcing the view that, although structurally related, these two genes exert distinct functions. Molecular characterization of the four sry delta mutations revealed that these mutations correspond to single amino acid replacements in the sry delta protein. Three of these replacements map to the same (third out of seven) zinc finger in the carboxy-terminal DNA binding domain; interestingly, none affects the zinc finger consensus residues. The fourth mutation is located in the NH2-proximal part of the protein, in a domain proposed to be involved in specific protein-protein interactions.

Alleles↗
PubMed1992

The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein.

The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region.

Alleles↗
PubMed1992

Zinc fingers and other domains cooperate in binding of Drosophila sry beta and delta proteins at specific chromosomal sites.

The closely related Drosophila serendipity (sry) beta and delta zinc finger proteins display consensus in vitro DNA recognition sequences differing by 4 of 13 nucleotide positions and bind in vivo to distinct sets of sites on polytene chromosomes. We compared the pattern of in vivo chromosomal binding of deleted forms of the sry delta protein fused to beta-galactosidase and expressed in Drosophila transgenic lines. Results show that the carboxy-terminal DNA-binding finger domain is required and sufficient for binding at specific chromosomal sites but that this binding does not nearly reproduce the wild-type pattern. An NH2-terminal domain of the sry delta protein is essential to its specificity of in vivo interaction with chromatin. In vitro and in vivo experiments using reciprocal finger swap between the sry beta and delta proteins suggest that the in vivo specificity is dependent on selective protein-protein contacts at defined chromosomal sites, in addition to DNA specific recognition.

Animals↗
PubMed1992

Search for cross-reactive idiotypes on monoclonal and myasthenia gravis acetylcholine receptor antibodies.

Myasthenia gravis patients have serum anti-acetylcholine receptor antibodies that compete with monoclonal antibodies for binding to epitopes on the human acetylcholine receptor. To investigate the presence of shared idiotypes we immunised syngeneic mice with each of ten well-characterised monoclonal antibodies, previously raised against purified human acetylcholine receptor, and tested the polyclonal antisera and seven monoclonal anti-idiotype antibodies, for binding to the antigen-combining site, to framework idiotopes, and by ELISA. The polyclonal sera were mostly directed against antigen-combining site idiotopes and cross-reacted only with monoclonal anti-acetylcholine receptor antibodies that bound to the same region on the acetylcholine receptor. In contrast, five of the seven IgM monoclonal anti-idiotypic antibodies raised, none of which demonstrated antigen-combining site specificity in solution, cross-reacted with mAbs binding to more than one region. None of the antisera showing reactivity with the antigen-combining site inhibited the binding of MG anti-acetylcholine receptor antibody.

Animals↗
PubMed1992

[Aseptic necrosis of the femoral head following renal transplantation: assessment of a 25-year experience].

From June 1963 to December 1988 aseptic necrosis of the femoral head has been treated surgically in 84 renal transplant recipients (150 surgical procedures). The long-term results of drilling of the neck and head of the femur (16), cup arthroplasty (32), cemented cup (1) and hemiarthroplasty (8) were unsatisfactory, as 23 of these 57 hips underwent a secondary procedure. Total hip arthroplasty progressively became the standard procedure for treatment of hip disease in transplanted patients. Since 1971, 63 renal transplant recipients underwent 92 cemented total hip replacement (THR) as a primary (73), secondary (16) or third (3) surgical procedure for severely symptomatic femoral head necrosis. Hospital stay averaged 22 days, and follow-up averaged 53 months. Two deaths related to the surgical procedure occurred in the first 4 years of our experience (one major local sepsis, one pulmonary infection). Other postoperative complications were urinary tract infection (12), pulmonary infection 1, transient sciatic nerve irritation (3), wound hematoma (6), reversible deterioration of renal function (3) and rejection of the graft (2). Thromboembolic complications did not occur. All operated hips showed a marked symptomatic improvement. Loosening of one or both components was definite in one, probable in two and possible in three of the 33 hips followed up more than 5 years. Other late complications included dislocation (6), painful class III heterotopic ossification (4), recurrence of previous sepsis (1) and late hematogenous sepsis. Late hip revision was required in 5 cases (recurrent dislocation, 1, ossification, 2, sepsis, 2). Two renal complications (one graft infarction and one reversible acute tubular necrosis) occurred after these revisions. The functional results of THR compare favourably with the results of other surgical procedures used in our early experience. We conclude that THR has become the treatment of choice for symptomatic established osteonecrosis of the femoral head in renal transplant patients. A relatively high rate of early and late complications is nevertheless to be expected.

Adolescent↗
PubMed1992

[Antenatal surveillance and risks of prematurity and fetal growth retardation].

The essential aim of this work was to investigate the relationship between antenatal care and preterm delivery or low birth weight. This study has been done by means of a case-control survey carried out among 435 women who delivered in 4 Maternity Hospitals in Aix-en-Provence-Pertuis area, between November 20th, 1987 and September 30th, 1988. Cases consisted of 124 women having delivered single livebirths before 37 weeks' gestation and 69 women having delivered, at term, single livebirths weighting less than 2,500 g. Controls were 242 women who delivered normal single livebirths. Results showed that, within the geographic area of the study, low birth weight and preterm delivery rates were respectively 6% and 5.4%. Antenatal care was generally according to medical profession recommendations: average number of visits: 7.9; first visit achieved, for 98.8% of women, within first trimester; intervention of a specialist in 97.1% of pregnancies; average number of ultrasound examinations: 3.5. Only mothers of low birthweight infants had more often an inadequate antenatal care (OR = 2.63, 95% confidence interval: 1.22-5.70). The risk factors for low birth weight were: previous history of preterm and/or low birth weight delivery, single marital status, low lever father's education, smoking during pregnancy, no contact with maternity team and for preterm delivery: previous history of preterm and/or low birth weight delivery, complications during the penultimate pregnancy, hypertension, metrorragies. These results suggest that it seems unlikely, in the future, to decrease unfavorable pregnancy outcomes by increasing antenatal care.

Case-Control Studies↗