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Biomedical subjects

A Vincent

Publications and source records attributed to A Vincent.

At least 325 records · Page 18Linked to original sources
PubMed1989

cis-regulatory elements of the Drosophila blastoderm-specific serendipity alpha gene: ectopic activation in the embryonic PNS promoted by the deletion of an upstream region.

The Drosophila serendipity alpha gene (sry alpha) is specifically expressed at the blastoderm stage in all somatic cells. By deletion analysis of sry alpha-lacZ fusion genes, the sry alpha cis-acting regulatory elements have been restricted to the [-311, +130] 5'-region of the gene and separated in two domains. The [-118, +130] domain is sufficient for transcriptional activation at the blastoderm stage. The [-311, -118] domain is required for a full level of expression. Deletion of this upstream domain leads to a secondary pattern of lacZ expression in precursor cells of the peripheral nervous system (PNS). The sry alpha gene is not itself secondarily expressed in the PNS, as shown by in situ hybridization. The patterns of expression of the different sry alpha-lacZ fusion genes suggest a combinatorial mode of regulation of sry alpha expression at blastoderm.

Animals↗
PubMed1989

Serendipity delta, a Drosophila zinc finger protein present in embryonic nuclei at the onset of zygotic gene transcription.

Serendipity delta (sry delta) is a member of a set of Drosophila zinc finger protein genes showing maximal transcription during oogenesis. By using transformant lines, we monitored the zygotic expression of the sry delta gene and characterized some biochemical properties of a sry delta/beta-galactosidase fusion protein-containing fingers. Further analysis made use of anti-sry delta specific antibodies. During oogenesis, while sry delta mRNAs transcribed by nurse cells are transferred to the oocyte starting in stage 10, translation into protein occurs in the ooplasm starting in stage 12. The maternally inherited protein concentrates in embryonic nuclei during early cleavages, prior to the onset of zygotic transcription. At the blastoderm stage, the sry delta protein is localized in all somatic nuclei. Later in embryogenesis and up to the adult stage, the zygotic protein is present in nuclei of transcriptionally active cells (both somatic and germ line). These data are consistent with the sry delta protein being a transcription factor, with a role in zygotic activation of general cellular functions.

Animals↗
PubMed1989

Autoimmunity to the voltage-gated calcium channel underlies the Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder.

The Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular transmission, often associated with small cell lung carcinoma (SCLC), and characterized by reduced quantal release of acetylcholine from the motor nerve terminals. Another neuromuscular transmission disorder, myasthenia gravis, has a well-understood autoimmunological cause. This review discusses the evidence for a similar autoimmunological effect in the development of LEMS. Injection of LEMS IgG into mice passively transfers the physiological and morphological abnormalities, which include paucity and disorganized arrangement of active zone particles believed to represent the voltage-gated calcium channels (VGCCs). Calcium influx via VGCCs into SCLC cells is reduced by LEMS IgG suggesting that in SCLC-associated LEMS, antibodies may be triggered by VGCCs expressed on these cells; this immunological cross-reactivity may lead to the neurological abnormality. Similar VGCCs on neuronally derived cells may trigger the disorder in those without a tumour. The disorder provides another example of the complicated relationships between the nervous and immune systems and tumorigenic processes.

Autoimmune Diseases↗
PubMed1989

The polymorphic marker DXS304 is within 5 centimorgans of the fragile X locus.

The fragile X syndrome, which is the most common cause of inherited mental retardation, poses important diagnostic problems for genetic counseling. The development of diagnostic strategies based on DNA analysis has been impaired by the lack of polymorphic markers very close to the disease locus. Here we report that the polymorphic probe U6.2 (locus DXS304) is much closer to the fragile X locus than all the previously reported markers. A recombination fraction of 0.02 between DXS304 and the fragile X locus was estimated by multipoint linkage analysis (confidence interval 0.002 to 0.05). Our data suggest that DXS304 is distal to the fragile X locus. This marker thus represents a major improvement for carrier detection and prenatal diagnosis in fragile X families.

Chromosome Mapping↗
PubMed1989

Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region.

We are using pulsed-field gel electrophoresis (PFGE) to establish a physical map of the human Xq28 region. We have identified a new probe 35.239 (DXYS64), localized in Xq28 by somatic hybrid mapping and belonging to a region of greater than 99% homology between the X and the Y chromosomes. PFGE data show that probes 35.239 and the polymorphic locus DXS115 (probe 767) map within a common 300-kb BssHII fragment. Both probes, in addition, hybridize to 575-kb BssHII and 590-kb ClaI fragments that contain the gene coding for coagulation factor VIII (F8C). The order F8C-DXS115-DXYS64 could be determined. Our results also provide evidence for linkage between the red/green color vision locus (RCP,GCP) and probes MD13 and T1.7 (GdX, DXS254) within a 750-kb ClaI fragment. Although the latter two probes are located within 50 kb of the 3' end of the G6PD gene, a G6PD cDNA probe did not hybridize to this fragment. G6PD, on the other hand, could be linked to F8C on a 290-kb BssHII fragment. All these data allow us to propose the order (RCP,GCP)-MD13-GdX-G6PD-F8C-DXS115-DXYS 64. We also linked probes St14 (DXS52), MN12 (DXS33), and DX13 (DXS15) to a member of a small family of X-linked dispersed sequences (DNF22S3) within a 575-kb BssHII fragment. The preliminary physical map presented here should be useful for further fine mapping of disease genes in the Xq28 region and should be helpful in orientating efforts toward the cloning of sequences close to the fragile X syndrome.

Animals↗
PubMed1989

Strategies for assessing learning and memory, 1978-1987: a comparison of behavioral toxicology, psychopharmacology, and neurobiology.

Tests of learning and memory are currently not typically included in first-tier screening batteries even though there is ample evidence that chemical exposure can produce deficits in these cognitive processes. The approach taken in behavioral toxicology has been to restrict these cognitive tests to second tier or hazard characterization studies, yet there is little agreement on which tests are most appropriate. The present survey was designed to determine the current testing strategies in toxicology for detecting and characterizing the effects of chemical treatment on learning and memory, and to make comparisons to similar data from the fields of psychopharmacology and neurobiology. The survey data revealed a number of discipline-dependent effects on the selection of tests. A number of these effects were clearly related to the subject matter as well as the particular chemical/treatment being examined. Given the youth of the field, behavioral toxicology has the advantage of gaining valuable information from both of these disciplines. Behavioral testing in neurotoxicology should consider strategies which maximize unification of these closely related fields of neuroscience.

Animals↗
PubMed1989

Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae.

We examined meiotic and mitotic gene conversion events involved in deletion of Ty elements and other insertions from the genome of the yeast Saccharomyces cerevisiae. We found that Ty elements and one other insertion were deleted by mitotic gene conversion less frequently than point mutations at the same loci. One non-Ty insertion similar in size to Ty, however, did not show this bias. Mitotic conversion events deleting insertions were more frequently associated with crossing over than those deleting point mutations. In meiosis, conversion events duplicating the element were more common than those that deleted the element for one of the loci (HIS4) examined.

Blotting, Southern↗
PubMed1989

Comparative in vivo and in vitro study of the cardiac effects of midalcipran and imipramine.

Midalcipran is a new antidepressant drug inhibiting both noradrenaline and serotonin uptake without any postsynaptic and anticholinergic activities. Its cardiac effects were compared with those of imipramine, a tricyclic antidepressant drug. In anaesthetised guinea-pigs intravenous perfusion of imipramine and midalcipran (1 ml/min from a solution at 0.66 mg/ml) brought about ventricular arrhythmias, respectively at 16.5 and 26.4 mg/kg and cardiac arrest at 58 and 97 mg/kg. The safety index (ratio of i.v. lethal dose and ED50 evaluated by the yohimbine test) is 22 times wider for midalcipran than imipramine. In in vitro studies on guinea-pig ventricular myocardium, imipramine exerted a greater class 1 antiarrhythmic effect than midalcipran. The reduction of Vmax was significant at 3 X 10(-6) M for imipramine and 1 X 10(-5) M for midalcipran in normal (4 mM K+) and hyperpolarizing (2.7 mM K+) conditions. At the concentration of 1 X 10(-5) M midalcipran significantly lengthened, whereas imipramine non significantly shortened the action potential durations (APD50, APD90). The results provide confirmation of a lesser depression in sodium conductance with midalcipran as compared to imipramine. Therefore it is proposed that less adverse cardiac effects may be observed at therapeutic doses.

Action Potentials↗
PubMed1989

Transcriptional and posttranscriptional regulation contributes to the sex-regulated expression of two sequence-related genes at the janus locus of Drosophila melanogaster.

We investigated the structure and developmental pattern of expression of two genes clustered at the janus locus, located at 99D.3R. Data obtained from genomic and cDNA sequencing and from a combination of S1 mapping and primer extension experiments indicated a very unusual organization of this locus, which appeared to be composed of two partially overlapping genes, designated janA and janB. These two genes were found to be transcribed in the same direction. janA encoded one minor and two major transcripts. The 5' end of the janB mRNA mapped within the 3' untranslated region of the janA transcribed sequence. The overlapping region was 118 bases long. Similarities observed between these two genes with respect to both peptidic sequence and intron position strongly suggested that this locus originated from the duplication of an ancestral transcription unit. However, each of the resulting genes has acquired its own specificity of expression linked to sex determination. The janB transcript was detected only in males, and its expression at the adult stage was restricted to germ line cells. The janA gene displayed a much more complex expression; one of the major mRNAs was found in both sexes and at all stages, whereas the two other janA transcripts were expressed only in males.

Amino Acid Sequence↗
PubMed1989

Recombination in yeast and the recombinant DNA technology.

The development of methods to isolate eukaryotic genes, alter these genes in vitro and reintroduce them into the cell has had a major impact on the study of recombination in the yeast Saccharomyces cerevisiae. In this paper we discuss how recombinant DNA techniques have been employed in the study of recombination in yeast and the results that have been obtained in these studies.

DNA, Fungal↗
PubMed1989

Spontaneous healing of aneurysmal bone cysts. A report of three cases.

We report three cases of spontaneous healing of aneurysmal bone cysts (ABC). In one case histological material was obtained after resection of the already ossified expansile mass discovered as a lytic lesion seven months previously. In the two other patients, spontaneous ossification of a radiologically presumed ABC in the lytic and expansile phase was observed after nine and seven months respectively. The healed lesions have remained stable at 12, 32, and 36 months respectively. These findings suggest that when the diagnosis can be made with confidence, and the lesion is in a location and at a stage that does not entail any risk of fracture or compression, expectant management should be considered. Our three patients were aged 22, 19 and 18 years, older than usual for developing ABC. This is also true for many of the few other reported cases of spontaneous or almost spontaneous healing and suggests that ABC has a greater tendency to stabilise in older patients.

Adolescent↗
PubMed1988

Finger proteins and DNA-specific recognition: distinct patterns of conserved amino acids suggest different evolutionary modes.

Finger proteins, the first example of which was Xenopus TFIIIA, share Zn2+ finger-like folded domains capable of binding to nucleic acids. A large number of this type of protein have been characterised from diverse organisms, indicating a wide evolutionary spread of the DNA-binding fingers. At least two classes of finger proteins may be distinguished. Class I proteins contain variable numbers of the tandemly repeating TFIIIA-like finger motif, (Y/F-X-C-X2-4-C-X3-F-X5-L-X2-H-X3-H). Class II finger proteins display a single (C-X2-C-X13-C-X2-C) motif and a facultative second putative finger. The relation between the structure of finger proteins and their recognised DNA sequences is discussed.

Amino Acid Sequence↗
PubMed1988

Two functionally distinct forms of guanosine cyclic 3',5'-phosphate stimulated cation channels in a bovine rod photoreceptor disk preparation.

Cyclic nucleotide stimulated efflux of 22Na+ and 45Ca2+ from a purified bovine rod outer segment disk preparation was measured on the 25-100-ms time scale by a novel rapid superfusion method. Activation of cation efflux by 8-bromoguanosine cyclic 3',5'-phosphate (8-Br-cGMP) was maximal within 25 ms. Over a wide range of concentrations of 8-Br-cGMP, the kinetics of termination of efflux precisely conformed to the sum of two exponential decay processes: a rapid phase (decay constant of 200 ms) and a slower phase (decay constant of 1.6 s). The kinetics of the biphasic decay of efflux cannot be explained by depletion of a pool of releasable 22Na but appear to reflect an intrinsic process for inactivation of the channels. 8-Br-cGMP-stimulated release of actively accumulated 45Ca exhibited identical biphasic decay kinetics. The maximum rate of Ca release [5 nmol.(mg of disk protein)-1.min-1] may be sufficient to produce a 1 microM change in local cytoplasmic [Ca] within 20 ms. The Ca:Na selectivity ratio is approximately 0.5:1 for both decay phases. 8-Br-cGMP demonstrated a lower potency (EC50 of 8.4 microM vs 2.8 microM) but a higher degree of cooperativity in its activation of the rapid vs the slower decay phase of 22Na efflux. The slower phase of decay was selectively inhibited by 25 microM l-cis-diltiazem, a relatively weak inhibitor of the rapid decay phase. Sodium ion (5-10 mM) selectively inhibited the rapid decay phase of 8-Br-cGMP-stimulated 45Ca release. These two kinetically and pharmacologically distinct phases of decay are hypothesized to represent two functionally distinct forms of cGMP-stimulated cation channels.

Amiloride↗
PubMed1988

Massive bone allografts in large skeletal defects after tumor surgery: a clinical and microradiographic evaluation.

Massive deep-frozen bone allografts were implanted in 13 patients after en bloc tumor resection. Patients were followed up for 14 months to 17 years. Most of the reconstructive procedures included a segmental bone allograft with knee or ankle fusion. Graft infections were the most critical complications in regard to the end results, finally requiring amputation in two cases. There were three stress fractures; two of which were successfully treated without further complication. Graft incorporation was assessed by bone scintimetry in four cases. Isotope uptake by the center of the graft was found to be superior to control bone segments at only 15 years after surgery. Two recovered allograft specimens were available for a microradiographic study. Creeping substitution was a very slow process, initiated at the outer surface of the graft and characterized at 2-3 years after implantation by large, incompletely filled osteons. The present investigation demonstrates that massive bone allografts are very slowly revascularized and are intimately anchored by the host bone. Provided that tumor control is effective and graft infection is avoided, reconstructive surgery with massive bone allografts represents a successful alternative to prosthetic implants in young adult with a long life expectancy.

Adolescent↗
PubMed1988

Congenital ring-constriction syndrome of the limbs; a report of 19 cases.

The authors report 19 cases of congenital ring-constriction syndrome of the limbs. Complications arose in eight of the pregnancies. The limb anomalies were always congenital ring-constrictions together with distal amputation. Moreover, 13 patients also had syndactyly and 15 associated anomalies were registered in 9 patients--8 of the limbs, 3 craniofacial and 4 visceral. One patient had a family history of hypospadias and cardiac malformation. Treatment usually required several operations, staged Z-plasty being the procedure of choice in surgical release of constriction bands. The acrosyndactylies were released early in life. More extensive fusions required division and skin grafting even if the webs did exist. The aetiology of the condition is still under discussion. The number of cases in the literature that cannot be explained by the exogenous theory of the congenital ring-constriction syndrome is increasing. Among them are four cases in our series.

Abnormalities, Multiple↗
PubMed1988

Passive transfer of myasthenia gravis by immunoglobulins: lack of correlation between AChR with antibody bound, acetylcholine receptor loss and transmission defect.

The effects of serum Ig from 7 myasthenia gravis patients on neuromuscular transmission was investigated by passive transfer to mice. A protocol of 60 mg/day for 3 days produced mouse serum levels of anti-mouse AChR that were similar to those in the MG patients, and resulted in corresponding levels (2-76%) of mouse muscle AChR with antibody bound in situ. However, AChR loss was only greater than 20% with one MG preparation. Nevertheless, there was a marked neuromuscular defect in mice injected with 3 preparations which did not necessarily correlate with the degree of AChR loss or the amount of AChRs with antibody bound in situ. We conclude that in some MG patients part of the defect in neuromuscular transmission may result from antibodies binding to other components of the neuromuscular junction.

Adolescent↗
PubMed1988

Plasma from myasthenia gravis patients reduces acetylcholine receptor agonist-induced Na+ flux into TE671 cell line.

Plasma from myasthenia gravis patients was tested for its ability to inhibit agonist-induced 22Na+ influx into the TE671 cell line that expresses human acetylcholine receptors. Reduced 22Na+ influx correlated weakly with the total anti-acetylcholine receptor antibody level in the plasma, and was also related to the presence of antibody directed against the agonist binding site, as detected by inhibition of 125I-alpha-bungarotoxin binding. However, in some cases there was inhibition of 22Na+ flux without evident anti-alpha-bungarotoxin binding site antibody. We conclude that in most patients antibodies that interfere with 22Na+ influx do so by blocking the agonist binding site. However, in some cases antibodies may be directed at the Na+ ion channel or some important functional determinant.

Adult↗