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A C Vincent

Publications and source records attributed to A C Vincent.

15 recordsLinked to original sources
PubMed2000

Amino- and urea-substituted thiazoles inhibit photosynthetic electron transfer.

Amino- and urea-substituted thiazoles exhibited in vivo herbicidal activity on duckweed (Lemna paucicostata Hegelm. strain 6746) cultures and appeared to act via inhibition of photosynthetic electron transport system. A small number of the thiazole derivatives tested were active but only at relatively high concentrations. The most active structures were the amino-substituted thiazoles with isopropyl and n-butyl side chains and the urea-substituted thiazole with p-chlorophenyl side chain. Decreasing the length of the side chain had a negative effect on the PSII inhibitory activity. The urea-substituted series was as a group less active than the amino series, and the free acid series had no biological activity. The most active compounds competed for the same binding site as atrazine on PSII. Computer modeling highlighted the structural similarities between some of the thiazoles and the commercial herbicides diuron and atrazine.

Amines↗
PubMed1994

Molecular cloning and characterization of a novel liver-specific transport protein.

Monoclonal antibodies that specifically recognize a membrane component located on the sinusoidal domain of the hepatocyte have been used to screen a rat liver cDNA expression library and a clone encoding a novel transporter (NLT) protein has been identified. Analysis of the deduced 535 amino acid protein sequence indicates that it is unique, but shares the twelve-transmembrane domain hydrophathicity profile as well as the presence of transporter-specific amino acid motifs with bacterial and mammalian transporters. Since overall homology of NLT to known transporter genes is low (20-25% identity) it may represent a new subgroup within the transporter family of proteins. The NLT was characterized further with respect to its tissue distribution and its expression during liver development. A 2.1 kb transcript has been found in liver and at lower levels in kidney, but not in several other tissues tested. Studies on the developing liver indicate that NLT transcripts are present at a very low level from 19 through 21 gestation days with a 4- to 5-fold increase within two weeks after birth. Overall, we have cloned a novel transporter that is preferentially expressed in liver, is located on the sinusoidal domain of the plasma membrane and represents a marker for the late stage of liver development.

Amino Acid Sequence↗
PubMed1992

ACR1, a yeast ATF/CREB repressor.

Members of the mammalian ATF/CREB family of transcription factors, which are associated with regulation by cyclic AMP and viral oncogenes, bind common DNA sequences (consensus TGACGTCA) via a bZIP domain. In the yeast Saccharomyces cerevisiae, ATF/CREB-like sequences confer either repression or activation of transcription, depending on the promoter context. By isolating mutations that alleviate the repression mediated by ATF/CREB sites, we define a new yeast gene, ACR1, which encodes an ATF/CREB transcriptional repressor. ACR1 contains a bZIP domain that is necessary for homodimer formation and specific DNA binding to an ATF/CREB site. Within the bZIP domain, ACR1 most strongly resembles the mammalian cyclic AMP-responsive transcriptional regulators CREB and CREM; it is less similar to GCN4 and YAP1, two previously described yeast bZIP transcriptional activators that recognize the related AP-1 sequence (consensus TGACTCA). Interestingly, deletion of the ACR1 gene causes increased transcription through ATF/CREB sites that does not depend on GCN4 or YAP1. Moreover, extracts from acr1 deletion strains contain one or more ATF/CREB-like DNA-binding activities. These genetic and biochemical observations suggest that S. cerevisiae contains a family of ATF/CREB proteins that function as transcriptional repressors or activators.

Amino Acid Sequence↗
PubMed1990

Characterization of the glucagon receptor and its functional domains using monoclonal antibodies.

Four monoclonal antibodies, designated 4H11, 6E10, 2C5, and 3E9 were prepared against partially purified rat hepatic glucagon receptor. These antibodies were characterized by their ability to recognize the glucagon receptor in target tissues using immunoblot and immunoprecipitation procedures. The antibodies recognized a 62-kDa receptor band in rat liver, kidney, and adipose tissue but not in lung, adrenals, and erythrocytes, indicating a high degree of specificity. These antibodies recognize different antigenic determinants; the 6E10 and 2C5 bind protein epitopes, while 4H11 and 3E9 bind carbohydrate epitopes. Furthermore, proteolytic mapping of the glucagon receptor established that monoclonal antibodies 6E10 and 2C5 recognize different domains of the receptor molecule. These antibodies were used to study the immunochemical similarities among the receptors from different species and to assess the topological location of the ligand-binding site. By combining the techniques of affinity cross-linking, proteolytic mapping, and antibody binding, we have identified the location of the glucagon-binding site near to the COOH-terminal domain of the receptor.

Animals↗
PubMed1990

Mutations that define the optimal half-site for binding yeast GCN4 activator protein and identify an ATF/CREB-like repressor that recognizes similar DNA sites.

The yeast GCN4 transcriptional activator protein binds as a dimer to a dyad-symmetric sequence, indicative of a protein-DNA complex in which two protein monomers interact with adjacent half-sites. However, the optimal GCN4 recognition site, ATGA(C/G)TCAT, is inherently asymmetric because it contains an odd number of base pairs and because mutation of the central C.G base pair strongly reduces specific DNA binding. From this asymmetry, we suggested previously that GCN4 interacts with nonequivalent and possibly overlapping half-sites (ATGAC and ATGAG) that have different affinities. Here, we examine the nature of GCN4 half-sites by creating symmetrical derivatives of the optimal GCN4 binding sequence that delete or insert a single base pair at the center of the site. In vitro, GCN4 bound efficiently to the sequence ATGACGTCAT, whereas it failed to bind to ATGAGCTCAT or ATGATCAT. These observations strongly suggest that (i) GCN4 specifically recognizes the central base pair, (ii) the optimal half-site for GCN4 binding is ATGAC, not ATGAG, and (iii) GCN4 is a surprisingly flexible protein that can accommodate the insertion of a single base pair in the center of its compact binding site. The ATGACGTCAT sequence strongly resembles sites bound by the yeast and mammalian ATF/CREB family of proteins, suggesting that GCN4 and the ATF/CREB proteins recognize similar half-sites but have different spacing requirements. Unexpectedly, in the context of the his3 promoter, the ATGACGTCAT derivative reduced transcription below the basal level in a GCN4-independent manner, presumably reflecting DNA binding by a distinct ATF/CREB-like repressor protein. In other promoter contexts, however, the same site acted as a weak upstream activating sequence.

Base Sequence↗
PubMed1989

Experimental autoimmune myasthenia gravis induced in mice without adjuvant: genetic susceptibility and adoptive transfer of weakness.

The induction of experimental autoimmune myasthenia gravis (EAMG) in mice in the absence of adjuvant was investigated. The essential biochemical features of the disease were induced using a protocol including a primary intrasplenic immunization (1 microgram Torpedo acetylcholine receptor, AChR) followed by booster immunizations with the same dose at 2 and 6 weeks (intraperitoneal) and at 14 weeks (intrasplenic). These features included serum antibodies reactive with mouse AChR, antibody complexed with AChR in vivo, and AChR loss from motor endplates. None of the mice immunized with AChR in adjuvant developed weakness. By contrast, a few mice (less than 5%) immunized without adjuvant became overtly weak and these clinical signs could be adoptively transferred to irradiated recipients, suggesting a possible model for testing immunotherapeutic strategies. Of the nine mouse strains immunized (on six different H-2 haplotypes: a, b, d, k, q, and s) only those with the H-2k haplotype did not develop the biochemical features associated with EAMG. In an F1 cross the genotype (H-2b) was dominant in conferring susceptibility to CBA mice (H-2k).

Adjuvants, Immunologic↗
PubMed1989

Parasitic infection of the seahorse (Hippocampus erectus)--a case report.

This report details the development of a microsporidan infection in a colony of seahorses (Hippocampus erectus) caused by Glugea heraldi. Of 76 animals imported from Florida Bay (USA), two survived. A myxosporidan (Sphaeromyxa sp.) and an unidentified nematode infection were also diagnosed in the same colony, but these infections were not considered important, causative factors in the mortalities.

Animals↗
PubMed1988

Are spontaneous anti-idiotypic antibodies against anti-acetylcholine receptor antibodies present in myasthenia gravis?

The presence of anti-acetylcholine receptor anti-idiotypic antibodies in sera from 102 myasthenia gravis patients and from 33 first-degree relatives was investigated by: (a) Enzyme linked immunosorbent assay (ELISA) using monoclonal antibodies raised against human acetylcholine receptor, (b) immunoprecipitation of 125I-monoclonal anti-acetylcholine receptor antibodies; (c) inhibition of anti-acetylcholine receptor monoclonal antibody binding to the receptor and/or (d) inhibition of autologous and heterologous anti-acetylcholine receptor antibody binding to the receptor. No clear evidence for the presence of abnormal levels of spontaneous anti-idiotypic antibodies to anti-acetylcholine receptor antibodies was found.

Antibodies, Monoclonal↗
PubMed1987

Hepatobiliary MR contrast agents: 5-substituted iron-EHPG derivatives.

A series of iron(III) ethylenebis(2-hydroxyphenyl)glycine [Fe(EHPG)]- derivatives have been examined for their role as paramagnetic hepatobiliary contrast agents for magnetic resonance (MR) imaging. The 5-substituted complexes, Fe(5-Me-EHPG)-, Fe(5-Cl-EHPG)-, and Fe(5-Br-EHPG)-, have been compared to the parent compound in rat biodistribution and MR imaging studies; correlative in vitro parameters for the complexes, including octanol-buffer partition coefficients and albumin binding affinity, have also been obtained. The three new derivatives exhibited higher degrees of lipophilicity and albumin binding affinity and varying degrees of improvement in liver-to-blood and bile-to-liver concentration ratios measured at 30 min postinjection. The 5-Cl complex had the best overall performance in terms of these tissue ratios as well as in terms of total biliary excretion. Sequential MR images of rats after administration of the complexes revealed subtle pharmacokinetic differences among the derivatives and, in general, correlated well with and complemented the biodistribution results. This study points to the sensitivity of hepatocellular uptake and excretion to simple chemical modifications and, moreover, demonstrates the importance of screening multiple derivatives to select optimal hepatobiliary MR imaging agents.

Animals↗
PubMed1981

[Experimental arrhythmia models. Critical study of correlations with arrhythmias observed in clinical practice].

A number of different in vitro or in vivo experimental tests or models are now available for the demonstration of antiarrhythmic properties. In vitro electrophysiological studies on cells or healthy tissues usually establish the properties of antiarrhythmic agents, rather than their actual antiarrhythmic properties. New information has recently been provided by studies on abnormal tissues or tissues which have been made abnormal experimentally. The methods used to cause this dysfunction are discussed to determine their possible clinical relevance. There are over 50 in vivo arrhythmia models but only 2 or 3 are in common usage: aconitine or digitalis intoxication and experimental myocardial infarction (Harris' method and variants). The study of thresholds to ventricular fibrillation is more a study of an electrophysiological parameter than a study of an arrhythmia. Statistical studies require the uniformity of an experimental model and its stability (or relative stability) over a sufficiently long period from one animal or preparation to another. These conditions widen the gap between some experimental models and clinical reality. Present experimental models are essentially models of acute arrhythmias as experimental animals with chronic degenerative heart disease are not usually available (the problem of cardiomyopathic hamsters and Japanese woodcocks is discussed). The failure to appreciate the differences between species, the direct action of the drug under study (particularly on the autonomic nervous system), the hemodynamic changes induced by the experimental conditions, and the pharmacokinetics of the drug, often make extrapolations to clinical practice very difficult. Although the recent advances in our understanding of the mechanisms of arrhythmias derived from these models have not lead to any significant changes in the clinicians' attitude to the choice of antiarrhythmic therapy or to the introduction of new criteria of antiarrhythmic efficacity, none of the active antiarrhythmic agents used in clinical practice have been submitted to these antiarrhythmic screening tests. These models even provide an "honourable" classification of the relative efficacity of antiarrhythmic drugs.

Animals↗
PubMedDate not supplied

Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies.

The paramagnetic metal complex iron(III) ethylenebis-(2-hydroxyphenylglycine) [Fe(EHPG)-] is an effective hepatobiliary contrast agent for liver enhancement in magnetic resonance (MR) imaging. The intravenous administration of 0.2 mmol/kg of Fe(EHPG)- to rats yields a 200% increase in the signal intensity of the liver when using a T1-weighted inversion recovery pulse sequence on a 1.4 T imaging system. Biodistribution studies in rats and a rabbit, along with imaging studies in a dog at 0.6 T, confirm that the complex has significant hepatocellular uptake and appears to be excreted unaltered into the bile. Control experiments with a different iron complex, iron(III) diethylenetriaminepentaacetic acid, reveal little hepatic affinity and poor enhancement capability due to its extracellular distribution. This initial evaluation of Fe(EHPG)- demonstrates that paramagnetic metal complexes with hepatobiliary specificity are well suited for enhancement of normal liver parenchyma and may increase the sensitivity of MR in the detection of liver disease.

Animals↗
PubMedDate not supplied

Digoxin-induced toxicity and experimental atrioventricular block in dogs. Relation between ventricular arrhythmias and oscillatory afterpotentials.

In anesthetized dogs, digoxin intoxication was performed after and before production of a definitive complete atrioventricular (A-V) block induced by formaldehyde injection in A-V node area, compared to intoxication in dogs in sinus or junctional rhythm. The results showed that digoxin toxicity was decreased in dogs with previous A-V block. This A-V block protective effect was abolished by resetting initial sinus-like frequency with ventricular pacing before digoxin administration. Ventricular arrhythmias were suppressed by production of complete A-V block. The A-V block protective effect can be explained by a lesser myocardial uptake of digoxin because of the low idioventricular frequency. However, ventricular arrhythmias in dogs with A-V block presented similarities both in occurrence and spreading with the development of oscillatory afterpotentials (OAPs) and rhythmical triggered activity demonstrated in isolated digitalis-poisoned Purkinje fibers and ventricular myocardium: the repetitive discharge of toxic foci masked normal idioventricular pacemakers and was interrupted by variable pauses followed by the resumption of either a very slow idioventricular rhythm or a toxic focus. It is suggested that because of the low idioventricular frequency, competition and/or superimposition of slow enhanced diastolic depolarization and OAPs can be electrocardiographically displayed. The terminal event was asystole in dogs with unpaced A-V block, and ventricular fibrillation in dogs with sinus, junctional and paced A-V block rhythms. The asystole (at least 30 seconds of electrical quiescence) may be explained partly as an intense depression of normal idioventricular pacemaker being overdriven by the discharge of toxic pacemakers, and partly as a consequence of the suppression of local autonomic influences in the A-V node area induced by the formaldehyde injection.

Animals↗
PubMedDate not supplied

[Electrophysiological effects of subtherapeutic levels of procainamide on hypoxic myocardial cells (author's transl)].

1. The electrophysiological effects of hypoxia alone or combined with subtherapeutic concentrations of procainamide superfusion were investigated in guinea-pig ventricular muscle fibres in order to elucidate the procainamide activity on suffering myocardial cells. 2. A first 30 minute-long hypoxia depressed action potential characteristics but never induced cellular inexcitability. These alterations were entirely reversible. A second consecutive hypoxia period similarly affected cellular activity. 3. After a control hypoxia period, procainamide 0.15 microM and 1.5 microM further depressed or abolished the hypoxia-altered transmembrane potentials. 4. In procainamide 0.15 microM and 1.5 microM pretreated cells, hypoxia more extensively depressed or abolished the myocardial cell activity than in unpretreated cells. 5. It has been demonstrated that antiarrhythmic drugs only slowly and incompletely reached the ischaemic myocardium. The present results suggest that in clinical situations, such weak concentrations may be efficient for inducing pronounced modifications in ischaemic areas and rapid antiarrhythmic effects.

Action Potentials↗