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Biomedical subjects

P Potier

Publications and source records attributed to P Potier.

At least 37 records · Page 2Linked to original sources

Pyrrolidinoindoline alkaloids from Psychotria oleoides and Psychotria lyciiflora.

The chemical study of two Rubiaceae from New Caledonia, Psychotria lyciiflora and Psychotria oleoides, led to the isolation of several pyrrolidinoindoline alkaloids. Two dimers, the known meso-chimonanthine (9) and the new Nb-desmethyl-meso-chimonanthine (5), and a known trimer, hodgkinsine (1), have been isolated from P. lyciiflora. Hodgkinsine (1), quadrigemine C (2), isopsychotridine B (3), psychotridine (4), and three new alkaloids, quadrigemine I (6), oleoidine (7), and caledonine (8), have been isolated from P. oleoides. Structural assignments of the compounds were based on mass spectra analysis and 2D NMR experiments. A tentative stereochemical determination is made from 2D NMR experiments, circular dichroism study and chemical correlations. Some of these compounds are functional antagonists of somatostatine (SRIH).

Alkaloids↗

Cytotoxicity of natural ginseng glycosides and semisynthetic analogues.

The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were active against the human lung carcinoma GLC4 and adenocarcinoma COLO 320 cell lines. The natural glycosides displayed the lowest cytotoxicity. The triterpenes of the dammarane series used as starting aglycones for semisynthetic derivatives were moderately cytotoxic. The dammarane triterpenes possessing keto groups and their semisynthetic glucosides were the most active compounds tested. Cytotoxic effects of the dammarane glucosides were inversely proportional both to the number of sugars attached to the aglycones and to the number of hydroxy groups of the aglycones. The type of side chain and the configuration of the hydroxy group at C-3 in aglycones did not have a significant influence on the cytotoxicity.

Antineoplastic Agents, Phytogenic↗

Disruption of narG, the gene encoding the catalytic subunit of respiratory nitrate reductase, also affects nitrite respiration in Pseudomonas fluorescens YT101.

The Pseudomonas fluorescens YT101 gene narG, which encodes the catalytic alpha subunit of the respiratory nitrate reductase, was disrupted by insertion of a gentamicin resistance cassette. In the Nar(-) mutants, nitrate reductase activity was not detectable under all the conditions tested, suggesting that P. fluorescens YT101 contains only one membrane-bound nitrate reductase and no periplasmic nitrate reductase. Whereas N(2)O respiration was not affected, anaerobic growth with NO(2) as the sole electron acceptor was delayed for all of the Nar(-) mutants following a transfer from oxic to anoxic conditions. These results provide the first demonstration of a regulatory link between nitrate and nitrite respiration in the denitrifying pathway.

Anaerobiosis↗

Familial occurrence of nodular regenerative hyperplasia of the liver: a report on three families.

BACKGROUND/AIMS: Nodular regenerative hyperplasia of the liver is a histological lesion usually associated with systemic diseases, haematological malignancies, or drugs. Its prognosis depends on portal hypertension, which usually is well tolerated and requires medical management only. PATIENTS: Three unrelated families, in which two sibling adult male patients presented with nodular regenerative hyperplasia of the liver, were studied. METHODS: Complete clinical charts and liver biopsy specimens were available for all patients. In addition, explanted livers were available for examination for the two transplanted patients. RESULTS: There was no evidence of any of the various clinical situations known to be associated with nodular regenerative hyperplasia of the liver. Portal hypertension was severe, requiring surgical treatment in two cases. Renal lesions were present in three patients. In two patients, progressive evolution to liver atrophy and hepatic failure, associated with renal failure, led to combined liver and renal transplantation. CONCLUSIONS: This report describes the existence of familial cases of nodular regenerative hyperplasia of the liver, occurring without underlying or associated systemic disease, characterised by a poor clinical course and often associated with progressive renal failure.

Adult↗

Cold shock response and low temperature adaptation in psychrotrophic bacteria.

Psychrotrophic bacteria are capable of developing over a wide temperature range and they can grow at temperatures close to or below freezing. This ability requires specific adaptative strategies in order to maintain membrane fluidity, the continuance of their metabolic activities, and protein synthesis at low temperature. A cold-shock response has been described in several psychrotrophic bacteria, which is somewhat different from that in mesophilic microorganisms: (i) the synthesis of housekeeping proteins is not repressed following temperature downshift and they are similarly expressed at optimal and low temperatures (ii) cold-shock proteins or Csps are synthesized, the number of which increases with the severity of the shock (iii) a second group of cold-induced proteins, i.e. the cold acclimation proteins or Caps, comparable with Csps are continuously synthesized during prolonged growth at low temperature. Homologues to CspA, the major cold-shock protein in E. coli, have been described in various psychrotrophs, but unlike their mesophilic counterparts, they belong to the group of Caps. Although they have been poorly studied, Caps are of particular importance since they differentiate psychrotrophs from mesophiles, and they are probably one of the key determinant that allow life at very low temperature.

Adaptation, Physiological↗

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP or Goralatide), a physiological regulator of hematopoiesis, inhibits the entry into the S-phase of murine and human hematopoietic stem cells. It has been shown to reduce the damage to specific compartments in the bone marrow resulting from treatment with chemotherapeutic agents, ionizing radiations, hyperthermy, or phototherapy. The present study was performed to assess the therapeutic potential of AcSDKP in vivo in reducing both the toxicity and the hematopoietic damage induced by fractionated administration of doxorubicin (DOX), a widely used anticancer drug. Here we showed that AcSDKP could reduce DOX-induced mortality in mice and could protect particularly the long-term reconstituting cells (LTRCs) in addition to colony forming units-spleen, high proliferative potential colony-forming cells, and colony-forming units-granulocyte-macrophage (CFU-GM) from DOX toxicity. The protection against DOX-induced mortality in mice was improved when AcSDKP was administered for 3 days, at a dose of 2.4 micrograms/d, by continuous subcutaneous (SC) infusion or fractionated s.c. injections starting 48 hours before DOX treatment. Moreover, the recovery of the CFU-GM population in the AcSDKP-DOX-treated mice was optimized by the subsequent administration of granulocyte colony-stimulating factor (G-CSF). The coadministration of AcSDKP with DOX may improve its therapeutic index by reducing both acute hematotoxicity on late stem cells and progenitors and long-term toxicity on LTRCs. Optimization of these treatments combined with G-CSF may provide an additional approach to facilitate hematopoietic recovery after cancer chemotherapy.

Animals↗

NAcSDKP analogues resistant to angiotensin-converting enzyme.

Two series of analogues of the tetrapeptide NAcSDKP, an inhibitor of hematopoietic stem cell proliferation, were prepared, and their enzymatic stability toward rabbit lung angiotensin-converting enzyme (ACE) was evaluated as well as their capacity to inhibit NAcSDKP hydrolysis by this enzyme. In the first series, each of the peptide bonds has been successively replaced by an aminomethylene bond. In the second one, the C-terminus of the peptide has been modified by decarboxylation or amidation. The results reported here indicate that all of these molecules but one have good stability toward the enzyme but none of the compounds is able to inhibit NAcSDKP hydrolysis by ACE.

Animals↗

Purification of the dissimilative nitrate reductase of Pseudomonas fluorescens and the cloning and sequencing of its corresponding genes.

The dissimilative membrane-bound nitrate reductase from Pseudomonas fluorescens strain AK15 was purified and the alpha subunit of the enzyme partially sequenced. On the basis of this partial amino acid sequence and of conserved stretches of amino acids between Escherichia coli and Bacillus subtilis, degenerate primers were design to amplify the narG gene and part of the narH gene in a PCR approach. The deduced amino acid sequence of narG shows 72% and 52% and narH 78% and 62% identity to the homologous subunit of E. coli and B. subtilis, respectively.

Amino Acid Sequence↗

capA, a cspA-like gene that encodes a cold acclimation protein in the psychrotrophic bacterium Arthrobacter globiformis SI55.

By use of Arthrobacter globiformis SI55, a psychrotrophic bacterium capable of growth between -5 and +32 degrees C, we cloned and sequenced capA, a gene homologous to cspA encoding the major cold shock protein in Escherichia coli. The deduced protein sequence has a high level of identity with the sequences of other CspA-related proteins from various sources, and no particular residue or domain that could be specific to cold-adapted microorganisms emerged. We show that CapA was produced very rapidly following cold shock, but unlike its mesophilic counterparts, it was still expressed during prolonged growth at low temperature. Its synthesis is regulated at the translational level, and we showed that growth resumption following a temperature downshift correlated with CapA expression. Transient inhibitions in protein synthesis during the first stages of the cold shock response severely impaired the subsequent acclimation of A. globiformis SI55 to low temperature and delayed CapA expression. The cold shock response in A. globiformis SI55 is an adaptative process in which CapA may play a crucial role. We suggest that low-temperature acclimation is conditioned mainly by the ability of cells to restore an active translational machinery after cold shock in a process that may be different from that present in mesophiles.

Arthrobacter↗

Catabolism of the hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro: a new insight into the physiological role of the angiotensin-I-converting enzyme N-active site.

The tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) was first isolated from bone marrow extracts and shown to be involved in the negative control of hematopoiesis by preventing the recruitment of primitive stem cells into S-phase. In vitro studies on AcSDKP catabolism in human plasma revealed that AcSDKP was cleaved by plasmatic angiotensin-I converting enzyme (ACE). The evaluation of the respective involvement of the two active sites of ACE in AcSDKP degradation in vitro revealed that the N-active site was preferentially involved in this catabolism. Moreover, an in vivo study on healthy volunteers of the catalytic efficiency of ACE towards AcSDKP after administration of Captopril demonstrated that AcSDKP was a physiological substrate of ACE. AcSDKP might represent the first natural specific substrate of the N-active site of the enzyme. These results pose the question of a potential role of ACE in the control of hematopoiesis as well as possible applications of ACE inhibitors to cope with dysfunctions in which AcSDKP might exert physiological control.

Binding Sites↗

Cold shock and cold acclimation proteins in the psychrotrophic bacterium Arthrobacter globiformis SI55.

The psychrotrophic bacterium Arthrobacter globiformis SI55 was grown at 4 and 25 degrees C, and the cell protein contents were analyzed by two-dimensional electrophoresis. Cells subjected to cold shocks of increasing magnitude were also analyzed. Correspondence analysis of protein appearance distinguished four groups of physiological significance. Group I contained cold shock proteins (Csps) overexpressed only after a large temperature downshift. Group II contained Csps with optimal expression after mild shocks. Group III contained proteins overexpressed after all cold shocks. These last proteins were also overexpressed in cells growing at 4 degrees C and were considered to be early cold acclimation proteins (Caps). Group IV contained proteins which were present at high concentrations only in 4 degrees C steady-state cells and appeared to be late Caps. A portion of a gene very similar to the Escherichia coli cspA gene (encoding protein CS7.4) was identified. A synthetic peptide was used to produce an antibody which detected a CS7.4-like protein (A9) by immunoblotting two-dimensional electrophoresis gels of A. globiformis SI55 total proteins. Unlike mesophilic microorganisms, this CS7.4-like protein was still produced during prolonged growth at low temperature, and it might have a particular adaptive function needed for balanced growth under harsh conditions. However, A9 was induced at high temperature by chloramphenicol, suggesting that CS7.4-like proteins have a more general role than their sole implication in cold acclimation processes.

Acclimatization↗

A new synthetic flavonoid protects endothelium-derived relaxing factor-induced relaxation in rabbit arteries in vitro: evidence for superoxide scavenging.

A new synthetic flavone derivative, 6,7-dimethoxy-8-methyl-3',4',5-trihydroxyflavone, was studied for its capacity to protect the acetylcholine-induced relaxation of rabbit ear and cerebral arteries from inhibition by superoxide anion. This property was evaluated via two types of in vitro experiments, using rabbit ear or basilar arteries mounted in organ baths equipped for isometric tension measurement. When a high level of superoxide anion was generated by adding 3 x 10(-4) M pyrogallol to the bath, the relaxation to acetylcholine was substantially inhibited. This inhibition was significantly reversed by both superoxide dismutase (25 and/or 50 U/mL) and the flavonoid (3 x 10(-6) M and/or 10(-5) M) in both types of arteries. In the presence of the basal level of superoxide anion, the responses to acetylcholine were significantly potentiated by the flavonoid (10(-5) M) in the ear but not the basilar artery. Thus this flavonoid protects endothelium-dependent relaxation from high levels of superoxide anion possibly by scavenging superoxide anion and may have a certain therapeutic value as an agent capable of promoting natural vasodilatation.

Animals↗

Synthetic routes to 4-amino-3-carboxy-beta-carboline derivatives: incidental formation of novel furo[3,4-c]-beta-carbolin-2-ones displaying high affinities for the benzodiazepine receptor.

The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rearrangement. During the course of these transformations, a number of furo[3,4-c]-beta-carbolin-2-ones, differing in substituents at the C-10 position, were formed. While these beta-carboline lactones (15,25,26,33) generally displayed good affinities for the central type benzodiazepine receptor in vitro (IC50's in the 10-50 nM range), one compound, 29, demonstrated an exceptionally high binding affinity (IC50 = 0.2 nM). Compound 29 was shown in electrophysiological and behavioral studies to act as a benzodiazepine receptor antagonist. The unusually high binding affinity of compound 29 corroborates the hypothesis that the benzodiazepine receptor preferentially recognizes the C-3 carbonyl function of 3-carboxy-beta-carbolines in an s-cis conformation (i.e., the carbonyl oxygen on the same side as the pyridinyl nitrogen).

Animals↗

Interactions between docetaxel (Taxotere) and Plasmodium falciparum-infected erythrocytes.

Taxotere (docetaxel) inhibits Plasmodium falciparum erythrocytic development in vitro at nanomolar concentrations, both in chloroquine-sensitive (F32/Tanzania) and chloroquine-resistant (FcB1/Colombia, FcR3/Gambia) strains. The dose-response assays performed on asynchronous cultures during 42 hr showed clear biphasic curves with a plateau from 50 microM to 10 nM and a single sigmoid curve with a concentration inhibiting 50% of growth (IC50) of 3-6 nM observed after a 72-hr incubation. Addition of Taxotere to different stages of FcB1 revealed two types of targets: one type on ring/trophozoite-infected erythrocytes (RBCs), at the micromolar level, and another type on schizont-infected RBCs with Taxotere at micromolar concentrations inhibited the merozoite invasion of erythrocytes and parasite growth. These Taxotere-RBC interactions were stable, at least for 1 day. Pulse experiments of 5 hr with Taxotere efficiently inhibit parasite development regardless of the period of the parasite's erythrocytic life cycle. However, different cellular effects were obtained depending upon periods of drug incubations. The inhibition of P. falciparum development by Taxotere should provide additional strategies to block parasite development.

Animals↗

Effect of growth temperatures on the protein levels in a psychrotrophic bacterium, Pseudomonas fragi.

Pseudomonas fragi has the ability to grow between 0 and 35 degrees C and grows optimally at 30 degrees C. Cellular proteins from mid-log-phase cells growing from 4 to 34 degrees C were labeled with L-[35S]methionine during 1 generation time and analyzed by two-dimensional gel electrophoresis. The electrophoretic patterns revealed differences in the patterns of protein synthesis over this temperature span. A qualitative comparison of cellular proteins led to their separation into five thermal classes. The first class contained proteins whose relative rates of synthesis were unaffected by the growth temperature. Three other classes included proteins with optimal expression at 4 to 10, 15 to 20, and 25 to 30 degrees C. A fifth class contained proteins which were more specifically synthesized at a supraoptimal growth temperature (34 degrees C). Two low-molecular-mass proteins, designated C7.0 and C8.0, were highly concentrated at 4 to 10 degrees C, and their relative rates of synthesis steadily increased with decreasing temperature. Polyclonal antibodies were separately raised against these two proteins. Immunological analyses revealed cross-reaction between these two proteins and between two additional low-molecular-mass proteins which were maximally produced at elevated temperatures. Antisera directed against C8.0 recognized the major cold shock protein of Escherichia coli, CspA, indicating the presence of similarities between these proteins.

Adaptation, Physiological↗

Taxoids, a new class of antitumour agents of plant origin: recent results.

The taxoids are natural products isolated from the yew tree (Taxaceae). Certain compounds of this family possess interesting antitumour properties. The discovery of one such compound, taxol and the development of an even more active derivative, Taxotere, are described. Taxotere represents a major progress in the domain of cancer chemotherapy.

Antineoplastic Agents, Phytogenic↗