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Biomedical subjects

B Gabriel

Publications and source records attributed to B Gabriel.

At least 37 records · Page 2Linked to original sources

Proton long-range migration along protein monolayers and its consequences on membrane coupling.

It has been shown with lipid layers and more recently with purple membranes that protons have slow surface-to-bulk transfer. This results in long-range proton lateral conduction along membranes. We report here that such lateral transfer can take place along a pure protein film. It is strongly controlled by the packing. Subtle reorganizations of the protein-protein contact can be biological switches between interfacial and delocalized proton pathways between sources and sinks.

Fluorescence↗

Syntheses and selective inhibitory activities of terphenyl-bisamidines for serine proteases.

Biphenyl nitriles 5a-c, terphenyl dinitriles 11a-d, and naphthalene-bis(benzonitrile) 11c were prepared by palladium-catalyzed cross coupling reactions and subsequently converted to biphenyl amidines 8a-c and bis(benzamidines) 4a-e. Among the biphenyl amidines 8 only the meta-derivative 8b inhibits factor Xa and trypsin (Ki = 10 microM). The terphenyl bisamidine 4c does not inhibit factor Xa, trypsin, thrombin, and plasmin, while 4a and 4d are almost equipotent inhibitors of these enzymes (Ki 1-6 microM), and 4b and 4e are selective for trypsin (Ki = 0.2 and 0.3 microM; but Ki > 1 microM for factor Xa, thrombin, and plasmin). X-ray analysis of crystals of 4b complexed with bovine trypsin revealed a unique binding mode: one benzamidino group binds in the S1 site to the side chain carboxylate of Arg189. The central phenyl group is twisted away from the S2/S3 sites and the second amidino group contacts the Asn143 side chain.

Amidines↗

Control by electrical parameters of short- and long-term cell death resulting from electropermeabilization of Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells were pulsed by using brief intense square-wave electric field pulses. The electrical treatment induced a transient local permeabilization of the cell membrane. The growth of CHO cells after electropulsation in an iso-osmotic pulsing buffer with low ionic content was measured. Parallel experiments evaluated cell death which took place in the minute range after electropulsation (short-term death) and the cell death upon 24 h (long-term death). Short-term cell death was defined as the case of cells with membrane still permeable to Direct-blue at 15 min after electropulsation. It was observed only under stringent pulsing conditions where electropermeabilization of the two sides of the cell was triggered. The long-term cell death, i.e., the inability of some pulsed cells to grow was observed as soon as permeabilization had been triggered. The higher the permeabilization level of the cell population was, the higher the long-term cell death level was. The cell death was linearly related to the reciprocal of the electric field intensity, i.e., to the fraction of the membrane area electrically brought to the permeable state. From this work, it appeared that for high levels of permeabilization of a cell suspension, best cell survivals were obtained if limited alterations were triggered over a large area of the plasma membrane (single pulse with high intensity) than if a small area of the membrane was strongly altered (repetitive pulses with small intensity). The highest yield of viable permeabilized cells was achieved when using one single pulse of duration up to 1 ms.

Animals↗

Spatial compartmentation and time resolution of photooxidation of a cell membrane probe in electropermeabilized Chinese hamster ovary cells.

When electropulsed by short strong electric field pulses, cells can be permeabilized transiently (electropermeabilization). The transient electroinduced membrane restructuration which supports enhanced membrane permeability is topologically well defined on the surface of the cell. Exchange of polar species only takes place on the part of the cell surface which is controlled by the field intensity. Electropermeabilization is a stress for the cell and metabolic responses associated with this stress must be studied. A key point is to discover whether this stress affects the whole cell surface or especially the permeabilized part. This was investigated by photochemical time-dependent methodology. Analysis of the photooxidation reaction of 5-(N-hexadecanoyl)-aminofluorescein, an interfacial light-sensitive fluorescent probe, inserted into the Chinese hamster ovary cell membrane showed that the rate of reaction was accelerated when the cell population was electropermeabilized. This increase in the rate constant depended on the field strength. A theoretical approach suggested that modulation of the photooxidation reaction was restricted to the electropermeabilized part of the cell surface. The difference of reactivity could be correlated with an activator effect of oxygen-reactive species generated by an electro-induced oxidative jump and suggested that these species were localized in the permeabilized part of the plasma membrane. Using fluorescence digitized videomicroscopy imaging on a single cell, such spatial heterogeneity of the photooxidation reaction was indeed directly observed when the cell was electropermeabilized. There was heterogeneous compartmentation of the membrane reaction into two independent domains with specific reactivity. The direct observation is that long-lived electropermeabilization only affects a restricted part of the pulsed cell surface, from both a structural and a metabolic point of view.

Animals↗

[Renal complications from intravenous immunoglobulins. Role of renal hemodynamic factors].

In idiopathic thrombocytopenic purpura, intravenous immunoglobulin therapy is currently a treatment of choice. It is usually effective with little side-effects. Acute renal failure has been recently identified as a potential, though rare, complication of intravenous immunoglobulins. However, the mechanism remains unclear. A 53 year-old-woman with idiopathic thrombocytopenic purpura developed oliguric renal failure after high doses of intravenous immunoglobulins. Her renal function returned to normal after dialysis and plasmapheresis. This rapid normalization suggested that acute renal failure was functional. Since laboratory tests showed an increase in protidemia concomitant to the immunoglobulin therapy, acute renal failure was likely to be related to hyperosmolar renal damage.

Acute Kidney Injury↗

[Diabetes insipidus disclosing metastasis of breast adenocarcinoma].

We are reporting on a case of diabetes insipidus (DI) and anterior pituitary failure revealing a breast cancer metastasis. Ten years after being diagnosed with a unilateral breast cancer, the patient presented with asthenia, thirst, polyuria and nocturia improved by subcutaneous DDAVP. MRI revealed a thickened pituitary stalk. DI is uncommon, late and usually asymptomatic in breast cancer. The association with an anterior pituitary failure is even more rare. In our patient the metastasis is in the pituitary stalk and seems to be due to meningeal deposits. MRI appears to be the best procedure to perform, showing a thickening stalk. Extension to the pituitary gland is related to direct tumor invasion from adjacent structures rather than haematogenous spread.

Adenocarcinoma↗

[Apropos of 2 cases of severe malaria contracted in the port of Marseille].

Acute Plasmodium falciparum malaria occurred during summer 1993 in two inhabitants living close to Marseille harbour. History of blood transfusion and travel outside France were excluded as was also discarded airport malaria. Entomological investigations confirmed the absence of Anopheles breeding sites in the port area. An hypothesis is a vectorial transmission following introduction of one or several anopheles arrived on a ship coming from tropical Africa. During this season, the weather conditions were favourable to the survival of anopheles and the completion of P. falciparum sporogonic cycle. Physicians were advised to take into consideration malaria in the differential diagnosis of fever from unknown origin in any patient working or living inside or around the harbour area regardless history of previous travel in malaria endemic region.

Aged↗

Proton lateral conduction along a lipid monolayer spread on a physiological subphase.

A localized lateral proton pathway is present along the phospholipid polar heads and bound water molecules when the lipids are spread in monolayers at the air/water interface. Conduction can be detected on concentrated buffers as found under physiological conditions if the lateral proton gradient is large enough. The localized movement supports the occurrence of microlocalized proton circuits along a membrane and of lateral proton gradients.

Buffers↗

Generation of reactive-oxygen species induced by electropermeabilization of Chinese hamster ovary cells and their consequence on cell viability.

Cells can be permeabilized transiently when pulsed by a brief intense external electric field. The molecular and cellular bases of cell electropermeabilization are still unclear. This process can be described by a local transient membrane organisation in which high permeability exists. In this study, using the chemiluminescent probe lucigenin, we showed that electropulsation of Chinese hamster ovary cells induced generation of reactive oxygen species at the electropermeabilized cell level. This generation was directly associated with the part of the membrane surface which is electrically restructured, as shown by its dependence on electric parameters. The electroinduced cell process was activated by Ca2+ and Mg2+ ions, and by exogenous adenosine 5'-triphosphate. A metal-ion-catalyzed Haber-Weiss reaction was thought to occur in the process, as shown by the action of effector molecules of Haber-Weiss reaction such as the chelating agent EDTA, and the hydroxyl radical scavenger dimethylsulfoxide. The modulation of the oxygen species electroinduction and the use of antioxidant products (dimethylsulfoxide, sodium L-ascorbate) showed that cell survival after electric treatment was directly correlated to the oxidative jump intensity. This observation had to be associated with the cell-damaging action of oxygen-reactive species.

Adenosine Triphosphate↗

Electric field-mediated glycophorin insertion in cell membrane is a localized event.

Purified soluble glycophorin, an intrinsic protein, can be back 'electroinserted' in the membrane of Chinese hamster ovary cells by submitting the cell/protein mixture to short electric field pulses. Previous studies showed that this complex between pulsed cells and proteins, which is detected only when the cell membrane is electropermeabilized, was very stable. This strongly suggested that the protein was indeed inserted in the membrane. The basic processes involved in this phenomena are studied in the present work. The association is observed at the single cell level by means of videoimmunofluorescence. Electric field-mediated insertion occurs firstly in a limited patch of the cell surface, which size is in agreement with the prediction of Electropermeabilization theory. A free diffusion of the inserted proteins then follows on the cell surface. The diffusion coefficient is computed to be less than 10(-10) cm2/s as observed for transmembranous proteins. This slow process gives an homogeneous distribution of the inserted protein.

Animals↗

Lateral communication by fast proton conduction: a model membrane study.

Lateral communication of information along biological membranes is thought to be a key process for many cellular activities. Support for this hypothesis comes from physicochemical experiments that show that an efficient facilitated lateral proton conduction exists along lipid-water interfaces. The existence of a local two-dimensional hydrogen bond network between the lipid headgroups and their associated water molecules would explain this phenomenon.

Biological Transport↗

[Transient involuntary movement disorders and thalamic infarction].

Stroke-related nonepileptic transient dyskinesias are rare, and the site of ischemia remains often undetermined. Five cases out of 47 consecutive thalamic infarcts (10.6 per cent) are reported. Patients presented with monochorea (1 case), hemiballism-hemichorea (2 cases), choreoathetosis (1 case with subsequent arm painful dystonia and hand tremor), and asterixis (1 case). Magnetic resonance imaging demonstrated that the subthalamic nucleus was spared in all cases. Transient dyskinesias occurred at any time in the course of infarction (as a warning sign in 1 case, as an associated symptom in 3 cases, or during recovery in 1 case). Moreover, this study suggests that: 1) transient dyskinesias are mainly related to thalamic ischemic injury, and 2) small vessels disease is the main etiology.

Aged↗

[Weber syndrome caused by Listeria abscess].

A 63-year old diabetic man presented with left Weber's syndrome and meningitic syndrome. CSF examination showed moderate lymphocytic pleocytosis and elevated proteins with normal glucose content and sterile culture. Blood cultures yielded Listeria monocytogenes and the patient received ampicillin. While his neurological condition had partially improved, he died of heart failure. Several mesencephalic abscesses were found at autopsy.

Brain Abscess↗