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P Leprince

Publications and source records attributed to P Leprince.

At least 19 recordsLinked to original sources
PubMed1999

Identification of PSF, the polypyrimidine tract-binding protein-associated splicing factor, as a developmentally regulated neuronal protein.

The polypyrimidine tract-binding protein-associated splicing factor (PSF), which plays an essential role in mammalian spliceosomes, has been found to be expressed by differentiating neurons in developing mouse brain. The sequence of a fragment of mouse PSF was found to be remarkably similar to that of human PSF. Both the expression of PSF mRNA in cortex and cerebellum and PSF immunoreactivity in all brain areas were high during embryonic and early postnatal life and almost disappeared in adult tissue, except in the hippocampus and olfactory bulb where various neuronal populations remained PSF-immunopositive. Double-labeling experiments with anti-PSF antibody and anti-neurofilaments or anti-glial fibrillary acidic protein antibodies on sections of cortex, hippocampus, and cerebellum indicate that PSF is expressed by differentiating neurons but not by astrocytic cells. In vitro, mouse PSF was found to be expressed by differentiating cortical and cerebellar neurons. Radial glia or astrocyte nuclei were not immunopositive; however, oligodendrocytes differentiating in vitro were found to express PSF. The restricted expression of PSF suggests that this splicing factor could be involved in the control of neuronal-specific splicing events occurring at particular stages of neuronal differentiation and maturation.

Amino Acid Sequence↗
PubMed1998

Pacemaker infective endocarditis.

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.

Adult↗
PubMed1998

Effects of macrophage transplantation in the injured adult rat spinal cord: a combined immunocytochemical and biochemical study.

Early and robust invasion by macrophages may be one of the reasons why axonal regeneration is more effective in the PNS than in the CNS. Therefore, we have grafted autologous peritoneal macrophages labeled with fluorescent latex microspheres into spinal cord compression lesions. At various survival times, we have studied their effect on the expression of neuronal (neurofilaments [NF], calcitonin gene-related peptide [CGRP], 5-hydroxytryptamine [5-HT]) and nonneuronal markers (myelin-associated glycoprotein [MAG], glial fibrillary acidic protein [GFAP], laminin) by using semiquantitative Western blot and immunohistochemical techniques. After 1 month, we observed a significant decrease of the expression of MAG as well as an important invasion of the lesion site by neurites, chiefly peptidergic axons of presumed dorsal root origin, in macrophage-grafted animals compared with controls. In addition, angiogenesis and Schwann cell infiltration were more pronounced after macrophage grafts, providing an increase in laminin, a favorable substrate for axonal regrowth. By using reverse transcription-polymerase chain reaction (RT-PCR), mRNAs for tumor necrosis factor-alpha (TNF-alpha) were detected in the transplanted cells, whereas results were negative for nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), or acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Thus, macrophage grafts may represent an interesting strategy to promote axonal regeneration in the CNS. Our study suggests that they may exert their beneficial effects by degrading myelin products, which inhibit axonal regrowth, and by promoting a permissive extracellular matrix containing notably laminin. No evidence for a direct synthesis of neurotrophic factors by the transplanted macrophages was found in this study, but resident glial cells could secrete such factors as a result of stimulation by macrophage-released cytokines.

Animals↗
PubMed1998

[The cardiowest total artificial heart: experience of 29 cases].

The authors studied the outcome of multi-organ failure in 29 patients with terminal cardiac failure and maintained with a Cardiotest total artificial heart whilst waiting for cardiac transplantation. Pre-implantation organ dysfunction was defined by the following criteria; assisted respiration of over 3 days, total billirubin and creatinine levels of over 2 mg/dL, a platelet count of less than 80,000/mL or a prothrombin ratio of less than 50% and central nervous system disturbances. Fourteen patients died during the period of circulatory assistance and 71% of deaths were due to multi-organ failure. Pre-implantation plasma total bilirubin levels were significantly higher in patients who died of multi-organ failure (p = 0.04). Eighty per cent of patients who died of multi-organ failure had at least 3 criteria of organ dysfunction before implantation of the artificial heart compared with only 37% in the other patients (p = 0.04). Finally, systemic vascular resistances before implantation were significantly lower in patients who died of multi-organ failure. The results of this study suggest that multi-organ failures does not develop during the period of circulatory assistance but represents an aggravation of a preexisting morbid condition. This observation should lead to a limitation of the indications of total circulatory assistance in some cases and, above all, to earlier intervention before multi-organ failure becomes irreversible.

Adult↗
PubMed1997

Position-related factors in mitral and tricuspid bioprostheses degenerative changes.

We report clinicopathological findings in 15 patients in whom the same bioprosthesis (BP) had been implanted simultaneously in both mitral and tricuspid positions. The aim of the study was to investigate whether position-related factors played an important role in BP degeneration. There were 14 women and 1 man with a mean age of 34 +/- 11 years. The indications for the initial operation were rheumatic in 14 cases and endocarditis in one patient. The mean interval before reoperation was 7.5 +/- 3.3 years. Predominant cause of reoperation was: structural deterioration of both mitral and tricuspid BPs (6), mitral regurgitation (5), tricuspid BP dysfunction (1), para-aortic leak (1), mitro-aortic thrombi (1). Calcific deposits were the principal cause of early deterioration of mitral BPs and the major cause of late tricuspid BPs dysfunction. This lesion was predominantly related to local factors. Cuspal tears were the principal cause of late (> 9 yrs) mitral BP failure and most probably related to mechanical stress. Extensive fibrosis affected only tricuspid bioprostheses. In 7 patients more extensive degenerative changes occurred in bioprostheses in the mitral rather than the tricuspid position (Group I). However, in the remaining eight the magnitude of the changes was very similar in the two positions (Group II). The interval before reoperation was significantly longer in patients of Group II (9.8 yrs, range 5-13) than patients in Group I (4.9 yrs, range 3-6), (p < 0.01). We concluded that position-related factors exert a major role in bioprosthetic failure. These factors are more deleterious in the mitral position than in the tricuspid position.

Adolescent↗
PubMed1996

Protein kinase- and staurosporine-dependent induction of neurite outgrowth and plasminogen activator activity in PC12 cells.

We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the generation of neurite outgrowth by PC12 cells. To that aim, cells were treated with agents that interact with the trk receptor and with protein kinases A and C. Nerve growth factor induced only the formation of large neurites. The release of the protease and the production of short neurite outgrowth were found to be protein-kinase-A-dependent events that could be enhanced by simultaneous activation of protein kinase C with phorbol ester. At high concentration, staurosporine, a nonselective inhibitor of protein kinases, induced the production of short neurites and mimicked the protein-kinase-A-dependent effect on tPA release. Such a response was not observed with K-252a, an analogue of staurosporine devoid of neurite-outgrowth-promoting activity. The responses to protein kinase A stimulation and the addition of staurosporine, although similar, seemed to occur through an activation of distinct, yet interacting, signalling pathways. In conclusion, tPA release and large neurite outgrowth from PC12 cells are controlled by parallel, albeit interacting, pathways, suggesting that these two potentially antagonistic events in PC12 cell differentiation can be modulated in a concerted way or independently of each other, depending on the activity of several protein kinases.

Animals↗
PubMed1996

Astroglia-released factor with negative allosteric modulatory properties at the GABA A receptor.

We have previously shown, using whole-cell patch-clamp techniques, that astrocytes release a negative allosteric modulator of the gamma-aminobutyric acid type A receptor (GABAA receptor) with beta-carboline-like properties, thus, likely to act at the benzodiazepine site. Here, using patch-clamp and binding techniques, we confirm that the low-molecular-weight fraction of astroglia-conditioned medium (ACM lmf) contains a factor(s) that negatively modulates GABAA-receptor function. This factor, like beta-carbolines, enhances the specific binding of [35S]t-butyl bicyclophosphorothionate (TBPS) to adult rat cortical membranes in the presence of GABA. However, it fails to interact with various ligands of the benzodiazepine (BZD) site of the GABAA receptor ([3H]flunitrazepam, [3H]Ro 15-1788 and [3H]Ro 15-4513). The question of the actual binding site of the astroglia-derived factor on the GABAA receptor, thus, remains open and can be addressed only after the purification of the active molecule(s) of ACM Imf has been completed, and a labeled form of the endogenous ligand becomes available. Taken together, however, the data suggest that type 1 astrocytes are able to modulate the effects of the main inhibitory neurotransmission in the central nervous system.

Allosteric Regulation↗
PubMed1996

Morphometric and metabolic profile of the distal segment of the internal mammary artery: caution on its use for coronary anastomoses.

OBJECTIVE: Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibility to develop intimal changes were undertaken in order to evaluate the reliability of its use as an anastomotic site for bypass grafting. METHODS: Twenty distal segments of IMA were harvested from patients who had undergone myocardial revascularization. Histologic, enzyme-histochemical and morphometric studies were undertaken on these arterial segments. RESULTS: Histologic examinations indicated an elastomuscular structure in 13 patients, a muscular structure in 6 and an elastic structure in 1. Of the 20 IMAs, none was found to have intimal thickening of greater than 25% of the diameter of the lumen. The enzyme-histochemical profile of the proliferating cells found in the intimal thickening differed from normal contractile smooth muscle medial cells in the loss of myosin and mitochondrial ATPase, plasma membrane 5' nucleotidase, moderately decreased aerobic dehydrogenase and increased lactate dehydrogenase activity and ribonucleoprotein-linked pyroninophilia. Lysosomal beta-glucuronidase and sulfatase were strongly active. This enzyme behavior is unfavorable to contractile function and favorable to cell proliferation and lipid accumulation, two events strongly involved in the atherogenic process. CONCLUSION: Intimal proliferative changes were observed in the distal segment of the IMA. Although there was no histologic evidence of atherosclerotic plaque, the enzyme-histochemical profile of this intimal thickening was favorable to cell proliferation and lipid accumulation. These findings suggest that it may be beneficial to avoid coronary anastomoses with the distal end of the IMA and to use a more proximal/elastic segment.

5'-Nucleotidase↗
PubMed1996

[Reoperation for aortic valve replacement after myocardial revascularization].

A series of 13 patients (11 male, 2 female, average age 61 +/- 6 years) with previous aortocoronary bypass surgery and reoperated for aortic valve replacement (AVR) were analysed retrospectively. At coronary bypass, 8 patients (Group I) has insignificant aortic stenosis (AS) (mean transvalvular pressure gradient < 40 mmHg and/or aortic valve surface > 1 cm2). The other 5 had no aortic valvular lesion (Group II). The average time interval between the two operations was 7 +/- 3.3 years (Group I: 6.7 +/- 3.5 years; Group II: 7.4 +/- 3.2 years). In Group I, 2 patients required early AVR (2 years) whereas the time of reoperation varied from 6 to 12 years in the other 6 patients. No operative complications related to the sternotomy or dissection of adhesions were observed. In 3 cases, it was necessary to free the implanted grafts on the right coronary artery to gain access to the initial part of the aorta. A transverse low aortotomy allowed AVR in good conditions in all cases. One patient in Group II died on the 5th postoperative day of a low output syndrome complicated by pneumonia. After an average follow-up of 3 +/- 2 years, 9 patients are still alive. Three patients in Group I died, two of cardiac failure and one of unknown causes. The authors conclude that "prophylactic" AVR in cases of insignificant AS in patients referred for coronary bypass surgery is not justified. Regular echocardiographic follow-up should lead to AVR at the most appropriate moment, sometimes after an interval of several years, with a low operative risk.

Aged↗
PubMed1995

[Septicemia and endocarditis related to transvenous pacing leads of pacemakers: surgical indications and results].

Endocarditis of transvenous pacing leads is a rare condition. The authors review a series of 15 patients who developed bacteriologically proven septicaemia and/or endocarditis related to transvenous pacing leads, operated between 1988 and 1993. The interval between the last manipulation of the pacemaker and the onset of endocarditis was about 6 months. Six patients had had haematoma and/or infection of the pacemaker site. Endocarditis presented with chronic pyrexia (14 cases) associated with septicaemia (6 cases) and chronic local suppuration (1 case). The interval between the beginning of the pyrexia and the diagnosis was 3.4 months. Echocardiography showed a mass attached to the pacing lead in 8 cases and tricuspid valve vegetations in 4 cases. Blood cultures were positive in 13 patients and local wound swabs identified the organism in 1 patient. The commonest causal agent was the staphylococcus (epidermis in 7 cases, aureus in 4 cases). Appropriate antibiotic therapy was only effective in 1 case. The surgical indication in 13 cases was persistence of infection associated with pulmonary embolism (3) or tricuspid regurgitation (2). Complete ablation of the prosthetic material was performed by a peripheral vascular approach (2 cases), by a right atrial approach (1 case) and under cardiopulmonary bypass in 12 cases. The peroperative findings were of tricuspid valve vegetations (4 cases), thrombi on the pacing lead (7 cases) or in the right heart chambers (2 cases) or pulmonary artery (2 cases). The associated procedures performed under cardiopulmonary bypass were tricuspid valve repair (2 cases) and pulmonary thrombectomy (2 cases). Temporary and permanent epicardial leads were implanted in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Astroglia-released factor shows similar effects as benzodiazepine inverse agonists.

Media conditioned by cultured neonatal cerebral cortex microexplants (CCM) or astrocytes (ACM) contain low molecular weight (< 1,000 Da) substance(s) which inhibits the gamma aminobutyric acid (GABA)-induced inward current recorded in cerebellar granule cells and hippocampal neurons in culture using the whole-cell patch-clamp technique. This effect is specific for CCM and ACM, as medium conditioned by PC12 cells (PC12CM) does not affect the GABA response of these cells. It is also specific for GABA-induced currents because glutamate-induced currents do not change either in amplitude or in shape in the presence of CCM or ACM. The inhibitory effect on the GABA response in cerebellar granule cells of both ACM and CCM could be suppressed by flumazenil, a specific benzodiazepine (BZD) antagonist and could be mimicked by two BZD inverse agonists. These data thus demonstrate the presence of a BZD inverse agonist-like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA-induced current in GABA-responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogeneity of the GABAA receptors present in these different neuronal subsets. By the release of such an endogenous BZD inverse agonist-like activity, glia cells could possibly modulate GABAA receptor-mediated responses.

Animals↗
PubMed1993

Transforming growth factor beta as a neuronoglial signal during peripheral nervous system response to injury.

In contrast to the central nervous system (CNS), the peripheral nervous system (PNS) displays an important regenerative ability which is dependent, at least in part, on Schwann cell properties. The mechanisms which stimulate Schwann cells to adapt their behavior after a lesion to generate adequate conditions for PNS regeneration remain unknown. In this work, we report that adult rat dorsal root ganglion (DRG) neurons are able, after a lesion performed in vivo or when they are dissociated and cultured in vitro, to synthesize transforming growth factor beta (TGF beta), a pleiotropic growth factor implicated in wound healing processes and in carcinogenesis. This TGF beta is tentatively identified as the beta-1 isoform. Adult rat DRG neurons release a biologically active form of TGF beta which is able to elicit multiple Schwann cell responses including a stimulation to proliferate. Moreover, purified TGF beta-1 produces a Schwann cell morphology alteration and decreases the secretion of tissue-type plasminogen activator (tPA) and enhances the secretion of plasminogen activator inhibitor (PAI) by Schwann cells. This generates conditions which are thought to favor a successful neuritic regrowth. Furthermore, purified TGF beta-1 stimulates type IV collagen mRNA expression in Schwann cells. This subtype of collagen is associated with the process of myelinization. Finally, TGF beta-1 decreases nerve growth factor (NGF) mRNA expression by Schwann cells, an effect which could participate in the maintenance of a distoproximal NGF gradient during nerve regeneration. We propose that neuronal TGF beta plays an essential role as a neuronoglial signal that modulates the response of Schwann cells to injury and participates in the successful regeneration processes observed in the PNS.

Animals↗
PubMed1993

Plasticity of developing and adult dorsal root ganglion neurons as revealed in vitro.

We review recent data on the plasticity of dorsal root ganglion (DRG) neurons as revealed during cultivation in vitro. Some experiments on cultured developing DRG neurons and on adult DRG neurons in vivo are also mentioned. Cultured developing and adult DRG neurons can be switched from an apolar to a multipolar phenotype by fetal calf serum or fibronectin. The effect is concentration dependent and occurs through an early modification of cell-substratum interaction. Adult DRG neurons synthesize and release within hours after injury TGF beta-1, which is a mitogen and a differentiation factor for Schwann cells. Finally, adult DRG neurons express in vitro neurotransmitters that are not expressed in vivo. This neurotransmitter plasticity can be modulated in vitro by some growth factors and in vivo by distal or proximal axotomy.

Animals↗
PubMed1993

Syngeneic grafting of adult rat DRG-derived Schwann cells to the injured spinal cord.

A subdural inflatable micro-balloon was used to induce closed traumatic contusion to adult rat spinal cord. This spinal cord injury model was associated with reproducible and graded neurological deficits and histopathological alterations. At various delays after injury, transplantations of syngeneic adult cultured dorsal root ganglion-derived Schwann cells were performed into the spinal cord lesion. The transplants were well integrated and reduced the microcystic posttraumatic cavitation as well as the gliosis. Schwann cells transplants were invaded by numerous regenerating neurites most of which, based upon their neurotransmitter contents, seem to originate from the dorsal root ganglion.

Animals↗
PubMed1992

Experimental acute traumatic injury of the adult rat spinal cord by a subdural inflatable balloon: methodology, behavioral analysis, and histopathology.

We describe an experimental model to produce closed traumatic injuries to the spinal cord of adult rats. This model uses an inflatable balloon that is introduced in the dorsal subdural space and moved to a location rostral to the laminectomy site. The spinal cord trauma can be graded by varying either the duration of compression or the volume of saline used to inflate the balloon. The locomotor deficit of animals with various degrees of injury has been assessed at increasing delays after trauma. The parameters generating transient or definitive deficits of varying intensity were defined. Some injured animals underwent nuclear magnetic resonance imaging. Detailed histopathological studies demonstrated that the extent of the spinal lesion was significantly correlated with the physical parameters of compression and with the severity of the behavioral deficit.

Animals↗
PubMed1992

In vitro and in vivo modulation of 5-hydroxytryptamine-, thyrotropin-releasing hormone- and calcitonin-gene related peptide-like immunoreactivities in adult rat sensory neurons.

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect.

Animals↗