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Biomedical subjects

J Paysant

Publications and source records attributed to J Paysant.

35 records · Page 2Linked to original sources

Comparison of the contractile responses of human coronary bypass grafts and monkey arteries to human urotensin-II.

Human urotensin-II (hU-II) is a cyclic peptide recently cloned in humans and present in human cardiac tissue and human arteries. The effects of hU-II were studied on human coronary bypass grafts in vitro. In three out of eight human mammary arteries, and two out of three human radial arteries, hU-II caused contraction; human saphenous veins did not respond to hU-II. When it exists, the contraction slowly develops and has a low-to-moderate intensity. All radial arteries obtained from young healthy non-human primates contracted strongly to hU-II.

Aged↗

[Georges Gilles of Tourette, pioneer of gait analysis in the nervous system diseases].

Georges Gilles de la Tourette's contribution to neurology goes beyond the description of the neurological disorder named after him. On December 28, 1885, he defended his doctoral thesis devoted to "gait in the diseases of the nervous system, studied by the method of imprints". In collaboration with Albert Londe, he worked for two years in Charcot's department on "a simple method applicable to both healthy and unhealthy patients", establishing the scientific and modern basis of functional exploration of human gait. The purpose was to "record the modifications of the gait and to fix them permanently, using suitable devises to guarantee not only rigorous comparison, but also to prevent observers, making use of the same method, from disputing or canceling the results completely independent of the experimenter himself". Georges Gilles de la Tourette defined the various characteristic parameters and provided the normal reference values in males and females, determining the physiological asymmetry of steps. He described spastic gait, shaking palsy, and locomotor ataxia. He distinguished between disorders of nervous control and related joint diseases. He also classified gait disorders occurring during hemiplegia. Modern development of kinetic, kinematic and biomechanical studies is a good illustration of the current relevancy of Gilles de la Tourette's contribution.

France↗

[Illusions of body normality in amputees and paraplegic patients].

Phantom limbs in amputees, or body illusion in hemiplegics, have been the subject of wide ranging descriptions. The detected abnormalities involve morphological, postural and/or kinetic features. The aim of this prospective study carried out in 25 amputees and 10 adult paraplegics was to describe the typology of these perceptions. Data were collected from free and semi-directive investigations before and after caloric vestibular stimulation. Amputees and paraplegics perceived normal, deformed and painful body phantom segments, reffered perceptions and "normal limbs" which took on the request posture considering the general body position (illusion of body normality). This perception corresponds to an image of the body, such as it should be and not such as it is. In amputees, the limb follows the movements of the prothesis. These perceptions conform quite well reality so that the loss of the paralyzed limb is not perceived as a missing limb. This illusion of body normality should be distinguished from the normal phantom limb, characterized by a stronger perception of the lost limb compared with the other. In both amputees and paraplegics, vestibular stimulation can generate or modify phantoms limbs or body illusion and can abolish painful phantom limbs. The neuromatrix, which rebuilds body representations, could get its information from reorganized cortical areas (instantaneous body image), autobiographical engrams (painful phantoms limbs), or innate engrams (identity body schema) that, via congruence mechanisms, could be identified as a somatic reference, particularly for motor programming. This interpretation is compatible with current knowledge and suggests how amputees can easily use a prothesis.

Adult↗

Buccal hemineglect.

OBJECTIVES: To determine whether the peripersonal and intrapersonal buccal space can be affected by a hemispheric stroke and to evaluate the clinical signs resulting from buccal neglect. METHODS: A prospective study comparing 2 groups of patients with hemiplegia, 1 with a right hemispheric lesion and the other with a left hemispheric lesion. Patients were selected consecutively on the basis of specific criteria at least 1 month after stroke. RESULTS: Buccal hemineglect was usually concomitant with other hemineglect phenomena resulting from lesions of the right hemisphere (10 of 12 in right lesions and 1 of 12 in left lesions). Clinical signs associated with this condition consisted of impaired swallowing (retention, defective insalivation, presence of food debris in the left hemibuccal space, loss of saliva from the left side of the mouth, and choking); loss of the ability to perceive salty, sweet, or acid tastes; and impaired buccal representation. These problems were usually incorrectly diagnosed initially. Outcome was usually favorable, but functional disorders persisted in some patients for more than 18 months. The underlying attention and representation mechanisms are discussed with reference to experimental lesions of the postarcuate (area 6) cortex in rhesus monkeys. The area around the mouth may be considered to be, as in monkeys, a peripersonal space, ie, probably of little functional importance. The lesion may involve area 6 or its projections to the thalamus or posterior parietal cortex. CONCLUSIONS: Buccal hemineglect, which is likely to cause social embarrassment, should be considered whenever the oral phase of swallowing is impaired in a context of neglect syndromes. Prophylactic measures and rehabilitation can reduce the impact and complications of the condition (food bolus).

Adult↗

Factors influencing the effect of the soluble IL-6 receptor on IL-6 responses in HepG2 hepatocytes.

The soluble IL-6 receptor (sIL-6R) can increase IL-6-induced signalling by forming a complex with IL-6 and membrane-bound gp130 (the receptor beta chain which transduces signals). The conditions affecting this response to sIL-6R were studied using fibrinogen release from HepG2 hepatocytes. Exogenous sIL-6R had no effect alone or in the presence of a submaximal concentration of IL-6, but increased responses to supramaximal IL-6 concentrations in a concentration-related manner. Dexamethasone increased the expression of the membrane IL-6R and endogenous sIL6R release, and increased responses to supramaximal but not submaximal IL-6 concentrations. The amount of endogenous sIL-6R released is relatively small and is unlikely to influence the effects of the exogenous sIL-6R. The observed concentration-related decrease in sIL-6R production in the presence of IL-6 may indicate internalization of ligand/receptor complexes. This would significantly decrease the amount of IL-6R (soluble or membrane) available for signalling and limit continued functional response later in the cultures. These data indicate that the major factor influencing responses to exogenous sIL-6R is an excess of IL-6 which is necessary to form complexes with the sIL-6R, which can then interact with gp130 to increase signalling.

Carcinoma, Hepatocellular↗

Imaging of the painful lower limb stump.

Several postoperative complications associated with pain may develop in the stump of an amputated lower limb. Clinical findings are often nonspecific; however, radiologic evaluation, especially with magnetic resonance (MR) imaging, is useful in the early diagnosis of these complications, thereby helping minimize physical disability with its psychologic and socioeconomic implications. Conventional radiography can demonstrate evidence of osseous origins of pain (eg, aggressive bone edge, heterotopic ossification, osteomyelitis) and should be the first imaging study performed after clinical examination. Videofluoroscopy can help evaluate improper prosthetic fit by demonstrating abnormal residual limb motion, piston action, rolling of soft tissues, and abnormal angle between the limb axis and the prosthesis during gait. Ultrasonography can demonstrate inflammatory changes in the stump as well as soft-tissue fluid collections. However, MR imaging is the modality of choice when clinical and other imaging findings are indeterminate. Because of its high spatial and contrast resolution, MR imaging can demonstrate subtle inflammatory changes, fluid collections, cancers, neuromas, and subtle traumatic bone lesions. Knowledge of various surgical and rehabilitation techniques is required for accurate diagnosis of complications associated with stump pain. Correct diagnosis allows choice of the most appropriate therapy, which may involve treating the stump, remodeling the prosthesis, or both.

Amputation Stumps↗

Asymmetric leg activity in healthy subjects during walking, detected by electrogoniometry.

AIM: To show asymmetric leg activity during walking in healthy subjects. DESIGN: Two electrogoniometers were used to measure the amplitude of the flexion-extension movements of both knees during walking. BACKGROUND: Walking is considered to be a symmetrical activity. Quantitative studies of walking often only consider one side of the body or remove differences between individuals by averaging results. METHODS: The handedness, lateral eye dominance and footedness of 31 healthy subjects were determined. A strain gauge electrogoniometer was then fitted to the outside of each knee to analyze the flexion-extension movements. The results were recorded automatically. The subject walked a distance of 30 m three times, with different attention levels: free walking (with no other task assigned), walking with attention diverted (whilst performing a mental task), and focused walking (walking as straight as possible in a straight line). RESULTS: 51.6% of the subjects tested displayed asymmetry of the total flexion-extension movement of more than 5 degrees between the two knees during free walking. The side favored (preponderance) by this asymmetry was not related to the handedness or other lateral dominance. The different attention levels did not significantly affect the characteristics of motion of the sub-groups studied (symmetric, right-favoring and left-favoring). CONCLUSIONS: The origin of this asymmetry, which is independent of handedness or attention level, could be the spinal stepping generator for which there is evidence in both animals and humans. Walking should not be considered to be a strictly symmetrical phenomenon. RELEVANCE: The demonstration of asymmetric leg activity during walking may lead to a better understanding of the way in which walking controlled. The presence of such asymmetry is normal, and it should be borne in mind during explorations of walking in both healthy and pathologic individuals.

Adult↗

Increased expression of u-PA and u-PAR on monocytes by LDL and Lp(a) lipoproteins--consequences for plasmin generation and monocyte adhesion.

Monocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 microg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 microg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 microg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 microg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation ( .9-fold increase with 200 microg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 microg/ml of ox-Lp(a)], due to the increase of micro-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

Cell Adhesion↗

IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34+ cells.

Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF), has multiple effects on T lymphocytes and natural killer cells. In this study, the effect of IL-12 on human hematopoiesis was studied by analyzing the growth of CD34+ peripheral blood stem cells (PBSC), in steady state. In the presence of Epo, IL-12 alone or in combination with IL-3 or SCF had no effect on the formation of colonies from CD34+ cells. In culture with Epo, G-CSF, and IL-3, the effect of Flt3-ligand (FL) on CD34+ PBSC was investigated in the presence or absence of IL-12. No additional effect of IL-12 was observed when combined with FL. We evaluated 5-FU-treated human CD34+ PBSC proliferation in cultures with Epo, G-CSF, and IL-3, in the presence or absence of IL-12. No cytokine combination enhanced colony formation from 5-FU-treated CD34+ cells. However, in cultures of 5-FU-treated human CD34+ cells, the most efficient combination was IL-3 + Epo + G-CSF + Accessory cells (CD34-). Furthermore, IL-12 enhanced this colony formation significantly. To investigate whether immature CD34+ cells were responsible for FL or SCF, 5-FU-treated human CD34+ cells were cultured with or without IL-12. Whereas no synergistic effect was observed in combination with IL-12, SCF alone significantly enhanced colony formation. However, the colony number was found to be smaller than with the potent combination of accessory cells in the presence of IL-12. These results indicate that accessory cells, lost in CD34+ cell purification, could be partly responsible for an IL-12 effect on immature human PBSC proliferation.

Adult↗

Regulation of interleukin 3 receptor alpha chain (IL-3R alpha) on human monocytes by interleukin (IL)-4, IL-10, IL-13, and transforming growth factor beta (TGF-beta).

Human interleukin 3 receptor (IL-3R) is constitutively expressed on committed haematopoietic stem cells, where it mediates proliferation and differentiation. This receptor is also expressed by monocytes and may induce functional activation. Interleukin (IL)-4, IL-10, IL-13, and transforming growth factor beta (TGF-beta) have different effects on human monocytes. As IL-3R may be regulated by different cytokines, whether the above-mentioned cytokines were able to modulate the alpha chain of IL-3R (IL-3R alpha) on monocytes was examined. Effects on IL-3R alpha antigen (Ag) expression were analysed by direct immunofluorescence and flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect variations in IL-3R alpha mRNA expression. IL-10 and TGF-beta were found to downregulate IL-3R alpha Ag. In contrast, IL-4 and IL-13 both caused a dose- and time-dependent increase. A maximum effect was observed at 1 ng/ml of IL-4 for 18 h. Furthermore, in RT-PCR, IL-4 was found to slightly up-regulate IL-3R alpha mRNA expression. These observations suggest that IL-4 and IL-13 play a role in the regulation of IL-3R alpha expression and the effects of cytokines on human monocytes may be mediated, in part, through the regulation of IL-3R.

Antigens↗

Regulation of the uPAR/uPA system expressed on monocytes by the deactivating cytokines, IL-4, IL-10 and IL-13: consequences on cell adhesion to vitronectin and fibrinogen.

Urokinase (uPA) and its receptor (uPAR) have been proposed to be involved in monocyte migration by inducing degradation of matrix proteins. In addition, uPAR is also implicated in cell adhesion to the vascular wall. The adhesive function of uPAR depends on a direct interaction with vitronectin which is increased by uPA and by modification of cell surface integrin (such as CD11b-CD18) when associated to uPAR. In this study we analysed the role of three deactivating cytokines, IL-4, IL-10 and IL-13, on the surface expression of uPA, uPAR and CD11b by monocytes and their consequences on monocyte adhesion to immobilized fibrinogen and vitronectin. IL-10 induced a decrease in uPA and CD11b after 18 h incubation and a delayed decrease in uPAR which was only significant after 48 h incubation. These results may explain the decrease in monocyte adhesion, which was observed after an 18 h incubation with IL-10, on immobilized vitronectin and fibrinogen. In contrast, IL-4 and IL-13 induced a decrease in uPAR after 18 h and a significant increase in uPA both in the cell lysates and at the cell surface, as well as an increase in cell surface associated CD11b. These cytokines did not modify cell adhesiveness to vitronectin or fibrinogen despite the increase in CD11b-CD18. This could be due to the decrease in uPAR because CD11b-CD18/uPAR forms a cell adhesion complex. In addition, the increase in uPA induced by IL-4 could counterbalance the direct interaction of uPAR with vitronectin. The increase in uPA suggests that IL-4 and IL-13 could induce plaque fissuring by monocytes, whereas IL-10 may induce protection against matrix protein degradation by decreasing uPA.

Cell Adhesion↗

In-vitro effect of oncostatin M on the release by endothelial cells of von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1.

Epidemiological studies have demonstrated that levels of plasma fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) are associated with the incidence of vascular disease. Since oncostatin M dramatically induces fibrinogen biosynthesis by hepatocytes and could be implicated in vascular injury leading to atherosclerosis, we have analyzed the effect of oncostatin M on PAI-1, vWf and tPA secretion by endothelial cells. A 2-h incubation of human umbilical vein endothelial cells with oncostatin M increases thrombin-induced secretion of vWf to the same extent as tumour necrosis factor-alpha or interleukin-1 (137+/-26% of control for 5 ng/ml oncostatin M, P < 0.001, n=5). The effects on tPA and PAI-1 secretion were different depending on the type of endothelial cells tested. On human umbilical vein endothelial cells, oncostatin M induced an increase in PAI-1 and a decrease in tPA secretion, which could explain the thrombogenicity of oncostatin M on large vessels. On a human microvasculature endothelial cell line, oncostatin M did not modify PAI-1 but induced an increase in tPA secretion. This observation of the effects of oncostatin M on both macro- and microvasculature could explain the increased levels of vWf, PAI-1 and tPA in the plasma of atherosclerotic subjects identified in epidemiological studies, suggesting that oncostatin M could play a key role in the development of atherosclerotic lesions.

Arteriosclerosis↗

Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk.

High level of fibrinogen in plasma is recognised as an important vascular risk factor. However, it is not known if the increase in fibrinogen is directly responsible for the vascular risk or is a marker of vascular inflammation. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on vascular injury was noted. Among the cytokines which induce the synthesis of fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human hepatoma cell line). Interestingly at the same concentrations needed for fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect against vascular injury leading to atherosclerosis, dose dependently down regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6 induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in fibrinogen secretion in the medium and beta chain mRNA expression and to an inhibition of production of the hepatocyte-stimulating activity for fibrinogen biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a significant decrease of the production of OSM by LPS-activated monocytes. In situ activation of monocytes by cytokines in the vessel wall could also contribute to the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.

Arteriosclerosis↗

Temporary phantom limbs evoked by vestibular caloric stimulation in amputees.

OBJECTIVE: Relationships between the vestibular system and the body schema have been suggested but never demonstrated in amputees. We studied the effects of vestibular stimulation on body representation in amputees focusing on the phantom limb phenomenon. METHOD: Prospective study in 31 amputated subjects of one or several limbs before the age of 16 years. The amputees underwent a caloric vestibular stimulation test, ipsilateral (n = 31) and contralateral (n = 8) to the side of amputation. Amputees were asked to report their perceptions spontaneously and to answer open questions. Four types of perceptions were analyzed: normal phantom, deformed phantom, painful phantom, and no phantom, before, during, and after the vestibular stimulation test. Data were compared between the two groups for pre- and post-test perceptions (chi2 test). RESULTS: Vestibular caloric stimulation provoked temporary perception of a normal phantom limb in 16 of 17 amputees who previously did not experience phantoms. For 12 of 12 amputees who currently experienced deformed or painful phantom limbs, caloric stimulation led to temporary replacement of the abnormal phantom with a non-painful normal phantom. CONCLUSIONS: The phenomena observed: 1) throw light on assumed mechanisms controlling construction of static and dynamic engrams used to produce the body schema; 2) complete the neuromatrix theory proposed to explain the phantom limb phenomenon; and 3) suggest that the vestibular system triggers the procedure of reconstruction of the global body schema.

Adult↗