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Biomedical subjects

L Michel

Publications and source records attributed to L Michel.

At least 37 records · Page 2Linked to original sources
PubMed2001

HLA-G and NK receptor are expressed in psoriatic skin: a possible pathway for regulating infiltrating T cells?

Recent data have suggested that in psoriasis, the T-infiltrating cells could be submitted to regulatory pathways, possibly through natural killer receptors. HLA-G binds to different natural killer receptors and is able to inhibit T-cell functions. Because this molecule is induced by interferon-gamma, a major cytokine in psoriasis, we asked whether HLA-G and its receptor might be expressed in this disease. Specific RNAs for HLA-G1 and HLA-G5 were consistently found in lesional skin specimens, soluble HLA-G5 transcripts being found only in psoriasis. HLA-G protein was found in all psoriatic sections, but never in normal skin controls. Double labeling demonstrated that HLA-G-positive cells were CD68(+), CD11c(+) macrophages. The NKR ILT2 was also present in psoriatic skin, the T CD4(+)-infiltrating cells expressing indeed ILT2. The demonstration of HLA-G and ILT2 expression in psoriatic skin suggests that this pathway may act as an inhibitory feed back aimed to down-regulate the deleterious effects of T-cell infiltrate in this disease.

Alternative Splicing↗
PubMed2001

UV-A irradiation induces a decrease in the mitochondrial respiratory activity of human NCTC 2544 keratinocytes.

UV-A irradiation caused a dose-dependent decrease in cellular oxygen consumption (56%) and ATP content (65%) in human NCTC 2544 keratinocytes, one hour after treatment. This effect was partially reversed by maintaining the irradiated cells in normal culture conditions for 24 h. Using malate/glutamate or succinate as substrates for mitochondrial electron transport, the oxygen uptake of digitonin-permeabilised cells was greatly inhibited following UV-A exposure. These results strongly suggest that UV-A irradiation affects the state 3 respiration of the mitochondria. However, under identical conditions, UV-A exposure did not reduce the mitochondrial transmembrane potential. The antioxidant, vitamin E inhibited UV-A-induced lipid peroxidation, but did not significantly prevent the UV-A-mediated changes in cellular respiration nor the decrease in ATP content, suggesting that these effects were not the result of UV-A dependent lipid peroxidation. UV-A irradiation also led to an increase in MnSOD gene expression 24 hours after treatment, indicating that the mitochondrial protection system was enhanced in response to UV-A treatment. These findings provide evidence that impairment of mitochondrial respiratory activity is one of the early results of UV-A irradiation for light doses much lower than the minimal erythemal dose.

Adenosine Triphosphate↗
PubMed2000

Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions.

Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.

Administration, Oral↗
PubMed2000

Humoral and cellular responses to histamine and pollen allergen in a skin chamber model: effect of mizolastine.

BACKGROUND: Mizolastine is a new non-sedative antihistamine and antiallergic drug proven to be effective and safe in the treatment of allergic rhinitis and urticaria. OBJECTIVE: To quantitatively explore the time course of mediator release and cell recruitment during allergen challenge and the effects of mizolastine on the event, using the skin chamber model. METHODS: Twelve pollen-sensitive patients (23+/-6 years) were included in a double-blind crossover study. Patients received 10 mg mizolastine or placebo once daily in the first 4-day period and, after a 3-week washout period, vice-versa in the crossover period. On day 4 of each period, a non-invasive in vivo skin chamber technique was used to determine the alteration of vascular permeability, mast cell mediator release, the release of soluble intercellular adhesion molecule -1(sICAM-1) in skin sites challenged with exogenous histamine or grass pollen allergen extract, over an 8-hour period. RESULTS: Challenge with allergen-induced significant mast cell activation, as indicated by the release of histamine, tryptase and LTC4, in chamber fluids 2 hours after initiation of the allergic reaction and during the following 6 hours. Both exogenous histamine and allergen induced significant vasodilatation, which was sustained during the 8-hour challenge, as indicated by the accumulation of protein in the chamber fluids. Likewise, both histamine and allergen induced the release of significant amounts of ICAM-1 throughout the 8-hour period. Mizolastine significantly inhibited the histamine- and allergen-induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2 hours, P = .044; after 8 hours, P = .003 respectively) and the histamine- and allergen-induced--ICAM-1 release (after 2 hours, P = .004; after 8 hours, P = .05; after 2 hours, P = .03 respectively). CONCLUSION: Mizolastine strongly inhibited the local response to histamine in this skin chamber model with, of interest, inhibition of the release of the soluble adhesion-molecule ICAM-1.

Adolescent↗
PubMed1999

Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis.

Caryophyllene oxide, an oxygenated terpenoid, well known as preservative in food, drugs and cosmetics, has been tested in vitro as an antifungal against dermatophytes. Its antifungal activity has been compared to ciclopiroxolamine and sulconazole, commonly used in onychomycosis treatment and chosen because of their very different chemical structures. So, a new model has been tested, utilizing sheep hoof plates in order to simulate human nails, which are almost unobtainable for in vitro tests. Three protocols were utilized: pre-treatment, simultaneous treatment and post-treatment. Among these, the post-treatment method was the best to simulate antifungal therapy, as it permitted testing and comparing the efficiency of different antifungal drugs.

Animals↗
PubMed1999

Laparoscopic adrenalectomy for phaeochromocytoma: endocrinological and surgical aspects of a new therapeutic approach.

OBJECTIVES: To evaluate the results of laparoscopic resection of phaeochromocytoma with a focus on pre- and intra-operative endocrinological and pharmacological aspects. DESIGN: Retrospective study based on review of case notes and intraoperative anaesthetic records. PATIENTS: Eight patients (four men, four women) aged 13 to 70 (median: 45) years with symptomatic phaeochromocytoma (two patients with MEN IIa syndrome) diagnosed 6-36 months before adrenalectomy in four patients and just before operation in the four remaining patients. All patients presented with hypertension. MEASUREMENTS: Pre- and postoperative blood pressure (BP) was assessed using a sphygmomanometer, intraoperative measurements being obtained by intra-arterial line. Adrenaline (A), noradrenaline (NA), metadrenaline (metA), normetadrenaline (normetA) and vanillylmandelic acid (VMA) were measured in 24-h urine samples. Adrenal imagery consisted in all patients of abdominal computed tomography and [131I] metaiodobenzylguanidine (MIBG) scintigraphy, and in 2 patients, adrenal magnetic resonance imaging and octreotide scintigraphy. Determination of plasma volume was performed by isotopic method. RESULTS: Median (range) preoperative systolic and diastolic BP was 140 (130-240) and 90 (80-150) mm Hg, respectively. Predominant catecholamine secretion consisted of A in four patients (A pattern) and of NA (NA pattern) in the other four. Tumours smaller than 30 mm usually secreted A while larger ones secreted NA. Pre- and intra-operative BP control was straightforward in all but two patients with preferential NA secretion. The median number of systolic and diastolic BP peaks were higher in patients with NA pattern (n = 6, range: 3-9) than in those with A pattern (n = 1.5, range: 1-6). Total duration of pneumoperitoneum ranged from 120 to 240 (median: 195) min. Intra- and post-operative complications included intra-abdominal bleeding, laparoscopically controlled (in one case), and upper pole kidney ischaemia in another. Postoperative hospital stay ranged from 4 to 11 days. All patients were asymptomatic postoperatively and pharmacologically controlled hypertension persisted in two of them. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and efficient technique to remove phaeochromocytoma in terms of intra- and postoperative morbidity, with a low complication rate. Pre- and intra-operative pharmacological blood pressure control is as effective as in conventional adrenalectomy, with greater instability in noradrenaline secreting tumours.

Adolescent↗
PubMed1999

Contact allergens, but not irritants, alter receptor-mediated endocytosis by human epidermal Langerhans cells.

Allergic contact dermatitis is a T-cell-mediated inflammation, induced by contact with sensitizers and occurring through the release of epidermal cytokines and the activation of epidermal Langerhans cells (LCs). The aim of this study was to analyse early events of LC activation induced either by contact allergens or by irritants devoid of any contact allergenic properties. in order to obtain an in vitro method to discriminate between these two groups of molecules. Various contact sensitizers and irritants were studied for their effects on the endocytosis of major histocompatibility complex class II (MHC-II) molecules by freshly-isolated human epidermal LCs. As observed by flow cytometry, a spontaneous decrease in the surface expression of MHC-II (HLA-DR) molecules, linked to spontaneous internalization of the MHC-II molecules by LCs, was obtained by moving freshly-isolated LCs from 4 degrees C to 37 degrees C. Pre-incubation of LCs with either sensitizers or irritants increased the spontaneous internalization of HLA-DR molecules with a similar magnitude, but no clear discrimination between sensitizer and irritant effects was obtained by flow cytometry analysis. In contrast, confocal microscopy enabled discrimination between the effects of sensitizers and irritants: sensitizer-treated samples showed internalized HLA-DR molecules aggregated in large vesicles with very bright fluorescence; irritant-treated samples were not different from untreated controls and showed compact HLA-DR molecules in small vesicles with diffuse fluorescence, and mostly localized in the submembranous zone. Electron microscopy demonstrated that sensitizer-treated LCs internalized HLA-DR molecules preferentially in lysosomes collected near the nucleus, whereas the irritant-treated and non-treated LCs internalized these molecules in the prelysosomes only near the cell membrane. We conclude that contact allergens and irritants induce distinct patterns of HLA-I)R endocytosis, which may be useful for the development of in vitro screening tests.

Adult↗
PubMed1999

Heart failure induced by pheochromocytoma: laparoscopic treatment and intraoperative changes of several new cardiovascular hormones.

Since 1992, adrenalectomy for pheochromocytoma has been recognized as a safe and efficient technique when performed by a laparoscopic approach. Most of the cases of pheochromocytomas treated as such and published in the literature were not associated with malignant hypertension and acute heart failure. We report the case of a 23-year-old woman who presented with this clinical picture and show that laparoscopic adrenalectomy may be as safe and efficient as conventional adrenalectomy when performed in this situation. The intraoperative changes in the secretion of catecholamines, endothelin-1, angiotensin II, N- and C-terminus of atrial natriuretic factor prohormone were also analyzed. Noradrenaline release during tumor dissection was associated with a stimulation of atrial natriuretic factor.

Adrenal Gland Neoplasms↗
PubMed1998

Angiosarcoma of the thyroid and concurrent hyperthyroidism.

We describe the exceptional association of an angiosarcoma of the thyroid and hyperthyroidism in a 74-year-old woman who presented with a toxic multinodular goiter of recent growth. This association reported in two other cases may not be fortuitous but due a vascular effect of the angiosarcoma contributing to the development of thyrotoxicosis. This case also illustrates the diagnostic difficulties and the poor prognosis of this tumor.

Aged↗
PubMed1998

Cognitive skill learning and schizophrenia: implications for cognitive remediation.

The ability to acquire a motor and cognitive skill was investigated in 26 patients with schizophrenia and 26 normal participants using repeated testing on the Tower of Toronto puzzle. Seven patients with defective performance were retested using additional trials and immediate feedback designed to facilitate problem solving. A component analysis of performance was used based on J. R. Anderson's (1987) model of cognitive skill learning. Patients exhibited a performance deficit on both motor and cognitive skills. However, their acquisition rate was similar to that of normal participants on most parameters, indicating that skill learning suffered little or no impairment. Performance deficit was accounted for by poor problem-solving ability, explicit memory, and general intellectual capacities. It was remediable in some, but not all, patients. Remediation failure was also related to severe defects of cognitive functions.

Adult↗
PubMed1997

Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line.

The human immature K562 erythroid cell line was studied for its capacity to produce and to metabolize the phospholipid molecule platelet-activating factor (PAF). K562 cells produced PAF under calcium ionophore stimulation. Lyso PAF and acetyl-CoA (the acetate donor molecule for the acetylation of lyso PAF into PAF) had no effect on the amounts of PAF produced by ionophore-stimulated cells. The metabolism of PAF and lyso PAF by K562 cells was compared to that of freshly-isolated human bone marrow erythroblasts and blood erythrocytes. K562 cells rapidly metabolized [3H]PAF and [3H]lyso PAF with 1-alkyl analogue of phosphatidylcholine as the major metabolic product. In contrast, blood erythrocytes did not. PAF acetylhydrolase activity levels in K562 cells and bone marrow erythroblasts were similar and higher than in blood erythrocytes. PAF (1-100 nM) stimulated [3H]thymidine incorporation in K562 cells grown in low serum concentration, a non-metabolizable PAF agonist being more potent than PAF to stimulate thymidine incorporation. PAF receptor mRNA was detected in K562 cells by polymerase chain reaction on reverse transcripts. The present study demonstrates that K562 cells produce and metabolize PAF and underlines the putative role of erythroid precursors in the modulation of bone marrow PAF concentrations. The effect of PAF on the growth of K562 cells might be mediated through PAF receptors suggesting a potential role of PAF on the proliferation and functions of human erythroid marrow precursors.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Acquisition of granzyme B and Fas ligand proteins by human keratinocytes contributes to epidermal cell defense.

In vertebrate tissues, cell integrity is maintained by at least three mechanisms. During an immune response, injured cells are eliminated by cytotoxic lymphoid cells that produce perforin, granzyme B, and Fas ligand (FasL). Second, epithelial cells can produce FasL as an immunosuppressive protein, probably to protect the tissue against immune-mediated damage. Third, locally secreted antimicrobial peptides can be operative in the protection of animal and human epithelia. In this work, as another contribution to local mechanisms of host defense, the ability of human epidermal keratinocytes to produce cytotoxic proteins was investigated. To address this question, freshly isolated human epidermal cells and keratinocytes grown in vitro were studied. Freshly isolated epidermal cells did not express the cytolytic proteins. In contrast, keratinocyte growth to confluence was associated with granzyme B, perforin, and FasL mRNA and protein synthesis. These proteins were secreted in the culture medium. Further analysis showed that they were identical with the ones used by cytotoxic lymphocytes. Their function was then investigated with a view to a potential role in epidermal cell integrity. The data showed that activated human keratinocytes were able to protect against invading pathogens through granzyme B expression. This was demonstrated by the ability of granzyme B to greatly decrease the bacterial growth of Staphylococcus epidermidis. In addition, keratinocytes expressing FasL were found to prevent immune epidermal cell damage. Apoptosis of Fas-sensitive T cells occurred during coculture with confluent epidermal keratinocytes and was largely reduced by the addition of a FasL inhibitor. The data favor keratinocyte involvement in the regulation of dermal inflammatory responses.

Apoptosis↗
PubMed1997

Urokinase localization and activity in isolated eosinophils.

Urokinase-type plasminogen activator is implicated in cell invasion and migration. In this study, we provide evidence for the presence of urokinase-type plasminogen activator (3.5 +/- 1.5 ng/mg of cell protein) in isolated peripheral blood eosinophils, in comparison to 6.7 +/- 2.3 ng/mg of protein in neutrophils. Both immunocytochemical and immunogold staining of urokinase-type plasminogen activator on electron microscopy showed its localization in granules of resting cells. Mild stimulation by platelet-activating factor induced a translocation of urokinase-type plasminogen activator from the granules to the cell membrane and a formation of urokinase-type plasminogen activator capping, suggesting a role for urokinase-type plasminogen activator in eosinophil migration. The activation of eosinophils led to the release of factor(s) which, after activation of pro-urokinase-type plasminogen activator, induced an inactivation of generated urokinase-type plasminogen activator. Our results suggest that urokinase-type plasminogen activator is implicated in activated eosinophils invasiveness because the exposure of urokinase-type plasminogen activator is regulated both in space and time.

Biological Transport, Active↗
PubMed1997

Multicentric experience of the Belgian Group for Endoscopic Surgery (BGES) with endoscopic adrenalectomy.

BACKGROUND: Adrenalectomy is not a frequent operation. Therefore the newly developed laparoscopic approach is sporadically performed by surgeons dealing with endocrine disorders. METHODS: Some 54 videoendoscopic adrenalectomies performed on 52 patients by five surgical teams between October 1993 and December 1996 were prospectively evaluated. RESULTS: Indications for endoscopic adrenalectomy were pheochromocytoma (n = 17), primary hyperaldosteronism (n = 15), Cushing's adenoma or disease (n = 7), nonsecreting adenoma (n = 7), single metastasis from adenocarcinoma (n = 2), adenoma with dehydroepiandrostenedione (DHEAS) hypersecretion (n = 3), and ACTH-secreting metastases from a thymoma (n = 1). Of the 54 adrenalectomies performed, 31 were of the left gland, 19 of the right and two bilateral. Laparoscopic adrenalectomy was successful in 50 patients (96%). Median tumor size was 4 cm (range 1.5-12), median operation duration was 80 min (range 59-360), and median postoperative stay was 4 days (range 2-13). One patient required blood transfusion. CONCLUSIONS: Endoscopic adrenalectomy can safely be performed-even sporadically-by surgeons well versed in adrenalectomy techniques for endocrine disorders and trained in endoscopic surgery.

Adenoma↗
PubMed1996

Protein tyrosine kinases in activation signal of human basophils through the immunoglobulin E receptor type l.

Human basophils activated through high-affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) are involved in the late phase of the allergic reaction. To investigate the possible involvement of protein-tyrosine kinases in this activation we used human acute basophilic leukemia (ABL) cells in culture as well as a pure population of normal basophils in vitro-derived from human bone marrow precursor cells (HBMB). ABL cells were 50-80% basophils at various stages of maturation as assessed by staining, morphology, ultrastructure, and flow cytometry analysis, and only basophils in ABL cells expressed Fc epsilon RI. Aggregation of Fc epsilon RI by IgE and anti-IgE, IgE and antigen, or anti-Fc epsilon RI monoclonal antibodies on ABL cells or on HBMB, led to increased tyrosine phosphorylation of 120-, 100-, 80-, 72-, 50- to 65-, and 38-kDa substrates. Tyrosine phosphorylations in ABL cells were in basophils because 1) they were detected after a 5-s stimulation, 2) they were observed under conditions where mediator release is minimal, i.e., in the absence of extracellular calcium, 3) hapten addition during antigen stimulation resulted in almost total disappearance of tyrosine phosphorylations within 30 s. There was correlation between histamine release and tyrosine phosphorylation in anti-IgE dose-responses and in dose-responses of the tyrosine kinase inhibitor genistein. The tyrosine kinase p72syk was detected in the cells. Stimulation of ABL cells for 1 min resulted in extracellular calcium-independent tyrosine phosphorylation and activation of p72syk. Therefore, tyrosine kinases are involved in the early steps of human Fc epsilon RI signaling in basophils. Tyrosine kinases and their substrates could represent new potential therapeutic targets to prevent the development of the allergic reaction.

Aged↗
PubMed1996

[Acute left-side appendicitis: diagnostic contribution of tomodensitometry].

BACKGROUND: Some cases of left-sided appendicitis related to malrotation or situs inversus have been reported. Another type of left-sided appendicitis is reported. CASE REPORT: A 9 year-old boy was admitted suffering from a 2-day history of severe left-sided abdominal pain of the lower quadrant with fever at 38 degrees C. He presented abdominal tenderness and guarding, maximal in the left lower quadrant. His leukocyte count was 22,000/mm3. Ultrasonography showed a digestive tubular structure with thick walls in the left lower quadrant. CT scan revealed a dilated right-sided appendix with localized perforation, whose extremity was located in the left lower quadrant along the lateral wall. The diagnosis was confirmed by median laparotomy. CONCLUSION: Left-sided appendicitis can also be related to a dilated right appendix with its extremity in the left lower-quadrant near the lateral wall. CT scan can then be helpful for diagnosis when ultrasonography remains unconclusive.

Appendicitis↗