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Biomedical subjects

Philippe Bernard

Publications and source records attributed to Philippe Bernard.

At least 19 recordsLinked to original sources
PubMed2006

Elastin fragments induce IL-1beta upregulation via NF-kappaB pathway in melanoma cells.

In a previous work, we reported the influence of elastin fragments (EFs) on matrix metalloproteinases-2 and -14 expression and activation in melanoma cells in vitro. We hypothesized that EFs might also modulate expression of other mediators involved during melanoma progression. Therefore we investigated the contribution of EFs on IL-1beta expression, a cytokine playing a key role in melanoma cells activation. Our results evidenced that high tumorigenic melanoma cells (M3Da cells) treated with EFs led to IL-1beta mRNA and protein upregulation. The effects of EFs on M3Da cells were found to be mediated by receptor (spliced galactosidase) occupancy, as being suppressed by lactose and reproduced by cell stimulation with the VGVAPG peptide. Binding of EFs to their receptor induced a rapid activation of extracellular signal-regulated kinase 1/2; and p38 mitogen-activated protein kinase pathways. However, these pathways were not associated with IL-1beta mRNA upregulation by EFs. Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs-mediated IL-1beta mRNA overexpression. These results demonstrate that EFs induce NF-kappaB activation, leading to IL-1beta upregulation in invasive melanoma cells.

Base Sequence↗
PubMed2005

Discriminating nevus and melanoma on paraffin-embedded skin biopsies using FTIR microspectroscopy.

FTIR microspectroscopy, in combination with cluster analysis, has been used to characterise skin tissues, in order to discriminate cancerous from non-cancerous ones. The main objective of this in vitro study was to demonstrate the applicability of infrared spectral imaging to separate, on paraffinised biopsies, pigmented nevi (benign skin lesions) from melanomas (malignant skin lesions). Infrared spectra were collected from paraffin-embedded samples of nevi and melanomas, without deparaffinisation. Despite the important contribution of the paraffin in these spectra, it was possible to find meaningful and discriminating spectral regions. Spectral imaging was first performed to localize different skin layers (dermis and epidermis). Spectra extracted from the images were subjected to hierarchical classification algorithm, which allowed the discrimination of melanomas from the nevi, using selected spectral windows that correspond to vibrations of DNA and melanin content. The diversity of skin lesions and direct accessibility to the skin make this organ an interesting field of investigation using this technique.

Biopsy↗
PubMed2005

Amyloid arthropathy and Waldenström macroglobulinemia.

Amyloid arthropathy occurs chiefly as a manifestation of beta(2) microglobulin amyloidosis in patients receiving chronic hemodialysis. AL amyloidosis complicating multiple myeloma is a less common cause. Amyloid arthropathy is exceedingly rare in patients with Waldenström macroglobulinemia. We report a case characterized by lymphoplasmocytoid malignancy with monoclonal IgM production and amyloid arthropathy manifesting as bilateral symmetric polyarthritis. A synovial membrane biopsy established the diagnosis. Chemotherapy was effective in alleviating the joint manifestations. Joint symptoms in patients with monoclonal gammopathies, including those characterized by IgM secretion, should suggest amyloid arthropathy. Treatment of the blood disease may improve the joint symptoms.

Aged↗
PubMed2005

Elastin-derived peptides induce a T-helper type 1 polarization of human blood lymphocytes.

OBJECTIVE: Increased level of elastin-derived peptides (EDPs) is observed in the serum of patients with manifestations of arterial diseases. We here investigated whether EDPs might exert, at systemic level, a regulatory role for the T-helper type 1 (Th-1)/Th-2 cellular immune response by human peripheral blood lymphocytes (PBLs) expressing the spliced-galactosidase (S-gal)-elastin receptor. METHODS AND RESULTS: Using flow cytometry and Western blot analysis, we demonstrated that EDPs led to an activation of the S-gal-elastin receptor associated with cytokine production on PBLs and CD4+ T cell subpopulations. The constitutive expression of the S-gal-elastin receptor at the surface of human PBLs was upregulated at the mRNA (RT-PCR) and protein (ELISA) levels on cell activation. In nonactivated and phytohemagglutinin-activated conditions, expressions of the predominant Th-2 cytokine interleukin-5 (IL-5) and IL-10 were reduced, whereas those of the major Th-1 cytokines interferon-gamma and IL-2 were enhanced by EDPs. Furthermore, we evidenced that EDPs could not only potentiate the IL-12-induced Th-1 profile but also could reverse the Th-2 (over Th-1) profile induced by IL-4. Finally, Th-1 cytokine upregulation was associated to an increased activator protein-1 DNA binding and enhanced pro-matrix metalloproteinase-9 secretion. CONCLUSIONS: This study highlights the importance of EDPs as stimuli for Th-1 differentiation, whether T cells are in an inactivated state or already orientated toward a Th-1 (IL-12) or Th-2 (IL-4) response.

Cell Differentiation↗
PubMed2005

Optimization and validation of a docking-scoring protocol; application to virtual screening for COX-2 inhibitors.

To exploit available structural information about the cyclooxygenase enzyme for the virtual screening of large chemical libraries, a docking-scoring protocol was tuned and validated. The screening accuracy was assessed using a series of known inhibitors and a set of diverse a priori inactive compounds that was seeded with known active ligands. The major parameters of the DOCK algorithm were investigated. A large improvement of the results was obtained on tweaking some of them. The generated complexes were rescored using six scoring functions. In this way, the striking importance of this step was demonstrated, as well as the good performances of DOCK energy and SCORE for this target. The results were further improved via a consensus approach. As a first application, a subset of a large compound library was screened using this protocol. Among the compounds that were selected for biological testing, a third of them turned out to have a significant enzyme inhibition.

Crystallography, X-Ray↗
PubMed2005

Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study.

OBJECTIVE: To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides while increasing cutaneous tolerance. DESIGN: Prospective nonrandomized study conducted from November 1999 to November 2002. SETTING: Eleven university or hospital dermatology departments in France. PATIENTS: Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5). INTERVENTIONS: Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period. MAIN OUTCOME MEASURES: The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response. RESULTS: Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months. CONCLUSIONS: A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.

Administration, Topical↗
PubMed2005

Hearing thresholds and tympanic membrane sequelae in children managed medically or surgically for otitis media with effusion.

OBJECTIVE: To determine the long-term effects of ventilation tube insertion on hearing thresholds and tympanic membrane pathologic abnormalities in children with otitis media with effusion. DESIGN: Prospective cohort study. SETTING: Tertiary care children's hospital, otorhinolaryngology and audiology service. PARTICIPANTS: Patients aged 8 to 16 years who participated in a randomized controlled trial of medical vs surgical (ventilation tube [VT]) treatment for recurrent otitis media with effusion at ages 2.5 to 7 years. MAIN OUTCOME MEASURES: Hearing thresholds and tympanic membrane sequelae. METHODS: One hundred thirteen of 125 children who had participated in the trial underwent blinded audiometric, tympanometric, otomicroscopic, and parental questionnaire evaluation 6 to 10 years following the trial. Thirty of 57 [corrected] medical subjects received ventilation tubes and 18 of 56 [corrected] VT subjects received more than 1 set of tubes. To evaluate sequelae risk associated with ventilation tubes independent of disease severity, we compared 27 medical subjects who never received ventilation tubes and 38 subjects randomized to VT who only received 1 set of tubes. RESULTS: Tympanic membrane pathologic abnormalities were present in 81% of VT subjects and 19% of medical subjects (relative risk, 4.4; 95% confidence interval, 2.2-9.9). Hearing thresholds were 2.1 to 8.1 dB higher in subjects treated with tubes (P = .005). CONCLUSIONS: In children who were candidates for ventilation tube insertion randomly assigned to receive medical or VT treatment for otitis media with effusion, elevated hearing thresholds and tympanic membrane pathologic abnormalities were more common in VT subjects 6 to 10 years after insertion.

Adolescent↗
PubMed2005

Reverse pharmacognosy: application of selnergy, a new tool for lead discovery. The example of epsilon-viniferin.

The aim of reverse pharmacognosy is to find new biological targets for natural compounds by virtual or real screening and identify natural resources that contain the active molecules. To demonstrate the applicability of this concept, we report here a study on epsilon-viniferin, an active ingredient for cosmetic development. Nevertheless, this natural substance is weakly defined in terms of biological properties. SELNERGY, an inverse docking computer software, was used to identify putative binding biological targets for epsilon-viniferin. Among the 400 screened proteins two targets were retained. For cosmetic application, cyclic nucleotide phosphodiesterase 4 (PDE4) was the most interesting candidate. Moreover, other PDE subtypes (1, 2, 3, 5 and 6) were not retained, indicating a selectivity for PDE4. The experimental binding tests on the 6 subtypes of PDE revealed a significant selectivity of epsilon-viniferin for the PDE4 subtype. This selectivity was confirmed by evaluation of epsilon-viniferin on the secretion of TNF-alpha and Interleukin-8. Our data demonstrated that epsilon-viniferin possesses anti-inflammatory properties by inhibiting PDE4 subtype. In conclusion, reverse pharmacognosy and its inverse docking component cannot only be integrated into a program for new lead discovery but is also a useful approach to find new applications for identified compounds.

Benzofurans↗
PubMed2005

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗
PubMed2004

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Adult↗
PubMed2004

Stromal reaction in cutaneous melanoma.

Cutaneous melanoma is a highly malignant tumor type which is characterized by its tendency to give rise to metastases. Stromal relationships are essential for growth and metastasis of solid tumors. In cutaneous melanoma, microscopic level of invasion (Breslow index), overall architecture of cells (horizontal or vertical growth phase), angiogenesis, vessel invasion are morphological features which may carry prognostic significance. As demonstrated by in vivo studies, stromal reaction in melanoma is mainly characterized by collagen and elastin proteolysis preferentially localized around the tumor at the invasive front along with variable angiogenesis and lymphocyte infiltration. On the basis of recent findings, it becomes increasingly evident that resident stromal cells (fibroblasts, endothelial cells) are implicated in the metastatic process, including proliferation, matrix degradation, or migration of melanoma cells through cell-cell cross-talk by soluble factors (proteases, cytokines, growth factors) or by direct contact.

Disease Progression↗
PubMed2004

RS3PE revealing recurrent non-Hodgkin's lymphoma.

A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin's malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed.

Aged↗
PubMed2004

Osteoarticular complications of erysipelas.

BACKGROUND: Rare osteoarticular complications occurring after erysipelas have been reported. We describe 9 patients in whom various osteoarticular complications developed during erysipelas. OBJECTIVE: We sought to analyze osteoarticular complications during erysipelas, paying special attention to clinical, bacteriologic, and radiologic data. METHODS: Data were retrospectively recorded from the files of patients seen in 3 dermatologic centers between 1998 and 2000. They included laboratory tests, bacteriologic cultures, radiologic investigations, and treatment modalities and outcome of both erysipelas and osteoarticular complications. RESULTS: We observed 9 patients (7 men and 2 women; mean age 49.6 years) who first presented with typical erysipelas of the lower limb and then osteoarticular complications developed during the course of their disease, always localized to a joint contiguous to the erysipelas plaque. These complications included: relatively benign complications, ie, bursitis (n = 5) or algodystrophy (n = 1), occurring after erysipelas with favorable course; and more severe complications, ie, osteitis (n = 1), arthritis (n = 1), and septic tendinitis (n = 1), occurring after erysipelas characterized by local cutaneous complications (abscess, necrosis). CONCLUSIONS: Osteoarticular complications of erysipelas can be divided into the 2 groups of nonseptic complications (mainly bursitis), which are characterized by a favorable outcome, and septic complications (osteitis, arthritis, tendinitis), which require specific, often prolonged treatment and, sometimes, operation. Their diagnosis is on the basis of clinical and radiologic findings rather than joint aspirations, which are usually not possible through infected skin tissue.

Adult↗
PubMed2004

Cutaneous malignant melanoma and neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well.

Adult↗
PubMed2004

BP230- and BP180-specific auto-antibodies in bullous pemphigoid.

Bullous pemphigoid is a subepidermal blistering disease associated with auto-antibodies (auto-ab) to BP180 and BP230. We developed ELISAs utilizing baculovirus-encoded recombinant proteins of BP230 and BP180 and studied their diagnostic and prognostic values by assessing the profile of the auto-ab response in 127 patients with BP. 39 patients had focal involvement, whereas 88 had generalized disease; 51 individuals served as controls. The results indicate: (1) BP180 IgG reactivity was associated with an overall sensitivity of 0.953 and specificity of 0.940; (2) 105 of 127 BP patients also displayed BP230 auto-reactivity, the global diagnostic performance of which, however, was moderate compared to BP180-auto-reactivity (sensitivity 0.815 vs 0.953, specificity 0.648 vs 0.940); (3) 101 patients (79.5%) had concordant BP180 and BP230 reactivity; (4) the association between the presence of BP230 auto-reactivity and focal involvement was stronger than in generalized disease (odds ratio (OR) 17.7 vs 10.2), independently from BP180 auto-ab profile; (5) correlation of total IgG with IgG1 and IgG4 was variable for both BP180 and BP230. Collectively, the global diagnostic properties of the BP180-ELISA outperform those of the BP230-ELISA. Presence of BP230 auto-reactivity, however, supports the diagnosis of BP and might be indicative for the extent of the disease.

Adult↗