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Biomedical subjects

Louis Dubertret

Publications and source records attributed to Louis Dubertret.

45 records · Page 3Linked to original sources

Peripheral blood lymphocyte subset counts in patients with dermatomyositis: clinical correlations and changes following therapy.

Lymphocytopenia has been reported in patients with connective tissue diseases, including dermatomyositis (DM). However, the risk of infectious complications and the changes of lymphocytic subsets during treatment have been poorly investigated in these patients. We investigated the alterations of peripheral blood lymphocyte counts in patients with DM. A retrospective analysis was conducted in patients with an ascertained diagnosis of DM admitted from 1994 to 2000 in both departments of Dermatology of the Saint-Louis Hospital in Paris. All patients had a peripheral blood absolute lymphocyte count available before therapy. From an initial set of 63 patients, 47 were included in the study. The median absolute lymphocyte count was 888/mm(3) (range, 400-4,070). Low peripheral blood CD4+ and CD8+ T-cell and B-cell counts were consistent findings (median CD4+: 382/mm(3); CD8+: 211/mm(3); CD19+: 122/mm(3)). There was a significant increase in lymphocyte count after 1 month (p < 0.0001), 3-6 months (p = 0.001), and 6-12 months (p = 0.0005) of corticosteroid treatment. Infectious events, mainly pneumonia (PCP), occurred in 12 patients. Their initial lymphocyte count was lower than that of patients who did not develop infections (p = 0.0001). These results support the high prevalence of lymphocytopenia in patients with DM and emphasize the risk for opportunistic infections, mainly PCP, in these patients. Further studies are warranted to evaluate the risk/benefit balance of PCP prophylaxis in patients with DM and severe lymphocytopenia.

Adolescent↗

Modulation of gene expression induced in human epidermis by environmental stress in vivo.

Environmental insults on the skin induce biologic responses through the modulation of expression of genes implicated in different cell functions. The aim of this study was to investigate the modulation of gene expression profile in human epidermis in vivo following different stresses. We determined the modulations of gene expression using cDNA macroarray in the epidermis of 28 healthy volunteers, following mild and physiologic insults, including: (1), tape stripping; (2) application of 10% sodium dodecyl sulfate; (3) daily application of vaseline; and (4), exposure to one minimal erythema dose of solar-simulated radiation. The analysis was performed 19 h after treatment. The reverse transcription-polymerase chain reaction method was used to confirm our results. We showed that: (1) the intensity of gene modulation was variable among the volunteers following the same skin stress; (2) the nature and intensity of skin treatment modified the pattern of gene expression; and (3) some genes were modulated only by specific stress, some others are modulated irrespective of the stress. GADD45, Bax, SAS, and granulocyte chemotactic protein-2 were overexpressed exclusively following solar-simulated radiation, whereas tape stripping led to the modulation of genes implicated in different pathways (inflammation, cell proliferation, cell differentiation, detoxification, etc.). Concerning common gene modulation, MRP8 and MRP14 were highly upregulated in human skin epidermis after solar-simulated radiation, vaseline application or tape stripping, and to a lower extent after sodium dodecyl sulfate. Such upregulation of the MRP 8/14 genes was confirmed at the protein level in an ex-vivo skin culture model following tape stripping and solar-simulated radiation. Together, these results suggest that MRP8 and MRP14 may be general, yet highly sensitive, markers for a great variety of skin stresses and that they are implicated in several epidermal repair pathways.

Adult↗

p38 mitogen-activated protein kinase activation by ultraviolet A radiation in human dermal fibroblasts.

UVA radiation penetrates deeply into the skin reaching both the epidermis and the dermis. We thus investigated the effects of naturally occurring doses of UVA radiation on mitogen-activated protein kinase (MAPK) activities in human dermal fibroblasts. We demonstrated that UVA selectively activates p38 MAPK with no effect on extracellular-regulated kinases (ERK1-ERK2) or JNK-SAPK (cJun NH2-terminal kinase-stress-activated protein kinase) activities. We then investigated the signaling pathway used by UVA to activate p38 MAPK. L-Histidine and sodium azide had an inhibitory effect on UVA activation of p38 MAPK, pointing to a role of singlet oxygen in transduction of the UVA effect. Afterward, using prolonged cell treatments with growth factors to desensitize their signaling pathways or suramin to block growth factor receptors, we demonstrated that UVA signaling pathways shared elements with growth factor signaling pathways. In addition, using emetine (a translation inhibitor altering ribosome functioning) we detected the involvement of ribotoxic stress in p38 MAPK activation by UVA. Our observations suggest that p38 activation by UVA in dermal fibroblasts involves singlet oxygen-dependent activation of ligand-receptor signaling pathways or ribotoxic stress mechanism (or both). Despite the activation of these two distinct signaling mechanisms, the selective activation of p38 MAPK suggests a critical role of this kinase in the effects of UVA radiation.

Cells, Cultured↗

A prospective study on the evolution of the T-cell repertoire in patients with Sézary syndrome treated by extracorporeal photopheresis.

Sézary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4(+) T cells. Extracorporeal photochemotherapy may induce a transient improvement of the clinical signs, but its efficiency is discussed. To investigate the frequency of the T-cell clone in the peripheral blood of patients with Sézary syndrome and to monitor its evolution in patients treated using extracorporeal photopheresis or chemotherapy, we used the immunoscope technique. In one patient, we observed a decrease of the relative frequency of the clone from 15.6% to 0%, paralleling a complete remission of the clinical disease and a disappearance of the circulating Sézary cells. In the other cases, the evolution of the relative frequency paralleled the initial improvement of the clinical status and the absence of long-term efficiency in patients treated with extracorporeal photopheresis or chemotherapy. We observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on the T-cell clone. The immunoscope technique appears to be an efficient tool to appreciate the amount of tumoral cells and to monitor the evolution of the clonal component in the Sézary syndrome.

Aged↗

B-cell lymphomas involving the skin associated with hepatitis C virus infection.

BACKGROUND: A role for hepatitis C virus (HCV) infection has been suggested in the pathogenesis of non-Hodgkin lymphomas (NHL). AIM: To evaluate the characteristics of cutaneous lymphomas occurring in HCV-infected patients, and to investigate the hypothesis of a direct infection of malignant cells. METHODS: Three patients showing a positive serology for HCV and a cutaneous lymphoma were studied. Analysis of HCV replication was performed using reverse transcriptase-polymerase chain reaction. The presence of HCV RNA was also assessed in biopsies from lesional skin and in a lymph node in one case. Genotype characterization was carried out on the basis of LiPA genotyping assays using viral genomic amplification products. RESULTS: Cutaneous NHL occurred in patients with chronic and replicative HCV infection, and exhibited a B-cell phenotype (one diffuse large B-cell lymphoma, one follicular lymphoma, and one marginal zone B-cell lymphoma). All patients were male; two of them were former intravenous drug abusers, while the HCV contamination route was unknown in the third. The search for HCV RNA in the skin and in lymph nodes yielded negative results. HCV genotypes were 1b in two cases and 3a in one case. CONCLUSION: These results show that a subset of B-cell cutaneous NHL is associated with a replicative HCV infection and suggest that HCV is not involved in lymphomagenesis through a direct infection of malignant cells. The ability of HCV to trigger a chronic B-cell lymphoproliferation could represent another mechanism, while a fortuitous association cannot be excluded.

Adult↗

Paraneoplastic acral vascular syndrome: epidemiologic features, clinical manifestations, and disease sequelae.

BACKGROUND: Acral vascular syndromes associated with malignancy have rarely been reported. OBJECTIVE: Our purpose was to assess the clinical and evolving features of paraneoplastic acral vascular syndromes. PATIENTS AND METHODS: Two cases of paraneoplastic gangrene are described and analyzed together with previously reported cases identified by a MEDLINE search. RESULTS: Among the 68 patients identified, 40 had gangrene, 16 had acrocyanosis, and 12 had Raynaud's phenomenon. The male to female ratio was 0.89; median age was 59 years. Fingers were affected in 94%. Adenocarcinomas were the predominant associated malignancies (41%), and metastases were observed in 41%. The acral vascular syndromes in 48% of the patients definitively regressed after tumor treatment. Forty-four percent of the patients died within 2 years. A favorable cutaneous outcome was obtained with prostacyclin infusions in 6 patients. CONCLUSION: A neoplastic origin of acral vascular syndrome should be considered in elderly patients, especially men, in the absence of usual causative conditions.

Aged↗

The use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens.

We compared the efficacy and safety of lymecycline 300 mg od vs lymecycline 150 mg bid or placebo in the treatment of moderate to severe acne. 271 patients received either oral lymecycline 300 mg od + placebo od, lymecycline 150 mg bid, or placebo bid, for 12 weeks. Reduction in inflammatory lesion counts at week 12 was the primary efficacy variable (global improvement was a primary efficacy parameter vs placebo) and safety was assessed by adverse events. Lymecycline 300 mg od was non-inferior to lymecycline 150 mg bid at all time points and superior to placebo throughout the study. Drug-related adverse events were similar for all treatment groups. Lymecycline 300 mg od is as effective and safe as lymecycline 150 mg bid in the treatment of moderate to severe acne. This new, once daily formulation could potentially contribute towards improved compliance rates with oral tetracyclines.

Acne Vulgaris↗