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Biomedical subjects

B Dreno

Publications and source records attributed to B Dreno.

At least 19 recordsLinked to original sources

[Lymphomatoid papulosis].

Lymphomatoid papulosis is a distinct entity in which recurring crops of haemorragic and necrotic papules display a cytologically malignant infiltrate. The aberrent cell is now generally accepted to be an active T helper phenotype. The expression of Ki-1 (CD30) on a significant portion of the infiltrating cells characterizes lymphomatoid papulosis and relates this disorder with Hodgkin's disease, mycosis fungoides and anaplasic T cell lymphoma which may be associated in 10 to 20% of lymphomatoid papulosis. The categorization of this disease as a benign disorder versus lymphoma remains controversial. Studies of T cell receptor gene rearrangement demonstrate clonality in many cases. So, this monoclonal population could have a malignant transformation induced by a triggering stimulus such as genetic translocation, or viral infection. Finally, recent opinions consider that lymphomatoid papulosis and Ki-1 (CD30) lymphomas are different parts of a clinical and histological spectrum constituted by cutaneous Ki-1 lymphoid infiltrates.

Antigens, CD

HLA class II-restricted recognition of common tumor epitopes on human melanoma cells by CD4+ melanoma-infiltrating lymphocytes.

CD4+ T cell clones derived from lymphocytes infiltrating four human melanomas specifically recognized melanoma-derived tumor epitopes as shown by secretion of tumor necrosis factor (TNF) in vitro upon interaction with autologous melanoma cells, whereas they did not recognize HLA class II-expressing autologous lymphoblasts or HLA class II mismatched allogeneic melanoma cells. Specificity was further established by demonstrating that TNF responses to tumor cells were inhibited by HLA-DR or HLA-DQ monoclonal antibodies. Most of these clones cross-reacted with allogeneic melanoma cells expressing a potentially restricting HLA allele or a structurally similar one. These data show that shared epitopes of human melanoma cells presented on HLA class II molecules are frequently recognized by autologous CD4+ T lymphocytes.

Alleles

[Combination of dacarbazine, vindesine and interferon alpha in the treatment of metastatic melanoma].

INTRODUCTION: The aim of this work was to study the effectiveness and safety of a combined therapy with dacarbazine, vindesine and alpha-interferon in the treatment of metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients (20 with visceral metastases and 11 with regional skin and lymph nodes metastases) were treated with dacarbazine (400 mg/m2 i.v. every 28 days), vindesine (3 mg/m2 i.v. every 14 days) and recombinant interferon alpha 2b (Introna) 10 x 10(6) UI subcutaneously three times weekly. RESULTS: All patients at least received 3 cures of chemotherapy. The response rate was 22.6 p. 100 with an average of 3.6 months and an average deviation of 7.2 months. The responders were predominantly patients with lymph nodes (50 p. 100) and lung metastases (25 p. 100). Response was better in patients with no more than two metastatic sites. The treatment was well tolerated. DISCUSSION: This combined chemotherapy with 3 drugs not significantly increase either the response rate or its duration. However, the quality of life was good.

Antineoplastic Combined Chemotherapy Protocols

Induction of myelo-monocytic My7 antigen (CD13) expression by interferon-alpha in basal cells of cutaneous T-cell lymphomas.

The My7 antigen that is expressed on the basal cells in normal skin and inflammatory disorders is absent in the lesions of cutaneous T-cell lymphoma (CTCL). Induction of My7 expression in basal cells in the cutaneous lesions of 12 patients with mycosis fungoides and three with Sézary syndrome treated with interferon-alpha 2a (IFN-alpha 2a) for 10 months was investigated. Biopsies were taken from the same area before treatment and after 2, 6 and 10 months of therapy with IFN-alpha 2a. My7 antigen was expressed on the basal cells only in those patients who showed either a complete or partial response to therapy with IFN-alpha 2a.

Antigens, CD

Zinc salts effects on granulocyte zinc concentration and chemotaxis in acne patients.

To explore the mechanism by which zinc acts on cutaneous inflammatory lesions, we studied granulocyte zinc levels and in vitro polymorphonuclear leukocyte chemotaxis in 20 acne patients before and after 2 months of zinc therapy (200 mg/day zinc gluconate). The zinc level was assayed by flame absorption spectrophotometry and chemotaxis was performed by agarose assay. After 2 months of treatment, a significant decrease in granulocyte zinc level associated with inhibition of chemotaxis (r = 0.69) was observed in 16 patients. This suggests that zinc anti-inflammatory action is related to inhibition of polymorphonuclear leukocyte chemotaxis induced by a decreased granulocyte zinc level.

Acne Vulgaris

[Changes in cutaneous zinc during skin aging].

Variations of epidermal zinc concentration with aging were studied by measuring zinc levels in the epidermis of two groups of healthy subjects: group A aged less than 35 years; group B aged more than 65 years. The epidermis was obtained from a suction blister, and zinc levels measurements were performed by absorption spectrophotometry. There was a significant decrease (p less than 0.01) of epidermal zinc concentration with aging, and zinc contents of the epidermis were the same in men and women. On the other hand, no significant difference was found in zinc blister fluid levels between the two groups, confirming the absence of relationship between plasma zinc and epidermal zinc. The decrease of epidermal zinc concentrations observed in elderly subjects might be due to a decrease of enzyme activities in the epidermis induced by aging; conversely, a low epidermal zinc level might induce, by itself, a fall in enzyme activities. Thus, zinc might play an important role in the development of alterations in keratinocytes with aging.

Adult

High-fold expansion of human cytotoxic T-lymphocytes specific for autologous melanoma cells for use in immunotherapy.

We set up a culture protocol that consistently allows high-fold expansion of tumor-specific T-lymphocytes from most melanoma-invaded biopsies with low doses of recombinant interleukin-2 (rIL-2). Between 2-60 x 10(6) T-lymphocytes could be obtained and cryopreserved from 12 out of 13 patients, by culturing only 50 mm3 tumor tissue with rIL-2. Thawed lymphocytes from 11 of these patients could then be expanded by a median factor of 32,800 by culturing them successively in microplates on irradiated feeder cells with rIL-2 for approximately 2 weeks and then in culture bags or flasks with only rIL-2 for 1-2 additional weeks. Dead feeder cells disappeared during the last phase of the lymphocyte culture with rIL-2. Interestingly, each time they were expanded under these conditions, tumor-infiltrating lymphocytes (TIL) or lymph-node lymphocytes developed a lytic activity apparently restricted to the autologous melanoma line. Tumor-specific lysis, which was maximum at around the end of T-lymphocyte expansion, ranged between 31-63% lysis at an effector:target (E:T) ratio of 20:1. This culture method would thus appear to be suitable for reliable production of over 10(10) T-lymphocytes with good tumor-specific lytic activity from most melanoma-invaded biopsy. It should permit analysis of the immunotherapeutic potential of these populations reinjected into cancer patients.

Cell Division

Mucocutaneous side effects of chemotherapy.

Increasing numbers of chemotherapeutic agents are being used to treat patients with cancer. They have only a slight margin of safety between the tumoricidal and toxic doses. The skin is a frequent target for the side effects of these drugs, and the clinician should be alert to these manifestations so that needless diagnostic work up is avoid.

Combined Modality Therapy

Epidermal interleukin 1 in normal skin of patients with HIV infection.

Interleukin 1 (IL-1) in the epidermis plays an important role together with Langerhans cells in the activation of the T cells. To determine whether IL-1 could be located in the normal epidermis of 54 patients with HIV infection and related to the stage of the disease, an indirect immunofluorescence technique was used. Intense epidermal fluorescence to IL-1 was noted in the asymptomatic stage II of the disease, whereas there was minimal reactivity in the other stages.

Acquired Immunodeficiency Syndrome

[Treatment of metastatic melanoma with dacarbazine recombinant interferon alfa 2A combination: results of multicentric study].

Fifty patients suffering from histologically proven metastatic melanoma were treated with a combination of DTIC (400 mg/m2 i.v. every 28 days) and recombinant alpha 2A interferon (Roferon-A) 10 x 10(6) U/m2 daily, administered intramuscularly or subcutaneously for 2 months followed by 7 x 10(6) U/m2 3 times a week. Treatment was carried out for a period of 12 months unless progressive disease was noted after 3 months. Among the 49 evaluable patients, 6 achieved a complete response (CR) and 4 a partial response (PR) (response rate, 20%) at 2 months, 8 CR and 3 PR (25%) and 8 CR and 2 PR (23%; 95% confidence limits, 13-40%) occurred at month 6 and 12 respectively These responses occurred notably in patients with cutaneous (3 cases) or lymph node metastases (4 cases), but 3 responses included visceral sites: lung (1 CR), liver (1CR and 1PR). Average response duration was 16.5 months (range 4-29 + months). The time required for objective response can be up to 6 months, which suggest that treatment should receive a reasonable trial period (at least 3 months). Clinical toxicity consisted mainly of a flu-like syndrome, anorexia and fever, and occurred in more than 50% of patients; hematologic and hepatic toxicities required a dose reduction in 54% of patients but in only one case did treatment have to be terminated because of this. Seventeen (35%) of the patients are still alive, 4 with metastases (follow-up period: 18-34 + months) and 13 without metastases (follow-up period: 13-32 + months). A combined regimen of r-IFN alpha 2A and dacarbazine is effective in treating patients with metastatic melanoma, with acceptable toxicities and a reasonable quality of life (out-patient treatment or district nurse care). The objective response rate (23% at 12 months) compares favourably with those of earlier trials using the same combination of drugs, and occurred not only in cutaneous and lymph node metastases but also in visceral metastases.

Adolescent

MY7 monoclonal antibody for diagnosis of cutaneous T-cell lymphoma.

Infiltrate in cutaneous T-cell lymphomas (CTCLs) is composed mainly of CD4 helper cells with a phenotype very similar to that of benign cutaneous lymphoid infiltrate. MY7 (CD13) is a monoclonal antibody that is normally expressed on peripheral granulocytes and monocytes but also cross-reacts with an antigen expressed on epidermal basal cells. We studied MY7 expression on basal cells of the epidermis and CD4 cell infiltrate in 34 CTCLs, 11 pseudolymphomas, and 29 other benign cutaneous lesions. An indirect immunofluorescence technique with double labeling and an immunoperoxidase technique were used. We found that in benign inflammatory infiltrate, less than 10% of CD4 cells expressed MY7 antigen associated with normal MY7 monoclonal antibody labeling of basal cells, whereas in CTCLs more than 50% of CD4 tumoral cells in dermis expressed MY7 antigens; however, basal cells were MY7 negative. Thus, it is demonstrated that MY7 monoclonal antibody with its double modulation on epidermis (basal cells) and dermis (CD4 cells) has diagnostic value for differentiating CTCLs with CD4+ MY7+ tumor cells in dermis and MY7-negative basal cells from benign inflammatory lesions with CD4+ MY7- cells in dermis and MY7-positive basal cells. This modulation of MY7 labeling could be related to the secretion of epidermal cytokines.

Antibodies, Monoclonal

Interleukin 2-like material in human epidermis: a ligand for the human interleukin 2-receptor 55 kD alpha chain.

The antirecombinant interleukin 2 (rec-IL-2) monoclonal antibody (moAb) 15.2 cross-reacts with a skin antigen located at the cell surface of human keratinocytes within the granular layer. This study extends the analysis of this IL-2-like material to its reactivity with eight antibodies raised against natural IL-2, rec-IL-2 or IL-2 peptides. Four among them were found to react with the granular epidermal layer as well as with a simian virus 40 (SV40) transformed human keratinocyte cell line. Each of these four antibodies gave similar labeling patterns, although with different intensities, and competitively inhibited each other. Analysis at the messenger RNA level in epidermal cells and SVK 14 also indicated that this material is very likely different from IL-2. From the knowledge, for some of these antibodies, of the amino-acid regions they recognize on the IL-2 molecule, it is inferred that the skin antigen shares with IL-2 at least two overlapping epitopes located in the 33-54 amino-acid region of IL-2, a region that has been shown to be involved in the binding of IL-2 to the IL-2-receptor (IL-2-R) 55 kD chain. Indeed, a purified recombinant soluble species of this IL-2-R is shown in this study to bind specifically to the IL-2-like skin material. As far as IL-2-R bearing cells are found in normal epidermis (Langerhans cells) and as important infiltrates of IL-2-R positive T lymphocytes are often encountered in cutaneous diseases, a potential role for this IL-2-like material in skin immunophysiopathology is suggested.

Antibodies, Monoclonal

Low doses of zinc gluconate for inflammatory acne.

The effect of zinc on acne is unclear. In this study, only patients with an inflammatory acne were included in a double-blind trial using low doses of zinc gluconate (200 mg/day, corresponding to 30 mg zinc metal). We obtained a significantly different result between zinc and placebo groups in the inflammatory score (p less than 0.02). This efficiency could be explained by the action of zinc on inflammatory cells, especially granulocytes.

Acne Vulgaris