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Biomedical subjects

M Bagot

Publications and source records attributed to M Bagot.

At least 109 records · Page 6Linked to original sources
PubMed1994

Immunosuppressive effects of 1,25-dihydroxyvitamin D3 and its analogue calcipotriol on epidermal cells.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)2D3, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T-cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)2D3 and calcipotriol on the human allogeneic mixed epidermal cell-lymphocyte reaction. All experiments were performed both with 1,25(OH)2D3, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)2D3 resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC-depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle-treated LC. These calcitriol-pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected, LC-depleted keratinocytes failed to stimulate allogenic lymphocytes. When added to autologous unmodified EC, however, calcitriol-pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle-treated keratinocytes. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2-h or 24-h pulse with 1,25(OH)2D3 or calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1994

Epidemiology of IDDM in Switzerland. Increasing incidence rate and rural-urban differences in Swiss men born 1948-1972.

OBJECTIVE: To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in Switzerland by undertaking a retrospective analysis of the registry of the Swiss army, which contains updated medical files for all male Swiss citizens. Nation-wide data for IDDM epidemiology have not been available in Switzerland. RESEARCH DESIGN AND METHODS: Every male Swiss citizen is obliged to enlist in the Swiss military service at 19 years of age, when a personal, continuously updated medical file is established. Diabetes is an exclusion condition for military service and is clearly marked in the file. A total number of 514,747 files, corresponding to birth year cohorts 1948-1950, 1955-1957, 1962-1964, and 1970-1972, have been manually checked for the diagnosis of IDDM. RESULTS: IDDM was identified in 926 cases in the four groups of three age-cohorts. The incidence at < or = 15 years (per 100,000/year) was 4.5 in the age cohorts 1948-1950 and 7.2 in the age cohorts 1970-1972 (P < 0.005). An additive age-cohort Poisson regression model fits the nationwide incidences adequately, neither a period effect nor age x cohort interactions being required. In the oldest age cohorts, the age-specific incidence of IDDM was calculated up to the age of 43 and was approximately 7/100,000/year in men between 20 and 40. In these age cohorts, we found an approximately 50% higher risk to develop IDDM at age < or = 19 for men living in an urban region and a significantly (P < 0.005) increased incidence between 20 and 40 years in rural regions compared with urban regions. CONCLUSIONS: The incidence of IDDM in Switzerland is comparable to other countries in central Europe and has been increasing in the last 20 years. This is in accordance to most recent epidemiological studies worldwide. In addition, the data suggest exogenous factors inducing IDDM at a younger age in urban regions.

Adolescent↗
PubMed1994

Additive effects of calcipotriol and cyclosporine A: from in vitro experiments to in vivo applications in the treatment of severe psoriasis.

We report that calcipotriol (CPT) is a potent inhibitor of lymphocyte proliferation in mixed epidermal cell lymphocyte reactions. In this model, CPT and cyclosporine A (CsA) have synergistic effects. These results have led to a randomised double-blind therapeutic study protocol in patients with severe psoriasis. In these patients, topical CPT and sub-therapeutic doses of CsA (2mg/kg/d) induce disappearance of cutaneous lesions. This therapeutic association may minimize secondary side effects of both drugs.

Adult↗
PubMed1994

Nonepidermotropic cutaneous lymphomas. A histopathological and immunohistological study of 52 cases.

We report the detailed histological and immunohistological findings in 52 cases of nonepidermotropic cutaneous lymphoma, as revealed by cutaneous lesions. The patients presented mainly with cutaneous nodules and, more rarely, with infiltrated plaques, annular erythema, or erythroderma. The staging procedure following the diagnosis revealed lymph node and/or bone marrow involvement in half of the cases. Nearly 60% of the nonepidermotropic cutaneous lymphomas were of the large-cell type. The reticular dermis was involved in all of the cases, and the papillary dermis was involved in only 11 of them. Nonepidermotropic cutaneous lymphomas were of the B-cell, T-cell, and non-B-, non-T-cell type in 38, 13, and 1 case(s), respectively. A monotypic immunoglobulin light chain expression was detected in 33 of 35 tested cases of the B-cell lymphomas, and a loss of one or several pan-T-cell antigens was observed in all of the cases of the T-cell lymphomas. In seven cases (13%), the diagnosis of malignancy was based only on these immunohistological criteria. This study shows that nonepidermotropic cutaneous lymphomas are B-cell lymphomas in 75% of the cases, most often of the large-cell type. It also emphasizes the value of immunohistochemistry to firmly establish malignancy when routine light microscopical findings are questionable.

Adolescent↗
PubMed1993

Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus.

We report the case of a previously healthy 54-year-old woman, without any family history, who developed an angioneurotic edema with acquired C1 inhibitor deficiency and systemic lupus erythematosus. The search for a lymphoproliferative disorder was negative. Hydroxychloroquine therapy induced simultaneous resolution of lupus and angioedema. The pathophysiology of this association is discussed.

Angioedema↗
PubMed1993

[Progress in the diagnosis and physiopathology of cutaneous lymphoma].

During the last few years, the diagnosis of cutaneous lymphoma has benefited from new techniques. Immunohistochemical staining helps in the early diagnosis of mycosis fungoides and has contributed to a better characterization of non-epidermotropic lymphomas. The possibility of immunohistochemical staining on paraffin-embedded sections has facilitated its execution. CD 30 antigen expression seems to have a prognostic value for nonepidermotropic giant T-cell lymphomas. The prognostic value of expression of one of the two types of T-cell receptors for the antigen, alpha/beta or gamma/delta, remains to be established. The anti-V region antibodies may constitute a marker of clonality for some T-cell lymphomas and demonstrate that in some cases of mycosis fungoides the infiltrate is strictly intraepidermal. Genotype determination represents an advance in the diagnosis of certain nonepidermotropic lymphomas which cannot be characterized on the basis of immunohistochemical data alone. On the other hand, the Southern blot test has been unable to solve the difficult problem of the early diagnosis of mycosis fungoides. Polymerase chain reaction is a novel and very promising technique the usefulness of which remains to be determined. It can already be predicted that it will confront the clinicians with a problem: the significance of demonstrating very small clonal populations. A better knowledge of various cytokines makes it easier to understand the course of cutaneous lymphomas. Finally, advances in molecular biology techniques in the field of retroviruses suggest that defective retroviruses might be the cause of some cutaneous lymphomas.

Antigens, CD↗
PubMed1993

Bullous amyloidosis. Report of 3 cases and review of the literature.

We report 3 cases of bullous immunoglobulinic amyloidosis and review 25 published cases. In 2 of our patients, amyloid deposits were not detected with special staining, but by means of ultrastructural methods. Investigations of the skin lesions permitted the diagnosis of associated plasma cell dyscrasia in 2 patients. Unexplained bullous lesions should be investigated for amyloid deposits and the presence of monoclonal gammopathy by methods including electron microscopy and immunochemical analysis of serum and urine.

Aged↗
PubMed1993

Impaired antigen presentation in toxic epidermal necrolysis.

BACKGROUND AND DESIGN--The pathophysiology of toxic epidermal necrolysis (TEN) remains largely unknown. Toxic epidermal necrolysis is considered a hypersensitivity reaction to drugs, but direct evidence of an immunologic mechanism is still lacking. Lymphopenia and a decrease in the numbers of circulating CD3- and CD4-positive lymphocytes have been reported in acute phase, but, to our knowledge, no study of cellular immune functions of patients with TEN has been reported so far. Herein, we investigated several T-cell functions in a series of 11 patients with TEN. Peripheral blood mononuclear cells (PBMC) obtained in the acute phase were tested together with PBMC obtained after the patient's recovery and compared with those of age- and sex-matched healthy control subjects. RESULTS--Phytohemagglutinin-induced proliferations and lymphocyte responses in allogeneic mixed lymphocyte reactions were not impaired in the acute phase compared with those after recovery in the same patients and with those in control subjects. In contrast, natural killer cytotoxicity and allogeneic cytotoxic responses were significantly decreased in early TEN. The most striking feature was the significantly impaired ability of acute-phase lymphoid cells to activate allogeneic T cells. Patient PBMC in acute-phase TEN did not inhibit the proliferation induced by patient PBMC after recovery, suggesting that their defect was not related to the presence of radioresistant suppressor cells. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on circulating peripheral blood lymphocytes was then assessed by immunoalkaline phosphatase staining and flow cytometry. Results showed decreased percentages of HLA-DR-positive mononuclear cells and a decreased density of HLA-DR antigens, mainly on monocytes, in acute-phase TEN. CONCLUSIONS--These results demonstrate that peripheral blood lymphocytes of patients with TEN have an impaired ability to activate allogeneic T cells. This defective antigen presentation is not secondary to the presence of suppressor lymphocytes, but it is probably related to a decreased expression of HLA-DR antigens on circulating mononuclear cells in acute-phase TEN.

Adolescent↗
PubMed1992

Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases.

BACKGROUND: Sclerodermatous chronic graft-versus-host disease is a disabling complication after allogeneic bone marrow transplantation from HLA-identical sibling donors. Only a few series of patients have been reported and the dermatologic features have never been extensively described. OBJECTIVE: The purpose of the study was to describe clinical and biologic features of chronic sclerodermatous graft-versus-host disease and to compare them with scleroderma. METHODS: We reviewed 196 patients grafted between April 1973 and July 1987 with survival times sufficient to be at risk of chronic graft-versus-host disease. Seven had the sclerodermatous form. RESULTS: Most patients had disseminated sclerosis of the trunk and the proximal portions of the limbs. In two cases, atrophy of the skin was predominant, corresponding with a severe clinical evolution. Periorbital pigmentation was observed as an initial manifestation in three cases. Visceral manifestations resembled those observed in scleroderma but histologic and immunologic studies demonstrated clear differences. Response to therapy was variable. CONCLUSION: Chronic sclerodermatous graft-versus-host disease may realize two different patterns. Major atrophy is associated with a more severe progression.

Adolescent↗
PubMed1992

Intraepidermal localization of the clone in cutaneous T-cell lymphoma.

BACKGROUND: No immunohistologic techniques are currently available to demonstrate clonality of T-cell lymphomas. Monoclonal antibodies to the variable region of the T-cell receptor (TCR) have been produced that identify minor populations of normal peripheral blood T lymphocytes. OBJECTIVE: We investigated the expression of TCR V-region genes in cutaneous lymphomas to determine whether immunostaining with these antibodies may be a simple method to detect clonal T-cell proliferations and help to distinguish benign lymphoid infiltrates from malignant lymphoma. METHODS: Cutaneous samples were obtained from 18 cutaneous T-cell lymphomas (14 mycosis fungoides, 1 Sézary syndrome, 2 pleomorphic T-cell lymphoma, and 1 large cell anaplastic lymphoma) and 8 benign lymphoid infiltrates. Frozen sections were incubated with monoclonal antibodies and stained by the alkaline phosphatase-antialkaline phosphatase technique. Staining was performed with a panel of 7 anti-TCR V-region antibodies, 6 T-cell markers, 1 anti-beta chain antibody, and 1 anti-delta chain antibody. RESULTS: Clonality could be demonstrated in 2 of 18 cutaneous lymphomas. We observed the strictly intraepidermal localization of clonal proliferation in one case of early-stage mycosis fungoides. CONCLUSION: Anti-TCR V-region antibodies may identify a strictly epidermotropic clone in early mycosis fungoides. However, the panel of antibodies currently available stains only a minority of cutaneous T-cell lymphomas. The usefulness of these antibodies as a clonotypic marker needs to be reevaluated when a larger panel of antibodies becomes available.

Adult↗
PubMed1992

Interleukin-7 is a growth factor for Sézary lymphoma cells.

Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.

Adult↗
PubMed1992

Clinical and biological analysis of peripheral T-cell lymphomas: a single institution study.

Peripheral T-cell lymphoma (PTCL) accounts for 15-20% of non-Hodgkin's lymphoma in the Western World. Clinical, histopathologic, phenotypic and genotypic data were received from 33 cases of PTCL referred to our institution. The median age order was 50 years, 78% were males, and 18% had a history of a preceding disorder of the lymphoid system. 60% had stage 4 at diagnosis and B symptoms were also present in 60%. The most frequent sites of extranodal involvement were bone marrow (54%), liver (45%) and skin (33%). Twenty-eight of 33 cases were histologically classified according to the Working Formulation (most in the diffuse mixed and large-cell subgroups) and the Kiel updated system. Phenotypic and genotypic studies of malignant cells showed a considerable heterogeneity with respect to the expression of either T-cell receptor (TCR) alpha beta and gamma delta and pan-T differentiation molecules. Of the studied cases 63% expressed TCR-alpha beta. All five patients with PTCL of the TCR-gamma delta subtype had a peculiar extra-nodal presentation. The vast majority of cases expressed an abnormal T-cell phenotype with respect to the expression of pan-T antigens, including the lack of expression of the TCR-associated CD3 molecule in 2 cases. Rearrangements of the TCR beta and/or delta-chain genes showed clonality in 21 of the 23 studied cases. Twenty-five patients were treated with a multiagent chemotherapy regimen with curative intent and the remainder received a less intensive palliative regimen. Only 9 patients achieved CR (8 of whom had received an anthracycline-containing regimen) and the 4-year survival rate was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗