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Biomedical subjects

M Bagot

Publications and source records attributed to M Bagot.

At least 145 records · Page 8Linked to original sources
PubMed1989

[Mixed lympho-epidermal cell cultures: value in bone marrow grafts].

Graft-versus-host disease (GVHD) is the major complication of allogeneic HLA-identical bone marrow transplantation. GVHD is induced by the activation of mature T cells in the graft which react against minor antigens of the recipient. Mixed epidermal cell-lymphocyte cultures (MELC), which constitute an in vitro model of epidermal cell-lymphocyte interactions, make it possible to study the presentation of antigens to the lymphoid cells by epidermal Langerhans cells. We performed MELC in 66 patients who had received an HLA-identical bone marrow transplant for malignant blood disease. The bone marrow received by 29 recipients had been depleted of mature T cells, whereas 37 recipients had received a non-depleted bone marrow. A complete, uni- and multivariate statistical analysis was carried out on recipients of non-depleted bone marrow to evaluate the risk factors for acute and chronic GVHD. This study showed that MELC between donor and recipient was the most predictive parameter for the occurrence of GVHD. Other factors were a history of previous pregnancies in female donors and a diagnosis of chronic myelogenous leukaemia. These results may be of value in the selection of donors and for a better determination of the need for bone marrow depletion.

Animals↗
PubMed1989

Acral erythema and systemic toxicity related to CHA induction therapy in acute myeloid leukemia.

Seventy-two adult patients with previously untreated acute myeloid leukemia received the CHA regimen as induction chemotherapy: CCNU 80 mg/m2 on day 1, Adriamycin 35 mg/m2 i.v. on days 1, 2 and 3, and continuous infusion of cytarabine 100 mg/m2/24 h from day 1 to 10. Forty-nine patients (68%) presented at least one of the following symptoms: acral erythema with dysesthesias in the palms and/or soles (39%); cholestatic hepatitis (39%); profuse sterile diarrhea associated with abdominal distention (33%); acute cerebellar dysfunction (32%) and non-cardiogenic pulmonary edema (21%). Most of these toxic symptoms appeared 8-20 days after the first dose. As these clinical features were absent or exceptional in patients treated with another regimen within a controlled trial, they are reported as toxic-side-effects of the chemotherapy regimen. Acral erythema was found to be predictive of complete remission (P less than 0.01, odds ratio: 6.33); neurotoxicity was prognostic for death in aplasia (P less than 0.05); the absence of any of the five symptoms was associated with failure of the induction regimen (P less than 0.02).

Adolescent↗
PubMed1989

Synthetic retinoids inhibit the antigen presenting properties of epidermal cells in vitro.

The clinical efficacy of retinoids in benign and malignant skin diseases involving immune mechanisms suggests that they affect the immunologic functions of the epidermis. However, these effects have yet to be demonstrated. The action of vitamin A (retinol) and the synthetic retinoids, isotretinoin, etretinate, acitretin, and arotinoid-free acid have been studied on the lymphocyte proliferation induced by phytohemagglutinin (PHA), by the mixed lymphocyte reaction (MLR), and the mixed epidermal cell-lymphocyte reaction (MECLR). The results for PHA-induced proliferations were highly variable for all the retinoids. However, in MECLR, the synthetic retinoids consistently reduced the proliferation by 20%-30%. This occurred at therapeutic drug concentrations of about 10(-7)M. In MLR, a minor decrease of 10%-15% was only found for higher concentrations (10(-5)M). Retinol induced no effect in either reaction. Further analysis of acitretin on MECLR showed that it reduced lymphocyte proliferation in a dose-dependent fashion. This reduction was combined with a decrease in cytotoxic T-lymphocyte induction (CTL). Addition of 10(-6)M acitretin at various times also revealed that its presence at cell culture initiation was necessary to inhibit proliferation significantly. Furthermore, cell treatments prior to MECLR showed that exposure of epidermal cells to acitretin was essential to produce this inhibition, suggesting that it acts directly on epidermal cells. Consequently, it is suggested that the specific inhibitory effect of synthetic retinoids on lymphocyte activation in MECLR may partly account for their therapeutic action on the skin.

Acitretin↗
PubMed1989

[Negativity of Borrelia burgdorferi serology in scleroderma en plaques].

The occurrence of morphea has been attributed to Borrelia, burgdorferi infection, but the relationship between localised scleroderma and borreliosis remains controverted. Antibodies directed against B. burgdorferi were looked for in 21 patients (18 female and 3 male, aged from 8 to 63 years) whose disease had been present for 6 weeks to 13 years. One patient had a single morphea, two had monomelic scleroderma and 18 had multiple localised morpheas. The search for antibodies was conducted in these 21 patients and in 200 blood donors from the Paris region by indirect immunofluorescence techniques, using the CDC method where only antibody titers of 1/256 or more are significant. Serology was lower than 1/256 in 20 cases and equal to 1/256 in one case. Among the 200 blood donors, five (2.5%) had antibody titers of 1/256 or more. None of the patients studied had been exposed to tick bite due to their occupation or place of residence. We therefore found no evidence of a link between B. burgdorferi infection and morphea in the Paris region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

The mixed epidermal cell lymphocyte-reaction is the most predictive factor of acute graft-versus-host disease in bone marrow graft recipients.

Risk factors for acute graft-versus-host disease (GvHD) remain controversial. We performed uni- and multivariate statistical analyses on a series of 37 patients receiving a non-depleted allogeneic bone marrow transplant from an HLA-identical sibling donor for a haematological malignancy, in order to identify risk factors for GvHD. Three factors were associated with development of moderate to severe GvHD: a positive mixed epidermal cell-lymphocyte reaction (MECLR) between donor and recipient, previous pregnancies in female donors and chronic myeloid leukaemia diagnosis. The MECLR was the most important predictive factor, selected in first rank by the stepwise linear discriminant analysis. Combining these three prognostic factors in the jackknifed procedure, we could correctly classify 33/37 patients in two groups: grade O-I versus grade II-IV acute GvHD. These results should apply to donor selection and to predict donor/recipient pairs at high risk of GvHD who might benefit of bone marrow T-cell depletion and those at low risk for whom depletion could be avoided.

Adolescent↗
PubMed1988

Reconstructed human epidermis: absence of Langerhans cells and failure to stimulate allogeneic lymphocytes in vitro.

Whole human skin can be reconstructed in vitro, using dermal equivalents made of fibroblasts in a collagen matrix. We recently described a new method of epidermalization of dermal equivalents, based on the insertion of punch biopsies and the migration of epidermal cells (EC) on the reconstructed dermis. In the present study, we show that no MHC class II or T6 positive Langerhans cells (LC) can be detected in this new epidermis. Functional studies with EC of this reconstructed epidermis show that these EC completely fail to induce proliferation of allogeneic lymphocytes in mixed epidermal cell lymphocyte reactions and to raise an allogeneic T cell response. In contrast, fresh EC from the same donors induce a strong proliferative and cytotoxic response of the same effector cells. Moreover, the addition of fresh LC-containing EC autologous to effector lymphocytes does not restore an allogeneic proliferative and cytotoxic response directed against class I different EC of the new epidermis. Such a non-immunogenic whole skin model composed of two compartments, dermis and epidermis, completely devoid of class II-bearing antigen presenting cells, is thus a very promising technique for allogeneic skin grafting in the treatment of burns.

Culture Techniques↗
PubMed1988

[The mixed lympho-epidermal culture: a predictive test of the graft-versus-host reaction in receivers of bone marrow grafts].

Mixed lymphocyte reactions (MLR) and mixed epidermal cell-lymphocyte reactions (MECLR) were performed concurrently before grafting in patients scheduled to receive a bone marrow graft from an HLA-identical sibling for an hematological malignancy. For each donor-recipient pair, the ratio of the counts per minute (cpm) for MECLR to the cpm for MLR was calculated. This ratio was significantly higher in the group of patients who subsequently developed grade II to IV graft-vs-host (GVH) disease as compared to the group who had grade O-I GVH. Statistical analysis showed that this parameter was the most significant risk factor for acute GVH, as it was the leading factor selected by stepwise discriminant analysis. The other significant risk factors for acute GVH were previous pregnancies in female donors and chronic myeloid leukemia in recipients. Thus, these parameters allow more accurate evaluation of the risk for GVH in individual recipients before grafting and therefore of the indications for T-cell depletion.

Bone Marrow Transplantation↗
PubMed1987

Reconstitution of cytotoxic T lymphocyte activity following allogeneic bone marrow transplantation in man.

Longitudinal studies over an eight-month period have been performed to follow the T killer response restoration after allogeneic bone marrow transplantation (BMT). The capacity of the patient's peripheral blood mononuclear cells (PBM) to develop cytotoxic effector cells directed either against allogeneic cells or against Epstein-Barr virus (EBV) or Herpes-simplex virus-1 (HSV-1)-infected syngeneic cells was tested monthly. The data suggest that in most cases the cytotoxic T lymphocyte (CTL) activity, either allospecific or directed against EBV and the HSV-1 specific killer (HNK) responses, is quickly reconstituted in BMT patients. Roughly, these activities seem to be normal after two months following classic nondepleted grafting. However, in the two patients who had received a T-cell-depleted graft, the restoration was delayed. Furthermore, in the majority of the patients, once reconstituted the killer responses were relatively stable and the occurrence or absence of graft-versus-host diseases (GVHD) did not significantly modify these responses.

Adolescent↗